What is the diagnosis and recommended treatment for a 35-year-old patient with a history of brain swelling, previously treated with steroids, who presents with severe headache, photophobia, and elevated lab results, including leukocytosis (White Blood Cell Count), neutrophilia, and elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)?

Diagnostic Assessment: Likely Aseptic Meningitis or Inflammatory CNS Process

This patient most likely has an inflammatory CNS process (possibly recurrent aseptic meningitis or autoimmune encephalitis) given the history of brain swelling previously responsive to steroids, severe headache with photophobia/phonophobia, and markedly elevated inflammatory markers (CRP 139 mg/L, ESR 18 mm/h, WBC 15.21 × 10⁹/L with neutrophilia). The preceding vomiting may represent a viral prodrome or early CNS inflammation.

Critical Immediate Actions

Urgent Neuroimaging and Lumbar Puncture

• Obtain brain MRI with gadolinium immediately to assess for cerebral edema, meningeal enhancement, or other inflammatory changes, as this is essential for detecting structural lesions and inflammatory patterns in patients with suspected CNS inflammation 1
• Perform lumbar puncture (after imaging rules out mass effect) to analyze CSF for cell count, protein, glucose, cultures, and consider autoimmune panels 1
• The combination of severe headache, photophobia, phonophobia, and history of brain swelling warrants urgent evaluation for increased intracranial pressure 1

Interpretation of Laboratory Findings

• CRP of 139 mg/L is markedly elevated (normal <10 mg/L), indicating significant systemic inflammation 1, 2
• ESR of 18 mm/h is within normal range for women (<30 mm/h), creating a discordance pattern where CRP is dramatically elevated but ESR is not 2
• This CRP-ESR discordance suggests an acute inflammatory process, as CRP rises and falls rapidly with inflammation while ESR remains elevated longer 2
• WBC 15.21 × 10⁹/L with neutrophils 12.49 × 10⁹/L represents leukocytosis with neutrophilia, consistent with either infection or inflammatory process 1, 3

Differential Diagnosis Priority

Most Likely: Recurrent Inflammatory CNS Disease

The history of "brain swelling" previously treated with steroids suggests:

• CLIPPERS syndrome (Chronic Lymphocytic Inflammation with Pontocerebellar Perivascular Enhancement Responsive to Steroids) - a steroid-responsive autoimmune encephalitis 4
• Autoimmune/aseptic meningitis
• Neurosarcoidosis
• Behçet disease with CNS involvement 1

Must Rule Out: CNS Infection

• Bacterial meningitis (though patient appears stable enough to have slept all day, making fulminant bacterial meningitis less likely) 3
• Viral meningoencephalitis
• The combination of positive CRP (>10 mg/L) in 93% and elevated ESR in 90% of septicemia/endocarditis cases means infection cannot be excluded on labs alone 3

Consider: Other Inflammatory Conditions

• Giant cell arteritis (though ESR <40 mm/h makes this less likely, as ESR >40 mm/h has 93.2% sensitivity for GCA) 2
• Polymyalgia rheumatica (bilateral temple pain could suggest this, but typically presents with shoulder/hip girdle pain) 2

Immediate Management Algorithm

If Imaging Shows Cerebral Edema Without Mass Lesion

Initiate high-dose corticosteroids immediately:

• Methylprednisolone 1000 mg IV daily for 3-7 days, followed by oral prednisone taper over 2-3 months 1, 5
• This approach is supported by the patient's previous response to steroids for brain swelling 1, 5
• Critical caveat: If CNS lymphoma is suspected on imaging, avoid steroids until after biopsy, as they can obscure diagnosis 1

Supportive measures for cerebral edema:

• Elevate head of bed to 30 degrees to optimize cerebral perfusion pressure 1, 5
• Consider osmotic therapy (mannitol 1 g/kg of 20% solution or hypertonic saline 0.686 mL/kg of 23.4%) if clinical deterioration occurs 1
• Monitor for signs of deterioration: declining level of arousal, pupillary changes, worsening motor responses 1

If Infection Cannot Be Excluded

Do NOT withhold antibiotics while awaiting CSF results:

• Start empiric broad-spectrum antibiotics (ceftriaxone 2g IV q12h + vancomycin) immediately if any concern for bacterial meningitis
• Blood cultures before antibiotics 1, 3
• Steroids can be given concurrently with antibiotics in bacterial meningitis (dexamethasone 10 mg IV before or with first antibiotic dose)

Monitoring Strategy

Serial inflammatory markers:

• Repeat CRP in 24-48 hours - should decrease rapidly if treatment is effective, as CRP normalizes faster than ESR 2
• CRP is superior to ESR for monitoring acute treatment response 2
• If CRP remains >10 mg/L after 48-72 hours of appropriate therapy, re-examine for alternative diagnoses 2

Watch for steroid-induced leukocytosis:

• High-dose steroids can increase WBC by up to 4.84 × 10⁹/L within 48 hours 6
• Any WBC increase beyond this, or continued rise after 48 hours, suggests worsening infection rather than steroid effect 6, 7

Critical Pitfalls to Avoid

1. Do not assume leukocytosis is solely from steroids - in patients with acute infections on chronic steroids, WBC increases average 5 × 10⁹/L, but larger increases suggest true infection 7

2. Do not delay imaging for LP - obtain MRI first to rule out mass effect and assess for inflammatory patterns 1

3. Do not use lowest steroid dose in acute deterioration - while guidelines recommend lowest effective dose for chronic management, acute CNS inflammation with edema requires high-dose pulse therapy 1

4. Monitor for steroid complications given history of previous steroid use: hyperglycemia, GI bleeding (consider PPI prophylaxis), psychiatric symptoms, and myopathy 1, 8

5. If patient has history of steroid-induced psychosis (not mentioned but important given steroid history), consider budesonide alternatives or close psychiatric monitoring, though CNS inflammation may necessitate systemic steroids despite risks 8

Expected Clinical Course

• Symptoms should improve within 24-48 hours if inflammatory CNS disease responsive to steroids 1, 4
• CRP should decrease significantly within 48 hours of appropriate treatment 2
• If no improvement or worsening despite steroids, consider adding immunosuppressives (azathioprine 2.5 mg/kg/day or cyclophosphamide) or alternative diagnoses 1
• Plan for slow steroid taper over 2-3 months to prevent relapse 1, 5