Parkinson's Disease Update

Parkinson’s disease (PD) is a progressive neurodegenerative condition resulting from the death of the dopamine-containing cells of the substantia nigra.

Epidemiology

Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease. It is estimated to affect 100-180 people per 100,000 of the population (between 6 and 11 people per 6000 of the general population in the UK) and has an annual incidence of 4–20 per 100,000. There is a rising prevalence with age (0.5% of people aged 65 to 74 and 1-2% of people aged 75 and over) and a higher prevalence and incidence of PD in males.

Clinical features

Patients with Parkinson’s disease classically present with the following clinical features:

Hypokinesia (poverty of movement)
Bradykinesia (slowness of movement)
Rest tremor (typically 4-6 cycles per second)
Rigidity (increased tone and ‘cogwheel’ rigidity)

Other commonly encountered clinical features include:

Gait disturbance (characteristic ‘shuffling’ gait with loss of arm swing)
Loss of facial expression
Monotonous, slurred speech
Micrographia (small, cramped handwriting)
Increased salivation and dribbling
A difficulty with fine movements

The signs are generally unilateral at the time of diagnosis but are progressive and may become bilateral as the disease progresses. In the later stages of the disease, additional clinical features may become apparent, including:

Postural instability
Cognitive impairment
Orthostatic hypotension

Although PD is predominantly a movement disorder, patients also frequently develop psychiatric problems, such as depression and dementia. Autonomic disturbances and pain can also occur, and the condition progresses to cause significant disability and handicap with impaired quality of life for the affected person. Family and carers may also be affected indirectly.

Diagnosis

The diagnosis of Parkinson’s disease is primarily a clinical one. NICE recommend that the diagnosis should be based on the UK Parkinson’s Disease Society (PDS) Brain Bank Criteria. There is no consistently reliable test that can distinguish PD from other conditions that have similar clinical presentations.

NICE state that if Parkinson’s disease is suspected, the patient should be referred quickly and untreated to a specialist with expertise in the differential diagnosis of the condition.

The diagnosis of Parkinson’s disease should be reviewed regularly, and the diagnosis reconsidered if atypical clinical features develop. People diagnosed with Parkinson’s disease should be seen at regular intervals of 6–12 months to review their diagnosis.

Associated diseases

The two most common diseases associated with Parkinson’s disease are dementia and depression:

Dementia: occurs in between 20 and 40% of all patients with Parkinson’s disease
Depression: occurs in around 45% of all patients with Parkinson’s disease.

Drug-induced Parkinsonism

About 7% of people with parkinsonism have developed their symptoms following treatment with particular medications. This form of parkinsonism is called ‘drug-induced parkinsonism’.

The drugs involved are generally those that block the action of dopamine, including the following:

Neuroleptic or antipsychotic drugs
Prochlorperazine
Metoclopramide
Calcium-channel blockers

First-line treatment

There is no universally accepted first-line drug therapy for Parkinson’s disease and the decision as to which medications to prescribe depends upon the extent of the clinical features, patient preference and lifestyle characteristics.

The current NICE guidance recommends that levodopa is 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 monoamine oxidase B (MAO‑B) inhibitors should be considered for people in the early stages of Parkinson’s disease whose motor symptoms do not impact on their quality of life.

Ergot-derived dopamine agonists should not be offered as a first-line treatment for Parkinson’s disease.

The potential benefits and harms of levodopa, dopamine agonists and MAO‑B inhibitors are summarised in the table below:

	Levodopa	Dopamine agonists	MAO B inhibitors
Motor symptoms	More improvement in motor symptoms	Less improvement in motor symptoms	Less improvement in motor symptoms
Activities of daily living	More improvement in activities of daily living	Less improvement in activities of daily living	Less improvement in activities of daily living
Motor complications	More motor complications	Fewer motor complications	Fewer motor complications
Adverse events	Fewer specified adverse events*	More specified adverse events*	Fewer specified adverse events*

*Specified adverse events include excessive sleepiness, hallucinations and impulse control disorders.

Adjuvant treatment of motor symptoms

If a patient with Parkinson’s disease develops dyskinesia and/or motor fluctuations, including medicines ‘wearing off’, then advice should be sought from a specialist with expertise in Parkinson’s disease before modifying therapy. Drug treatment choices in these circumstances include dopamine agonists, MAO‑B inhibitors and catechol‑O‑methyl transferase (COMT) inhibitors as an adjunct to levodopa.

The potential benefits and harms of dopamine agonists, MAO‑B inhibitors and catechol‑O‑methyl transferase (COMT) inhibitors are summarised in the table below:

	Dopamine agonists	MAO B inhibitors	COMT inhibitors
Motor symptoms	Improvement in motor symptoms	Improvement in motor symptoms	Improvement in motor symptoms
Activities of daily living	Improvement in activities of daily living	Improvement in activities of daily living	Improvement in activities of daily living
Off time	More off-time reduction	Off-time reduction	Off-time reduction
Adverse events	Intermediate risk of adverse events	Fewer adverse events	More specified adverse events
Hallucinations	More risk of hallucinations	Lower risk of hallucinations	Lower risk of hallucinations

If dyskinesia is not adequately managed by modifying existing therapy, consider amantadine.

Anticholinergics should not be offered to people with Parkinson’s disease who have developed dyskinesia and/or motor fluctuations.

Non-pharmacological management

The NICE guidance on the non-pharmacological management of Parkinson’s disease is as follows:

Physiotherapy and physical activity are key interventions:

Early referral to a physiotherapist with experience of Parkinson’s disease for disease-specific physiotherapy should be considered
The Alexander Technique should be considered for people with Parkinson’s disease who are experiencing balance or motor function problems
Disease-specific occupational therapy should be considered for people who are having difficulties with activities of daily living.

Speech and language therapy (SALT) are also important:

Referral should be considered in the early stages for assessment, education and advice
SALT is particularly important for those who are experiencing problems with communication, swallowing or saliva
Expiratory muscle strength training (EMST) minimises the risk of aspiration

Nutritional support is a key component of the management of Parkinson’s disease:

Consider referring people with Parkinson’s disease to a dietitian for specialist advice.
A diet in which most of the protein is eaten in the final main meal of the day (a protein redistribution diet) can be helpful for people with Parkinson’s disease on levodopa who experience motor fluctuations.
Advise people with Parkinson’s disease to take a vitamin D supplement.

Parkinson-plus syndromes

The Parkinson-plus syndromes are a group of neurodegenerative disorders featuring the classical features of Parkinson’s disease with additional clinical features that distinguish them from idiopathic Parkinson’s disease (iPD). These include:

Multiple System Atrophy (MSA)
Progressive Supranuclear Palsy (PSP)
Corticobasal degeneration (CBD)
Dementia with Lewy Bodies (DLB)

Multiple System Atrophy (MSA)

MSA results from a loss of cells in multiple different areas of the nervous system. It is much less common than PD, and also less common than PSP. MSA progresses rapidly, often resulting in people being wheelchair bound 3-4 years from the time of diagnosis. The distinguishing features of MSA include:

The development of autonomic dysfunction
Bladder control problems
Erectile dysfunction
Blood pressure changes and associated syncope
Early-onset balance problems
Neck or facial dystonia
High-pitched voice.

Progressive Supranuclear Palsy (PSP)

PSP is a progressive syndrome resulting in weakness of the muscles involved in eye movement. The term “supranuclear” refers to the nature of the eye problem seen in individuals affected by this syndrome. PSP affects cells in the brain that control mobility, balance, speech, swallowing and behaviour. The distinguishing features of PSP include:

A very rapid progression of symptoms leading to balance problems and falls within the first year of diagnosis
Imbalance and stiffness progress over 5-8 years resulting in great difficulty with mobility, making walking nearly impossible
The development of an eye movement abnormality that makes it difficult for affected patients to move their eyes vertically (especially downwards)
Early changes in mood and behaviour
Slurring of speech
Difficulty swallowing

Corticobasal Degeneration (CBD)

CBD results from a loss of cells in the cerebral cortex as well as in the basal ganglia. CBD progresses much quicker than iPD, with people typically becoming immobile within 5 years of symptom onset. The distinguishing features of CBD include:

The gradual loss of function of one hand or leg (apraxia)
The affected limb, typically an arm, may be held in an abnormal dystonic (cramped) posture and may demonstrate rapid jerking movements (called myoclonus)
Problems with thinking and memory may occur early, but true dementia typically occurs only in the advanced stages of the disease

Dementia with Lewy Bodies (DLB)

DLB is a progressive dementing illness that results from a build-up of Lewy body proteins inside areas and cells of the brain that control memory and motor function. Like PD, individuals with DLB show signs of slowness and stiffness. The average survival after diagnosis is 8-9 years. The distinguishing features of DLB include:

A progressive and rapid decline in mental function
Prominent visual hallucinations and fluctuations in attention or alertness
Response to levodopa is typically mild and short-lived, and treatment is geared towards managing cognitive and psychiatric symptoms

The following table summarises the distinguishing features of the Parkinson-plus syndromes, comparing them with idiopathic Parkinson’s disease:

	iPD	MSA	PSP	CBD	DLB
Symptom onset	One side of the body affected more than the other	Both sides equally affected	Both sides equally affected	One side of the body affected more than the other	Both sides equally affected
Tremor	Typically starts at rest on one side of the body	Not common but may occur	Less common, if present affects both sides	Not common but may occur	Not common but may occur
Levodopa response	Excellent response	Minimal response (but often tried in early stages of disease)	Minimal response (but often tried in early stages of disease)	Minimal response (but often tried in early stages of disease)	Minimal response (but often tried in early stages of disease)
Mental changes	Depression	Depression	Personality changes, depression	Depression
Balance/falls	Late in the disease	Within 1-3 years	Within 1 year	Within 1-3 years	Within 1-3 years
Common eye abnormalities	Dry eyes, trouble focusing	Dry eyes, trouble focusing	Dry eyes, difficulty in looking downwards	Dry eyes, trouble focusing	Dry eyes, trouble focusing