Acute Disorders of Brain Function – Vocabulary Review

Brain Anatomy and Functions

• Frontal lobe

– Motor control (premotor cortex)

– Problem-solving, judgment, personality (prefrontal area)

– Speech production (Broca’s area)

• Parietal lobe

– Primary somatosensory cortex: touch, pain, temperature

– Spatial/body-orientation & sensory discrimination

• Temporal lobe

– Auditory processing

– Language comprehension (Wernicke’s area)

– Memory & information retrieval

• Occipital lobe

– Visual reception & interpretation (visual cortex)

• Cerebellum

– Balance, posture, fine motor coordination

• Brain-stem

– Midbrain, pons, medulla

– Cardiovascular & respiratory centers, consciousness, most cranial-nerve nuclei

– Site of life-sustaining autonomic reflexes

Mechanisms of Brain Injury

• Eight classic overlapping mechanisms

– Mechanical trauma

– Ischemia

– Cellular energy failure (↓ ATP)

– Reperfusion injury (oxygen free-radicals, inflammatory burst)

– Excitotoxins (excess glutamate → \text{Ca}^{2+} influx → cell death)

– Cytotoxic & vasogenic edema

– Vascular failure

– Injury-induced apoptosis / necroptosis

• Primary vs Secondary injury

– Primary: instantaneous structural damage occurring at impact/onset

– Secondary: delayed biochemical & physiologic cascades that amplify tissue loss (ischemia, swelling, metabolic derangements, infection, etc.)

Ischemia & Hypoxia cascade

• Ischemia = inadequate blood-flow to meet metabolic demand

• Hypoxia = inadequate O₂ at cellular level (may be d/t ischemia or hypoxemia)

• Critical events

– Rapid depletion of glucose / glycogen in < 2 min

– Failure of Na⁺/K⁺-ATPase → depolarization

– Glutamate release → NMDA/AMPA activation → \uparrow \text{Ca}^{2+} & \bullet
•OH formation

– Mitochondrial permeability transition → apoptosis

• Reperfusion injury = paradoxical worsening as oxygen re-enters → ROS, BBB breakdown, neutrophil adherence

• Abnormal autoregulation: loss of normal CPP ( cerebral perfusion pressure )–ICP coupling results in regions of hyper- or hypo-perfusion

Increased Intracranial Pressure (ICP)

• Normal adult ICP ≈ 0\text{–}15\,\text{mm Hg}

• Pathologic elevation produced by mass, edema, ↑ CSF, obstructed venous flow, etc.

• Cardinal clinical triad: headache, nausea/vomiting, altered LOC (earliest sign = drowsiness)

• Additional signs: papilledema, cranial-nerve palsies, Cushing triad (↑BP, bradycardia, irregular respirations)

Herniation syndromes

• ICP ↑ → shift of tissue across rigid dural reflections or foramen magnum

– Subfalcine (cingulate)

– Central transtentorial

– Uncal

– Tonsillar (fatal apnea)

• Compression of mid-brain/brain-stem = rapid neurologic demise

ICP Management Targets

• Goal: \text{ICP} < 20\,\text{mm Hg} and \text{CPP} = \text{MAP} - \text{ICP} \ge 50\,\text{mm Hg}

• Interventions

– Emergent CT/MRI

– Surgical decompression / hematoma evacuation

– Ventricular catheter → CSF drainage

– Hyperosmolar therapy (\hypertonic saline, mannitol)

– Moderate hyperventilation (maintain \text{PaCO}_2 \approx 30\text{–}35\,\text{mm Hg})

– Head-of-bed ≥ 30°, neck midline, normothermia, sedation/analgesia, seizure prophylaxis

Clinical Manifestations & Bedside Assessment

• Global Level-of-Consciousness

– Glasgow Coma Scale (eye 4, verbal 5, motor 6; max = 15)

• Brain-stem reflexes

– Pupil size & reactivity (CN II ↔ III)

– Corneal reflex (CN V ↔ VII)

– Oculocephalic (“doll’s eyes”) & oculovestibular (cold calorics)

Traumatic Brain Injury (TBI)

• Epidemiology

– Leading cause of death/disability in <45 y olds

– Mechanisms: falls, MVA, sports, firearms, assault

• Severity: mild (concussion), moderate, severe (GCS ≤ 8)

• Location: focal (vs diffuse axonal)

• Mechanism: closed (blunt) vs penetrating vs blast

Primary intracranial hematomas

• Epidural (arterial, middle meningeal; lucid interval)

• Subdural (venous bridging veins; slower)

• Subarachnoid (traumatic or aneurysmal; xanthochromic CSF)

Secondary injury

• Exceeds initial damage: excitotoxicity, inflammation, edema, ischemia

• Treatment bundle: surgical evacuation, aggressive ICP control, CSF drain, antiseizure drugs, antibiotics when open skull fracture

Cerebrovascular Disease & Stroke

• 5ᵗʰ leading U.S. death; #1 cause of long-term disability; #2 worldwide death

Ischemic stroke (≈ 85 %)

• Occlusion by thrombus or embolus → focal infarction

• Therapeutic priorities

– Rapid imaging (non-contrast CT) to exclude bleed

– Recanalization: IV tPA within 4.5 h; mechanical thrombectomy up to 24 h in select LVO

– Goal BP < 185/110 pre-tPA; permissive HTN otherwise – Avoid hyperglycemia, hypoxia (maintain \text{SpO}_2>94\%)

• Secondary prevention

– Lifestyle (smoking cessation, diet, exercise)

– Antiplatelet or anticoagulation for AF

– Statins, BP control, DM management

Hemorrhagic stroke (≈ 15 %)

• Intracerebral haemorrhage usually from chronic HTN; can be aneurysm, AVM, coagulopathy

• Acute priorities: secure airway, reverse anticoagulation, control BP (target \text{SBP}\le140), neurosurgical evaluation

• Larger focus on ICP control & prevention of secondary ischemia

Typical deficits

• Contralateral hemiplegia/hemisensory loss

• Contralateral homonymous hemianopia

• Aphasia (if dominant hemisphere)

• Neglect, apraxia (usually R hemisphere)

Stroke Prevention Highlights

• Hemorrhagic: strict BP control

• Embolic (cardioembolic): chronic oral anticoagulation (e.g., DOAC for AF)

• Thrombotic/atherosclerotic: antiplatelet + aggressive atherosclerosis risk reduction

Cerebral Aneurysms & Arteriovenous Malformations

Cerebral (saccular/berry) aneurysm

• Congenital focal defects in arterial media at circle-of-Willis bifurcations

• Incidence: 10 per 100,000 /yr (~30,000 U.S.)

• “Sentinel leak” = warning headache from minor hemorrhage

• Rupture → aneurysmal subarachnoid hemorrhage (SAH)

– Abrupt “worst headache of my life,” photophobia, nuchal rigidity

– High risk of vasospasm (peaks day 3-7; monitored by TCD)

• Management = neurosurgical emergency

– Endovascular coiling or surgical clipping depending on neck/size

– Nimodipine to reduce ischemic deficit

– ICU monitoring for hydrocephalus, hyponatremia, rebleed

Arteriovenous malformation (AVM)

• Tangled congenital collateral where arterial blood dumps into veins w/o capillary bed → high-flow

• Second most common spontaneous SAH etiology; M>F

• Mass effect, seizure, or hemorrhage presentation

• Therapy: stereotactic radiosurgery, microsurgical resection, or endovascular embolization

Central Nervous System Infections

Meningitis

• Inflammation of leptomeninges & CSF

• Bacterial (Neisseria, Strep pneumo, H flu, Listeria) most virulent; viral (enteroviruses, HSV), fungal

• Classic tetrad: headache + fever + nuchal rigidity + altered sensorium

• Positive Kernig/Brudzinski signs

• Empiric IV antibiotics + dexamethasone; isolate pathogen → target therapy

Encephalitis

• Inflammation of brain parenchyma, majority viral (HSV-1, West Nile, enteroviruses); bacterial, fungal, parasitic possible

• Mortality 5-20 %; HSV untreated mortality ~70 %

• Gradual onset (HSV) vs abrupt (arboviruses); fever, headache, seizures, focal deficits

• Tx: Supportive care + high-dose IV acyclovir for HSV; seizure control

Brain abscess

• Localized intraparenchymal pus (polymicrobial anaerobes, staph, gram-negative rods)

• Routes: contiguous otitis/sinusitis, hematogenous endocarditis, penetrating trauma

• Presents 1-4 weeks: headache, focal deficits, ↑ ICP

• Management: stereotactic drainage ± long-term IV antibiotics (6–8 wks)

Key Neurological Signs & Maneuvers

• Kernig’s sign – supine hip flexed 90°, knee extension causes back/leg pain → meningeal irritation

• Brudzinski’s sign – passive neck flexion → involuntary hip/knee flexion

• Papilledema: optic-disc swelling from raised ICP

• Sluggish pupils & cranial-nerve III palsy: early brain-stem compression

High-Yield Numeric & Formula Summary

• Normal ICP 0\text{–}15\,\text{mm Hg}

• Treat ICP goal < 20\,\text{mm Hg}; maintain \text{CPP}\ge50\,\text{mm Hg}

• Cerebral perfusion: \text{CPP} = \text{MAP} - \text{ICP}

• Hyperventilation set-point: \text{PaCO}_2 = 30\text{–}35\,\text{mm Hg}

• tPA window ≤ 4.5 h from LKW; thrombectomy ≤ 24 h (selected)

• Nimodipine dosing for SAH: 60\,\text{mg PO/NG q4h} for 21 days

• GCS severe TBI threshold: \le8

Clinical Connections & Ethical Considerations

• Rapid neuro-imaging and time-to-reperfusion directly correlate with neurologic outcome → ethical duty for streamlined stroke protocols (“time = brain”).

• Aggressive ICP management can preserve function yet carries risks (hypotension from osmotic diuresis, infection from ventricular drains); shared decision-making with family essential when prognosis unclear.

• Rehabilitation and long-term support after stroke/TBI address not only motor deficits but cognitive, language, and psychosocial reintegration—holistic, inter-professional care is critical.