off-state (off-time) (Parkinson’s disease)

The period in the middle to late stages of Parkinson’s disease when dosages of anti-parkinson’s medications are on the downward side of peak effectiveness or can no longer fully suppress symptoms and symptoms “break through.” Most people with Parkinson’s disease structure their medication dosages to provide the most substantial relief during waking hours (oN-state). Medication coverage is lowest in the early morning, when symptoms such as tremors and bradykinesia (slowed movement) are likely to be prominent. Early-morning off-state dystonia, in which the person with Parkinson’s awakens to find a foot, most commonly, “frozen” in an awkward and sometimes painfully contorted position, is particularly distressing. Sometimes a muscle relaxant medication such as baclofen can help relieve this off-state symptom, but it has a high risk of causing sedation and thinking problems. Other dyskinesias and dystonia (intense muscle rigidity) are common during off-state episodes as well, and cognitive impairment, particularly dementia and memory loss, can become more pronounced.

As Parkinson’s disease progresses and dopamine depletion in the brain becomes more severe, current anti-Parkinson’s medications are no longer able to compensate for the changes in the brain’s neurochemistry. Medication dosages reach the threshold at which the adverse effects of the drug outweigh the benefits; the medications begin to cause symptoms, such as dystonia, chorea (involuntary fidgeting movements often described as dancelike) and athetosis (involuntary slow, writhing, repetitious movements), that are as debilitating as the symptoms of Parkinson’s. As well, remaining dopamine receptors in the brain become sensitized to activation by the exogenous (from a source outside the body) dopamine the brain metabolizes from Levodopa or the exogenous dopaminergic activity from dopamine agonists.

Altering adjunct therapies—adjusting the kinds and combinations of medications, dosages, and timings—often provides short-term improvements in the balance between on-state and off-state when off-state episodes begin. In the late stages of Parkinson’s, this approach becomes less effective. medication management becomes strategic, as the person takes dosages for maximal benefit during times when he or she desires the greatest relief from symptoms and plans activities around peak on-states. patience, empathy, and humor are helpful in coping with off-state episodes, which often are frustrating and can be frightening for the person with Parkinson’s as well as for loved ones.

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