Neurological Disorders and Their Pathophysiology

Cerebrovascular accident (CVA STROKE)

Lack of blood brain tissue damage.

Ischemic stroke

Most common type of stroke, accounting for 85% of cases.

Thrombus/Thrombosis

Most common cause of ischemic stroke.

Affected arteries in ischemic stroke

MCA, ICA, and ECA which causes prolonged immobilization.

Triad of Thrombosis

Hypercoagulability, Intimal wall damage, venous stasis.

Lacunar Stroke

Small vessel thrombosis.

Lacunar infarct

Common in basal ganglia.

Hemorrhagic stroke

Least common type of stroke, accounting for 15% of cases.

Intracerebral hemorrhage

Most common subtype of hemorrhagic stroke.

Charcot bouchard

Common site is PUTAMEN, associated with abnormal movements.

Subarachnoid hemorrhage

Secondary to intracerebral hemorrhage.

Berry aneurysm

Affected artery is ACOM.

AVM (Arteriovenous Malformation)

Congenital defect with a triad of Hemorrhage, seizures, headache (HSH).

Risk factors for stroke (modifiable)

Hypertension, Smoking, Diabetes Mellitus, Obesity/Lifestyle.

Risk factors for stroke (non-modifiable)

Common race - African American, Family history of Stroke, Age > 55 for males, Age > 40 for females.

Symptoms of stroke

FAST (Face drooping, arm weakness, speech difficulty, time to call).

MCA manifestations

Left MCA affects language and speech (Broca/Global aphasia), Right MCA causes hemineglect (left side).

Weber syndrome

CN 3 contralateral paralysis for corticospinal tract.

Benedikt syndrome

CN 3 ipsilateral loss of pain and temperature, ataxia (Red nucleus).

Locked in syndrome

All cranial nerves affected, resulting in upward gaze.

Millard Gubler syndrome

Lateral Pons CN 6 & 7, causing facial palsy, internal strabismus, diplopia.

Wallenberg syndrome

Lateral Medulla CN 5, 7, 8, 9, 10, causing Horner's syndrome and triad of Wallenberg (ptosis, myosis, anhidrosis).

Traumatic brain injury (TBI)

Injury of the brain caused by trauma.

Closed Injury (Non-penetrating)

Common causes include falls, violence, and motor vehicle accidents.

Open injury (penetrating)

Includes gunshot wounds and blast injuries.

Primary Injury in TBI

Diffuse axonal injury (DAI) causing temporary LOC, present a few hours after the injury.

Common site of DAI

Corpus Callosum.

Coup-countercoup injuries

Injuries that occur on the opposite side of the impact.

Severity classifications of TBI

MILD TBI (concussion) - GCS 13-15, Moderate - GCS 9-12, Severe - GCS <8.

Parkinson's Disease

Loss of dopamine-producing neurons in the substantia nigra affecting motor control.

Symptoms of Parkinson's Disease

Tremor at rest, Rigidity, Akinesia/Bradykinesia, Postural instability.

Etiology

Most common - Idiopathic; Drugs that block dopamine

Risk Factors

M sex & Old age >60; Fam. History; Rural living (exposure to chemicals)

Pathophysio

Neuron loss Dopamine in substantia nigra dies; Basal Ganglia dysfunction

D1

Direct pathway promotes/facilitates movements

D2

Indirect pathway suppresses/inhibits movement

Chemical imbalance

Dopamine deficiency weakens direct pathway, too much acetylcholine causes Tremors and Rigidity

Lewy bodies

Misfolded proteins build up in brain cells which causes more damage

Spread

Affects thinking, emotions, and automatic functions over time

Clinical features

TRAP mnemonic; Non-motor - Constipation, depression, anosmia, sleep issues

MOST disabling symptoms

Bradykinesia; Makes daily activities hard (e.g. walking, eating)

Phases of Parkinson's

Preclinical phase; Prodromal phase; Clinical phase

Preclinical phase

No symptoms yet; Neuron dmg and lewy bodies start forming; Early signs: anosmia

Prodromal phase

Non-motor symptoms appear; Ex: anosmia, constipation, REM sleep behavior disorder, depression

Clinical phase

Early stage: mild tremor, stiffness, asymmetrical onset, responds well to levodopa; Moderate stage: Worsening symptoms, motor fluctuations, dyskinesia, non-motor symptoms worsen; Advanced stage: Falls, dementia, incontinence, medications less effective

Diagnostic highlights

Clinical diagnosis (Trap symptoms); Asymmetrical onset is typical; Improves with levodopa

Key reminders

Dopamine decrease means Motor issue increase; MRI/CT rules out other causes; Levodopa challenge test - confirms response; Not just movement - affects mood, thinking and sleep; Early signs are ANOSMIA, CONSTIPATION, and SLEEP ISSUES

Spinal Cord injury (SCI)

= damage to the sc that results in PARTIAL or COMPLETE loss of Motor, sensory, and/or autonomic function below the lvl of injury

Etiology of SCI

Traumatic SCI (MOST common); Non-Traumatic SCI

Traumatic SCI causes

MVA; Falls (elderly); Sports injuries; Violence

Non-Traumatic SCI causes

Tumors; Infections (Pott's disease = TB of Spine); Degenerative diseases (Cervical stenosis); Vascular issues

COMPLETE vs INCOMPLETE SCI

Complete SCI - TOTAL loss of motor & sensory function BELOW the level of injury; Incomplete SCI - some functions remain (movement, sensation)

ASIA impairment scale

A - COMPLETE no sensory/motor below injury; B - INCOMPLETE sensory only preserved; C - INCOMPLETE motor preserved, but weak; D - INCOMPLETE Motor preserved, stronger; E - Normal function

Complications of SCI

Autonomic dysreflexia - Sudden INCREASE BP, Bradycardia (T6 UP level); Motonomic Heightened sympathetic nervous system

Multiple Sclerosis

= CHRONIC autoimmune disorder that causes inflamm and demyelination of neurons in the CNS - Brain, sc, and optic nerves.

Pathophysiology of Multiple Sclerosis

Immune system MISTAKENLY attacks myelin (protective coating of nerve fibers); Demyelination slows or blocks nerve signal transmission; Leads to plaques (sclerotic lesions) seen in white matter; Over time neurodegeneration and axon loss

Common sites affected by Multiple Sclerosis

Optic nerves - vision; Brainstem - Speech, swallowing; Sc - motor/sensory; Cerebellum - Bal.

Charcot's triad

S - Scanning speech - broken or irregular speech pattern; I - Intention tremor - Shaking happens during movement; N - Nystagmus - Involuntary, rhythmic eye movements.

Relapsing-remitting ms (RRMS)

MOST COMMON type of Multiple Sclerosis.

Secondary progressive ms (SPMS)

A type of Multiple Sclerosis that follows relapsing-remitting MS.

Primary progressive ms (PPMS)

A type of Multiple Sclerosis characterized by a gradual worsening of symptoms from the onset.

Progressive-relapsing ms (PRMS)

A type of Multiple Sclerosis that has a progressive course from the beginning with occasional relapses.

Motor manifestations of MS

Weakness, spasticity, foot drop.

Sensory manifestations of MS

Numbness, tingling, Lhermitte's sign (shock-like sensation on neck flexion).

Visual manifestations of MS

Optic neuritis.

Balance manifestations of MS

Ataxia, tremors, dizziness.

Speech manifestations of MS

Dysarthria (slurred speech).

Cognitive manifestations of MS

Slowed thinking, poor concentration.

Fatigue in MS

MOST COMMON and disabling symptom.

Diagnosis of MS

MRI, CSF (Lumbar puncture) - Oligoclonal bands, Evoked potentials.

Guillain-barre syndrome (GBS)

An autoimmune condition where the body attacks the myelin of peripheral nerves, causing weakness, numbness, and sometimes paralysis, starting in the legs and moving up (ascending paralysis).

Etiology of GBS

Most common: Infection 1-3 weeks before onset (e.g., Campylobacter, CMV, EBV); Others: Surgery, trauma, rare vaccine reactions.

Risk factors for GBS

Recent infection, male gender, older age, genetic predisposition.

Pathophysiology of GBS

1. Triggering Infection → immune response starts; 2. Molecular mimicry: Antibodies mistake nerve myelin as foreign; 3. Immune attack: Myelin (or axon) gets damaged; 4. Saltatory conduction fails → slowed or blocked signals; 5. Weakness ascends: Legs → arms → face; possible breathing difficulty; 6. Recovery: Myelin slowly regenerates (weeks to months).

Clinical features of GBS

Onset - Rapid; hrs to days; Pattern - Ascending, symmetrical weakness; Reflexes - Absent or reduced; Sensory - Mild numbness or tingling; Cranial - Facial weakness, eye movement problems; Autonomic - BP swings, irregular heartbeat; Respiratory - May need ventilator in severe cases; Bowel/Bladder - Usually Spared.

Diagnostics for GBS

CSF (Lumbar Tap): ↑ protein, normal WBC (albuminocytologic dissociation); Nerve studies (EMG/NCS): slowed conduction, block; MRI: Rule out spinal cord issues; Rule out: Stroke, myelitis, or spine compression.

AIDP

Classic type of GBS - demyelination.

AMAN

Axon damage (motor only) in GBS.

AMSAN

Axon damage (motor & sensory) in GBS.

Miller Fisher syndrome

Eye paralysis + ataxia + areflexia.

Pharyngeal-Cervical-Brachial syndrome

Facial/neck/arm weakness only.

Myasthenia Gravis (MG)

A chronic autoimmune disease where antibodies block acetylcholine receptors at the neuromuscular junction, causing muscle weakness that worsens with activity and improves with rest.

Etiology of MG

Autoantibodies: Anti-AChR (most common), Anti-MuSK, Anti-LRP4; Thymus abnormalities: Thymoma or hyperplasia; Unknown trigger: Possibly viral or environmental.

Risk factors for MG

Women < 40 yrs; men > 60 yrs; Autoimmune diseases (thyroid, lupus); Thymic tumor; Genetic predisposition.

Pathophysiology of MG

1. Autoantibodies block or destroy acetylcholine (ACh) receptors; 2. Less ACh binding → weak end-plate potential → no muscle contraction; 3. Fewer working receptors → fatigable weakness; 4. Muscles with frequent use (eyes, face, throat) affected first.

Ocular MG

A form of Myasthenia Gravis that affects only the eye muscles.

Generalized MG

A form of Myasthenia Gravis that includes weakness in the limbs, face, and throat.

MuSK-MG

A subtype of Myasthenia Gravis that is more common in younger women and has more bulbar symptoms.

Thymoma-associated MG

A form of Myasthenia Gravis linked to the presence of a thymic tumor.

Key feature of MG

Fatigability: symptoms worsen with activity and improve with rest.

Ice Pack Test

A diagnostic test where cooling the eyelid improves ptosis.

Edrophonium Test

A diagnostic test that shows temporary strength improvement in MG patients.

Antibody Tests

Tests for Anti-AChR and Anti-MuSK antibodies to help diagnose Myasthenia Gravis.

Repetitive Nerve Stimulation (EMG)

A diagnostic test that shows a decreased response in Myasthenia Gravis.

Single-fiber EMG

The most sensitive diagnostic test for Myasthenia Gravis.

Carpal Tunnel Syndrome (CTS)

A condition caused by median nerve entrapment at the wrist leading to neuropathy.

Pathophysiology of CTS

Increased tunnel pressure leads to median nerve compression, ischemia, and demyelination.

Clinical manifestations of CTS

Paresthesia in the thumb and radial half of the ring finger, pain worse at night, and weakness.

Phalen's Test

A clinical test where wrist flexion induces tingling in CTS patients.

Muscular Dystrophy (MD)

Genetic disorders causing progressive muscle degeneration, with Duchenne Muscular Dystrophy being the most common.