Non-motor Symptoms in Parkinson Disease

Non-motor symptoms (NMS) are a defining feature of Parkinson disease (PD) and may precede classical motor signs by years to decades. They reflect alpha-synuclein pathology beyond the substantia nigra, including the dorsal motor nucleus of the vagus, olfactory bulb, locus coeruleus, raphe nuclei, and cortical regions, supporting Braak's staging hypothesis.

Major NMS domains are autonomic dysfunction (orthostatic hypotension, constipation, urinary urgency, erectile dysfunction, sialorrhea), neuropsychiatric symptoms (depression, anxiety, apathy, psychosis, impulse control disorders), cognitive impairment progressing to dementia, sleep disorders (REM sleep behavior disorder, restless legs, excessive daytime sleepiness), sensory symptoms (hyposmia, pain), and fatigue.

Validated tools such as the NMS Questionnaire and the MDS-Non-Motor Scale guide systematic assessment. Management is multidisciplinary and includes targeted pharmacotherapy (midodrine and droxidopa for orthostasis, pimavanserin for psychosis, quetiapine and clozapine, SSRIs/SNRIs for depression, melatonin and clonazepam for RBD), physiotherapy, dietary management, and caregiver support. Recognizing the prodromal NMS phase (RBD, hyposmia, constipation, depression) supports early diagnosis and disease-modifying trials.