Parkinson's Disease

Question 1

What is Parkinson’ disease (PD)?

Answer 1

Parkinson’s disease (PD) is a chronic progressive neurological disorder characterised by motor symptoms of resting tremor, rigidity, bradykinesia, and postural instability.

There is a progressive reduction of dopamine in the basal ganglia of the brain, leading to disorders of movement.

Question 2

Is PD symmetrical or asymmetrical?

Answer 2

The symptoms are characteristically asymmetrical, with one side affected more than the other.

Question 3

What is the triad of symptoms of PD?

Answer 3

There is a classic triad of features in Parkinson’s disease:

• Resting tremor
• Rigidity
• Bradykinesia

Question 4

What causes PD?

Answer 4

The aetiology of PD is unknown, although several factors have been implicated. There is probably a genetic predisposition, with subsequent environmental factors/exposures contributing to the evolution of clinical disease. Within this multifactorial model, age is the only undisputed risk factor.

Question 5

What are the risk factors for PD?

Answer 5

• Increasing age
• Familial PD
• 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure
• Mutations in the gene encoding glucocerebrosidase (GBA)

Question 6

Briefly describe the pathophysiology of PD

Answer 6

The basal ganglia are a group of structures situated in the middle of the brain. They is responsible for coordinating habitual movements such as walking or looking around, controlling voluntary movements and learning specific movement patterns. Part of the basal ganglia called the substantia nigra produces a neurotransmitter called dopamine. Dopamine is essential for the correct functioning of the basal ganglia. In Parkinson’s disease, there is a gradual but progressive fall in the production of dopamine.

Question 7

Review the anatomy of the basal ganglia and substantia nigra

Answer 7

Question 8

What are the clinical features of PD?

Answer 8

• Bradykinesia
• Resting tremor
• Rigidity
• Postural instability
• Masked facies
• Hypophonia
• Hypokinetic dysarthria
• Stooped posture
• Shuffling gait

Question 9

Briefly describe the unilateral tremor experienced in PD

Answer 9

The tremor in Parkinsons has a frequency of 4-6 Hz, meaning it occurs 4-6 times a second. This is described as a “pill rolling tremor” because it looks like they are rolling a pill between their fingertips and thumb. It is more pronounced when resting and improves on voluntary movement. The tremor is worsened if the patient is distracted. Asking them to do a task with the other hand, such as miming the motion of painting a fence, can exaggerate the tremor.

Question 10

Briefly describe the “cogwheel” rigidity experienced in PD

Answer 10

Rigidity is a resistance to passive movement of a joint. If you take their hand and passively flex and extend their arm at the elbow, you will feel a tension in their arm that gives way to movement in small increments (like little jerks). This is what leads to the cogwheel description.

Question 11

Briefly describe the bradykinesia experienced in PD

Answer 11

Bradykinesia describes how their movements get slower and smaller. This presents in a number of ways:

• Their handwriting gets smaller and smaller (this is a classic presenting complaint in exams)
• They can only take small steps when walking (“shuffling gait”)
• They have difficulty initiating movement (e.g. from standing still to walking)
• They have difficulty in turning around when standing, having to take lots of little steps
• They have reduced facial movements and facial expressions (hypomimia)

Question 12

Give examples of other features that affect PD patients

Answer 12

• Depression
• Sleep disturbance and insomnia
• Loss of the sense of smell (anosmia)
• Postural instability
• Cognitive impairment and memory problem

Question 13

Briefly differentiate between Parkinson’s tremor and benign essential tremor

Note: symmetry, hertz, at rest, with intentional movement, other features and alcohol

Answer 13

Question 14

How is PD diagnosed?

Answer 14

Parkinson’s disease is diagnosed clinically based on symptoms and examination. The diagnosis should be made by a specialist with experience in diagnosing Parkinson’s. NICE recommend using the UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria.

Question 15

What is the role of dopaminergic agent trial in diagnosing PD?

Answer 15

The diagnosis of PD is made clinically, and in cases without atypical features no additional diagnostic testing is indicated.

If diagnostic testing is warranted due to atypical features or unclear clinical diagnosis, tests may include dopaminergic agent trial.

This is useful to confirm diagnosis. Symptoms should improve with dopamine.

Question 16

What is the basis in using pharmacological treatment to treat PD?

Answer 16

Pharmacological treatment is designed to supplement depleted dopamine stores in the substantia nigra, thus minimising or eliminating symptoms and improving quality of life.

Initiation of treatment is based on severity of symptoms. Patients with mild disease may elect to postpone treatment until disability occurs.

Question 17

Briefly describe the treatment of PD

Answer 17

There is no cure, so treatment is focused on controlling symptoms and minimising side effects.

Patients describe themselves as “on” when the medications are acting and they are moving freely, and “off” when the medications wear out, they have significant symptoms and their next dose is due.

Pharmacological treatments:

• Levodopa
• COMT inhibitors
• Dopamine agonists
• Monoamine oxidase-B inhibitors

Question 18

Briefly describe the use of levodopa in treating PD

Answer 18

This is synthetic dopamine given orally to boost their own dopamine levels. It is usually combined with a drug that stops levodopa being broken down in the body before it gets the chance to enter the brain. These are peripheral decarboxylase inhibitors. Examples are carbidopa and benserazide.

Combination drugs are:

• Co-benyldopa (levodopa and benserazide)
• Co-careldopa (levodopa and carbidopa)

Levodopa is the most effective treatment for symptoms but becomes less effective over time. It is often reserved for when other treatments are not managing to control symptoms.

Question 19

What are the main side effects of dopamine?

E.g. when using levodopa

Answer 19

The main side effect of dopamine is when the dose is too high patients develop dyskinesias. Theses are abnormal movements associated with excessive motor activity. Examples are:

• Dystonia
  
  • This is where excessive muscle contraction leads to abnormal postures or exaggerated movements
• Chorea
  
  • These are abnormal involuntary movements that can be jerking and random
• Athetosis
  
  • These are involuntary twisting or writhing movements usually in the fingers, hands or feet

Question 20

Briefly describe the use of COMT inhibitors in treating PD

Answer 20

The main example of this is entacapone. These are inhibitors of catechol-o-methyltransferase (COMT). The COMT enzyme metabolises levodopa in both the body and brain. Entacapone is taken with levodopa (and a decarboxylase inhibitor) to slow breakdown of the levodopa in the brain. It extends the effective duration of the levodopa.

Question 21

Briefly describe the use of dopamine agonists in treating PD

Answer 21

These mimic dopamine in the basal ganglia and stimulate the dopamine receptors. They are less effective than levodopa in reducing symptoms. They are usually used to delay the use of levodopa and are then used in combination with levodopa to reduce the dose of levodopa that is required to control symptoms. Examples are:

• Bromocryptine
• Pergolide
• Carbergoline

Question 22

What is the main side effect of dopamine agonist use?

Answer 22

One notable side effect with prolonged use is pulmonary fibrosis.

Question 23

Briefly describe the use of monoamine oxidase-B inhibitors in treating PD

Answer 23

Monoamine oxidase enzymes break down neurotransmitters such as dopamine, serotonin and adrenaline. The monoamine oxidase-B enzyme is more specific to dopamine and does not act on serotonin or adrenalin. These medications block this enzyme and therefore help increase the circulating dopamine. Similarly to dopamine agonists, they are usually used to delay the use of levodopa and then in combination with levodopa to reduce the required dose. Examples are:

• Selegiline
• Rasagiline

Question 24

What are the complications of PD?

Answer 24

• Levodopa-induced dyskinesias
• Motor fluctuations
• Dementia
• Constipation
• Depression
• Anxiety
• Psychosis
• Impulse control disorder

Question 25

What differentials should be considered for PD?

Answer 25

• Essential tremor
• Progressive supranuclear palsy (PSP)
• Lew body dementia
• Drug-induced parkinsonism
• Corticobasal degeneration

Question 26

What is multi system atrophy?

Answer 26

This is a rare condition where the neurones of multiple systems in the brain degenerate. It affects the basal ganglia as well as multiple other areas. The degeneration of the basal ganglia lead to a Parkinson’s presentation. The degeneration in other areas lead to autonomic dysfunction (causing postural hypotension, constipation, abnormal sweating and sexual dysfunction) and cerebellar dysfunction (causing ataxia).

Question 27

Briefly describe lewy body dementia

Answer 27

This is a type of dementia associated with features of Parkinsonism. It causes a progressive cognitive decline. There are associated symptoms of visual hallucinations, delusions, disorders of REM sleep and fluctuating consciousness.

Question 28

What drugs may cause drug-induced parkinsonism?

Answer 28

• Metoclopramide
• Reserpine
• Tetrabenazine
• Lithium
• Calcium-channel blocker