Cranial Mononeuropathies in Adults: Clinical Practice Guidelines

List of Abbreviations

ALT – alanine aminotransferase

AST – aspartate aminotransferase

BF – Biofeedback

BoNT-A – Botulinum toxin type A**

TMJ – Temporomandibular joint

HBO – hyperbaric oxygenation

GCS – Glucocorticosteroids

HFS – Hemifacial spasm

DNA – deoxyribonucleic acid

PRFA – Pulsed radiofrequency ablation

MAB FN – Marginal mandibular branch of the facial nerve

CBCT – Cone-beam computed tomography

CBT – cognitive behavioral therapy

CT – computed tomography

PT – physical therapy

ICD – International Classification of Diseases

ICHD – International Classification of Headache Disorders

ICOF – International Classification of Orofacial Pain

MOFSM – Myofascial orofacial pain associated with muscle spasm

DLI – Depressor labii inferioris (muscle)

MRI – magnetic resonance imaging

NVC – Neurovascular conflict

FNP – Facial nerve neuropathy

NSAIDs – non-steroidal anti-inflammatory and antirheumatic drugs

GLN – Glossopharyngeal neuralgia

CVA – cerebrovascular accident

MUAP – motor unit action potential

PIFP – Persistent idiopathic facial pain

РКИ – randomized controlled trial

SB – The Sunnybrook Facial Grading System

ESR – erythrocyte sedimentation rate

BMS – Burning mouth syndrome

CRP – C-reactive protein

SRFA – Standard (thermal) radiofrequency ablation

rTMS – Transcranial magnetic stimulation

TN – Trigeminal neuralgia

US – ultrasound examination

HB – House-Brackmann Grading System

COX – cyclooxygenase

ALP – alkaline phosphatase

SNEMG – Stimulation electroneuromyography

EMG – Needle electromyography

AMPA – α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

DN-4 (fr. la douleur neuropathique – neuropathic pain)

IL – Interleukin

ICOP – International Classification of Orofacial Pain

NMDA – N-methyl-D-aspartate

SUNCT – Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing

TNF – Tumor necrosis factor

Terms and Definitions

Trigeminal nerve disorders:

Trigeminal neuralgia (TN) is a disorder characterized by unilateral, recurrent, brief paroxysms of pain resembling electric shocks in semiology, sudden in onset and termination, clearly provoked by non-noxious stimuli and restricted to one or more branches of the trigeminal nerve.

Neurovascular conflict (NVC) is a condition of nerve-vessel interaction in which a vulnerable portion of a nerve root is affected by an adjacent blood vessel.

Allodynia is pain resulting from a stimulus that normally does not provoke pain, which can be contact-induced (tactile/mechanical or thermal allodynia) or movement-induced (kinesigenic allodynia).

Anesthesia is the complete loss of one or more modalities of sensation (tactile, thermal, proprioceptive, vibratory).

Anesthesia dolorosa is pain felt in an area of anesthesia.

Hyperalgesia is increased pain sensitivity to noxious stimuli: intense pain from mild nociceptive stimulation within the innervation zone of the damaged part of the nervous system (primary hyperalgesia) or adjacent and even distant areas (secondary hyperalgesia).

Hyperesthesia is increased sensitivity to various stimuli (tactile, thermal, cold) that is disproportionate to the stimulus.

Hyperpathia is an enhanced or altered sensation with an unpleasantly emotional component that may persist after the cessation of a painful, tactile, or thermal stimulus. The sensory threshold may be elevated.

Hypesthesia is a partial impairment of one or more modalities of sensation (tactile, thermal, proprioceptive, vibratory);

Dysesthesia – an unpleasant abnormal sensation, whether spontaneous or evoked.

Paresthesia is a spontaneous or evoked (by light tactile, thermal stimulus, or movement) sensation of tingling, pins and needles, pressure, or tightening in any part of the body.

Prosopalgia is pain in one half of the face.

Spontaneous pain is pain occurring without any external stimulus.

Amaurosis fugax is transient monocular blindness.

Facial nerve disorders:

Facial nerve neuropathy (FNN) is a disorder of the facial nerve characterized by acutely developed or progressively worsening facial asymmetry due to unilateral weakness of facial muscles, impaired eye closure, and—depending on the site of the lesion—symptoms such as dry eyes or tearing, taste disturbances, hyperacusis-type hearing impairment; later symptoms may include increased muscle tone on the healthy or affected side of the face, and synkinesis leading to post-paralytic hemispasm.

Bell's palsy is an idiopathic form of FNN.

Prosoparesis is a decrease in muscle strength on one half of the face.

Prosoplegia is the absence of movement in the muscles of one half of the face.

Hemifacial spasm (HFS) is a facial nerve disorder characterized by chronic, paroxysmal, painless, involuntary, unilateral tonic or clonic contractions of a group of facial muscles, including at rest and during sleep.

Facial myokymia is a facial nerve disorder characterized by spontaneous, recurrent, unilateral, self-limiting, low-amplitude, pulsating twitches in one of the facial muscles (most commonly the lower portion of the palpebral part of the orbicularis oculi muscle) lasting from a few seconds to a few hours, or less frequently up to a few weeks. These twitches are more noticeable to the patient than to others, may be exacerbated by voluntary movements, but are not initiated by them.

Stimulation electroneuromyography (SNEMG) is a functional diagnostics method that assesses the presence and severity of peripheral nerve damage.

M-wave amplitude is an EMG parameter that indirectly characterizes the number of fascicles in the motor nerve trunk capable of conducting nerve impulses.

Needle electromyography (EMG) is a functional diagnostics method that evaluates the bioelectrical activity of a muscle using a bipolar concentric needle electrode at rest or during voluntary contraction.

Motor unit potential (MUP) is an EMG parameter that characterizes the electrical activity of muscles during contraction.

Physical therapy (PT) is a group of rehabilitation methods characterized by the effect on the patient using physical exercises.

Biofeedback (BFB) is a rehabilitation method based on developing the patient's skills of self-control and self-regulation of various body functions to improve general well-being.

Surgical treatment is a method of treating diseases by dividing and uniting tissues during a surgical operation.

Level of evidence – the degree of confidence that the observed effect of a medical intervention is true.

Level of убедительности рекомендаций (Grade of Recommendation) is the degree of certainty in the validity of the intervention effect and that following the recommendations will bring more benefit than harm in a particular situation.

Working group means two or more people of the same or different professions working together and harmoniously to create clinical guidelines and bearing joint responsibility for the results of this work.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

1.1.1 Trigeminal nerve disorders

All trigeminal nerve lesions can be divided into four blocks (Figure 1):

Figure 1. Classification of trigeminal nerve lesions

1.1.1.1 Trigeminal neuralgia

Trigeminal neuralgia (TN) is a disorder characterized by recurrent unilateral brief episodes of pain, semiologically corresponding to electric shocks, sudden in onset and termination, with clear provocation by innocuous stimuli limited to one or more divisions of the trigeminal nerve. It may develop without apparent causes or be a consequence of another diagnosed disorder. In addition, concomitant continuous pain of moderate intensity may be present within the distribution of the affected trigeminal nerve branch(es) [1,2].

1.1.1.2. Atypical facial pain

Persistent atypical (idiopathic) facial pain includes the following conditions (Figure 2):

1. Persistent idiopathic facial pain;

2. Myofascial orofacial pain associated with muscle spasm;

3. Burning mouth syndrome.

Figure 2. Classification of atypical facial pain

Persistent idiopathic facial pain (PIFP) (previously classified as: "atypical odontalgia", "atypical facial pain") is a persistent facial pain with a variable clinical presentation, recurring daily for more than 2 hours per day for more than 3 months in the absence of clinically apparent neurological deficits or a preceding cause [3–8].

Comment: The International Classification of Orofacial Pain (ICOP) criteria define two types: persistent idiopathic facial pain and persistent idiopathic dentoalveolar pain. In both cases, the pain is constant, but with possible periodic exacerbations.

Myofascial orofacial pain associated with muscle spasm (MOFAMS) is pain caused by a sudden, involuntary, reversible tonic contraction of a muscle. Such a spasm can occur in any muscle involved in mastication. An acute malocclusion may develop [5].

Burning mouth syndrome (BMS) is an intraoral burning or dysesthetic sensation, recurring daily for more than 2 hours per day for more than 3 months without clinically evident signs of an underlying disease [5].

1.1.1.3. Other trigeminal nerve disorders, unspecified trigeminal nerve disorder

Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system [9,10].

Trigeminal neuropathic pain is facial pain in the area of one or more branches of the trigeminal nerve caused by another disorder and indicating nerve damage [5].

1.1.1.4. Trigeminal autonomic cephalalgias

Trigeminal autonomic cephalalgias (TACs) are a group of primary headache disorders. According to the International Classification of Headache Disorders, 3rd edition (ICHD-3), the following types of TACs are distinguished [1]:

• Cluster headache (episodic, chronic)

• Paroxysmal hemicrania (episodic, chronic)

• Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing, SUNCT syndrome (episodic, chronic)

• Short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms, SUNA syndrome (episodic, chronic)

• Hemicrania continua (remitting subtype, unremitting subtype)

• Probable trigeminal autonomic cephalalgias (probable cluster headache, probable paroxysmal hemicrania).

Cluster headache (CH) is a type of TAC characterized by unilateral, short-lasting attacks of excruciating, extremely severe pain localized in the orbital, suborbital, or temporal region, usually accompanied by ocular and nasal autonomic symptoms. The intensity of cluster headache is so high that it is also referred to as suicide headache.

Paroxysmal hemicrania is strictly unilateral pain in the orbital, suborbital, temporal region, or a combination of these regions, lasting from 2 to 30 minutes and occurring several or many times a day; attacks are usually accompanied by autonomic symptoms (conjunctival injection, lacrimation, nasal congestion, rhinorrhea, forehead and facial sweating, miosis, ptosis, and/or eyelid edema), responsive to indomethacin [1].

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT syndrome) are brief unilateral pain attacks localized in the orbital and periorbital region, always accompanied by conjunctival injection and lacrimation [1]. Unlike SUNCT, during an attack of short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA), one or none of the following is present: conjunctival injection and lacrimation [1].

Hemicrania continua (HC) is a rare type of primary headache disorder characterized by continuous unilateral moderate-intensity headache, with exacerbations of pain, cranial autonomic symptoms, and an absolute positive response to indomethacin [1].

1.1.2. Facial nerve disorders

Facial nerve lesion (peripheral type of impairment) is characterized predominantly by motor disorders (Figure 3). There are 2 groups of disorders: with deficit symptoms (FNP) and with irritation symptoms (involuntary movements).

Figure 3. Classification of facial nerve lesions

1.1.2.1. Facial nerve neuropathy

Facial nerve neuropathy (FNN) clinically presents with the acute development or progressive onset of facial asymmetry due to unilateral weakness of facial muscles (if movements are present – prosoparesis, if movements are absent – prosoplegia), impaired eye closure, and, depending on the level of the lesion, symptoms such as dry eye or lacrimation, taste disturbance, hyperacusis-type hearing impairment; at later stages, symptoms such as increased muscle tone of the healthy or affected side of the face, synkinesias up to the development of post-paralytic hemifacial spasm may develop [11–14].

Taking into account anatomical features, facial nerve lesion is possible at the following levels:

• cerebellopontine angle,

• internal acoustic meatus,

• bony canal proximal to the origin of the greater petrosal nerve,

• bony canal proximal to the origin of the stapedius nerve,

• level of exit through the stylomastoid foramen,

• parotid gland,

• individual branches penetrating the facial muscles.

1.1.2.2. Hemifacial spasm

Hemifacial spasm clinically manifests as chronic paroxysmal painless involuntary unilateral tonic or clonic contractions of a group of facial muscles, including at rest and during nighttime [15].

1.1.2.3. Facial myokymia

Facial myokymia clinically presents as spontaneous, periodically recurring, and lasting from several seconds to several hours, less frequently up to several weeks, unilateral self-limiting, low-amplitude, pulsating twitches in one of the facial muscles (most commonly the lower portion of the palpebral part of the orbicularis oculi muscle), which are more obvious to the patient than to others, may increase with voluntary movements, but are not initiated by them [16,17].

1.1.3. Disorders of other cranial nerves

Cranial neuropathy or cranial nerve neuropathy is defined as any damage to a cranial nerve at any level [18].

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

1.2.1 Trigeminal nerve disorders

1.2.1.1 Trigeminal neuralgia

Depending on the etiology, classical, idiopathic, and symptomatic trigeminal neuralgia are distinguished [2,19].

Classical (primary) TN occurs due to neurovascular conflict. Compression of the nerve by a vein or artery leads to focal demyelination at the transition zone between the central and peripheral myelin sheaths, which stimulates the generation of ectopic impulses and ephaptic transmission, clinically manifesting as shooting pains. Most commonly, compression of the cisternal portion of the nerve by the superior cerebellar artery is observed.

Symptomatic (secondary) TN occurs due to irritation of the nerve root against the background of an underlying disease (nerve compression by a tumor or arteriovenous malformation, demyelination in patients with multiple sclerosis, and other rare causes).

In patients with idiopathic TN, the cause is unknown.

1.2.1.2 Atypical facial pain

Persistent idiopathic facial pain is a polyetiological syndrome that includes a myogenic or iatrogenic source of peripheral sensitization in the facial region, deficiency of central pain-inhibitory systems, as well as the presence of comorbid emotional-affective disorders [20–26].

Myofascial orofacial pain associated with muscle spasm — muscle spasm can be defined as a persistent involuntary muscle contraction (excluding spasticity, which is a phenomenon of central nervous system origin). The main cause of pain in muscle spasm is muscle ischemia, leading to the release of algogens such as bradykinin, ATP, and H+, as well as the presence of comorbid emotional-affective disorders [23].

Burning mouth syndrome — recent neurophysiological, psychophysical, neuropathopathologic, and imaging studies have shown that several neuropathic mechanisms, mostly subclinical, are involved in the pathophysiology of BMS. Small-fiber changes in the tongue epithelium explain the thermal hypesthesia and elevated taste perception thresholds found on quantitative sensory testing. Functional MRI in patients with BMS demonstrated reduced brain activation to thermal stimuli. Nevertheless, it appears that the diagnosis of primary BMS encompasses at least three distinct subclinical types of neuropathic pain that may overlap in individual patients. The first subgroup (50–65%) is characterized by mucosal small-fiber neuropathy. The second subgroup (20–25%) consists of patients with subclinical pathology of the lingual nerve, the mandibular branch of the trigeminal nerve, or the entire trigeminal system, which can be detected by careful neurophysiological examination. The third subgroup (20–40%) corresponds to the concept of central pain, which may be associated with decreased activity of brain dopaminergic systems [6,27].

1.2.1.3. Other disorders of the trigeminal nerve, trigeminal nerve disorder, unspecified

Trigeminal neuropathic pain occurs after nerve trauma, herpes virus infection, and other factors. The etiology may also remain undetermined [5].

The pathogenesis of the disease is not fully understood. Damage to the structures of the somatosensory nervous system cannot be considered as the cause of neuropathic pain, but rather serves as a predisposing factor [28]. Peripheral and central mechanisms are distinguished in the formation of neuropathic pain [29].

Peripheral mechanisms:

1. Decrease in pain threshold, activation of nociceptors;

2. Appearance of spontaneous (ectopic) activity in primary sensory neurons in the absence of peripheral stimulus;

3. Impaired neurotransmitter production in the spinal ganglia (Gasserian ganglion).

Central mechanisms:

• Increased excitability of glutamate receptors (AMPA and NMDA subtypes) in the spinal cord and higher levels, or the "wind-up" phenomenon — enhanced response to incoming sensory stimuli;

• Increased spontaneous background activity of the spinal cord (impaired inhibitory activity);

• Increased activity in the brainstem and higher divisions.

The development of trigeminal postherpetic neuralgia is based on the reactivation of Herpes Zoster [30–32]. Following viral reactivation, complex changes occur in pain signaling pathways, leading to enhanced pain stimuli due to nociceptor sensitization, sensitivity to local inflammatory mediators, hyperexcitability of pain pathways, and impaired inhibitory control. Herpes Zoster replication can cause acute damage to sensory neurons, aggravating inflammatory tissue damage. In various cell and tissue types, Herpes Zoster directly or indirectly causes increased levels of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-2, IL-6, IL-17, IL-18, and tumor necrosis factor-alpha (TNF-α). The presence of viral proteins combined with immune responses initiates inflammation at the affected site and promotes pain and hypersensitivity.

1.2.1.4. Trigeminal autonomic cephalalgias

Cluster headache

Currently, CH is considered a multifactorial disorder caused by genetic predisposition and environmental factors (stress, alcohol, histamine, sleep disturbances, sleep apnea, testosterone levels). Among first-degree relatives, the risk of developing CH is 5–18 times higher than in the general population. The mechanism of CH attack development is not fully understood. Disruption of hypothalamic circadian activity plays a role in the pathogenesis of CH, contributing to the disinhibition of nociceptive and autonomic pathways and the activation of the trigeminal system, with the release of neuropeptides (CGRP, substance P) leading to pain syndrome. The trigeminovascular complex also activates the superior salivatory nucleus of the facial nerve, which accounts for the autonomic symptoms.

Paroxysmal hemicrania

The pathogenesis of PH is less studied than that of other primary headaches. The development of a PH attack is associated with an increase in the levels of calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide, which leads to the activation of the trigeminovascular complex and the autonomic nervous system. Functional MRI data indicate the involvement of the posterior hypothalamus in the formation of the attack.

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing

The etiology and pathogenesis of SUNCT and SUNA are poorly understood. According to functional MRI during a SUNCT/SUNA attack, the hypothalamic region is activated; the hypothalamic zone is functionally connected with the pain system as well as with the superior salivatory nucleus, which explains the pain syndrome and autonomic symptoms during the attack. Most cases are considered primary headaches, but the literature describes cases of SUNCT and SUNA in patients with lesions (tumor, demyelination, infarction, infection) in the posterior cranial fossa and pituitary region, which necessitates neuroimaging [1].

Hemicrania continua

The etiology of hemicrania continua involves the activation of the trigeminal system, with elevated levels of calcitonin gene-related peptide (CGRP), substance P, and vasoactive intestinal peptide.

1.2.2 Facial nerve disorders

1.2.2.1. Facial nerve neuropathy

Facial neuropathy depending on the cause can be idiopathic (Bell's palsy) and symptomatic, for example, infectious, otogenic, traumatic, etc. (Figure 4).

Figure 4. Classification of forms of facial neuropathy

Idiopathic form of facial neuropathy (Bell's palsy) is a diagnosis of exclusion [33], however, several hypotheses for the development of FN exist, the main ones being viral and autoimmune. According to the autoimmune hypothesis, Bell's palsy is a mononeuritic variant of Guillain-Barré syndrome, an acute inflammatory demyelinating disease. According to the viral hypothesis, Bell's palsy is associated with the reactivation of a latent viral infection (main pathogens being HSV-1, HSV-2, and VZV) triggered by stress, cold, another type of infection, etc. [34]. At the same time, Chang B. et al. (2020) detected 84 pathogens in 30 epineurium samples from patients with FN, among which only 4 were viral species, while 10 were fungal species and 70 were bacterial species [35].

The disease is associated with seasonality (autumn), weather conditions (temperature fluctuations), and comorbid background (diabetes mellitus) [36–39].

Symptomatic form of FN includes:

Ramsay Hunt syndrome — a variant of FN due to herpetic infection of the geniculate ganglion, characterized by unilateral facial weakness/paralysis accompanied by pain and skin rashes [37,38]. The disease in 50–85% of patients is more severe than classical Bell's palsy and is characterized by a high tendency to recur [40,41].

Melkersson-Rosenthal syndrome — a variant of FN, a genetic disorder characterized by recurrent unilateral facial weakness/paralysis combined with lip edema and fissured tongue [42].

«Other causes of facial nerve palsy» in 8–12% of cases are space-occupying lesions [43,44], such as facial nerve tumors (intra- and extracranial schwannomas / neuromas), cerebellopontine angle tumors, and parotid gland tumors. Frequent causes of facial nerve neuropathy (FNN) include complications of surgical, cosmetic, and dental interventions, traumatic brain injury, neurological disorders, infections, and metabolic disorders [45,46]. Less commonly, FNN develops as an early or late complication of radiosurgical treatment for vestibular schwannomas [47]. A high percentage of isolated FNN cases (34–56%) is observed in Lyme disease (borreliosis), which must be taken into account during differential diagnosis [48].

In clinical situations where the cause of FNN remains entirely unclear, the diagnosis of «unspecified facial nerve disorder» is established.

1.2.2.2. Hemifacial spasm

Hemifacial spasm, depending on the motor pattern, can be clonic, tonic, or clonic-tonic. In origin, it can be primary, occurring due to compression of the nerve root by a blood vessel (most commonly the anterior inferior cerebellar artery, less commonly the posterior inferior cerebellar artery, or a dystopic vertebral or basilar artery), or secondary (symptomatic)—resulting from compression of the facial nerve by a cerebellopontine angle or parotid gland tumor, vascular anomalies (arteriovenous malformations, intracranial arterial aneurysms, arteriovenous fistulas, angiomas), Chiari malformation and other structural anomalies of the posterior cranial fossa, middle ear and mastoid infections (otitis media, cholesteatoma), trauma, brainstem lesions (multiple sclerosis, stroke), following previous FNN (post-paralytic hemispasmodic syndrome), etc. HFS may also result from an idiopathic lower motor neuron lesion of the facial nerve (Figure 5) [15,49].

Figure 5. Classification of hemifacial spasm forms

The etiology of primary HFS involves chronic irritation of the facial nerve nucleus and/or its root. The root entry/exit zone is the transition site from oligodendroglia (central myelination) to Schwann cells (peripheral myelination). Compression of the root by blood vessels leads to axonal demyelination in this region and hyperexcitability of the facial nerve. Meanwhile, irritation of peripheral afferent fibers of the facial nerve leads to aberrant signal transmission to the central facial nerve nucleus, causing abnormal nuclear excitation and involuntary myoclonic contractions of the facial muscles on the affected side. In typical presentation, blood vessels compress the anterocaudal region of the nerve, whereas in atypical presentation, they compress the posterorostral region [50]. Precipitating factors that intensify spasms include cold, bright light, and stress.

Secondary hemifacial spasm differs in pathogenesis depending on the etiology. If the cause is a space-occupying lesion, facial nerve irritation occurs. One of the most complex in pathogenesis and insufficiently studied (with over 9 proposed theories of origin) is post-paralytic hemispasm.

Post-paralytic hemispasm is a secondary hemifacial spasm following prior FNN. It is known that idiopathic or non-traumatic symptomatic forms of FNN resolve in 60–70% of cases with complete or partial recovery of facial nerve function within 3–6 months [36,37,51,52], with more than 80% of these patients achieving recovery to House-Brackmann grade I–II [37]. In the remaining patients, consequences persist in the form of facial asymmetry and complications that may progress over time—such as hypertonus of mimic muscles up to contractures, synkinesias, and others. Pathological synkinesias are involuntary simultaneous contractions of one muscle group (или активация функции железы) in response to the voluntary contraction of another unrelated muscle group. Their development is based on mechanisms associated with the severity of facial nerve damage, such as aberrant regeneration, the "cross-talk" (vertical fibers) mechanism, ephaptic transmission, facial nerve nucleus reorganization, cerebral cortex reorganization, and "latent circuit activation." When designating synkinesias, the "triggering" muscle is indicated first, followed by the "responding" muscle. The most common are oculo-malar and oculo-oral synkinesias (more than 90% of all cases; forceful eye closure results in deepening of the nasolabial fold and twitching of the upper lip), oro-ocular synkinesias (59%; narrowing of the palpebral fissure when pouting the lips), the "crocodile tears" syndrome (lacrimation from the eye on the affected side during chewing), and others [53,54]. The combination of multiple synkinesias is referred to as post-paralytic hemispasm.

When performing reinnervation surgeries, associated movements may be caused by the involvement of the recipient nerve (hypoglossal, masseter, etc.), which is also referred to as post-paralytic hemispasm [55].

1.2.2.3. Facial myokymia

Facial myokymia, depending on the etiology, can be primary or secondary. Primary facial myokymia occurs as a result of physical or emotional overexertion, caffeine consumption, etc. In such cases, the condition is benign, is not a disease, and resolves spontaneously after eliminating the adverse factor [16]. In cases of a continuous course, diagnostic evaluation is required to identify the cause of secondary (symptomatic) facial myokymia. The symptom can be a side effect of medications (e.g., topiramate [56], gabapentin [57]), as well as an early sign of conditions such as multiple sclerosis [58], brainstem space-occupying lesions [16], vestibular schwannoma [59], and autoimmune diseases such as thyrotoxicosis.

1.2.3. Disorders of other cranial nerves

The pathogenesis of cranial neuropathy may be based on any damage to a cranial nerve due to compression, autoimmune inflammation, or leptomeningeal involvement of the cranial nerves resulting from an oncological or inflammatory process [18].

Based on etiology, glossopharyngeal neuralgia is classified into classical, secondary, and idiopathic. Thus, the following causes of the disease can be distinguished: for the classical etiology – neurovascular conflict (NVC); for the secondary etiology – an underlying disease (neck trauma, multiple sclerosis, tonsillar or regional tumors, cerebellopontine angle tumor, and Chiari malformation); and for the idiopathic etiology – neither NVC nor an underlying disease is diagnosed [1]. Glossopharyngeal neuropathy, including its painful form, is a secondary manifestation of another disease (e.g., trauma, tumor). Damage to the olfactory nerve, oculomotor nerves, and caudal group nerves is considered a manifestation of another disease (cerebrovascular accident, head and neck trauma, dural venous sinus thrombosis, inflammatory diseases of the paranasal sinuses, head and neck tumors, systemic and metabolic diseases, ocular and bulbar forms of myasthenia gravis, amyotrophic lateral sclerosis, vascular malformations).

1.3 Epidemiology of the Disease or Condition

1.3.1 Trigeminal nerve disorders

1.3.1.1 Trigeminal neuralgia

The prevalence of TN is 0.03–0.3% [60], and the disease most commonly develops in older age groups.

1.3.1.2 Atypical facial pain

Persistent idiopathic facial pain – the prevalence of persistent idiopathic facial pain is unknown. Observations [61] indicate that 60–70% of patients with this form of prosopalgia are middle-aged women. In specialized pain centers, patients with persistent idiopathic facial pain are encountered somewhat more frequently than patients with trigeminal neuralgia. A large epidemiological study [62] involving 34,242 patients treated by dentists showed that chronic facial pain is observed in 5.2%. Among patients with chronic facial pain, persistent idiopathic facial pain was noted in 5.8% of cases and was among the top three most frequent causes of chronic prosopalgia. Risk factors for developing persistent idiopathic facial pain include a history of widespread pain syndrome, genetic predisposition, female sex, and passive coping strategies [63].

Myofascial orofacial pain associated with muscle spasm: prevalence is unknown.

Burning mouth syndrome – a 1999 study showed that BMS is most frequently diagnosed in middle-aged women. Factors associated with BMS most commonly include subjective dry mouth, taste disturbances, depression, and anxiety [27].

1.3.1.3. Other disorders of the trigeminal nerve, trigeminal nerve disorder, unspecified

The prevalence of neuropathic pain ranges from 3% to 18% in the population. Risk factors include older age, female sex, unemployment, and low educational level [29].

The risk of developing trigeminal postherpetic neuralgia in patients with acute herpetic infection is 5–20%. The risk increases with age, approaching 30% in the patient group over 80 years of age [10,64,65].

1.3.1.4. Trigeminal autonomic cephalalgias

Cluster headache

Cluster headache is the most frequent type of headache among trigeminal autonomic cephalalgias; however, it is significantly less common than migraine. The prevalence of cluster headache is approximately 1 per 1,000 individuals. Cluster headache affects men more frequently, with a male-to-female ratio of 4.3:1. Disease onset typically occurs between the ages of 20 and 29 years, although it can begin at any age. In women, onset is more common after the age of 50.

Paroxysmal hemicrania

The prevalence of paroxysmal hemicrania is 1 per 50,000 population, making it significantly rarer than cluster headache (1–3% of the number of patients with cluster headache). Paroxysmal hemicrania is significantly more frequent in women. The female-to-male ratio for this condition is 7:1.

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing

SUNCT and SUNA are rare disorders with an incidence of 6.6 per 100,000 population [1].

Hemicrania continua

The true incidence of the disease remains unknown, although some authors consider hemicrania continua to be not so rare; approximately 200 cases of this condition have been described in the world literature over 30 years. There is a predominance of women, with a ratio of 1 man to 1.6 women for hemicrania continua [1].

1.3.2 Facial nerve disorders

1.3.2.1. Facial nerve neuropathy

According to a study based on data from the Unified Medical Information and Analytical System, the incidence of facial nerve neuropathy (Table 1) in Moscow for 2019 was determined across adult and child/adolescent age groups (number of initial cases per 100,000 population) [66]. Overall, the obtained data refine the statistics of the epidemiological indicators presented previously.

Table 1. Incidence of facial nerve neuropathy

Bell's palsy (idiopathic form) has an incidence of 8 to 32 cases per 100,000 population per year, occurring with equal frequency in men and women, predominantly between the ages of 40 and 60 [36–39]. The incidence of Bell's palsy in pregnant women is 0.05%, with 2/3 of these cases developing in the third trimester of pregnancy [67,68]. The average recurrence rate of facial nerve neuropathy is 6.5%, of which 66% achieve recovery; the side of recurrence does not affect recovery [69]. It should be noted that among all recurrent facial nerve neuropathies, ultimately only 77.4% are idiopathic, while the rest are symptomatic: Melkersson-Rosenthal syndrome (7.5%), neurosarcoidosis (3.7%), traumatic neuroma (1.9%), Ramsay Hunt syndrome (1.9%), granulomatosis with polyangiitis (1.9%), neoplastic processes (5.7%), facial nerve schwannoma (3.7%), and metastatic squamous cell carcinoma to the deep lobe of the parotid gland (1.9%) [42].

Ramsay Hunt syndrome accounts for approximately 12% of all forms of facial nerve neuropathy [70,71] and 1.9% of recurrent facial nerve neuropathies [42].

Melkersson-Rosenthal syndrome accounts for 0.8% of cases among all forms of facial nerve neuropathy [72] and 7.5% among recurrent facial nerve neuropathies [42]. Symptom onset occurs at 25–40 years of age, and it is twice as common in women.

Facial nerve schwannomas (neurinomas) — over 90% of these are intracranial tumors, while about 10% are extracranial tumors involving the peripheral portion of the facial nerve and located within the parotid salivary gland [73,74].

1.3.2.2. Hemifacial spasm

Hemifacial spasm (primary) has an incidence of 14.5 per 100,000 women and 7.4 per 100,000 men, with symptom onset at 40–79 years of age [75].

The incidence of secondary hemifacial spasm, including post-paralytic, has not been established. Pathological synkinesias develop in up to 55% of cases after idiopathic facial nerve neuropathy [54,76], and in 28.2% after reinnervation surgeries [77]. Some authors believe that synkinesias of varying severity develop in all patients with incomplete recovery. The average time to development of synkinesias is 4 months from the onset of facial nerve neuropathy. Risk factors for developing synkinesias in patients with non-traumatic facial nerve neuropathy include the idiopathic form or infectious etiology, severe grade of involvement, and nerve electrical stimulation [53].

1.3.2.3. Facial myokymia

Facial myokymia (primary) affects healthy young individuals, more frequently women; its incidence has not been established [17].

1.3.3. Disorders of other cranial nerves

The prevalence of glossopharyngeal neuralgia accounts for 1% of the prevalence of trigeminal neuralgia [78]. Glossopharyngeal neuralgia accounts for 0.2 to 1.3% of all types of cranial neuralgias [79,80].

The prevalence of other cranial nerve disorders (olfactory nerve, oculomotor and caudal cranial nerve groups) corresponds to the prevalence of the underlying conditions leading to involvement of these nerves.

1.4 Features of Coding the Disease or Condition

1.4.1 Trigeminal nerve disorders

1.4.1.1 Trigeminal neuralgia

G50.0 – Trigeminal neuralgia

G50.1 – Atypical facial pain

1.4.1.3. Other trigeminal nerve disorders, unspecified trigeminal nerve disorder

G50.8 – Other disorders of trigeminal nerve

G50.9 – Disorder of trigeminal nerve, unspecified

G53.0 (B02.20) – Postherpetic trigeminal neuralgia

1.4.1.4. Trigeminal autonomic cephalalgias

G44.0 (G50.8) – Cluster headache (episodic, chronic)

G50.8 – Paroxysmal hemicrania (episodic, chronic), SUNCT / SUNA (episodic, chronic), Hemicrania continua (remitting subtype, non-remitting subtype)

G90.0 – Probable trigeminal autonomic cephalalgias (probable cluster headache, probable paroxysmal hemicrania, idiopathic peripheral autonomic neuropathy)

1.4.2 Facial nerve disorders

G51.0 – Bell's palsy

G51.1 – Geniculate ganglionitis (Ramsay Hunt syndrome)

G51.2 – Melkersson-Rosenthal syndrome

G51.3 – Clonic hemifacial spasm

G51.4 – Facial myokymia

G51.8 – Other disorders of facial nerve

G51.9 – Facial nerve disorder, unspecified

1.4.3. Disorders of other cranial nerves

G52.0 – Disorders of olfactory nerve

G52.1 – Disorders of glossopharyngeal nerve

G52.3 – Disorders of hypoglossal nerve

G52.7 – Multiple cranial nerve disorders

G52.8 – Disorders of other specified cranial nerves

G52.9 – Cranial nerve disorder, unspecified

1.5 Classification of the disease or condition

1.5.1 Trigeminal nerve disorders

1.5.1.1 Trigeminal neuralgia

According to the International Classification of Orofacial Pain (ICOP) and the International Classification of Headache Disorders, trigeminal neuralgia is classified as follows [1,5]:

Classic trigeminal neuralgia,

Idiopathic trigeminal neuralgia,

Symptomatic trigeminal neuralgia.

In addition, type 1 and type 2 TN are distinguished according to the Burchiel classification [81]. Patients with type 1 TN experience only typical neuropathic paroxysms, whereas type 2 TN may also present with constant background pain in the innervation zone of the affected trigeminal branches.

1.5.1.2 Atypical facial pain

According to the International Classification of Orofacial Pain (ICOP), atypical (idiopathic) facial pain is classified as follows [5]:

1. Idiopathic orofacial pain

   • Burning mouth syndrome

   • Burning mouth syndrome without somatosensory changes

   • Burning mouth syndrome with somatosensory changes

   • Possible burning mouth syndrome

2. Persistent idiopathic facial pain

   • Persistent idiopathic facial pain without somatosensory changes

   • Persistent idiopathic facial pain with somatosensory changes

   • Possible persistent idiopathic facial pain

According to the International Classification of Headache Disorders (ICHD-3) [1]:

Painful cranial neuropathies and other facial pains

Burning mouth syndrome (BMS)

Persistent idiopathic facial pain (PIFP)

According to the International Classification of Orofacial Pain (ICOP) [5]:

Secondary myofascial orofacial pain

Myofascial orofacial pain associated with muscle spasm

Comments:

Persistent idiopathic facial pain without somatosensory changes – persistent facial pain with varying characteristics, recurring daily for more than 2 hours per day for more than 3 months, in the absence of clinically apparent neurological deficits or a preceding cause, not accompanied by somatosensory changes [5].

Persistent idiopathic facial pain with somatosensory changes – persistent facial pain with varying characteristics, recurring daily for more than 2 hours per day for more than 3 months, in the absence of clinically apparent neurological deficits or a preceding cause, accompanied by negative (hypoalgesia or hypesthesia) and/or positive (hyperalgesia or allodynia) somatosensory changes [5].

Possible persistent idiopathic facial pain – persistent facial pain with a varying clinical presentation, recurring daily for more than 2 hours per day for less than 3 months, in the absence of clinically apparent neurological deficits or preceding causes. After 3 months, the diagnosis is coded as persistent idiopathic facial pain (or one of its subtypes) [5].

Burning mouth syndrome without somatosensory changes – burning sensation or dysesthesia in the oral cavity, recurring daily for more than 2 hours per day for more than 3 months, without clinically apparent signs of an underlying disorder and without accompanying somatosensory changes [5].

Burning mouth syndrome with somatosensory changes – burning sensation or dysesthesia in the oral cavity, recurring daily for more than 2 hours per day for more than 3 months, without clinically apparent signs of an underlying disorder, and accompanied by negative and/or positive somatosensory changes [5].

Possible burning mouth syndrome – burning sensation or dysesthesia in the oral cavity, recurring daily for more than 2 hours per day for less than 3 months, without clinically apparent signs of an underlying disorder. After 3 months, the diagnosis is coded as burning mouth syndrome (or one of its subtypes) [5].

1.5.1.3. Other trigeminal nerve disorders, trigeminal nerve disorder, unspecified

Two classifications of trigeminal neuropathic pain are used. The diagnostic criteria and nosological structure do not contradict each other; there are minor differences in the naming of individual disorders.

I. International Classification of Orofacial Pain (ICOP) [5]:

Other trigeminal neuropathic pain:

• Trigeminal neuropathic pain associated with Herpes zoster

• Trigeminal postherpetic neuralgia

• Post-traumatic trigeminal neuropathic pain

  • Possible post-traumatic trigeminal neuropathic pain

• Trigeminal neuropathic pain associated with another disorder

  • Possible trigeminal neuropathic pain associated with another disorder

• Idiopathic trigeminal neuropathic pain

II. International Classification of Headache Disorders (ICHD-3) [1]:

Painful trigeminal neuropathy:

• Painful trigeminal neuropathy attributed to Herpes zoster infection

• Trigeminal postherpetic neuralgia

• Painful post-traumatic trigeminal neuropathy

• Painful trigeminal neuropathy attributed to other disorder

• Idiopathic painful trigeminal neuropathy

1.5.1.4. Trigeminal autonomic cephalalgias

Cluster headache

Episodic and chronic cluster headache are distinguished. The majority of patients (about 80%) suffer from episodic cluster headache

Episodic cluster headache – at least 2 cluster headache periods lasting from 7 days to 1 year per year, separated by a remission period of at least 3 months.

Chronic cluster headache – a type of cluster headache in which pain attacks persist for 1 year without remission or with remissions lasting less than 3 months.

Paroxysmal hemicrania

Episodic and chronic paroxysmal hemicrania (PH) are distinguished. In episodic PH, attacks occur for 7 days to 1 year, separated by a remission period of 1 month or more. In chronic PH, attacks last for more than 1 year without a remission period or with a remission period of less than 1 month. About 20% of patients suffer from episodic PH, and 80% suffer from chronic PH [1].

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing

Episodic and chronic SUNCT are distinguished [1].

In episodic SUNCT, attacks occur for a period of 7 days to a year, separated by a remission period of 3 months or more.

In chronic SUNCT, attacks occur for more than 1 year without remission, or the remission period lasts less than 3 months.

Episodic and chronic SUNA are distinguished.

Episodic SUNA: attacks occur for a period of 7 days to 1 year, separated by a remission period of 3 months or more.

Chronic SUNA: attacks occur for more than 1 year without remission, or the remission period lasts less than 3 months.

Hemicrania continua

The following subtypes of hemicrania continua are distinguished [1]:

Remitting (with a remission period of at least 1 day without treatment),

Non-remitting (without a remission period of at least 1 day without treatment).

1.5.2 Facial nerve disorders

Figure 6. Classification of facial nerve disorders according to ICD-10

1.5.2.1. Facial nerve neuropathy

Facial nerve neuropathy is divided into idiopathic (G51.0) and symptomatic forms (G51.1, G51.2, G51.8, G51.9) [82], as well as lesions of individual branches of the facial nerve (G51.8) (Figure 6).

1.5.2.2. Hemifacial spasm

Hemifacial spasm is divided into primary (G51.3), secondary (symptomatic), and idiopathic (Figure 6) [15].

1.5.2.3. Facial myokymia

Facial myokymia is divided into primary (G51.4) and secondary (Figure 6).

1.5.3. Disorders of other cranial nerves

According to the International Classification of Orofacial Pain (ICOP), glossopharyngeal nerve disorders are classified as follows [5]:

I. Glossopharyngeal neuralgia:

• Classical glossopharyngeal neuralgia;

• Idiopathic glossopharyngeal neuralgia;

• Secondary glossopharyngeal neuralgia.

II. Glossopharyngeal neuropathic pain:

• Glossopharyngeal neuropathic pain attributed to an established cause;

• Idiopathic glossopharyngeal neuropathic pain.

1.6 Clinical presentation of the disease or condition

1.6.1 Trigeminal nerve disorders

1.6.1.1 Trigeminal neuralgia

The diagnosis of TN is established clinically based on a detailed analysis of the pain syndrome. To establish the diagnosis, certain clinical criteria according to the International Classification of Headache Disorders must be met [1]. The diagnosis of TN can be established in the presence of recurring paroxysms of unilateral facial pain in the innervation area of one or more branches of the trigeminal nerve. The pain syndrome must exhibit the following semiological characteristics:

• duration from a fraction of a second to 2 minutes;

• severe intensity;

• pain is electric shock-like, shooting, stabbing, or sharp;

• presence of painless triggering (tactile, thermal, or dynamic) by stimulation of trigger points.

In rare cases, patients with a long history of pain syndrome show an increase in the duration of prosopalgia paroxysms to more than 2 minutes, primarily due to a serial pattern. In such situations, it is especially important to clarify the character of the pain and the presence of attacks triggered by dynamic, tactile, and thermal stimulation [1, 83]. Most patients report pain triggered by cold air, brushing teeth, washing, talking, or eating. During a standard neurological examination, this phenomenon may be elicited, although this is not always possible due to antalgic behavior.

Patients with TN should not exhibit sensory deficits during a neurological examination (with the exception of patients with symptomatic TN, who may show signs of trigeminal nerve irritation and damage) [1, 83, 84].

1.6.1.2 Atypical facial pain

Persistent idiopathic facial pain.

The main patient complaint is continuous pain, which may vary in intensity, but as a rule, does not occur in the form of attacks [5,85,86]. An important diagnostic criterion is the mismatch between the pain and the innervation zones of the trigeminal nerve branches. Most commonly, the pain is localized in the maxilla and may spread to the periorbital region, nose, cheek, temple, and mandible. In some patients, pain can spread to the head, neck, and even the arms. In some cases, pain is localized in a single tooth and is termed atypical odontalgia. Although pain persists throughout the day, it is typically absent at night; however, 50-70% of patients experience sleep disturbances [63]. In character, the pain is dull, deep, aching, and exhausting. Sometimes patients describe the pain as unbearable and agonizing, although in most cases the intensity is moderate, around 7 points on the VAS [3]. Unlike neuralgias, patients with persistent idiopathic facial pain do not experience attacks or lancinating pain, and trigger zones are absent. In some cases, patients note an intensification of pain that may resemble an attack; nevertheless, this does not exclude the diagnosis of persistent idiopathic facial pain. Pain exacerbation can be triggered by cold, psychological stress, as well as surgical and dental procedures [63]. Neurological examination reveals dysesthesia, paresthesia, or a subjective feeling of numbness in 60-75% of patients with persistent idiopathic facial pain, but objective sensory loss or other neurological symptoms are absent [4][86]. Quantitative sensory testing in patients with persistent idiopathic facial pain yields contradictory results: according to some researchers, it reveals no sensory impairments [87], while according to other authors, thermal hypoesthesia is detected in 45% and thermal allodynia in 10% [4]. Clinical somatosensory assessment using pinprick or light touch very rarely reveals mild somatosensory changes. A diagnosis of persistent idiopathic facial pain implies that quantitative sensory testing was not performed. If performed, one of two subtypes must be specified: Persistent idiopathic facial pain without somatosensory changes or Persistent idiopathic facial pain with somatosensory changes [5].

Myofascial orofacial pain associated with muscle spasm.

A sudden, involuntary, reversible tonic contraction of a muscle. The spasm can affect any masticatory muscle. It is characterized by a sudden onset of pain and limited jaw range of motion (in the case of jaw-closing muscle spasm, mouth opening is limited to <40 mm; for the lateral pterygoid muscle, ipsilateral movement is limited to <7 mm). Sometimes the patient describes a stepwise change in pain intensity [88].

Burning mouth syndrome.

An intense, chronic sensation of pain in the oral cavity. It is characterized by spontaneous burning pain occurring in the area of a visually normal oral mucosa, with normal clinical examination results and the absence of any identifiable local dental pathology. The pain is constant, its intensity varies from moderate to severe, often decreasing in the morning and increasing towards the evening, but only rarely disrupting sleep. Most commonly, the pain is localized in the tongue, but it can be felt anywhere on the mucosa. The pain is usually bilateral, although rarely it may occur unilaterally, and it does not correspond to the innervation zones of peripheral nerves. In addition, patients frequently complain of taste alterations or dry mouth despite normal salivation [7][6].

1.6.1.3. Other trigeminal nerve disorders, trigeminal nerve disorder, unspecified

The clinical presentation of neuropathic pain includes the following sensory symptoms [28].

I. Negative symptoms (hypoesthesia, anesthesia);

II. Positive symptoms (hyperalgesia, allodynia, hyperpathia, spontaneous pain or paresthesia).

Allodynia is one of the main positive symptoms of neuropathic pain, representing the occurrence of a pain sensation in response to a non-painful stimulus [28]. The following types of allodynia are distinguished [28]:

• Mechanical (tactile) – occurs in response to mechanical stimuli – palpation, brush stroke;

• Thermal – occurs in response to cold or warm stimuli;

• Kinesigenic (movement-induced) – occurs in response to movement.

Neuropathic pain may be spontaneous (stimulus-independent) and/or induced (evoked, stimulus-dependent). Spontaneous pain may be superficial in the skin or deep. The duration of pain is prolonged or constant, sometimes paroxysmal. Constant superficial pain is usually stabbing, burning, cutting, or stinging in character; deep pain is spasmodic, dull, throbbing, or constricting. Paroxysmal pain is described as shooting, twitching, piercing, or like an electric shock. The intensity of neuropathic pain ranges from mild to excruciating [28].

Depending on the ongoing pathophysiological processes, various manifestations of neuropathy may predominate in the clinical picture (Table 3).

Table 3. Clinical symptoms and their underlying pathophysiological mechanisms [28].

Patients with trigeminal postherpetic neuralgia report pain with various characteristics, including deep, burning, continuous or paroxysmal, stabbing, or even diffusely piercing pain [89,90]. The pain is combined with paresthesia, dysesthesia, hyperalgesia, and pruritus. Chronic postherpetic neuralgia can have various phenotypes, for example, meeting the criteria for hemicrania continua or SUNCT, which can complicate diagnosis. Most patients with postherpetic neuralgia experience sensory loss and allodynia, although in rare cases thermal hyperalgesia and/or paresthesias may be observed. In addition, severe painless itching at the site of the rash is frequently reported.

1.6.1.4. Trigeminal autonomic cephalalgias

Cluster headache

Patients with cluster headache suffer from unilateral high- or very-high-intensity headache localized in the orbital, infraorbital, and temporal regions. A cluster headache attack most frequently occurs at night; due to the high intensity of the pain, the patient experiences motor restlessness and cannot find a place to stay, which distinguishes a cluster headache attack from a migraine attack. The pain is unilateral; in very rare cases, the pain can be bilateral. In a third of patients, the pain side can change from one attack to another; in the remaining patients, the pain side does not change. The duration of an attack ranges from 15 to 180 minutes.

During an attack, the following autonomic symptoms may occur:

• lacrimation (91%);

• conjunctival injection (77%);

• nasal congestion (75%);

• ptosis;

• eyelid edema;

• rhinorrhea;

• forehead and facial sweating;

• miosis;

• facial flushing.

Autonomic symptoms resolve after the end of the cluster headache attack, but ptosis and miosis may persist outside the attack. Episodic and chronic cluster headache (see classification) can transform into one another, with transformation from chronic to episodic cluster headache being more common (30%).

Triggers for a cluster headache attack can include alcohol, vasodilators, sleep deprivation, pressure changes (air travel, scuba diving), weather changes, and certain odors.

Paroxysmal hemicrania

Patients suffer from high-intensity headache localized in the orbital region and accompanied by autonomic symptoms lasting from 2 to 30 minutes. Short-lasting unilateral neuralgiform headache attacks occur throughout the day, which also helps differentiate them from cluster headache. Most short-lasting unilateral neuralgiform headache attacks occur spontaneously, about 10% of patients report the attack being triggered by neck movement, 7% by alcohol intake, and an even smaller number of patients note the onset of an attack against the background of stress or physical exercise [1].

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing

Patients suffer from short attacks of unilateral pain in the orbital and periorbital region, within the innervation zone of the 1st branch of the trigeminal nerve, ranging from moderate to high intensity, burning, stabbing in character, or presenting as an electric shock sensation lasting from several seconds to minutes. Touching the skin can frequently act as an attack trigger.

SUNA attacks are more frequently localized to the temple and the V2 and V3 trigeminal nerve innervation areas. Autonomic symptoms commonly include lacrimation, nasal congestion, and rhinorrhea. Compared to SUNCT, spontaneous attacks are more common in SUNA. Another typical feature of SUNA is the absence of a refractory period, which distinguishes it from trigeminal neuralgia [1].

Hemicrania continua

Hemicrania continua is typically characterized by a unilateral headache localized in the temporal (82%), orbital (67%), frontal (64%), retroorbital (59%), or occipital (64%) regions. The pain is of moderate intensity with periodic exacerbations [1].

1.6.2 Facial nerve disorders

1.6.2.1. Facial nerve neuropathy

The clinical presentation of facial nerve disorders is varied and depends on the lesion level and severity. Motor disorders are always present, manifesting as nerve deficit or irritation symptoms, which can be primary or secondary, and of varying degrees of severity.

Facial neuropathy is characterized by deficit symptoms: unilateral prosoparesis (decreased muscle strength) or prosoplegia (absence of movement) of the facial muscles. Depending on the lesion level, in addition to motor impairments (prosoparesis/prosoplegia), additional symptoms are identified to help determine the lesion level (Table 4).

Table 4. Additional symptoms of facial neuropathy according to the lesion level

The diagnosis of facial neuropathy must be based on a comprehensive assessment of clinical examination results (including history taking and complaints), MRI, and ENMG [91,92].

Bell's palsy (the idiopathic form of facial neuropathy) develops quite rapidly (within 24–48 hours), unlike facial neuropathy caused by a space-occupying lesion, for example. The maximum development time for symptoms in Bell's palsy is 72 hours [34]. Weakness limited to the lower group of facial muscles on one side may indicate a central lesion level [33,93] or involvement of individual branches [94]. In 6.5% of cases, Bell's palsy may recur [69]. However, a history of facial neuropathy casts doubt on the idiopathic etiology [42]. Hearing impairment in the form of increased sensitivity to sounds (hyperacusis), taste disturbance, or dry mouth characterizes a peripheral lesion level, specifically above the origin of the stapedius muscle [91]. Facial neuropathy should not be accompanied by ipsilateral hearing loss; a space-occupying lesion should be suspected [95,96]. Ear pain or retroauricular pain prior to or at the onset of asymmetry may be a symptom of idiopathic facial neuropathy [91,97] or a sign of an otogenic process.

Critical clinical symptoms ("red flags") indicating the need for further investigations and consultations in facial neuropathy:

• symptoms progressing for more than 72 hours,

• fluctuation in facial muscle paresis severity,

• weakness limited to the lower group of facial muscles on one side,

• history of facial muscle weakness episode,

• involvement of facial muscles on both sides,

• hearing loss,

• dizziness,

• presence of other neurological symptoms.

Idiopathic or non-traumatic symptomatic forms of facial neuropathy result in complete or partial recovery of facial nerve function within 3–6 months in 60–70% of cases [36,37,51,52]; however, due to the frequent development of complications, it should be considered a progressive disease requiring monitoring.

Unilateral prosoparesis or prosoplegia provokes increased tone in the muscles of the healthy side, leading to a shift in the facial midline [82,98,99]. Facial muscle hypertonus develops as early as the 7th day of the disease on the healthy side of the face in an average of 67% of patients, and in the absence of timely treatment – in over 90% of patients with incomplete facial nerve recovery or its absence [82]. Stretching of the weakened muscles on the affected side occurs, hindering the recovery of their function. In severe innervation impairment, muscle atrophy develops [100]. If nerve function begins to recover, an increase in muscle strength is accompanied by an increase in muscle tone on the affected side of the face, including the development of a pain syndrome [82,97]. Additionally, between 4 months and a year, their excessive activity appears – synkinesias [82,101].

Lagophthalmos — incomplete eyelid closure due to weakness of the orbicularis oculi muscle — occurs in 3/4 of patients of varying degrees of severity [102]. Upper eyelid malposition (retraction) and/or lower eyelid malposition (ectropion) may occur. Incomplete eyelid closure leads to xerosis of the anterior segment of the eyeball and its complications: keratitis, ulcer [82].

Primary motor impairments of facial neuropathy are:

• decreased muscle strength on the affected side;

• decreased muscle tone on the affected side;

• lagophthalmos.

Secondary motor impairments of facial neuropathy are:

• hypertonus or contractures of the facial muscles on the healthy or affected side;

• muscle atrophy on the affected side;

• synkinesias progressing to post-paralytic hemispasm of the affected side [82].

Risk factors for the development of contractures and synkinesias include:

1. severe nerve damage (clinically — prosoplegia, instrumentally — facial nerve involvement greater than 90% according to ENMG data)

2. active muscle stimulation (therapeutic exercise at maximum active movement amplitude, electrical stimulation) [82]. The success of recovery in facial neuropathy depends on identifying the risks of developing complications and implementing their prevention [82].

Isolated lesion of the marginal mandibular branch of the facial nerve

Acute onset of smile asymmetry may be associated with involvement of just a single branch of the facial nerve, which outwardly also manifests as unilateral decreased muscle strength in the lower half of the face, and is therefore mistakenly interpreted as a central lesion. An isolated lesion of the marginal mandibular branch of the facial nerve is common after dental interventions, cosmetic procedures, head and neck surgeries, trauma to the facial skeleton and adjacent soft tissues (exact statistics are unknown). The branch innervates the depressor anguli oris and mentalis muscles [94].

The standard neurological examination protocol detects muscle weakness but does not differentiate weakness of a specific muscle. A detailed clinical protocol with step-by-step testing of all facial muscles allows for the detection of pronounced smile asymmetry during the test when the patient is asked to say "Ee-Ee" [94].

1.6.2.2. Hemifacial spasm

Hemifacial spasm is characterized by motor symptoms of irritation — spontaneous unilateral clonic and/or tonic spasms of the facial muscles, i.e., a monosymptomatic paroxysmal hyperkinetic disorder. However, muscle spasm may be accompanied by clicking sounds in the ear (caused by contractions of the stapedius muscle) or neuropathic pain with features of trigeminal neuralgia [15]. The attack occurs at rest, sometimes even during sleep.

In a typical course of the disease, the spasm begins with rare contractions of the orbicularis oculi muscle, gradually progressing to involve the entire half of the face with closure of the palpebral fissure.

In an atypical course — the spasm begins with contractions of the cheek muscles, then spreads upward across the face [50].

With a prolonged disease course, facial muscle weakness (symptomatic facial neuropathy) may develop due to prolonged subclinical damage to the distal part of the facial nerve along with its hyperexcitability in the proximal sections [15]. Bilateral hemifacial spasm may occur, but accounts for less than 5% of cases.

1.6.2.3. Facial myokymia

Facial myokymia manifests as spontaneous, periodic, unilateral, self-limiting, low-amplitude, pulsating twitches in one of the facial muscles (most commonly the lower portion of the palpebral part of the orbicularis oculi muscle) lasting from a few seconds to a few hours, rarely up to a few weeks. These are more apparent to the patient than to others, are enhanced by voluntary movements, but are not initiated by them [17,59].

"Red flags" in facial myokymia:

• twitches also in other facial muscles and/or body parts,

• bilateral process,

• eye opens with difficulty,

• drooping eyelid,

• redness or swelling of the eyelid,

• pain,

• symptoms do not resolve within several weeks.

• presence of other neurological symptoms [17].

Differential diagnosis of involuntary facial movements is performed clinically based on complaints, medical history, and examination, distinguishing between facial myokymia, blepharospasm, facial paraspasm, synkinesia, tics, and epileptic seizures (Table 5). If somatic pathology, poisoning, or organic brain pathology is suspected, laboratory and instrumental diagnostics are required.

Table 5. Differential diagnosis of involuntary facial movements

1.6.3. Disorders of other cranial nerves

The diagnosis is established clinically based on a neurological examination.

Symptoms of olfactory nerve lesion include decreased sense of smell (hyposmia), absence of sense of smell (anosmia), and heightened sense of smell (hyperosmia) [103].

Lesions of the oculomotor group of cranial nerves (oculomotor, trochlear, and abducens) include motor and autonomic manifestations: upper eyelid ptosis, divergent or convergent strabismus, diplopia, changes in pupil size on the affected side, impaired convergence and accommodation, and impaired conjugate movements of the eyeballs in any direction [103].

Glossopharyngeal nerve lesions include neuralgia and neuropathy. Glossopharyngeal neuralgia presents as paroxysmal, electric shock-like pain in the posterior part of the tongue, tonsil, pharynx, or angle of the lower jaw and/or ear, as well as in the auricular and pharyngeal branches of the vagus nerve. Glossopharyngeal neuropathy includes taste disorders in the posterior third of the tongue and decreased sensitivity in the upper half of the pharynx. Painful glossopharyngeal neuropathy manifests as constant or near-constant pain in the innervation area of the glossopharyngeal nerve, with or without short paroxysms [1].

Vagus nerve lesions are rarely isolated, more often occurring together with other cranial nerves of the caudal group. Lesions of the peripheral motor fibers of the vagus nerve lead to paresis of the pharyngeal and vocal cord muscles, manifested by swallowing disorders (dysphagia), hoarseness (dysphonia), and speech slur (dysarthria). Manifestations of impaired cardiac innervation by the vagus nerve include changes in heart rate (tachy- and bradycardia), with symptoms being mild in unilateral lesions. In bilateral vagus nerve lesions, respiratory rhythm disturbances are also noted.

Accessory nerve lesions result in head deviation toward the affected side, while head rotation toward the healthy side is sharply limited and shoulder elevation is impaired. Long-term accessory nerve lesion leads to atrophy of the sternocleidomastoid and trapezius muscles. In bilateral lesions, the head is tilted back, and head rotation is impossible. Irritation of the accessory nerve causes tonic spasms of the muscles innervated by the accessory nerve [103].

Peripheral hypoglossal nerve lesions result in paresis of the ipsilateral half of the tongue; persistent impairment leads to atrophy of the muscles of half of the tongue and fibrillary twitching (in nuclear lesions). When protruded, the tongue deviates toward the affected muscle. Bilateral hypoglossal nerve lesions cause tongue paresis (glossoplegia), rendering the tongue immobile, speech slurred (dysarthria), or absent (anarthria). In central hypoglossal nerve lesions, the tongue deviates to the side opposite to the lesion focus upon protrusion [103].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Trigeminal nerve lesions

Trigeminal neuralgia

Diagnosis of TN is based on the evaluation of clinical presentation (Appendix B1) [1]. The presence of neurovascular conflict according to brain MRI is not a basis for diagnosing classic TN.

Atypical facial pain

Diagnostic criteria for persistent idiopathic facial pain [5]:

1. Persistent idiopathic facial pain

   A. Facial pain meeting criteria B and C.

   B. Recurs daily for more than 2 hours per day for more than 3 months

   C. Pain has all of the following characteristics:

   1) poorly localized and does not follow the innervation zone of a peripheral nerve

   2) dull, aching, or nagging

   D. Clinical or imaging evaluation reveals no pathology, and local causes have been excluded

   E. Not better accounted for by another ICD-11 or ICHD-3 diagnosis

2. Persistent idiopathic facial pain without somatosensory changes

   A. Facial pain meeting the criteria for persistent idiopathic facial pain.

   B. Qualitative or quantitative testing reveals no somatosensory changes.

3. Persistent idiopathic facial pain with somatosensory changes

   A. Facial pain meeting the criteria for persistent idiopathic facial pain.

   B. Qualitative or quantitative testing reveals somatosensory changes.

4. Possible persistent idiopathic facial pain

Facial pain meeting the criteria for persistent idiopathic facial pain, except that it has lasted for less than 3 months

Comments: The diagnosis of "persistent idiopathic facial pain" implies that quantitative sensory testing was not performed. If performed, one of two subtypes must be specified: persistent idiopathic facial pain without somatosensory changes or persistent idiopathic facial pain with somatosensory changes.

Diagnostic criteria for orofacial pain associated with muscle spasm [5]:

A. Myofascial pain meeting the criteria for secondary myofascial orofacial pain and criterion C below.

B. Muscle spasm diagnosed in one or more masticatory muscles.

C. At least two of the following characteristics demonstrating a causal relationship:

1) myofascial pain develops in close temporal association with the onset of the spasm;

2) myofascial pain significantly worsens in parallel with the progression of the spasm;

3) myofascial pain is significantly relieved or

ceases in parallel with the relief or resolution of the spasm.

D. Not better accounted for by another ICOAP diagnosis.

Comments:

Diagnostic criteria for secondary myofascial orofacial pain:

A. Myofascial pain in any masticatory muscle meeting criteria C and D.

B. A condition known to be able to cause

myofascial pain has been diagnosed

C. Myofascial pain meets both of the following

characteristics:

1) occurs in the jaw, temple, ear and/or in front of the ear, meeting

both of the following criteria:

a) confirmed by examination in the affected muscles or tendons;

b) elicited by palpation of the affected muscle or tendon

and/or maximum passive or active mouth opening

2) triggered by mandibular movement, function, or parafunction (e.g., teeth grinding or clenching).

D. A causal relationship with the underlying disorder is established.

Diagnostic criteria for burning mouth syndrome [5]:

A. Oral pain fulfilling criteria B and C.

B. Recurs daily for more than 2 hours per day for more than 3 months

C. Pain has all of the following characteristics:

1) burning character;

2) perceived superficially in the oral mucosa.

D. The oral mucosa has a normal appearance,

and local or systemic causes have been excluded.

E. Not better accounted for by another ICD-11 or ICHD-3 diagnosis

Other disorders of trigeminal nerve, trigeminal nerve disorder, unspecified

The diagnosis of trigeminal neuropathic pain is based on clinical manifestations of neuropathic pain, documented history of trigeminal nerve injury, and, when necessary, laboratory or instrumental confirmation.

Table 6. Diagnostic criteria for specific forms of trigeminal neuropathic pain [5]. Trigeminal neuropathic pain associated with Herpes zoster.

Comment: In rare cases, pain occurs without herpetic rash (zoster sine herpete). The diagnosis in such cases is confirmed by the detection of Varicella zoster virus DNA in the cerebrospinal fluid using polymerase chain reaction.

Table 7. Diagnostic criteria for specific forms of trigeminal neuropathic pain [5]. Trigeminal post-herpetic neuralgia (previously used term: post-herpetic trigeminal neuropathy).

Note 1: pain usually develops while active rashes persist, but sometimes also after they have healed. In such cases, pale or light purple scars may remain as sequelae of the herpetic eruptions.

Table 8. Diagnostic criteria for specific forms of trigeminal neuropathic pain [5]. Post-traumatic trigeminal neuropathic pain (previously used terms: anaesthesia dolorosa, painful post-traumatic trigeminal neuropathy).

Notes:

1. This includes intraoperative or neuroimaging confirmation of compression or other trigeminal nerve lesion, nerve conduction studies, evoked potentials, or skin biopsy data confirming reduced nerve terminal density, as well as corneal reflex assessment. Such studies are essential for determining the cause of pain, but must always be evaluated in conjunction with clinical findings.

2. The degree of nerve injury may range from mild to severe and may be associated with direct trauma or iatrogenesis related to dental treatment: local anesthetic injections, root canal treatment, tooth extraction, and other oral surgical procedures.

3. In cases of radiation injury to postganglionic fibers, pain may occur more than 3 months after exposure.

4. Somatosensory (neurosensory) symptoms may be negative (e.g., hypoesthesia and/or hypoalgesia) and/or positive (e.g., hyperalgesia and/or allodynia). Note that positive somatosensory symptoms are not specific to neuropathy. The presence of negative or positive somatosensory symptoms in the area of pain serves as a reliable sign of trigeminal nerve lesion. The clinical examination is supplemented by laboratory tests such as quantitative sensory testing.

Comment: the diagnosis of Possible post-traumatic trigeminal neuropathic pain is made based on the diagnostic criteria for Post-traumatic trigeminal neuropathic pain without criterion B2.

Table 9. Diagnostic criteria for specific forms of trigeminal neuropathic pain [5]. Trigeminal neuropathic pain associated with another disorder.

Note:

1. Somatosensory symptoms may be negative (e.g., hypoesthesia and/or hypoalgesia) and/or positive (e.g., hyperalgesia and/or allodynia).

Comment: the diagnosis of Possible trigeminal neuropathic pain associated with another disorder does not meet the criteria for Trigeminal neuropathic pain associated with another disorder.

Table 10. Diagnostic criteria for specific forms of trigeminal neuropathic pain [5]. Idiopathic trigeminal neuropathic pain.

Note:

1. Somatosensory symptoms may be negative (e.g., hypoesthesia and/or hypoalgesia) and/or positive (e.g., hyperalgesia and/or allodynia).

Trigeminal autonomic cephalalgias

Diagnosis is based on characteristic complaints and patient history (Appendix B4, Appendix B5). The criteria of the International Classification of Headache Disorders, 3rd edition (ICHD-3) are used to establish the diagnosis [1].

Cluster headache

Diagnosis of cluster headache [1]:

A. At least 5 attacks fulfilling criteria B–D

B. Severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 min (untreated)

C. One or both of the following:

1. At least one of the following symptoms or signs on the side of the headache:

   a. conjunctival injection and/or lacrimation;

   b. nasal congestion and/or rhinorrhea;

   c. eyelid edema;

   d. forehead and facial sweating;

   e. miosis and/or ptosis.

2. Feeling of restlessness or agitation

D. Occurs with a frequency ranging from 1 every 2 days to 8 attacks per day.

C. Not better accounted for by another ICHD-3 diagnosis.

Outside of attacks, physical examination is typically unremarkable, though some patients may exhibit persistent ptosis and miosis.

Paroxysmal hemicrania

The following criteria from the International Classification of Headache Disorders, 3rd edition (ICHD-3) are used for the diagnosis:

A. At least 20 attacks fulfilling criteria B–E

B. Severe unilateral orbital, supraorbital, and/or temporal pain lasting from 2 to 30 minutes

C. One or both of the following:

1. At least one of the following symptoms or signs on the side of the headache:

   a. conjunctival injection and/or lacrimation;

   b. nasal congestion and/or rhinorrhea;

   c. eyelid edema;

   d. forehead and facial sweating;

   e. miosis and/or ptosis.

2. Feeling of restlessness or agitation

D. Occurs with a frequency of > 5 attacks per day.

E. Absolute prevention by therapeutic doses of indomethacin.

F. Not better accounted for by another ICHD-3 diagnosis [1].

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing

Brief diagnostics for Short-lasting Unilateral Neuralgiform Headache attacks with Conjunctival injection and Tearing (SUNCT syndrome) [1]:

A. At least 20 attacks fulfilling criteria B–D

B. Moderate or severe unilateral headache in the orbital, suborbital, temporal region and/or other trigeminal distribution, lasting from 1 to 600 seconds as a single stab, a series of stabs, or having a sawtooth pattern [1].

C. At least one of the following autonomic symptoms or signs ipsilateral to the headache:

a. conjunctival injection and/or lacrimation;

b. nasal congestion and/or rhinorrhea;

c. eyelid edema;

d. forehead and facial sweating;

e. miosis and/or ptosis.

D. Occurs with a frequency of at least once a day.

C. Not better accounted for by another diagnosis from the International Classification of Headache Disorders, 3rd edition (ICHD-3) [1].

Diagnosis of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing – SUNA syndrome [1]:

A. Short-lasting unilateral neuralgiform headache attacks fulfilling the criteria for chronic or episodic SUNA (see item 1 or 2 below):

1. Episodic SUNA: attacks occur in periods ranging from 7 days to 1 year, separated by remission periods of 3 months or longer.

2. Chronic SUNA: attacks occur for more than 1 year without remission, or with remission periods lasting less than 3 months.

B. Not more than one of the following ipsilateral to the pain:

1. conjunctival injection

2. lacrimation

Hemicrania continua

Diagnosis of hemicrania continua [1]:

A. Unilateral headache fulfilling criteria B–D

B. Present for > 3 months with exacerbations of moderate to high intensity.

C. One or both of the following:

1. At least one of the following symptoms or signs on the side of the headache:

   a. conjunctival injection and/or lacrimation;

   b. nasal congestion and/or rhinorrhea;

   c. eyelid edema;

   d. forehead and facial sweating;

   e. hyperemia, burning sensation in the forehead and facial region

   f. feeling of fullness in the ear

   e. miosis and/or ptosis.

2. Feeling of restlessness or agitation

D. Absolute efficacy of therapeutic doses of indomethacin.

C. Not better accounted for by another diagnosis from the International Classification of Headache Disorders, 3rd edition (ICHD-3)

Facial nerve disorders

Generally accepted clinical and instrumental diagnostic criteria for facial nerve disorders have not been established. The diagnosis is made based on characteristic complaints, medical history, physical examination, and instrumental findings.

In facial neuropathy, the diagnostic goal is to determine the level of the facial nerve lesion and the cause (etiology), assess the severity, and predict the recovery dynamics.

Disorders of other cranial nerves

The diagnosis of TN is clinical and based on the characteristics of the pain syndrome (Appendix B3) [1,79]. The presence of neurovascular conflict on brain MRI is not a basis for the diagnosis of classical TN.

Diagnosis of olfactory nerve, oculomotor, and caudal group nerve disorders is based on patient complaints and neurological examination findings, and involves identifying the underlying disease that caused the lesion of the specified cranial nerves (see the etiology section).

2.1 Complaints and Anamnesis

2.1.1. Trigeminal nerve disorders

2.1.1.1. Trigeminal neuralgia

Complaints and medical history are described in the section "Clinical Presentation".

2.1.1.2. Atypical facial pain

Complaints and medical history are described in the section "Clinical Presentation".

When taking the medical history, it is important to pay attention to "red flags" that may indicate a secondary etiology [104,105]:

• Sudden onset of pain.

• Fever, rash, meningeal signs.

• Pain aggravated by changes in body position, physical activity, coughing, or sneezing.

• Progressive nature of the pain.

• Pain resistant to adequately prescribed therapy.

• Pain first occurring at an age over 50 years.

• Changes in neurological status.

• Unexplained weight loss, hyperhidrosis.

• History of cancer.

• History of immunodeficiency state, history of long-term glucocorticosteroid use.

Comment: The International Classification of Orofacial Pain, approved by the International Headache Society and the International Association for the Study of Pain, is the primary diagnostic tool for any forms of headache and facial pain (Appendix B2).

2.1.1.3. Other trigeminal nerve disorders, unspecified trigeminal nerve disorder

Complaints are described in the "clinical presentation" section.

Medical history is described in the "disease etiology" section.

Comments:

1. Confirmation of the neuropathic nature of pain is carried out using questionnaires that have undergone Russian-language linguistic adaptation and validation – DN-4, painDETECT, the Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale (LANSS).

2. Depending on the damaging factor, a specific form of trigeminal neuropathic pain should be determined in accordance with the diagnostic criteria of the latest version of the International Classification of Orofacial Pain or the International Classification of Headache Disorders (tables 6-10).

2.1.1.4. Trigeminal autonomic cephalalgias

Complaints and medical history are described in the "clinical presentation" section.

2.1.2. Facial nerve disorders

2.1.2.1. Facial nerve neuropathy

Complaints and medical history are described in the "Clinical presentation" section. Features of taking complaints and medical history:

Comments: It is necessary to clarify the duration of the disease and the rate of its development, the sequence of symptom onset, the presence of motor disorders in the form of weakness of the upper and lower groups of facial muscles on one half of the face, hearing impairment in the form of hyperacusis, taste disorders or dry mouth, ear pain or pain in the retroauricular region shortly before or at the time of asymmetry development; a history of trauma, surgeries, cosmetic procedures, or dental interventions; the presence of other diseases (hypertension, diabetes mellitus), including neurological ones; pregnancy; elevated body temperature; enlarged lymph nodes; redness or swelling of the head and neck tissues; rashes on the skin of the face, parotid region, or inside the auricle; and travel to endemic regions (tick-borne encephalitis) within a month prior to symptom onset.

2.1.2.2. Hemifacial spasm

Complaints and medical history are described in the section "Clinical Presentation".

2.1.2.3. Facial myokymia

Complaints and medical history are described in the section "Clinical Presentation".

2.1.3. Disorders of other cranial nerves

Complaints and medical history are described in the "Clinical presentation" section.

2.2 Physical Examination

2.2.1. Trigeminal nerve disorders

2.2.1.1. Trigeminal neuralgia

2.2.1.2. Atypical facial pain

Clinical diagnostics of all forms of atypical facial pain includes a neurological examination, as well as an assessment of somatic and local status.

Comments: When examining the neurological status, 60–75% of patients with persistent idiopathic facial pain (PIFP) may present with dysesthesia, paresthesia, and a subjective sensation of numbness, whereas objective sensory loss or other neurological symptoms are absent [4,86]. In burning mouth syndrome (BMS) and myofascial orofacial pain associated with muscle spasm, the neurological examination is likewise unremarkable. A comprehensive examination of the patient's head and neck region is recommended. Visual inspection of the head and neck should focus on skin lesions, skin discoloration, or localized edema. Palpation of lymph nodes and salivary glands should be performed to detect and rule out any palpable masses in this area [108]. Palpation of the facial muscles should be performed as follows: apply a pressure of 1 kg for 2 seconds to provoke pain at the palpation site, and a pressure of 1 kg for 5 seconds to elicit referred or radiating pain. Notably, palpation force is more significant than its duration for identifying pathology [5].

2.2.1.3. Other disorders of the trigeminal nerve, trigeminal nerve disorder, unspecified

Comment:

1. It is advisable to assess sensory disturbances using questionnaires that have undergone Russian-language linguistic adaptation and validation – DN-4, painDETECT, the Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale (LANSS);

2. An important role in establishing the diagnosis is played by assessing the dynamics of the pain syndrome and other sensory disturbances, especially following neuroablative procedures targeting the trigeminal ganglion or trigeminal nerve root;

3. In case of pain recurrence, the differences or stereotyped nature of pain paroxysms and other sensory changes should be taken into account to exclude new facial pain or a relapse of previously diagnosed facial pain.

2.2.1.4. Trigeminal autonomic cephalalgias

2.2.2. Facial nerve disorders

2.2.2.1. Facial nerve neuropathy

Physical examination findings are described in the "Clinical Presentation" section. Physical examination features:

Comments: it is necessary to assess the presence, nature, and severity of motor disorders in the face, such as decreased muscle strength in the upper and lower groups of facial muscles, increased muscle tone on the conventionally healthy and/or affected side of the face, synkinesias, and deviation of the facial midline. Physicians assess the muscle strength of the lower third of the face in only 1/3 of cases, and insufficient attention is paid to assessing muscle tone and recording involuntary movements [112, 113]. To assess facial muscle strength, step-by-step testing should be performed: tests to evaluate the range of active movements (strength) of each facial muscle (Table 11) [94]. Muscle tone should be assessed visually and by palpation on both the healthy and affected sides, taking into account not only its decrease, but also its increase [82]. The presence of facial midline deviation is assessed both at rest and during movement, taking into account the direction of deviation – toward the affected or healthy side. Deviation of the facial midline indicates increased muscle tone [82]. To assess involuntary movements, the patient is given a series of instructions, and during each movement, it is evaluated which muscle contracts synchronously (Table 12). When designating a pathological synkinesia, the "provoking" muscle is indicated first, followed by the "responding" one. The most frequent are oculo-zygomatic (90%) and oro-ocular (59%) [53].

Table 11. Protocol for assessing the range of active movements of facial muscles [94].

Table 12. Main patterns of pathological synkinesias [53]

Comments: The SB system is more comprehensive and sensitive for dynamically assessing facial nerve function in facial nerve neuropathy [118].

Comments: The patient is asked to close their eyelids without effort (close eyes gently), and then to squeeze them shut forcefully. During the tests, the completeness of eyelid closure is visually assessed, the distance in mm between the upper and lower eyelids is measured, the position of the upper and lower eyelids is then recorded separately, and the presence of conjunctival injection is visually assessed.

2.2.2.2. Hemifacial spasm

Physical examination findings are described in the "Clinical Presentation" section. Physical examination features:

Comments: involuntary movements on one half of the face resembling tonic, clonic, or tonic-clonic muscle spasms develop at rest and may intensify during tests. Facial nerve paresis (prosoparesis) and muscle hypertonus on the affected side may be detected.

2.2.2.3. Facial myokymia

Physical examination findings are described in the "Clinical Presentation" section. Physical examination features:

2.2.3. Disorders of other cranial nerves

2.3 Laboratory Diagnostics

2.3.1. Trigeminal nerve disorders

2.3.1.1. Trigeminal neuralgia

Specific laboratory diagnostics for trigeminal neuralgia have not been developed.

2.3.1.2. Atypical facial pain

Burning Mouth Syndrome

Comments: nutritional deficiency, diabetes mellitus, and menopausal disorders are diagnosed through hematological assessment of nutritional status, blood glucose levels, and estrogen/progesterone concentrations, respectively. If laboratory evaluation reveals one or more of these systemic factors, such a patient should be considered as having secondary burning mouth syndrome, whereas the absence of these factors points to a definitive diagnosis of primary burning mouth syndrome [7].

2.2.1.3. Other disorders of the trigeminal nerve, trigeminal nerve disorder, unspecified

Comment: laboratory determination of antibodies to the varicella-zoster virus is of no major clinical significance due to its high prevalence in the population [130].

Comment: diagnostically significant for giant cell arteritis is an ESR ≥ 50 mm/h or CRP ≥ 10 mg/L as part of other diagnostic criteria for the disease [109].

2.3.1.4. Trigeminal autonomic cephalalgias

Not required in case of a typical clinical presentation.

2.3.2. Facial nerve disorders

2.3.2.1. Facial nerve neuropathy

Laboratory diagnostics are aimed at determining the etiological factor and detecting the acute phase of the process.

Comments: hemoglobin concentration, erythrocyte, platelet, and leukocyte counts are determined; a leukocyte formula shift towards neutrophils indicates an unfavorable prognosis.

Comments: metabolic disorders (diabetes mellitus, liver or kidney dysfunction) are detected.

Comments: hypothyroidism increases the risk of developing facial nerve neuropathy [138].

2.3.2.2. Hemifacial spasm

Comments: presence of inflammation and metabolic disorders is excluded.

2.3.2.3. Facial myokymia

In case of a typical disease course and absence of "red flags", laboratory diagnostics are not performed.

2.3.3. Disorders of other cranial nerves

Specific laboratory diagnostics for cranial nerve lesions have not been developed.

2.4 Instrumental Diagnostics

2.4.1. Trigeminal nerve disorders

2.4.1.1. Trigeminal neuralgia

Comment:

1. The names of the recommended sequences may vary depending on the manufacturer of the magnetic resonance scanner;

2. If a mass lesion, demyelinating disease, or other structural alterations (neurosarcoidosis, metastases, etc.) are suspected, contrast enhancement is indicated. The preferred slice thickness for the contrast sequence is up to 2 mm;

Comment:

1. According to the International Classification of Headache Disorders, neurovascular conflict is diagnosed when structural changes in the nerve root (dystopia, atrophy) are present;

2. The names of the recommended sequences may vary depending on the manufacturer of the magnetic resonance scanner;

3. The preferred slice thickness for the FIESTA (CISS, DRIVE) sequence is 0.4–0.6 mm;

4. For diagnosing structural changes in the trigeminal nerve root, scanners with a magnetic field strength of 3 T are preferred, but not less than 1.5 T.

Comment: the choice of additional diagnostic methods is determined by the clinical picture and preliminary diagnosis.

2.4.1.2. Atypical facial pain

Persistent idiopathic facial pain

Comments: Differential diagnosis of persistent idiopathic facial pain is carried out with a number of conditions: pain associated with cranial bone pathology, ear diseases, sinusitis, pathology of the jaws, teeth and surrounding tissues, temporomandibular joint pathology; cranial nerve pathologies such as trigeminal compression, diabetic oculomotor neuropathy, herpes zoster, postherpetic neuralgia, Tolosa-Hunt syndrome, cervical-lingual syndrome; trigeminal neuralgia; glossopharyngeal neuralgia; nervus intermedius neuralgia; neuralgia of terminal branches of cranial nerves; headache attributed to external pressure; cold stimulus headache; central post-stroke pain, intracranial tumors, oral cavity tumors [20,26,151,152].

Myofascial orofacial pain associated with muscle spasm

Comments: The study is performed only in cases where the diagnosis requires confirmation, for example, unilateral or atypical pain. The study can be performed using either surface or needle electrodes. In both cases, a sign of ongoing muscle spasm will be the recording of motor unit action potentials at rest within the projection of the muscles (or directly in the muscle if a needle electrode is used) [5,154].

2.4.1.3. Other disorders of the trigeminal nerve, unspecified trigeminal nerve disorder

If signs of trigeminal nerve compression are detected based on instrumental examination findings, a mandatory basis for diagnosing neuropathic trigeminal pain is the combination of the identified changes with the clinical presentation, i.e. topographic correspondence of the instrumental findings with the manifestations of neuropathy.

Comments:

1. If intraoperative confirmation of trigeminal nerve injury or compression is available, additional instrumental diagnostic methods are not required;

2. If necessary, the study may be supplemented with contrast enhancement, an angiographic sequence (3D TOF), a fat-suppression sequence (FatSat), and others;

3. The preferred slice thickness for T1 and T2 sequences is up to 2 mm.

Comment: if another instrumental study or intraoperative visualization confirming damage or injury to the trigeminal nerve is available, an evoked potential study is not mandatory.

Comment: for diagnosing odontogenic causes of the disease among radiological methods, CBCT is preferred; orthopantomography and targeted radiography can also be used. For diagnosing inflammatory diseases of the paranasal sinuses, CT or radiography can be used.

2.4.1.4. Trigeminal autonomic cephalalgias

Cluster headache

Comment: If the nature of symptoms changes during attacks, the study must be repeated. In individual cases, in patients with an atypical clinical picture or newly onset symptoms over the age of 60, the following may be performed as indicated:

• Computed tomography of the brain (CT of the skull base, if brain MRI cannot be performed);

• General (clinical) cerebrospinal fluid analysis;

• Duplex scanning of the intracranial segments of brachiocephalic arteries;

• Magnetic resonance angiography of intracranial vessels (to rule out arteriovenous malformations or arterial dissection).

Differential diagnosis is carried out with the following conditions:

• paroxysmal hemicrania;

• short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing, SUNCT syndrome (episodic, chronic);

• short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms, SUNA syndrome (episodic, chronic);

• migraine;

• temporal arteritis;

• trigeminal neuralgia;

• sinusitis;

• glaucoma;

• brain tumor;

• arteriovenous malformation

• acute cerebrovascular accident;

• carotid or vertebral artery dissection [158–160].

Paroxysmal hemicrania

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing

Hemicrania continua

2.4.2. Facial nerve disorders

2.4.2.1. Facial nerve neuropathy

Determination of the cause and localization of facial nerve lesions

Contrast-enhanced brain MRI, including the parotid gland, is the method of choice, as it allows assessment of the condition of the facial nerve along its length. The idiopathic form of facial neuropathy (Bell's palsy) is characterized (though not specifically) by contrast enhancement of the facial nerve on the side of clinical symptoms [164–166].

Emergency MRI is indicated for patients with an atypical clinical presentation of facial neuropathy and other neurological symptoms, including to rule out acute cerebrovascular accident [167]. In typical clinical presentations, emergency MRI is not advisable [168].

Elective MRI is performed even in patients with a typical clinical presentation of Bell's palsy [33]. In typical cases of facial neuropathy, space-occupying lesions are detected in 8–12% of cases, 30% of which are malignant [44]. An extended contrast-enhanced protocol is required [115]. In current clinical practice, MRI is performed in only 13% of cases, of which contrast-enhanced is used in every 4th–5th patient [112]. Because recommended MRI protocols vary, the study is often performed incorrectly, and the results do not allow differentiation between inflammatory and neoplastic processes, even when interpreted by experienced physicians [44,113].

International guidelines recommend performing contrast-enhanced MRI in all patients within 1 month of symptom onset [115]. While spontaneous nerve function recovery is possible in facial neuropathy, in 80% of patients (among all who recover), it occurs within the first 2–3 weeks [37]. It is advisable to order MRI in patients with a typical clinical presentation of Bell's palsy only if symptoms persist for more than 2–3 weeks, as well as in all patients with an atypical clinical presentation characterized by the presence of red flags.

Neurosonography is an emerging diagnostic method for cranial nerve lesions (including the facial nerve). It is rarely used in clinical practice, primarily in children [169].

Comment: The study is performed using an extended protocol in patients with a typical clinical presentation of Bell's palsy if symptoms persist for more than 2–3 weeks, as well as in all patients with an atypical clinical presentation, specifically the presence of red flags. The most optimal combination of sequences is: T1 WI, T2 WI, FLAIR (with 1 mm slice thickness), DWI, 3D-TOF, steady-state free precession sequences (such as SSFP, FIESTA-C, CISS, FFE, etc.), magnetic field inhomogeneity-sensitive sequences (such as T2*, SWI, SWAN, etc.), and T1 WI after intravenous contrast enhancement [170,172]. Whenever possible, the protocol includes imaging of the extracranial segment of the facial nerve (MRI of the parotid gland – MRI of soft tissues with intravenous contrast) [171]. If brain MRI is not feasible, contrast-enhanced brain CT should be performed.

Comments: if temporal bone CT is not feasible, temporal bone radiography should be performed.

Instrumental assessment of nerve function – grading severity

The key instrumental methods for assessing the severity of functional facial nerve damage are electroneuromyography (ENMG) and needle electromyography (EMG), which allow prediction of nerve function recovery for the timely identification of patients at risk of unfavorable outcomes and referral for surgical treatment [82,177].

ENMG assesses nerve impulse conduction along the nerve. The study should be performed no earlier than 8 days from the onset of symptoms [178]. An unfavorable prognosis for spontaneous recovery of facial palsy is indicated by an electrographic pattern where the amplitude of the M-wave on the affected side is ≥90% lower than the amplitude of the M-wave obtained from the homologous muscle innervated by the healthy facial nerve. In this case, to avoid false results due to impulse desynchronization caused by uneven de- and remyelination of facial nerve axons, EMG using a concentric needle electrode during attempted voluntary contraction of the corresponding muscle must be performed [178].

EMG evaluates muscle electrical activity—at rest (spontaneous) or during an attempted voluntary contraction of the muscle into which the bipolar concentric electrode is inserted. If nerve innervation of the muscle is preserved, motor unit potentials (MUPs) are recorded during voluntary contraction.

An M-wave amplitude asymmetry >90% combined with the absence of MUPs during attempted voluntary contraction is assessed by most authors as severe axonal degeneration of the facial nerve [33], an unfavorable prognosis of facial neuropathy, and, accordingly, as an indication for surgical treatment [177]. At the same time, the absence of MUPs during attempted voluntary muscle contraction may lack prognostic value until the 15th day from symptom onset [179]. Therefore, if they are absent, the study should be repeated dynamically.

Comments: The study must be performed bilaterally, assessing at least the orbicularis oculi and orbicularis oris muscles, with the report indicating the percentage ratio of the M-wave amplitude obtained from the muscle on the affected side to the M-wave amplitude of the homologous muscle on the healthy side. An amplitude difference of more than 90% in at least one of the muscles indicates an unfavorable prognosis for spontaneous recovery of facial neuropathy, but requires EMG to detect subclinical myofibrillar contractions during voluntary contraction. The result determines the indications for surgical treatment (Appendix B8).

Comments: The failure to record MUPs during voluntary contraction of the examined muscles indicates total damage to the facial nerve trunk and an unfavorable recovery prognosis. The orbicularis oculi and orbicularis oris muscles are the most convenient for examination.

Comments: In cases of isolated paralysis of the muscles of the lower face within the innervation zone of the marginal mandibular branch of the facial nerve, needle EMG was performed with recruitment of MUAPs during voluntary contraction of these muscles bilaterally, assessing the difference in maximum amplitudes of the interference pattern on the affected side relative to the healthy side to determine the degree of nerve injury and management strategy [94]. In traumatic injuries, MUAPs may appear only by the fourth month from symptom onset; therefore, follow-up serial studies are required [184].

Comments: The study can be repeated earlier—at 3 months from symptom onset in the absence of recovery and a history of nerve trauma. It should be noted that in some cases, with sequential combination therapy and rehabilitation, nerve function recovery is possible even with unfavorable ENMG predictors [185].

Comments: The study is uninformative because clinical preservation of movements indicates a favorable prognosis for facial movement recovery and an absence of indications for surgical treatment. In this case, instrumental assessment of facial nerve function is not required. An exception is made for cases of isolated muscle weakness within the innervation area of a single branch [94].

Instrumental diagnostics of secondary movement disorders in facial neuropathy

Comments: Chronic facial neuropathy was defined as a disease duration of more than 3 months. In patients with signs of denervation on ENMG on the affected side, ultrasound revealed a decrease in muscle volume (atrophy), and after reinnervation procedures, an increase (recovery).

Comments: In patients with total facial nerve palsy, denervated muscles rapidly undergo atrophy, making delayed surgical treatment potentially impractical. Monitoring muscle status is required for timely treatment. Since one of the main goals of surgical treatment is smile restoration, assessing the condition of the zygomatic muscles is of primary importance.

2.4.2.2. Hemifacial spasm

Comments: In HFS, the most optimal combination of sequences for identifying neurovascular conflict (NVC) is: 3D-T2 WI, 3D-TOF, and steady-state free precession sequences (such as SSFP, FIESTA-C, CISS, FFE, etc.), performed alongside a standard MRI protocol including T1 WI, T2 WI, FLAIR (with 1 mm slice thickness), DWI, and magnetic susceptibility-weighted sequences (such as T2*, SWI, SWAN, etc.), [189]. In some patients, NVC not identified at 1.5T showed better diagnostic visibility at 3T [190] The most common vessels causing compression are: the anterior and posterior inferior cerebellar arteries, the vertebral artery, the internal auditory artery, small arterioles, and veins; less commonly, compression is caused by venous developmental anomalies, arteriovenous malformations, dural arteriovenous fistulas, arterial aneurysms, and vertebral artery dissections. In most cases, the NVC zone is the nerve root exit zone from the brainstem (up to several mm). In typical HFS presentation, the NVC is located more distally, while in atypical cases, it is located on the rostral side or in the cisternal segment of the facial nerve root [189].

Comments: alternative imaging methods (MRI) may be performed.

2.4.2.3. Facial myokymia

In typical disease courses and the absence of "red flags", neuroimaging is not performed.

2.4.3. Disorders of other cranial nerves

Comment:

1. The names of the recommended sequences may vary depending on the manufacturer of the magnetic resonance scanner;

2. If indicated, routine brain MRI should be supplemented with intravenous contrast enhancement and a slice thickness of up to 2 mm on the contrast-enhanced sequence.

Comment:

1. According to the International Classification of Headache Disorders, neurovascular conflict is diagnosed when structural changes in the nerve root (dystopia, atrophy) are present;

2. The names of the recommended sequences may vary depending on the manufacturer of the magnetic resonance scanner;

3. The preferred slice thickness for the FIESTA (CISS, DRIVE) sequence is 0.4–0.6 mm;

4. For diagnosing structural changes in the trigeminal nerve root, scanners with a magnetic field strength of 3 T are preferred, but not less than 1.5 T.

2.5 Other Procedures

2.5.1. Trigeminal nerve disorders

2.5.1.1. Trigeminal neuralgia

2.5.1.2. Atypical facial pain

Specialist consultations

Burning Mouth Syndrome

Comments: To meet the diagnostic criteria for burning mouth syndrome, clinical evaluation of the oral mucosa must reveal a complete absence of lesions or other abnormalities. Examination of the oral mucosa plays a key role; the absence of mucosal lesions points toward a diagnosis of burning mouth syndrome, whereas mucosal changes suggest an alternative condition. Microbiological analysis of mucosal sites where pain is localized may be effective in ruling out potential bacterial or fungal infections. Patients with painful erythematous lesions may require allergy skin testing to rule out allergic reactions. A dental examination is performed to exclude acute gingivitis, periodontitis, and/or other painful oral conditions. Erosive and ulcerative lesions that do not resolve within 2 weeks should be considered an indication for perilesional biopsy [7][27][198].

Comments: Many patients with burning mouth syndrome exhibit high levels of anxiety and depression, as well as pain relief following appropriate administration of psychotropic medications such as antidepressants or benzodiazepines. Notably, high levels of anxiety and depression are widespread among patients with various types of chronic pain syndromes [7,154].

Persistent idiopathic facial pain

Comments: Patients with persistent idiopathic facial pain may present with chronic pain syndromes in other locations, such as chronic back pain, neck pain, myofascial pain, migraine, irritable bowel syndrome, or dysmenorrhea. 50% of patients with persistent idiopathic facial pain report chronic fatigue [63] The prevalence of emotional-affective and other psychiatric disorders is higher among patients with persistent idiopathic facial pain than in the general population [103].

Myofascial orofacial pain associated with muscle spasm

Comments: Patients with myofascial orofacial pain exhibit high levels of anxiety and depression. Patients with myofascial orofacial pain may present with comorbid conditions such as migraine, irritable bowel syndrome, chronic fatigue, or restless legs syndrome [199–201].

2.5.1.3. Other disorders of the trigeminal nerve, trigeminal nerve disorder unspecified

2.5.1.4. Trigeminal autonomic cephalalgias

Not required for typical clinical presentations.

2.5.2. Facial nerve disorders

2.5.2.1. Facial nerve neuropathy

Specialist consultations

Comments: audiometry makes it possible to detect conductive hearing loss and suspect a facial nerve tumor within the petrous part of the temporal bone, or sensorineural hearing loss and suspect facial nerve compression by a space-occupying lesion located in the cerebellopontine angle. Tympanometry evaluates the acoustic reflex of the stapedius muscle [95,96].

Comments: complicated lagophthalmos is characterized by the onset of inflammatory processes (ocular redness, discomfort, burning, pain, photophobia), and in the absence of treatment, corneal erosions and ulcers develop. Severe complications include corneal perforation and inflammation of the eyeball, which can lead to loss of the eye [102,119].

Comments: referral for a psychological consultation is of a recommendatory nature when the patient expresses complaints of: 1) social maladjustment associated with the disease (deteriorated quality of life, restricted social contacts, dismissal from work, or rejection by a partner); 2) non-acceptance of own appearance, preoccupation with one's attractiveness; 3) uncontrolled anxiety, depressed mood, apathy, obsessive thoughts about what happened; 4) sleep and appetite disturbances; 5) difficulties in expressing and recognizing emotions; 6) tension due to physical discomfort, inability to cope with pain [208].

Consultations with surgical specialists to address the issue of surgical treatment

Surgical treatment is performed in the acute and chronic periods of the disease in patients with unfavorable clinical and myographic predictors. If the disease duration is less than 3 months in patients with idiopathic facial neuropathy (IFN), pathogenetic surgical treatment is considered – decompression of the labyrinthine segment of the facial nerve in the temporal bone pyramidal canal. Further, regardless of the form of the disease (idiopathic, symptomatic), re-innervating surgery is performed for a disease duration of up to 18 months, and reconstructive-plastic surgery for a duration of more than 18 months [177]. In cases of surgical treatment, patient management and rehabilitation follow the same algorithm [82].

Comments: Careful patient selection is recommended for referral to a neurosurgeon. The diagnosis of idiopathic IFN (Bell's palsy) must be reliably established based on a comprehensive clinical and instrumental evaluation, specifically: the severity of damage according to the HB scale must correspond to grades V–VI; according to stimulation ENMG, the difference in M-wave amplitudes between the affected and healthy sides must exceed 90%; recurrent IFN and other causes of facial nerve damage must be excluded [92] (LeveL of Evidence – 1). Surgical decompression of the facial nerve is recommended to be performed within 14 days, preferably via the middle cranial fossa approach compared to the transmastoid approach [209] (Level of Evidence – 1). However, the surgery requires careful patient selection and preoperative preparation, which takes time. Surgical decompression can be performed up to 3 months from symptom onset [210–212]. In case of positive dynamics during this period (clinical or myographic), surgical treatment is not performed.

Comments: The degree of facial nerve impairment is established based on a comprehensive clinical and instrumental evaluation, specifically: the severity of damage according to the HB scale must correspond to grades V–VI; according to stimulation ENMG, the difference in M-wave amplitudes between the affected and healthy sides must exceed 90%. The presence or absence of muscle atrophy according to ultrasound or MRI is taken into account. Re-innervating surgeries are performed within a period of up to 18 months, after which reconstructive-plastic surgeries are performed.

Comments: patients with mild to moderate post-paralytic hemifacial spasm undergo conservative treatment – administration of botulinum toxin for diseases of the peripheral nervous system and physical rehabilitation.

Comments: Consultation with a physical therapy physician is mandatory for patients with a severe degree of IFN (grades V–VI on the HB scale), as well as upon the development of complications – muscle hypertonus, synkinesias, which limit recovery. In other cases, patients undergo home self-rehabilitation in accordance with a standard set of exercises.

2.5.2.2. Hemifacial spasm

Specialist consultations

2.5.2.3. Facial myokymia

Not required in the typical course of the disease.

2.5.3. Disorders of other cranial nerves

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1. Trigeminal nerve disorders

3.1.1. Trigeminal neuralgia

Conservative therapy

Preventative drug treatment

Antiepileptic drugs and centrally acting muscle relaxants are used for the preventative therapy of trigeminal neuralgia (Table 13).

Table 13. Drugs used for the preventative therapy of trigeminal neuralgia [236,237].

General management recommendations for patients with TN include:

1. When choosing a drug, contraindications to use and individual tolerability should be considered. To improve treatment tolerability, it is possible to switch to a generic drug with the same active substance and dose;

2. To assess tolerability, treatment should be initiated with monotherapy. If combination therapy is necessary, drugs should be prescribed sequentially to assess the tolerability of each.

3. Carbamazepine** (ATC code - N03AF01) and #Oxcarbazepine** (ATC code - N03AF02) are classified as first-line drugs, while the rest are second-line therapy. Second-line drugs can be used as monotherapy or in combination with first-line drugs [235];

4. Switching from one antiepileptic drug to another should be done gradually, according to the drug prescribing information;

5. In case of intolerance to #Baclofen** (ATC code - M03BX01), prescribing #Clonazepam** may be considered;

6. Once remission is achieved, i.e., absence of pain for at least 4 weeks, the dose of ongoing medications should be slowly tapered according to their instructions, and conservative treatment may be discontinued completely [238];

7. In case of pain recurrence, medical treatment should be gradually resumed up to the minimum effective dose [235];

8. During regular intake of antiepileptic drugs, blood parameters should be monitored every 3–6 months: complete blood count (platelets, leukocytes, neutrophils, eosinophils), general clinical blood biochemistry (glucose, ALP, ALT, AST, total bilirubin), serum electrolytes (sodium, potassium). If necessary, perform an ECG and assess serum anticonvulsant concentrations (therapeutic drug monitoring).

9. If there is no analgesic effect from any drug treatment despite good tolerability, a psychiatric consultation should be recommended to clarify the genesis of the pain syndrome;

10. It is not necessary to prescribe every listed drug before referring a patient for neurosurgical treatment. It is important to inform the patient about surgical treatment options in a timely manner [235].

Other prophylactic treatment.

Botulinum therapy and transcranial magnetic stimulation (TMS) are acceptable in the treatment of TN in adults.

Comment: botulinum toxin (ATC code – M03AX01) is used – #botulinum toxin type A** and #botulinum toxin type A-hemagglutinin complex** preparations at a dose of 1.25–5 IU intradermally, 15–20 mm apart at trigger points, up to 25–100 IU in total.

Relief of acute pain episodes in trigeminal neuralgia

Comments: The list of drugs is presented in Table 14. Frequent use of #Lidocaine** spray (ATC code - D04AB01, N01BB02) is associated with the risk of mucosal damage due to the ethanol content in the solution. Before performing a trigeminal nerve branch block, a skin test must be performed in accordance with the drug's instructions.

Table 14. Drugs for the treatment of acute pain episodes in adults with TN.

Comments: The mechanism of action of NSAIDs is related to the relief of pain and inflammation by blocking the COX system, which is effective in nociceptive pain. Given the pathogenesis of pain in TN, the use of NSAIDs is ineffective. In cases where pain is relieved by NSAIDs, local inflammatory processes should be ruled out as the cause of the pain syndrome.

Specifics of treating chronic pain caused by trigeminal neuralgia in adults

Table 15. Drugs used for the treatment of chronic pain caused by TN in adults

Comments: special considerations for antidepressant use:

1. Before initiating antidepressant therapy, it is important to explain the treatment goals, expected effects, and timeline to the patient;

2. Patients should be warned about temporary adverse effects during the first weeks of administration. Informing the patient about their transient nature will increase treatment adherence;

3. It is also worthwhile to dispel the patient's main fears associated with antidepressant use, address all counterarguments, and provide a reasoned response.

Comments: psychotherapeutic methods include the following: cognitive behavioral therapy (CBT) [255], biofeedback [253,254], relaxation techniques [255][256], mindfulness [257] and others.

Minimally invasive puncture procedures in patients with trigeminal neuralgia

Minimally invasive puncture procedures in patients with classical TN

Comments: This recommendation is supported by two retrospective studies (Ren H, Xie K). The studies demonstrate a high level of safety and efficacy of supraorbital SRFA over a follow-up range of 24 to 36 months. Given that SRFA is a destructive procedure, it is advisable to perform a preliminary diagnostic block of the supraorbital nerve with a local anesthetic and glucocorticosteroid to confirm the diagnosis.

Comments: To support this recommendation, 1 double-blind RCT (Luo F), 1 observational study (Jia Y), and 1 retrospective study (Sun Z) are cited. Patient selection for PRFA and/or TRFA was based, among other things, on the positive effect of a therapeutic and diagnostic block. Studies demonstrate a high level of safety and efficacy of PRFA and/or TRFA of the infraorbital nerve with a follow-up period of up to 2 years. A higher efficacy of high-voltage (96V) PRFA of the infraorbital nerve compared to the 50V PRFA mode has been demonstrated. The high efficacy of combined prolonged (10 minutes) PRFA followed by TRFA of the infraorbital nerve has also been demonstrated.

Minimally invasive puncture interventions in patients with idiopathic and symptomatic TN

Surgical treatment

Surgical intervention is considered in pharmacoresistant pain courses and impaired patient quality of life. It is necessary to timely inform the patient about the possibilities of surgical treatment and refer the patient to a neurosurgical center. Surgical treatment should be performed in specialized neurosurgical departments with experience in brain surgery and surgical management of TN.

Comment:

1. Pharmacoresistance is defined in patients in whom conservative treatment fails to achieve adequate pain control or causes pronounced side effects [235].

2. There is no conclusive data on the criteria for pharmacoresistance and the necessary observation period for patients [194].

3. From 25 to 40% of patients choose surgical treatment within 2 years of symptom onset [236].

4. The success of surgical treatment largely depends on the diagnostic accuracy and the proper technical execution of the surgery.

Surgical treatment of patients with classical TN

Comment: the prerequisite for choosing microvascular decompression of the trigeminal nerve root is the visualization of a neurovascular conflict with structural changes of the trigeminal root (dystopia, atrophy) on brain MRI [1]. Despite publications showing successful outcomes, in patients over 75 years of age, microvascular decompression must be considered on an individual basis, taking into account the patient's somatic status and surgical risks. The retrosigmoid suboccipital approach is the primary surgical access. Interposition is a widespread decompression technique, and vessel transposition is performed whenever possible. According to the literature, there are no advantages of transposition [272]. If the patient refuses microvascular decompression of the trigeminal nerve root, other neurosurgical procedures may be performed [273].

Comment: irradiation using a Gamma Knife device is preferred; treatment on linear accelerators capable of stereotactic radiosurgery with a maximum dose of 70–90 Gy to the cisternal portion of the trigeminal nerve root is also acceptable. Repeat stereotactic radiosurgery can be performed no earlier than 1 year after the previous one.

Comment: a mandatory prerequisite prior to implanting a neurostimulator for trigeminal nerve branch stimulation is performing test invasive stimulation to determine the efficacy of the method. If adequate pain control is achieved with test peripheral stimulation, the patient is offered implantation of a chronic stimulation system.

Surgical treatment of patients with idiopathic TN

Comment: a mandatory prerequisite prior to implanting a neurostimulator for trigeminal nerve branch stimulation is performing test invasive stimulation to determine the efficacy of the method. If adequate pain control is achieved with test peripheral stimulation, the patient is offered implantation of a chronic stimulation system.

Surgical treatment of patients with TN associated with multiple sclerosis

Comment:

1. The safest target for intervention is the cisternal portion of the trigeminal nerve root with a maximum dose of up to 90 Gy;

2. Medial thalamotomy using stereotactic radiosurgery or focused ultrasound may be performed in patients with TN associated with multiple sclerosis when stereotactic radiosurgery of the cisternal portion of the trigeminal nerve root is ineffective.

Comment: there are no compelling comparative data on the superiority of any particular surgical treatment method. Patients should be informed about all possible surgical treatment methods and their specific features. Given the equivalent efficacy of all surgical treatment methods and the recurrence rate, it is safer to perform stereotactic radiosurgery or minimally invasive percutaneous interventions [278].

Comment: a mandatory prerequisite prior to implanting a neurostimulator for trigeminal nerve branch stimulation is performing test invasive stimulation to determine the efficacy of the method. If adequate pain control is achieved with test peripheral stimulation, the patient is offered implantation of a chronic stimulation system.

Surgical treatment of patients with symptomatic TN

Comment: it is advisable to perform surgical treatment aimed at treating the underlying condition (e.g., tumor removal) along with decompression of the trigeminal nerve root from compressing factors.

Comment: there are no compelling comparative data demonstrating the superiority of any single destruction method [235].

Comment: a mandatory prerequisite prior to implanting a neurostimulator for trigeminal nerve branch stimulation is performing test invasive stimulation to determine the efficacy of the method. If adequate pain control is achieved with test peripheral stimulation, the patient is offered implantation of a chronic stimulation system.

3.1.2. Atypical facial pain

Conservative treatment

Persistent idiopathic facial pain

Comments: Therapy is started with a minimum dose taken at bedtime, as even a minimum dose of tricyclic antidepressants proves effective, and is increased by gradual titration to the average therapeutic dose in accordance with the drug's instructions for use [282].

Table 16. Medications for the treatment of PIFP

Comments: special considerations for antidepressant use:

1. Before initiating antidepressant therapy, it is important to explain the treatment goals, expected effects, and timeline to the patient;

2. Patients should be warned about temporary adverse effects during the first weeks of administration. Informing the patient about their transient nature will increase treatment adherence;

3. It is also worthwhile to dispel the patient's main fears associated with antidepressant use, address all counterarguments, and provide a reasoned response.

Table 17. Drugs for the treatment of neuropathic pain due to lumbar radiculopathy

Comment: botulinum toxin (ATC code – M03AX01) – #botulinum toxin type A** and #botulinum toxin type A-hemagglutinin complex** preparations are administered into the pain area and surrounding tissues.

Burning Mouth Syndrome

Comments: Therapy is started with a minimum dose taken at night, since even a minimal dose of tricyclic antidepressants proves effective, and is increased with gradual titration up to the average therapeutic dose according to the drug's instructions for use (average daily dose of 10–50 mg).[282].

Comments: the recommended daily dose of the drug is 600 mg. One study demonstrated higher efficacy with the combined use of #alpha-lipoic acid and gabapentin (ATC code: N02BF01) [285–287].

Myofascial orofacial pain associated with muscle spasm

Comments: When choosing an NSAID, it is necessary to take into account the presence and nature of risk factors for adverse events, concomitant diseases, and drug interactions. NSAIDs are not combined with each other and should not be used long-term (it is advisable to limit treatment to 10–14 days), which significantly reduces the risk of complications from the gastrointestinal tract, cardiovascular, and other systems. NSAIDs are contraindicated in erosive and ulcerative lesions of the gastrointestinal tract (especially in the acute stage), severe hepatic and renal impairment, individual intolerance, pregnancy, and severe heart failure. In patients at risk for gastrointestinal complications, it is recommended to use NSAIDs with the minimum risk of such complications, at low doses and for a short duration, and/or to consider gastroprotection for the prevention of such complications. When choosing a specific NSAID, it is necessary to check the instructions for medical use for the presence of the corresponding indication and the absence of contraindications [288–293].

Comments: Therapy is started with a minimum dose taken at night (10 mg per day), since even a minimal dose of tricyclic antidepressants proves effective, and is increased with gradual titration up to the average therapeutic dose according to the drug's instructions for use (up to 150 mg per day) [282].

Comments: Therapy is started with a dose of 300 mg and increased by 300 mg every 3 days up to a maximum of 4200 mg.

Comment: botulinum toxin is used (ATC code – M03AX01) – botulinum toxin type A** and #botulinum toxin type A-hemagglutinin complex** preparations intramuscularly into the target muscles.

Other treatment

Persistent idiopathic facial pain

Comments: Behavioral therapy is recommended for patients with persistent idiopathic facial pain as it helps reduce anxiety levels and fosters realistic self-assessment for better coping strategies in managing pain [20,298].

Burning Mouth Syndrome

Myofascial orofacial pain associated with muscle spasm

Interventional treatment

Persistent idiopathic facial pain

Comments: a pterygopalatine ganglion block using the subzygomatic approach should be performed first. If adequate but temporary relief is achieved after the block, the option of performing pulsed RFA of the pterygopalatine ganglion should be considered [303].

3.1.3. Other trigeminal nerve disorders, unspecified trigeminal nerve disorder

Conservative treatment

Table 18. Drugs for the treatment of trigeminal neuropathic pain.

Comments: the starting dose of the drug is 300 mg per day with a gradual increase of 300 mg every 3 days up to 1800 mg per day in two divided doses.

Table 19. Antidepressants for the treatment of trigeminal neuropathic pain

Comments: special considerations for antidepressant use:

1. Before initiating antidepressant therapy, it is important to explain the treatment goals, expected effects, and timeline to the patient;

2. Patients should be warned about temporary adverse effects during the first weeks of administration. Informing the patient about their transient nature will increase treatment adherence;

3. It is also worthwhile to dispel the patient's main fears associated with antidepressant use, address all counterarguments, and provide a reasoned response.

Table 20. Levels of recommendation grades and levels of evidence for opioid analgesics in the treatment of neuropathic pain.

Comments: Special considerations for opioid analgesic use:

1. Drugs of this group are classified as third-line therapy due to the risk of drug dependence and adverse events with long-term use;

2. When choosing a drug, one should consider the history of opioid analgesic use and any history of drug dependence;

3. The drug dosage is selected individually based on the product labeling, tolerability, efficacy, and the presence of concomitant cancer pain in the patient.

Comments: the recommended daily dose is 600 mg.

Other treatment

Comments: among psychotherapeutic methods, the following types are used: cognitive behavioral therapy (CBT) [255], biofeedback [253], relaxation techniques [255,256], mindfulness [257] and others.

Comment: botulinum toxin is used (ATC code – M03AX01) – #botulinum toxin type A** and #botulinum toxin type A-hemagglutinin complex** preparations in the pain area.

Comments: at least 10 HBOT sessions are recommended.

Specifics of treatment for post-traumatic trigeminal neuropathic pain caused by radiation injury

Comments: during the administration of high doses of #alpha-tocopherol acetate (ATC code - A11HA03) (exceeding 400 mg per day), prophylactic treatment for retinol acetate** deficiency (ATC code - D10AD02, R01AX02, S01XA02, A11CA01) should be carried out – simultaneous prescription of retinol** with #alpha-tocopherol acetate**(ATC code - A11HA03) is recommended.

Comments: the recommended dose of the drug is 400 mg 2 times a day for 4–6 weeks.

Comments: at least 10 HBOT sessions are recommended.

Comments: both #dexamethasone** (ATX code - H02AB02) and #prednisolone** (ATX code - H02AB06) can be used in the treatment of clinically significant post-traumatic trigeminal neuropathic pain caused by radiation injury. The decision to prescribe GCS should be made taking into account the benefit-risk ratio for the patient's health, concomitant diseases, and potential complications of GCS therapy. The initial effective dose of dexamethasone is at least 8 mg per day (and no more than 20 mg) per day for 3-5 days, followed by a gradual taper. Administration of prednisolone is possible in equivalent doses.

Surgical treatment

Minimally invasive percutaneous and surgical interventions in patients with trigeminal neuropathic pain

For various types of pharmacoresistant trigeminal neuropathic pain, the following treatment methods are considered:

1. Radiofrequency ablation of peripheral nerves, plexuses, and autonomic ganglia;

2. Neurostimulator implantation;

3. Trigeminal nucleotractotomy.

Comment: given the delayed onset of the motor cortex stimulation effect, the necessity of test stimulation is a debatable issue. The efficacy of the method is controversial, but the decision on surgical treatment should be made taking into account a combination of factors: the efficacy of transcranial magnetic stimulation, the patient's psychological state, functional status, the reserve of conservative treatment methods, etc.

Minimally invasive percutaneous and surgical interventions in patients with trigeminal postherpetic neuralgia

Comments: To support this recommendation, we cite a randomized trial without placebo control [338] and a retrospective case series description [339]. Studies show a high level of safety and efficacy of PRFA and SRFA of the supraorbital nerve within a follow-up range of up to 1 year. The study demonstrated a higher efficacy of high-voltage (65V) supraorbital nerve PRFA compared to 45V PRFA.

Comment: a mandatory condition is the performance of test invasive stimulation to determine the efficacy of the method. With adequate pain control during test peripheral stimulation, the patient is offered the implantation of a system for chronic stimulation.

Surgical treatment of post-traumatic trigeminal neuropathic pain

Comment: a mandatory condition is the performance of test invasive stimulation to determine the efficacy of the method. With adequate pain control during test peripheral stimulation, the patient is offered the implantation of a system for chronic stimulation.

Comment: microsurgical or percutaneous trigeminal nucleotractotomy can be performed depending on the number and degree of involvement of trigeminal dermatomes. Despite the sufficiently high efficacy of the method, surgical treatment carries a certain risk of temporary and persistent neurological complications.

3.1.4. Trigeminal autonomic cephalalgias

Cluster headache treatment consists of acute attack treatment and prophylactic treatment.

Treatment of acute cluster headache attacks.

Comment: Preference should be given to masks with an oxygen valve to ensure an adequate oxygen flow [350,351]. If home oxygen therapy is not feasible, it can be administered in a day hospital setting with oxygen delivery at a rate of 12-15 L/min for 20 min.

Comment: preference should be given to zolmitriptan (ATC code: N02CC03) at a dose of 5-10 mg intranasally into the contralateral nostril [357], as oral forms are less effective due to a longer onset of drug action.

Comment: instillation of #lidocaine** (ATC Code: N01BB02) can be offered as initial therapy since it causes no side effects, and the duration of action is about 2 hours.

Prophylactic treatment of cluster headache

The goal of prophylactic treatment is to prevent the development of cluster headache attacks and to extend the periods of disease remission.

Comment: A double-blind, placebo-controlled study has established the efficacy of #verapamil for the prophylaxis of cluster headache. In clinical practice, treatment should be initiated with a daily dose of 240 mg (240 mg of sustained-release #verapamil once daily or 80 mg of #verapamil 3 times daily). An ECG must be performed before starting treatment. The dose of #verapamil is increased by 80 mg every 3–4 days. After reaching a daily dose of 480 mg, ECG monitoring should be performed for every additional 160 mg [355]. A gradual dose titration up to 960 mg (four 240 mg tablets) under the supervision of a cardiologist is possible. As a rule, high doses are required for effective treatment; therefore, titration of #verapamil may take from 14 to 21 days. Due to the prolonged titration to an effective dose, the use of #verapamil is debatable in patients with episodic cluster headache with a symptomatic period of 1–3 weeks. #Verapamil is generally well tolerated by patients; possible side effects include fatigue, constipation, and lower extremity edema. Cardiac side effects of #verapamil (negative inotropic and chronotropic effects) pose a major risk; bradycardia and atrioventricular conduction disturbances may also occur. It should be borne in mind that cardiac side effects of #verapamil can also develop in patients on a previously established maintenance dose (periodic ECG monitoring is recommended) [360].

Comment: #Prednisolone** at a dose of 100 mg orally in the morning for 5 days with a gradual dose reduction by 20 mg every 3 days. Upon reaching a dose of 10–20 mg, cluster headache may recur.

Comment: #Lithium carbonate is used at a dose of 353–900 mg. Blood plasma lithium levels must be monitored. The minimum therapeutic level is 0.4 mmol/L, 0.6–0.8 mmol/L is considered the ideal level, and reaching a level of 1.2 mmol/L is not recommended. Laboratory monitoring is required before starting treatment. It is necessary to assess blood electrolyte levels (blood sodium assay, blood potassium assay), renal function (general clinical biochemical blood test, including blood urea assay, blood creatinine assay), thyroid hormones (blood thyroid-stimulating hormone (TSH) assay), and an initial primary appointment (examination, consultation) with an endocrinologist, a complete blood count (with mandatory ESR determination), and then regularly at least once a month, a blood lithium assay 12 hours after taking the last dose, and an ECG are also required.

Comment: A double-blind controlled study has established the efficacy of #melatonin (ATX code: N05CH01) at a dose of 10 mg for the preventive treatment of cluster headache [365], whereas another case-control study did not confirm the efficacy of melatonin [366].

Comment: gradual titration of the drug is recommended, starting with 50 mg once daily, followed by an increase in the dose by 25 mg once a week until a dose of 50 mg is reached. In case of insufficient efficacy, a further gradual increase to a dose of 100 mg is possible. The most frequent side effects of #topiramate** are cognitive impairment, weight loss, and paresthesia.

Interventional treatment of cluster headache

Comments: The results of two randomized trials indicate the efficacy of periodic blockade of the occipital nerve with a local anesthetic solution with/without a glucocorticoid for the relief of episodic and chronic cluster headache with daily attacks. The effect persisted for 2–4 weeks; the procedure may be repeated [369,370]. The mechanism of action is based on the temporary suppression of the trigeminal-autonomic reflex through an effect on the interrelated systems of the occipital and trigeminal nerves [371].

Comments: The results of a randomized trial indicate a greater efficacy of transnasal non-invasive blockade (using a cotton pledget soaked in the solution inserted into the nasal passage) with 10% #lidocaine compared to placebo. The effect (relief of the attack) occurred within 30–40 minutes and persisted for at least 5 hours [372].

Comments: The recommendation is based on the results of 2 retrospective studies. In the study by Sanders M et al., following standard radiofrequency ablation of the sphenopalatine ganglion, complete pain relief was demonstrated in 61% and partial relief in 25% of patients with pharmacoresistant episodic cluster headache over a follow-up period of 29 months [373]. In the study by Fang L et al., pulsed radiofrequency ablation of the sphenopalatine ganglion was used for the same patient category; the procedure was effective in 85% of cases, and during the 17-month follow-up period, patients experienced an extension of the remission period from 8.7 to 16.6 months, as well as a reduction in the cluster period duration from 2 to 0.5 months [374].

Comments: In a retrospective study by Narouze S et al., following standard radiofrequency ablation of the sphenopalatine ganglion in patients with chronic cluster headache, a statistically significant reduction was noted in pain intensity, attack frequency, and pain-related disability over 18 months of follow-up after the procedure [375]. A case series presented by Bendersky DC et al. demonstrated the efficacy of standard radiofrequency ablation following the failure of this procedure in pulsed mode in patients with pharmacoresistant cluster headache [376].

Surgical treatment of cluster headache

Comments: The recommendation is based on the results of 3 non-comparative cohort studies. In the study by Miller S et al., following implantation of the ONS system, a 50% or greater reduction in seizure frequency was achieved in 52.9% of patients with drug-resistant chronic cluster headache [377]. The patients demonstrated a reduction in the duration and intensity of pain attacks, decreased use of triptans for pain relief, as well as improved working capacity and quality of life. In the study by Leone M [378] patients were followed for 6 years after ONS system implantation, and a decrease in cluster headache frequency was observed in 66.7% of patients. In the work by Fontaine D [379] et al., with a 1-year follow-up after ONS initiation, a reduction in attack frequency of more than 30% was noted in 64% of patients, and by more than 50% in 59% of patients; prophylactic medication dosages were reduced in 40% of patients, and a significant improvement in quality of life, functional, and emotional domains was reported.

Comments: The recommendation is based on the results of 2 randomized comparative [381,382] and 1 observational non-comparative [383] studies. In the study by Schoenen J et al., over 70% of patients reported cessation of attacks or a significant decrease in their frequency after implantation of the sphenopalatine ganglion stimulation system. In the study by Goadsby P, in the sphenopalatine ganglion stimulation group, relief within 15 minutes occurred in 62.46% of patients, whereas in the control group only in 38.87% of patients; patients in the sphenopalatine ganglion stimulation group also noted a significant decrease in attack frequency. The work by Barloese M et al. demonstrated that following implantation of the sphenopalatine ganglion stimulation system, 55% of patients with pharmacoresistant chronic cluster headache reported a more than 50% reduction in attack frequency, 67% experienced a significant improvement in quality of life, 67% of patients who took acute medications were able to reduce their use by 52%, and 74% of patients were able to decrease the dosage or completely discontinue prophylactic medications.

Conservative treatment

Comment: The maximum daily dose of #indometacin (ATC code: M01AB01) is 250 mg.

Since SUNCT and SUNA attacks are very brief, no treatments for individual attacks have been developed. The goal of therapy is the prevention of attack onset.

Comment: titration of #lamotrigine should be started at a dose of 50 mg per day and gradually increased, based on the response and side effects. Nevertheless, #lamotrigine treatment was not as effective in patients with SUNA.

Comment: starting dose is 300 mg with further increases of 300 mg every 3 days up to a maximum of 4200 mg.

Comments: In one case, it was reported that the positive effect of #lidocaine** administered via intravenous infusion at a dose of 1.3 mg/kg/hour for 14 days persisted for 2 months after the end of the infusion [392].

Comment: The standard therapeutic dose of #indometacin is 25 mg 3 times a day for 5-7 days; in case of inefficacy, the dose is increased to 50 mg 3 times a day for 5-7 days; in case of further inefficacy, 75 mg 3 times a day for 2 weeks. However, given potential gastrointestinal side effects, it is recommended to start titration with low doses.

3.2. Facial nerve disorders

3.2.1. Facial neuropathy

Medical treatment

In the treatment of patients with idiopathic facial neuropathy (Bell's palsy), most authors confirm the efficacy of glucocorticosteroid and antiviral therapy; symptomatic treatment is prescribed depending on the etiology of the disease. Isolated studies recommend the use of B vitamins, thioctic acid. At the same time, physical rehabilitation plays a major role (Appendix B6).

Bell's palsy

Comments: Treatment with glucocorticosteroids increases the rate of complete recovery of nerve function by 17% and should be prescribed as early as possible regardless of disease severity, since muscle weakness may increase in the first few days [395]. The drugs of choice are #prednisolone** (ATX code – H02AB06) and #methylprednisolone** (ATX code – H02AB04). Recommended doses in clinical practice vary [398]. #Prednisolone** is recommended for oral administration at a total daily dose of 60 mg for the first 5 days, followed by a gradual taper of 10 mg per day over the next 5 days [121,399–401] or 1 mg/kg of the patient's weight for 7–10 days; in severe cases (House-Brackmann grade V-VI) and in the absence of contraindications, 2 mg/kg of the patient's weight per day may be prescribed for 10 days [115]. In accordance with the drug instructions, the entire daily dose is taken once in the morning at 6:00–8:00 after a meal, or it can be divided into 2 doses in the first half of the day. In cases where treatment is initiated within 3 days and the severity of facial neuropathy is higher than grade IV according to the House-Brackmann scale, preference should be given to a single intravenous administration of #methylprednisolone** at a dose of 500 mg instead of oral prednisolone [396,399–401]. Daily intratympanic administration of glucocorticosteroids for up to 10 days combined with systemic therapy may improve the outcome, but data are still insufficient and RCTs are needed [402] (LOE - 1).

Comments: Systemic antiviral agents are prescribed in combination with glucocorticosteroids because, according to the viral hypothesis, idiopathic facial neuropathy is associated with infection caused by Herpes zoster, shingles[403,404](as monotherapy they have not shown efficacy[406–408]), in the early stages of the disease in patients with severe facial neuropathy and/or confirmed viral infection[120,121]. The drugs of choice are aciclovir** (ATX code – J05AB01) and valaciclovir (ATX code – J05AB11) [115], prescribed in accordance with the instructions for use. In most studies, the recommended dosing regimen for aciclovir is 800 mg 5 times a day, and for valaciclovir – 1000 mg 3 times a day[409].

Ramsay Hunt syndrome

Comments: Systemic antiviral drugs are prescribed in combination with glucocorticosteroids – #prednisolone** (ATX code – H02AB06) or #methylprednisolone** (ATX code – H02AB04) as a 7-day course [115].

Lyme disease (borreliosis)

Comments: "Standard" antibacterial therapy for Lyme disease includes doxycycline** (ATX code - J01AA02), amoxicillin** (ATX code - J01CA04), or cefuroxime** (ATX code - J01DC02) in accordance with the instructions for use.

Comments: it is advisable to prescribe ibuprofen** (ATX code – M01AE01) in accordance with the instructions for use [290,413].

Botulinum therapy

Botulinum therapy is performed in patients during the acute and chronic periods of the disease [416].

In the acute period of facial neuropathy, botulinum neurotoxin (BoNT) injections are performed into the muscles of the healthy half of the face in cases of muscle hypertonus development or a high risk of its development due to active mimic activity, which leads to a shift in the midline of the face and worsens the prognosis for functional recovery. The main goal is to restore facial symmetry [82,417,418]. It is advisable to use BoNT in the acute period of facial neuropathy after neurosurgical operations [98,419].

In the chronic period of facial neuropathy, BoNT injections are performed on the affected side to treat synkinesias (post-paralytic hemifascial spasm), while the drug is also administered to the healthy side to achieve facial symmetry [97,420,421]. On average, the interval between injections is 5 months. In most studies, injections are performed into the orbicularis oculi and orbicularis oris muscles [418,422]. Achieving an optimal clinical effect in the treatment of synkinesias is made possible by chemical denervation of the lower portion of the palpebral part of the orbicularis oculi muscle, the buccinator muscle, the perinasal muscles, and the platysma [101,423–425]. Adverse effects may include hematoma, excessive weakness of the injected muscle, or weakness of an adjacent muscle (diplopia/speech impairment) [422]. Botulinum therapy is more effective when combined with physical rehabilitation [82].

Comment: Relaxation of facial muscles is performed on the conventionally healthy side, as an additional method to the standard set of exercise therapy (which is prescribed depending on the severity of paresis). Botulinum toxin (ATX code – M03AX01) – #botulinum toxin type A** and botulinum toxin type A-hemagglutinin complex** preparations – is administered intramuscularly into the muscles of the contralateral side of the face in a total dose of up to 50 IU.

Comment: Relaxation of facial muscles is performed on both sides, as an additional method to the standard set of exercise therapy (which is prescribed depending on the severity of paresis) [101]. The drug brand, dose, time interval, and injection sites are selected [422]. Botulinum toxin (ATX code – M03AX01) – botulinum toxin type A** or botulinum toxin type A-hemagglutinin complex** preparations – is administered intramuscularly into the muscles of the ipsilateral and contralateral sides of the face in a total dose of up to 100 IU.

Comment: Relaxation of facial muscles is performed on both sides, as an additional method to the standard set of exercise therapy (which is prescribed depending on the severity of paresis) [101]. The drug brand, dose, time interval, and injection sites are selected [422]. Botulinum toxin (ATX code – M03AX01) – botulinum toxin type A** or botulinum toxin type A-hemagglutinin complex** preparations – is administered intramuscularly into the muscles of the ipsilateral and contralateral sides of the face in a total dose of up to 100 IU.

Comments: injections are performed on the healthy side into the depressor anguli oris / depressor labii inferioris muscle; botulinum toxin (ATX code – M03AX01) – #botulinum toxin type A** or botulinum toxin type A-hemagglutinin complex** preparations – is administered intramuscularly at a dose of 5 IU at a single point [426] or at a dose of 2 IU at 2 points [184].

Prevention and treatment of lagophthalmos symptom and its complications

In facial neuropathy, lagophthalmos—incomplete eyelid closure—is one of the frequent symptoms, leading to ophthalmological complications such as keratitis and corneal ulcers, up to the loss of vision. Main objectives:

restoration of the integrity of the tear film (moisturization),

restoration of eyelid closure – see Medical rehabilitation in facial neuropathy, Appendix B7 [102,119].

Comments: the most frequent regimen is the daytime instillation of artificial tear drops and other indifferent preparations (ATX code – S01XA20) in accordance with the instructions; at night – dexpanthenol (ATX code – S01XA12) in accordance with the instructions [102,119].

Surgical treatment

In facial neuropathy, the method of surgical treatment is determined by the time elapsed from symptom onset, anatomical level (localization) of the lesion, etiology, severity, and clinical manifestations (severity of dysfunction and deformity) (Figure 8). Surgical treatment is classified into pathogenetic—aimed at eliminating the cause of the disease; and symptomatic—aimed at improving the outcome (Appendix B8).

In patients with facial neuropathy of the idiopathic form, pathogenetic surgical treatment is facial nerve decompression in the temporal bone canal, which is performed only in cases of severe nerve damage established clinically (grade V-VI on the House-Brackmann scale) and instrumentally confirmed (difference in M-wave amplitudes of the affected and healthy sides greater than 90% according to stimulation electroneuromyography [ENMG]). Patients with an M-wave amplitude difference greater than 90% must undergo EMG with registration of motor unit potentials (MUPs). The absence of MUPs according to EMG data is regarded as a sign of complete damage to the facial nerve trunk with an unfavorable prognosis for spontaneous recovery, which is an indication for surgical treatment [429].

In patients with facial neuropathy, symptomatic surgical treatment, regardless of the disease form (idiopathic or symptomatic), is a reinnervating operation (neuroplasty) or reconstructive-plastic surgery, which are also performed only in cases of severe nerve damage (Appendix B9) [177]. Surgical treatment (reinnervation of facial muscles) is indicated in the absence of positive dynamics within 6 months from symptom onset and the absence of dynamics according to myography data; it can be performed after pathogenetic surgical treatment.

Figure 8. Surgical treatment of patients with facial nerve lesions

The essence of reinnervating procedures lies in restoring the function of the facial muscles by restoring the anatomical integrity of the facial nerve (Table 21). If restoring the anatomical integrity of the facial nerve is not possible, peripheral anastomoses must be formed between the facial nerve (cranial nerve VII) and regional nerves in the maxillofacial region: the hypoglossal nerve (CN XII) to CN VII, the masseteric nerve (CN V), as well as cross-face reinnervation using the facial nerve from the healthy side. The timeframe for such surgery is up to 2 years (optimally up to 18 months) from symptom onset.

The essence of reconstructive and plastic surgery consists of a two-stage microsurgical treatment (myoneuroplasty). Specifically, the first stage involves harvesting an autologous graft from a donor site (sural nerve or superficial peroneal nerve) and routing it from the healthy side to the affected side. A key feature of the surgery is preparing the recipient nerve for the reinnervation of the transferred muscle. It is necessary to adhere to the rules for restoring the anatomical and functional integrity of the innervation zone, with an emphasis on establishing myodynamic balance. Surgical treatment for patients with severe facial nerve neuropathy is fundamental, but only a comprehensive approach with timely and systematic specialized care can ensure optimal functional and aesthetic treatment outcomes and complete rehabilitation for patients [82,177,430].

Table 21. Patient categories and types of symptomatic surgical treatment for facial nerve lesions

Idiopathic facial nerve neuropathy (Bell's palsy)

Comments: The procedure requires careful patient selection. The diagnosis of Bell's palsy must be reliably established based on a comprehensive clinical and instrumental assessment, specifically: the severity of damage according to the House-Brackmann (HB) scale must correspond to grade V–VI; stimulation electroneurography (ENMG) must show an amplitude difference of the M-wave between the affected and healthy sides exceeding 90%; recurrent neuropathies and other causes of facial nerve injury must be excluded [92] (LoE - 1). Surgical decompression of the facial nerve is recommended to be performed within 14 days, preferably via the middle cranial fossa approach compared to the transmastoid approach [209] (LoE - 1). However, the procedure requires careful patient selection and preoperative preparation, which takes time. Surgical decompression can be performed up to 3 months from symptom onset [210–212]. If positive dynamics (clinical or myographic) are observed during this period, surgical treatment is not performed.

Comments: the risk of ipsilateral hearing loss with this type of surgical intervention is 2–5% [212].

Idiopathic or symptomatic facial nerve neuropathy

Comments: The severity of facial nerve damage is established based on a comprehensive clinical and instrumental assessment, specifically: the severity of injury according to the House-Brackmann scale must correspond to grade V–VI, and stimulation ENMG must show an amplitude difference of the M-wave between the affected and healthy sides exceeding 90%. The presence or absence of muscle atrophy according to ultrasound or MRI is taken into account.

Comments: The severity of facial nerve damage is established based on a comprehensive clinical and instrumental assessment, specifically: the severity of injury according to the House-Brackmann scale must correspond to grade V–VI, and stimulation ENMG must show an amplitude difference of the M-wave between the affected and healthy sides exceeding 90%. The presence or absence of muscle atrophy according to ultrasound or MRI is taken into account.

Comments: taking into account side effects such as facial muscle weakness, careful patient selection is required.

Surgical treatment methods for patients with prosoplegia

Comments: in cases of contraindications to surgical treatment or if the patient refuses, static correction using threads is possible.

Surgical treatment methods for patients with facial nerve palsy

Surgical treatment methods for patients with paralytic lagophthalmos

Comments: Treatment methods for paralytic lagophthalmos include: upper eyelid gold weight implantation, skin-cartilage graft from the auricle, lateral and medial canthopexy using temporal fascia and/or auricular cartilage, blepharorrhaphy, correction of upper eyelid retraction using temporal fascia, correction of upper eyelid retraction using auricular cartilage, lateral and medial canthopexy.

3.2.2. Hemifacial spasm

Medical treatment

Comments: The presented drugs have unproven efficacy in relieving spasm and have side effects such as excessive sedation and fatigue. The standard dosage for these drugs is: #carbamazepine** 400-1200 mg per day, #gabapentin 600-1200 mg per day, #clonazepam** 0.5-4 mg per day, other benzodiazepines (#diazepam** and #lorazepam**) in equivalent doses, #baclofen** 15-80 mg per day, #levetiracetam** 500-1500 mg per day, #zonisamide** 150 mg 2 times a day for 6 weeks [440,441].

Botulinum therapy

In primary and secondary hemifacial spasm, first-line treatment is the administration of botulinum toxin, which is confirmed by numerous clinical studies [15]. Botulinum therapy for hemifacial spasm has symptomatic and pathophysiological mechanisms of action. On the one hand, by blocking neuromuscular transmission, injections suppress myoclonic hyperkinesia. On the other hand, by suppressing muscle hyperactivity, botulinum therapy prevents the formation of hyperexcitability, sensitization, and neuroplasticity at the nuclear and supranuclear levels of facial muscle innervation. Based on these circumstances, botulinum toxin type A injections should be prescribed at the stages of minimal spasm manifestations and short disease duration [15]. Injections are performed into the facial muscles on both sides in order to not only reduce the clinical manifestations of spasm, but also to improve symmetry [442,443]. Target muscles in hemifacial spasm are the orbicularis oculi, buccinator, and platysma. When injecting into the zygomatic muscles, there is a high risk of developing smile asymmetry; into the orbicularis oris – lip biting, speech and eating disorders [15]. In 76-100% of patients with hemifacial spasm, clinical improvement occurs within 7 days after drug administration with an effect duration of up to 90 days; the recommended interval between injections is starting from 3 months [15].

Comments: Botulinum toxin (ATC code – M03AX01) – botulinum toxin type A** and botulinum toxin type A-hemagglutinin complex** preparations in a total dose of up to 100 IU are injected intramuscularly into the muscles of the ipsilateral and contralateral sides of the face.

Comments: Botulinum toxin (ATC code – M03AX01) – botulinum toxin type A** and botulinum toxin type A-hemagglutinin complex** preparations in a total dose of up to 100 IU are injected intramuscularly into the muscles of the ipsilateral and contralateral sides of the face.

Surgical treatment

In patients with primary hemifacial spasm in the presence of confirmed neurovascular conflict according to MRI data, vascular decompression is performed as the only pathogenetically substantiated treatment method; the essence of the operation is the separation of the vessel and the nerve (Appendix B10) [49].

In patients with secondary hemifacial spasm the type of surgical intervention is determined by its cause. Thus, in case of nerve compression by a space-occupying lesion, removal of the space-occupying lesion is performed (pathogenetic treatment). If hemifacial spasm developed after previous facial neuropathy, selective neurotomy, selective neurorrhaphy, or neurolysis are performed to reduce spasm severity (symptomatic treatment) – see surgical treatment for facial neuropathy.

Figure 8. Surgical treatment of patients with facial nerve lesions

Comments: Contraindications to surgical treatment include: severe comorbid pathology preventing surgical intervention or the patient's refusal of surgical intervention [49]. When observing patients for 1 year, recovery occurred in more than 90% of patients [231].

• Comments: the target in radiosurgical treatment is the facial nerve at the section immediately before its entry into the internal acoustic meatus. The recommended dose is 8 Gy once or 15 Gy in 5 fractions of 3 Gy each.

3.2.3. Facial myokymia

Medical treatment

Comments: Primary facial myokymia resolves within a few days or weeks with rest and the elimination of triggering factors (smoking, alcohol, and caffeine consumption). Secondary facial myokymia is managed by treating the underlying condition.

Botulinum therapy

Comments: in facial myokymia lasting more than 3 months, other causes of facial nerve lesion must first be excluded. Botulinum toxin type A (BTX) injection therapy is symptomatic. A single or, if necessary, repeated dose of 5–20 IU of BTX is injected into the hyperkinetic muscle (in eyelid myokymia, into the orbicularis oculi muscle). Medications used include #botulinum toxin type A** and #botulinum toxin type A-hemagglutinin complex**.

Surgical treatment

Surgical treatment is not indicated.

3.3. Disorders of other cranial nerves

Conservative therapy

Preventative drug treatment

Comments: the drug is prescribed according to the dosing rules for trigeminal neuralgia; the average therapeutic dose in patients with glossopharyngeal neuropathy is 100–2000 mg per day.

Comments: the drug should be prescribed starting at 300 mg per day with a gradual increase up to 1200 mg per day.

Comments: the drug is prescribed according to the dosing rules for trigeminal neuralgia; the average therapeutic dose in patients with glossopharyngeal neuralgia is 100–5000 mg per day.

General recommendations for the management of patients with glossopharyngeal neuralgia include:

When choosing a drug, contraindications for use and individual tolerance should be taken into account. To improve treatment tolerability, the drug may be switched to a generic with the same active substance and dose;

To assess tolerability, treatment should be initiated with monotherapy. If combination therapy is necessary, drugs should be prescribed sequentially to evaluate the tolerability of each.

Other preventive treatments

Minimally invasive intervention in patients with glossopharyngeal neuralgia

Minimally invasive intervention in patients with glossopharyngeal neuralgia

Surgical treatment

Surgical intervention is considered in cases of pharmacoresistant pain syndrome and impaired patient quality of life. The patient must be informed in a timely manner about the possibilities of surgical treatment and referred to a neurosurgical center.

Surgical treatment should be performed in specialized neurosurgical departments with experience in brain surgery and glossopharyngeal neuralgia operations.

Comment: A comparative study was conducted on the efficacy of microvascular decompression of the glossopharyngeal nerve root versus microvascular decompression with simultaneous rhizotomy. No statistically significant differences were found regarding pain control and complications [456].

Comment: Irradiation using a Gamma Knife is preferred; treatment using linear accelerators with stereotactic radiosurgery capabilities is also acceptable.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

4.1. Trigeminal nerve disorders

4.1.1. Trigeminal neuralgia

Patient information (Appendix B1).

4.1.2. Atypical facial pain

Data not available.

4.1.3. Other trigeminal nerve disorders, unspecified trigeminal nerve disorder

Data not available.

4.1.4. Trigeminal autonomic cephalalgias

Patient information (Appendix B2).

4.2. Facial nerve disorders

4.2.1. Facial neuropathy

Physical rehabilitation measures consist of:

1. discussing the disease, its clinical course options, potential complications, and prevention measures with the patient,

2. discussing the importance of self-rehabilitation and limiting factors that may worsen the course of the disease (heat exposure, rough massage, electrical stimulation, avoiding active facial expressions and intensive exercise therapy within the maximum active range of motion, etc.) with the patient,

2. prescribing a standard set of therapeutic exercises depending on the degree of facial muscle paresis,

3. prescribing an additional set of therapeutic exercises depending on the presence and severity of complications (muscle hypertonicity, synkinesis),

4. prescribing an additional set of therapeutic exercises depending on the presence and severity of lagophthalmos,

5. training self-monitoring skills for the development or worsening of facial nerve palsy complications,

6. rehabilitation using external physical factors [459].

The standard set of therapeutic exercises depends on the degree of muscle paresis (Appendix B5, Appendix B3), and in severe facial nerve palsy (grade V-VI on the House-Brackmann scale) includes:

"positional treatment" using adhesive tape tension or kinesio taping to "lift the muscles" and restore the facial midline;

massage / self-massage to improve muscle blood supply;

passive exercises mimicking muscle contraction to prevent the development of contractures;

in mild or moderate facial nerve palsy (up to grade IV on the House-Brackmann scale), it includes:

massage / self-massage to improve muscle blood supply;

active exercises with metered symmetrical load mimicking muscle contraction, aimed at increasing the range of motion, strength, endurance, and contraction speed characteristics. An important condition is symmetrical contraction (adjusting the healthy side of the face to the affected one).

It should be noted that when conducting physical rehabilitation in general, all methods are grouped into 2 approaches:

active – when the patient actively moves their own muscles during exercises (specific muscle strengthening, including using biofeedback),

passive – when muscle movement is facilitated by an external force—a person or a device (massage, muscle stretching) [120,460].

The additional set of therapeutic exercises depends on the presence and severity of complications (muscle hypertonicity, synkinesis) (Appendix B3)

The patient is informed that the most frequent complications of facial nerve palsy are muscle hypertonicity on the healthy or on the affected side prior to the development of contractures, and pathological synkinesis prior to the development of post-paralytic lagophthalmos. Self-monitoring methods for their development are explained, enabling the detection of complications at the reversible stage.

To prevent the development of muscle hypertonicity and synkinesis or in mild cases, stretching of the corresponding muscles is performed (relaxation with elements of post-isometric relaxation and buccal massage) [82]. In moderate or severe cases, botulinum toxin type A injections are additionally administered [418]. If complications develop on the conventionally unaffected side, muscle relaxation (via physical rehabilitation or botulinum toxin therapy) is performed only on the unaffected side [99]; if complications develop on the affected side, it is performed bilaterally to preserve facial symmetry (Appendix B5) [101].

When synkinesia develops, a number of authors consider botulinum toxin therapy combined with physical rehabilitation as the first-line therapy, including gentle massage, muscle relaxation techniques, and exercises aimed at neuromuscular re-education, i.e., movement control exercises [54].

Comments: Physical rehabilitation includes medical facial massage, facial muscle stretching and relaxation exercises, facial and neck muscle strengthening exercises, neuromuscular re-education, and the use of biofeedback.

Comments: Active exercise therapy is not recommended for patients with severe facial nerve neuropathy because the muscle strength of the affected side is insufficient to produce movement; meanwhile, the unaffected side takes on hyperfunction, and the muscles become active, shorten, and shift the midline of the face, which worsens the disease outcome [82].

Comments: A mirror is used as biofeedback [466]. Biofeedback using myography can also be used [467].

Comments: Muscle tone imbalance in acute facial nerve neuropathy (FNN) causes muscle shortening on the contralateral (conventionally healthy) side, leading to contractures. Excessive activity of the contralateral muscles lengthens/stretches the ipsilateral muscles beyond their physiological length, limiting the potential for muscle strength gains. Short daily sessions aimed at stretching the hyperactive contralateral muscles and strengthening the ipsilateral muscles help restore balance, improve symmetry, and enhance facial muscle function [468]. This exercise set is effective for preventing contralateral muscle hypertonus and for mild impairments. It can be used in patients with moderate to severe muscle hypertonus when botulinum toxin therapy is not feasible [99].

Comments: As nerve function recovers and muscle strength increases on the affected side, ipsilateral muscle tone simultaneously increases, and from the 3rd month of the disease, synkinesias appear, leading to structural changes—the development of contractures and post-paralytic hemispasm, respectively. Short daily sessions aimed at stretching (and thereby relaxing) the ipsilateral muscles help improve facial symmetry and muscle function. This exercise set is effective for mild impairments.

Comments: In FNN, rehabilitation is long-term and continuous, carried out not only in specialized centers but largely consisting of daily home exercises. In a multicenter RCT (Japan, 2020), patients with severe FNN (House-Brackmann V–VI) within up to 2 months from symptom onset were prescribed a physical rehabilitation program (selective exercise therapy using biofeedback, muscle stretching exercises, avoidance of excessive movements, "rough exercises," and electrical stimulation) for home self-rehabilitation, 30 minutes per day with weekly monitoring. Recovery of voluntary movement was observed without exacerbation of synkinesias. The authors suggested using this approach as early as possible in the course of the disease [469]. Every patient must receive training during the initial neurological consultation according to a standardized program (see patient information leaflet) [459].

Comments: apply a patch or kinesio tape to the upper eyelid during the day for patients with lagophthalmos and upper eyelid malposition; perform "pulling up" of the lower eyelid in the presence of ectropion; perform eyelid occlusion before sleep if the palpebral fissure closure is greater than 4 mm to improve palpebral fissure closure and prevent mechanical damage to the eyeball [102].

Comments: The exercise program includes self-massage; stimulation of movement through elements of muscle stretching and contraction; and control of muscle contraction. It has low variability in exercises both in type and number of repetitions, performed two to three times daily. Basic rules for performing the exercises: using biofeedback (mirror), symmetrically, all movements must be point-targeted, dosed, without using maximum force, and without triggering associated movements (synkinesias) of the muscles in the upper third of the face. With a favorable myographic prognosis, smile symmetry is achieved after 4–5 months of exercises [94]

Comments: Reflexotherapy is used only as an additional method of physical rehabilitation in patients with facial nerve neuropathy receiving standard treatment. RCTs have demonstrated the benefits of reflexotherapy in treating patients with symptomatic facial nerve neuropathy (associated with diabetes mellitus, HIV infection) [470–472]. The use of reflexotherapy is more effective in the acute period of the disease [473].

Comments: as they lead to the shortening of muscle fibers, increase the risk of synkinesia development, and hinder favorable recovery.

Comments: as it leads to the shortening of muscle fibers, increases the risk of synkinesia development, and hinders favorable recovery.

4.2.2. Hemifacial spasm

Medical rehabilitation is not provided for this category of patients. The patient is provided with information about the disease and its treatment methods (Appendix B4).

4.2.3. Facial myokymia

Medical rehabilitation is not provided for this category of patients. The patient is provided with information about the disease and its treatment methods (Appendix B5).

4.3. Disorders of other cranial nerves

Data not available.

5. Prevention and Dispensary Observation

5.1. Trigeminal nerve disorders

Data not available.

5.2. Facial nerve disorders

5.2.1. Facial neuropathy

5.2.2. Hemifacial spasm

5.2.3. Facial myokymia

5.3. Disorders of other cranial nerves

Data not available.

6. Organization of Medical Care

6.1. Trigeminal nerve disorders

6.1.1. Trigeminal neuralgia

Indications for emergency hospitalization to a medical organization (inpatient facility, including day hospital):

1. first-onset episode of intense pain in the area of the ophthalmic branch of the trigeminal nerve, accompanied by autonomic symptoms / one of the symptoms (eyelid edema, scleral hyperemia, forehead sweating, pupil size changes, lacrimation, rhinorrhea/nasal congestion) on the side of clinical manifestations (hospitalization to rule out other intracranial pathology — mass and vascular lesions in the cavernous sinus area);

2. presence of other focal neurological symptoms that arose in close connection with facial pain (hospitalization to rule out other central nervous system pathology — demyelinating brain diseases, intracranial tumors);

3. uncontrolled pain syndrome (hospitalization to a day or 24-hour hospital to relieve/reduce the severity of acute pain, selection of conservative therapy).

Indications for elective hospitalization to a medical organization (inpatient facility, including day hospital):

1. performance of minimally invasive puncture interventions to relieve/reduce the severity of pain syndrome;

2. performance of surgical treatment to relieve/reduce the severity of pain syndrome.

Indications for patient discharge from a medical organization:

1. establishment of a diagnosis;

2. reduction/relief of pain syndrome;

3. stabilization of the condition.

6.1.2. Atypical facial pain

Indications for emergency hospitalization to a medical organization:

1. Facial pain accompanied by altered consciousness;

2. Facial pain accompanied by fever and meningeal signs;

3. Facial pain with progressive focal neurological symptoms;

4. Facial pain with progressive general cerebral symptoms.

Indications for planned hospitalization in a medical organization:

1. Progressive nature of the pain.

2. Pain resistant to adequately prescribed therapy for botulinum therapy and/or interventional treatment.

Comments: botulinum therapy and interventional treatment can also be performed in a day hospital setting.

Indications for patient discharge from a medical organization:

1. Reduction of pain intensity according to the VAS or NRS.

6.1.3. Other disorders of the trigeminal nerve, unspecified trigeminal nerve disorder

Indications for emergency hospitalization to a medical organization:

1. suspected trigeminal neuropathic pain associated with Herpes zoster in elderly patients, as well as in patients with immunodeficiency and oncological diseases, for the treatment of the causative viral infection.

Indications for planned hospitalization in a medical organization:

1. performance of minimally invasive puncture interventions to relieve/reduce the severity of pain syndrome;

2. performance of surgical treatment to relieve/reduce the severity of pain syndrome.

Indications for patient discharge from a medical organization:

1. stabilization of the condition after minimally invasive puncture interventions or surgical treatment of trigeminal neuropathic pain;

2. reduction/relief of pain syndrome.

6.1.4. Trigeminal autonomic cephalalgias

Indications for emergency hospitalization to a medical organization:

Facial pain accompanied by altered consciousness.

Facial pain accompanied by fever and meningeal signs.

Facial pain with progressive focal neurological symptoms.

Facial pain with progressive general cerebral symptoms.

Refractory cluster headache for oxygen inhalation to interrupt the cluster period.

Indications for planned hospitalization in a medical organization:

Progressive nature of the pain.

Pain resistant to adequately prescribed therapy for botulinum therapy and/or interventional treatment (which is also possible on an outpatient basis).

Indications for patient discharge from a medical organization:

Reduction of pain intensity according to the VAS.

6.2. Facial nerve disorders

6.2.1 Facial neuropathy

Indications for emergency hospitalization to a medical organization (inpatient facility, including day hospital):

1. presentation of a patient with facial paresis/paralysis within the first 72 hours from symptom onset (hospitalization for a single high-dose intravenous administration of #methylprednisolone** when choosing the intravenous route of glucocorticosteroid administration),

2. presence of other neurological symptoms (weakness or numbness in a limb, dizziness, swallowing disorders, etc.),

3. clinical deterioration accompanied by altered consciousness, fever, and meningeal signs, facial paresis / facial paralysis against the background of decompensation of comorbid conditions (increased blood pressure, elevated blood sugar levels) or pregnancy,

Indications for elective hospitalization to a medical organization (inpatient facility):

1. surgical treatment.

Indications for patient discharge from a medical organization

1. establishment of a diagnosis;

2. stabilization of the condition.

6.2.2 Hemifacial spasm

Indications for elective hospitalization to a medical organization (inpatient facility):

1. surgical treatment.

6.2.3 Facial myokymia

Outpatient treatment.

6.3. Disorders of other cranial nerves

Indications for emergency hospitalization to a medical organization (inpatient facility, including day hospital): none.

Indications for elective hospitalization to a medical organization (inpatient facility, including day hospital):

1. performance of minimally invasive puncture interventions to relieve/reduce the severity of pain syndrome;

2. performance of surgical treatment to relieve/reduce the severity of pain syndrome.

Indications for patient discharge from a medical organization:

1. establishment of a diagnosis;

2. reduction/relief of pain syndrome;

3. stabilization of the condition.

7. Additional Information

7.1. Trigeminal nerve disorders

Data not available.

7.2. Facial nerve disorders

In patients with facial nerve neuropathy, the frequency of complete functional recovery correlates with the initial symptom severity and ranges from 61% in total facial paralysis to 94% in less severe facial paresis [37]. Clinical examination results do not always correspond to the true severity of nerve damage. ENMG is a mandatory diagnostic method in patients with grade V–VI according to the House-Brackmann scale. ENMG predictors of an unfavorable outcome include an M-wave amplitude asymmetry of more than 90% in 1 or more branches of the facial nerve, and a favorable outcome — less than 90% in all branches [99].

In 68.5% of patients with facial nerve neuropathy who sought medical care within 3 months from symptom onset, hypertonicity of the muscles on the healthy side of the face was detected, which in most cases leads to a shift in the facial midline — a significant factor limiting the recovery of facial nerve function [99]. Early initiation of treatment and medical rehabilitation (including correction of muscle hypertonicity), identification of patients with ENMG predictors of an unfavorable outcome for timely surgical treatment, and a comprehensive and multidisciplinary approach increase the proportion of recovery cases [82].

7.3. Disorders of other cranial nerves

Data not available.

Criteria for Evaluating the Quality of Medical Care

8.1. Trigeminal nerve disorders

8.1.1. Trigeminal neuralgia

8.1.2. Atypical facial pain

8.1.3. Other trigeminal nerve lesions, unspecified trigeminal nerve lesion

8.1.4. Trigeminal autonomic cephalalgias

8.2. Facial nerve disorders

8.2.1 Facial neuropathy

8.2.2 Hemifacial spasm

8.2.3 Facial myokymia

8.3. Disorders of other cranial nerves

References

Appendix A1. Working Group Composition

Asratyan Sarkis Albertovich, Candidate of Medical Sciences, Neurosurgeon, Deputy Chief Physician for Surgical Care, City Clinical Hospital named after V.M. Buyanov of the Moscow Healthcare Department.

Volkanevsky Alexey Valerievich, Anesthesiologist-Resuscitologist, Regional Perinatal Center of the Yaroslavl Region.

Genov Pavel Gennadievich, Doctor of Medical Sciences, Head of the Department for the Treatment of Patients with Chronic Pain Syndromes, Anesthesiologist-Resuscitologist, City Clinical Hospital No. 52 of the Moscow Healthcare Department. President of the Interventional Pain Management Association (IPMA), Member of the Pain Treatment Committee of the Federation of Anesthesiologists and Resuscitologists,

Gekht Alla Borisovna, Doctor of Medical Sciences, Corresponding Member of the Russian Academy of Sciences, Professor, Director of the Scientific and Practical Psychoneurological Center named after Z.P. Solovyov of the Moscow Healthcare Department. Honored Doctor of the Russian Federation, Academic Secretary of the All-Russian Society of Neurologists.

Glebov Maxim Vladimirovich, Candidate of Medical Sciences, Head of the Day Hospital, Neurologist, City Clinical Hospital named after V.M. Buyanov of the Moscow Healthcare Department. Secretary of the Interventional Pain Management Association (IPMA).

Grin Andrey Anatolyevich, Doctor of Medical Sciences, Corresponding Member of the Russian Academy of Sciences, Head of the Scientific Department of Emergency Neurosurgery, Sklifosovsky Research Institute for Emergency Medicine of the Moscow Healthcare Department, Professor at the Department of Fundamental Neurosurgery, Faculty of Additional Professional Education, Pirogov Russian National Research Medical University.

Dzafarov Vijay Maisovich, Neurosurgeon, Federal Center for Brain Research and Neurotechnologies of the Federal Medical-Biological Agency of Russia.

Evdokimova Olga Liverievna, Radiologist, Head of the Radiosurgery Center Department, Junior Researcher at the Department of Emergency Neurosurgery, Sklifosovsky Research Institute for Emergency Medicine of the Moscow Healthcare Department.

Lesya B. Zavaliy, Candidate of Medical Sciences, Senior Researcher at the Research Department of Emergency Neurology and Restorative Treatment, neurologist at the N.V. Sklifosovsky Research Institute of Emergency Medicine of the Moscow Healthcare Department.

Kalantarova Marina Vitalievna, Medical Psychologist, Sklifosovsky Research Institute for Emergency Medicine of the Moscow Healthcare Department, Senior Lecturer, Moscow State University of Psychology and Education.

Kirillova Elizaveta Pavlovna, Neurologist, City Clinical Hospital named after V.M. Buyanov of the Moscow Healthcare Department.

Krylov Vladimir Viktorovich – Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Head of the Department of Fundamental Neurosurgery, Faculty of Additional Professional Education, Institute of Continuing Professional Education, Pirogov Russian National Research Medical University of the Russian Ministry of Health, Chief Researcher, Sklifosovsky Research Institute for Emergency Medicine of the Moscow Healthcare Department. Chief freelance neurosurgeon of the Russian Ministry of Health.

Kulakov Anatoly Alekseevich, Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Scientific Advisor, National Medical Research Center for Dentistry and Maxillofacial Surgery of the Russian Ministry of Health. Honored Worker of Science of the Russian Federation. Chief freelance maxillofacial surgeon of the Russian Ministry of Health.

Natalya Yu. Kutrovskaya, Candidate of Medical Sciences, ophthalmologist, associate professor at the Department of Ophthalmology, Russian University of Medicine of the Russian Ministry of Health.

Makashova Elizaveta Sergeevna, Neurologist, Loginov Moscow Clinical Scientific Center of the Moscow Healthcare Department, National Medical Research Center for Neurosurgery named after Academician N.N. Burdenko of the Russian Ministry of Health.

Martynov Mikhail Yuryevich, Doctor of Medical Sciences, Professor, Corresponding Member of the Russian Academy of Sciences, Professor at the Department of Neurology, Neurosurgery and Medical Genetics, Faculty of General Medicine, Pirogov Russian National Research Medical University, Head of Administration, National Medical Research Center for Neurology. Honored Doctor of the Russian Federation.

Petrikov Sergey Sergeevich, Doctor of Medical Sciences, Corresponding Member of the Russian Academy of Sciences, Director of the Sklifosovsky Research Institute for Emergency Medicine of the Moscow Healthcare Department.

Polunina Natalia Alekseevna, Candidate of Medical Sciences, Associate Professor at the Department of Fundamental Neurosurgery, Faculty of Additional Professional Education, Institute of Continuing Professional Education, Pirogov Russian National Research Medical University, Senior Researcher at the Neurosurgical Department, Neurosurgeon, Sklifosovsky Research Institute for Emergency Medicine of the Moscow Healthcare Department.

Ramazanov Ganipa Ramazanovich, Candidate of Medical Sciences, Deputy Director – Head of the Regional Vascular Center, Head of the Scientific Department of Emergency Neurology and Restorative Treatment, Sklifosovsky Research Institute for Emergency Medicine of the Moscow Healthcare Department.

Rakhmanina Anastasia Alekseevna, Researcher, Senior Medical Psychologist at the Department of Medical Psychology, Sklifosovsky Research Institute for Emergency Medicine of the Moscow Healthcare Department.

Rozhnova Elizaveta Nikolaevna, Junior Researcher at the Department of Emergency Neurosurgery, Neurologist, Sklifosovsky Research Institute for Emergency Medicine of the Moscow Healthcare Department.

Salikov Alexander Viktorovich, Candidate of Medical Sciences, Surgeon, Chief Physician, City Clinical Hospital named after V.M. Buyanov of the Moscow Healthcare Department.

Salikhov Kamil Salamovich, Candidate of Medical Sciences, Senior Researcher at the Scientific and Methodological Department of the Scientific and Organizational Direction, Maxillofacial Surgeon, Plastic Surgeon, National Medical Research Center for Dentistry and Maxillofacial Surgery of the Russian Ministry of Health.

Sinkin Mikhail Vladimirovich, Doctor of Medical Sciences, Leading Researcher, Neurologist, Functional Diagnostics Physician, Sklifosovsky Research Institute for Emergency Medicine of the Moscow Healthcare Department.

Seliverstova Ekaterina Gennadievna, Junior Researcher, Neurologist, Functional Diagnostics Physician, Sklifosovsky Research Institute for Emergency Medicine of the Moscow Healthcare Department.

Talypov Alexander Ernestovich – Doctor of Medical Sciences, Leading Researcher at the Department of Emergency Neurosurgery, Neurosurgeon, Sklifosovsky Research Institute for Emergency Medicine of the Moscow Healthcare Department.

Kholmogorova Alla Borisovna – Doctor of Psychological Sciences, Professor, Dean of the Faculty of Counseling and Clinical Psychology, Moscow State University of Psychology and Education, Leading Researcher, Sklifosovsky Research Institute for Emergency Medicine of the Moscow Healthcare Department.

Sharinova Irina Anatolyevna, Candidate of Medical Sciences, Neurologist at the Department for the Treatment of Patients with Chronic Pain Syndromes, City Clinical Hospital No. 52 of the Moscow Healthcare Department.

Shamalov Nikolay Anatolyevich, Doctor of Medical Sciences, Professor, Director of the Institute of Cerebrovascular Pathology and Stroke, Federal Center for Brain Research and Neurotechnologies of the Federal Medical-Biological Agency of Russia. Chief freelance neurologist of the Russian Ministry of Health.

Conflict of interest: none.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. neurologist;

2. otorhinolaryngologist;

3. functional diagnostics physician;

4. radiologist;

5. neurosurgeon;

6. maxillofacial surgeon;

7. ophthalmologist;

8. infectious disease physician;

9. medical rehabilitation physician;

10. general practitioner (family physician);

11. internist;

12. district general practitioner;

13. admitting department physician;

Table 1. Scale for assessing levels of evidence (LE) for diagnostic methods (diagnostic interventions)

Table 2. Scale for grading levels of evidence certainty (LEC) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3. Scale for grading grades of recommendation (GR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

1. Federal Law No. 323-FZ of November 21, 2011 (as amended on July 2, 2021) "On the Fundamentals of Protecting the Health of Citizens in the Russian Federation" (Collected Legislation of the Russian Federation, 2011, No. 48, Art. 6724) (with amendments and additions, effective from October 1, 2021) (https://roszdravnadzor.gov.ru/documents/100)

2. Order of the Russian Ministry of Health No. 203n dated May 10, 2017, "On Approval of Criteria for Assessing the Quality of Medical Care"; (Registered with the Ministry of Justice of Russia on May 17, 2017, No. 46740); (http://publication.pravo.gov.ru/Document/View/0001201705170016?rangeSize=1);

3. Order of the Ministry of Health of the Russian Federation No. 103n dated February 28, 2019, "On Approval of the Procedure and Deadlines for the Development of Clinical Practice Guidelines, Their Revision, Standard Template of Clinical Practice Guidelines and Requirements for Their Structure, Composition and Scientific Validity of Information Included in Clinical Practice Guidelines."

4. International Statistical Classification of Diseases and Related Health Problems (ICD-10) (https://mkb-10.com/);

5. State Register of Medicines (http://www.grls.rosminzdrav.ru/grls.aspx);

6. Order of the Russian Ministry of Health No. 804n dated October 13, 2017, "On Approval of the Nomenclature of Medical Services", registered with the Ministry of Justice on November 7, 2017, registration No. 48808 (as amended on March 24, 2020)

Appendix B. Physician Action Algorithms

Appendix B1

Management algorithm for a patient presenting with facial pain and typical triggers

Appendix B2

Algorithm for identifying atypical facial pain in a patient

Appendix B3

Management algorithm for a patient presenting with pain in the root of the tongue, tonsils, pharynx, or soft palate

Appendix B4

Differential diagnosis of trigeminal autonomic cephalalgias (TACs) [480]

Appendix B5

Appendix B6

Management algorithm for a patient with facial neuropathy

Appendix B7

Management algorithm for a patient with lagophthalmos according to its severity [102]

Appendix B8.

Algorithm for selecting a surgical treatment method for a patient with facial nerve injury depending on severity and disease duration3

Appendix B9.

Algorithm for selecting a surgical treatment method for a patient depending on the level of facial nerve injury

Appendix B10

Management algorithm for a patient with hemifacial spasm

Appendix C. Patient Information

Appendix B1. Patient information leaflet for facial pain

The onset and intensification of pain are linked not only to neurological but also to psychological aspects. Various processes are constantly occurring in the body. Some sensations are interpreted by us as safe and tolerable (itching, mild muscle pain); we do not focus on them and continue our usual activities, while others may seem unfamiliar, causing anxiety and apprehension, which attracts our attention and intensifies their character.

Emotions (anxiety, anger, sadness) associated with the evaluation of bodily sensations can amplify pain. The intensity of physical pain (arising as a result of mechanical injury) depends on the attention directed toward it; therefore, it is important to perform exercises aimed at voluntary attention shifting and relaxation.

Perfectionism is the belief that an ideal is attainable and that any deviation from it is wrong or unpleasant. Perfectionists are more sensitive to pain because they are intolerant of any deviations from their habitual state of well-being, repeatedly checking their condition (whether their head hurts, what the sensation in the face is right now). Such repeated checks require shifting attention.

Exercise 1.

• Sit up straight or lie on your back

• Place your hand on your abdomen

• Inhale deeply through your nose, while the hand on your abdomen should rise (chest moves slightly)

• Exhale through your mouth

• Try to focus on your breathing

• If any thoughts come to mind, simply note them: "I was thinking about..." (this also applies to focusing on discomfort in the facial area)

• Return to observing your breathing

Exercise 2.

• Find 5 objects you haven't paid attention to before

• Try to hear 4 sounds surrounding you

• Feel 3 surfaces: what material is this? what does it feel like (hard, soft, cold, warm, smooth, textured)?

• Sense 2 odors (you can smell an aroma that calms you down)

• Taste 1 item: what does it taste like?

Exercise 3.

• It is important to know how to distract yourself not only with techniques, but also with everyday activities

• Check your daily schedule

• Fill your free time with interesting activities

• While completing the tasks, focus on the process of doing them rather than evaluating your work or your current sensations.

Appendix B2. Patient information leaflet for cluster headache

Cluster headache is characterized by periodic attacks of extremely intense headache, or clusters. The pain is unilateral, localized behind or around the eye, and can radiate to other parts of the face, head, and neck. Cluster headache attacks are accompanied by restlessness, unlike migraine attacks, which limit the patient's physical activity. Cluster headache is a rare type of headache accompanied by autonomic symptoms.

The following autonomic symptoms are common:

Lacrimation during the attack, eye redness.

Nasal discharge may also occur during the attack.

Facial and/or forehead sweating.

Change in facial skin color on the affected side.

Swelling around the eye on the affected side.

What is a cluster period?

A cluster period may begin at the same time of year and last for the same duration as before. For example, a cluster period may start every spring or autumn. For most people with cluster headaches, a cluster period lasts from a week to a year. After the cluster period, a remission period begins lasting three months or more, but no more than a year. Such a cluster headache is called episodic. If the cluster period lasts longer than a year, the cluster headache is called chronic.

When should you see a doctor?

cluster headache has appeared for the first time;

change in the nature of the pain.

You must seek medical attention immediately if you experience the following symptoms: sudden, thunderclap intense headache resembling a "blow to the head"; headache accompanied by fever, nausea, nuchal rigidity, seizures, limb weakness, speech disturbances; progressive headache following a head injury.

What are the causes of cluster headaches?

Experts do not fully understand what causes cluster headaches. A connection with the area of the brain responsible for the body's biological clock, known as the hypothalamus, is suspected.

What are the triggers for cluster headaches?

There are several triggers for cluster headaches. The most common of these is alcohol consumption. Other triggers may include weather changes and certain medications.

What are the risk factors for cluster headaches?

Male sex. Men suffer from cluster headaches more often than women.

Age. Most people who experience cluster headaches are between 20 and 50 years old. However, this condition can begin at any age. • Smoking. Many people with cluster headaches are smokers.

Alcohol consumption. If you have cluster headaches, drinking alcohol during a cluster period can increase the risk of an attack.

Hereditary factors. Having a close relative with cluster headaches increases the risk of developing cluster headaches.

Diagnosis of cluster headache

The diagnosis is based on the patient's complaints, the history of the disease's development, the frequency and nature of the headache, and additional symptoms accompanying the attack. For newly onset cluster headaches, the doctor may prescribe an MRI or CT scan of the brain.

What questions might the doctor ask during the appointment?