Motor Complications of Parkinson's Disease

Parkinson’s disease (PD), caused by dopamine deficiency due to degeneration of striato-nigral fibres and accumulation of Lewy bodies in dopaminergic striatal neurons, is generally treated by dopamine replacement therapy. In the initial stage the response to levodopa/carbidopa therapy is smooth, patient being unaware when the response comes and when it dwindles. The response is good initially if the dose of levodopa/carbidopa is high enough and hence, the patient feels he/she is free from any PD symptoms throughout the day. However, over several years the response becomes less optimum and patients experience that they are not the same throughout the day. They experience the response to start several minutes (about 10-15 minutes) after the ingestion of dose and peak in few minutes (about 30 minutes or so), remain good for 3-5 hours and then slowly wear off. Even when the effect is present, it is not 100% as it used to be initially. They remain “off” i.e. when Parkinsons’ symptoms appear between two doses of levodopa/carbidopa. Over years the effect becomes further less and the therapeutic window also becomes smaller, effect starting about an hour after ingestion of dose, lasting about 2-3 hours and when present it is only 40-50% of normal. Initially they are not perturbed about this behaviour of treatment effect, but when “off” period become longer and the therapeutic effect is sub optimal, they seek modification of treatment. Thus, we come to the concept of “wearing off” effect and “on-off” periods. These motor fluctuations form integral part of treatment of PD with levodopa/carbidopa. Further, some of the doses may not be able to kick off effect at all (”no on”) or may kick off after a prolonged period (”delayed on”). After some years, “on” period may come on suddenly and “off” period may also come suddenly. This is likened to a switch turning “on and off”. “Wearing off” effect has been described earlier when the shift from “on” to “off” is gradual. Over certain years some patients develop abnormal choreic movements. If they appear when the effect of levodopa/carbidopa dose is at the peak, it is known as “Peak dose dyskinesia”. At times, it starts as the effect of a dose kicks in and again as it wears off - “Biphasic dyskinesia”. Some patients during off period get dystonic postures especially of toes and feet. These are “off period dystonias”. These may be painful or painless.