2. • Parkinsonism is a clinical syndrome characterized primarily by
bradykinesia , with associated increased tone (rigidity),tremor and loss of
postural reflexes.
• There are many causes but the most common is Parkinson’s disease.
• PD has an annual incidence of about 18/100 000 in the UK and a
prevalence of about 180/100 000.
• Average age of onset is about 60 years and fewer than 5% of patients
present under the age of 40.
3. • It is progressive and incurable, with a variable prognosis.
• While motor symptoms are the most common presenting features, non-
motor symptoms (particularly cognitive impairment, depression and
anxiety) become increasingly prominent as the disease progresses, and
significantly reduce quality of life.
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7. • The pathological hallmarks of PD are depletion of the pigmented
dopaminergic neurons in the substantia nigra and the presence of α-
synuclein and other protein inclusions in nigral cells (Lewy bodies). It is
thought that environmental or genetic factors alter the α-synuclein protein,
rendering it toxic and leading to Lewy body formation within the nigral
cells. Lewy bodies are also found in the basal ganglia, brainstem and
cortex, and increase with disease progression. PD is recognized as
asynucleinopathy along side multiple system atrophy and dementia with
Lewy bodies. The loss of dopaminergic neurotransmission is responsible
for many of the clinical features.
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10. • The motor symptoms are almost always initially asymmetrical. The
hallmark is bradykinesia, leading to classic symptoms such as increasingly
small handwriting (‘micrographia’),difficulty tying shoelaces or buttoning
clothes, and difficulty rolling over in bed.
• Tremor is an early feature but may not be present in at least 20% of
people with PD. It is typically a unilateral rest tremor affecting limbs, jaw
and chin but not the head. In some patients, tremor remains the dominant
symptom for many years. Rigidity causes stiffness and a flexed posture.
Although postural righting reflexes are impaired early on in the disease,
falls tend not to occur until later. As the disease advances, speech
becomes softer and indistinct.
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13. • The diagnosis is clinical.
• Structural imaging (CT or MRI) is usually normal for age and thus rarely
helpful, although it may support a suspected vascular cause of
parkinsonism. Functional dopaminergic imaging (SPECT or PET) is
abnormal, even in the early stages , but does not differentiate between the
different forms of degenerative parkinsonism and so is not specific for PD.
• In younger patients, specific investigations may be appropriate (e.g.
exclusion of Huntington's or Wilson’s diseases). Some patients with family
histories may wish to consider genetic testing, although the role of genetic
counselling is uncertain at present.
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15. Management
• Drug treatment for PD remains symptomatic rather than curative.
• Levodopa (LD) remains the most effective treatment available but other
agents include dopamine agonists, anticholinergics, inhibitors of
monoamine oxidase (MAOI)-B and catechol-O-methyl-transferase
(COMT), and amantadine.
16.
17. Levodopa
• Levodopa is the precursor to dopamine.
• When administered orally, more than 90% is decarboxylated to dopamine peripherally in
the gastrointestinal tract and blood vessels, and only a small proportion reaches the brain.
This peripheral conversion is responsible for the high frequency of adverse effects. To
avoid this, LD is combined with a dopa decarboxylase inhibitor ; the inhibitor does not
cross the blood–brain barrier, thus avoiding unwanted decarboxylation-blocking in the
brain.
• LD is most effective for relieving akinesia and rigidity; tremor response is often less
satisfactory and it has no effect on many motor (posture, freezing) and non-motor
symptoms.
• Adverse effects include postural hypotension, nausea and vomiting, which may be offset
by domperidone. LD may exacerbate or trigger hallucinations, and abnormal LD-seeking
behavior (dopamine dysregulation syndrome), in which the patient takes excessive doses
of LD, may occur uncommonly.
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23. Amantadine
• This has a mild, usually short-lived effect on bradykinesia and is rarely
used unless patients are unable to tolerate other drugs. It is more
commonly employed as a treatment for LD-induced dyskinesias, although
again benefit is modest and short-lived. Adverse effects include livedo
reticularis, peripheral oedema, delirium and other anticholinergic effects.
24. Anticholinergic drugs
• These were the main treatment for PD prior to the introduction of LD. Their role now is limited by
lack of efficacy (apart from an effect on tremor sometimes) and adverse effects, including dry
mouth, blurred vision, constipation, urinary retention, delirium and hallucinosis, as well as long-term
concerns regarding cognitive impairment.
• Several anticholinergics are available, including trihexyphenidyl(benzhexol) and orphenadrine.
25.
26. Physiotherapy, occupational therapy and
speech therapy
• Patients at all stages of PD benefit from physiotherapy, which helps reduce
rigidity and corrects abnormal posture. Occupational therapists can
provide equipment to help overcome functional limitations, such as rails for
stairs and the toilet, and bathing equipment. Speech therapy can help
where dysarthria and dysphonia interfere with communication, and advice
may also be provided to those with dysphagia.
• As with many complex neurological disorders, patients with PD should
ideally be managed by a multidisciplinary team, including PD specialist
nurses.
