Nocturnal Hypokinesia and Early Morning OFF in Parkinson's Disease: State-of-the-Art and Systematic Review of Treatment Availability.

PURPOSE OF REVIEW: To review the pathophysiology, clinical presentation, evaluation methods, and current treatment strategies of nocturnal hypokinesia and early morning OFF in Parkinson's disease. A comprehensive literature search was conducted using PubMed, ScienceDirect, and the Cochrane Library for relevant treatment strategies.

RECENT FINDINGS: We identified 31 clinical trials. Pharmacologic treatments include standard and sustained-release levodopa, dopamine agonists (rotigotine, ropinirol, pramipexole, and apomorphine), MAO-B inhibitors (rasagiline, safinamide), COMT inhibitors (opicapone), and rescue therapies like inhaled or dispersible levodopa or apomorphine injection. We propose a tiered treatment algorithm based on disease stage and symptom severity. Non-pharmacological treatment is recommended in all stages. For mild, disturbing symptoms in early PD, inhaled or dispersible levodopa or apomorphine injection are advised. In moderate to advanced stages, treatment options include long-acting dopamine agonists, MAO-B inhibitors, sustained-release levodopa, or COMT inhibitors selected based on factors such as daytime motor symptoms, and non-motor symptoms.