Meningitis: Causes, Symptoms, and Treatment

• Meningitis is the inflammation of the protective membranes (meninges) covering the brain and spinal cord, typically caused by an infection.
• Viruses, bacteria, fungi, or other microorganisms can cause it.
• Bacterial infections can lead to severe and life-threatening meningitis.
• Fever, headache, stiff neck, and sensitivity to light are common symptoms.
• Early treatment is effective, but requires urgent medical attention to prevent complications.

Epidemiology and History

• Meningitis has been recognized since ancient times, but advancements in understanding and treatment occurred in the 19th and 20th centuries.
• Prior to the discovery of antibiotics, meningitis had a high mortality rate.
• Meningitis can occur worldwide but varies by region.
• Bacterial meningitis, especially meningococcal meningitis, is more common in sub-Saharan Africa ("meningitis belt").
• Infants, young children, and the elderly are more susceptible to meningitis.
• The mortality rate varies with the causative agent and speed of treatment.
• Bacterial meningitis has a higher mortality rate compared to viral meningitis.

Causes of Meningitis

• Bacterial Meningitis can be caused by Neisseria meningitidis (meningococcal meningitis) and Streptococcus pneumoniae.
• Viral Meningitis can be caused by Enteroviruses, Herpes simplex virus (HSV-2, HSV-1), Varicella zoster virus (VZV), and HIV.
• Fungal Meningitis can be caused by Cryptococcus neoformans, Coccidioides immitis, and Histoplasma capsulatum.
• Parasitic Meningitis can be caused by Naegleria fowleri (amoebic meningitis).
• Non-infectious causes include Autoimmune diseases (e.g., systemic lupus erythematosus) and Cancer (meningeal carcinomatosis).

Pathophysiology

• In Bacterial Meningitis pathogens enter the bloodstream or by direct extension from nearby infections (e.g., otitis media, sinusitis).
• Invasion of the meninges leads to inflammation and edema, increases intracranial pressure (ICP), disrupts the blood-brain barrier, and may cause neuronal damage.
• In Viral Meningitis, viral agents enter the meninges, causing inflammation without the significant tissue destruction seen in bacterial meningitis.
• The immune response typically resolves the infection without causing severe long-term effects.
• Fungi and parasites can enter the meninges, often in immunocompromised individuals, causing chronic inflammation and slower disease progression in Fungal and Parasitic Meningitis.

Treatment Protocols for Bacterial Meningitis

• Start broad-spectrum antibiotics immediately after lumbar puncture and blood cultures, before awaiting microbiological confirmation.
• Ceftriaxone (2g IV every 12 hours) or cefotaxime (2g IV every 4-6 hours) are part of the regimen.
• Vancomycin (15-20 mg/kg IV every 8-12 hours) for resistant S. pneumoniae
• Dexamethasone (0.15 mg/kg IV every 6 hours for 2-4 days) to reduce inflammation and prevent neurological sequelae in adults and children with pneumococcal meningitis.

Treatment Protocols for Viral Meningitis

• Most cases of viral meningitis are self-limiting and do not require specific antiviral therapy.
• Acyclovir for herpes simplex virus (HSV) or varicella zoster virus (VZV).
• Supportive care (hydration, pain management, antipyretics) are needed in some cases.

Treatment Protocols for Fungal and Parasitic Meningitis

• Amphotericin B (lipid formulation) and/or Fluconazole is the treatment for Fungal Meningitis.
• Miltefosine for Naegleria fowleri infection although often fatal, early treatment can help Parasitic Meningitis.

Mechanism of Action for Drugs

• Antibiotics inhibit bacterial cell wall synthesis (effective against S. pneumoniae, N. meningitidis).
• Cephalosporins (e.g., Ceftriaxone) inhibit bacterial cell wall synthesis (broad-spectrum activity against many pathogens).
• Vancomycin inhibits bacterial cell wall synthesis by binding to precursors of peptidoglycan.
• Amphotericin B binds to ergosterol in fungal membranes, causing cell membrane damage.
• Acyclovir inhibits viral DNA synthesis by blocking viral DNA polymerase (effective against HSV and VZV).
• Steroids (e.g., Dexamethasone) reduces inflammation and swelling in the brain, which is essential in reducing mortality and neurological sequelae.

Dosage Regimen

• Ceftriaxone 2g IV q12h as empiric regimen for Bacterial Meningitis.
• Vancomycin 15-20 mg/kg IV q8-12h can be used as empiric regimen for Bacterial Meningitis.
• Dexamethasone 0.15 mg/kg IV q6h for 2-4 days can be used as empiric regimen for Bacterial Meningitis.
• Acyclovir for HSV/VZV: 10 mg/kg IV q8h for 10-14 days as treatment for Viral Meningitis.
• Amphotericin B: 3-5 mg/kg IV once daily for several weeks as treatment for Fungal Meningitis.

Adverse Effects

• Ceftriaxone: Diarrhea, rash, hypersensitivity reactions
• Vancomycin: Red man syndrome (if infused too rapidly), nephrotoxicity, ototoxicity
• Amphotericin B: Nephrotoxicity, infusion reactions, electrolyte imbalances
• Acyclovir: Nausea, renal toxicity (rare with IV form)
• Dexamethasone: Hyperglycemia, gastrointestinal irritation, immunosuppression

Guidelines for confirming Meningitis

• A lumbar puncture is essential for confirming the diagnosis, with cerebrospinal fluid (CSF) analysis.
• CSF tested for white blood cell count, glucose, protein, and Gram stain.

Prevention

• Vaccination (e.g., MenACWY, Hib, pneumococcal vaccines).
• Prophylactic antibiotics for close contacts of meningococcal cases.

Monitoring

• Regular clinical monitoring of neurological status.
• Monitoring of drug levels, renal function, and electrolyte balance during treatment.