Cns Infections

Front 1

4 ways infections can get into the CNS:

Back 1

1. Hematogenous
2. Neural Route
3. Contiguous Spread
4. Direct Inoculation

Front 2

What's the most common route that infections use to reach the CNS?

What steps are often involved in developing meningitis? 12

Back 2

*Most cases are Hematogenous
1. Nasopharyngeal Colonization
2. Mucosal adherence and IgA proteases
3. Breakdown of epithelial cell tight junctions
4. Sloughing of ciliated cells and ciliostasis
5. Organisms preferentially invade nonciliated cells
7. Multiplication of organisms
8. Invade epithelium via intracellular and intercellular
9. Enter submucosa
10. Enter bloodstream
11. Cross BBB
12. Meningitis           

Front 3

So how do bugs actually break through the BBB? 2 ways

Back 3

*Enter where there is a lack of tight junctions between endothelial cells- paracellular (e.g., meningococcus); this is via circumventricular organs.

*Direct infection of endothelial cells-move through the interior of the cells (e.g., viruses, S. pneumoniae, H.influenzae)

Front 4

Describe the Neural Route to CNS infection:
examples?

Back 4

*Peripheral nerves
Example: Rabies
*Virus Latency: Infection of ganglia
Example: HSV(reactivation)
*Olfactory Endings (nasal)
Example: Arbovirus, HSV (primary infection)

Front 5

Describe the Contiguous Spread/Direct Inoculation route to CNS infection:
examples?

Back 5

*Adjacent foci as sinusitis, otitis media (inner ear infection)
*Rupture of Brain Abscess
*Foreign body
*Skull fracture

Front 6

Immune disadvantages to the CNS?

What immune assets does it have?

Back 6

*Local immunodeficiency
-Low complement
-No immunoglobulins
*They use their immunologic surveillance
-Microglial cells
-Virchow-Robin spaces

Front 7

What happens to the BBB in a bad infection?

Back 7

*Increased permeability of the blood-brain barrier results in:
-Vasogenic edema
-Cerebrocortical hypoperfusion (‘low- flow’ state to the brain)
-Increased intracranial pressure

Front 8

Two types of meningitis?

Back 8

*Bacterial Meningitis (septic)
-Routine bacteria: streptococci, staphlococci, gram negatives
*Aseptic Meningitis
-Infectious
Viruses, mycobacteria, fungi, spirochetes
-Noninfectious Etiologies
Autoimmune, drug induced, neoplasm, subarachnoid hemmorhage

Front 9

Agents of meningitis according to age group:

Back 9

<1mo compared to >60 yr

Front 10

Describe the age-related specificity of meningitis:

Back 10

*Birth to 3 mos: group B streptococcus, E. Coli, Listeria monocytogenes
*3 mos to 5 yrs: N. meningitidis (meningococcus), S. pneumoniae, H. flu B
*5 yrs to 35 yrs: N. meningitidis, S. pneumoniae
*35-60 yrs: S. pneumoniae, N. meningitidis
*>60: S. pneumoniae, Listeria monocytogenes

Front 11

Epidemiology of community-acquired meningitis:

Back 11

*Age is an important risk factor
*Person-to-person spread via airborne droplets (close contact)
*Carriers >> meningitis cases (asymptomatic>>symptomatic)
*Crowding
-military, day-care centers, college dorms
*Chemoprophylaxis may be employed: Neisseria or H. flu B
*Risk assessment for exposure: Listeria

Front 12

Describe acquired meningitis:

Back 12

*Disease of neurosurgical patients (incidence 0.3-1.5% after surgical procedures)
*Bacteria
-gram negative bacilli (33%)
-streptococci (9%)
-S. aureus (9%)
-coagulase negative staphlococcus (9%)

Front 13

Describe acute meningitis:

Back 13

*Causative agents: Viral > Bacterial
*Onset over a few hours to a few days
*Quatrad: fever, headache, photophobia, stiff neck
*Altered mental state may be present (irritability, confusion, lethargy, coma)
*Vomiting may occur

Front 14

Describe subacute/chronic meningitis:

Back 14

*Fluctuating symptoms over weeks, months, years
*Causative agents:
-TB, syphilis, Cryptococcus
-Chronic viral (enteroviral) infections

Front 15

Clinical findings in meningitis:

Back 15

*Confusion, delerium, lethargy to coma
*Nausea, vomiting
*Photophobia
*Weakness, myalgias, sweating
*10-20% have cranial nerve palsies (IV, VI, VII)
*May have hemiparesis, other focal neurologic findings
*Seizures ( up to 40% of cases)
*K&B signs

Front 16

Poor prognostic indicators in meningitis:

Back 16

*Signs of increased intracranial pressure, bradycardia, hypertention, coma
*III nerve palsy -- poor prognosis

Front 17

Unique findings in meningococcemia:

Back 17

Front 18

With pneumococcal meningitis look for:

Back 18

*Pneumonia
*Otitis
*Sinusitis

Front 19

Clinical findings in neonates with meningitis:

Back 19

*meningismus and fever often absent—listless, irritable

Front 20

What's the initial work up for meningitis?

Back 20

*Suspect bacterial meningitis?
-Blood cultures (positive in 50-75% or cases), lumbar puncture (LP), then antibiotics
*CT prior to LP?
-IF >60yrs, history of CNS disease, immunocompromised, seizures, abnormal neurological exam
-Children: present with seizures more often than adults; risk of herniation is small-can sometimes feel for bulging fontanelle in kids <18mos

Front 21

Typical CSF fluid findings in bacterial vs aseptic meningitis:

Back 21

Front 22

Hallmarks of Bacterial Meningitis:

Back 22

*>5-10 wbc’s is abnormal (clean CSF should NOT contain neutrophils)
*increased protein
*↓ glucose
*Gram stain positive for bacteria in 60-90% of cases
*Rapid diagnostic tests: bacterial antigens in CSF – limited value, but use if pt was on antibiotics prior to LP.

Front 23

Utility of Gram Stain in assessing meningitis:

Back 23

*Likelihood of visualizing the bacterium on gram stain correlates with the CSF concentration of bacteria [>10(5) CFU/ml yield a gram stain result in 97% cases]
*Likelihood of having positive gram stain depends on bacteria:
-90% of cases by S. pneumoniae
-86% of cases by H. influenzae
-75% of cases by N. meningitidis
-50% of cases by gram negatives
-30% of cases by Listeria
*Yield 20% lower in cases pretreated with antibiotics
*Use cytospin techniques to increase yield

Front 24

Hallmarks of Viral Meningitis:

Back 24

*Hallmark is lymphocytic CSF pleocytosis
-In early clinical disease there may be a neutrophil predominance
*Culture often negative; find a specific etiology in < ½ of cases
*PCR testing has raised the odds of finding and etiology with:
-HSV (or other herpesviruses)
-Enterovirus

Front 25

Etiologies of Viral Meningitis:

Back 25

*Common
-Enterovirus (Coxsackie and Echovirus in summer/fall)
-Arbovirus (arthropod-borne-West Nile)
-HSV (generally HSV2)

*Uncommon
-Mumps, LCM, HIV

*Rare
-VZV, CMV and EBV, Influenza
-A and B, Parainfluenza, Measles, Rotavirus,
-Coronovirus, Parvovirus B19, HHV6

Front 26

Discuss significance of Enteroviruses in viral meningitis:

Back 26

*Encompass Coxsackie, echovirus, other non-poliovirus enteroviruses
*Causes 6-10% of cases of viral meningitis in the winter and spring despite being more common in late summer and fall
*Rash, diarrhea, and upper respiratory symptoms may also be present.

Front 27

What does the LP look like with enterovirus meningitis?

Back 27

*Spinal fluid: WBC <250 cells, a modest elevation in CSF protein and a normal glucose concentration
*2/3 of patients have a PMN predominance in the CSF when examined early in the course of the illness. THIS CAN BE TRICKY.
-Repeat LP after 12 to 24 hours, if performed, shows an evolution to a lymphocytic predominance.
*Diagnosis: PCR positive in up to 75%.

Front 28

DISCUSS Mollaret's Meningitis:

Back 28

*Recurrent, benign lymphocytic meningitis associated with herpesvirus
-Greater than three episodes of fever and meningismus lasting 2-5 days followed by spontaneous resolution
-Some patients have neurological manifestations (seizures, diplopia, cranial nerve abnormalities)
*Pathophysiology
-Dormant virus in sacral dorsal root ganglia reactivates, causing CSF inflammation

Front 29

Most common etiology of Mollaret's Meningitis:
Diagnosis?
Treatment?

Back 29

*Most common etiology: HSV-2
-Most presentations are not associated with concomitant genital lesions
-Occasionally can be HSV-1
-Pap stain of CSF with large granular plasma cells
*Diagnosis: PCR
*Treatment? Suppression with acyclovir
-Important: recurrent meningitis should have imaging as an MRI (CSF fistula or parameningeal focus)

Front 30

Treatment of bacterial meningitis with antibiotics:

Back 30

*IV antibiotics
-Entry into the CNS dependent on:
-Dose of drug (concentration relative to minimum bactericidal concentration)
-Protein binding
-Meningeal inflammation
*Use empiric antibiotic first and pick according to age and epidemiologic risk
*Adjust antibiotic based on sensitivity data

Front 31

Role of steroids in treating bacterial meningitis:

Back 31

*Inhibit cytokine production
*Attenuate effects of LPS
*May decrease cerebral edema, increased ICP, altered cerebral blood flow, cerebral vasculitis, neuronal injury

-There is a problem…the studies are varied!
*Not all placebo controlled
*Different antimicrobials (sometimes inadequate) were used
*Steroids administered at different times
*Patients had various levels of illness severity

*BOTTOM LINE: Corticosteroids have been demonstrated to decrease hearing loss in children with H. flu B meningitis
No definitive data on use with other pathogens

Front 32

Should you re-LP someone with Bacterial Meningitis?

Back 32

*Not routinely!
*If they have not responded clinically within 48 hours
*Neonate with gram negative infection (determines duration of antibiotic therapy)

Front 33

COMPLICATIONS OF BACTERIAL MENINGITIS:

Back 33

*Seizures
*Septic shock
*Disseminated intravascular coagulation (DIC)
*Subdural effusions (rarely empyema)
*Herniation of cerebral tissue as a result of increased ICP
*Focal neurologic deficits (vasculitis, infarctions, cortical necrosis)
*Hydrocephalus (obstruction of CSF flow--shunt helps)

Front 34

MORBIDITY AND MORTALITY FROM BACTERIAL MENINGITIS:

Back 34

*Mortality
<5% for H. influenzae
10% for meningococcus
20% for pneumococcus

*Morbidity
Kids who survive have 15-20% risk of significant
sequelae (mental retardation, deafness, perceptual
handicaps)

Front 35

Prevention of meningococcal and H. flu infection:

Back 35

*H. influenza B and Meningococcus: chemoprophylaxis
*Immunization indications:
1) H. influenza
*Infants >2mos
2) Meningococcus
*Age 11-before high school (age 15); At risk: college, microbiologists, US recruits, splenectomy, complement deficiency, travelers to countries, exposure during outbreak
3) S. Pneumococcus
*Infants > 2mos; all adults > 65, immunocompromised (including connective tissue diseases, DM, on steroids), CSF leaks, Chronic cardiac/respiratory issues

Front 36

Clinical presentation of encephalitis:

Back 36

*altered level of consciousness, lethargy
*hallucinations, confusion
*delirium, personality change, even psychosis
*seizures common
*Cranial nerve palsies, hemiparesis, ataxia may occur

Front 37

Diagnostic findings in encephalitis:

Back 37

*CSF pleocytosis (lymphocytic)
*CSF cultures usually negative
*Most common cause of viral encephalitis is Herpes virus
-PCR for HSV DNA is extremely sensitive
*CT/MRI/EEG may reveal focal areas of inflammation
-(e.g., HSV localizes to temporal lobes)
*Brain biopsy may be needed to elucidate diagnosis and to help determine treatment
*Prognosis varies based on etiology

Front 38

Etiologies of Acute Encephalitis:
viral and bacterial

Back 38

*Viral
-Common: HSV-1, arboviruses
-Less Common: Herpesviruses, HIV, Enteroviruses, Adenovirus, LCM, mumps, influenza, rabies

*Bacteria
-Borrelia burgdorferi (Lyme)
-Partially treated bacterial meningitis
-Parameningeal infection (epidural or dural based abscess)
-Mycobacterium tuberculosis
-Leptospira spp
-Brucella
-Mycoplasma pneumoniae

Front 39

Etiologies of Acute Encephalitis:
fungi and other

Back 39

*Fungi
-Endemic mycoses (Cryptococcus, Coccidiodes, Histoplamsa, Blastomyces)
-Candida spp

*Other
-Toxoplamsa gondii
-Autoimmune disorders
-Behcet’s sydrome
-Drugs
-Malignancy and paraneoplastic syndromes

Front 40

Pathophysiology of Brain Abscess:

Back 40

*Hematogenous spread of infection → gray-white junction (poor collateral circulation)
-More commonly multiple
-Distribution of Middle cerebral artery

*Contiguous spread
-Otitis Media: inferior temporal lobe and cerebellum
-Frontal or ethmoid sinuses: frontal lobes
-Dental infection: frontal lobes

*Direct inoculation from open head trauma

Front 41

What predisposes the brain to an abscess?

Back 41

*Predisposition
-Areas of ischemia or infarction are more vulnerable to infection (locus minoris resistenciae)
-Host factors: localized vascular disorders (R → L shunting, septic embolization)
-Virulence factors: capsules, focal suppuration from Streptococcus milleri group

Front 42

Most common bacterial organisms in brain abscess:

Back 42

*Streptococci, especially S. intermedius (S. milleri group)
*Staphylococci
*Gram- negatives
*Anaerobes (often mixed with streptococcus if oral source)

Front 43

Table 1 summarizing pre-disposing conditions for brain abscess:

Back 43

Front 44

Table 2 summarizing pre-disposing conditions for brain abscess:

Back 44

Front 45

Brain abscess symptoms:

Back 45

*Headache
*Focal neurologic findings
*Fever (only about 50% of patients)
*Nausea, vomiting, seizures (increased intracranial pressure)-25% of patients
*Acute meningismus with fever: Periventricular abscesses may rupture into the ventricles

Front 46

Back 46

*Mastoiditis with Intracranial Abscess
-petrous bone has eroded
-evolved from middle ear

Front 47

Diagnosis of brain abscess:

Back 47

*Diagnosis
-CT scan or MRI
-Needle aspiration with cultures

*Treatment
-Antimicrobial therapy with surgical drainage/excision (stereotactic needle aspiration)
-Use bactericidal drugs which penetrate the blood brain barrier well
-Mannitol, hyperventilation to decrease intracranial pressure
-Use 4-6 weeks of therapy

Front 48

Prognosis and mortality from brain abscesses:

Back 48

*Prognosis
-5-10% of brain abscesses recur after effective antibiotic treatment
->70% of survivors develop epilepsy

*Mortality
-5-10%
-Increases with:
Multiple lesions
Ventricular rupture
Deep abscesses
Older host