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Microbiology F2014 > CNS infections > Flashcards

CNS infections Flashcards

1
Q

Bacterial meningitis

A
  • Neonates up to 2 mo: Strep, agalactiae, E. coli, Listeria monocytogenes
  • Infancy & child: Strep. Pneumonia, N. meningitides, H. influenza
  • Ado: N. meningitides, Strep. Pneumonia
  • 20-60 YO: Strep. Pneumonia, N. meningitides, Listeria monocytogenes, Gram –ve
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2
Q

CNS pathogens and assoc med conditions

A
  • S. pneumoniae: Alcoholism, skull fractures, myeloma, splenectomy
  • H. influenzae: Alcoholism, post splenectomy, hypogammaglobulinemia
  • N. meningitides: Post splenectomy, complement deficiency
  • L. monocytogenes: CM1 (centrocyte/-blast marker 1) defects (Hodgkin’s disease, steroid therapy), elderly
  • C. neoformans:AIDS, other CM1 defects
  • S. aureus: CSF shunts
  • Herpes B encephalitis: Monkey handlers or monkey bite
  • Meningococcal meningitis: Overcrowding
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3
Q

Meningitis & Encephalitis: CSF analysis

A

Opening Pressure
– Lateral decubitus position
– Normal pressure: 70-180 mm H2O

General Appearance of CSF

– Normal: clear, colorless

– Abnormal: cloudy/turbid (↑ WBC, ↑RBC, bacteria, protein)

Detailed Apperance of CSF

  • Yellow -> Blood breakdown products; Hyperbilirubinemia; CSF protein ≥150mg/dL (1.5g/L), >100,000 RBC/mm3
  • Orange -> Blood breakdown products; Xanthochromia
  • Pink -> Blood breakdown products
  • Green -> Hyperbilirubinemia, Purulent CSF
  • Brown -> Meningeal melanomatosis (Metastatic Melanoma)
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4
Q

Normal CSF values

A
  • WBC count: children & adults 0-5/mm3
    • 70% lymphocytes, 30% monocytes
    • neonates 32/mm3
  • RBC count:None
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5
Q

Streptococcal meningitis: Pathogenesis

A
  • *Pathogenesis:**
  • enzymes to cleave cell surface receptors
  • IgA proteases on membranes
  • Hyaluronate lyase: tears up BM
  • Pneumolysin: hole making

Sx

  • Rapid 1-2 days (or gradual)
  • Impaired consciousness common
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6
Q

Neisseria meningitidis

A

Neisseria meningitidis

  • RTI; Most commonly: children & young adults
  • Serotype B, C & Y endemic (US) bc Type B capsule not included in vaccine
  • Non-motile, Gram -ve diplococci
  • Oxidase+
  • encapsulated
  • Kidney-bean shaped
  • Fastidious
    • 5-10% CO2, (Chocolate agar, Modified Martin-Thayer agar)
    • Modified Martin-Thayer w antibiotics to select for N.meningitidis
    • uses Maltose & Glucose
  • Virulence:
    • Capsule (serogroups A, B, C, X, Y & W-135)
    • IgA protease: allows growth on mucosal surface
    • Pili
    • LOS (lipooligosacharide)
    • Fimbri w antigenic variation

Sx

  • Quick onset
  • Acute photophobia
  • Skin petechiae → ecchymoses/diffuse petechial rash -> DIC

C&C

  • hypovolemia
  • shock
  • Waterhouse-Friedrichson

Dx

  • Tumbler test: press tumbler on rash and N. meningitidis rash will not go away -> know these images
  • easily spread in college dorms
  • Pt w SCA and asplenic susceptible

Rx:

  • Ceftriaxone
  • Rifampin

Prevention: quadrivalent vaccine

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7
Q

Haemophilus influenzae: meningitis

A
  • 7% cases
  • Human carriage: 80% children, 20-50% adults (URT) – Many are encapsulated but not all serotypes

Etiopath

  • Non-motile, Gram –ve rods
  • Fastidious
  • NADP (V) & Haematin (X), (Chocolate agar) – Virulence:
  • Capsule (polyribitol phosphate)
    • Pili
    • LPS

Sx

  • Slower onset (meningococcal meningitis), 3-4d
  • Follows: nasopharyngitis, sinusitis or otitis media
  • 1/3 survivors – neurologic sequelae

**Prevention: **Hiberix vaccine

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8
Q

Listeria monocytogenes: meningitis

A
  • 8% cases (US)
    • – Infants - <1 mnth (10%)
    • – Adults >60y, alcoholics, cancer patients, renal transplant.
  • Mortality rate:15-29%
  • Serotypes: 1/2b & 4b (80% cases)
  • Food-borne

Etiopath

  • Gram +ve rod
  • Virulence:
    • Internalin A & B
    • Listeriolysin O
        • tears up membrane
        • allows to get out of phagocytes and into cell.

Clinical features:

  • – Subclinical-gastrointestinal like
  • – Neonatal
  • – Immunocompromised
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9
Q

Aerobic Gram-negative bacilli : meningitis

A
  • Klebsiella, E. coli, S. marcescens, P. aeruginosa
  • Head trauma/neurosurgery
  • Neonates: E. coli K1, common
    • – 50% Pregnant woman: rectum
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10
Q

Staphylococci: meningitis

A
  • Uncommon: Early postneurosurgical/post-trauma
  • Underlying conditions
    • – Diabetes mellitus
    • – Alcoholism
    • – Chronic renal failure (hemodialysis)
  • Hospital Acquired CNS infection: MRSA
  • CSF shunts: S. epidermidis
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11
Q

Treponema pallidum: meninigitis

A

Spirocheteal meningitis
– Similar presentation to aseptic meningitis (viral)

Pathogenesis:
- can pass thru tight junctions

Clinical neurosyphilis

  • – Syphilitic meningitis (0.3-2.4% untreated cases)
  • – Meningovascular syphilis
  • – Parenchymatous neurosyphilis
  • – Gummatous neurosyphilis (rare)
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12
Q

Borrelia burgdorferi: meningits

A
  • In 10-15% of untreated Lyme disease
  • 2-10 wks post erythema migrans
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13
Q

Viral meningitis

A
  • Most common (US): Enteroviruses
  • Others
    • – Mumps, Herpesvirus (including EBV, HSV, VZV), measles, & influenza
    • – Arboviruses
    • – Rare cases LCMV (lymphocytic choriomeningitis virus)

Etiopath

  • mucosal surface colonisation RTI/GIT -> viremia -> CNS invasion -> virus spread within CNS
  • Ex. human poliovirus receptor (hPVR) binding and transported retrograde on MT
  • Ex2. (Non-polio) Enteroviruses: picornavidiridae, echoviruses, coxsackieviruses, enterviruses
    • 85-95% all cases
    • Age:Infants & Young children (no previous exposure & immunity)
    • Adults (common)
    • Geographic consideration - Worldwide distribution
    • Seasonal consideration:
    • – Temperate climate: summer/fall (water)
    • – Tropical: year round (faecal-oral)

Sx

  • – Usually acute benign, self-limiting, monophasic
  • – Symptoms: cranial neuropathy
  • – raised intracranial pressure uncommon
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14
Q

Mumps viral meninigitis

A
  • Non-immunized population (meningoencephalitis) – 10-30% mumps patients
  • If No parotitis (40-50% mumps meningitis)
  • Benign & self-limiting
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15
Q

Herpes viral meningitis

A
  • HSV have been linked to recurrent Mollaret’s meningitis *USMLE*
    • characterized by sudden attacks of meninigitis sx that usually last for 2 to 7 days
  • Herpes simplex 1 & 2 (0.5-3% cases)
    • Post neonatal: Important to differentiate encephalitis from meningitis
    • Most common: HSV 2
      • 1o genital infection
      • 36% women, 13% men
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16
Q

Other viruses causing meningitis

A
  • Arboviruses (Arthropod-borne): Mainly encephalitis
  • Lymphocytic choriomeningitis virus (Rare)
    • Contact with rodents & excreta (hamsters, rats, mice)
    • Lab workers, pet owners, unhygienic housing conditions
  • HIV
    • 1o infection/already infected or silent -> can also cause meningitis during early phase of infection
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17
Q

Chronic meningitis

A
  • usually in immunocompromized host
  • Must be distinguished from recurrent aseptic meningitis or encephalitis
  • Symptoms: wax & wane (careful history)
  • Fungal causes: Cryptococcus & Histoplasma
  • Tubercular (M. tuberculosis)
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18
Q
A

Cryptocococcus neoformas (gattii): fungal meningitis

  • Most common fungal cause – Via inhalation
  • Immunosupressed & previously infected healthy – Mainly encephalitis
  • Diagnosis: india ink (capsule)
  • narrow-based budding
  • encapsulated yeast
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19
Q
A

Histoplasma capsulatum: fungal meningitis

  • Geographic location: Ohio & Mississippi river valley, Central America
  • Able to infect immunocompetent hosts as well
  • Immunosuppressed
    • – AIDS
    • – Solid organ transplants
  • Pulmonary symptoms(minimal/absent)
  • Diagnosis
    • – Histoplasma antigen (CSF)
    • – Cultures -ve
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20
Q

Coccidioides spp: fungal meningitis

A
  • Geographic location: Central & Southern Arizona + Central Valley of California
  • CA-pneumonia, Immunosuppressed individuals (AIDS)
  • Mold in nature
  • Yeast in tissue
  • Spherule with endospores
  • Diagnosis
    • – Eosinophils (CSF) Wright-Giemsa Stain
    • – Complement fixation test
      *
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21
Q

Blastomyces spp: fungal meningitis

A

Blastomyces Dermatitidis

  • Mold in nature
  • Organic debris, rotting wood
  • Characteristic morphology: Broad-based budding

Etiopath

  • Inhalation
  • Disseminates to skin
  • Yeast form in tissue-
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22
Q
A

Candida: fungal meningitis (rare)

  • – Neonatal ICU (use of IV catheters)
  • – Postneurosurgery
  • – Immunosuppressed
    • oral cavity, ears (infants), vagina, catheters
    • yeast form @ body temp
    • fungus @ RT
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23
Q

Fungal meningitis: preservative-free MPA (methylprednisolone actete) steroid injections from NECC

A
  • Exserophilum rostratum
  • Aspergillus fumigatis: black mold in bathrooms and ventilation systems
24
Q

M. Tb: chronic meningitis

A
  • most common cause of chronic menigitis
  • – Rupture in subarachnoid space
  • – Children (haematogenous disseminated tuberculosis): Rapid
  • – Adults: Indolent
25
Q

Encephalitis: general features

A
  • Inflammation of brain parenchyma
  • Syndrome similar to acute meningitis – Fever, headache, altered mental health
    • – Speech & behavioral disturbances
    • – Seizures & hemiparesis
  • Coexist: meningoencephalitis
    • – Fever, headache, altered mental health – Speech & behavioral disturbances
    • – Seizures & hemiparesis
  • Significant morbidity & mortality
    • – Viruses

Sx

  • Irritability
  • Altered personality
  • Drowsiness
  • Ataxia
  • Excessively brisk tendon reflexes
  • Encephalitis usually not severe unless caused by HSV
    • HSV-1 reactivation in immunocompromised state of DM (focal deficit), HSV-2 results in more global deficits
26
Q
A

HSV & HHV-6 encephalitisa affecting Temporal lobe & limbic

HSV-1 & 2

  • HSV-1 reactivation in immunocompromised state of DM (focal deficit), HSV-2 results in more global deficits.
  • S2 to S5 ganglion
  • Causes apoptosis of neuronal cells
  • Stress reactivates HSV-1
  • Secondary viremia allows viral access to CNS
27
Q
A

VZV vasculopathy: Multifocal haemorrhagic infarctions & demyelinating lesions

28
Q
A

WNV-induced encephalitis and damage to thalami and substantia nigra.

29
Q
A

Enterovirus induced encephalitis causing acute disseminated or postinfectious encephalomyelitis.

30
Q

Possible causes of viral encephalitis

A
  • Herpes viruses HSV-1, HSV-2, VZV, CMV, EBV, HHV6
  • Enteroviruses
  • Paramyxoviruses (measles, mumps) & Togavirus (rubella)
  • Rabies
  • Arboviruses: E.g., Japanese B encephalitis, St Louis encephalitis virus, West Nile encephalitis virus, Eastern, Western, and Venezuelan equine encephalitis virus, tick borne encephalitis viruses
  • Bunyaviruses: E.g., La Crosse strain of California virus
  • Reoviruses: E.g., Colorado tick fever virus
  • Arenaviruses: E.g., LCMV
31
Q

HSV-induced encephalitis

A
  • Most common: sporadic encephalitis
  • – 1/250,000 population/year
  • – 1250-2000 cases/year (US)
  • Immunocompetent adults: HSV-1 (90%)

Clinical features

  • – Incubation period uncertain: Rapid onset – several days
  • – Fever (90-100%)
  • – Altered consciousness (97-100%)
  • – Headache (70-81%)
32
Q

Other HHV-induced encephalitis

A

VZV
– Remember: latency – dorsal root ganglia
– Myelitis (immunocompetent focal)

CMV: most common cause of encephalitis in AIDS+
– AIDS (CD4+ T cell <50 cells/mm3) + organ transplant

• HHV-6
– Immunocompromised (allogenic bone marrow transplants)

33
Q

WNV-induced encephalitis

A
  • Flavivirus
  • horses and humans are dead end hosts
  • US: Most common epidemic
  • Distribution: Africa, Europe, Middle East, US
  • neuroinvasive disease (<1% & >60 years of age)
    • – Brain parenchymal involvement
    • – CSF: pleocytosis, ↑ protein, normal glucose
    • – MRI: thalamus, basal ganglia, brain stem

Sx: Poliomyelitis-like (acute flaccid paralysis)

  • – Motor neuron injury (anterior horn of spinal cord)
  • – Brain parenchymal involvement

Diagnosis

  • – WNV-specific IgM in CSF by ELISA
34
Q

St. Louis Encephalitis Virus

A
  • Flavivirus
  • Distribution: Canada, US, Central & Southern America
  • 1 in 300 infected individuals: symptomatic
    • <20 years (40% meningitis, 50% encephalitis)
    • >60 years (90% encephalitis)
    • CSF: pleocytosis, ↑ protein, normal glucose
  • MRI: normal, or substantia nigra

Dx
– Anti-SLEV IgM antibodies in serum or CSF

35
Q

Eastern Equine Encephalitis Virus

A
  • Alphavirus (Togaviridae family)
  • Distribution: US, Southern America, Caribbean
  • Humans are deadend hosts
  • Brain stem involvement
    • – Mortality rate 33% (50% >60 years of age)
    • – CSF: pleocytosis (neutrophil predominance (2/3)), ↑ protein, norm glucose, RBC’s common
    • – MRI: thalamus, basal ganglia, brain stem

Diagnosis
– EEE IgM antibodies in CSF by ELISA

36
Q

Western Equine Encephalitis (WEE) Virus

A
  • Alphavirus
  • Distribution: Western US, Western Canada, S. America
  • Febrile prodrome → encephalitis
    • – Mortality rate 4-10% (↑ infants & elderly)
    • – CSF: pleocytosis (lymphocytic), normal-↑ protein, normal glucose

Diagnosis
– WEE IgM antibodies in CSF or serum

37
Q

Venezuelan Equine Encephalitis Virus

A
  • Alphavirus
  • Distribution: Southern US, Central & S. America
  • Rare neurologic disease
    • CSF: pleocytosis (lymphocytic), ↑ protein, normal-↑ glucose

Diagnosis
– VEE IgM antibodies in CSF or serum

38
Q

California Encephalitis Group

A
  • Bunyaviridae
  • CaliforniaEncephalitis,LaCrosse,Jamestown Canyon & Tahyna viruses
  • Distribution: CEV, La Crosse & Jamestown – US; Tahyna - Russia
  • La Crosse: Mississippi & Ohio river basins

Sx: Focal neurologic disease
– Hemiparesis, aphasia, dysarthria, chorea
– CSF: pleocytosis (lymphocytic), ↑ protein, normal glucose

Diagnosis
– IgM antibodies in CSF or serum

39
Q

Japanese Encephalitis Virus

A
  • Flaviviridae
  • Distribution: Asia, Western Pacific, Australia
  • 1-2 wk incubation
    • – Altered consciousness & Seizures: (85% Children, 10% adults)

Sx: Focal neurologic disease

– Hemiparesis, aphasia, dysarthria, chorea

– CSF: pleocytosis (lymphocytic), mildly↑ protein, normal glucose

– MRI: normal

Diagnosis
– IgM antibodies in CSF by ELISA – PCR

40
Q

Colorado Tick Fever Virus

A
  • Reoviridae
  • Distribution:WesternUS&Canada(Mountains)
  • 0-2 wk incubation (3 days)
    • – Complications: encephalitis or meningitis (Children 5-10%)

Neurologicsigns/symptoms

– Nuchal rigidity, photophobia, mild altered mental state

– CSF: pleocytosis (mildly lymphocytic), normal-mildly↑ protein, normal glucose

Diagnosis
– IgM by ELISA

41
Q

Non-polio Enteroviruses-induced encephalitis

A
  • Aseptic meningitis, encephalitis, acute anterior poliomyelitis (muscle pain), acute cerebellar ataxia, optic neuritis, cranial neuritis
  • Neonates: sepsis-like (10% mortality)
  • Most Common
    • Enterovirus 71,
    • Echovirus 18: small non-enveloped linear single-stranded RNA virus that spreads by faecal-oral transmission in warmer months,
    • Coxsackieviruses
42
Q

Rabies virus

A
  • Rhabdoviridae
  • Zoonotic disease (infected animal bite)
  • 150 countries worldwide
  • mostly Asia & Africa – Developing countries: domestic & feral animals
    • – Developed countries: bats, skunks, racoons, foxes

Diagnosis

– Skin biopsy: Immunohistochemical staining - Rabies Ag

– Negri bodies: Intracytoplamsic inclusions in neurons

– Corneal smears – Rabies Ag

– Rabies virus neutralizing Ab – CSF or serum (unimmunized) Direct Ab Test

Treatment

  • Postexposure prophylaxis
  • Wash wounds: soap & water + providone-iodine – Vaccine
  • Human rabies immunoglobulin (HRIG)
  • Wash all wounds with soap and water
  • 1 dose of HRIG & 4 doses of vaccine (Days 1, 3, 7 & 14 + 2 boosters on Day 0 and 3)
  • HRIG: Administer majority in bite wound site
  • remainder IM in same limb (distant to vaccination site)
43
Q

Measles virus-induced encephalitis

A
  • 0.1% cases: acute postinfectious encephalitis
  • 20% mortality
  • SSPE: sub acute sclerosing panencephalitis
    • – Slow progression of symptoms
    • – Most 5-15 years post initial infection (but the post initial infection can range from 1 month to 27 years )
  • Immunization:
44
Q

Polio virus-induced encephalitis

A
  • RNA virus
  • Faecal-oral transmission
  • Pharyngeal spread (epidemics)

Sx

  • Inapparent-mild 90% cases
  • – Non-paralytic: Meningitis 8% cases (self-limiting) – Paralytic disease 1% cases
  • – Polio encephalitis: Rare
  • – Incubation 1-2 wks
  • – Infection & death anterior horn cells (grey matter)

Dx

  • – CSF: PMN early→lymphocytes, ↑protein, normal glucose
  • – CSF: RT-PCR
45
Q

CSF Shunt

A

Bacteria Etiology mostly:

– Staphylococci (epidermidis & aureus)

– Gram negative bacteria (E. coli, Klebsiella, Proteus & Pseudomonas)

– Streptococci

– Diphtheroids (Propionibacterium acnes)

– Anaerobes

– Mixed culture

Pathogenesis

  • – Retrograde infection
  • – Skin
  • – Haematogenous seeding
  • – Colonization at surgery
46
Q

Brain abscess

A

1. Direct extension from contiguous site (Most common, ~50%)

  • Focal, intracerebral infection – Fatality rate: 0-24%
  • Both bacterial and fungal causes
  • continguous infections (sinusitis, otitis media) most common

Causative agents

  • Streptococcus pneumoniae
  • Other aerobic & anaerobic streptococci
  • Haemophilus influenza
  • Staph. aureus
  • Clostridia from surgery

Etiopath

  • Sinusitis
  • Dental abscess
  • Otitis
  • Mastoiditis
  • Endovascular
  • Respiratory tract
  • Postoperative
  • Trauma

Symptoms:

  • Rapid but Subacute: less severe than acute, lasting longer
  • Recognition of predisposing conditions important (see fig. below)
  • Headache, Changes in mental status, Generalized seizure, nausea, vomiting, incr ICP

Dx

  • – CT scan
  • – Hypodense centre
  • – Peripheral uniform ring
  • – Brain oedema
47
Q

Subdural Empyema (SDE)

A
  • 15-20% localized cranial infections
  • Sinusitis: male:female (3:1)

Etiology

  • – Streptococci (25-45%)
  • – Staphylococci (10-15%)
  • – Enterobacteriacea (3-10%)
  • – Anaerobic bacteria (33%)
  • – Polymicrobial

**Sx: **Fever (↑39oC), headache

**Dx: **MRI showing high density interhemispheric fissure

48
Q

Epidural Abscess

A

– Less common (<2%)
– SDE often accompanies

**Etiology: **Similar to SDE

Clinical presentation: Similar to SDE

Diagnosis: MRI pachymeningeal enhancement, superficial area of diminished intensity

49
Q

Prion pathogenesis

A

– Normal cellular glycoprotein: PrPc (↑

50
Q

Amoebas affecting CNS

A
  • Entamoeba histolytica

– normally found in large intestine

– can become invasive (primarily liver)

  • Free-living Amoebas (see fig below)
51
Q

CASE: Brain biopsy showing Filamentous, branching gram positive rod, Weakly AFB +

A
  • Actinomyces
  • Nocardia

Athas lecture 73

52
Q

Nocardia

A
  • Aerobe
  • Partially AFB +
  • Catalase +
  • Urease +
  • Found in soil
    • filamentous rod
  • Ubiquitous in the environment
  • AFB due to Mycolic acids in cell wall
  • Delayed up to 7 days
  • Colonies appear dry, waxy, white, or pigmented; beaded apperance

Clinical illness in immunocompromised:

  • Skin
  • Lung – patient likely had Nocardia pneumonia
  • CNS
  • Indolent course
    • Cough
    • Skin nodules
    • CNS symptoms when lesion enlarges
53
Q

Actinomyces israeli

A
  • Gram +ve filamentous rod
  • Anaerobe
  • AFB –
  • Respiratory/GI tract

Clinical illness:

  • Jaw/recent dental work, lung, intraabdominal infection
  • Fistula formation
  • formation of sinus tracts

Dx: Sulfur granules (yellow)

Rx: Penicillin G

54
Q

Progressive multifocal leukoencephalopathy

A
  • Causative agent: JC virus
  • Demyelinating disease of white matter
  • Reactivation of virus when individual becomes immunosuppressed
  • HIV (CD4 <50 mm3), organ transplantation, chemotherapy

Clinical presentation

  • Ataxia
  • Cerebellar involvement
  • Visual disturbance
  • Cranial nerve or occipital lobe disease

Dx

  • Lumbar puncture:
  • “Bland” CSF
  • Detection of myelin basic protein
    • As result of demyelination
    • Also seen in multiple sclerosis
  • CSF JC virus PCR
  • ?Biopsy
  • MRI: Multiple nonenhancing lesions

Treatment: Reversal of immunosuppression & ARVs

55
Q

Ring enhancing brain lesions with mass effect/edema in individuals with advanced HIV

A
  • Lymphoma CD4 <50 mm3
    • EBV
  • Toxoplasmosis CD4 <100 mm3

Microbiology F2014 (36 decks)

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