Chapter 16 NEUROLOGICAL DISORDERS

NEURODEGENERATION

Progressive loss of neurons caused by protein aggregation, oxidative stress, mitochondrial failure, or genetic mutations.

SPORADIC vs. FAMILIAL (HEREDITARY) DISEASE

Sporadic: Not directly inherited; 95% of Alzheimer's & Parkinson's. Familial: Direct genetic mutation; Earlier onset; Clear inheritance patterns.

PARKINSON'S DISEASE (PD)

Degeneration of dopaminergic neurons in the substantia nigra → ↓ dopamine in basal ganglia.

BRADYKINESIA

Slowness of movement.

AKINESIA

Difficulty initiating movement.

RESTING TREMOR

Shaking at rest.

POSTURAL INSTABILITY

Balance issues.

BASAL GANGLIA CIRCUITRY

Direct pathway → initiates movement; Indirect pathway → inhibits movement.

LEWY BODIES

Aggregates of misfolded α-synuclein inside neurons; cause neuronal death → hallmark of PD.

PARKIN GENE MUTATION

Normal Parkin = tags proteins with ubiquitin for degradation; Mutation → toxic buildup of proteins.

PARKINSON'S TREATMENTS (DRUGS)

L-DOPA converts to dopamine in the brain; Combined with carbidopa; MAO-B inhibitors prevent dopamine breakdown; Dopamine agonists mimic dopamine at receptors.

PARKINSON'S TREATMENTS (SURGERY)

DBS (Deep Brain Stimulation): stimulates subthalamic nucleus; Pallidotomy / Lesioning STN: reduces overactivity.

ALZHEIMER'S DISEASE (AD)

Progressive neurodegenerative disease beginning in the hippocampus.

Aβ (BETA-AMYLOID) PLAQUES

Formed by cleavage of APP → Aβ; Accumulate between neurons; Cause inflammation & synaptic loss.

TAU NEUROFIBRILLARY TANGLES

Tau normally stabilizes microtubules; Hyperphosphorylated tau → tangles → neuronal death.

GENETIC RISKS FOR AD

Early-Onset AD: APP, Presenilin 1 (PSEN1), Presenilin 2 (PSEN2); Late-Onset AD: APOE-4 = major risk allele, APOE-2 protective, APOE-3 neutral.

PITTSBURGH COMPOUND B (PIB) — Aβ IMAGING

Binds to amyloid plaques; Used in PET scans to visualize AD pathology.

ALZHEIMER'S TREATMENTS

Cholinesterase inhibitors (↑ ACh); Memantine (NMDA antagonist → reduces excitotoxicity).

CEREBROVASCULAR SYSTEM

Key arteries: Carotids, Vertebral, Basilar, Circle of Willis (backup circulation).

STROKE

Types: Ischemic stroke: blockage; Hemorrhagic stroke: vessel rupture; Brain damage mechanism: Glutamate excitotoxicity: Ca²⁺ overload → neuron death.

STROKE TREATMENT — tPA

tPA (Tissue Plasminogen Activator); Breaks down clots; Must be given within ~3 hours; Risky if BBB compromised.

CONSTRAINT-INDUCED MOVEMENT THERAPY (CI THERAPY)

Restrict healthy limb to force use of impaired limb; Increases cortical plasticity; Used post-stroke.