Parkinson Disease

Excerpt

Parkinson disease (PD), also known as Idiopathic or primary parkinsonism, hypokinetic rigid syndrome, or paralysis agitans, is the second most common progressive neurodegenerative disorder, affecting 2% to 3% of people older than 65. The degeneration of dopaminergic neurons in the substantia nigra, accompanied by the intracellular accumulation of alpha-synuclein (α-synuclein) (Lewy body), represents the neuropathological hallmark of the disease. PD usually presents in later life with the cardinal clinical motor features of bradykinesia, resting tremor, and rigidity, often in various combinations. Postural instability emerges later in the disease course as another defining feature (see Image. An Illustration of Parkinson Disease). The motor symptoms of PD are typically asymmetric, which helps differentiate it from other Parkinsonian syndromes. By the time a clinical diagnosis is made, more than 50% and up to 80% of the dopaminergic neurons have degenerated. Recognition is growing that the pathology of PD begins a decade or more before clinical diagnosis, with α-synuclein deposition in other neurons, including those of the gastrointestinal tract, olfactory structures, hypothalamus, and autonomic nervous system. These early changes contribute to premotor and nonmotor symptoms such as anosmia or hyposmia, constipation, and sleep dysfunction, especially rapid eye movement sleep behavior disorder. Additional nonmotor features include depression, orthostatic hypotension, dementia, and psychosis.

Current estimates suggest that PD affects at least 1% of individuals over the age of 60, and the disorder is the fastest-growing neurodegenerative condition worldwide. Most cases are idiopathic, though approximately 10% have a genetic cause, with 3% to 5% of patients carrying inherited pathogenic variants in known PD genes. Onset is generally insidious, but progression is inevitable (see Image. Progression of Symptoms in Parkinson Disease). Tremor is often the first clinical sign and may later be accompanied by bradykinesia and rigidity. Postural instability typically develops in the later stages, significantly impairing quality of life. Dopamine transporter single-photon emission computed tomography scans can aid in uncertain cases or help exclude other neurological disorders. Management focuses on dopaminergic therapies to address motor symptoms, while nonmotor manifestations often require additional targeted treatments. No disease-modifying therapy has yet been proven. However, stereotactic neurosurgical interventions, such as deep-brain stimulation, offer effective options for patients with advanced motor complications.