VROEG of LAAT… in de ziekte van Parkinson Nycteumdag huisartsen Donderdag 22 april 2010 Dr. EMJ Foncke bewegingsstoornissen neuroloog Afdeling Neurologie VU medisch centrum

Inleiding Mythen en sagen over de medicamenteuze behandeling Op zoek naar de holy grail: de nieuwe therapieën

Inleiding ziekte van Parkinson Prevalentie: 100-250/100.000 Prevalentie neemt toe met leeftijd Debuut: 50-60 jaar Man>vrouw The prevalence of PD is estimated between 100-250 cases per 1000000 persons

Diagnose ziekte van Parkinson Anamnese Klinische diagnose Beeldvorming MRI-scan hersenen DAT-SPECT Neurologisch onderzoek The diagnosis of PD is in the first place a clinical diagnosis based on the patients history in combination with a careful neurological examination with emphasis on the extrapyramidal system. Imaging is important to exclude other causes of parkinsonism and in case of doubt a DATspect may support the clinical diagnosis. But I’ll come back to this later.

Diagnose Parkinsonisme rigiditeit monotone spraak bradykinesia hypomimiek micrografie rust tremor (4-6 Hz) marche à petit pas Let’s move to the diagnostic steps in PD. First of all we have to make the clinical diagnosis of parkinsonism. Parkinsonism is characterised by bradykinesia in combination with one of the three symptoms displayed here. Rigidity, resting tremor or postural instability. Examples of bradykinesia are decreased expression of the face, smaller writing, walking with short steps and decreased speech volume. posturale instabiliteit

Tremor video

Hypokinesie video

MYTHEN EN SAGEN over de medicamenteuze behandeling De Angst levodopa = neurotoxisch = responsfluctuaties = verliest werkzaamheid De Feiten non dopaminerge functiestoornissen kwaliteit van leven dyskinesieën

De ANGST LEVODOPA=NEUROTOXISCH

Parkinson study group, NEJM

Levodopa= Responsfluctuaties Response Threshold Dyskinesia Threshold Time (h) Vroege PD Levodopa Clinical Effect 2 4 6 Response Threshold Time (h) 4 Dyskinesia Threshold 2 Matige PD Clinical Effect Levodopa 6 Gevorderde PD Time (h) Clinical Effect Levodopa 2 4 6 Dyskinesia Threshold Response Threshold Pulsatiele dopaminerge stimulatie

Levodopa verliest werkzaamheid Postsynaptische dopamine receptoren verdwijnen Ogenschijnlijke ongevoeligheid

De FEITEN Non dopaminerge functiestoornissen Preklinisch Vroeg klinisch Due to the work of Braak, a german neuropathologist we know that the degeneration proces in PD starts at a lower level than the sn in the brainstem, affecting non dopaminergic structures. The so called preclinical stage of pd. The degeneration proces progresses in a rostral direction affecting the sn at the early clinical stage where at that time motor symptoms become manifest. At the late clinical stage there is also involvement of different cortical structures often leading to dementia Laat klinisch BRAAK stadia

Kwaliteit van leven

Dyskinesieën

De PRAKTIJK Levodopa Dopamine-agonist MAO-B remmer

De HOLY GRAIL en nieuwe therapieën Diepe hersenstimulatie Duodopa pompbehandeling

Rationale: Continue dopaminerge stimulatie

Diepe hersenstimulatie Copyright restrictions may apply.

Diepe hersenstimulatie Wie? Wanneer? Waar?

Duodopa pompbehandeling

VROEG of LAAT OP MAAT