CNS Infections Flashcards
Acute Bacterial Meningitis - Delayed Treatment
- Meningococcal meningitis: kill in 6-12 hrs, patient may deteriorate in ER while undergoing diagnostic testing
- treat empirically & as soon as you suspect diagnosis
Acute Bacterial Meningitis - Pathogenesis
- blood born (bacteremia, sepsis)
- nearby infection (sinusitis, ear infection)
- CSF communication with outside (cranial trauma, neurosurgical procedure, myelomeningocele, spinal dermal sinus)
Acute Bacterial Meningitis - Pathophysiology
- bacterial surface (capsule, pili) penetrate endothelial cells & cross BBB
- meningeal inflammation
- vasculitis
- thrombophlebitis
- brain ischemia, infarction, & edema
- raised intracranial pressure
- brain herniation
- cardiovascular collapse
Exudative (Pus) Meningitis
- it’s not the pathogen that causes the CNS damage
- meningeal inflammation is responsible
- abx - lyse bacteria - wall fragments - cytokines interleukins, & inflammatory cascade - vasculitis & thrombophiebitis
-Dexamethasone inhibits inflammatory cascade & reduces CNS damage
Causes of Meningitis: Community Acquired
- streptococcus pneumoniae (pneumococcus)
- neisseria meningitidis (meningococcus)
Causes of Meningitis: Neonates
- Group B Strep
- E. coli
- Listeria
Causes of Meningitis: Immune Suppressed, Pregnancy, Elderly
-Listeria monocytogenes
Causes of Meningitis: Trauma, post-neurosurgical
- Straphylococcus aures
- Gram neg (E. coli)
- Pneumococcus
Meningococcal Meningitis
- colonizes nasopharynx in 5% “normal” pop.
- spread by respiratory droplets, close contact
- epidemics in military, boarding schools, (3 ft rule)
- Fluminant course: shock, Waterhouse-Friderichsen syndrome - hemorrhagic necrotic adrenals
Pneumococcal Meningitis
- alcoholics
- chronic otitis
- sinusitis, mastoiditis
- CSF leaks (head trauma)
- Pneumococcal pneumonia
- Sickle cell disease
- Asplenia
Listeria Meningitis
- up to 10% of all meningitis
- older patients above 50
- immune-suppressed: autoimmune, organ transplant, pregnant women, neonates & elderly
- Chronic illness: renal failure, liver disease
- Unpasteurized diary
- Meat counters, hot dogs
Clinical Presentation of Bacterial Meningitis in Infants?
- fever
- irritability
- vomiting
- high pitched cry
- lethargy
- convulsions
- bulging fontanel
Clinical Presentation of Bacterial Meningitis in Older Kids, Adults?
- URI prodrome, sore throat
- fever
- headache
- stiff neck
- vomiting
- lethargy & confusion
- cranial neuropathy
- seizures, coma
Physical Exam for Bacterial Meningitis?
- VItal Signs: high fever, shock (low BP, high pulse)
- Skin: petechiae, purpura, dermal sinus
- Cranial: trauma, CSF leak, otitis, sinusitis, mastoiditis, ventricular shunt
- Neck: stiff, Kerning’s & Brudzinski signs
- ausculate for pneumonia, endocarditis
- urinary tract infection
Meningismus
- neck stiffness, rigid & hard to move
- Kerning’s sign: + if knee can’t be fully extended when patient lies supine with hip flexed at 90 deg.
- Brudzinski sign: + when passive neck flexion causes reflex flexing of both legs & thighs
Aseptic Meningitis
- Viral
- Drug induced: Ibuprofen/NSAIDS, sulfa-containing abx (bactrim), isoniazid, immune modulation (OKT3, IVIG, Cyclocsporine)
- Craniopharyngioma (leakage of contents)
- Lead poisoning
- Parameningeal inflammation
- Viral encephalitis
- Fulminant TB or fungal meningitis
- Lyme disease, neurosyphilis, Rocky Mountain Spotted Fever
Labs for Bacterial Meningitis
-CBC & Diff.
-Electrolytes (Syndrome of Inappropriate Antidiuretic Hormone or SIADH, metabolic acidosis)
-PT, PTT, INR (DIC)
-Cultures: nasal nares, throat, sputum, skin lesions, urine, blood, CSF
-Gram stain of blood
-Blood bacterial PCR
-Much higher in bacterial meningitis than viral
Serum Procalcitonin (>2 ng/mL)
C-reactive protein (>40 mg/L)
-Cranial CT
-Lumbar Puncture
Lumbar Puncture Tests
-opening pressure, CBC/differential, Glucose, Protein, Latex agglutination, Gram Stain, Cultures for bacteria, TB, fungi & viruses, cryptococcal antigen, VDRL (veneral disease research lab), Special (PCR, IgM, IgG)
CSF Abnormalities
Purulent Bacterial: inc. WBC, neutrophils, 0-25 glucose, inc. protein
Non-purulent Bacterial: lymphs, 25-50 glucose, inc. protein
Treatment for Bacterial Meningitis
- don’t wait for diagnostic studies
- Steroids 1st: dexamethasone 10mg within 15 min of abx) and next 4 days (every 6 hrs), suppresses cytokines & inflammatory cascade induced by lysed cell components (IL-1, TNF)
- ABX: empirical: Vancomycin, 3rd or 4th gen cephalosporin or meropenem, Ampicillin (Listeria), Acyclovir (Herpes virus), Doxycycline (tics)
- Gram stain directed
Treat Bacterial meningitis
- fluids, electrolytes
- ventriculostomy for high intracrainal pressure & coma
- isolation
- prophylaxis for close contacts (rifampin)
Subacute Bacterial Endocarditis
- veggies, infection on heart valves, usually with gram + cocci, widespread septic embolism
- splinter hemorrhage
- Presentation: fever, delirium to coma. Possible meningeal signs, septic emboli to brain causes:
1. stroke
2. cerebritis to abscess (single/multiple)
3. Mycotic aneurysm
-streptococcus viridans 50%
Septic Emboli Cause:
- Splinter Hemorrhages
- Osler’s Nodes
- Janeway Lesions
- Roth’s spots (retinal hemorrhage with central clearing)
How to treat Subacute Bacterial Endocarditis
- antibiotics
- heart failure occurs, valve replacement may be necessary
- large cerebral abscesses must be drained
Clinical Diagnosis of Cerebral Abscess
- Headache (worse lying down, present upon awakening) “tumor headache”
- Papilledema & transient visual obscurations
- Seizures
- Focal neurological deficits
- Contract CT or MRI: ring enhancing mass with surrounding edema
- Risk factors: pulmonary AV shunt (hereditary hemorrhagic telangiectasia), sinusitis, sepsis
Spinal Epidural Abscess: Clinical Diagnosis
- Severe back pain, worse lying down, point tenderness
- Fever & Malaise
- Bowel & bladder dysfunction (incontinence or constipation) & male impotence
- Paraparesis or quadriparesis depending on level
- Sensory Level (absent pin prick sensation below level of involvement)
- High sed rate
- Elevated WBC with left shift
- Spinal MRI or CT myelogram
- Blood cultures
Spinal Epidural Abscess: Risk Factors
- staphylococcus is most common pathogen
1. Skin infection (IV drugs) - staphylococcus
2. Trauma (surgery) - staphylococcus
3. Osteomyelitis - staphyloccus
4. GU instrumentation - Gram - (elderly)
5. Sepsis
6. Often accompanied by local discitis & osteomyelitis
Spinal Epidural Abscess: Treatment
- High dose steroids
- Abx to cover staph, strep, & anaerobes
- Surgical drainage
Rocky Mountain Spotted Fever
- Rickettsia
- gram - obligate intracellular coccalbacillary rods
- attack vascular endothelia cells
- cause systemic vasculitis
- transmitted by ticks
Rocky Mountain Spotted Fever: Symptoms
- Fever, headache, flu-like symptoms 3-14 days after bite
- early petechial rash in distal extremities
- delirium - coma - death
- nromal CSF or mild inc. lymphocytes
- IgG and IgM (indirect immunofluorescence)
- Treatment: IV doxycycline
CNS Lyme Disease (Neuroborreliosis)
- spirochete transmitted by ticks (attached for 36 hrs)
- endemic in northeast United States
- Rare in Memphis
- 2-30 days: target skin rash (erythema migrans) at bite site
- weeks: flu-like sx, acute arthritis, heart block, headache, stiff neck, meningo-radiculitis, facial nerve paresis (often bilateral)
- months: encephalopathy, radiculopathy
- Diagnosed with Elisa, confirmed by Western blot
- Treat with IV ceftriaxone for 6-8 weeks
Syphilis (Treponemal pallidum)
- primary syphilis: painless genital chancre 3 weeks after infection
- secondary syphilis: 2-3 weeks after chancre, macular-papular rash on palms, soles & body, adenopathy, iridocyclitis, arthritis, meningitis or meningo-vascular stroke
- tertiary syphilis: if untreated, skin, osseous, cardiovascular, & neurologic complications occur after 15-20 yrs. (rare b/c of widely available treatment)
- immunocompromised (HIV) at higher risk for meningitis & stroke
Neurosyphilis Diagnosis
- Serum VDRL
- FTA (Fluorescent Treponemal ab)
- RPR (rapid plasma reagin)
- CSF VDRL
- CSF pleocytosis
Neurosyphilis Treatment
-high dose IV penicillin & monitor CSF for improvement in abnormalities every 6 months for 2 years in HIV+ patients
Chronic Meningitis: Clinical Symptoms
- Fever
- Headache
- Lethargy
- Poor appetite/ weight loss
- Cranial neuropathy
- Personality change
- Cognitive impairment
TB Meningitis - Pathophysiology
- primary lung (or GI) infection
- bacteremia
- bacterial lodge in brain (miliary TB)
- cellular immune system encapsulates foci
- years later, tubercle reactivation (meninges)
TB Meningitis - Pathology
- Meningitis: maximum at base of brain, communicating hydrocephalus common, cranial nerves trapped in exudate
- Vasculitis: thrombosis, multiple brain infarcts
- Tuberculoma: caseating granuloma, fibrous encapsulation
TB Meningitis - Diagnosis
- early clinical features: confusion, lethargy, low grade fever, headache, vomiting, stiff neck
- late: obtundation & coma, hemiparesis, cranial nerve palsies, seizures
- Ribosomal RNA PCR test (~3 days)
- Isolating TB from CSF is volume dep. (~3 weeks)
- Repeat LP (3 x day) for total 30 cc for culture
+ chest x-ray in 75%
+ PPD in 50%
CSF: elevated opening pressure, lymphocytic pleocytosis, modestly dec. glucose, high protein
CT or MRI detects tuberculoma in 10-20%
Risk factor: 3rd world, HIV homeless alcoholics
CNS Tuberculosis - Treatment
- Isoniazid, rifampin, pyrazinamide
- Streptomycin or Ethambutol
-corticosteroids: dexamethasone taper over 6 weeks
Viral Meningitis - Etiology
- more common than bacterial
- patients don’t appear extremely ill, are not encephalopathic
- 80% caused by enterovirus (ECHO, Coxsackie, enterovirus 71)
- 7% attributed to Mumps, even less to arborvirus, herpes simplex virus
- HSV2 (genital herpes) recurrent viral meningitis
- Herpes zoster, HIV
Viral Meningitis - Clinical
-fever & malaise, headache, neck stiffness, low back pain (overshadowed by headache)
- self-limiting, lasts 10-14 days
- if recurrent, probably due to Herpes simplex 2
Viral Meningitis - Diagnosis & Treatment
- raised CSF opening pressure (>180 mmH20)
- inc. CSF lymphocytes (some neutrophils)
- Normal CSF glucose, mild inc. in protein
- Neg. gram stain & bacterial culture
- Differential diagnosis same as aseptic meningitis
- CSF IgM, IgG Index (acute & one month later), PCR
Treatment: symptomatic
Early Diagnosis of HSV1 encephalitis
MRI
Viral Encephalitis - Etiology
30% arborvirus (St. Louis, West Nile)
23% enterovirus
27% Herpes Simplex Virus Type 1
Predominantly a disease of children & youth
Summer epidemics (arborviruses) transmitted by mosquitos
-Family epidemics via URI, GI flu (enterovirus)
Viral Encephalitis - Clinical Course
- the illness ranges from mild to fatal
1. Prodromal upper respiratory infection
2. Fever
3. Headache (meningismus - usually mild)
4. Lethargy
5. Confusion (parenchmal involvement)
6. Seizures
7. Stupor
8. Coma
Viral Encephalitis - Treatment & Prognosis
- outcome depends on specific virus, timely treatment, ICU care
- HSV-1 responds to acyclovir
- CMV responds to ganciclovir
- Poorer prognosis associated with California, La Cross, Eastern Europe
- Rabies is uniformly lethal
Herpes Zoster Virus
- latent HZV infection in sensory ganglia x years
- Activation: dorsal root ganglia to radiculitis (shingles), trigeminal ganglion, 1st division (ophthalmic Zoster)
- Zoster myelitis
- Zoster encephalitis
- Zoster vasculitis (giant cell angiitis of CNS & stroke)
HZV: Pathophysiology
- Risk factors: >50 yrs of age, immunosuppression (HIV, lymphoma)
- Reactivation of latent virus in a cranial nerve sensory ganglia or dorsal root ganglia
- Thoracic dermatomes most frequently involved
- Axonal transport to periphery (vesicular eruption in a dermatomal distribution)
- Pain & paresthesia precede vesicular eruption by 2-3 days
- Post-herpetic neurologia weeks later can be incapacitation
HZV: Treatment
-anti-herpetic drug acyclovir & steroids limit Zoster & prevents this major complication
HIV & Directly Related Neurologic Disease
- Acute aseptic meningitis
- chronic meningitis
- HIC dementia
- Vacuolar myelopathy
- Peripheral neuropathy
- Cranial neuropathy
- Inflammatory myopathy
- Vasculitis, Neoplasms (primary CNS lymphoma, Kaposi’s sarcoma)
- Nutritional & Metabolic Disorders
- Drug toxicity of anti-retroviral therapy
Opportunistic Infections
- toxoplasmosis is by far most frequent
- cryptococcal meningitis
- TB
- JC virus (progressive multifocal leukodystrophy)
