What are the key concepts and management strategies in neurology, including stroke, cerebral vasculature disorders, headaches, CNS infections, and intracranial pressure management?

Comprehensive Neurology: Stroke, Cerebrovascular Disorders, and Intracranial Pressure Management

Golden Hour in Stroke

The "golden hour" refers to the first 60 minutes from stroke symptom onset, during which thrombolytic therapy has the highest efficacy and lowest side effects. 1 Achieving treatment within this window is associated with significantly better outcomes, with one study demonstrating a 6-fold increase in golden hour thrombolysis rates (31.0% vs 4.9%) when specialized prehospital stroke units were deployed. 2 Patients receiving golden hour thrombolysis were nearly twice as likely to be discharged home (adjusted OR 1.93,95% CI 1.09-3.41) without increased mortality risk. 2

CT Scan Differentiation: Infarct vs Hemorrhage

Acute ischemic infarction appears as hypodense (darker) areas on non-contrast CT, while acute hemorrhage appears hyperdense (brighter/white). 3

• Ischemic stroke findings: Early signs include loss of gray-white matter differentiation, insular ribbon sign, and hyperdensity of the affected vessel (dense MCA sign). 3
• Hemorrhagic stroke findings: Acute blood appears bright white (hyperdense) immediately, with mass effect and surrounding edema developing over hours. 3
• Timing consideration: CT should be completed within 25 minutes of ED arrival, with interpretation within 45 minutes (door-to-interpretation time) for thrombolysis candidates. 3, 4

Dense MCA Sign

The dense MCA sign is a hyperdense (bright) appearance of the middle cerebral artery on non-contrast CT, indicating acute thrombus within the vessel. 3 This early CT finding suggests large vessel occlusion and predicts larger infarct size if reperfusion is not achieved.

Surgical Indications for Hemorrhagic CVD

Decompressive surgical evacuation is potentially life-saving for space-occupying cerebellar infarction with good clinical recovery potential. 3

• Cerebellar hemorrhage/infarction: Surgical decompression is recommended when there is mass effect, hydrocephalus, or neurological deterioration. 3
• Acute hydrocephalus: Ventricular drain placement is indicated for hydrocephalus secondary to ischemic stroke, most commonly from cerebellar lesions. 3
• Malignant hemispheric infarction: Decompressive hemicraniectomy should be considered for patients with large MCA territory infarctions causing refractory intracranial hypertension, particularly when performed early before profound neurological dysfunction develops. 3

Alteplase Dosing

The standard dose of alteplase (rtPA) for acute ischemic stroke is 0.9 mg/kg (maximum 90 mg), with 10% given as bolus and 90% infused over 60 minutes. 3

• General population: 0.9 mg/kg IV (maximum 90 mg total dose). 3
• Asian populations: Some evidence suggests considering lower doses due to potentially higher hemorrhagic transformation rates, though current AHA/ASA guidelines do not specify different dosing for Asians. 3
• Time window: Must be administered within 3-4.5 hours of symptom onset. 4

Alteplase Contraindications

Absolute Contraindications 3:

• Active internal bleeding
• Recent intracranial or intraspinal surgery (within 3 months)
• Serious head trauma within 3 months
• History of intracranial hemorrhage
• Intracranial neoplasm, arteriovenous malformation, or aneurysm
• Current severe uncontrolled hypertension (>185/110 mmHg)
• Ischemic stroke within 3 months

Relative Contraindications 3:

• Minor or rapidly improving stroke symptoms
• Major surgery or serious trauma within 14 days
• Gastrointestinal or urinary tract hemorrhage within 21 days
• Seizure at stroke onset with postictal neurological impairments
• Recent arterial puncture at non-compressible site
• Recent lumbar puncture
• Pregnancy
• Platelet count <100,000/mm³
• Current anticoagulant use with INR >1.7 or PT >15 seconds

Glasgow Coma Scale (GCS) Computation

GCS ranges from 3-15 points, calculated by summing three components: Eye opening (1-4), Verbal response (1-5), and Motor response (1-6). 3

Eye Opening (E):

• 4: Spontaneous
• 3: To voice
• 2: To pain
• 1: None

Verbal Response (V):

• 5: Oriented
• 4: Confused conversation
• 3: Inappropriate words
• 2: Incomprehensible sounds
• 1: None

Motor Response (M):

• 6: Obeys commands
• 5: Localizes to pain
• 4: Withdraws from pain
• 3: Flexion to pain (decorticate)
• 2: Extension to pain (decerebrate)
• 1: None

Headache Red Flags

Red flags indicating potentially serious secondary headache include: 3

• Sudden onset ("thunderclap" headache)
• New headache in patients >50 years old
• Progressive worsening pattern
• Headache with fever, neck stiffness, or altered mental status
• Headache with focal neurological deficits
• Headache following head trauma
• Headache with papilledema or visual changes
• New headache in immunocompromised or cancer patients
• Headache triggered by Valsalva, exertion, or position change

Primary Headache Causes

The three main primary headache disorders are migraine, tension-type headache, and cluster headache. 3

• Migraine: Unilateral, pulsating, moderate-to-severe intensity, aggravated by routine physical activity, with nausea/vomiting or photophobia/phonophobia
• Tension-type: Bilateral, pressing/tightening quality, mild-to-moderate intensity, not aggravated by routine physical activity
• Cluster headache: Severe unilateral orbital/supraorbital/temporal pain lasting 15-180 minutes, with ipsilateral autonomic features (lacrimation, nasal congestion, ptosis)
• Trigeminal autonomic cephalalgias: Include cluster headache, paroxysmal hemicrania, and SUNCT syndrome

Epidural vs Subdural Hemorrhage

Epidural Hemorrhage:

• CT appearance: Biconvex (lens-shaped) hyperdense collection that does not cross suture lines. 3
• Vessel involved: Middle meningeal artery (most common). 3
• Mechanism: Typically traumatic skull fracture causing arterial bleeding between skull and dura.

Subdural Hemorrhage:

• CT appearance: Crescentic (crescent-shaped) hyperdense collection that crosses suture lines but not midline (limited by falx cerebri). 3
• Vessel involved: Bridging veins between cortex and dural sinuses. 3
• Mechanism: Venous bleeding, often from acceleration-deceleration injury or in elderly/anticoagulated patients.

Subarachnoid Hemorrhage (SAH)

CT Findings:

Acute SAH appears as hyperdense (bright) blood in the subarachnoid spaces, particularly in the basal cisterns, sylvian fissures, and sulci. 3

Grading Systems:

• Hunt and Hess Scale: Grades I-V based on clinical severity, from asymptomatic/mild headache (I) to deep coma/decerebrate posturing (V). 5
• Fisher Scale: Grades 1-4 based on CT appearance, predicting vasospasm risk.

Nimodipine Administration:

Nimodipine is given to prevent cerebral vasospasm and reduce neurological deficits following SAH, though its exact mechanism remains unclear. 5 The drug is highly lipophilic, crosses the blood-brain barrier effectively, and preferentially affects cerebral arteries. 5 Despite lack of arteriographic evidence of vasospasm relief, clinical trials demonstrate significant reduction in severe neurological deficits and improved outcomes. 5

• Dosing: 60 mg orally every 4 hours for 21 days. 5
• Mechanism: Calcium channel blocker with preferential cerebral vascular effects, though it does not demonstrably prevent or relieve angiographic vasospasm. 5

SAH Etiology:

The most common non-traumatic cause of SAH is ruptured intracranial aneurysm. 5 Trauma is the most common overall cause of SAH.

Hypertensive Hemorrhage Location

The most common site of hypertensive intracerebral hemorrhage is the basal ganglia (particularly putamen), followed by thalamus, pons, and cerebellum. 3

Intracranial Aneurysm Location

The most common location for intracranial aneurysms is the anterior communicating artery, followed by the posterior communicating artery and middle cerebral artery bifurcation. 6

CNS Infection Diagnosis

Lumbar puncture with cerebrospinal fluid (CSF) analysis is the diagnostic test of choice for CNS infections. 3

• Timing: Should be performed after neuroimaging if there are signs of increased intracranial pressure or focal neurological deficits. 3
• Contraindications to immediate LP: Mass effect on imaging, signs of herniation, coagulopathy, thrombocytopenia. 3

Brudzinski and Kernig Signs

Brudzinski Sign:

Passive flexion of the neck causes involuntary flexion of the hips and knees. The examiner places one hand behind the patient's head and flexes the neck forward; a positive sign occurs when the patient reflexively flexes the hips and knees.

Kernig Sign:

With the hip flexed to 90 degrees, passive extension of the knee causes pain and resistance. The examiner flexes the patient's hip and knee to 90 degrees, then attempts to extend the knee; a positive sign is pain and resistance to extension beyond 135 degrees.

Both signs indicate meningeal irritation but have limited sensitivity for meningitis.

CSF Findings in CNS Infections

Bacterial Meningitis:

• Opening pressure: Elevated (>25 cm H₂O)
• Appearance: Turbid/cloudy
• WBC count: >1000 cells/μL (predominantly neutrophils)
• Protein: Elevated (>100 mg/dL)
• Glucose: Low (<40 mg/dL or CSF:serum ratio <0.4)
• Gram stain: May show organisms

Viral Meningitis:

• Opening pressure: Normal to mildly elevated
• Appearance: Clear
• WBC count: 10-1000 cells/μL (predominantly lymphocytes)
• Protein: Normal to mildly elevated (50-100 mg/dL)
• Glucose: Normal (>45 mg/dL)

Tuberculous Meningitis:

• Opening pressure: Elevated
• Appearance: Clear to slightly cloudy
• WBC count: 100-500 cells/μL (lymphocyte predominance)
• Protein: Markedly elevated (>100 mg/dL)
• Glucose: Low (<45 mg/dL)

Cushing's Triad and Monro-Kellie Doctrine

Cushing's Triad:

The classic triad of increased intracranial pressure consists of hypertension (with widened pulse pressure), bradycardia, and irregular respirations. 3 This represents a late and ominous sign of brainstem compression from herniation.

Monro-Kellie Doctrine:

The cranial vault contains three components—brain parenchyma, blood, and CSF—with a fixed total volume. An increase in any one component must be compensated by a decrease in the others, or intracranial pressure will rise. Once compensatory mechanisms are exhausted, small volume increases cause exponential ICP rises.

Medications to Decrease Intracranial Pressure

Mannitol 7:

• Dose: 0.25-0.5 g/kg IV over 20 minutes every 6 hours (maximum 2 g/kg). 3, 7
• Mechanism: Osmotic diuretic that creates an osmotic gradient, drawing water from brain parenchyma into the intravascular space. 7
• Onset: Rapid (within 15-30 minutes).
• Cautions: Monitor serum osmolality (hold if >320 mOsm/L), renal function, and volume status. 7

Hypertonic Saline (3% NaCl) 8:

• Dose: Variable protocols; commonly 250 mL bolus or continuous infusion.
• Mechanism: Creates hyperosmolar state, drawing water from brain tissue into circulation; may also improve cerebral perfusion and reduce inflammation. 8
• Advantages: Does not cause osmotic diuresis like mannitol, may be superior in traumatic brain injury. 8
• Monitoring: Serum sodium (target 145-155 mEq/L), avoid rapid correction. 8

Hyperventilation:

• Target: PaCO₂ 30-35 mmHg (temporary measure only).
• Mechanism: Hypocapnia causes cerebral vasoconstriction, reducing cerebral blood volume and ICP.
• Cautions: Only as temporizing measure; prolonged hyperventilation can worsen ischemia. 3

Barbiturates:

• Mechanism: Reduce cerebral metabolic rate and blood flow.
• Use: Reserved for refractory intracranial hypertension unresponsive to other measures. 3

Critical caveat: No evidence indicates that these interventions improve outcomes in ischemic brain swelling, though they are used as temporizing measures before definitive treatment. 3, 8 Mortality remains 50-70% despite intensive medical management. 3, 8

Levels of Sensorium

Consciousness exists on a spectrum from alert to coma:

• Alert: Fully awake, oriented to person, place, time, and situation
• Lethargic: Drowsy but arousable to voice, returns to sleep when not stimulated
• Obtunded: Difficult to arouse, requires repeated stimulation, confused when awake
• Stuporous: Arousable only to vigorous or painful stimulation, minimal interaction
• Comatose: Unarousable, no purposeful response to painful stimuli

Corneal Reflex Testing

Gently touch the cornea (not the sclera) with a wisp of cotton or tissue while approaching from the side to avoid triggering the blink reflex from visual threat. A normal response is bilateral eye closure (direct and consensual blink).

• Afferent pathway: Trigeminal nerve (CN V, ophthalmic division)
• Efferent pathway: Facial nerve (CN VII)

Doll's Eyes (Oculocephalic Reflex) Testing

With the patient's eyes open, rapidly rotate the head horizontally from side to side. In a normal response (intact brainstem), the eyes move conjugately in the direction opposite to head movement, maintaining fixation on a point in space. Absent or dysconjugate eye movements indicate brainstem dysfunction.

• Contraindication: Do not perform if cervical spine injury is suspected.
• Afferent pathway: Vestibular nerve (CN VIII)
• Efferent pathway: Oculomotor (CN III), trochlear (CN IV), and abducens (CN VI) nerves

Pupillary Light Reflex Pathways

• Afferent: Optic nerve (CN II) → pretectal nucleus
• Efferent: Edinger-Westphal nucleus → oculomotor nerve (CN III) → ciliary ganglion → pupillary sphincter muscle

Corneal Reflex Pathways

• Afferent: Trigeminal nerve (CN V, ophthalmic division)
• Efferent: Facial nerve (CN VII) → orbicularis oculi muscle

Initial Management of Elevated ICP 8:

1. Elevate head of bed 20-30 degrees to facilitate venous drainage. 8
2. Ensure adequate oxygenation and ventilation with intubation if needed; avoid hypoxia and hypercarbia. 8
3. Treat hyperthermia aggressively as fever worsens cerebral edema. 8
4. Restrict free water and avoid hypotonic fluids (especially D5W). 8
5. Avoid antihypertensive agents causing cerebral vasodilation. 8
6. Administer osmotic therapy (mannitol or hypertonic saline) for symptomatic ICP elevation. 8, 7
7. Consider external ventricular drainage for persistent intracranial hypertension. 8
8. Decompressive craniectomy for refractory cases, particularly malignant MCA infarction. 8

Critical timing consideration: Cerebral edema typically peaks 3-4 days after large ischemic strokes, but early reperfusion can accelerate edema development within 24 hours ("malignant edema"). 8 Preventive measures should begin before clinically significant ICP elevation occurs. 8