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Meningitis with Altered Sensorium - Management

1. Initial Recognition & Triage

• Headache + nuchal rigidity + fever
• Altered sensorium (confusion, stupor, coma)
• Diffuse or focal neurologic findings
• New-onset seizures

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2. Immediate Stabilization (First 30 Minutes)

A-B-C-D priorities:

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3. "Do Not Delay Antibiotics" Rule

Early initiation of empirical antimicrobial therapy is recommended before imaging or lumbar puncture in cases of suspected acute CNS infection with altered sensorium.

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4. CT Head Before LP?

• Altered level of consciousness (GCS < 15)
• New focal neurologic deficit
• Papilloedema
• History of CNS disease, immunocompromise, or seizure within 1 week

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5. Empiric Antibiotic Therapy

Adult (immunocompetent):

Add Ampicillin 2g IV q4h if:

• Age >50 years
• Immunocompromised
• Alcoholism / liver disease
• Suspected Listeria monocytogenes

Suspected Viral Encephalitis (HSV):

• Add Aciclovir 10 mg/kg IV q8h - HSV encephalitis causes altered sensorium and is a common pathogen in meningoencephalitis

Neonates (<1 month):

• Ampicillin + Cefotaxime (covers Group B Strep, E. coli, Listeria)

Age-based empiric regimens:

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6. Adjunctive Dexamethasone

• Dose: 10 mg IV every 6 hours for 4 days (adults)
• Benefits: Reduces CSF inflammation, lowers mortality in pneumococcal meningitis, reduces hearing loss and neurologic sequelae in children

"One expert consensus panel opined that dexamethasone treatment can be administered up to 4 hours after initiation of antibiotic treatment." (Tintinalli's Emergency Medicine)

• Pneumococcal and H. influenzae meningitis
• Adults: reduces mortality
• Children: reduces severe hearing loss (from 11% to 6.6%)

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7. Lumbar Puncture & CSF Interpretation

CSF findings in bacterial meningitis:

Note: CSF sterilization can occur within 2 hours for meningococcal and 6 hours for pneumococcal meningitis after starting antibiotics - so LP should be done early if safe.

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8. Managing Raised ICP (Critical in Altered Sensorium)

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9. Monitoring for Complications

• SIADH / Cerebral salt wasting - monitor serum sodium serially
• DIC / Coagulopathy - especially in meningococcemia
• Septic shock - vasopressors if needed (norepinephrine first-line)
• Subdural empyema - new focal deficits, seizures, altered sensorium
• Cerebral venous thrombosis - consider if altered sensorium + focal deficit
• Brain herniation - midriasis, Cushing's triad

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10. Specific Situations

Tuberculous Meningitis:

• Suspect if subacute onset over 1-2 weeks, altered sensorium evolving gradually
• CSF: lymphocytic pleocytosis, low glucose, very high protein
• Treatment: HRZE (Isoniazid + Rifampicin + Pyrazinamide + Ethambutol) + Dexamethasone
• (Harrison's Principles of Internal Medicine 22E, 2025)

Cryptococcal Meningitis (HIV/Immunocompromised):

• Amphotericin B + Flucytosine (induction), then Fluconazole (consolidation/maintenance)
• Monitor opening pressure - often markedly elevated; therapeutic LP may be needed

Herpes Simplex Encephalitis:

• Classic: fever, altered sensorium, focal temporal lobe signs, seizures
• MRI: temporal lobe signal change
• Treatment: Aciclovir 10 mg/kg IV q8h x 14-21 days

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11. Chemoprophylaxis for Contacts

• Rifampicin 600 mg PO q12h x 2 days (adults)
• Ciprofloxacin 500 mg PO single dose (alternative)
• Ceftriaxone 250 mg IM single dose (pregnant women)
• Initiate within 24 hours of contact

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12. Disposition

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Quick Summary Algorithm

Suspected Meningitis + Altered Sensorium
           ↓
   ABCs, IV access, monitoring
           ↓
Blood cultures + CBC + BMP + coagulation
           ↓
DEXAMETHASONE 10mg IV  ←──────────────┐
           ↓                           │
ANTIBIOTICS (Ceftriaxone +             │
Vancomycin ± Ampicillin                │
± Aciclovir for HSV)   ────────────────┘
           ↓
CT Head (if altered sensorium)
           ↓
LP (if no contraindication)
           ↓
Manage raised ICP, seizures, SIADH
           ↓
ICU admission

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• Rosen's Emergency Medicine, 9th Ed., pp. 2267-2270
• Tintinalli's Emergency Medicine, pp. 1213-1216
• Harrison's Principles of Internal Medicine 22E (2025)
• Bradley & Daroff's Neurology in Clinical Practice
• Harriet Lane Handbook 23e

• GBD 2023 Meningitis Study confirms ongoing high global burden (PMID: 41911930, Lancet Neurol 2026)
• Practice Guidelines (PMID: 38843370, 2024; PMID: 40393410, 2025) continue to support early antibiotic + dexamethasone approach

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Meningitis / Encephalopathy - Comprehensive Review

1. Definitions & the Continuum

"These disease states are not mutually exclusive and exist on a continuum of meningoencephalitis. Greater degrees of encephalitis portend a worse prognosis, as more tissue is involved." (Rosen's Emergency Medicine)

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2. Pathophysiology of Encephalopathy in Meningitis

1. Direct neuronal injury - pathogen invasion and replication causing focal necrosis, inflammatory glial nodules, and perivascular lymphoid cuffing
2. Indirect host-response injury - cerebral edema, raised ICP, inflammation, microvascular thrombosis, "luxury perfusion" (normal/increased blood flow with low O₂ extraction)

• Depth of parenchymal involvement
• Pathogen virulence (HSV temporal lobes, JEV basal ganglia)
• Host immune response
• Speed of treatment initiation

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3. Causes - Infectious vs. Non-Infectious

Infectious Causes

Non-Infectious Causes of Encephalopathy (Must Exclude)

• Autoimmune encephalitis - Anti-NMDA receptor (most common autoimmune encephalopathy), LGI-1, CASPR2, AMPA, GABA-B, GAD65 antibodies
• Paraneoplastic - Anti-Hu, Yo, Ma2, amphiphysin, CRMP5 (associated with occult malignancy)
• Metabolic - Hepatic encephalopathy (hyperammonemia), uremic encephalopathy, hyponatremia, hypoglycemia
• Toxic - Drug intoxication, alcohol withdrawal
• Hashimoto's encephalopathy - Anti-thyroglobulin / anti-TPO antibodies
• Prion diseases - Rapidly progressive dementia + myoclonus
• Cerebrovascular - Stroke, CVT, subarachnoid hemorrhage

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4. Clinical Features

Classic Triad of Meningitis:

Features of Encephalopathy/Encephalitis:

• Altered consciousness - confusion, disorientation, stupor, coma
• Behavioral/personality change - especially HSV (temporal lobe) - may mimic psychiatric illness
• Seizures - focal or generalized; may be presenting feature
• Focal neurologic deficits - hemiparesis, aphasia, cranial nerve palsies
• Autonomic dysfunction - fever, tachycardia, hyper/hypotension

HSV Encephalitis - Classic Presentation:

Sensitivity/Specificity of Signs (Rosen's - for CSF pleocytosis):

Note: Classic signs are highly specific but poorly sensitive - their absence does NOT rule out meningitis/encephalitis.

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5. Diagnostic Workup

Step 1: Bloods (immediate)

• CBC, CRP, Procalcitonin
• Blood cultures x2 (before antibiotics)
• BMP, LFTs, coagulation (PT/aPTT, platelets)
• Blood glucose (for CSF comparison)
• Serum lactate
• HIV testing
• Serum autoimmune antibody panel (if autoimmune suspected)

Step 2: Neuroimaging

• CT head with contrast - mandatory before LP if altered sensorium, focal deficits, papilloedema, seizures, immunocompromise
• MRI brain (gold standard) - more sensitive; FLAIR/DWI sequences
  • HSV: temporal lobe T2/FLAIR hyperintensity (unilateral or bilateral)
  • Japanese encephalitis: thalamic T2 changes, basal ganglia involvement
  • TB meningitis: basal meningeal enhancement, hydrocephalus
  • CMV: periventricular T2 signal, subependymal enhancement
  • Autoimmune (anti-NMDA): medial temporal/limbic system changes

Step 3: Lumbar Puncture - CSF Analysis

Additional CSF Tests:

• PCR panel: HSV-1/2, VZV, CMV, EBV, Enterovirus, West Nile, JC virus
• India Ink + Cryptococcal antigen (HIV/immunocompromised)
• AFB smear + TB PCR + adenosine deaminase (ADA)
• Autoimmune antibodies: anti-NMDA receptor, LGI-1, CASPR2 etc.
• Cytology (if malignant meningitis suspected)

Step 4: EEG

• Essential in encephalopathy to detect non-convulsive status epilepticus (NCSE)
• HSV encephalitis: periodic lateralizing epileptiform discharges (PLEDs) over temporal leads - classic finding
• Diffuse slowing in metabolic/toxic encephalopathy

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6. Emergency Management

IMMEDIATE SEQUENCE (do not delay antibiotics):

↓  Secure AIRWAY (intubate if GCS ≤8)
↓  IV access x2, monitor, bloods + blood cultures
↓  DEXAMETHASONE 10 mg IV
↓  EMPIRIC ANTIBIOTICS + ACYCLOVIR (see below)
↓  CT head (if altered sensorium/focal signs)
↓  LP (once safe)
↓  Manage ICP, seizures, metabolic derangements
↓  ICU admission

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7. Empiric Drug Therapy

A. Antibiotics (for bacterial coverage)

B. Acyclovir (MANDATORY - empirically for ALL encephalitis)

"Acyclovir is of benefit in the treatment of HSV and should be started empirically in patients with suspected viral encephalitis, especially if focal features are present, while awaiting viral diagnostic studies." (Harrison's Principles of Internal Medicine 22E)

C. Dexamethasone (Adjunctive)

• 10 mg IV q6h x 4 days (adults) - before or with first antibiotic dose
• Reduces mortality in pneumococcal meningitis
• Reduces hearing loss and neurologic sequelae in children

D. Antifungals (if Cryptococcal/Fungal suspected)

• Amphotericin B 0.7-1 mg/kg/day IV + Flucytosine 25 mg/kg qid (induction x2 weeks)
• Then Fluconazole 400 mg/day (consolidation x8 weeks, then maintenance)

E. Anti-TB Therapy (TB meningitis)

• HRZE: Isoniazid + Rifampicin + Pyrazinamide + Ethambutol x2 months
• Then HR x7-10 months
• + Dexamethasone (significant mortality benefit in TB meningitis)

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8. Autoimmune Encephalitis - Special Consideration

Anti-NMDA Receptor Encephalitis:

• Demographics: Young women (often with ovarian teratoma)
• Stages: Prodrome (fever, headache) → Psychiatric symptoms (psychosis, agitation) → Seizures → Movement disorders (orofacial dyskinesias) → Autonomic instability → Decreased consciousness
• Diagnosis: Anti-NMDA receptor antibodies in CSF > serum; MRI often normal; EEG shows delta brush pattern
• Treatment:
  • Immunotherapy (first-line): Methylprednisolone 1g/day IV x5d + IVIG 2g/kg over 5d ± Plasmapheresis
  • Second-line: Rituximab, Cyclophosphamide
  • Remove teratoma if present (tumor removal alone can cause remission)

Important: NMDA receptor antibodies develop in up to 25% of patients following HSV encephalitis - can cause new/worsening symptoms weeks after HSV recovery. Do not let NMDA antibody presence exclude testing for HSV.

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9. Raised ICP Management in Encephalopathy

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10. Monitoring & Complications

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11. Differential Diagnosis of Encephalopathy in Meningitis

• Non-convulsive status epilepticus - always get EEG
• Autoimmune encephalitis triggered by prior HSV (NMDA abs post-HSV)
• Drug toxicity (e.g., acyclovir nephrotoxicity → crystalline nephropathy → drug accumulation)
• Cerebral venous thrombosis (CVT) - MR venography
• Subdural empyema / brain abscess extension
• Metabolic - hyponatremia (SIADH), hypoglycemia

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12. Disposition

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• Harrison's Principles of Internal Medicine 22E (2025) - Chapter on Viral Encephalitis
• Rosen's Emergency Medicine 9E - CNS Infections
• Tintinalli's Emergency Medicine - Bacterial Meningitis Management
• Kaplan & Sadock's Comprehensive Textbook of Psychiatry - Autoimmune Encephalitis
• Sherris & Ryan's Medical Microbiology 8E - HSV/PCR Diagnosis