1. Involuntary movements in Parkinson’s disease: not always what it seems
Teaching NeuroImages
Neurology
Resident and Fellow Section
© 2017 American Academy of Neurology

2. Vignette
56-year-old man with an 8-year history of Parkinson’s disease, heralded by left-hand resting tremor and slow gait.
Early and robust response to levodopa was followed by motor complications, including generalized dyskinesia initially interpreted as peak-dose (Video)
Verhagen et al.
© 2017 American Academy of Neurology

3. Video Verhagen et al. Video Legend
Parkinson disease patient with generalized but leg-predominant ballistic-dystonic movements with kicking and bicycling, initially interpreted as peak-dose dyskinesia. The behavior markedly attenuated within 7 minutes after a self-administered subcutaneous injection of apomorphine, confirming its diphasic nature.
Verhagen et al.
© 2017 American Academy of Neurology

4. Time course of diphasic dyskinesia according to three different theoretical plasma levodopa concentrations
OFF (re-emergence of parkinsonian features)
ON without dyskinesia (optimal clinical benefit)
ON with peak-dose dyskinesia
DiDysk (diphasic dyskinesia)
LD = levodopa
A = high dose B = medium dose C = low dose
Supratherapeutic window A
Therapeutic window B
plasma LD concentration
Transitional window C
Undertherapeutic window
LD dose
Single LD dose cycle
LD dose
Figure. Time course of diphasic dyskinesia according to three different theoretical plasma levodopa concentrations (A,B,C).
At the lowest dose (C), diphasic dyskinesia becomes dominant between levodopa doses and may be clinically mistaken as peak dose. Pharmacotherapeutic strategies will differ in each scenario: LD dose should be reduced (or amantadine considered) in A but increased in C; LD dose interval may be shortened in B.
OFF
DiDysk ON
ON with peak-dose dyskinesia ON
DiDys
OFF
Dose A
OFF
DiDysk
ON without dyskinesia
DiDys
OFF
Dose B
OFF
DiDysk
OFF
Dose C
At the lowest dose (C), diphasic dyskinesia becomes dominant between levodopa doses and may be clinically mistaken as peak dose.
Verhagen et al.
© 2017 American Academy of Neurology

5. Diphasic dyskinesia in Parkinson disease
Peak-dose dyskinesia is a common motor complication in levodopa-treated Parkinson disease (PD) patients, associated with higher doses, greater disease severity and longer disease duration.
Diphasic dyskinesia (beginning-of-dose or end-of-dose) may be confused with peak-dose, as exemplified in the Video.
Management differs: while dopaminergic stimulation needs reduction in peak-dose dyskinesia, it should be increased in diphasic.
References
1. Verhagen Metman L. Recognition and treatment of response fluctuations in Parkinson's disease: review article. Amino Acids 2002;23:
2. Durif F, Deffond D, Dordain G, Tournilhac M. Apomorphine and diphasic dyskinesia. Clin Neuropharmacol 1994;17:
Verhagen et al.
© 2017 American Academy of Neurology