CLASSIFICATION OF FLUCTUATIONS IN PATIENTS WITH PARKINSONS-DISEASE

Patients with Parkinson's disease (PD) are subject to a wide range of fluctuations in their clinical state, most of them treatment-related b ut some more disease-related. Short-duration motor fluctuations includ e freezing and paradoxic kinesis, lasting seconds to minutes. It is im portant to distinguish between ''off'' period freezing, which may be h elped by measures to increase time ''on,'' and freezing that is presen t in both ''on'' and ''off'' periods, which is difficult if not imposs ible to treat. Medium-duration fluctuations associated with chronic L- dopa treatment include wearing-off and ''on-Off'' responses, which can involve (a) return of parkinsonism, (b) dyskinesias, and (c) non-moto r fluctuations. A poorly understood long-duration pharmacodynamic resp onse to L-dopa lasting up to 2 weeks may also be seen. This may manife st as late deterioration after L-dopa is withdrawn. More importantly, and more commonly, it is important to recognize that the ultimate effe ct of an alteration in L-dopa treatment may take 2 weeks to equilibrat e in the brain. ''Optimization'' of L-dopa therapy is therefore not a realistic expectation during an inpatient admission and is instead pri marily a long-term outpatient procedure. The ''off'' state is not the same as untreated PD, and may represent rebound worsening after the be neficial effect of L-dopa has worn off. Sometimes there is also transi ent worsening at the onset of effect of a dose. ''Off'' period dyskine sias tend to be relatively fixed, painful, and dystonic. Biphasic (beg inning and/or end of dose) dyskinesias are often severe, ballistic, an d stereotypic. Peak dose or ''square wave'' dyskinesias comprise a mix of mobile dystonia or chorea that is usually painless. Many patients experience any combination of panic, anxiety, and depression in their ''off'' periods, and many also experience pain, with instant relief as they turn ''on.'' Other parameters that may vary between the ''on'' a nd ''off'' states include urinary and bowel dysfunction, blood pressur e, respiratory function, and sweating attacks. Most but not all of the se phenomena can be related to a simplistic but nevertheless usually p ractically useful model of differing levels of central dopaminergic st imulation. In difficult cases, an acute apomorphine challenge analogou s to the effects of a ''Tensilon test'' in myasthenia gravis may help to determine whether a given clinical feature represents over- or unde rstimulation of central dopamine receptors.