Lecture 22: CNS Infections

(CNS infections) Lecture 22 Central and Peripheral Nervous System · brain and spinal cord both enclosed by bone ↳ protections, CSF cushions brain · all nerves in body connected to spinal cord · motor nerves: CNS to PNS, message to muscles · sensory nerves: PNS to CNS, message to brain Neuron · axon: long extensions of nerve cells, transmits impulses · ganglia: small bodies containing sensory nerve cells located near the spinal column · motor nerve cells in spinal column CSF (cerebrospinal fluid) · manufactured in brain · fills four ventricles in brain, flows into sub-arachnoid space ↳ cushions spinal cord · normally low levels of antibodies and complement · Sterile, usually low WBC · nutrient rich, bacteria and fungi love to grow · blood-brain barrier (BBB) ↳ thin cell layer: restricts cells and molecules from blood to CSF ↳ can also prevent antibiotics when BBB is intact eg. ceftriaxone (beta lactam) can enter intact BBB Routes to the CNS · bloodstream and lymphatics: main source of CNS infections, but have to pass BBB first · nerves: some viruses can travel up the axon cytoplasm and travel along nerve bundles ↳ rabies, HIV · bone: skull fractures, osteomyelitis, mastoiditis Bacterial Meningitis · majority of cases: ↳ S. pheumoniae ↳ H. influenzae type b ↳ N. meningitidis · all may have capsules and evade phagocytosis in the bloodstream (most important virulence factor) General Symptoms of Meningitis · +/- sore throat · fever, headache* · irritability · neck stiffness · +/- photophobia Pyogenic Meningitis (acute) · neutrophils "pus forming " · elevated neutrophils and protein, and decreased glucose in CSF as compared to the blood · "positive" gram stain/culture ↳ just means bacteria are present not which kinds · caused by: S. pneumoniae, N. meningitidis, H. influenzae, S. agalactiae Granulomatous and Lymphocytic Meningitis (chronic) · predominant cell: lymphocyte/monocyte · CSF protein moderately increased, glucose moderately decreased · "negative" gram stain/culture (bacteria hard to find) · reduced alertness · loss of consciousness, confusion ↳ M. tuberculosis, L. monocytogenes, viral agents not visible H. influenzae Meningitis S. pneumoniae Meningitis · infants <4 protected by maternal antibodies, but · often acute onset · aerobic G- bacilli, serotype b invasive strain when they go down there is a window of opportunity · onset usually insidious (comes slowly then symptoms hit fast/hard)(days) · virulence factors: capsule, IgA protease, pili, endotoxin, OMP (outer membrane proteins) · vaccine exists · very high mortality of all ages · highest chance of complications of all types of meningitis · vaccines exist N. meningitidis Meningitis · main serotypes: A, B, Y, W-135 · virulence factors: capsule, IgA protease, endotoxin and pili · infections characterized by acute onset, skin rash (petichiae, purpura, ecchymoses) · 30% of patients develop DIC, endotoxinemia, and shock · mortality 100% if untreated, 10% if treated, < 1% sequale (complications) · vaccines exist Neonatal Meningitis · most common cause is S. agalactiae (strep group B), then E. coli · symptoms and signs are hard to recognize and diagnose ↳ fever, poor feeding, vomiting, respiratory distress, diarrhea · complications devastating: 1/3 cases have cerebral or cranial nerve palsy, epilepsy, mental deficits or hydrocephalus Viral Meningitis · viruses are the major cause of "acute aseptic meningitis syndrome" · abrupt onset, varies in intensity · characterized by lymphocytic pleocytosis (lots of lymphocytes in CSF) · difficult to diagnose (very very small), most caused by enterovirus or Herpes viruses · usually self-limiting Botulism · Clostridium botulinum: anaerobic spore forming G+ bacillus ↳ normally found in soil and water · can cause food poisoning due to an exotoxin in canned vegetables · can also result from a wound · different strains can produce different exotoxins, but all have same result · exotoxin inactivated by boiling for 5 min · symptoms: ↳ progressive flaccid paralysis 1-10 days ↳ nausea, double vision ↳ difficulty swallowing ↳ general weakness BOTOX · botulinum toxin is very toxic and can be used as a bioweapon Infant Botulism · associated with ingestion of honey (endospores) · infants do not have good stomach acidity or protective gut flora · symptoms: lethargy, constipation · treatable if caught in time ↳ treat with anti-toxin (BabyBIG) · tiny amounts can be used under the skin to prevent frown lines and wrinkles · paralysis of the peripheral nerves and prevents release of acetylcholine across the synaptic cleft Poliomyelitis (Polio) · enterovirus: RNA, nonenveloped small virus · disease initiated by ingestion (often of contaminated water) · most cases asymptomatic < 1% results in paralysis · multiplies in throat and small intestine, then invades through peyer's patches in intestine to get to lymph and then blood · death of motor neurons in anterior horn · transmission: oral fecal ↳ tropism: GI tract Iron lung Types of Polio · Abortive poliomyelitis: most common form, minor flu-like illness · Non-paralytic poliomyelitis: aseptic meningitis, minor flu-like symptoms and stiff neck and back · Paralytic poliomyelitis: major illness, flaccid paralysis ↳ affects CNS, first symptoms are usually severe myalgia in one limb, motor or sensory disturbances, and weakness ↳ Bulbar: involves one or more cranial nerve centers, including respiratory center in medulla oblongata ↳ Spinal: 30% affect lower limbs · PPMA or PPS: post polio muscle atrophy or post polio syndrome · vaccines: ↳ Salk: inactivated virus, needs boosters ↳ Sabin: oral vaccine, live attenuated with three strains of polio - small change of virus reverting to wildtype Rabies (hydrophobia) · zoonotic viral disease: RNA, rhabdovirus, enveloped (can infect all species of animals) · transmission: bite or lick of rabid animal · death if symptoms develop (mortality 100% ) · virus initially multiplies in muscle cells, then travels up nerves to CNS, causes encephalitis ↳ muscles affected, may drown from drinking water · incubation period 30-50 days or up to a year · symptoms: sore throat, headache, fever, discomfort at site, muscle spasms and convulsions · if bitten: immediately wash wound with soap and water, then get medical help ↳ RIG (rabies immunoglobulin) and inactivated vaccine West Nile Virus (WNV) · family: flaviviridae ↳ small enveloped RNA virus · virus inhabits birds, mosquitoes bite bird then transfer to human "accidental infection" · most cases asymptomatic or mild · mortality only in elderly and immunocompromised Most Common Birds: · if symptomatic: fever, headache, body aches, +/- rash, swollen lymph glands · ravens · symptoms 3-15 days after bite of rector ↳ development of encephaliths/meningitis very rare · long term neurological effects in 50% of WNV neurological syndrome · complications: ↳ in elderly with pre-existing chronic conditions and immunocompromised · crows · jay · magpie ↳ rapid onset: severe headache, high fever, stiff neck, vomiting, drowsiness, confusion, muscle weakness, coma ↳ meningitis or encephalitis ↳ polio-like paralysis syndrome · transmission: mosquitoes after biting bird then human ↳ not transmitted human-human (unless blood transfusion) · prevention: avoid mosquito bites, use DEET containing repellents · treatment: Supportive treatment, no vaccine or antiviral yet (mutates quickly) Culex mosquito Prion Disease Human Diseases: TSE · protein misfolding disease ↳ self protein becomes changed and nonfunctional · examples: ↳ mad cow disease (BSE, bovine spongiform encephalitis) ↳ scrapie in sheep ↳ kuru in N. Guinea (Cannibalism) · transmissable spongiform encephalitis · kuru (cannibalism) · Creutzfelt-Jacob Syndrome (CJD) and vCJD · Gerstmann-Straussler Scheinker ↳ CJD, vCJD in humans syndrome ↳ fatal familial insomnia · prions affect the brain and Spinal cord, resulting in accumulation of · fatal familial insomnia "amyloid fibers" and large holes in brain tissue (filled with fat) BSE: · scrapie in sheep and goats · mink, mule, deer, elk contract TSE (CWD) chronic wasting disease · cats in UK · incubation up to ten years in cattle vCJD: CJD: · hereditary or sporadic · 5% iatrogenic (transmitted from surgical instrument or natural growth hormone) · lifespan ~3 months from diagnosis · affects younger patients around age 29 (instead of 65) · longer duration of illness: 14 months to death · one of first characteristics is dementia