# Seminar 09: Neuroinfectious Diseases ## Year 3: Neurology Clerkship --- ## Learning Objectives By the end of this seminar, students will be able to: 1. Recognize clinical presentations of meningitis and encephalitis 2. Differentiate bacterial from viral CNS infections 3. Interpret cerebrospinal fluid analysis 4. Apply empiric and targeted antimicrobial therapy 5. Identify special populations at risk for specific pathogens 6. Manage complications of CNS infections --- ## Seminar Outline ### I. Approach to CNS Infections Central nervous system infections encompass several distinct clinical syndromes determined by the anatomical structures primarily affected. Meningitis involves inflammation of the meninges and presents with the classic triad of headache, fever, and neck stiffness, though the complete triad is present in only a minority of patients. Encephalitis involves inflammation of the brain parenchyma itself, manifesting with altered mental status, cognitive dysfunction, seizures, and focal neurological deficits. Meningoencephalitis describes combined involvement of both meninges and brain parenchyma, with features of both syndromes. Brain abscess represents a focal suppurative collection within the brain parenchyma, producing headache, focal neurological deficits, and signs of increased intracranial pressure. Recognizing these syndromic presentations guides initial evaluation and empiric treatment. The clinical presentation of CNS infection shares common features while varying based on the specific syndrome and pathogen. Headache is nearly universal in meningitis, often severe and generalized. Fever is present in most cases but may be absent in immunocompromised patients or those receiving corticosteroids. Neck stiffness, reflecting meningeal irritation, is more characteristic of bacterial than viral meningitis. Altered mental status, ranging from confusion to obtundation to coma, suggests parenchymal involvement as in encephalitis or severe meningitis with increased intracranial pressure. Seizures occur more commonly in encephalitis, particularly herpes simplex encephalitis, than in uncomplicated meningitis. Focal neurological deficits suggest either focal parenchymal involvement as in abscess or herpes encephalitis, or vascular complications. Physical examination should specifically assess for signs of meningeal irritation. Nuchal rigidity manifests as resistance to passive neck flexion, though this sign may be absent in early or mild cases and in patients with altered consciousness. Kernig sign is elicited with the patient supine by flexing the hip and knee to ninety degrees and then extending the knee, with resistance or pain indicating meningeal irritation. Brudzinski sign is positive when passive neck flexion causes reflexive flexion of the hips and knees. Jolt accentuation of headache, assessed by having the patient turn the head horizontally two to three times per second, has high sensitivity for meningitis when positive. Fundoscopic examination should assess for papilledema suggesting increased intracranial pressure. Risk factors help predict likely pathogens and guide empiric therapy. Age significantly influences the spectrum of pathogens, with neonates at risk for Group B Streptococcus, Escherichia coli, and Listeria monocytogenes, while Streptococcus pneumoniae and Neisseria meningitidis predominate in older children and adults. Elderly patients, particularly those over fifty years, are again at increased risk for Listeria meningitis. Immunocompromised patients face an expanded range of pathogens including Cryptococcus, Listeria, tuberculosis, and cytomegalovirus. Neurosurgical procedures or head trauma with cerebrospinal fluid leak predispose to infections with Staphylococcus aureus and gram-negative organisms. HIV infection creates susceptibility to numerous opportunistic pathogens depending on the degree of immunosuppression. Panel A: CNS infection syndromes comparison showing meningitis, encephalitis, meningoencephalitis, and brain abscess with characteristic features and anatomical involvement. Panel B: Clinical presentation frequency chart showing headache, fever, neck stiffness, altered mental status, and seizures by syndrome. Panel C: Physical examination signs illustration demonstrating nuchal rigidity, Kernig sign, and Brudzinski sign with proper technique. Panel D: Pathogen risk stratification by age group and immune status with likely organisms for each category. --- ### II. Lumbar Puncture and CSF Analysis Lumbar puncture provides essential diagnostic information in suspected CNS infection and should be performed promptly unless contraindications exist. Contraindications include signs of significantly increased intracranial pressure such as papilledema or posterior fossa mass effect, focal neurological deficits suggesting a mass lesion, and severe coagulopathy. Neuroimaging should precede lumbar puncture in patients with immunocompromise, history of CNS disease, new-onset seizures, focal neurological deficits, papilledema, or altered consciousness to exclude mass lesions. However, imaging should not significantly delay initiation of empiric antibiotics in suspected bacterial meningitis; blood cultures should be obtained and antibiotics administered if imaging will delay lumbar puncture. Normal cerebrospinal fluid parameters provide the reference for interpreting abnormal results. Opening pressure measured with the patient in lateral decubitus position normally ranges from ten to twenty centimeters of water in adults. The cerebrospinal fluid should appear clear and colorless; turbidity suggests elevated white blood cells or protein. White blood cell count normally does not exceed five cells per microliter, with lymphocyte predominance. Protein concentration ranges from fifteen to forty-five milligrams per deciliter. Glucose concentration is normally at least sixty percent of a simultaneously measured serum glucose, typically forty-five to eighty milligrams per deciliter. Red blood cells are normally absent unless introduced by traumatic tap. Cerebrospinal fluid patterns suggest specific diagnostic categories. Bacterial meningitis produces marked pleocytosis often exceeding one thousand cells per microliter with neutrophil predominance, significantly reduced glucose often below forty milligrams per deciliter or less than forty percent of serum glucose, and elevated protein frequently exceeding one hundred milligrams per deciliter. Viral meningitis and encephalitis typically show modest pleocytosis usually under one thousand cells per microliter with lymphocyte predominance, normal glucose, and mildly elevated protein. Tuberculous and fungal meningitis produce lymphocytic pleocytosis, reduced glucose, and markedly elevated protein, sometimes exceeding two hundred milligrams per deciliter. These patterns provide initial guidance, though overlap exists and results should be interpreted in clinical context. Additional cerebrospinal fluid tests provide specific diagnostic information. Gram stain offers rapid identification of bacteria in approximately sixty to ninety percent of untreated bacterial meningitis cases, with yield decreasing after antibiotic administration. Culture remains the gold standard for bacterial identification and susceptibility testing. Polymerase chain reaction testing for herpes simplex virus, varicella-zoster virus, enteroviruses, and other pathogens provides rapid and sensitive detection. Cryptococcal antigen testing is essential in immunocompromised patients. VDRL testing screens for neurosyphilis. Cytology may identify malignant cells in carcinomatous meningitis. Multiplex PCR panels allow simultaneous testing for multiple pathogens and have become standard in many settings. Panel A: Lumbar puncture indications and contraindications diagram showing when imaging should precede LP and when empiric antibiotics should not await LP. Panel B: Normal CSF parameters reference table with units and typical ranges for opening pressure, appearance, WBC, protein, and glucose. Panel C: CSF pattern comparison grid showing bacterial, viral, and TB/fungal patterns with cell count, differential, protein, and glucose characteristics. Panel D: CSF diagnostic test menu showing Gram stain, culture, PCR panel, cryptococcal antigen, VDRL, and cytology indications. --- ### III. Bacterial Meningitis Bacterial meningitis remains a medical emergency with significant morbidity and mortality despite advances in antimicrobial therapy. The pathogen spectrum varies by age and clinical context. In neonates under one month of age, Group B Streptococcus, Escherichia coli, and Listeria monocytogenes predominate, reflecting vertical transmission and neonatal immune characteristics. In infants and children, Streptococcus pneumoniae and Neisseria meningitidis are most common, with Haemophilus influenzae type b now rare due to vaccination. Adults are most commonly affected by Streptococcus pneumoniae and Neisseria meningitidis. Adults over fifty years and immunocompromised patients face additional risk for Listeria monocytogenes. Post-neurosurgical or post-traumatic meningitis involves Staphylococcus aureus and gram-negative organisms. The clinical presentation of bacterial meningitis includes the classic triad of fever, neck stiffness, and altered mental status, though only approximately forty-four percent of patients present with all three features. Almost all patients have at least two of the four symptoms of headache, fever, neck stiffness, and altered mental status. The course is typically acute, with symptoms progressing over hours. Petechial or purpuric rash strongly suggests Neisseria meningitidis infection and may indicate evolving disseminated intravascular coagulation. Cranial nerve palsies, particularly sixth nerve palsy, may develop from increased intracranial pressure or direct inflammation. Seizures occur in approximately twenty to thirty percent of patients. Empiric antibiotic therapy must begin immediately in suspected bacterial meningitis, ideally within one hour of presentation. For community-acquired meningitis in adults, the standard regimen combines ceftriaxone (two grams intravenously every twelve hours) and vancomycin (fifteen to twenty milligrams per kilogram every eight to twelve hours). The combination provides coverage for penicillin-resistant pneumococcus while vancomycin covers resistant organisms pending susceptibility data. Ampicillin (two grams every four hours) should be added for patients over fifty years, immunocompromised patients, and those with alcoholism to cover Listeria monocytogenes, which is intrinsically resistant to cephalosporins. Post-neurosurgical or post-traumatic meningitis requires vancomycin plus an antipseudomonal beta-lactam such as ceftazidime or meropenem. Adjunctive dexamethasone reduces mortality and neurological sequelae in adult bacterial meningitis, particularly pneumococcal meningitis. The optimal benefit is achieved when dexamethasone is administered before or concurrent with the first antibiotic dose, with diminishing benefit if delayed. The standard regimen is dexamethasone 0.15 milligrams per kilogram every six hours for four days. If cerebrospinal fluid gram stain or culture confirms Streptococcus pneumoniae, dexamethasone should be continued. If an organism other than pneumococcus is identified, many experts recommend discontinuing dexamethasone, though practice varies. The primary mechanism of benefit involves reducing inflammation and its contribution to neuronal injury, cerebral edema, and hearing loss. Panel A: Bacterial meningitis pathogen distribution by age group showing neonatal, pediatric, adult, and elderly or immunocompromised organisms. Panel B: Clinical presentation statistics showing frequency of classic triad components and other common features. Panel C: Empiric antibiotic regimen selection flowchart based on patient age, immune status, and clinical context with specific dosing. Panel D: Dexamethasone protocol showing timing relative to antibiotics, dosing, duration, and indications to continue or discontinue based on pathogen identification. --- ### IV. Viral Meningitis and Encephalitis Viral meningitis represents the most common cause of aseptic meningitis and typically follows a benign, self-limited course. Enteroviruses account for the majority of cases, particularly in summer and fall months. Herpes simplex virus type 2 causes meningitis as a manifestation of primary genital infection or reactivation, sometimes termed Mollaret meningitis when recurrent. Varicella-zoster virus causes meningitis in association with herpes zoster, sometimes without rash. Clinical presentation includes headache, fever, photophobia, and neck stiffness, with cerebrospinal fluid showing lymphocytic pleocytosis, normal glucose, and mildly elevated protein. Treatment is supportive for most viral meningitis, with symptoms typically resolving within one to two weeks. Specific antiviral therapy is not indicated for enteroviral meningitis but may be considered for herpes simplex or varicella-zoster meningitis. Herpes simplex encephalitis is the most common cause of sporadic viral encephalitis and represents a medical emergency requiring prompt recognition and treatment. The causative agent is usually herpes simplex virus type 1 in adults, with HSV-2 more common in neonates. Clinical presentation includes fever, headache, altered mental status, and often focal neurological deficits or seizures reflecting the predilection for temporal lobe involvement. Psychiatric symptoms and behavioral changes may occur. The characteristic MRI finding is T2 and FLAIR hyperintensity involving the temporal lobes, often asymmetrically, with possible extension to the insular cortex and orbitofrontal regions. Cerebrospinal fluid shows lymphocytic pleocytosis, and red blood cells may be present reflecting the hemorrhagic nature of the infection. HSV PCR of cerebrospinal fluid provides sensitive and specific diagnosis. Treatment of suspected herpes simplex encephalitis with acyclovir should begin immediately and not await diagnostic confirmation. Intravenous acyclovir is administered at 10 milligrams per kilogram every eight hours for fourteen to twenty-one days. Early treatment significantly improves survival and neurological outcomes, while delayed treatment is associated with worse outcomes. Acyclovir may be discontinued if an alternative diagnosis is established and HSV PCR is negative at least seventy-two hours after symptom onset. Mortality with treatment remains approximately fifteen to twenty percent, and neurological sequelae including memory impairment, personality changes, and seizures are common among survivors. Repeat lumbar puncture near the end of treatment may be performed to confirm viral clearance. Additional viral causes of encephalitis merit recognition. Varicella-zoster virus causes encephalitis, particularly in immunocompromised patients, sometimes without rash. West Nile virus, transmitted by mosquitoes, causes encephalitis with a predilection for motor neurons, producing flaccid paralysis resembling poliomyelitis. Eastern equine encephalitis and other arboviruses cause seasonal outbreaks. Cytomegalovirus causes encephalitis in severely immunocompromised patients, particularly those with AIDS. Rabies, though rare, is virtually always fatal once symptoms develop and should be considered with animal bite exposure. The approach to suspected viral encephalitis includes empiric acyclovir pending diagnostic testing, MRI to identify temporal lobe or other characteristic involvement, and lumbar puncture with comprehensive viral PCR panel. Panel A: Viral meningitis etiology pie chart showing enterovirus predominance with HSV-2, VZV, and other causes, with seasonal variation and clinical features. Panel B: Herpes simplex encephalitis imaging showing characteristic temporal lobe T2/FLAIR hyperintensity on MRI with clinical presentation features. Panel C: Acyclovir treatment protocol showing dosing, duration, and criteria for discontinuation with outcome data. Panel D: Viral encephalitis differential showing West Nile, VZV, CMV, and rabies with distinguishing features and diagnostic approaches. --- ### V. Tuberculous and Fungal Meningitis Tuberculous meningitis represents the most common form of central nervous system tuberculosis and carries significant morbidity and mortality, particularly when diagnosis and treatment are delayed. Risk factors include HIV infection, immunosuppression, residence in or travel to endemic areas, and close contacts of tuberculosis patients. The clinical presentation is typically subacute, developing over weeks rather than the acute presentation of bacterial meningitis. Symptoms include headache, fever, malaise, and weight loss, with progressive neurological deterioration. Cranial nerve palsies, particularly affecting cranial nerves VI and III, occur commonly due to basilar meningeal involvement. Hydrocephalus develops frequently and may require management. Cerebrospinal fluid findings in tuberculous meningitis include lymphocytic pleocytosis typically ranging from one hundred to five hundred cells per microliter, reduced glucose, and markedly elevated protein often exceeding one hundred milligrams per deciliter. Acid-fast bacilli smear has low sensitivity, and mycobacterial culture, while more sensitive, requires weeks for growth. Nucleic acid amplification testing provides more rapid diagnosis. MRI demonstrates basilar meningeal enhancement, hydrocephalus, and potentially tuberculomas. Treatment requires prolonged multidrug therapy, typically with isoniazid, rifampin, pyrazinamide, and ethambutol for two months followed by isoniazid and rifampin for seven to ten additional months. Adjunctive corticosteroids reduce mortality and are recommended for all patients with tuberculous meningitis. Cryptococcal meningitis is the most common cause of fungal meningitis and occurs predominantly in immunocompromised patients, particularly those with HIV/AIDS with CD4 counts below one hundred cells per microliter. The causative organism, Cryptococcus neoformans, is acquired through inhalation of environmental spores with subsequent hematogenous dissemination to the central nervous system. Presentation is subacute with headache, fever, and altered mental status. Elevated intracranial pressure is characteristic and may be severe, requiring management with serial lumbar punctures or lumbar drain. Cerebrospinal fluid may show minimal pleocytosis despite active infection, but cryptococcal antigen testing is highly sensitive. India ink preparation demonstrating encapsulated yeast is diagnostic but less sensitive than antigen testing. Treatment of cryptococcal meningitis in HIV patients involves an induction phase of amphotericin B (preferably liposomal) plus flucytosine for at least two weeks, followed by consolidation with fluconazole for eight weeks, and then maintenance fluconazole until immune reconstitution with antiretroviral therapy. Management of elevated intracranial pressure is critical, with therapeutic lumbar punctures performed to reduce pressure when opening pressure exceeds twenty-five centimeters of water. Other fungal causes of meningitis include Coccidioides immitis in the southwestern United States causing chronic meningitis, Histoplasma capsulatum in the Ohio and Mississippi River valleys, and Aspergillus species in severely immunocompromised patients. Chronic meningitis, defined as symptoms and cerebrospinal fluid abnormalities persisting for more than four weeks, should prompt consideration of tuberculosis, fungi, and non-infectious causes including sarcoidosis and carcinomatous meningitis. Panel A: Tuberculous meningitis clinical features showing subacute course, cranial neuropathies, and basilar meningeal enhancement on imaging with CSF profile. Panel B: TB meningitis treatment regimen showing four-drug induction, continuation phase, total duration, and role of adjunctive corticosteroids. Panel C: Cryptococcal meningitis in HIV showing CD4 threshold, clinical features, elevated ICP management, and diagnostic tests including cryptococcal antigen. Panel D: Antifungal treatment phases for cryptococcal meningitis showing induction, consolidation, and maintenance with specific agents and durations. --- ### VI. Brain Abscess Brain abscess develops through several mechanisms including contiguous spread from adjacent infections, hematogenous dissemination from distant sources, and direct inoculation following neurosurgical procedures or penetrating trauma. Contiguous spread from sinusitis, otitis media, mastoiditis, or dental infection accounts for a significant proportion of cases, with abscess location determined by the primary source. Hematogenous spread occurs from pulmonary infections, endocarditis, or other systemic sources, typically producing multiple abscesses at the gray-white junction in the distribution of the middle cerebral artery. The microbiology reflects the source, with streptococci and anaerobes common in odontogenic and sinus-related abscesses, Staphylococcus aureus in post-traumatic cases, and polymicrobial infections frequent. Clinical presentation of brain abscess includes headache, which is the most common symptom, present in the majority of patients. Fever is present in only approximately fifty percent, distinguishing abscess from meningitis where fever is nearly universal. Focal neurological deficits occur in half of patients and reflect abscess location. Seizures occur in approximately twenty-five percent. Signs of increased intracranial pressure including papilledema, nausea, and vomiting may be present. The classic triad of fever, headache, and focal deficit is present in fewer than half of patients. The presentation may be acute or indolent over weeks depending on the virulence of the organism and host factors. Neuroimaging demonstrates a characteristic ring-enhancing lesion on contrast-enhanced CT or MRI. MRI is preferred for its superior sensitivity and ability to characterize the lesion. The ring enhances smoothly and is typically thinner on the ventricular side. Surrounding vasogenic edema is often extensive relative to abscess size. Diffusion-weighted MRI shows restricted diffusion within the abscess cavity, producing bright signal on DWI and corresponding low signal on ADC mapping, distinguishing abscess from necrotic tumor which typically does not restrict diffusion. Multiple lesions should raise concern for hematogenous spread and prompt investigation for systemic source. Lumbar puncture is contraindicated with significant mass effect due to herniation risk, and cerebrospinal fluid findings are often non-specific. Management of brain abscess combines antimicrobial therapy with surgical intervention in most cases. Empiric antibiotic therapy typically includes a third-generation cephalosporin (ceftriaxone) for streptococci and gram-negative coverage, metronidazole for anaerobes, and vancomycin when staphylococcal infection is suspected, particularly in post-traumatic or post-surgical cases. Antibiotic duration is prolonged, typically six to eight weeks, with duration extended for patients not undergoing surgical drainage. Surgical intervention, either stereotactic aspiration or open excision, is indicated for abscesses larger than 2.5 centimeters, those causing significant mass effect, and those not responding to antibiotics. Serial imaging monitors treatment response, with follow-up MRI at regular intervals until complete resolution. Dexamethasone may be used short-term for significant perilesional edema causing mass effect. Panel A: Brain abscess mechanism pathways showing contiguous spread from sinuses, otitis, and dental sources, hematogenous spread, and post-surgical or traumatic inoculation with typical pathogens for each. Panel B: Clinical presentation frequency chart showing headache, fever, focal deficits, seizures, and complete triad occurrence. Panel C: MRI characteristics showing ring enhancement, surrounding edema, and restricted diffusion distinguishing abscess from tumor. Panel D: Management algorithm showing empiric antibiotics selection, indications for surgical intervention, treatment duration, and monitoring approach. --- ### VII. Special Populations HIV-associated CNS infections encompass a broad spectrum of opportunistic pathogens with specific associations to the degree of immunosuppression. Cryptococcal meningitis typically occurs when CD4 counts fall below one hundred cells per microliter, presenting with subacute headache, elevated intracranial pressure, and often minimal cerebrospinal fluid pleocytosis despite active infection. Toxoplasma gondii causes cerebral toxoplasmosis with characteristic multiple ring-enhancing lesions showing predilection for the basal ganglia, also occurring with CD4 counts below one hundred. Cytomegalovirus encephalitis develops in severely immunocompromised patients with CD4 counts below fifty, causing ventriculitis visible as periventricular enhancement. Progressive multifocal leukoencephalopathy, caused by JC virus reactivation, produces progressive focal neurological deficits with asymmetric white matter lesions lacking enhancement or mass effect. Primary CNS lymphoma occurs in the setting of profound immunosuppression and must be distinguished from toxoplasmosis. Differentiating cerebral toxoplasmosis from primary CNS lymphoma has important therapeutic implications. Both can present with ring-enhancing brain lesions in patients with advanced HIV infection. Toxoplasmosis typically produces multiple lesions with basal ganglia predilection and is associated with positive toxoplasma serology. Primary CNS lymphoma is more commonly single or periventricular and may be negative for toxoplasma antibodies. The standard approach involves empiric treatment for toxoplasmosis in seropositive patients with typical imaging findings, with clinical and radiological improvement expected within one to two weeks. Failure to improve should prompt consideration of brain biopsy for definitive diagnosis. Thallium SPECT or FDG-PET may help differentiate, with lymphoma showing increased uptake and toxoplasmosis decreased uptake relative to normal brain. Post-transplant patients face an evolving risk of CNS infections depending on time from transplantation. In the early post-transplant period (first month), bacterial infections predominate, including those related to surgical complications and hospital-acquired pathogens. During the intermediate period (one to six months), opportunistic infections emerge as immunosuppression takes full effect, including cytomegalovirus, Aspergillus, Listeria, and progressive multifocal leukoencephalopathy. In the late period (beyond six months), community-acquired infections occur alongside continued risk for opportunistic pathogens in patients on ongoing immunosuppression. Cryptococcosis and Nocardia brain abscess represent important considerations in this population. Neurocysticercosis is the most common parasitic infection of the central nervous system worldwide and the leading cause of acquired epilepsy in endemic regions including Latin America, Africa, and Asia. The infection occurs through ingestion of Taenia solium (pork tapeworm) eggs, with larvae migrating to the brain and forming cysts. The most common presentation is seizures, occurring as cysts degenerate and provoke inflammation. Imaging demonstrates cystic lesions in various stages, from viable cysts with scolex visible as an eccentric dot, to degenerating cysts with surrounding edema and enhancement, to calcified remnants. Treatment depends on stage and number of cysts, with antiparasitic therapy (albendazole or praziquantel) combined with corticosteroids to reduce inflammation, and antiepileptic drugs for seizure management. Panel A: HIV-associated CNS infections stratified by CD4 count threshold showing cryptococcus, toxoplasmosis, CMV, PML, and primary CNS lymphoma with typical features. Panel B: Toxoplasmosis versus lymphoma differentiation algorithm showing imaging features, serology, empiric treatment approach, and criteria for biopsy. Panel C: Post-transplant CNS infection timeline showing early bacterial, intermediate opportunistic, and late period infection patterns. Panel D: Neurocysticercosis lifecycle, imaging stages, and treatment approach with antiparasitic therapy and corticosteroids. --- ### VIII. Neurological Complications of Systemic Infections Septic encephalopathy represents a common cause of altered mental status in hospitalized patients with systemic infection. This condition occurs in the absence of direct central nervous system invasion, resulting instead from systemic inflammatory responses, metabolic derangements, and microvascular dysfunction. Clinical presentation ranges from mild confusion to deep coma, with the severity generally correlating with the severity of systemic illness. Examination may reveal asterixis, tremor, and diffuse hyperreflexia. Electroencephalography shows non-specific slowing without epileptiform activity. Cerebrospinal fluid is normal or shows only mild protein elevation. Management focuses on treating the underlying infection and supporting organ function; specific therapy for the encephalopathy is not available. Infective endocarditis produces neurological complications in approximately twenty to forty percent of patients through several mechanisms. Septic emboli from cardiac vegetations cause ischemic stroke, which may undergo hemorrhagic transformation. Mycotic aneurysms develop from infection of arterial walls by septic emboli and carry risk of rupture and subarachnoid or intracerebral hemorrhage. Meningitis occurs through direct seeding or extension from embolic foci. Brain abscess results from septic emboli, particularly with Staphylococcus aureus infection. Neuroimaging with MRI often reveals clinically silent embolic lesions in patients with endocarditis. Management involves appropriate antimicrobial therapy with surgical intervention for cardiac indications; anticoagulation decisions are complex given competing risks of emboli and hemorrhage from mycotic aneurysms. Post-infectious neurological syndromes follow systemic infections by days to weeks through immune-mediated mechanisms rather than direct infection. Acute disseminated encephalomyelitis is a monophasic inflammatory demyelinating disorder occurring after viral infections or vaccinations, presenting with encephalopathy and multifocal neurological deficits with characteristic multifocal white matter lesions on MRI. Post-infectious cerebellar ataxia occurs in children following varicella infection, causing acute ataxia that typically resolves. Guillain-Barre syndrome follows Campylobacter jejuni and other infections, producing acute inflammatory demyelinating polyradiculoneuropathy. Transverse myelitis may occur as a post-infectious phenomenon. Recognition of these immune-mediated conditions guides appropriate treatment with immunomodulatory therapy rather than antimicrobials. Prion diseases, though rare, represent a distinct category of transmissible central nervous system disorders caused by misfolded prion protein. Sporadic Creutzfeldt-Jakob disease accounts for the majority of cases and presents with rapidly progressive dementia, myoclonus, ataxia, and visual disturbance evolving over months to death. MRI demonstrates characteristic restricted diffusion in the cortex (cortical ribboning) and basal ganglia. Electroencephalography may show periodic sharp wave complexes. Cerebrospinal fluid testing for 14-3-3 protein is supportive, while real-time quaking-induced conversion assay for prion protein provides high sensitivity and specificity. Variant Creutzfeldt-Jakob disease, linked to bovine spongiform encephalopathy, presents with psychiatric symptoms in younger patients. Prion diseases are invariably fatal, and treatment is supportive with no disease-modifying therapy available. Panel A: Septic encephalopathy mechanism showing systemic inflammation, metabolic derangements, and microvascular dysfunction contributing to brain dysfunction without direct invasion. Panel B: Endocarditis neurological complications showing septic emboli causing stroke, mycotic aneurysm formation and rupture risk, meningitis, and abscess. Panel C: Post-infectious immune-mediated syndromes showing ADEM, post-infectious cerebellar ataxia, GBS, and transverse myelitis with temporal relationship to infection. Panel D: Creutzfeldt-Jakob disease features showing rapid progression, myoclonus, and characteristic MRI (cortical ribboning) and EEG findings. --- ### IX. Prevention and Prophylaxis Vaccination represents the most effective strategy for preventing bacterial meningitis. Pneumococcal vaccination, including conjugate vaccine (PCV13 or PCV15) and polysaccharide vaccine (PPSV23), significantly reduces the incidence of invasive pneumococcal disease including meningitis. Meningococcal vaccination protects against serogroups A, C, W, and Y (quadrivalent vaccine) and serogroup B (separate vaccine), with recommendations including routine adolescent vaccination and vaccination of high-risk individuals including those with complement deficiency, asplenia, or exposure during outbreaks. Haemophilus influenzae type b conjugate vaccine has dramatically reduced Hib meningitis incidence in countries with routine childhood vaccination. Measles vaccination prevents subacute sclerosing panencephalitis, a late complication of measles infection. Chemoprophylaxis for close contacts of patients with bacterial meningitis prevents secondary cases for certain pathogens. Neisseria meningitidis chemoprophylaxis is indicated for household contacts, daycare contacts, and individuals with direct exposure to respiratory secretions. Options include rifampin (600 milligrams twice daily for two days), ciprofloxacin (single 500-milligram dose), or ceftriaxone (single 250-milligram intramuscular injection). Prophylaxis should be administered as soon as possible, ideally within twenty-four hours of case identification. Haemophilus influenzae type b prophylaxis with rifampin is indicated for household contacts when unvaccinated children under four years are present. Prophylaxis is not routinely indicated for contacts of pneumococcal meningitis patients. Pre-exposure prophylaxis applies to certain high-risk situations. Patients with cerebrospinal fluid leaks from trauma or surgery are at increased risk for pneumococcal meningitis and should receive pneumococcal vaccination; prophylactic antibiotics are not routinely recommended but may be considered in certain circumstances. Cochlear implant recipients should receive pneumococcal vaccination due to increased meningitis risk. Patients with anatomic or functional asplenia require vaccination against encapsulated organisms (pneumococcus, meningococcus, Haemophilus influenzae) and are often placed on prophylactic antibiotics. HIV-infected patients with CD4 counts below one hundred should receive trimethoprim-sulfamethoxazole prophylaxis, which provides protection against toxoplasmosis in addition to Pneumocystis jirovecii pneumonia. Post-exposure prophylaxis prevents infection following specific high-risk exposures. Rabies post-exposure prophylaxis, consisting of thorough wound cleaning, rabies immune globulin infiltrated at the wound site, and rabies vaccination series, effectively prevents this otherwise fatal infection when administered promptly after exposure to a potentially rabid animal. Meningococcal post-exposure prophylaxis should be administered within twenty-four hours of identifying the index case. HIV post-exposure prophylaxis with antiretroviral therapy is indicated following significant occupational or non-occupational exposures. Following exposure to a patient with tuberculous meningitis, evaluation for latent tuberculosis infection with subsequent treatment if positive prevents progression to active disease. Panel A: Vaccination schedule for meningitis prevention showing pneumococcal, meningococcal, and Hib vaccines with target populations and schedules. Panel B: Chemoprophylaxis indications for meningococcal exposure showing contact definitions, antibiotic options, and timing requirements. Panel C: Pre-exposure prophylaxis situations including CSF leak, cochlear implant, asplenia, and HIV with specific recommendations. Panel D: Post-exposure prophylaxis protocols for rabies, meningococcus, HIV, and tuberculosis exposure with timeframes and interventions. --- ### X. Outcomes and Complications Bacterial meningitis carries significant morbidity and mortality despite appropriate treatment. Mortality rates range from ten to thirty percent depending on the pathogen and patient factors, with pneumococcal meningitis carrying higher mortality than meningococcal disease. Acute complications include cerebral edema and herniation, hydrocephalus requiring cerebrospinal fluid drainage, seizures occurring in twenty to thirty percent, stroke from vasculitis or thrombosis, and syndrome of inappropriate antidiuretic hormone secretion. Management of acute complications requires intensive monitoring and intervention, including intubation and mechanical ventilation when needed, osmotic therapy for elevated intracranial pressure, external ventricular drainage for hydrocephalus, and antiepileptic drugs for seizures. Long-term sequelae affect a significant proportion of bacterial meningitis survivors. Hearing loss is the most common permanent sequela, occurring in approximately fifteen to twenty percent of survivors, particularly following pneumococcal meningitis. All patients should undergo audiological evaluation following recovery from bacterial meningitis. Cognitive impairment, ranging from subtle deficits to severe disability, affects a substantial proportion of survivors. Focal neurological deficits may persist from stroke or other complications. Post-meningitic epilepsy requires ongoing antiepileptic treatment in affected patients. Children are at risk for developmental delays and learning disabilities requiring long-term educational support and intervention. Prognosis varies considerably by infection type. Viral meningitis carries an excellent prognosis with full recovery expected in the vast majority of cases, though post-viral fatigue and headache may persist for weeks. Herpes simplex encephalitis, despite antiviral treatment, has mortality of approximately fifteen to twenty percent and neurological sequelae including memory impairment, behavioral changes, and seizures in the majority of survivors. Cryptococcal meningitis prognosis depends heavily on underlying immune status and adequacy of intracranial pressure management, with mortality rates varying widely. Brain abscess prognosis depends on neurological status at presentation and the ability to achieve source control. Repeat lumbar puncture has specific indications during treatment of CNS infections. In bacterial meningitis, routine repeat lumbar puncture is not necessary if the patient is improving clinically; however, persistent fever or clinical deterioration should prompt repeat cerebrospinal fluid analysis to assess treatment adequacy and exclude complications. For pneumococcal meningitis treated with dexamethasone, some experts recommend repeat lumbar puncture at forty-eight to seventy-two hours to document sterilization given the potential for dexamethasone to mask inadequate treatment response. In cryptococcal meningitis, repeat lumbar puncture is indicated both therapeutically to manage elevated intracranial pressure and to document clearance of infection. Tuberculous meningitis may warrant follow-up cerebrospinal fluid analysis to monitor treatment response. Panel A: Bacterial meningitis outcome statistics showing mortality by pathogen, acute complication rates, and long-term sequelae prevalence. Panel B: Acute complication management showing interventions for cerebral edema, hydrocephalus, seizures, and stroke. Panel C: Long-term sequelae monitoring showing hearing evaluation, cognitive assessment, and rehabilitation needs. Panel D: Repeat lumbar puncture indications algorithm for bacterial meningitis, cryptococcal meningitis, and tuberculous meningitis. --- ## Summary - Meningitis classic triad (fever, neck stiffness, altered mental status) is present in only forty-four percent; most patients have at least two of headache, fever, stiffness, and altered mental status - Bacterial meningitis CSF: neutrophilic pleocytosis (often greater than 1000 cells), low glucose (less than 40 mg/dL), high protein - Viral meningitis CSF: lymphocytic pleocytosis (usually less than 1000 cells), normal glucose, mildly elevated protein - Empiric bacterial meningitis treatment: ceftriaxone plus vancomycin plus dexamethasone; add ampicillin for Listeria coverage in patients over 50 years or immunocompromised - Dexamethasone in bacterial meningitis: give before or with first antibiotic dose; reduces mortality in pneumococcal meningitis - Herpes simplex encephalitis: temporal lobe involvement on MRI; start acyclovir empirically without waiting for PCR results - Cryptococcal meningitis: HIV/AIDS with CD4 less than 100; positive CSF cryptococcal antigen; manage elevated intracranial pressure with serial lumbar punctures - Brain abscess: ring-enhancing lesion with restricted diffusion; antibiotics plus surgical drainage for lesions larger than 2.5 centimeters - Toxoplasmosis in HIV: multiple ring-enhancing lesions, basal ganglia predilection; empiric treatment trial before biopsy - Close contacts of meningococcal meningitis require chemoprophylaxis within twenty-four hours; options include rifampin, ciprofloxacin, or ceftriaxone --- ## Key Terms | Term | Definition | |------|------------| | Meningitis | Inflammation of the meninges presenting with headache, fever, and neck stiffness | | Encephalitis | Inflammation of the brain parenchyma causing altered mental status, seizures, and focal deficits | | Nuchal rigidity | Stiff neck with resistance to passive flexion, indicating meningeal irritation | | Pleocytosis | Elevated white blood cell count in cerebrospinal fluid | | Albuminocytologic dissociation | Elevated CSF protein with normal or near-normal cell count, characteristic of GBS | | Ring-enhancing lesion | Peripheral contrast enhancement with central hypodensity, seen in abscess and tumor | | Opening pressure | Cerebrospinal fluid pressure measured during lumbar puncture | | Empiric therapy | Treatment initiated before definitive diagnosis based on likely pathogens | --- *This content is subject to the [MIT License](https://opensource.org/licenses/MIT). © 2024–2026 Hibbert School of Medicine.*