Fast review of CNS InfectionsHusain AlawadhiConsultant intensivist, pulmonologist and Infectious disease.

Guideline in Progress :summer 2008"The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of AmericaComing soon

ACUTE CNS INFECTIONS1.Bacterial meningitis2.Meningoencephalitis3.Brain abscess4.Subdural empyema5.Epidural abscess6.Septic venous sinusthrombophlebitis

EtiologyPathogenesisMicrobiologyDiagnosisTreatmentComplication Prevention

ETILOGY

Mucrobiology by age

Figure 24-8

Bacterial MeningitisImportant Changes in EpidemiologyMarked decline in the occurrence of Hibing incidence of S. pneumo (50+% of cases in US)Shift from peds disease to adult diseaseing incidence of ATB-resistant organisms, esp. S. pneumoPCN resistance ~ 35% (15-20% high level)Ceph resistance 15-20% (5-10% high level)

Risk Factors for Drug-Resistant S. pneumoniae (DRSP)Extremes of ageRecent ATB RxSignificant comorbid diseaseHIV infection or other immunodeficiencyDay care or day care parent/sibRecent hospitalizationCongregate settings (Institutions, military)

VIRAL MENINGITIS/ENCEPHALITISEnteroviruses Polioviruses Coxsackieviruses Echoviruses

Togaviruses Eastern equine Western equine Venezuelan equine St. Louis Powasson California West NileHerpesviruses Herpes simplex Varicella-zoster Epstein Barr Cytomegalovirus

Myxo/paramyxoviruses Influenza/parainfluenzae Mumps Measles

Miscellaneous Adenoviruses LCM Rabies HIV

Rare parsitic meningitisThe most important are in the genera Naegleria and Acanthamoeba. Naegleria fowleri, the main protozoan causing primary amebic meningoencephalitis in humans, has been recovered from lakes, puddles, pools, ponds, rivers, sewage waters.

DIAGNOSIS

CSF: Some CatchesProtein least specificTB: early neutrophilic predominanceEncephalitis, RMSF, tick-borne illnesses: inc CSF WBCListeria: misread as contamination/diphtheroidsListeria: bacterial meningitis that can have significant encephalitis and abscess, and CSF with lymphocytes!RBCs that do not clear: SAH or HSV

CSF: More PearlsCorrection factors for traumatic tap

trauma and RBCs increase protein and with an increase in RBCs come an increase in WBCsTrue CSF protein = subtract 1 mg/dL protein for every 1000 RBC/mm3True WBC in CSF: actual WBC in CSF (WBC in blood x RBC in CSF)/ RBC in blood

Contraindications to LPAbsolute:Skin infection over sitePapilledema, focal neuro signs, MSRelative:Increased ICP without papilledemaSuspicion of mass lesionSpinal cord tumorSpinal epidural abscessBleeding diathesis or plts

CSF pressureNormal opening pressure in adults is 90~180mmH2O, 10~100mmH2O in children.

Elevated in :Congestive heart failureMeningitisSuperior vena cava syndromeCerebral edemaMass lesionDecreased InSpinal-subarachnoid blockDehydrationCirculatory collapseCSF leakage

Diagnostic Accuracy of Signs of Meningeal Irritation in Pts with Suspected Meningitis Sign Sens Spec PPV NPV +LR -LR Nuchal 30% 68% 26% 73% 0.94 1.02 rigidity Kernigs 5% 95% 27% 72% 0.97 1.0 Brudzin- 5% 95% 27% 72% 0.97 1.0 skis Thomas KE et al, CID 2002, 35:46-52

CSF Findings

CSF SMEARS & STAINSGmS + in 60-90% of pts with untreated bacterial meningitisWith prior ATB Rx, positivity of GmS decreases to 40-60%REMEMBER: + GmS = Heavy organism burden & worse prognosis

CCT Before LP in Patients with Suspected Meningitis301 pts with suspected meningitis; 235 (78%) had CCT prior to LPCCT abnormal in 56/235 (24%); 11 pts (5%) had evidence of mass effectFeatures associated with abnl CCT were age >60, immunocompromise, H/O CNS dz, H/O seizure w/in 7d, & selected neuro abnls

Hasbun, NEJM 2001;345:1727

Guidelines : Do CT before LP in the following cases Any immunocompromised patient.New ConvulsionPapillodemaAny previous CNS pathologyAbnormal Lovel of consciousnessFocal neurological deficitsAge > 65

BACTERIAL VS VIRAL MENINGITISPredictors of bacterial etiology:CSF glucose < 40CSF protein > 60CSF neutrophil count > 80%CSF WBC count > 100CSF: Serum glucose ratio < 0.23[Presence of any ONE of the above findingspredicts bacterial etiology with > 75% certainty]

BACTERIAL VS VIRAL MENINGITISPredictors of bacterial etiology:CSF glucose < 34CSF: Serum glucose ratio < 0.23CSF protein > 220CSF WBC count > 2000CSF neutrophil count > 1180[Presence of any ONE of the above findingspredicts bacterial etiology with > 99% certainty]

Strep Pneumoniae MeningitisNow most common cause (H flu rare)30-50% cases of bacterial meningitis in elderlyOtitis 30%, sinusitis 8%, pneumonia 18%Elderly more often have pneumonia (bad)Bad markers: older age, low platelets, dec CSF glucose, no otogenic focusVaccination: recommended in all over age 65Efficacy in elderly/immunocompromised NOT clearDecrease bacteremia/meningitis

ListeriaFood-borne outbreaksHerd animalsCommon, likely cause of mild GI illnesses Invasive disease with bacteremia Increased risk with depressed cellular immunity: pregnant women, elderly, AIDS, lymphoma, steroid use, transplant patients Small, anaerobic gm + baccillusLook like diphtheroids, contaminants Diphtheroids in CSF: listeria unless proven otherwise

Cerebritis, brain abscessConfusion, altered LOC, seizure, movementMortality 22% in older patients with CNS dz20% of all cases of bacterial meningitis in patients over age 60Brain abscess: 10% CNS infectionsConcomitant meningitis in 25-40% (rare with other causes of brain abscess

ER management of meningitis

TREATMENT

Empirical threapy

Specific therapy

Review: Van Der Beek et al, Lancet March 2004Systematic reviewAge> 16At least 1 fatalityJadad ScaleRandomization 0-2Double Blinding 01Withdrawls/Dropouts 0-1kkfsfaOutcomesMortalityNeurological deficitsOrganismS.PneumoN. MeningitidisOtherAdverse Events

Conclusion: Steroid therapy in all pts with suspected bacterial meningitisBenefit in studies reviewed are seen when dexamethasone is started with or soon after antibiotics

NEJM, 2006;354, 44-53

NEJM, 2006;354, 44-53

BACTERIAL MENINGITISDuration of ATB Rx Pathogen Duration of Rx (d) H. influenzae 7 N. meningitidis 7 S. pneumoniae 10-14 L. monocytogenes 14-21 Group B strep 14-21 GNRs 21 NEJM 1997;336:708

THE PATIENT WITH SUSPECTED CNS INFECTIONRole of Repetitive LPs1. Rarely indicated in proven bacterial meningitis unless clinical response not optimal or as expected, fever recurs, or infection is due to ATB resistant pathogen2.Essential in pts with aseptic meningitis syndromes to monitor course &/or response to empiric therapies3.Essential in pts with subacute/chronic meningitis of proven etiology to assess response to Rx4.Not routinely indicated at end-of-therapy for bacterial meningitis

The available evidence supports the use of adjunctive dexamethasone in infants and children with H. influenzae type b meningitis. ( 0.15 mg/kg every 6 h for 2-4 days)

Dexamethasone in adults with the adjunctive dexamethasone be administered to all adult patients with suspected or proven pneumococcal meningitis. ( 0.15 mg/kg every 6 h for 2-4 days)

FDA warning 9/11/2007Rocephin (ceftriaxone sodium) for Injection Potential risk associated with concomitant use of Rocephin with calcium or calcium-containing solutions or productsCases of fatal reactions with calcium-ceftriaxone precipitates in the lungs and kidneys in both term and premature neonates were reported.

COMPLICATIONS

Extradural Abscess

Extradural abscess, associated with osteomyelitis, complication of sinusitis or a surgical procedure. When the process occurs in the spinal epidural space, it may cause spinal cord compression and constitute a neurosurgical emergency.

subdural empyema.fungal infection of the skull bones or air sinuses can spread to the subdural space subdural empyema may produce a mass effect. thrombophlebitis may develop in the bridging veins that cross the subdural space, resulting in venous occlusion and infarction of the brain.

CLINICAL MANIFESTATIONSSPINAL EPIDURAL ABSCESSFour clinical stages have been described: Fever and focal back pain; Nerve root compression with nerve root pain; shooting pain Spinal cord compression with accompanying deficits in motor/sensory nerves, bowel/bladder sphincter function; Paralysis (respiratory compromise may also be present if the cervical cord is involved).

Armstrong, ID, Mosby inc,2000

PREVENTION

Meningitis- PreventionChemoprophylaxis for close contacts of index case if Neisseria; treat contacts less than 4 years of age if H. fluVaccinate all children, especially those at risk or those with aspleniaH. fluS. pneumo- 7 valent up to 2 years, then 23 valent vaccineNeisseria- quadrivalent vaccine (A, C, Y, W-135) for high risk patients (asplenia, college age, military) over 2 years of ageDoes not cover group B, which causes close to of cases in US

Ventricular shunt infections

Intraventricular dose for shunt infections

ENCEPHALITIS

EncephalitisViralHSVArbovirusesVZV, CMV, EBV, HIV, rabiesEnteroviruses

BacterialListeria monocytogenes

Tick-borne illnessesRMSF: Rickettsia rickettsiiSTARI: Borrelia lonestariLyme: Borrelia burgdorferiEhrlichiosis: Ehrlichia chaffoensis

HSV MeningitisK Tyler (USA)

CSF in HSV Encephalitis vs. MeningitisWBCs/mm3202 (2-667)484 (58-1888)*

HSV Encephalitis

2-4 cases/million people/yearAcute infection or more commonly reactivation of latent infection (trigeminal nerve ganglion)Characteristic site of damage: temporal lobeMRI findings of necrosis in temporal lobeNecrosis = RBC s on CSF! 30% Mortality with treatment70% mortality without treatment

Definition of Recurrent Meningitis>2 episodes meningitisSymptom-free intervalsNormal CSF between episodesMust be differentiated from chronic meningitisCulture + versus Aseptic

BRAIN ABSCESS

MICROBIOLOGY OF BRAIN ABSCESSAGENT FREQUENCY (%)Streptococci (S. intermedius, including S. anginosus)6070Bacteroides and Prevotella spp. 2040Enterobacteriaceae2333Staphylococcus aureus1015Fungi * 1015Streptococcus pneumoniae

Frontal abscesses

When to aspirate ?If single or multiple ring-enhancing lesions are found, the patient should be taken urgently to surgery. All lesions greater than 2.5 cm in diameter should be excised or stereotactically aspirated and specimens sent to the microbiology and pathology laboratories (see earlier paragraphs). For abscesses in the early cerebritis stage or when the abscesses are 2.5 cm in diameter or less, the largest lesion should be aspirated for diagnosis and organism identification

Empirical therapy of brain abscess

T. Gondii Encephalitis

Most Common PathogensOtitis media, mastoiditis StreptococciParanasal sinusitis Streptococci

Pulmonary infection Strep, ActionomycesDental Mixed, Bacteroides spp.CHD Strep

Penetrating/Post-crani S. aureus

HIV Toxoplasma gondiiTransplant Aspergillus, Candida

TREATMENT Aspiration Or Open DrainageEmpirical Combination Antimicrobial TherapyDuration: 6 to 8 wks IVProphylactic Anticonvulsant TherapyGlucocorticoids( Severe Edema & ICP ) Serial CT-Scan or MRI

EBM-1The underlying arachnoid and subarachnoid spaces are usually unaffected, but a largeWith treatment, including surgical drainage, resolution of the empyema occurs from the dural side, and if it is complete, a thickened dura may be the only residual finding. Symptoms include those referable to the source of the infection. In addition, most patients are febrile, with headache and neck stiffness, and, if untreated, may develop focal neurologic signs, lethargy, and coma. The CSF profile is similar to that seen in brain abscesses, because both are parameningeal infectious processes. If diagnosis and treatment are prompt, complete recovery is usual.