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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Normal CSF values

A
  • WBC count: children & adults 0-5/mm3
    • 70% lymphocytes, 30% monocytes
    • neonates 32/mm3
  • RBC count:None
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Borrelia burgdorferi: meningits

A
  • In 10-15% of untreated Lyme disease
  • 2-10 wks post erythema migrans
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Mumps viral meninigitis

A
  • Non-immunized population (meningoencephalitis) – 10-30% mumps patients
  • If No parotitis (40-50% mumps meningitis)
  • Benign & self-limiting
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
      *
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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-
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
Encephalitis: general features
* 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
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
VZV vasculopathy: Multifocal haemorrhagic infarctions & demyelinating lesions
28
WNV-induced encephalitis and damage to thalami and substantia nigra.
29
Enterovirus induced encephalitis causing acute disseminated or postinfectious encephalomyelitis.
30
Possible causes of viral encephalitis
* 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
HSV-induced encephalitis
* 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
Other HHV-induced encephalitis
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
WNV-induced encephalitis
* 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
St. Louis Encephalitis Virus
* 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
Eastern Equine Encephalitis Virus
* 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
Western Equine Encephalitis (WEE) Virus
* 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
Venezuelan Equine Encephalitis Virus
* 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
California Encephalitis Group
* 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
Japanese Encephalitis Virus
* 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
Colorado Tick Fever Virus
* 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
Non-polio Enteroviruses-induced encephalitis
* 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
Rabies virus
* 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
Measles virus-induced encephalitis
* 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
Polio virus-induced encephalitis
* 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
CSF Shunt
**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
Brain abscess
* 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** #1. Direct extension from contiguous site (Most common, ~50%) * Sinusitis * Dental abscess * Otitis * Mastoiditis #2. Hematogenous from distant site * Endovascular * Respiratory tract #3. External * 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
Subdural Empyema (SDE)
* 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
Epidural Abscess
– 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
Prion pathogenesis
– Normal cellular glycoprotein: PrPc (↑
50
Amoebas affecting CNS
* Entamoeba histolytica – normally found in large intestine – can become invasive (primarily liver) * Free-living Amoebas (see fig below)
51
CASE: Brain biopsy showing Filamentous, branching gram positive rod, Weakly AFB +
* Actinomyces * Nocardia Athas lecture 73
52
Nocardia
* 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
Actinomyces israeli
* 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
Progressive multifocal leukoencephalopathy
* 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
Ring enhancing brain lesions with mass effect/edema in individuals with advanced HIV
* Lymphoma CD4 \<50 mm3 * EBV * Toxoplasmosis CD4 \<100 mm3