Parkinson's Disease: Causes, Symptoms, Diagnosis, Treatment and Prognosis

Parkinson's disease is a condition where a part of your brain gradually deteriorates, leading to ever-worse symptoms. Your senses, ability to think, mental health, and other aspects of yourself may be negatively impacted by this condition. It is most recognized for affecting mobility, balance, and muscular strength.

Symptoms of Parkinson's Disease

• Tremor, primarily at rest and characterized as a tremor in the hands that rolls pills; various types of tremor are conceivable
• Movement that is sluggish and infrequent (also known as bradykinesia and hypokinesia)
• Limb rigidity (stiffness)
• Issues with gait and balance (postural instability)
• Parkinson's symptoms can include both movement-related ("motor") and non-movement-related ("non-motor") symptoms. Non-motor symptoms of PD frequently have a greater negative impact on patients than do motor symptoms. Depression, anxiety, apathy, hallucinations, constipation, orthostatic hypotension, sleep difficulties, loss of smell, and a number of cognitive deficits are examples of non-motor symptoms.

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Causes of Parkinsonism

• Parkinson’s Disease is an Age related neurodegenerative disorder.
• Can be genetic or sporadic.
• Genes involved are- PARK SCN4A gene, PARKIN gene present on chromosome 6, Leads to 1⁰ parkinsonism / typical parkinsonism. It has a good response to levodopa.

Secondary Parkinsonism 

Causes includes

• Drugs. Haloperidol, Chlorpromazine and metoclopramide. These drugs reduce Dopamine and increase Ach. Benzhexol can be given (anticholinergic) as it decreases Ach and maintains the ratio.
• Hyperparathyroidism - more calcium - hypercalcification of basal ganglia.
• Toxins. CO, CS2, MPTP (insecticide).
• Carbon Monoxide Poisoning -Carboxyhemoglobin has 1000 times more affinity to oxygen so it Leads to development of anemic hypoxia.

Antemortem presentations

• Rigidity - due to basal ganglia malfunction.
• Headache - due to hypoxia.
• Paralysis agitans.

If the CO poisoning patient is brought to hospital on time: Hyperbaric oxygen therapy is given. Dissolved oxygen levels increase and Hypoxia of tissues is treated.

• Trauma / vascular damage / tumor / normal pressure hydrocephalus (NPH).
  • NPH - triad features:
    • Dementia
    • Ataxia
    • Incontinence 
  • Damage to substantia nigra occurs.
• Typical parkinsonism - Manifested with resting tremors but not the atypical parkinsonism. 

Atypical Parkinsonism

1. Multiple System Atrophy- it is Also called shy drager syndrome.
2. Autonomic Insufficiency- Associated with features like,

Orthostatic hypotension - BP of a patient is measured in supine position. After 3 minutes BP is measured in erect position.

• If systolic BP falls > 20 mmHg 
• If diastolic BP falls > 10 mmHg
• Indicates presence of orthostatic hypotension. 

Also associated with Constipation and diarrhea 

MRI finding - shows Hot Cross BUN sign.

3.  Progressive Supranuclear Gaze Palsy

• Patients have high chances of falling backwards.
• Superior colliculus is involved. 
• Vertical gaze helps in looking down and up unconsciously.
• When this is impaired the chances of falling increases. Mostly downward gaze is affected.
• Eyelid apraxia - Due to damage to the vertical gaze the patient can move the eyeball and not be able to look downwards.
• This creates mess while eating.
• As the patient can't look down he may not be able to put the food directly into the mouth.
• May hit the chin and spill the food on himself.
• Hyperextension of neck. As the patient can look down he lifts his neck up in order to look at things Inferior to him. This causes extension of the neck known as hyperextension. 

4. Alien Hand Syndrome. This condition is due to the damage in the corpus callosum which  coordinates the activity between left and right hemispheres. The condition is called - corticobasal degeneration syndrome. In this Tau protein is involved. The patient presents with the symptoms like rigidity, bradykinesia etc.
5. Pick's Disease. It is Also known as Frontotemporal Dementia. In this the Affected parts are frontal and temporal regions.
6. Wilson's Disease. This disease Has parkinsonism like symptoms. In this Lenticular nucleus damage occurs. It is also a neurodegenerative disorder. Copper deposition occurs in the lenticular nucleus. MRI finding shows  Giant face of panda appearance. We can also find Neurodegeneration in brain with iron accumulation: it is Differential diagnosis for Wilson's disease. In this condition More Iron is  in putamen. It was Previously known as  Halloverden Spatz

MRI finding  shows Eye of a tiger appearance. Both are pediatric onset neurodegenerative disorders.

7. Huntington Chorea. It is an Autosomal dominant disorder. Affected Age is 40 to 50 years. The Gene involved is Huntington gene present on 4th chromosome and the Protein involved is Ubiquitin protein. The Huntington gene leads to the Ubiquitin protein malfunction. In this there is Accumulation of Ubiquitin protein in cytoplasm of neurons. This protein is called Huntingtin protein, it  causes misfiring of neurons. This is a disorder of trinucleotide repeats. In this condition GABA decreases, Dopamine is excess. Levodopa is contraindicated. So for treatment Dopamine depletors are given.

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Clinical Features 

• Anticipatory - Severity of disease increases with generation.
• Chorea - fast involuntary movement.
  • May last for a longer time.
• Dementia - suboptimal dementia.
• Behavioral changes like aggressiveness.
• Rigidity
• Bradykinesia - poor control of the body.

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Diagnosis

MRI Head - Finding shows Boxcar ventricle.

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Treatment: 

Dopamine depletor - Tetrabenzine is given.

Typical Parkinsonism

Clinical Features of Parkinson's Disease

• Non motor symptoms
  • Anosmia 
  • Constipation 
  • Mood and sleep disorders
• Motor symptoms
  • Resting tremors - 4 to 6 Hz (low frequency).
    • Asymmetric
    • Pill rolling tremors
    • Worsens with anxiety
    • Disappears on sleep
    • Most common
    • Earliest symptom
• Bradykinesia - slow movement.
  • May lead to akinesia and akinetic mutism.
• Rigidity
  • Cogwheel - rigidity of upper limbs.
  • Lead pipe rigidity - rigidity of legs.
• Postural instability
  • Stiffness in legs.
  • Short shuffle gait
  • Center of gravity is more - high chances of falling.
  • Stupor posture is seen
  • Minimal movement of hands while walking - less arm swing.
  • Festinating gait
• From the first 3 motor symptoms even if 2 are present said to be Parkinson’s Disease. 
• All the 4 motor symptoms are called cardinal symptoms. 
• Leaving the Parkinson's person alone on an uneven surface not safe.
• As the patient is on treatment the symptoms follow on and off phenomena. 

Hesitancy / Freezing / Postural Instability

When a command is passed to a Parkinson’s  patient to do something like walking - there will be a time lag in starting the action. This is due to Stiffness of the body. When the patient is asked to turn around there are chances that he may fall, As there is no flexibility. The patient becomes slow and delays the actions.

• Other Clinical Features
  • Mask like facies
  • Depression - leading to pseudo dementia. 
  • Hypomimia (patients voice becomes so low), bradyphrenia.
  • Myerson sign is present 

Myerson sign

• When we tap on glabella with a finger,  a normal person Blink their eyes for the first time and Later on continuous tapping stops blinking as he understands it is a non noxious action. whereas the Parkinson’s patient  continues blinking all the time when we tap on glabella.

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Treatment of atypical  parkinson's disease

• Main drug used is levodopa.
• Rasagiline (MAO inhibitor) - exhibits neuroprotective effect.
  • Difficult to understand the improvement of the patient.
  • Efficacy of the drug can't be understood properly.
  • Prevents further worsening of symptoms.
• Preferred drug in younger patients - pramipexole or ropinirole.
  • Stimulates D2 receptors.
  • Has less side effects.
  • Rotigotine - has longer action.
  • Transdermal patches decrease the manifestations of the patient - can take care of himself as disability is reduced.
• Preferred drug in older patients - levodopa + carbidopa.
  • Levodopa is converted to Dopamine in the body.
  • When levels reach more than normal in blood - causes levodopa induced dyskinesia.
  • Also causes - nausea, vomiting and orthostatic hypotension. 
• Carbidopa reduces the side effects of levodopa.
  • It is a peripheral decarboxylase inhibitor.
  • Inhibits the formation of Dopamine in blood.

Reducing Levodopa Side Effects

• If the conversion of Dopamine to its metabolites is reduced -
  • Duration of action of Dopamine is increased.
  • Dose and frequency is reduced.
  • Finally, side effects can be reduced. 
• Achieved by adding COMT inhibitor or MAO-B inhibitor along with levodopa. 
• COMT (catechol o methyltransferase) inhibitors - Entacapone, tolcapone.
  • Tolcapone is hepatotoxic withdrawn.
  • On time increased. 
  • Off time decreased.
  • Safer than MAO-B inhibitors.
• MAO-B (Monoamine oxidase) inhibitors - Selegiline, rasagiline, safinamide
• Other drugs:
  • Amantadine - Parkinsonism with influenza A (H3N1).
  • Bromocriptine - Raynaud's phenomenon can occur.
  • Cabergoline - Longest acting drug, may cause
    • Cardiac valvular defects
    • Pulmonary fibrosis 

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Complications of parkinson's disease

• Depression
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• A laryngeal disorder
• Impaired autonomic function
• Kyphosis with cardiopulmonary dysfunction

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Prognosis of Parkinson's Disease

The following factors may be used to forecast how quickly the disease will progress

• Men who have problems with their walk or postural stability.
• Patients who have dementia, are older at the time of start, or do not react to conventional dopaminergic drugs are more likely to enter nursing homes early and have lower survival rates.
• Individuals who initially only exhibit tremors have a protracted benign course.
• When the condition is discovered in an older patient who also has hypokinesia or stiffness, the disease tends to advance significantly more quickly.
• The disorder causes the majority of patients to become disabled within 10 years; has a three times higher mortality rate than the general population.

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