Contents · 12 sections
In a nutshell. Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (α-synuclein). Clinical features: bradykinesia plus at least one of rigidity and 4–6 Hz resting tremor; asymmetric onset. Non-motor symptoms (hyposmia, REM sleep behavior disorder, constipation, depression) often precede motor manifestations. Clinical diagnosis based on MDS-2015 criteria; DAT-SPECT in case of doubt. Therapeutic backbone: levodopa (symptomatic efficacy), dopamine agonists, MAO-B inhibitors. For motor fluctuations — COMT inhibitors, amantadine, apomorphine, subthalamic nucleus DBS.
1. Epidemiology and pathogenesis
- Prevalence 0.3% in the general population, ~1% in individuals over 60 years of age.
- Mean age of onset is 60 years; juvenile and early-onset forms occur before 40 years.
- Etiology: genetic (LRRK2, GBA, SNCA, PARK2/PINK1/DJ-1), environmental (pesticides, heavy metals), idiopathic.
- Pathomorphology: depigmentation of the substantia nigra, Lewy bodies (α-synuclein), Braak staging (from the medulla oblongata to the cortex).
- By the time motor symptoms appear, ~60% of dopaminergic neurons have been lost.
2. Clinical presentation
Motor symptoms
- Bradykinesia — slowness and poverty of movement, micrographia, hypomimia, reduced arm swing.
- «Cogwheel» rigidity (presence of tremor) or «waxy flexibility».
- Resting tremor 4–6 Hz — «pill-rolling»; disappears during movement and sleep; asymmetric.
- Postural instability — in late stages (pull test).
- «Pleidian» posture, shuffling gait, freezing phenomenon, propulsion.
Non-motor symptoms
- Hyposmia (90%) — precedes motor symptoms by years.
- REM-sleep behavior disorder — «acting out» dreams, predicts synucleinopathy.
- Constipation, orthostatic hypotension, hyperhidrosis, sexual dysfunction.
- Depression, anxiety, apathy, anhedonia.
- Cognitive impairment, dementia (in late stages).
- Visual hallucinations (more often associated with therapy).
3. MDS-2015 diagnostic criteria
- Basis — parkinsonism: bradykinesia + (rigidity and/or resting tremor 4–6 Hz).
- Criteria for clinically established PD: parkinsonism + absence of «red flags» (see below) + ≥ 2 supportive criteria + absence of absolute exclusion criteria.
- Supportive criteria: response to levodopa, levodopa-induced dyskinesias, resting tremor, hyposmia, or cardiac sympathetic denervation (MIBG).
- Absolute exclusion criteria: cerebellar symptoms, supranuclear vertical gaze palsy, probable frontotemporal dementia / primary progressive aphasia within the first 5 years, leg-only parkinsonism > 3 years, D2 antagonist therapy, lack of response to high doses of levodopa, cortical sensory loss, normal DAT-SPECT, alternative diagnosis.
Red flags
- Rapid progression (< 5 years to wheelchair).
- Lack of progression > 5 years.
- Early prominent bulbar/pseudobulbar symptoms.
- Inspiratory stridor.
- Severe autonomic dysfunction within the first 5 years (syncope, incontinence).
- Falls in the first year.
- Anterocollis, severe limb contractures within the first 10 years.
- Absence of non-motor symptoms ≥ 5 years.
4. Differential diagnosis
| Condition | Key differences |
|---|---|
| Essential tremor | Action tremor, symmetric, familial, improves with alcohol |
| Multiple system atrophy (MSA) | Cerebellar and/or early autonomic dysfunction, poor response to levodopa |
| Progressive supranuclear palsy (PSP) | Vertical gaze palsy, early backward falls, symmetrical onset |
| Corticobasal degeneration | Apraxia, alien limb phenomenon, asymmetric rigidity unresponsive to levodopa |
| Dementia with Lewy bodies | Cognitive fluctuations, visual hallucinations, early dementia (< 1 year from motor onset) |
| Vascular parkinsonism | Lower body parkinsonism, risk factors, white matter changes |
| Drug-induced parkinsonism | Antipsychotics, metoclopramide; symmetric, regresses after withdrawal |
| Normal pressure hydrocephalus | Hakim's triad — dementia, gait apraxia, urinary incontinence |
| Wilson's disease | Young age, liver dysfunction, Kayser-Fleischer rings |
5. Diagnostics
- Clinical examination using MDS-UPDRS, Hoehn and Yahr scale.
- Brain MRI — exclusion of vascular and atypical parkinsonism ("hot-cross bun" sign in MSA, "hummingbird" sign in PSP).
- DAT-SPECT (FP-CIT) — differential diagnosis with essential tremor, vascular and drug-induced parkinsonism.
- Cardiac MIBG scintigraphy — cardiac denervation is pathognomonic for PD.
- In young patients (< 40 years): ceruloplasmin, 24-hour urinary copper, genetic testing.
6. Pharmacotherapy
Levodopa
- Most effective drug; combination with a DDC inhibitor (carbidopa/benserazide).
- Start with 100–150 mg/day in 3 divided doses, with titration.
- Indications: significant functional impairment, especially in the elderly.
- Long-term side effects: motor fluctuations (wearing-off, on-off), dyskinesias (2/3 of patients after 5–10 years).
- Levodopa should not be delayed out of fear of dyskinesias — quality of life is more important.
Dopamine agonists
- Pramipexole, ropinirole, rotigotine (transdermal), apomorphine (subcutaneous).
- Indicated for young patients as initial therapy (to delay levodopa), in combination with levodopa at advanced stages.
- Side effects: nausea, orthostatic hypotension, somnolence, peripheral edema, impulse control disorders (pathological gambling, hypersexuality, compulsive shopping).
MAO-B inhibitors
- Selegiline, rasagiline, safinamide.
- Mild symptomatic effect as monotherapy in early stages and as an adjuvant in wearing-off.
COMT inhibitors
- Entacapone, opicapone, tolcapone.
- Prescribed with levodopa to prolong its duration in wearing-off.
Amantadine
- NMDA antagonist + indirect dopaminergic effect.
- Reduces dyskinesias; moderate motor effect.
Anticholinergics
- Trihexyphenidyl, biperiden — only for tremor in young patients without cognitive impairment.
7. Advanced stages and therapy complications
- Wearing-off — waning of levodopa effect before the next dose.
- On-off — unpredictable fluctuations unrelated to dosing times.
- Freezing — sudden "freezing" at the initiation of walking or in doorways.
- Dyskinesias — peak-dose, diphasic, dystonic off-period.
- Management: fractionating the levodopa dose, adding COMT/MAO-B inhibitors, amantadine, subcutaneous apomorphine, levodopa-carbidopa intestinal gel, DBS.
8. Surgical treatment
- Deep brain stimulation (DBS) — subthalamic nucleus (STN) or internal segment of the globus pallidus (GPi).
- Indications: motor fluctuations and dyskinesias refractory to optimized pharmacotherapy; preserved response to levodopa; absence of dementia; age under 70 years.
- Effect: reduction in off-time and dyskinesias, reduction of the levodopa dose by 30–50%.
- Does not affect non-motor symptoms or the rate of progression.
- Alternatives: MRI-guided focused ultrasound pallidotomy/thalamotomy.
9. Non-motor symptoms — management
- Depression: SSRIs/SNRIs, pramipexole.
- Psychosis (hallucinations): reduce dopaminergic drug doses, quetiapine, clozapine, pimavanserin (not available in Russia).
- Dementia: rivastigmine, donepezil.
- REM sleep behavior disorder: clonazepam, melatonin.
- Orthostatic hypotension: increased water and salt intake, compression stockings, midodrine, fludrocortisone.
- Constipation: laxatives, macrogol.
- Sialorrhea: botulinum toxin injections into the salivary glands.
10. Non-pharmacological methods
- Exercise therapy, Tai Chi — reduction of falls.
- Speech therapy (LSVT LOUD) for hypophonia.
- Occupational therapy, safe home environment setup.
- Psychological support, patient support groups.
11. Prognosis
- The disease is progressive; average life expectancy is close to that of the general population with adequate therapy.
- Main causes of disability — falls, dementia, postural instability.
- Predictors of rapid progression: older age at onset, predominance of postural instability, early cognitive impairment.
12. FAQ
When to start therapy?
When functional limitations appear. "Delaying" is not justified — early initiation improves quality of life; studies have demonstrated the safety of early levodopa initiation.
Why does levodopa lose its effect?
Progressive neuronal loss → reduction in dopamine storage capacity → shorter and less predictable drug effect. Increasing dosing frequency, adding COMT/MAO-B inhibitors, DBS.
Can Parkinson's disease be cured?
No. Neuroprotective therapy (including rasagiline) has not proven an effect on progression. Anti-α-synuclein antibodies and cell therapy are currently being investigated.
What are impulse control disorders?
Pathological gambling, hypersexuality, compulsive shopping, binge eating — up to 15% in patients on dopamine agonists. Reduce/discontinue the agonist, behavioral therapy.
What does DAT-SPECT show in PD?
Reduction of presynaptic FP-CIT uptake in the striatum, asymmetrical, starting in the posterior putamen. Normal DAT-SPECT rules out neurodegenerative parkinsonism.
See also: Alzheimer's disease · Multiple sclerosis · Stroke · Antidepressants · Neurology catalog
This material is educational in nature and does not replace a doctor's consultation. Verify treatment regimens and dosages with current clinical guidelines.