Parkinson's disease

Question 1

What is Parkinson’s disease?

Answer 1

Parkinson’s disease is a movement disorder characterised by:

• Tremor at rest
• Rigidity
• Bradykinesia

The diagnosis is almost entirely based on clinical examination

Question 2

What is the pathogenesis of PD?

Answer 2

The ventral tier of the zona compacta of the substantia nigra is particularly affected with reduction of dopamine in the striatum.

Parkinson’s disease is used to describe the idiopathic syndrome of Parkinsonism. It is caused by degeneration of the dopaminergic pathways in the substantia nigra. Although Parkinson’s disease is mainly caused by dysfunction of dopaminergic neurons, nondopaminergic systems are also involved.

Question 3

What is the pathogenesis of drug-induced parkinsonism?

Answer 3

Drug-induced Parkinsonism is caused by drugs that block the dopamine receptors or reduce storage of dopamine.

This is mainly the major tranquilisers used to treat psychosis but the condition can also be seen with drugs used to treat nausea - e.g., metoclopramide.

Question 4

Which age group is most likely to be affected by PD?

Answer 4

Parkinson’s disease typically develops between the ages of 55 and 65 years, and occurs in 1-2% of people over the age of 60 years, rising to 3.5% at age 85-89 years.

Question 5

What is the presentation of PD?

Answer 5

Parkinson’s disease is a slowly progressing neurodegenerative disorder, causing impaired motor function with slow movements, tremor and gait and balance disturbances.

Various non-motor symptoms are common and include disturbed autonomic function with orthostatic hypotension, constipation and urinary disturbances, sleep disorders and neuropsychiatric symptoms.

Onset is insidious with peak age of onset at 55-65 years. It commonly presents with impairment of dexterity or, less commonly, with a slight dragging of one foot.

A fixed facial expression is characteristic with infrequent blinking. There may also be saliva drooling from the mouth, often due to impaired swallowing, and a quiet voice.

Main features are resting tremor, rigidity and bradykinesia

Question 6

What are the characteristics of the tremor seen in PD?

Answer 6

Tremor at 4-6 Hz is seen at rest and, if not immediately apparent, may be induced by concentration - e.g., asking the patient to recite months of the year backwards. It is absent during activity - e.g., tipping water from cup to cup. Tremor is usually apparent in one limb or the limbs on one side for months or even years before becoming generalised.

Question 7

What is rigidity in PD?

Answer 7

Rigidity presents as an increase in resistance to passive movement that can produce a characteristic flexed posture in many patients. It may be increased by asking the patient to perform an action in the opposite limb - contralateral synkinesis.

Question 8

How does bradykinesia present in PD?

Answer 8

Bradykinesia presents as a slowness of voluntary movement and reduced automatic movements. It is particularly noticeable in a reduced arm swing whilst walking.

It can also be seen as a progressive reduction in the amplitude of repetitive movements - e.g., asking the patient to repeatedly oppose middle finger and thumb. Patients may still retain the ability to move quickly in an emergency situation.

Typically, muscles are of normal strength if given time to develop power. There is no alteration in tendon reflexes or plantar responses.

Question 9

What is the gait disturbance seen in PD?

Answer 9

Gait disturbance: the patient may have difficulty in rising from a sitting position and starting to walk. Gait is characterised by small shuffling steps with unsteadiness on turning (taking several steps to turn) and difficulty in stopping (‘festination’). There may be a tendency to fall.

Gait disorders and postural instability are the leading causes of falls and disability in Parkinson’s disease. Cognition plays an important role in postural control and may interfere with gait and posture. It is very important to recognise gait, posture and balance dysfunction.

Question 10

What is gait apraxia?

Answer 10

When patients have a gait disorder without other Parkinsonian features, the most likely diagnosis is gait apraxia, which is more common and usually caused by small-vessel cerebrovascular disease.

Question 11

How is PD diagnosed?

Answer 11

NICE recommends using the UK Parkinson’s Disease Society (PDS) Brain Bank Criteria for diagnosis.

Question 12

What is step 1 of the PDS criteria?

Answer 12

Step 1: diagnosis of Parkinsonian syndrome

• Bradykinesia (slowness of initiation of voluntary movement with progressive reduction in speed and amplitude or repetitive actions) and at least one of the following:
• Muscular rigidity.
• 4- to 6-Hz resting tremor.
• Postural instability not caused by primary visual, vestibular, cerebellar or proprioceptive dysfunction.

Question 13

What is step 2 of the PDS criteria?

Answer 13

Step 2: exclusion criteria for Parkinson’s disease

• History of repeated strokes with stepwise progression of Parkinsonian features.
• History of repeated head injury.
• History of definite encephalitis.
• Oculogyric crises.
• Neuroleptic treatment at onset of symptoms.
• More than one affected relative.
• Sustained remission.
• Strictly unilateral features after three years.
• Supranuclear gaze palsy.
• Cerebellar signs.
• Early severe autonomic involvement.
• Early severe dementia with disturbances of memory, language and praxis.
• Babinski’s sign.
• Presence of a cerebral tumour or communicating hydrocephalus on CT scan.
• Negative response to large doses of L-dopa (if malabsorption excluded).
• Exposure to MPTP.

Question 14

What is step 3 of the PDS criteria?

Answer 14

Step 3: supportive prospective positive criteria of Parkinson's disease
Three or more are required for the diagnosis of definite Parkinson's disease:
-Unilateral onset.
-Rest tremor present.
-Progressive disorder.
-Persistent asymmetry affecting the side of onset most.
-Excellent response (70-100%) to L-dopa.
-Severe L-dopa-induced chorea.
-L-dopa response for five years or more.
-Clinical course of ten years or more.
-Hyposmia.
-Visual hallucinations.

Question 15

What are the long term problems of Parkinson’s disease?

Answer 15

Motor fluctuations
Axial problems such as balance, speech and gait disturbances not responding to treatment
PD dementia

Question 16

Which motor fluctuations does people with PD experience?

Answer 16

When Parkinson’s disease patients are moving well, they say they are ‘on’. When they are stiff and bradykinetic, they say they are ‘off’.

Wearing off of the treatment (before the next dose is due) may start to occur as well as ‘on-off’ fluctuations, which occur randomly.

Patients may also experience involuntary movements whilst ‘on’. These are dyskinesias.

Motor fluctuations are difficult to treat and are best managed by a specialist.

Question 17

Why do axial problems in PD not respond to treatment as the disease progresses?

Answer 17

Axial problems are balance, speech and gait disturbance which do not respond to Parkinson’s disease medication.

It is thought to be as a consequence of axonal degeneration outside the substantia nigra where dopamine is not the neurotransmitter.

If a patient cannot walk or speak well but has no limb Parkinsonism (ie is otherwise well medicated), they will not be improved by increasing their dose.

Their treatment options include physiotherapy, occupational therapy and speech and language therapy (SALT).

Question 18

What is PD dementia?

Answer 18

This is dementia occurring more than one year after diagnosis of Parkinson’s disease.

It is similar to Alzheimer-type dementia but has three typical features:
Presence of Parkinsonism in the limbs.
Frequent visual hallucinations.
Frequent fluctuations in lucidity.

Parkinson’s disease dementia is difficult to treat, as confusion and hallucinations may be worsened by the treatment of Parkinson’s disease - dopamine agonists.

Atypical antipsychotics (eg, quetiapine), are effective without worsening the Parkinsonism.

Question 19

What are the differentials for PD?

Answer 19

Benign essential tremor - far more common; tremor is worse on movement (eg, while trying to hold a cup of tea) and rare while at rest.
Drug- or toxin-induced - numerous drugs or toxins may cause tremor, notably selective serotonin reuptake inhibitors (SSRIs), caffeine, amfetamines, beta-adrenergic blockers, tricyclics, and lithium. Neuroleptics (eg, haloperidol, chlorpromazine) and anti-emetics (eg, prochlorperazine) can cause Parkinsonian features which look identical to Parkinson’s disease.
Vascular parkinsonism
Huntington’s disease - can present earlier with rigidity instead of chorea when Parkinsonism is not expected. Normally, there is family history.
Wilson’s disease - earlier onset with characteristic Kayser-Fleischer rings and hepatitis.
Corticobasal degeneration - manifest by obvious signs of cortical dysfunction - eg, apraxia, dementia and aphasia. Cortical sensory deficit, alien limb phenomenon.
Creutzfeldt-Jakob disease (CJD) - dementia usually apparent with myoclonic jerking, ataxia and pyramidal signs common.
Multi-infarct dementia - this is characterised by cognitive impairment, spasticity, and extrapyramidal signs.
Lewy body dementia - often mimics Parkinsonian features.
Pick’s disease - affects the frontal and/or temporal lobes. Level of consciousness is not affected (unlike in Alzheimer’s disease) and Parkinsonism is usually mild.
Cerebellar tremor - this presents as a unilateral or bilateral, low-frequency intention tremor. It may be caused by stroke, brainstem tumour, or multiple sclerosis.
Pyschogenic tremor - the tremor is variable, increases under direct observation, decreases with distraction and changes with voluntary movement of the contralateral limb.

Question 20

How does vascular parkinsonism present?

Answer 20

predominant lower body signs, tremor less common, rigidity especially lower limbs and lack of facial expression. Approx. 50% respond to levodopa.

Question 21

What are the atypical Parkinsonism syndromes?

Answer 21

The ‘atypical Parkinsonism syndromes’ are a group which look like Parkinson’s disease but are much more severe.
Median survival is only seven years compared with the normal lifespan in Parkinson’s disease. They include:
-Multiple system atrophy - may also present with Parkinsonian symptoms, often with a poor or temporary response to levodopa therapy. There are prominent early autonomic features (hypotension, bladder instability)
Presents with symmetrical parkinsonism
-Progressive supranuclear palsy - characterised by paresis of conjugate gaze with initially problems looking up and down on request, advancing to difficulty in following objects up and down. Early falls. There is a reduction in mid brain volume on MRI (‘humming bird sign’)

Question 22

When should people with suspected PD be seen by a specialist?

Answer 22

Refer people with suspected Parkinson’s disease quickly (and untreated) to a specialist (with expertise in the differential diagnosis of this condition) for diagnosis.

NICE states that people with suspected mild Parkinson’s disease should be seen within six weeks, but new referrals in later disease with more complex problems require an appointment within two weeks.

Question 23

Which investigations are done in a patient suspected of PD?

Answer 23

The diagnosis is clinical. Other investigations focus on excluding other causes of the presentation:
-CT or MRI brain scan:
For patients who fail to respond to therapeutic doses of L-dopa (at least 600 mg/day) administered for 12 weeks.
MRI scanning is needed to exclude rare secondary causes (eg, supratentorial tumours and normal pressure hydrocephalus) and extensive subcortical vascular pathology.
-123I-FP-CIT single photon emission computerised tomography (SPECT) should be considered for people with tremor if essential tremor cannot be clinically differentiated from Parkinsonism.
-Positron emission tomography (PET) scanning with fluorodopa can localise dopamine deficiency in the basal ganglia, while autonomic tests and sphincter electromyography may support a diagnosis of multiple system atrophy.
-Structural MRI may be considered in the differential diagnosis of other Parkinsonian syndromes.
-Transcranial sonography has been recommended for the differentiation of Parkinson’s disease from atypical and secondary Parkinsonian disorders, for the early diagnosis of Parkinson’s disease and for the detection of subjects at risk for Parkinson’s disease. However, the technique is not universally available and requires some expertise.
-Genetic testing may be required - e.g., Huntington’s gene. Fewer than 5% of all Parkinson’s disease cases are caused by known single-gene mutations.
-Olfactory testing to help differentiate Parkinson’s disease from other Parkinsonian disorders.
-Further investigations for young-onset or atypical disease may include measurement of ceruloplasmin levels (Wilson’s disease) and syphilis serology.

Question 24

What is the management of PD?

Answer 24

Treatment, as always, should be tailored to the needs of the individual. Patients should be helped to make informed decisions about their care, and try to involve the carers as much as the patient will allow.

Non-pharmacological management of motor and non-motor symptoms includes:

• Parkinson’s disease nurse specialists.
• Physiotherapy and physical activity.
• Occupational therapy.
  -Speech and language therapy.
• Nutritional support.

Maintenance

• Aims to establish a care package and lines of communication, build support for the patient and look out for any complications.
• Ensure regular access to specialist care - for clinical monitoring and medication adjustments.
• The diagnosis should be regularly reviewed, particularly if atypical symptoms or signs develop. NICE suggests review every 6-12 months.
• Assess disability and cognition regularly, both by the patient self-reporting (eg, time how long it takes the patient to walk 20 yards; whether the patient can dress alone; whether he or she can turn over in bed) and by objectively rating motor symptoms (as in the Unified Parkinson’s Disease Rating Scale).
• Don’t focus solely on motor symptoms - consider other common problems such as sleep disturbance, depression, dementia and psychosis.
• There is no universal first-choice drug - this depends on the patient’s age, clinical symptoms, lifestyle and personal preferences.

Question 25

What is the treatment of early PD?

Answer 25

The choice of drug depends on the impact of improving motor disability (better with levodopa) compared with the risk of motor complications (more common in younger patients) and neuropsychiatric complications (more common in older and cognitively impaired patients; greater with agonists).

Options include the following:

• Monoamine-oxidase-B inhibitors (MAO-BIs) - selegiline, rasagiline.
• Oral or transdermal dopamine agonist. Pramipexole, ropinirole and rotigotine are effective. Initial treatment with an agonist is recommended in younger patients.
• Levodopa is the most effective symptomatic drug. The use of controlled-release formulations or adding entacapone is not effective in the delay of motor complications.
• Amantadine or an anticholinergic.
• Ergot derivatives are not recommended as first-line medication because of the risk of fibrotic reactions.
• Levodopa should be offered to people in the early stages of Parkinson’s disease whose motor symptoms impact on their quality of life.
• A choice of dopamine agonists, levodopa or MAO-BIs should be considered for people in the early stages of Parkinson’s disease whose motor symptoms do not impact on their quality of life.

Question 26

Which drug is the most effective in the treatment of PD?

Answer 26

Levodopa is the most effective drug in the treatment of Parkinson’s disease.
Virtually all patients respond to it and treatment is associated with reduced morbidity:
-It is given with a peripheral dopa-decarboxylase inhibitor, which prevents peripheral conversion to dopamine. Sinemet® and Madopar® are the main preparations.
-It is usually well tolerated and adverse effects (nausea and dizziness) are quite rare and mild.
-Clinicians should be aware that prolonged levodopa use may be associated with weight loss.

Question 27

Why are dopamine agonists better than levodopa?

Answer 27

They are effective in treating motor features of Parkinson’s disease and can be used in early disease. In the long term they are associated with fewer dyskinesia and motor fluctuations compared with levodopa and may therefore be more appropriate for use in younger patients.

Acute adverse effects are similar to levodopa but more common and severe and are associated with increased treatment withdrawal and poorer motor scores. These occur at the start of treatment and abate over several days to weeks.
They are less effective than levodopa, and levodopa is eventually required.

Prolonged monotherapy (longer than one year) is not always successful because of side-effects. In people with response fluctuations to levodopa, adjuvant dopamine agonists reduce ‘off’ time, improve motor impairment and activities of daily living and reduce levodopa dose but increase dopaminergic adverse effects and dyskinesias.

Non-ergot-derived agonists are preferred (pramipexole and ropinirole).
Ergot-derived drugs (bromocriptine, cabergoline, lisuride and pergolide) should not be offered as first-line treatment for Parkinson’s disease.

Question 28

What is the management problems of PD?

Answer 28

Long-term levodopa treatment is associated with adverse motor effects that limit its use. These are motor fluctuations (on-off phenomena, wearing off, dose failures and freezing) and dyskinesias (peak-dose dyskinesias, diphasic dyskinesia and dystonia). They are best managed by a specialist.

A choice of dopamine agonists, MAO-B inhibitors or COMT inhibitors should be considered as an adjunct to levodopa for people with Parkinson’s disease who have developed dyskinesia or motor fluctuations despite optimal levodopa therapy.

Amantadine should be considered if dyskinesia is not adequately managed by modifying existing therapy. Anticholinergics should not be offered to people with Parkinson’s disease who have developed dyskinesia and/or motor fluctuations.

Question 29

What can be used for the treatment of advanced PD?

Answer 29

Deep brain stimulation should be considered for people with advanced Parkinson’s disease whose symptoms are not adequately controlled by best medical therapy.

Electrodes are placed in the basal ganglia and attached to an internal stimulator, which is placed subcutaneously below the clavicle.
May be used to provide unilateral or bilateral stimulation.

Question 30

What are the complications of PD?

Answer 30

Infections.
Aspiration pneumonia.
Bed sores.
Poor nutrition.
Falls.
Contractures.
Bowel and bladder disorders.
Psychotic symptoms such as hallucinations and delusions
Orthostatic hypotension
Depression 
Anxiety
Acute akinesia

Question 31

What is acute akinesia?

Answer 31

A rare but life-threatening complication of Parkinson’s disease, with a sudden worsening of motor symptoms and severe akinesia.
Triggers include infections, surgery, gastrointestinal disease and changes in medication.
Acute akinesia is difficult to treat and often needs hospital admission.