The nurse practitioner managing neurological conditions must integrate advanced neuroanatomical knowledge with evidence-based diagnostic and treatment algorithms. Neurodegenerative diseases involve progressive neuronal loss through disease-specific pathological protein accumulation: beta-amyloid plaques and tau neurofibrillary tangles in Alzheimer's disease, alpha-synuclein Lewy bodies in Parkinson's disease, and SOD1 mutations with TDP-43 inclusions in amyotrophic lateral sclerosis. Multiple sclerosis is an autoimmune demyelinating disease where autoreactive T cells cross the BBB and attack myelin sheaths, causing demyelination and axonal injury with relapsing-remitting or progressive patterns — disease-modifying therapies (interferon-beta, glatiramer acetate, natalizumab, ocrelizumab) target different immune mechanisms. Headache management requires differentiating primary headaches (migraine, tension, cluster) from secondary headaches using red flag features (thunderclap onset, focal deficits, fever, papilledema) and prescribing acute and preventive therapies based on headache type, frequency, and disability.