POM II - CNS Infxns - Exam 2

Meningitis

-an inflammatory disease of the leptomeninges

-abnormal amount of WBC in the CSF

-any infectious agent (bacterial, viral, mycobacterial, fungal, parasitic)

-inflammatory/noninfectious causes as well

acute

bacterial meningitis is usually ___________

Aseptic Meningitis

-negative CSF gram stain and culture

-viral (usually acute)

-mycobacterial (often subacute/chronic)

-fungal (often subacute/chronic)

-parasitic

-inflammatory/non-infectious

Meningitis - Pathophys

-colonization of skin, nasopharynx, respiratory, GI, or lower genital tracts

-invasion of bloodstream or direct contiguous spread

-survival in bloodstream

-entry into subarachnoid space

-once pathogen is past BBB, it is somewhat isolated from immune system and can continue to spread

Meningitis - Incidence/Etiology

-1.4 cases/100,000 in the US

-Pre-antibiotics, S. pneumoniae, and H. influenzae were virtually 100% fatal

-now <3-7% for H. influenzae and N. meningitidis

-20% for S. pneumoniae, even less w/ steroids

Group B strep

what is the usual microorganism for acute bacterial meningitis in infants <3 months?

ampicillin + cefotaxime

what is the standard therapy for acute bacterial meningitis in infants <3 months?

S. pneumoniae and N. meningitidis

what is the usual microorganism for acute bacterial meningitis in older infants/children?

S. pneumoniae and N. meningitidis

what is the usual microorganism for acute bacterial meningitis in adolescents/college-age?

S. pneumoniae and N. meningitidis

what is the usual microorganism for acute bacterial meningitis in 18-50 y/o?

Vanc + ceftriaxone

what is the standard therapy for acute bacterial meningitis in older infants, children, adolescents/college age, and 18-50 y/o?

S. pneumo, N. meningitidis, L. monocytogenes

what is the usual microorganism for acute bacterial meningitis in those over 50 y/o?

vanc + ampicillin + ceftriaxone

what is the standard therapy for acute bacterial meningitis in those over 50 y/o?

S. pneumo, L. monocytogenes, gram neg bacilli

what is the usual microorganism for acute bacterial meningitis in those with impaired cellular immunity?

vanc + ampicillin + cefepime

what is the standard therapy for acute bacterial meningitis in those with impaired cellular immunity?

S. pneumo, S. aureus, aerobic gram neg bacilli, coag-neg staph

what is the usual microorganisms for acute bacterial meningitis in post-surgical or post-traumatic patients?

vanc + cefepime

what is the standard therapy for acute bacterial meningitis in post-surgical or post-traumatic patients?

Chronic meningitis - Time course

>4 weeks with persistent, inflammatory response in CSF

Chronic Meningitis - Etiology

-infection, malignancy, autoimmune inflammatory disorders, chemical meningitis, parameningeal infections

-m/c pathogens are M. tuberculosis, atypical mycobacteria, fungi, and spirochetes

-up to 1/3 of pts may not be able to determine etiology

Chronic meningitis - Cardinal features

-persistent HA

-clinical signs of hydrocephalus

-cranial neuropathies

-radiculopathies

-cognitive or personality changes

Aseptic Meningitis

-acute community-acquired meningitis with a negative CSF gram stain and culture

-most commonly viral (enteroviruses, arboviruses, HSV)

-can also be mycobacteria, fungi, spirochetes, parameningeal infxn, meds, malignancies

N. meningitidis

what is the most common bacterial cause of meningitis in the college-aged patients who live in dorms?

Meningitis - S/S

-Classic Triad: fever, nuchal rigidity, headache

-(+) Kernig's and Brudzinski's

-papilledema

-focal neuro deficits - CN, motor, or sensory

-rash - petechiae, palpable purpura --> often assoc with N. meningitidis

Meningitis - Labs

-routine blood work can be unrevealing

-CBC w/ diff -- often, WBC count is elevated w/ left shift

-Two aerobic Blood Cx - often positive 50-90% of time

-serum electrolytes, BUN, Creatinine, Glucose

-Coag studies

-Procalcitonin, CRP, ESR

Meningitis - Lumbar Puncture

CSF gram stain (positive 60-90%) and culture (positive in over 90%)

Meningitis - CT First Indications

-immunocompromised state

-history of CNS disease

-new onset seizure (w/in one week of presentation)

-papilledema

-abn LOC

-focal neurologic deficit

Meningitis - CT purpose

-exclude mass lesion or increased ICP --> cerebral herniation during removal of large amounts of CSF w/ devastating consequences

-patients without CT scan indications should NOT undergo a CT scan as it is of no clinical benefit + delays therapy

Bacterial Meningitis - CSF Analysis

-opening pressure >200

-1000s WBC; neutrophilic pleocytosis

-protein level 100-500

-Glucose level <40

Viral Meningitis - CSF Analysis

-opening pressure >200

-100s WBC; lymphocytic pleocytosis

-protein level 15-200

-normal glucose

Fungal Meningitis - CSF analysis

-opening pressure >200

-100s WBCs; mononuclear pleocytosis

-protein level 15-200

-<40 glucose

TB Meningitis - CSF Analysis

-opening pressure >200

-100s WBCs; mononuclear pleocytosis

-protein level: 100-500

-Glucose <40

Meningitis - Abx Therapy

-H. influenzae - 7 days

-N. meningitidis - 3-7 days

-S. pneumoniae - 10-14 days

-L. monocytogenes - 14-21 days

-Gram neg bacilli - 21 days

Meningitis - Steroids

-dexamethasone 10 mg IV 15-20 min BEFORE or simultaneously w/ 1st dose

-continue q6hr for 4 days

-can stop if culture does not grow S. pneumoniae, N. meningitidis, or H. influenzae

Meningitis - Increased ICP Management

-hyperventilation, mannitol (25-50g IV bolus), drainage of CSF or IV catheter

-dexamethasone may also decrease cerebral edema

Increased ICP - Management

-blood cultures --> obtain immediately when suspected bacterial meningitis

-Dexamethasone --> 15-20 min BEFORE abx

-Empiric abx --> given without delay

-Acyclovir --> if s/s of encephalitis; crucial to not delay if HSV is possible

-Head CT --> only if indications

-LP --> if CT does NOT show Increased ICP

No Increased ICP - Management

-Blood Cx --> obtain immediately when suspect

-LP --> send CSF for gram stain + cultures

-Dexamethasone --> 15-20 min BEFORE abx

-Empiric Abx --> give abx without delay

-Acyclovir --> if s/s of encephalitis; crucial to not delay if HSV possible

Meningitis - Mortality Rate

-3-7% for meningitis caused by H. flu N. meningitidis, or Group B strep

-15% for L. monocytogenes

-20% for S. pneumo

Meningitis - Increased Mortality Risk

-decreased LOC on admission

-Onset of seizures w/in 24 hr of admission

-signs of increased ICP

-infancy or age >50

-comorbid conditions

-delay in initiation of treatment

Meningitis - Common sequelae

-decreased intellectual function

-memory impairment

-seizures

-hearing loss and dizziness

-gait disturbances

-transtentorial herniation

-metabolic derangement

-hyponatremia

-septic shock

-coma

-suppurative thrombophlebitis

Tuberculous Meningitis

-TB of CNS ~5% extrapulmonary cases in US

-caused by rupture of meningeal tuberculoma from pulmonary focus or miliary spread

-active TB or history of TB present in 75% of patients

-young children or immunosuppressed adults at higher risk

Tuberculous Meningitis - S/S

-gradual onset

-Prodromal (2-3 weeks): listlessness, irritability, anorexia, fever

-Meningitic: headache, vomiting, lethargy, confusion, nuchal rigidity

-Paralytic: convulsions, hemiparesis, coma; paresis of CN is a frequent finding

Tuberculous Meningitis - Dx

-LP

-smear infrequently shows AFB

-PCR has sensitivity of up to 80% and is preferred initial diagnostic test

-culture is diagnostic in up to 80% of cases - gold standard

Tuberculous Meningitis - complications

-seizures

-CN palsies

-stroke

-obstructive hydrocephalus w/ impaired cognitive function

-inflammatory exudate of basilar meninges and arteries

Tuberculous meningitis - Tx

-early therapy even if cx not positive

-Rifampin, isoniazid, and pyrazinamide all penetrate well into CSF

-ethambutol is more variable, but therapeutic concentrations can be achieved

-Dexamethasone 0.15 mg/kg IV or orally QID for 1-2 weeks, tapered over 5 weeks

few hours to days

what is the time course for acute bacterial meningitis and HSV meningoencephalitis?

days to weeks

what is the time course for other viral meningitis, cryptococcal meningitis, lyme dz, and RMSF?

over months

what is the time course for tuberculosis, coccidioides, and syphilis meningitis?

Encephalitis

-inflammation of the brain parenchyma - acute febrile illness

-about 20,000 cases per year

-in US, most common viral (enterovirus, HSV1, arthropod borne)

-less common: mumps, measles, VZV

Encephalitis

-cerebral function is often abnormal

-AMS

-motor or sensory deficits

-altered behavior and personality changes

-speech or movement disorder

Meningitis

-cerebral function is often normal

-uncomfortable

-lethargic

-distracted by HA, but cerebral function remains normal

Meningoencephalitis

both parenchymal and meningeal process w/ clinical features of both meningitis and encephalitis

Encephalitis - Dx

-LP --> CSF (unless increased ICP)

-CSF profile similar to viral meningitis

-CSF PCR is preferred over CSF culture for acute viral

-brain biopsy if unsure

Encephalitis - CSF Analysis

-lymphocytic pleocytosis

-mildly elevated protein

-normal glucose

-if >500 RBC in nontraumatic tap, may be indicative of punctate microhemorrhages seen with HSV

Encephalitis - Management

-may require ICU admission, monitor ICP, fluid restriction, avoidance of hypotonic IV solutions, fever suppression

-prophylactic anticonvulsants for seizures

-Due to AMS, risk for aspiration pneumonia, stasis ulcers, contractions, DVTs, infxn of indwelling lines and catheters

-HSV1 or VZV --> acyclovir 10 mg/kg q8h ASAP

Encephalitis - Complications

-nearly 80% have neurologic sequelae

-seizures, cognitive impairment, weakness, hyper- or hypokinetic movement disorders

-postinfectious encephalitis (autoimmune response)

-progressive multifocal leukoencephalopathy

-subacute sclerosing panencephalitis (usually measles)

Brain Abscess

-focal collection within brain parenchyma

-relatively uncommon

-etiology: hematogenous spread, direct/contiguous spread, head trauma

-Early lesion (1-2 weeks): localized edema, acute inflammation, no necrosis, cerebritis, poorly demarcated

-Later lesion (2-3 weeks): surrounded by fibrotic capsule, necrosis and liquefaction occur

Brain Abscess - Presentation

-HA, neck pain, AMS (altered mental status), N/V, papilledema

-focal neuro symptoms, seizures, +/- fever

-Cushing's Triad: bradycardia, irregular respiratory pattern, HTN (widened pulse pressure)

Brain Abscess - Dx

-CT/MRI, blood culture

-LP is CI because of high chance of increased ICP

-Serology as appropriate - CBC, BMP, Procalcitonin, ESR/CRP

-Bx/Culture of Lesion

Brain Abscess - Culture

-polymicrobial

-includes S. aureus, gram neg bacilli, streptococci, mouth anaerobes

Brain Abscess - Tx

-successful management usually requires abx and surgical drainage

-prolonged duration of abx therapy, 3-4 weeks or longer; 6-8 weeks if unable to drain

-Prophylactic anticonvulsants for at least 3 months

-steroids if increased ICP

vancomycin

if a brain abscess is positive for gram (+) or MRSA, what abx?

ceftazidime

if a brain abscess is positive for gram (-) or pseudomonas, what abx?

metronidazole

if a brain abscess is positive for anaerobes, what abx?

Brain Abscess - Prognosis

-mortality has decreased w/ development of increased neuroimaging techniques, procedures, and abx

-usually <15%

-significant sequelae: seizures, persisting weakness, aphasia, mental impairment in >=20% of survivors

Encephalitis

-diffuse brain inflammation

-acute onset (hours to days)

-early, prominent AMS

-focal deficits uncommon

-seizures common early

-variable HA or increased ICP

-diffuse edema +/- temporal lobe on imaging

-LP often performed

-Tx --> acyclovir

Brain Abscess

-focal, spare-occupying infxn

-subacute (days to weeks)

-mental status preserved early

-focal deficits common

-seizures common, often focal

-headache/increased ICP common

-ring enhancing lesion on imaging

-LP is contraindicated

-Tx --> IV abx + drainage

CNS Infxn Pathogens - HIV pt

-virtually all pts with HIV have some degree of NS involvement

-primary to pathogenic process of HIV

-secondary to opportunistic infxns/neoplasms

HIV CNS Infxn - CSF Analysis

-pleocytosis

-detection of viral RNA

-elevated protein

-anti-HIV Ab

Toxoplasma gondii

what is the most common cause of focal brain lesions in HIV patients?

cryptococcus neoformans

what is the most common cause of chronic meningitis in HIV patients?

JC virus

what is the most common cause of progressive multifocal leukoencephalopathy in HIV patients?

Cytomegalovirus

what is the most common cause of encephalitis and ventriculoencephalitis in HIV patients?

HSV

what is the most common cause of encephalitis in HIV patients?

VZV

what is the most common cause of meningitis/encephalitis in HIV patients?

Mycobacterium Tuberculosis

what is the most common cause of tuberculous meningitis/tuberculomas in HIV patients?

Treponema pallidum

what is the most common cause of neurosyphilis in HIV patients?

EBV

what is virus is associated with primary CNS lymphoma in HIV patients?

HIV Meningitis

-immune mediated disease

-occurs during primary HIV infxn or later stages

-HA, fever, photophobia

-CN palsies (V, VII, VIII) more common than other viral meningitides

HIV Meningitis - CSF

-lymphocytic pleocytosis

-mildly elevated protein

-normal glucose

-HIV RNA detectable

HIV Meningitis - Prognosis/Tx

-often self-limited

-improves with initiation of ART

Vacuolar Myelopathy

-common degeneration of spinal cord found in up to 1/2 AIDS patients at autopsy

-slowly progressive spastic paraparesis

-gait disturbance, urinary incontinence

-sensory ataxia

-resembles B12 deficiency

-CSF usually normal or mild protein elevation

Vacuolar Myelopathy - prognosis/tx

-no specific therapy

-partial stabilization with ART

-often slowly progressive - most die w/in 6 months of developing symptoms

AIDS Dementia Complex

-HIV-associated dementia or HIV encephalopathy

-subcortical dementia

-cognitive slowing

-memory impairment

-apathy, depression

-motor slowing, gait disturbance

AIDS Dementia Complex - CSF

-mild lymphocytosis

-mild increased protein

-elevated HIV RNA

AIDS dementia complex - Prognosis/Tx

-improves or stabilizes with ART

-progressive without treatment

HIV-associated cerebral vasculitis

-focal neurologic deficits

-headache

-stroke-like symptoms

-seizures

HIV-associated cerebral vasculitis - CSF

-lymphocytic pleocytosis

-elevated protein

-normal glucose

HIV-associated cerebral vasculitis - prognosis/tx

-treat underlying HIV

-immunosuppression in select cases

-variable prognosis

HIV meningitis

if a patient with HIV presents with HA + fever + mild meningismus + lymphocytic CSF, what should you think?

Vacuolar myelopathy

if a patient with HIV presents with spastic paraparesis + urinary symptoms + normal CSF, what should you think?

AIDS dementia complex

if a patient with HIV presents with subcortical dementia + slowed thinking + increased HIV RNA in CSF, what should you think?

HIV Cerebral Vasculitis

if a patient with HIV presents with focal deficits + stroke symptoms + inflammatory CSF, what should you think?

PNS Complications - HIV

-distal sensory polyneuropathy

-acute inflammatory demyelinating polyneuropathy

-Chronic Inflammatory demyelinating polyneuropathy

-mononeuritis multiplex

distal sensory polyneuropathy

-consequence of HIV or side effect of ART

-painful burning in feet/LE

-stocking-type sensory loss to pinprick, temperature, and touch sensation

-weakness of intrinsic foot muscles

acute inflammatory demyelinating polyneuropathy

-Guillain barre syndrome

-early in HIV course

-ascending weakness

Chronic Inflammatory demyelinating polyneuropathy

-progressive weakness

-areflexia

-minimal sensory changes

Mononeuritis Multiplex

-necrotizing arteritis of peripheral nerves

-AIDS

-asymmetric focal neuropathies

CD4 >500 - DDx Solitary Brain Lesion

-same as immunocompetent adults

-benign and malignant brain tumors

-brain metastases

-brain abscesses

CD4 200-500 - DDx Solitary Brain Lesion

-mostly same as immunocompetent adult unless:

-not taking ART or recently initiated ART

-existing or prior opportunistic infections

CD4 count <200

-opportunistic infxn, AIDS-associated tumors

-toxoplasmic encephalitis

-primary CNS lymphoma

-progressive multifocal leukoencephalopathy