Amyotrophic lateral sclerosis

Myasthenia gravis and myasthenic crisis

One of the most severe complications of neuromuscular junction pathology is myasthenic crisis. It is usually precipitated either by an abrupt cessation of prescribed therapy (or its incorrect management) or by concurrent infectious diseases. Clinically, the crisis presents with acute generalized muscle weakness. Patients rapidly develop bulbar symptoms: marked dysphagia (swallowing disorders), dysphonia, and dysarthria, as well as life-threatening respiratory disorders.

A comprehensive approach is used to confirm the diagnosis of myasthenia gravis:

• Exercise tests: aimed at objectively identifying pathological muscle fatigability.
• Proserine (neostigmine) test: holds key diagnostic significance. 1–3 ml of a 0.05% proserine solution (dose calculated by body weight) is administered subcutaneously along with 0.5 ml of 0.1% atropine. A positive result is considered to be a noticeable reduction in muscle weakness after 20–40 minutes (the effect persists for up to three hours).
• Electroneuromyography (ENMG): uses the method of repetitive nerve stimulation at a frequency of 3 impulses per second (3 Hz). A specific decrement (reduction in amplitude) of the M-response is recorded in 75% of patients.
• Chest computed tomography: is mandatory for all patients to exclude thymoma or thymic hyperplasia.

Treatment for myasthenia gravis is selected strictly on an individual basis. Symptomatic therapy is based on anticholinesterase drugs: proserine is used in short courses (including before meals for dysphagia), while pyridostigmine (kalimin) is used for long-term administration (30–60 mg up to 6 times a day). In severe cases, glucocorticosteroids are prescribed (prednisolone at an initial dose of 60–100 mg/day), along with plasmapheresis sessions and intravenous immunoglobulin administration (0.4 g/kg for 5 days). Surgical treatment—thymectomy—is indicated for patients under 70 years of age with the generalized form or in the presence of thymoma. Management of a crisis requires intravenous administration of proserine with atropine, high doses of prednisolone, and, if necessary, transferring the patient to mechanical ventilation.

Progressive muscular dystrophies (PMD)

This is a large group of hereditary diseases characterized by a primary, genetically determined lesion of muscle tissue. It is important to note that motor neurons, axons, and neuromuscular junctions remain completely unaffected in this pathology. Symptoms typically manifest in childhood or adolescence and present as steadily progressive symmetrical muscle weakness and atrophy, starting from the proximal limbs and girdles (pelvic or shoulder). Sensory function is not impaired, but tendon reflexes diminish up to areflexia.

The most common form is Duchenne muscular dystrophy (50–70 cases per 1 million). The condition is inherited in an X-linked recessive manner, which is why only boys are affected. The pathogenesis is based on a disruption in the synthesis of the muscle protein dystrophin, leading to fiber necrosis and their replacement by connective tissue.

The clinical presentation of Duchenne muscular dystrophy develops in stages:

1. In early childhood, there is a delay in motor development (children start walking later, experience difficulty running).
2. At 2–5 years of age, gait changes due to weakness in the pelvic girdle and proximal leg muscles.
3. The process spreads in an ascending manner to the back, shoulder girdle, and arm muscles.
4. A specific pattern appears—Gowers' sign («staircase» climbing), where the child has to step-by-step push off with their hands on their own legs when rising from the floor.

The disease is accompanied by cardiomyopathy and often intellectual impairment. The prognosis is unfavorable: by age 10, walking ability is severely restricted; by age 15, complete immobility ensues; and death due to cardiac or pulmonary failure occurs in the third decade of life. There is no etiopathogenetic treatment; only symptomatic support is applied (massage, orthopedic correction, gentle physical therapy without overload).

Hereditary myotonias and periodic paralysis

Myotonias comprise a group of genetic diseases whose main feature is delayed relaxation of skeletal muscle after contraction. This myotonic action phenomenon is characterized by the fact that with repeated contractions it gradually weakens and can temporarily disappear completely.

Several main forms are distinguished:

• Thomsen myotonia: inherited in an autosomal dominant manner. It manifests already in children (e.g., facial muscle spasm and voice changes when crying). It runs a benign course, with muscle strength preserved or even increased.
• Becker myotonia: has an autosomal recessive transmission type. It debuts at 4–12 years of age and has a more severe course. Weakness begins in the legs and becomes generalized. More than half of patients suffer from persistent weakness in the forearms and sternocleidomastoid muscles.
• Myotonic dystrophy: a multisystem autosomal dominant disease (debut at 15–35 years). In addition to myotonia and muscle atrophy, it is accompanied by cataracts and cardiac arrhythmias. It leads to severe disability within 15–20 years.

Treatment for myotonias is symptomatic and generally ineffective; diphenylhydantoin, nifedipine, or diacarb are used to reduce spasms.

A separate group is constituted by paroxysmal myoplegia (periodic paralysis). This is an autosomal dominant disorder characterized by attacks of flaccid peripheral paralysis due to transient impairment of muscle fiber cell membrane excitability.

Briefly: answers to topical questions

What else to study on this topic

• Pathogenesis of membrane excitability impairment in paroxysmal myoplegia
• Methodology of ENMG with repetitive stimulation (3 Hz) in myasthenia gravis
• Prenatal genetic diagnosis of progressive muscular dystrophies
• Tapering regimens for glucocorticosteroids in severe myasthenia gravis

Other topics in "Chapter 21. Neuromuscular Diseases. Motor Neuron Diseases"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.