Parkinson’s disease AskTheNeurologist.Com Author Anon

Essay on the shaking palsy James Parkinson 1817 “ involuntary tremulous motion,with lessened muscular power, in part not in action and even when supported ;with a propensity to bend the trunk forward, and to pass from a walking to a running pace , the senses and intellect being uninjured”

Pathology Loss of pigmented cells in substantia nigra Intracellular cytoplasmic inclusion bodies ( Lewy bodies )

Parkinson disease is characterised by loss of Dopaminergic cells in the substantia nigra leading to abnormal activity in the basal ganglia as a whole This leads to - A decrease in the activity of the direct GABAergic pathway - An increase in the activity of the indirect GABAergic pathway

Uptake of radio-labelled L-Dopa in striatum of normal compared to PD brain

Clinical Features T R A P Tremor Rigidity Akinesia / Bradykinesia Postural instability

Micrographia = manifestation of bradykinesia

Overview of drug treatment L-Dopa ( bypass rate limiting stem of Dopamine synthesis) Dopamine agonists ( direct effect on striatum ) COMT inhibitors ( less peripheral inactivation of L-Dopa ) Selegeline ( MAO b ) inhibitor ? Neuroprotective Muscarinic antagonists ( act on striatal interneurons) Amantadine ( mechanism unclear ? Dopamine release )

L-Dopa ( bypass rate limiting stem of Dopamine synthesis)

Dopamine agonists ( direct effect on striatum )

COMT inhibitors ( less peripheral inactivation of L-Dopa )

Selegeline ( MAO b ) inhibitor ? Neuroprotective

Muscarinic antagonists ( act on striatal interneurons)

Amantadine ( mechanism unclear ? Dopamine release )

Treatment strategies The conservative approach The neuroprotective approach The symptomatic approach

The conservative approach

The neuroprotective approach

The symptomatic approach

Conservative approach Avoid all drugs until symptoms are troublesome When symptoms become troublesome start amantadine and an anticholinergic When symptoms become disabling introduce L-Dopa or agonists at minimal doses

Avoid all drugs until symptoms are troublesome

When symptoms become troublesome start amantadine and an anticholinergic

When symptoms become disabling introduce L-Dopa or agonists at minimal doses

Neuroprotective approach All newly diagnosed cases should be started on Selegeline When symptoms become disabling add dopaminergic drugs

All newly diagnosed cases should be started on Selegeline

When symptoms become disabling add dopaminergic drugs

Symptomatic approach At diagnosis treatment immediately started with dopaminergic drugs Treatment continually modified in order to maintain maximum function for the maximum amount of time

Clinical fluctuations in PD Very difficult to treat Sustained release preparations On-Off phenomenon Increase dose of L-Dopa Increase dose frequency Give before meals “ Off ” periods Ensure L-Dopa not given with protein. Give antacids Delayed onset of response Decrease between dose interval Sustained release L-Dopa Add DA agonist Increase dose Add COMT inhibitor Wearing-off of L-Dopa effect Management Condition

Dyskinesias in PD Clonazepam Decrease L-Dopa Myoclonus Decrease each dose of L-Dopa Add Dopamine agonist Add amantadine Peak-dose dyskinesia Management Type

Psychosis in PD Increased incidence in - Elderly - Pre-existing psychiatric conditions Should only use atypical antipsychotic medications….in particular CLOZAPINE - needs monitoring of white cell count QUETIAPINE - no monitoring necessary - now possibly drug of choice

The End AskTheNeurologist.Com Author Anon