What is the best course of action for a patient experiencing persistent headache and vomiting, with potential underlying conditions such as meningitis, encephalitis, or brain tumor?

Persistent Headache and Vomiting: Diagnostic and Management Approach

Immediately rule out life-threatening causes—meningitis, encephalitis, intracranial hemorrhage, and brain tumor—through urgent neuroimaging and CSF analysis before attributing symptoms to benign etiologies. 1, 2

Initial Emergency Assessment

The combination of persistent headache and vomiting constitutes a red flag requiring immediate evaluation for serious intracranial pathology. 3, 4 The priority is excluding conditions with high morbidity and mortality:

Critical Clinical Features to Assess

• Level of consciousness: Glasgow Coma Scale <15 warrants ICU assessment for airway protection and management of raised intracranial pressure 1
• Fever presence: High fever with altered mental status suggests intracranial infection requiring urgent workup 5, 1
• Neurological deficits: Focal signs, seizures, neck stiffness, or cranial nerve palsies indicate serious pathology 5, 1
• Headache characteristics: Instant peak onset (thunderclap), "worst ever" quality, or association with physical activity raise concern for hemorrhage 6
• Behavioral changes: New confusion, altered behavior, or personality changes may indicate encephalitis rather than simple meningitis 7, 8

Diagnostic Workup Algorithm

Neuroimaging (First-Line)

MRI brain with and without gadolinium contrast is the preferred imaging modality, detecting early cerebral changes in 90% of cases versus only 25% for CT. 5, 1 However, in acute settings where immediate availability is limited, non-contrast CT head should be obtained first to rule out hemorrhage (98% sensitivity for acute subarachnoid hemorrhage). 5

Key MRI sequences to include: 5

• T2 FLAIR (sensitive for vasogenic edema and meningeal enhancement)
• Diffusion-weighted imaging (detects cytotoxic edema)
• Susceptibility-weighted imaging/gradient-recalled echo (sensitive for hemorrhage)
• Post-contrast T1 sequences

Lumbar Puncture and CSF Analysis

Perform lumbar puncture with comprehensive CSF analysis including: 7, 1

• Cell count with differential (lymphocytic pleocytosis suggests viral/autoimmune causes)
• Protein and glucose levels
• Gram stain and bacterial culture
• Viral PCR panel (HSV, VZV, enterovirus)
• Cytology to exclude leptomeningeal metastasis
• Consider autoimmune/paraneoplastic antibody testing if infectious workup negative

Critical caveat: In immunocompromised patients, CSF may be acellular despite active CNS infection, so negative CSF does not exclude infection in this population. 1

Additional Diagnostic Tests

• EEG: Obtain when distinguishing psychiatric versus organic causes or when subtle seizures suspected (abnormal in >80% of encephalitis cases) 1
• Blood work: Complete metabolic panel, blood cultures if febrile, malaria testing if travel to endemic areas 1

Differential Diagnosis Priority

Life-Threatening Causes (Rule Out First)

1. Bacterial meningitis: Requires immediate antibiotics before imaging if high clinical suspicion 1, 4
2. Encephalitis: Distinguished from meningitis by presence of altered behavior, confusion, seizures, or focal deficits 5, 1
3. Subarachnoid hemorrhage: Instant peak headache, thunderclap quality 6
4. Brain tumor/mass lesion: Chronic progressive pattern with signs of raised ICP 4
5. Intracranial hemorrhage: Detected on CT with 98-99% sensitivity/specificity 5

Immune-Related Causes (If on Checkpoint Inhibitors)

For patients receiving immunotherapy, neurologic adverse events occur in 3.8-12% depending on agent, with headache being the most common mild symptom. 5 However, severe manifestations including aseptic meningitis and encephalitis require:

• Immediate discontinuation of checkpoint inhibitor for grade 2 or higher symptoms 5
• Methylprednisolone 1-4 mg/kg depending on severity, with consideration of pulse-dose 1g daily for 3-5 days for grade 3+ toxicity 5
• IVIG should be strongly considered for severe cases 5

The distinction between aseptic meningitis and encephalitis is critical: Isolated headache suggests meningitis, but addition of confusion, altered behavior, aphasia, or memory loss indicates encephalitis requiring more aggressive treatment including pulse-dose steroids and autoimmune antibody evaluation. 5

Autoimmune/Inflammatory Causes

• MOGAD (myelin oligodendrocyte glycoprotein antibody-associated disease): Can present as aseptic meningitis mimic with chronic headaches, vomiting, and CSF pleocytosis despite negative infectious workup 3
• Lupus-related aseptic meningitis: Requires rigorous exclusion of infection before diagnosis, especially in immunosuppressed patients 7
• Neurocysticercosis: Consider in endemic areas; subarachnoid cysts cause eosinophilic meningitis with severe headache, meningism, and altered consciousness 5

Parasitic Causes (Travel History Dependent)

• Angiostrongylus cantonensis: Severe acute headache with marked peripheral eosinophilia in travelers to SE Asia; treat with corticosteroids (prednisolone 60mg daily for 14 days) 5
• Cerebral malaria: Obtain three thick/thin blood films; treat with quinine/artemether if suspected 1

Management Based on Etiology

Infectious Meningitis/Encephalitis

Immediate empiric treatment with appropriate antimicrobials/antivirals before diagnostic confirmation if high clinical suspicion, as delays worsen morbidity and mortality. 1 Patients require management in neurological wards, HDU, or ICU depending on severity. 1

Primary Headache (After Exclusion of Secondary Causes)

Most presentations are ultimately benign—viral illness or primary headache/migraine. 2, 9 However, never diagnose primary headache without adequate exclusion of secondary causes, particularly in first-ever severe presentations. 4, 9

For confirmed migraine in emergency settings: 5, 9

• NSAIDs or combination analgesics with caffeine for mild-moderate attacks
• Triptans or DHE for moderate-severe attacks
• Antiemetics (metoclopramide, prochlorperazine) for nausea
• Avoid opioids due to poor effectiveness and rebound risk 9

Disposition and Follow-Up

• Never discharge without definite or suspected diagnosis 1
• Arrange outpatient neurology follow-up and rehabilitation assessment, as sequelae may not be immediately apparent 1
• Lack of headache center referral results in high ED relapse rates 9

Common Pitfalls to Avoid

• Mistaking behavioral changes for primary psychiatric illness when they represent encephalitis, leading to dangerous delays in treatment 8
• Assuming negative initial imaging excludes serious pathology: Serial imaging may be necessary, particularly for inflammatory conditions like MOGAD 3
• Attributing symptoms to immunotherapy without excluding infection: Always rule out infectious causes before diagnosing immune-related adverse events 5, 7
• Performing lumbar puncture before imaging in patients with focal deficits or altered consciousness: Risk of herniation 1