Neurological System Pathophysiology

Resting Membrane Potential

• Normal: -70 mV (inside negative)
• Maintained by: Na+/K+ ATPase pump (3 Na+ out, 2 K+ in)
• Gradient: more K+ inside, more Na+ outside
• K+ permeability: higher at rest (causes negative potential)

Action Potential Phases

• Depolarization: stimulus reaches threshold → Na+ channels open → Na+ rushes in → positive peak (+30 mV)
• Repolarization: Na+ channels inactivate, K+ channels open → K+ rushes out → return to negative
• Hyperpolarization: K+ channels stay open too long → overshoots negative → returns to resting
• Refractory periods: absolute (can't fire), relative (harder to fire)

Synaptic Transmission

• Sequence: action potential → Ca2+ influx → vesicle fusion → neurotransmitter release → receptor binding
• Excitatory: glutamate, acetylcholine, norepinephrine (depolarize postsynaptic cell)
• Inhibitory: GABA, glycine (hyperpolarize, open Cl- channels)
• Plasticity: LTP (repeated stimulation → stronger signal), LTD (weaker signal)

Myelination & Conduction

• Unmyelinated: continuous conduction (0.5-2 m/sec)
• Myelinated: saltatory conduction between Nodes of Ranvier (5-120 m/sec)
• CNS myelin: oligodendrocytes
• PNS myelin: Schwann cells

Brain Structure & Function

• Cerebrum (4 lobes): frontal (motor, executive), parietal (sensory), temporal (auditory, memory), occipital (vision)
• Brainstem: midbrain, pons, medulla (vital functions)
• Cerebellum: coordination, balance, fine motor
• Gray matter: neuron bodies, synapses
• White matter: myelinated axons, tracts

Motor & Sensory Pathways

• Corticospinal (motor): motor cortex → cross at medulla → contralateral spinal cord
• Dorsal column (touch/vibration/proprioception): ipsilateral ascent → cross at medulla
• Spinothalamic (pain/temperature): immediately crosses (1-2 segments), contralateral ascent
• Result: crossed lesions → contralateral deficits (except at lesion level)

Meninges & CSF

• Layers: dura (tough outer), arachnoid, pia (adheres to brain)
• CSF: circulates between arachnoid/pia, protects/nourishes CNS
• Blood-brain barrier: tight junctions prevent most substances from entering

Ischemic Stroke

• Cause: sudden ↓ cerebral blood flow (thrombosis 80%, embolism 15%)
• Ischemic cascade: ATP depletion → Na+/K+ pump failure → cell swelling → Ca2+ dysregulation → apoptosis
• Penumbra: viable tissue around infarct core, salvageable with reperfusion
• Treatment window: tPA (<4.5 hrs), mechanical thrombectomy (<24 hrs)
• Territories: ACA (medial brain), MCA (lateral brain), PCA (occipital)

Hemorrhagic Stroke

• Intracerebral: bleeding into brain substance (hypertension common cause)
• Subarachnoid: bleeding into subarachnoid space (ruptured aneurysm)
• Epidural: bleeding between dura/skull (arterial, rapid accumulation)
• Subdural: bleeding between dura/brain (venous, slower in chronic)
• Complication: vasospasm (delayed ischemia hours-days after SAH)

Increased Intracranial Pressure (ICP)

• Monroe-Kellie: skull fixed volume = brain + blood + CSF
• Causes: edema (cytotoxic/vasogenic), hemorrhage, mass, CSF obstruction
• Normal ICP: 5-15 mmHg
• Cerebral Perfusion Pressure: MAP - ICP (normal 70-90 mmHg)
• Herniation: transtentorial (uncal), tonsillar → brainstem compression

Seizures

• Pathophysiology: abnormal excessive electrical activity
• Mechanisms: ↓ inhibition (GABA), ↑ excitation (glutamate), abnormal ion channels
• Generalized: tonic-clonic (stiffening + jerking), absence (staring), atonic (drop attacks)
• Focal/Partial: localized, consciousness variable
• Status Epilepticus: prolonged seizures (>5 min), life-threatening, requires IV benzodiazepines

Meningitis

• Inflammation of meninges
• Bacterial: S. pneumoniae, N. meningitidis (highest mortality)
• Viral: enteroviruses, HSV (better prognosis)
• Classic triad: fever, headache, neck stiffness
• Kernig's/Brudzinski's: meningeal signs
• Management: antibiotics, corticosteroids, supportive care

Encephalitis

• Brain parenchymal inflammation (usually viral)
• Diffuse inflammation: altered mental status, seizures, focal deficits
• Causes: HSV, enterovirus, West Nile, Zika, arboviruses
• Differs from meningitis: focal neurological findings more common

Neurodegenerative Diseases

• Alzheimer's: amyloid plaques, tau tangles, memory loss → language/visuospatial decline
• Parkinson's: dopamine-producing neuron loss, tremor/rigidity/bradykinesia/postural instability
• Multiple Sclerosis: autoimmune demyelination, white matter plaques, variable deficits
• ALS: motor neuron degeneration, progressive paralysis including respiratory, fatal

Traumatic Brain Injury

• Mild (concussion): LOC <30 sec, may have transient symptoms
• Moderate: LOC 30 sec-6 hours, some deficits
• Severe: LOC >6 hours, significant neurological injury
• Complications: epidural (arterial bleeding), subdural (venous), SAH
• Secondary injury: edema, increased ICP, hypoxemia, hypotension

Spinal Cord Injury

• Complete: no sensation/motor below injury level
• Paraplegia: thoracic/lumbar injury
• Tetraplegia: cervical injury
• Acute phase: spinal shock (flaccid paralysis, areflexia)
• Chronic: spasticity develops, UMN signs (hyperreflexia, Babinski)
• Patterns: Brown-Séquard (hemisection), central cord, anterior cord

Upper vs. Lower Motor Neuron Signs

• Upper Motor Neuron (UMN): lesion in motor cortex/brainstem → spasticity, hyperreflexia, Babinski sign, minimal atrophy
• Lower Motor Neuron (LMN): lesion in brainstem/spinal cord/nerves → flaccidity, hyporeflexia, atrophy, fasciculations
• Crossing: corticospinal tract crosses at medulla (90%) → contralateral weakness

Peripheral Neuropathy

• Causes: diabetes (most common), alcohol, toxins, chemotherapy, infection, nutritional deficiency
• Sensory: stocking-glove distribution, numbness, tingling, pain
• Motor: weakness, atrophy, LMN signs
• Guillain-Barré (GBS): acute inflammatory demyelination, ascending paralysis, respiratory failure risk

Stroke Screening (FAST)

• F - Face: asymmetry, droop
• A - Arm: weakness, drift
• S - Speech: slurred, difficulty
• T - Time: note onset (critical for treatment window)

Neurological Examination

• Mental status: alertness, orientation, cognition
• Cranial nerves: CN I-XII function
• Motor: strength (0-5 scale), tone, tremor
• Sensory: light touch, vibration, proprioception, pain
• Reflexes: deep tendon (0-4 scale), Babinski (normal=flexion, abnormal=extension)
• Coordination: ataxia, dysmetria, nystagmus

Diagnostic Tests

• CT head: acute bleeding, mass, fracture (fast, no radiation concerns)
• MRI brain: soft tissue detail, ischemic stroke, contraindications with metals
• CSF analysis: cell count, protein, glucose, culture, PCR for viral
• EEG: seizure activity, abnormal rhythms, coma assessment
• Neuropsychological testing: formal cognitive assessment

1. Explain the ischemic cascade in acute ischemic stroke, from arterial occlusion through neuronal death.

2. Compare epidural hematoma versus subdural hematoma in terms of arterial source, symptom timeline, and imaging.

3. Discuss pathophysiology of transtentorial herniation and how increased ICP causes uncal herniation with CN III compression.

4. A patient with cervical spinal cord injury has left leg weakness and right leg pain/temperature loss. What pattern does this indicate?

5. Discuss mechanisms by which bacterial meningitis causes meningeal inflammation and subsequent complications.