On this World Parkinson's day, we bring to you an article that highlights the early signs and symptoms of Parkinson's disease and also the treatment approach required as per the American Academy of Neurology.

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Parkinson’s disease is a progressive neurodegenerative disorder that can cause significant disability and decreased quality of life. It is characterised by tremor, rigidity, and slowness of movements, and is associated with progressive neuronal loss of the substantia nigra and other brain structures.

Aetiology

1. Low dopamine levels- Affects movement and coordination

2. Low norepinephrine levels

• Stiffness and rigidity
• Postural instability
• Tremor
• Anxiety
• Dementia
• Depression

3. Presence of Lewy bodies in the brain (protein clumps)

• Movement
• Behaviour
• Mood
• Dementia
• Genetic factors

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Early signs and symptoms

It is important to detect the early signs so as to start immediate intervention. These include slow progressive changes in the form of movement such as tremors in the body. There is a loss of coordination and balance, they often drop things, and there is a progressive loss of smell and control of facial expressions. The patient seems to have voice tremors and cramped handwriting and may present with sleep disorders associated with rapid eye movement.

Further common signs and symptoms include:

• Mood changes, including depression
• Difficulty chewing and swallowing
• Fatigue
• Constipation
• Skin problems
• Progressive dementia, delusions, and hallucinations

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Differential diagnosis

1. Drug-induced Parkinsonism
2. Head trauma
3. Encephalitis
4. Stroke
5. Multiple system atrophy
6. Progressive supranuclear palsy
7. Normal-pressure hydrocephalus

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Diagnosis

According to the UK Parkinson’s Disease Society Brain Bank's clinical diagnostic criteria:

Step 1: Diagnosis of a parkinsonian syndrome

Bradykinesia and at least one of the following:

• Muscular rigidity
• 4–6 Hz rest tremor
• Postural instability not caused by primary visual, vestibular, cerebellar or proprioceptive dysfunction

Step 2: Exclusion criteria for PD

1. History of repeated strokes with the stepwise progression of parkinsonian features
2. History of repeated head injury
3. History of definite encephalitis
4. Oculogyric crises
5. Neuroleptic treatment at the onset of symptoms
6. More than one affected relative
7. Sustained remission
8. Strictly unilateral features after 3 years
9. Supranuclear gaze palsy
10. Cerebellar signs
11. Early severe autonomic involvement
12. Early severe dementia with disturbances of memory, language and praxis
13. Babinski’s sign
14. Presence of cerebral tumour or communicating hydrocephalus on CT scan
15. A negative response to large doses of levodopa (if malabsorption excluded)

Step 3: Supportive criteria for PD (three or more required for a diagnosis of definite PD)

1. Unilateral onset
2. Rest tremor present
3. Progressive disorder
4. Persistent asymmetry affecting the side of onset most
5. Excellent response (70–100%) to levodopa
6. Severe levodopa-induced chorea
7. Levodopa response for 5 years or more
8. The clinical course of 10 years or more

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Treatment guidelines by the American Academy of Neurology

Key recommendations for practice:

1. Levodopa is the most effective pharmacologic treatment for Parkinson’s disease symptoms, especially bradykinesia and rigidity.
2. Dopamine agonists effectively treat early Parkinson’s disease.
3. Motor complications in patients with advanced Parkinson’s disease can be treated by adding a dopamine agonist, monoamine oxidase-B inhibitor, or catechol O-methyltransferase inhibitor to levodopa therapy.
4. Deep brain stimulation of the subthalamic nucleus can improve Parkinson’s disease symptoms.

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Early-stage treatment

Early-stage Parkinson’s disease includes patients who have had the disease for less than five years or those who have not developed motor complications from levodopa use.

1. Anticholinergics

• Benztropine
• Trihexyphenidyl

2. Carbidopa/levodopa- Immediate-and sustained-release carbidopa/ levodopa (Sinemet)

3. COMT inhibitors

• Entacapone
• Tolcapone

4. Dopamine agonists

• Bromocriptine
• Pergolide
• Pramipexole
• Ropinirole

5. MAO-B inhibitors

• Selegiline
• Rasagiline

6. NMDA receptor inhibitor- Amantadine

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Late-stage treatment

Late-stage Parkinson’s disease includes patients already receiving carbidopa/levodopa treatment who have developed motor complications. After five years of treatment with levodopa, most patients develop motor fluctuations and dyskinesia (i.e., involuntary choreiform or stereotypic movements involving the head, trunk, limbs, and, occasionally, the respiratory muscles).

1. These motor complications can be treated by further adding a Dopamine agonist, MAO-B inhibitor, or Catechol O-methyltransferase (COMT) inhibitors in parenteral or oral form.
2. Amantadine has also been used successfully in late-stage.
3. Surgery is also considered an option in severe cases in the form of deep brain stimulation of the subthalamic nucleus and Unilateral pallidotomy.

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Non-pharmacological intervention

1. Stretching, strengthening, and balance training may improve gait speed, balance, and participation in activities of daily living.
2. Specific voice training can effectively treat voice and speech disorders.
3. Nutritional interventions (e.g., a high-fibre diet) can help reduce constipation.
4. Dietary amino acids may interfere with levodopa absorption; therefore, protein restriction may be necessary for patients with decreased levodopa response.

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Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.