Extrapyramidal Diseases and Parkinson's Disease

Extrapyramidal Diseases

• Parkinsonism is a clinical syndrome characterized by resting tremor, bradykinesia, rigidity, loss of postural reflexes, flexed posture, and freezing.
  • It can be idiopathic (Parkinson's disease) or secondary to various factors like dopamine deficiency, vascular issues, post-encephalitic conditions, hydrocephalus, drug-induced, or toxic agents.
  • Degenerative disorders like Alzheimer's disease and Parkinson-dementia complex can cause Parkinsonism.
  • Genetic disorders like Wilson's disease, Huntington's disease, and Dopa-responsive dystonia are also associated with Parkinsonism.
  • Traumatic events like head trauma in boxers can, but rarely, cause Parkinsonism.

Parkinson's Disease (PD)

• This progressive neurodegenerative disorder is characterized by rest tremor, bradykinesia, and rigidity.
• As the disease progresses, gait and balance disturbances as well as non-motor features like dementia can occur.
• The cause is unknown, but age, sex (males are more likely), rural residence, and farming exposure to pesticides and herbicides are associated with increased risk.
• Caffeine consumption is associated with a decrease in risk.
• Pathophysiology involves degeneration of pigmented cells in the substantia nigra, resulting in dopamine deficiency.
  • When cell loss exceeds 60%, motor symptoms of PD become apparent.

Clinical Features of Parkinsonism & PD

• Rest tremor is regular, rhythmic, and occurs at 4-8 cycles per second. It begins unilaterally in the upper limb and spreads to all four limbs.
  • This tremor gives the hand a "pill-rolling" posture and increases with emotional stress and fatigue, disappearing during sleep and voluntary movements.
• Rigidity (hypertonia) affects proximal more than distal muscles, predominantly the flexors.
  • This results in a flexion attitude which may be continuous (lead-pipe rigidity) or accompanied by tremors (cogwheel rigidity).
  • Freezing and shuffling gait are common.
• Bradykinesia is a slowness of initiation and execution of voluntary movements, with progressive reduction in speed and amplitude with repetition.
• Emotional and associative movements are diminished, resulting in a "mask face" with immobile expressions, monotonous speech, and absent arm swinging.
• Postural instability is a significant feature of PD, not due to visual, vestibular, cerebellar, or proprioceptive dysfunction.
• Other features include diminished sense of smell, constipation, sleep disorders (restless legs syndrome), and dementia.
  • Dementia occurs in 20-40% of patients with idiopathic PD after 10-15 years.
  • Dopaminergic medication can exacerbate this.

Management of PD

• Medical Treatment:
  • Aims to restore the balance of acetylcholine and dopamine in the basal ganglia and substantia nigra.
  • Levodopa (LD), a dopamine precursor, is the most effective treatment for motor features, typically combined with carbidopa to inhibit extracerebral decarboxylation.
  • Dopamine agonists (DA) are an alternative, particularly in younger patients to delay the use of LD and its associated long-term complications.
    • DA is used as monotherapy in early disease and as adjuncts to LD in more advanced disease.
  • Anticholinergic agents have a limited role, mainly for severe tremor and dystonia in young patients.
    • Significant side effects are a concern, especially in the elderly.
  • Amantadine (antiviral) was previously used in early PD but is now less common.
    • Currently utilized to manage drug-related dyskinesias.
  • Monoamine oxidase B (MAO-B) inhibitors like selegiline and rasagiline are adjunct therapies for levodopa.
  • COMT inhibitors like entacapone or opicapone increase the amount of levodopa reaching the central nervous system.
    • These are used to manage "end-of-dose deteriorations" and are administered with each levodopa dose.
• Surgery/Other Procedures:
  • Can dramatically improve motor symptoms and reduce side effects of dopaminergic therapies.
  • Deep Brain Stimulation (DBS) of the thalamus, subthalamic nucleus, or globus pallidus is effective for treating motor symptoms.
    • Candidates are those who significantly improve with LD but cannot sustain the response throughout the day.
  • Intestinal infusion of LD (Duodopa®) utilizes an external pump to maintain LD benefits and reduce dyskinesias.
  • Thalamotomy and pallidotomy are less common surgical options.

Chorea

• Involuntary, static, irregular, dysrhythmic, sudden, jerky, pseudopurposive movements with an unpredictable pattern affecting any part of the body.
• Caused by a lesion in the caudate nucleus.
• Causes include inherited disorders, immune-mediated conditions, drug-induced effects, metabolic conditions, and hemichorea.

Rheumatic Chorea (Sydenham's Chorea)

• A major criterion of rheumatic fever, occurring alongside other rheumatic manifestations in approximately 10% of cases.
• Less common in the antibiotic era.
• Affects children aged 5-15 years, with females being more likely to be affected.
• Caused by an autoimmune response to group-A β-hemolytic streptococci infection.
  • Molecular mimicry to streptococcal antigens leads to autoantibody production against cells in the corpus striatum of the basal ganglia.
• Clinical picture includes choreic movements affecting the tongue, face, trunk, and extremities, more proximally than distally.
  • These movements increase with emotional stress and disappear during sleep.
• Hypotonia results in flexion at the wrist and overextension at the metacarpophalangeal and interphalangeal joints, with fanning of the fingers ("boat-shaped" or "scaphoid-shaped" hand).
• Emotional instability, with sudden laughter or crying, is common.
• Treatment involves complete rest in bed, acetylsalicylic acid, dopamine-receptor antagonists (antipsychotics like haloperidol), and corticosteroids in case of significant rheumatic activity or treatment failure.

Dystonia

• Involuntary movement characterized by sustained muscle contraction resulting in twisting and repetitive movements or postures.
  • This is due to co-contraction of antagonistic muscles.
  • Hypertonia occurs during the movement, while normal tone is present between movements.
• Dystonia can be generalized (dystonia muscularum deformans or torsion dystonia), which is a familial disorder starting in childhood, or partial.
  • Cervical dystonia (spasmodic torticollis or wry neck) is the most common focal dystonia, resulting in turning of the head to the opposite side, especially during walking.
  • Oromandibular dystonia affects the mouth and jaw muscles.
  • Blepharospasm is involuntary tight eye closure causing functional blindness.
  • Focal hand dystonia (writer's cramp) involves spasm and pain in the hand and forearm muscles during writing.

Treatment of Dystonia

• Anticholinergic drugs, if ineffective, especially in generalized dystonia, may be replaced by tetrabenazine, pimozide, or sulpiride.
• Baclofen, administered intrathecally by an implanted pump, can be effective for certain types of dystonia.
• Local botulinum toxin injection is used for focal dystonia, reducing muscle contraction for approximately 3 months without major complications.
• Thalamic Deep Brain Stimulation is reserved for patients with disabling dystonia when other treatments have failed.
• Levodopa should be tried in childhood-onset dystonia, proving effective in 10% of cases.

This quiz covers key concepts related to extrapyramidal diseases, focusing on Parkinsonism and Parkinson's Disease. You will learn about the clinical features, causes, and genetic factors involved in these conditions. Test your understanding of the complex interactions that lead to these neurodegenerative disorders.