Exit at Base of the Brain and Pierce Meninges to Exit

Cranial Nerves

- Exit at base of the brain and pierce meninges to exit

- CNI (olfactory)- contact w/ external environment

- CNII (Optic)- directly visualized; w/in SAS if ↑ ICP (papilledema)

- CNIII (oculomotor) passes under tentorium cerebella below temporal lobe and is compressed by intracranial herniation (presents as dilated pupil not reactive to light; ptosis, lateral deviation)

- CNVI(abducens)- longest tract, sensitive indicator of ↑ ICP (presents as failure to abduct the affected eye; ipsi)

- BBB- capillaries have tight junctions, no fenestrations, surrounded by foot processes; difficult for organisms to penetrate

CNS Infections- organisms enter via bloodstream, neuronal pathways, or direct inoculation

- Encephalitis- infection of brain parenchyma

- Meningitis- infection of leptomeninges; + parenchyma= meningoencephalitis; + SC= meningoencephalomyelitis

- Myelitis- infection of the SC

- Neuritis- infection of peripheral nerves

- Acute bacterial meningitis- infection of meninges by bacteria w clinical present w/in 24-48 hrs (CSF LEUKOCYTOSIS)

Intracranial abscess: abscess in brain parenychema, may or may not be associated w/ meningeal involvement

- 50%: contiguous foci, 25%: hematogenous dissemination, 10%: direct inoculation, 15%: primary abscess

- Pathogenesis:

- Frontal lobe: Sinuses, teeth, direct inoculation

- Temporal: otitis, mastoiditis, sphenoid sinusitis

- Cerebellum: otitis, astoiditis

- MCA circulation: hematogenous source for lung abscess, endocarditis

- Stages of Abscess formation- early cerebritis: 1-3 days; late cerebritis: 4-9 days: early capsule: 10-13 days; late capsule: >14 days

- Diagnose w/ MRI or CT scan w/ contrast (MRI very sensitive avoid LP

- Treatment: surgical drainage and management of increased ICP, search for source, culture abscess for everything except viruses; empiric ATB: metronidazole + 3rd gen ceph + nafcillin or vancomycin Encephalitis- inflammation of the brain, characterized by alteration in consciousness

- Many non-infectious disease: drug rxns, vasculitis

- Infectious is due to viral infection (bacteria, fungus, tubercular less common)

- Togavirus: EEE, WEE, VEE

- Flavi: SLE, West Nile

- Enteroviruses - Paramyxo- measles (rare)

- Rabies - Herpes: HSV 1, 2 and VZV (only treatable)

- Pathogenesis: Hematogenous (viral, rickettsia, bac, fungi, TB), Retrograde (rabies, VZV), olfactory nerves (virus)

- Diagnosis: EEG- slowing, MRI in HSV encephalitis shows temporal lobe involvement (PCR), LP w/ mild pleocytosis

- Treatment: acyclovir effective for HSV1, 2, VZV (always give, in case of false negative); supportive care

Subdural Empyema- pyogenic infection of space between dura and arachnoid

- Subdural space is crossed by small veins (emissary vessels); organisms reach subdural space this way or direct extension of osteomylitis of the skull

- Source: 50-80% frontal or ethmoid sinusitis; 10-20% otitis media/mastoiditis; 5% hematogenous dissemination

- Bacteriology: Polymicrobic infections are common: aerobic strep, staph, S. pneumo, H, inf, anaerobes, GNR

- 4:1 male to female; usually in 2nd or 3rd decade of life

- Diagnosis: MRI, very sensitive (diagnostic); CT scans will miss some; don’t do LP!

- Treatment: neurosurgery for burr holes or craniotomy; management of ↑ iCP (dexamethasone), culture of empyema fluid; simultaneous debridement of sinuses, mastoid, ear

- Treatment AB: min of 3 wks- cover anaerobes, GNR, GPC (metronidazole+cefriaxone+nafcillin or vancomycin

- Prognosis- 75% mortality if comatose, almost half develop seizures for life

Epidural abscess- located between bone and dura mater

- Intracranial epidural abscess- spills over into subdural space and forms subdural empyema too

- Treat/diagnosis same as subdural empyema

- Spinal epidural abscess- in spinal canal, epidural space-fat filled w/o emissary vessels, allows longitudinal spread

- Bacteria enter epidural space by direct extension (vertebral osteomyelitis) or hematogenous dissemin.

- Less often polymicrobial (S. aureus 60-90%, then streptococci, anaerobes, GNRs)

- Diagnosis: MRI, myelogram can visualize cord and look for compression, Blood cultures +, SED ↑

- Treatment: immediate surgical drainage; cover s. aureus, GNR and anaerobes pending cultures (Vanco+3rd gen ceph+metronidazole); prognosis if treated prior to paralysis is good

Abscess Intracranial Encephalitis Subdural Empyema Epidural Lesion Space occupying Rapidly expanding mass Focal deficit Yes (neuro) Yes (neuro) Yes (neuro) Yes (vertebral), spread/expand tenderness Fever <50% Yes Seizures Yes Yes Yes (later) Altered Mental Status Yes Yes Yes N/V Yes Yes Headache Yes Focal, later generalizes Ataxia Possible Visual field deficit Possible Personality Changes Yes ↓Consciousness Yes Hemiparesis Yes (later) Papilloedema <50% Radiculopathy Yes Motor/sensory Yes ↑ paralysis deficits Nuchal rigidity Yes Presentation of Acute Bacterial Meningitis

- Consider in patients w/ fever, neuologic symptoms, cerebral dysfunction

- Typical: HA, fever, lethargy, confusion, vomiting, stiff neck (varies); nuchal rigidity*

- Kernig’s (leg resistant to passive extension on inflammation)*

- brudzinski’s sign (flexion of neck causes pelvic thrust)*

- papilledema <1%

- *not good predictors

Pathogenesis of Meningitis- The outcome is Increased intracranial pressure

Nasopharyngeal colonization somehow get local invasion causing bactermia meningeal invasion replication SAS inflammation causes Increased BBB permeability (leads to vasogenic edema), cytotoxic edema, ↑ CSF outflow resistance (leads to hydrocephalus interstitial edema), and cerebral vasculitis and or infarction

Workup of Bacterial Meningitis

- CSF exam essential- Need to order WBC and DIFF, Glucose, Protein, Gram stain and Culture (special studies possible= hold last tube)

- Relative Contraindictation to LP (↑ ICP, platelet count <40,000, scoliosis, infected site over lumbar spine)

- To check ICP fast:

- Look at eyes, PERRL

- Look at optic disc to see if bulging (bad)

- Get them to follow finger w/ eyes (good= they can do it)

Treatment of Bacterial Meningitis

- If assessment for increased ICP is present you must obtain blood cultures, do empirical antimicrobial therapy CT scan of head if no mass lesion can do lumbar puncture

- If assessment for increased ICP is absent obtain blood cultures and perform lumbar puncture

- After LP- if consistent w/ bacterial meningitis then start treatment w/ dexamethasone and empirical antimicrobials by age if no positive gram stain and specific antimicrobials by agent if positive gram stain

- Cover commonly encountered pathogens: tx for 10-14 days

Cause Age Risk Vaccine Diagnosis Treatment

S. agalactiae 0-4 wks + bullet Amp or Pen G (gr. B) coccus E. coli 0-4 wks Neg rod 3rd gen ceph L. mono 0-4 wks, Neonates, pregnant women, elderly, + rod, Amp or Pen G >50 yr immune-compromise catalase + (trimeth-sulfa) H. influenza 4 wks- > 5 yo w/ sinusitis, otitis, epiglottis Type B type f Neg rod 3rd gen ceph 50 yrs pneumonia; Predisposing: DM, meningitis is ↑ ETOHism, asplenia, CSF leak, hypo- gammaglobenmia N. mening > 4 wks MAC complement defect (less fatal) A, C W135, Y; B Neg Amp or Pen G cause >50% infects diplococci S. pneumo > 4 wks #1 cause in 18-50 yo; w/ URTI, LRTI, Covers most + coccus Vanco+ 3rd gen endocarditis; Predisposing: see H. inf common serotypes ceph GNR > 50

Prime Bacteria Empirical treatment 0-4wks S. agalactiae, E. coli, L. monocytoes Amp+ 3rd gen ceph; or amp+AG 4wks-18 yrs H. inf, N. meningitides, S. pneumonia Vancomycin + 3rd gen ceph 18 yrs- 50 yrs H. inf, N. meningitides, S. pneumo Vancomycin + 3rd gen ceph 50 yrs L. monocytoes, N. meningitidies, S. pneumo, GNR Vancomycin + AG + 3rd gen ceph

Presentation of Acute Viral Meningitis

- Often aseptic meningitis

- Enteroviruses cause 80-85% of cases of viral meningitis; others include: arbovirus, herpes virus, HIV

Pathophysiology of Viral meningitis

- Muscosal colonization leads to viremia and virus crosses BBB (may travel along nerves)

- Virus enters SAS and spreads in the CSF inflammatory response specific for the virus (lymphocytes, Tcells)

Clinical Presentation of Viral meningitis

- Enterovirus in kids > 2 weeks old

- Sudden fever, frontal headache, photophobia, nuchal rigidity, and myalgias, d/v, anorexia, cough, sore throat

- Occurs more in summer months

- May be associated w/ enteroviral syndrome (classic rash, painful mouth vesicles)

- HSV 2 infection often associated w/ aseptic meningitis and signs of genital tract infections

- Initial episode of HIV may be associated w/ aseptic meningitis and AB may be negative

Treatment of Viral meningitis

- Enterovirus: consider use of gammaglobulin in extremely ill

- Herpes virus: acyclovir - HIV: consider triple drug therapy

Presentation of Chronic Meningitis

- Neurologic abnormalities or CSF abnormalities of > 4 wks duration

- Infections from: TB, nocardia, Cryptococcus, toxoplasmosis, syphilis, lyme disease, CMV

- Noninfectious causes: Behcet’s (autoimmune), carcinoma, vasculitis

- Often Insidious in onset: wax and wanes over weeks but w/ gradual neurologic decline

Diagnosis and Treatment of Chronic Meningitis

- Diagnostic workup is difficult: guide by history and PE plus lumbar punctures

- Treatment is guided by most likely initial diagnosis if the patient is critically ill or preferably by confirmation

CSF Findings

Bacterial Viral Fungal Tuberculosis WBC > 1000; PMNs <1000 (almost always <3,000); < 500; mononuclear < 1000; mononuclear lymphs Glucose < 45 or < 2/3 Normal Normal or low < 45 (abn. w/ AB) serum glucose (except HSV, LCM, mumps, EEE) Protein > 80 Mildly ↑ Protein >60 >>100 Grain stain + 80% of time negative negative AFB smear Culture + 80% of time Viral Culture difficult; PCR- HSV Special smears/culture Culture +