Meningitis Definition
inflammation of the meninges, defined by an abnormal number of WBC in the cerebrospinal fluid
Acute
- onset within hours to day.
- viruses, bacteria
Chronic
- onset within weeks to months
- spirochetes, mycobacteria, fungi
Epiemiology
Viruses:
-most prevalent about 30,000-75,000 cases/year in US
-most are enteroviruses (resolves spontaneously with or without specific treatment)
-usually a self-limited disease
Bacteria:
-approximately 4000 cases and 500 deaths per year in US
-higher incidence and mortality in the developing world
Stretococcus Pneumoniae Meningitis
- most common etiologic agent in US (58% of cases)
- mortality of 16-26%
- associated with other suppurative foci of infection:
- pneumonia (25%)
- otitis media or mastoiditis (30%)
- sinusitis (10-15%)
- endocarditis (<5%)
- head trauma with CSF leak (10%)
Neisseria Meningitidis Meningitis
- affects children and young adults; mortality 3-13%
- serogroups A, B, C, Y and W135
- epidemics usually caused by serogroups A and C
- serogroup B in recent outbreaks (universities)
- predisposition in those with congential deficiencies in terminal complement components (C5-C8, and perhaps C9) and properdin deficiencies
Streptococcus agalactiae meningitis
- important etiologic agent in neonates; mortality 7-27%
- early-onset septicemia (life-threatening infection) associated with prematurity, premature rupture of membranes, low birth weight
- late onset meningitis (> 7 days after birth)
- disease in adults less common
- infants can become infected in childbirth
Listeria monocytogenes meningitis
- rare cause in US (3%); mortality 15-29%
- outbreaks associated with consumption of contaminated cole slaw, raw vegetables, milk, cheese, processed meats
- common in neonates
- disease in adults associated with:
- elderly
- malignancy
- diabetes mellitus
- alcoholism
- immune suppression (primarily young and old)
Haemophilus influenzae meningitis
- causes 7% of cases in US; mortality 3-6%
- capsular type b strains were in >90% of serious infections
- concurrent pharyngitis or otitis media in >50%
- previously in children <6 years of age associated with:
- sickle cell disease
- diabetes mellitus
- pneumonia
- immune deficiency
- alcoholism
- head trauma with csf leak
incidence of bacterial meningitis in the US has
decreased over the decades
conjugate vaccines
uses an antigen. it is covalently bonded to a carrier protein and this allows it to be presented on an MHC molecule. the T cell is then able to recognize the carrier protein and activate the B cells which produce the antibodies.
conjugate vaccines against meningeal pathogens
haemophilus influenzae type b: -licensed in 1990 -decreased cases more than 90% streptococcus pneumoniae: -licensed in 2000 (7-valent vaccine) -13-valent vaccine neisseria meningitidis -licensed in 2005 -serogroups A, C, Y, and W135
Pathogenesis
- mucosal colonization and local invasion
- nasopharyngeal acquisition of a new organism
- fimbriae
- transport
- bacteremia
- bacterial capsule
- host defense mechanisms
- meningeal invasion
- they have cilia-like (fimbriae) or surface characteristics that allow them to attach to the mucosa and then they are transported in
blood-brain barrier
bacteria must either move through the interior of endothelial cells (transocytosis) or between them (paracellular)
- meningococci:paracellular
- pneumococci: transocytosis
pathophysiology
the bacteria can multiply unchecked once in the subarachnoid space. this causes separation of BBB or separation of tight junction and leads to neutrophils coming into the brain. now with these immunoglobulins, inflammation occurs where it should not.
- increased blood-brain barrier permeability
- subarachnoid space inflammation
- cerebral edema (excess accumulation of fluid in the intracellular or extracellular spaces of the brain)
- increased intracranial pressure
- altered cerebral blood flow
- neuronal injury
most prominent features
fever
headache
meningismus (stiff neck)
altered sensorium
What are the two signs used to help diagnose?
Kernig’s sign: resistance to hyperextension of the knee at a 90 degree angle of the hip
Brudzinski’s neck sign: laying flat, bringing the head forward and getting a reflex from the legs and knee thrust upward
Lumbar Puncture
diagnostically used to collect CSF
Complications of Lumbar Puncture
- headache
- painful paresthesias
- local bleeding or infection
- spinal subdural or epidural hematoma
- meningitis
- brain herniation
Prior to Lumbar Puncture, these things must be absent
- immunocompromised state
- history of CNS disease
- new onset seizure
- altered consciousness
- papilledema
- focal neurologic deficit
How many tubes are used for CSF Analysis and for what?
4 tubes. tube 1: cell count tube 2: glucose, protein tube 3: culture tube 4: cell count
Normal CSF Analysis
appearance: clear opening pressure: 70-180 mm H2O WBC: 0-5/mm3 (mononuclear) RBC: absent (if not traumatic) glucose: 50-80 mg/dL CSF/serum glucose: >0.6 protein: 15-45 mg/dL
CSF findings in bacterial meningitis
opening pressure: 200-500 mm H2O WBC count: 1000-5000/mm3 percentage of neutrophils: >= 80% protein: 100-500 mg/dL glucose: < 0.4
principles of antimicrobial therapy
penetration into CSF -penicillin 0.5-2% with uninflamed meningitis -penicillin 5% with inflamed meninges bacterial activity within purulent CSF -infection in area of impaired host defense -concentration exceeds MBC by 10-20 fold pharmacodynamics -time-dependent killing -concentration-dependent killing
