MENINGITIS
Background and Pathophysiology
Meningitis is the pathologic term for inflammation of the meninges. This can be divided by meningeal type (pachymeninges vs leptomeninges); infectious etiologies are much more commonly seen in leptomeningitis, which is discussed here. Certain vaccines against bacteria have become available to reduce the incidence/severity of meningitis, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae, although none of the current vaccinations covers all strains of the organism that cause meningitis, especially in adults.
Types
Acute
Acute meningitis presents within hours or days and is characterized by the triad of fever, headache, and neck stiffness. However, many will not have all three classic symptoms. Alteration in mental status in this context may indicate meningitis or encephalitis. Bacteria and viruses are the most common infectious causes of acute meningitis. Acute bacterial meningitis is a neurologic emergency that requires immediate intervention for the best outcomes. A list of common etiologies of acute meningitis in adults can be found in
Table 18-2.
Subacute/Chronic
Subacute-chronic meningitis (symptoms ≥4 weeks) has a wider range of etiologies including fastidious organisms, malignancy, and autoimmune diseases and varies by geography and host immunity. A list of infectious and noninfectious etiologies can be found in
Table 18-3.
Recurrent
Recurrent meningitis is rare and sometimes difficult to differentiate from chronic meningitis. Herpes simplex virus type 2 (HSV-2) is the most common infectious cause of recurrent meningitis.
Management
Management ultimately depends on the type of meningitis, but because outcomes depend on how quickly antimicrobials are initiated, early management for adults in developed countries has been standardized and should be initiated without delay on suspicion of the diagnosis.
1. Dexamethasone (0.15 mg/kg every 6 hours for 4 days) with or before the first dose of antimicrobials and continued for 4 days unless nonpneumococcal etiology is found, at which point this intervention can be stopped.
2. Third-generation cephalosporin to cover penicillin-sensitive S. pneumoniae and also N. meningitidis, Streptococcus agalactiae, and H. influenzae. If S. pneumoniae resistant to cephalosporins is identified, rifampin should be added to the regimen.
3. Vancomycin to cover penicillin-resistant strains of Streptococcus.
4. Ampicillin in patients over 50 years of age or those with known or suspected immune compromise to cover Listeria monocytogenes.
5. Acyclovir (10 mg/kg IV every 8 hours with dose adjustment for renal insufficiency) should be started in most cases as there is significant clinical overlap between HSV encephalitis (HSVE) and acute bacterial meningitis; this is stopped if bacterial meningitis is confirmed.
6. Source identification.
Treatment is then narrowed based on etiology and continued for 2 weeks. Additional supportive measures such as seizure control, intracranial pressure (ICP) monitoring/intervention, and pain control are often necessary.
Prognosis
Prognosis for bacterial meningitis depends greatly on how quickly appropriate antimicrobials are initiated, although sequelae are common. Viral etiologies in the immune competent have an excellent prognosis for full recovery. Tuberculous, fungal, and parasitic etiologies have varying outcomes.
ENCEPHALITIS
Background and Pathophysiology
Encephalitis is defined pathologically as inflammation of the brain parenchyma in the presence of neurologic dysfunction. It can be infectious or noninfectious. In the United States, the etiology is most commonly unknown, but for known entities, most common causes identified are HSV and anti-NMDA receptor antibody encephalitis. West Nile virus incidence periodically exceeds HSV during warm months when mosquitoes are active. Many infections can trigger an immune-mediated encephalitis without direct central nervous system (CNS) infection, for example, acute disseminated encephalomyelitis or autoimmune encephalitis.
Types
1. HSV: Most commonly identified sporadic encephalitis in the United States and most commonly caused by HSV-1. Affects both immune competent and compromised; occurs in both primary infection (20 years or younger) or reactivation (60 years and older). HSV polymerase chain reaction (PCR) of CSF is highly sensitive even after several days of antiviral treatment.
2. Varicella zoster virus (VZV): CNS manifestations of VZV are protean, but encephalitis is among them. Other infectious manifestations include meningitis, cranial neuritis, myeloradiculitis, and vasculitis. Intrathecal VZV immunoglobulin G (IgG) production or DNA detection is diagnostic.
3. Cytomegalovirus (CMV) and human herpes virus type 6 (HHV-6): Cause encephalitis only in immunocompromised. CMV is associated with ventriculitis in particular. HHV-6 tends to cause limbic encephalitis in solid organ transplant patients. Positive CSF HHV-6 PCR in normal hosts is common and almost always clinically irrelevant.
4. Enterovirus: More commonly associated with meningitis, this group of viruses can also cause an encephalitis and/or poliomyelitis. Diagnosis is by detection of viral RNA from CSF in the correct setting.
5. Arboviral: These are viruses carried by mosquitoes or ticks, and specific viruses vary by location (
Table 18-6). The most common arboviral encephalitis in the United States is West Nile virus, which has been reported from all 48 contiguous states with incidence ranging from 0.13 up to 1 case per 100,000 since 2002. Diagnosis is by presence of CSF immunoglobulin M (IgM), appropriate serologic evolution over time, or PCR on CSF (although viremia is early and brief so PCR is not sensitive).
6. Rabies: Common cause of encephalitis in Africa but extremely rare in the United States. Worldwide exposure to infected dogs is the source of human transmission, but in the United States, infected bats are most commonly the vectors.
7. Other: Less commonly, bacteria, parasites, spirochetes, fungi, and other viruses have been implicated in encephalitis. A listing can be found in
Table 18-7.
Management
1. General: Management of seizures, severely increased ICP, and cardiopulmonary compromise vary depending on severity of the disease. Reduction of inflammation with immune modulation, especially corticosteroids, is often implemented, as well, although clinical trial data are lacking.
2. HSV, VZV: 14 to 21 days of acyclovir 10 mg/kg every 8 hours (10-15 mg/kg for VZV) with adequate hydration and renal monitoring. Adjunctive corticosteroids are sometimes used with severe concomitant inflammation, but there are no strong data as yet for this to be standard. In some instances of severe edema, hemicraniectomy may be a management consideration.
3. CMV: Ganciclovir 5 mg/kg IV q12h + foscarnet 90 mg/kg IV q12h for 21d, followed by maintenance. In patients with HIV, antiretroviral therapy should be started immediately.
4. HHV-6: Ganciclovir 5 mg/kg IV q12h or foscarnet 90 mg/kg IV q12h for 21d, followed by maintenance.
5. Rabies: Vaccine is available for impending high-risk situations, and postexposure prophylaxis can be given immediately after a bite from an infected animal. Management is otherwise supportive.
6. Other: Specific antimicrobials are implemented depending on the disease entity identified.
Prognosis
Prognosis for HSVE depends on time to initiation of acyclovir, but permanent neurologic sequelae (memory loss, personality changes, seizures) are common. Treatment for less than 14 days carries a high risk of relapse. Nearly 50% of patients are rehospitalized within 1 year, usually for seizure. HSVE has been recognized to trigger anti-N-methyl D-aspartate (NMDA) receptor encephalitis. Rabies encephalitis is almost universally fatal. For most arboviruses, about half of survivors have permanent neurologic damage. Other encephalitides have varying prognosis.
