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Meningitis by huanghengdong


                                                            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

                                                            - 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

                                                            - 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

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
     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
        Ataxia                  Possible
  Visual field deficit          Possible
 Personality Changes                                        Yes
  ↓Consciousness                                            Yes
     Hemiparesis                                                                 Yes (later)
    Papilloedema                                                                   <50%
    Radiculopathy                                                                                           Yes
   Motor/sensory                                                                                       Yes ↑ paralysis
   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-
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
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 +

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