Acute CNS Infections, Encephalitis & Inflammatory Emergencies

Acute CNS Infections, Encephalitis & Inflammatory Emergencies

Acute infectious, inflammatory, and neurovascular encephalopathies are life-threatening neurological catastrophes frequently admitted to the neurocritical care unit. Rapid recognition, diagnostic lumbar puncture ($LP$), tailored neuroimaging, and emergent pathogen-directed or immunosuppressive therapy are essential to prevent irreversible neurological disability and death.

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Acute Bacterial Meningitis

Acute bacterial meningitis is an inflammatory infection of the arachnoid membrane, subarachnoid space, and cerebrospinal fluid ($CSF$). Rapid bacterial proliferation and autolysis trigger massive release of cell wall components (peptidoglycan, teichoic acid, lipopolysaccharide), eliciting subarachnoid cytokine cascades ($IL\text{-}1$, $TNF\text{-}\alpha$) that induce blood-brain barrier breakdown, purulent exudate accumulation, cerebral vasculitis, raised intracranial pressure, and secondary brain herniation.

Pathogen Stratification by Clinical Setting

• Community-Acquired Adults ($18\text{--}50\text{ years}$): Streptococcus pneumoniae ($50\%\text{--}60\%$), Neisseria meningitidis ($20\%\text{--}30\%$).
• Older Adults ($> 50\text{ years}$), Immunocompromised, Alcoholism, Cirrhosis, Pregnancy: Streptococcus pneumoniae, Neisseria meningitidis, and $Listeria\ monocytogenes$ ($10\%\text{--}15\%$).
• Post-Neurosurgical, External Ventricular Drains (EVD), Penetrating Head Trauma: Staphylococcus aureus, coagulase-negative staphylococci (Staphylococcus epidermidis), and aerobic Gram-negative bacilli (Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Enterobacter).

Empiric Antimicrobial Regimens

Adjunctive Dexamethasone

• Landmark Evidence (de Gans & van de Beek, NEJM 2002): In a multicenter randomized trial of 301 adults with acute bacterial meningitis, adjunctive dexamethasone reduced unfavorable outcomes from $25\%$ to $15\%$ ($p = 0.03$) and reduced mortality from $15\%$ to $7\%$ ($p = 0.04$), with the most profound mortality reduction in $Streptococcus\ pneumoniae$ meningitis ($34\%\text{ to }14\%$, $p = 0.02$).
• Dosing & Administration: $10\text{ mg}$ IV administered prior to or concurrently with the first dose of antimicrobial therapy, continued at $10\text{ mg}$ IV q6h for 4 days.
• Clinical Nuances:
  • If the pathogen is proven to be Streptococcus pneumoniae, complete the full 4-day dexamethasone course.
  • If another pathogen (N. meningitidis, L. monocytogenes, Gram-negative bacilli) or virus is identified, discontinue dexamethasone immediately.
  • If antimicrobial therapy has already been administered for several hours, the expected benefit of delayed steroid initiation is less certain; obtain infection-specific guidance rather than delaying antibiotics.

Diagnostic CSF Profiles in Meningitis & Encephalitis

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Viral Encephalitis: HSV-1 and Neurotropic Viruses

Herpes Simplex Virus Encephalitis (HSV-1)

HSV-1 is the most common cause of non-epidemic sporadic viral encephalitis in developed nations, carrying $> 70\%$ mortality if untreated:

• Pathophysiology: Retrograde axonal transport via olfactory tract or trigeminal sensory axons into limbic structures, producing asymmetric necrotizing, hemorrhagic encephalitis with marked predilection for the medial temporal lobes, insula, and inferior frontal lobes.
• Clinical Presentation: Acute/subacute onset of fever, headache, altered mental status, bizarre behavioral changes, personality disintegration, olfactory/gustatory hallucinations, memory loss, and focal temporal lobe seizures with impaired awareness.
• Diagnostic Hallmarks:
  • Brain MRI: Asymmetric hyperintensity on T2/FLAIR and restricted diffusion on DWI in the medial temporal lobes, uncus, amygdala, and insular cortex. Petechial gyral hemorrhage may be evident on gradient-recalled echo ($GRE$) or susceptibility-weighted imaging ($SWI$).
  • cEEG: Lateralized Periodic Discharges ($LPDs$) recurring every $1\text{--}2\text{ seconds}$ over the affected temporal lobe.
  • CSF Analysis: Lymphocytic pleocytosis ($50\text{--}500\text{ cells/}\mu\text{L}$), elevated protein, elevated red blood cells ($RBCs$), and normal glucose. CSF HSV-1 PCR exhibits $> 95\%$ sensitivity and specificity. If early PCR ($< 48\text{ hours}$) is negative but clinical suspicion remains elevated, continue acyclovir and repeat LP at $3\text{--}7\text{ days}$.
• Empiric Management: Immediate Intravenous Acyclovir ($10\text{ mg/kg}$ IV q8h with dosing weight, renal adjustment, and infusion plan selected according to the current protocol) for $14\text{--}21\text{ days}$.
  • Clinical Pitfall: Acyclovir is insoluble in urine and precipitates in renal collecting tubules, causing acute obstructive crystal nephropathy. Infuse acyclovir slowly over at least $1\text{ hour}$ with appropriate hydration and renal monitoring while respecting cardiac, lung, and brain fluid constraints.

Other Neurotropic Viral Emergencies

• Varicella Zoster Virus ($VZV$): Causes small- and large-vessel cerebral vasculopathy, producing multifocal ischemic and hemorrhagic strokes, aneurysmal dilatation, or temporal arteritis-like presentations. Treat with IV acyclovir when indicated; adjunctive steroids are a specialist, context-dependent decision with limited evidence rather than mandatory pulse treatment.
• West Nile Virus ($WNV$): Neuroinvasive disease presents with fever, aseptic meningitis, encephalitis, and acute asymmetric flaccid paralysis caused by viral destruction of anterior horn cells (poliomyelitis-like syndrome). Patients exhibit prominent postural/action tremors, myoclonus, and parkinsonian rigidity. Brain MRI reveals T2/FLAIR hyperintensities in the substantia nigra, basal ganglia, and thalamus.

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Distinguish Infectious and Immune Encephalitis

Psychiatric change, memory disturbance, seizures, dyskinesias, autonomic instability, and hypoventilation can indicate autoimmune encephalitis. Anti-NMDA receptor disease targets GluN1; LGI1 disease can produce brief faciobrachial dystonic seizures and hyponatremia; CASPR2 disease may combine encephalitis, neuromyotonia, dysautonomia, and severe insomnia. None of these patterns justifies omitting an infectious or toxic-metabolic evaluation. CSF and serum testing have different sensitivities and false-positive risks; interpret antibodies with the phenotype and appropriate paired testing.

MRI, EEG, CSF, and tumor screening support assessment. A normal MRI or initially mild CSF profile does not exclude immune disease. Tumor association varies with antibody, age, and sex. If a relevant tumor is present, coordinate treatment; removal is important but not a guaranteed immediate cure. First-line immunotherapy and escalation are expert-directed and depend on diagnosis, response, infection risk, and organ function. The dedicated immune-emergencies section develops this reasoning in detail rather than imposing a universal fixed drug sequence.

Reversible Neurovascular Encephalopathies: PRES and RCVS

Posterior Reversible Encephalopathy Syndrome (PRES)

PRES is a clinicoradiological neurovascular syndrome characterized by failed cerebral autoregulation:

• Pathophysiology: Acute severe blood pressure elevation exceeds the myogenic upper limit of cerebral autoregulation, causing arteriolar hyperperfusion, endothelial shear stress, blood-brain barrier breakdown, and extravasation of plasma and macromolecules into the interstitium (vasogenic edema). Vasogenic edema preferentially targets the parieto-occipital subcortical white matter because the posterior vertebrobasilar circulation possesses significantly less sympathetic adrenergic perivascular innervation compared to the carotid circulation.
• Etiologies & Triggers: Hypertensive emergency, preeclampsia/eclampsia, calcineurin inhibitors (tacrolimus, cyclosporine in solid organ transplant recipients), cytotoxic chemotherapy, and severe sepsis.
• Clinical Presentation: Subacute encephalopathy, throbbing headache, generalized seizures ($70\%\text{--}80\%$), visual disturbances (homonymous hemianopia, visual hallucinations, cortical blindness / Anton syndrome).
• Neuroimaging: Brain MRI demonstrates symmetric hyperintensity on T2/FLAIR in parieto-occipital white matter. Apparent diffusion coefficient ($ADC$) mapping reveals facilitated diffusion (bright on ADC), supporting vasogenic edema; restricted diffusion, infarction, or hemorrhage can coexist and must be assessed.
• Management:
  • Controlled BP Reduction: Titrate IV labetalol, nicardipine, or clevidipine. Lower MAP by no more than $20\%\text{--}25\%$ within the first 2 hours to prevent secondary cerebral watershed ischemia.
  • Seizure Control & Toxin Withdrawal: Intravenous magnesium sulfate ($4\text{--}6\text{ g}$ bolus then $1\text{--}2\text{ g/h}$) for eclampsia; immediately discontinue or reduce doses of calcineurin inhibitors or offending chemotherapeutic agents.

Reversible Cerebral Vasoconstriction Syndrome (RCVS)

RCVS is characterized by transient, reversible dysregulation of cerebral arterial tone:

• Clinical Hallmark: Recurrent "thunderclap" headaches—sudden, explosive, agonizing headaches reaching maximal $10/10$ intensity within seconds ("crashing waves"), recurring multiple times over $1\text{--}4\text{ weeks}$. Often triggered by Valsalva, coughing, exertion, or emotional stress.
• Triggers: Postpartum state, sympathomimetic and serotonergic vasoactive substances: SSRIs, SNRIs, nasal decongestants (pseudoephedrine), triptans, ergotamines, cocaine, amphetamines, and cannabis.
• Complications: Non-aneurysmal convexity subarachnoid hemorrhage ($cSAH$) ($30\%\text{--}35\%$), ischemic stroke in watershed distributions, and lobar intracerebral hemorrhage.
• Imaging: CTA, MRA, or catheter DSA reveals diffuse, multifocal, segmental narrowing and ectasia ("string of beads" appearance) affecting medium and large cerebral arteries, which completely resolves on follow-up imaging within 3 months. Catheter angiography may be normal during the first $3\text{--}5\text{ days}$ (delayed vasoconstriction).
• Therapy: Oral calcium channel blockers (Nimodipine $60\text{ mg}$ q4h or Verapamil) to relieve headache in selected patients; prevention of stroke or other complications is not established; strict cessation of all vasoactive medications.