2 This = movement disorder caused by degeneration of dopamine pathways in substantia nigra Characterised by:TREMORRIGIDITYBRADYKINESIA+/- postural instability
3 Epidemiology + Risk Factors Peak age of onset = 55-65Men > Women2nd most common neurodegenerative disease after Alzheimer’sRisk factors:AgeGenderSpring birthExposure to pesticides e.g. paraquat or Agent Orange
4 PathogenesisMost cases = idiopathic PD. Leading to a progressive degeneration + development of Lewy bodies in substantia nigra.Other pathways – mesocortical, mesolimbic + tubero-hypophysealGenetics (lead to early onset):mutations in c’some 6 = AR PDAlpha synuclein mutationParkin geneDopamine has a role in disinhibition of motor activity hence why reduced levels leads to dyskinesia.
5 PathophysiologyCell 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.
6 Clinical featuresResting tremor = usually unilateral before it becomes generalised. It is 4-6 Hz pill-rolling. Typically absent during activity.Rigidity = lead pipe. Cog-wheeling occurs when lead pipe rigidity is broken up by tremor.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.
7 Other features Progressive decline over years Mask-like face Impaired swallowing – drooling, choking on foodCognitive decline = depression + dementiaQuiet voice progressing to dysarthriaMicrographia (small + spidery writing)
8 DDx Wilson’s Lewy Body dementia: get visual hallucinations CJD: Dementia + myoclonic jerkingParkinson’s plusHuntington’s diseaseDrug-induced PDAntipsychotics (APAT side effects: acute dystonia, parkinsonism, akathisia, tardive dyskinesia)LithiumBenign essential tremorRarely at rest, worse on movementFamily hx
9 NICE criteria for Dx Exclude other causes Bradykinesia + at least 1 of:Rigidity4-6Hz resting tremorPostural instabilitySupportive criteria:UnilateralProgressive natureAsymmetry before bilateralResponse to L-Dopa
10 Investigations Typically a clinical diagnosis Use: Bedside: BP lying + standing, urine dipBloods: Genetic testing for Huntington’s or caeruloplasmin for Wilson’sImaging: CT/MRIFail to respond to L-DopaCan visualise structural defectsSpecial tests: DAT scan can differentiate between drug-induced + PD.
11 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, dieticianInform DVLAREHAB
12 Medical managementDrugs alter the natural progression – they just improve symptoms.LevodopaIs 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
13 Dopamine agonists e.g. Pramipexole = good for motor sx 1st line in younger patientsMAO-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
14 Surgical Deep brain stimulation Pallidotomy involves surgical destruction of the globus pallidus to control dyskinesia.