Parkinson’s DiseaseBy Nik Sanyal

This = movement disorder caused by degeneration of dopamine pathways in substantia nigra

Characterised by: TREMOR RIGIDITY BRADYKINESIA +/- postural instability

Epidemiology + Risk Factors

Peak age of onset = 55-65 Men > Women 2nd most common neurodegenerative disease

after Alzheimer’s

Risk factors: Age Gender Spring birth Exposure to pesticides e.g. paraquat or Agent

Orange

Pathogenesis Most cases = idiopathic PD. Leading to a

progressive degeneration + development of Lewy bodies in substantia nigra. Other pathways – mesocortical, mesolimbic +

tubero-hypophyseal

Genetics (lead to early onset): mutations in c’some 6 = AR PD Alpha synuclein mutation Parkin gene

Dopamine has a role in disinhibition of motor activity hence why reduced levels leads to dyskinesia.

Pathophysiology Cell death in substantia nigra

(particularly pars compacta) leads to reduced dopamine secreting cells.

Dopamine acts to facilitate release of inhibition and as such in PD there is greater exertion required to initiate a movement as there is less release of inhibition.

Clinical features1) Resting tremor = usually unilateral before

it becomes generalised. It is 4-6 Hz pill-rolling. Typically absent during activity.

2) Rigidity = lead pipe. Cog-wheeling occurs when lead pipe rigidity is broken up by tremor.

3) Bradykinesia = festinant gait (slow to start + small shuffling steps + difficult turns) Has diminished arm swing = leads to recurrent falls. You also get reduction in amplitude of repetitive movements.

Other features Progressive decline over years Mask-like face Impaired swallowing – drooling, choking

on food Cognitive decline = depression +

dementia Quiet voice progressing to dysarthria Micrographia (small + spidery writing)

DDx Wilson’s Lewy Body dementia: get visual hallucinations CJD: Dementia + myoclonic jerking Parkinson’s plus Huntington’s disease Drug-induced PD

Antipsychotics (APAT side effects: acute dystonia, parkinsonism, akathisia, tardive dyskinesia)

Lithium Benign essential tremor

Rarely at rest, worse on movement Family hx

NICE criteria for Dx Exclude other causes Bradykinesia + at least 1

of: Rigidity 4-6Hz resting tremor Postural instability

Supportive criteria: Unilateral Progressive nature Asymmetry before bilateral Response to L-Dopa

Investigations Typically a clinical diagnosis Use:

Bedside: BP lying + standing, urine dip Bloods: Genetic testing for Huntington’s

or caeruloplasmin for Wilson’s Imaging: CT/MRI

Fail to respond to L-Dopa Can visualise structural defects

Special tests: DAT scan can differentiate between drug-induced + PD.

Conservative management

Advice + explanation, consider non-physical problems (depression, poor sleep, dementia).

Limited time frame for meds so start when really needed + started by neurologist!

MDT: specialist nurses, OT, SALT, psychiatrist, GP, neurologist, dietician

Inform DVLA REHAB

Medical management Drugs alter the natural progression – they just

improve symptoms. Levodopa

Is the most effective drug. It crosses the BBB and enters the nigrostriatal

neurones and is converted to dopamine. Give with dopa-decarboxylase inhibitor e.g.

carbidopa to inhibit peripheral metabolism.

S/E = N+V, confusion, on-off phenomena, wearing off + dyskinesia, hallucination

Dopamine agonists e.g. Pramipexole = good for motor sx 1st line in younger patients

MAO-B inhibitors = selegiline = block dopamine breakdown. Good for motor sx.

COMT inhibitors = entacapone = inhibits peripheral break down. S/E = hepatotoxic, N+V, confusion.

Amantadine: can be used as monotherapy in early PD but has poor evidence base. Enhances dopamine release.

Apomorphine can reduce off periods given as s/c injection. S/E confusion + hallucinations

Surgical

Deep brain stimulation Pallidotomy involves surgical destruction

of the globus pallidus to control dyskinesia.

Complications Infection Aspiration pneumonia Bed sores Poor nutrition Falls PD dementia

Prognosis Slowly progressive Mean duration 15 years Variable severity Earlier age of onset = poorer prognosis Death usually from complications e.g.

pneumonia.

Parkinson’s plus syndromes Disorders with parkinsonism + additional

features + specific pathology. Vascular dementia Orthotic hypotension = multi-system

atrophy gives insomnia, somnolence, restless legs, hallucinations. Use fludrocortisone for BP

Dementia + vertical gaze palsy= progressive supra-nuclear palsy

Kayser-Fleischer rings = Wilson’s Apraxic gait – communicating hydrocephalus

Good luck! Parkinson’s notes

http://www.patient.co.uk/doctor/parkinsonism-and-parkinsons-disease

Extrapyramidal exam http://youtu.be/6PDxANv_ME8

Gait http://youtu.be/7SyTpEdhBLw