Bacterial and Fungal Brain Infections 1 Bacterial Meningitis

Bacterial and Fungal Brain Infections 1 Bacterial Meningitis ACUTE; CSF: high protein, high WBCs, low Glc. • A good way of grouping these guys is by the age ranges they affect • • • Neisseria meningitides • • G-, encapsulated, aerobic diplococci Associated with permanent neurological sequelae (they’ve started giving steroids with the antibiotics to reduce this Spreads hematogenously from an episode of pharyngitis + fever. During the bacteremic phases (aka meningococcemia), there can be sepsis, DIC, arthralgia and a non-blanching purpuric rash. These are mostly mediated by Type III Hypersensitivity Waterhouse-Freidrichsen Syndrome 13 serogroups identified; Serogroup B doesn’t have good protection from vaccination Meningococcal vaccine immunizes against the capsule Rifampin is used as post-exposure prophylaxis and to clear out carriers Haemophilus influenzae • • • Neonates E. coli (G-, oxidase positive encapsulated rod), GBS (G+, beta-hemolytic coccus), L. monocytogenes (G+, intracellular, beta-hemolytic pleomorphic rod). GBS and E. coli colonize the female urogenital tract. Listeria is transferred through the placenta. Kids H. influenzae (G-, encapsulated coccobacilli that grows on chocolate agar); not really the case, more likely to be Neisseria nowadays Teens/Young Adults N. meningitides (G-, encapsulated diplococci) Adults/Any Age S. pneumonia (G+, alpha-hemolytic, encapsulated lancet-shaped diplococci) G-, encapsulated, aerobic coccobacilli. Growth on chocolate agar fastidiously. Spreads from episode of otitis media, pharyngitis, epiglottitis, arthritis, etc. via blood stream to reach the meninges. Also associated with neurologic sequelae. Serotype B is the most virulent. Fortunately Hib vaccine has taken care of it. Streptococcus pneumonia • • • G+, encapsulated, aerobic, beta-hemolytic, catalase-, encapsulated lancet-shaped diplococci Spreads from episode of pharyngitis, pneumonia, bronchitis or otitis media hematogenously Positive Quellung reaction for capsule presence Patients who have diminished cough reflexes, impaired ciliary clearance or those that have undergone splenectomy are at increased risk Pneumovax protects Fungal Meningitis CHRONIC • Appropriate T Cell immunity (also NK, PMN and Macrophage) is required to take care of these guys, which is why its seen mostly in immunocompromised patients • Cryptococcus neoformans • • • Coccidiodes immitis • • • Encapsulated, monomorphic yeast associated with pidgeon droppings. Inhaled to cause a primary lung infection which then seeds to the meninges. Stains with India Ink; serology to capsular antigen Dimorphic fungues found in the SW USA. Inhaled to cause a primary lung infection (spherules in the lungs) which then seeds to the CNS. Spherules react with complement in the lungs and form granulomas after lymphocyte and macrophage chemotaxis. Dx with silver stain and ELISA The most common cause of chronic bacterial meningitis is MTB.

Bacterial and Fungal Meningitis 2 Brain Abscesses • Most commonly form via hematogenous seeding, but can be via local extension through venous sinuses or because of trauma. They are mainly a secondary focus of infection. Usually encapsulated and fibrotic, just like any other abscess. Most commonly anaerobes • • • Sinus/Dental Conditions Streptococcus (GAS, GBS, Enterococcus), Peptostreptococcus, Staphylococcus and G- aerobic rods Pulmonary Infection Streptococcus, G- anaerobic rods (Fusobacterium), G+ bacilli (Actinomyces, Nocardia) Congenital Heart Disease Staphylococcus. I, Streptococcus Trauma Streptococcus, Staphylococcus, Immunosuppression • Staphylococcus/Streptococcus seeds from septic emboli, mastoiditis, otitis media, and head injuries • Clinically, these lesions present with increased ICP (n/v), mental status change, fever, and headache. On scans, these are ring-enhancing lesions. • Actinomyces G+, filamentous and branching rod associated with lung, bone and skin infection. Also, Pross loves the case about the black kid that got punched in the mouth (Is that racist? Nowhere near as racist as Anand’s stand-up). • Nocardia G+, partially Acid Fast. Associated with primary lung infection which spreads to the CNS to form abscesses in immunosuppression. • Fungal abscesses are mainly caused by Blastomyces dermatidis. This guy is a thermally dimorphic, budding fungus which is endemic to Mississippi, Ohio and Missouri. Forms abscesses after systemic blastomycosis, which is most commonly seen in immunocompromised patients. Acquired by inhalation or inoculation into skin Toxins • Tetanospasmin is a heat-labile AB exotoxin produced by Clostridium tetani (G+, spore-forming anaerobic rod found in the soil; tennis-racquet shape). The bacteria contaminates a wound and releases toxins into circulation. A subunits act at the level of the inhibitory interneurons of the spinal cord and act to decrease release of GABA and Glycine, thereby creating increased motor tone which manifests as muscle spasms and lockjaw. • For the 1, 000 th time, Botulinum toxin is produced by Clostridium tetani (G+, spore-forming anaerobic rod). The bacteria are transmitted via ingestion (adult or infant) or wound contact (wound botulism). The toxin is an AB toxin which travels to the NMJ to block release of ACh at the synapse. This causes flaccid paralysis.

Viral and Parasitic Meningitis Viral meningitis (aka asceptic meningitis) is characterized by features similar to bacterial meningitis but with several differences. On pathology there is edema and hyperemia, however there is not a purulent exudate. Infiltrates contain mostly lymphocytes and CSF studies show increased protein, WBCs and normal glucose. By and far the most common offending agents are Echoviruses and Cocksackie viruses. Enteroviruses • Picornaviruses: non-enveloped (+)ss. RNA viruses. They are acid resistant (fecal-oral transmission) and live at body temperature. Diagnosis can be done with CSF PCR and stool sample molecular analysis. Also throat swab. Serology is only performed after isolation of the virus. • They most often present with diarrhea and respiratory symptoms and their peak prevalence is in late summer and autumn. Ingestion of the virus leads to a 1 st viremia in which the virus spreads to organs. There is then a 2 nd period of viremia after which it makes it to the CNS. On biopsy, a perivascular lymphocytic infiltrate along with cell death (poliomyelitis, encephalitis, meningitis) can be seen. Their incubation period ranges from 2 -10 days. • Secondary autoimmune effects can also be seen (e. g. myocarditis, pericarditis, nephritis, etc. ) • • • Cocksackie A and B Disease limited to the meninges. Cocksackie A causes Hand Foot and Mouth Disease (easily the most unoriginal name for a disease ever) because they cause exanthems and enanthems (r/o Measles Koplik Spots). Cocksackie B causes myocarditis and pleurodynia. ECHOviruses Parechoviruses Polioviruses Spreads hematogenously after the GI tract to cross the BBB to cause paralytic poliomyelitis, meningoencephalitis. Bulbar polio and a ton more. The Salk vaccine (viral-inactivated) is used for prevention. Sabin has resulted in reversal of attenuation. 90% don’t develop clinical symptoms. Only 1% have paralytic symptoms. Enterovirus 68 -71 70: conjunctivitis and encephalitis; 71: HFMD, encephalitis, polio-like disease • 90% of viral meningitis is caused by Cocksackie B and ECHO • Ig. A response important for controlling them. • Wash your damn hands. No treatment. Parasitic (Amoebic) Meningitis • Naegleria fowleri is contracted by diving into shallow water. The bug makes it through the cribiform plate of the ethmoid bone. Initially, this disease presents identically to bacterial meningitis (low Glc, increased WBC, increased protein), however there are no bugs in the CSF (e. g. negative Gram Stain). The amoeba literally eats away the brain and meninges causing meningoencephalitis with an altered sense of taste and smell. Neutrophilic

• Viral and Parasitic Encephalitis often presents with fever, headache, nausea, vomiting and altered mental status (it only causes stiff neck sometimes). It is mostly caused by viruses (HSV, HIV, Rabies, Arbo) and parasites (Toxo, Taenia, Malaria, etc. ) Viral Encephalitis • Herpes Simplex Virus ds. DNA, enveloped viruses • • Can cause seizures Virus tracks up nerves to produce encephalitis with a predilection for the temporal lobes where it causes necrosis and hemorrhage. On biopsy there is a perivascular mononuclear infiltrate with intranuclear inclusions HSV 2 is more common than HSV 1 but HSV 1 is more severe than HSV 2. Neurologic sequelae are common. It’s treatable! So it is very important to identify the etiology Acyclovir CSF NA analysis can give the diagnosis. So can brain biopsy. HIV diploid (+)ss. RNA enveloped retrovirus with intranuclear replication • • • Can be due to a primary infection (e. g. in infants) or due to reactivation of latent virus inside sensory ganglia Macrophages seem to be the ticket into the CNS from where the virus can spread to neurons and cause grey and white matter pathology which is either primary, secondary or both. Uses neuronal gangliosides as cell receptor Rabiesvirus (-)ss. RNA enveloped virus • Transmission via bite (bat, dog, raccoon) or inoculation. Depending on the site of transmission, the time course of clinical symptoms is variable since the virus tracks up nerves (e. g. a bite on the leg will take longer than one on the face to make it to the brain). • • Once in the brain, the virus causes disease by inhibiting neuronal function, rather than killing neurons. On biopsy Negri bodies are visible within the cytosol of neurons. Clinically presents with dysphagia, muscle spasms, altered mental status, coma, paralysis and/or excitement. Dx with brain biopsy, immunoflourescence and examining the animal. Tx includes washing the wound, IVIG, Vaccine, Ribavirin and putting the patient in a semi-comatose state Parasitic Encephalitis • • Toxoplasma gondi • • Fecal-oral transmission of cysts from cats when pregnant bitches change the litter. Fuck cats (sorry about your cat, Mike) • Trophozoites within cells. Bradyzoites encysted. Known to cause cerebral malaria where the protozoan replicates within the cerebral vasculature. It can then move on to produce a lethal encephalitis casuing seizures, fever and coma. Roundoworms formed from eating General Tso’s Cat or General Tso’s Dog at Gene’s apartment. They form CNS and optic granulomas (epilepsy and detached retinas) Echinococcus granulosus • • • Causes encephalitis along with abscesses within the brain parenchyma, usually multiple ones. This most commonly occurs in transplacental transmission (where it causes hydrocephalus and chorioretinitis) and in immunocompromised patients Toxocara cati/canis • • One of the To. RCHe. S agents. Plasmodium falciparum • • Ingestion of undercooked meats. Ingestion of dog tapeworm eggs by the fecal-oral route result in Hydatid Cyst Disease. Larvae spread to the liver, lungs and brain to form cysts which trigger anaphylaxis if ruptured and seizures/encephalopathy CT/MRI Taenia solium • Cystercircosis is caused by the larval form of the pork tapeword ( Taenia solium). Ingestion of eggs is followed by dissemination to the brain where the eggs hatch into the larval cystecerci and form nodules. These lesions cause encephalopathy and seizures. • CT/MRI