CM II Week 9 (CNS Infections)

meningitis definition and hallmark

- Inflammation of the leptomeninges (tissue surrounding the brain and spinal cord)

- Hallmark is abnormal WBC in the CSF

encephalitis definition and hallmark

- Inflammation of the brain parenchyma

- Hallmark is altered or depressed level of consciousness

explain the steps to acquiring bacterial meningitis from inoculation to brain

1. Colonization of mucus membranes

- Pathogens contain surface components that enhance colonization (fimbriae/pili)

2. Invasion of bloodstream

- Due to env't, host, genetic factors - i.e. smoking/alcohol abuse, immunosuppression

3. Survival in bloodstream

- Major meningeal pathogens possess a polysaccharide capsule which inhibits phagocytosis by neutrophils

4. Entry into subarachnoid space

- Facilitated by duration and degree of bacteremia

once in CSF what does the bacteria do? why?

rapid multiplication/inflammation:

- An area of impaired resistance

- Low complement concentration

- Low antibody concentration

Site of entry of S. auerus

bacteremia

skin

foreign body

Bacterial Meningitis - Sites of Entry:

Neisseria meningitidis

Listeria monocytogenes

Haemophilus influenzae

Staphylococcus epidermidis

Neisseria meningitidis - nasopharynx

Listeria monocytogenes - GI tract, placenta

Haemophilus influenzae - Nasopharynx

Staphylococcus epidermidis - Skin or foreign body

Bacterial Meningitis: Etiology by Age

Listeria = most concerning for neonate, elderly

Bacterial Meningitis: Etiology by Risk Factor

Immunocompromised state

S pneumoniae, L monocytogenes, N meningitidis, aerobic gram negative bacilli (Pseudomonas aeruginosa)

Bacterial Meningitis: Etiology by Risk Factor

Basilar skull fracture

S pneumoniae, H influenzae, group A beta-hemolytic streptococci

Bacterial Meningitis: Etiology by Risk Factor

Head trauma, post-neurosurgery

Staphylococcus aureus, coagulase negative staphylococci, aerobic gram-negative bacilli (Pseudomonas aeruginosa)

What is the most common agent of meningitis in the U.S.?

S. pneumoniae

Site of entry for S. pneumonia

Nasopharynx, URI, skull fracture

Pneumococcal Meningitis (S. pneumoniae) mortality and associations

•Mortality of 16-26%

Associated with other suppurative foci of infection:

- Pneumonia (25%)

- Otitis media or mastoiditis (30%)

- Sinusitis (10-15%)

- Endocarditis (<5%)

- Head trauma with CSF leak (10%)

Osler's Triad of pneumococcal infection

concomitant pneumonia, meningitis, and endocarditis

Meningococcal Meningitis (N. meningitidis)

epidemiology, acquisition

•Mostly children and young adults; mortality 3-13%

•Nasopharyngeal acquisition of infection

Those with congenital deficiencies in terminal complement components (C5-C8) have a predisposition for

Neisseria meningitides meningitis

congenital deficiencies in terminal complement components (C5-C8, and perhaps C9) is a risk factor bc they form the membrane attack complex (MAC) that normally attacks Neisseria to kill it...

if its deficient theres nothing to attack the pathogen = bad

listeria meningitis epidemiology

Rare cause of bacterial meningitis in US (2%, but ~20% of neonates)

mortality 15-29%

Disease in adults associated with:

Elderly

Alcoholism

Malignancy

Immune suppression

DM

Hepatic and renal disease

Iron overload

Collagen-vascular disorders

HIV infection

outbreaks of listeria meningitis are associated with

consumption of contaminated coleslaw, raw vegetables, milk, cheese, processed meats

Bacterial Meningitis: Clinical Manifestations

classic triad

- fever

- nuchal rigidity

- sudden onset (<24 hrs)

Bacterial Meningitis: Clinical Manifestations

presenting sx (in addition to triad)

•Severe Headache (84%)

•Fever (74%)

•Stiff neck (74%)

•GCS < 14 (71%)

•Nausea (62%)

•Less common: seizures, aphasia, hemi/monoparesis, coma, CN palsy, rash, papilledema

Nuchal rigidity

stiffness in cervical neck area; pts unable to put chin to chest

Budinski sign

Spontaneous flexion of hips during passive flexion of neck

Kernig sign (meningitis)

inability to fully extend the knees with hips flexed 90 degrees

clinical manifestations of N. meningitis

- Rash: petechiae, palpable purpura, purpura fulminans

- Myalgias

- shock/DIC

clinical symptoms of Listeria meningitis

- Seizure

- Focal Neuro deficits

- Rhombencephalitis (Triad sx: ataxia, CN palsy, nystagmus)

Bacterial Meningitis: Diagnosis

labs/tests

PE: Assess for meningeal inflammation

•Blood tests

•CBC: leukocytosis/left shift, leukopenia, thrombocytopenia

•Coagulation studies: Assess for DIC

•Chemistry: AG, hyponatremia

•Blood cultures

What test is diagnostic for meningitis?

CSF Studies/Cultures – Lumbar Puncture

precautions of LP

- Raised intracranial pressure

- Thrombocytopenia/bleeding risk

- Suspected spinal epidural abscess

Reasons for CT before LP

- Immunocompromised (HIV, chemo, transplant)

- h/o CNS lesion

- New seizure

- Papilledema

- Abnormal level of consciousness

- Focal neurologic deficit

Cerebrospinal fluid analysis

Hallmarks:

- high WBC ct (neutrophil predominance)

- low glucose (bacteria eat glucose)

- protein may be elevated

CSF gram stain results: Gram + diplococci

pneumococcus

CSF gram stain results: gram - diplococci

meningococcus

CSF gram stain results: small, pleomorphic, gram - coccobacillis

H. influenzae

CSF gram stain results: Gram + rods/coccobacillis

Listeria

organism that target infants <1 month

Group B strep & Listeria

Ampicillin/penicillin targets

Listeria

Organisms that target infants 1-3 months

GBS & Strep. Pneumoniae

Organisms that target infants 3mo.-50years

GBS

Strep. Pneumoniae

Organism that targets older than 50 yrs

Listeria

Meningitis treatment: Antibiotics used in <1 month

Ampicillin & Cefotaxime

Cefotaxime targets what bacteria

Group B Strep

Meningitis treatment: Antibiotics used < 1 month

Ampicillin + cefotaxime

Meningitis treatment: Antibiotics used in 1-3 months

Ampicillin/cefotaxime

OR

Ceftriaxone (CTX)

Meningitis treatment: Antibiotics used in 3 months - 50 yrs

Vancomycin + Third Generation Cephalosporin

Meningitis treatment: Antibiotics used in >50 years

Vancomycin

+

Ampicillin

+

Third Generation Cephalosporin

Meningitis treatment: Antibiotics used in Immunocompromised

Vancomycin + Ampicillin + Meropenem/Cefepime

Meningitis treatment: Antibiotics used in Basilar skull fracture

Vancomycin + 3rd generation cephalosporin

Meningitis treatment: Antibiotics used in Head Trauma/ Post Neurosurgery

Vancomycin + ceftazidime or cefepime or meropenem

Meningitis treatment: Antibiotics used in CSF shunt/drain

Vancomycin + ceftazidime or cefepime or meropenem

Bacterial Meningitis: Organism Specific Therapy

Streptococcus pneumoniae

Penicillin, 3rd generation cephalosporin, Vancomycin

Bacterial Meningitis: Organism Specific Therapy

Neisseria

3rd generation cephalosporin, penicillin/ampicillin if susceptible

Bacterial Meningitis: Organism Specific Therapy

Streptococcus agalactiae (GBS)

Ampicillin, Penicillin, 3rd generation cephalosporin

Bacterial Meningitis: Organism Specific Therapy

Listeria

Ampicillin or Penicillin

when would you add dexamethasone for bacterial meningitis?

Attenuates subarachnoid space inflammatory response resulting from antimicrobial-induced lysis:

- HIB and pneumococcal meningitis (kids)

- pneumococcal meningitis (adult)

Meningitis Prophylaxis

only needed for? goal?

•Only needed for Neisseria

•Goal: Eliminate nasopharyngeal carriage that could lead to infection

at risk individuals - who to target for Meningitis prophylaxis?

Close contact with index case

•Household members

•Close intimate contact

Health care members

•Suctioning

•Mouth to mouth resuscitation

Meningitis Prophylaxis regimen

•Rifampin 2x/d for 2 days

•Ciprofloxacin 1x

•Ceftriaxone IM X1 (pregnant)

Aseptic Meningitis

meningitis caused by nonbacterial organisms

•More common than bacterial

•Prognosis is much better than bacterial

•Short, benign, self-limited course

Leading cause of aseptic meningitis

other causes?

Enterovirus (most common in US)

•Viruses: Enterovirus (most common in US), Herpes viruses, Polio viruses, Mumps virus, Arboviruses, Measles, Rotavirus

•Spirochetes: Syphilis, Lyme

•Immunizations

•Drugs: NSAIDS, Sulfonamides, TMP-SMX, Immunosuppresives

Aspetic Meningitis: Clinical Manifestations

•Sick but clearly not bacterial meningitis

•Fever

•Stiff neck (mild)

•Photophobia

•Lymphadenopathy

•No petechial rash

Aseptic Meningitis: CSF Findings

Meningitis Sequela include?

Bacterial Meningitis:

•Mortality: Over 20%

•Morbidity: Hearing loss, Cognitive impairment, Seizures

Viral Meningitis:

•Mortality: less than 1% with the greatest mortality among the elderly and neonates

Encephalitis: Epidemiology

•20,000 cases annually/US

•10% in USA is attributed to Herpes simplex

•Most no etiology identified

Meningitis vs Encephalitis

in encephalitis there are abnormalities in brain function (altered mental status, motor/sensory deficits, changes in behavior, speech and movement)

Encephalitis Etiology

•Viral: ex. HSV, Arboviruses, West Nile Virus

•Autoimmune

•Medications

•Unknown

Encephalitis: Clinical Manifestations

•Acute onset of fever

•Headache

•Altered level of consciousness ***

•Behavioral and speech disturbances

•Neurologic signs: hemiparesis, cranial nerve palsies, seizures

HSV Encephalitis - epidemiology and where in parenchyma affected specifically?

•Biphasic age distribution

•Characteristic temporal lobe disease

•Focal neurological finding

symptoms of HSV encephalitis

fever, personality change, dysphasia, autonomic dysfunction

diagnostics for HSV encephalitis

•EEG: periodic lateralizing eliptiform discharges

•MRI

•CSF: lymphocytic meningitis, RBCs, pleiocytosis, normal 5-10% on initial evaluation; PCR, if negative repeat in 3-7 days

Treatment of HSV encephalitis

IV acyclovir

outcome of HSV encephalitis

•70% Mortality with no/ineffective treatment

•Mortality 20-30%, morbidity 50%

Herpesviruses and associated findings

VZV, EBV, HHV6, B virus, CMV

•Varicella-zoster virus: +/- rash, focal neurologic deficits and seizures

•EBV: Encephalitis +/- transverse myelitis

•HHV 6: immunocompromised/children

•B virus: primate bite/scratch

•CMV: immunocompromised/HIV

arbovirus encephalitis

•Viruses spread animal-animal by bite of an infected arthropod (commonly ticks/mosquitoes taking blood meal)

•Most asymptomatic or mildly symptomatic

arboviruses - severe disease risk especially in?

Severe disease: Risk in immunocompromised and elderly

• May have encephalitis or viral meningitis like picture

• Example - Japanese encephalitis and West Nile

Most common cause of epidemic encephalitis

west nile virus

most common cause of epidemic viral encephalitis in the United States

Route of transmission of west nile

•Bite of mosquitoes (Culex) infected with West Nile Virus

•Mosquitoes become infected when they feed on infected birds

•Humans are incidentally infected

West Nile Virus: Clinical Syndromes

Presentation

• mostly asymptomatic

• West Nile Fever: acute febrile flulike illness

• fever, HA, fatigue, anorexia, myalgias, amd lymphadenopathy.

• maculopapular rash of trunk/limbs

Severe WNV Disease (1%) in what populations

Severe WNV Disease (1%) usually older (>60)

•Meningitis

•Encephalitis/Meningoencephalitis

•Poliomyelitis-like flaccid paralysis

West Nile Virus: Diagnosis

•Serum IgM antibody (8-14 d of onset)

•CSF --> lymphocytic pleocytosis and elevated protein; glucose is normal

•CSF IgM (preferred for CNS infection)

•CSF PCR (<60% sensitivity)

•Neuroimaging

West Nile Virus: Treatment

Supportive

Powassan Virus transmission

tick vector

Powassan Virus symptoms

1-3 day prodrome of fevers, chills, malaise, somnolence, N/V

-->

CNS symptoms with confusion, coma, seizures, paresis, facial palsies, etc

Powassan Virus Diagnosis

Serum and CSF IgM testing

Powassan Virus treatment

supportive

Case Fataility: 10% with high incidence of neurologic dysfunction in survival

Other Arboviruses

•St. Louis encephalitis virus - mosquito vector

•Japanese encephalitis virus - most common mosquito vector encephalitis worldwide

•Tickborne encephalitis virus - Tick vector

•La Crosse virus- mosquito vector

•Eastern equine encephalitis virus - mosquito vector

CNS Infections: Key Points

•Meningitis is caused by the inflammation of leptomeninges due to bacterial, viral or non-infectious etiologies

•Encephalitis is caused by inflammation of the brain parenchyma and noted by altered or depressed level of consciousness

•Bacterial meningitis has a high rate of morbidity and mortality and requires immediate empiric treatment based on risk/age group while undergoing diagnostic work-up

•Most cause of encephalitis have no identified cause

•Among the causes of viral encephalitis - only HSV has an antiviral treatment, most other causes the treatment is supportive