KIATTISAK

KITCHONG. MD Infect topic 21 FEB 2011

Contents
Meningi+s Encephali+s Brain abscess Subdural empyema

Introduc+on
The most devasta+ng of diseases Meningi>s = inamma+on of the meninges Encephali>s = inamma+on of the brain parenchyma Meningoencephali>s = inamma+on of both Myeli>s = inamma+on of spinal cord Brain abscess = Collec+ons of infec+ve and purulent material coalesce within the CNS

Introduc+on
Risks for CNS infec/ons
Extremes of age Immunocompromised Neurosurgery, dural defect Head Trauma IVDA VP shunt Cancer Chronic alcoholi/cirrhosis

Introduc+on
4 routes 1. hematogenous spread most common usually via arterial route can enter retrogradely (veins) 2. direct inocula>on most oPen is trauma+c iatrogenic (rare) via lumbar puncture

Introduc+on
3. local extension (secondary to established infec+ons) most oPen from mastoid and frontal sinuses, infected tooth 4. PNS into CNS viruses rabies herpes zoster

Introduc+on
Pa2erns of CNS infec/ons Meningeal : Fever + Meningismus - s> neck, photophobia, brudzinsky, Kernig+ headache Parenchymal : Fever + Focal neurological sign/symptoms, AOC Meningoparenchymal : Fever + Meningismus + Focal neuro s/s Other : slow viruses, prions, HIV/AIDS

leptomeninges

Meningi+s
Classied based on the >me course 1. acute meningi+s: hrs- 7 days 2. subacute meningits : 8 days- 4 wks 3. chronic meningi+s : > 4 wks 4. recurrent meningi+s : resolve completely between dis+nct episodes Between types , causes and approaches to management are oPen dierent

Acute Meningi+s

Diagnosis of acute meningi+s

Should undergo neuroimaging prior to LP Head trauma Immunocompromised state Recent seizure (within the last 7 days) Altera+on of consciousness Focal weakness, abnormal speech Abnormal visual elds or gaze paresis Inability to follow commands A history of : mass , focal infec+on, or stroke Emerg Med Clin N Am 38 (2008) 28

Diagnosis of acute meningi+s

CSF proles

Emerg Med Clin N Am 27 (2009) 89100

Diagnosis of acute meningi+s

Trauma/c LP No more than 1 wbc per 500 rbc are allowed Gram Stain 60 - 90% sensi+ve depending on source Gram stain sensi+vity decreases 20% w/ ATB Clues on gram stain .... Gram -ve intracellular diplococci = Meningococcus Gram + diplococci = Pneumococcus Gram + bacilli = Listeria Gram -ve coccobacilli = H.u Gram -ve bacilli = E.coli

Diagnosis of acute meningi+s

India Ink Staining Budding microorganism = cryptococcus NOTE: only 30% sensi+ve thus must do cryptococcal an+gen tes+ng Cultures 85% sensi+ve with bacterial meningi+s Sensi+vity < 50% with previous ATB Viral cultures detect 25% Fungal cultures detect 75% TB cultures detect 55%

Diagnosis of acute meningi+s

An/gen Detec/on Counter Immuno Electrophoresis (CIE) Useful with prior an+bio+cs cause it looks for an+gen not live micro-organism Can look for all common bacteria Latex Agglu+na+on More sensi+ve, faster, replacing CIE Meningococcus: 50-90%, Pneumococcus: 80% Hu 80% , Cryptococcal agglu+na+on: 90% HSV PCR & TB PCR

Meningi+s Bacterial Asep+c

Non-bacterial

Non-infec+ons

Acute bacterial meningi+s

Pathogens responsible for bacterial meningi/s

a J Infect Dis 1990;162(6):131622 b New Engl J Med 1997;337(14):9706

Acute bacterial meningi+s

Empiric an/bio/c regimens

Neurol Clin 28 (2010) 10611088

Acute bacterial meningi+s

Tunkel et al. CID 2004:39 (1 November)

Acute bacterial meningi+s

Delay in administra+on of an>bio>cs has been associated with worsening clinical outcomes 3-hour delay from +me of presenta+on to the hospital to an+bio+c was independently associated increase in 3-month case fatality Neuroimaging or CSF tes+ng, must not delay empiric an+bio+c therapy
Crit Care Med 2006;34(11):275865

Specic ATB regimens

Acute bacterial meningi+s

Neurol Clin 28 (2010) 10611088

Acute bacterial meningi+s

Tunkel et al. CID 2004:39 (1 November)

Nosocomial bacterial meningi+s

N Engl J Med 362;2 january 14, 2010

Nosocomial bacterial meningi+s

Dosage : normal renal and hepa+c func+on
Vancomycin 15 mg/kg q 8 -12 hrs to maintain serum trough conc. of 15- 20 g/ml CeUazidime 2 g every 8 hours Meropenem 2 g every 8 hours CeUriaxone 2 g every 12 hours severe allergy to penicillin or cephalosporins ciprooxacin, 400 mg every Engl J12 h62;2 january 14, 2010 N 8 - Med 3 ours

Nosocomial bacterial meningi+s

N Engl J Med 362;2 january 14, 2010

Suppor+ve Treatment
Fluid resuscita>on Hyponatraemia is present in over 50% of children with meningi+s , It is associated with adverse neurodevelopmental outcomes (SIADH eect) Evidence to support the use of iv full maintenance uid, in preference to restricted uid, in the rst 48 h in children in developing country seZngs
Cochrane Databaseof Systema/c Reviews 2005

Adjunc+ve therapy
Dexamethasone Animal studies: CSF pres, lactate, brain edema Given before or at +me of rst an+bio+c dose to decrease mortality Adults: dexamethasone 10 mg iv q 6 hr Children: data is in group with H.u, shown to decrease hearing complica+ons
NEJM Nov 2002

Adjunc+ve therapy
Cor+costeroids signicantly reduced hearing loss and neurological sequelae, but did not reduce overall mortality No benecial eect in low-income countries Reduced severe hearing loss in H. inuenzae (RR 0.34, 95% CI 0.20 to 0.59) and reduced mortality in S. pneumoniae meningi0s (RR 0.84, 95% CI 0.72 to 0.98)
The Cochrane Library 2010, Issue 9

Adjunc+ve therapy
Glycerol Hyperosmo+c compound to intracerebral P. Trial of dexamethasone, glycerol, or glycerol and dexamathasone in 654 children with bacterial meningi+s in La+n America No sta>s>cally signicant eect on death or deafness was seen in the treatment groups
Clin Infect Dis 2007; 45: 127786

Contact prophylaxis
H.u prophylaxis required only if there is non-immunized siblings or contacts > 25 hr/wk who 4 yrs old Rifampin 20 mg/kg (max 600mg) od X 4 days Meningococcus prophylaxis required for all close contacts such as household members, daycare, including adults; medical personel only necessary if in contact with mucosal secre>ons Only eradicates nasopharyngeal coloniza+on Rifampin 10 mg/kg (max 600mg) bid X 2 days CePriaxone im, or cipro are alterna+ves
The Sanford guide to an/microbial therapy 2003. 33rd edi/on

Complica+ons and sequelae of bacterial meningi+s

Focal neurologic decits Deafness/sensorineural hearing loss (most common in H inuenzae) Blindness Paralysis Paresis

Complica+ons and sequelae of bacterial meningi+s

CNS structural sequelae/complica/ons Hydrocephalus Brain abscess Subdural abscess Subdural eusion Subdural empyema Epidural abscess Cerebral thrombosis Cerebral vasculi+s

Meningi+s Bacterial Asep+c

Non-bacterial Viral Non-viral Common Systemic Diseases

Non-infec+ons Neoplas+c Drugs

NSAIDS SLE , Sjogrens IVIG

Non-viral Par+ally Treated Bacterial Atypical and nonpyogenic bacteria Parasite Fungal Syphillis Meningeal Inamma+on Caused by Adjacent Pyogenic Infec+ons

Lyme Disease

Asep+c meningi+s
Meningeal inamma+on not caused by an iden+able bacterial pathogen in the CSF Subacute onset : fever, headache, meningismus, photophobia CSF pleocytosis WBC 10-1000 bacterial smear and culture : nega+ve normal-mild elevated pro+en normal-mild depressed sugar
Neurol Clin 26 (2008) 635655

Asep+c meningi+s
Common Causes in general popula/on virus Bacteria enteroviruses Borrelia burgdorferi arboviruses Par+ally treated HSV-2 Parameningeal (sinusi+s, o++s, mastoidi+s)

Neurol Clin 26 (2008) 635655

Asep+c meningi+s
Uncommon Causes in general pop. virus bacteria mumps TB LCMV Leptospira spp HIV Mycoplasma pneumoniae HHV-6 Fungus
Neurol Clin 26 (2008) 635655

Asep+c meningi+s
Rare Causes in General popula/on virus bacteria HSV-1, EBV Brucella spp VZV , CMV inuenza A, B measles, pavovirus B19
Neurol Clin 26 (2008) 635655

Asep+c meningi+s
Management Rx causes Appropriate interven+ons include aggressive uid, electrolyte and pain management, and close observa+on for poten+al neurologic and neuroendocrine sequelae (seizures, brain edema, SIADH)
Neurol Clin 26 (2008) 635655

Asep+c meningi+s
An/viral therapies Not been shown to accelerate clinical recovery in arthropod-borne viruses, mumps virus, LCMV and Herpes Against enterovirus immune serum globulin and pleconaril Pleconaril only shortened the course of the illness in a subgroup of adults with EV meningi+s

Neurol Clin 26 (2008) 635655

Chronic meningi+s
More indolent , week month Presen+ng symptoms are headache, s+neck, and fever do not present with the complete clinical spectrum, symptoms are usually mild Focal neurologic decits and hydrocephalus develop lead to signicant basal cerebral inamma+on, manifested by CN palsies, vasculi+s of the circle of Willis, and CSF ourlow obstruc+on

Chronic meningi+s
TB , spirochetal, fungal, parasi+c, sarcoid, and neoplas+c meningi+des are capable of severe basal inamma>on Asymmetric, mul+focal limb and truncal radiculopathies with sensory, motor, and reex changes Cauda equina syndrome

Chronic meningi+s

Recurrent Meningi+s
Recurrent Pyogenic Meningi>s episodes of neutrophilic pleiocytosis typical S&S of acute bacterial meningi+s Most commonly this is due to CSF leak Anatomic communica+on between the subarachnoid and a nonsterile cavity or skin Nosocomial acute bacterial meningi+s

Recurrent Meningi+s
Recurrent Pyogenic Meningi>s Agammaglobulinemia or complement deciency : recurrent meningococcal meningi+s CSF rhinorrhea, a sample tested for B-2 transferrin The ini+al treatment approach is the same as for acute bacterial meningi+s Deni+ve treatment is repair of the CSF leak

Recurrent Meningi+s
Recurrent Asep/c Meningi/s Mollaret meningi+s mul+ple selfresolving episodes of lymphocy>c meningi>s usually present acutely with headache, fever, and neck s>ness, but focal neurologic decits or seizures may occur resolve over day and recurrent by month atypical monocytes, so-called Mollaret cells

Recurrent Meningi+s
Recurrent Asep/c Meningi/s HSV-2 has been the most commonly Most experts recommend acute or suppressive an>viral treatment in proven or suspected HSV-2 recurrent meningi+s Recurrent chemical meningi>s may occur with rupture of contents from an epidermoid or dermoid cyst, or from a craniopharyngioma (cholesterol crystals)

Tuberculous Meningi+s
Risk factors include emigra+on from developing countries, advanced age, alcoholism, immunosup. medica+ons, malignancy, and HIV Foci of mycobacteria in the subependymal lining of the brain and meninges serve as a source of slow dissemina>on within the CSF , so-called Rich foci
Infec+ons of the central nervous system. 3rd edi+on. Philadelphia: Lippincot, Williams, and Wilkins; 2004. p. 44159

Consensus TB meningi+s diagnosis

Clinical entry criteria Symptoms and signs of meningi+s including 1of the following: headache, irritability, vomi+ng, fever, neck s+ness, convulsions, focal neurological decits, altered consciousness, or lethargy

Lancet Infect Dis 2010;10: 803

Lancet Infect Dis 2010;10: 803

Denite TB meningi+s
Pa+ents should fulll criterion A or B: A) Clinical entry criteria + 1 of the following: AFB + , M. tuberculosis c/s + or commercial NAATs + in CSF B) AFB seen in histological changes consistent with TB in the brain or spinal cord with sugges+ve symptoms or signs and CSF changes, or visible meningi+s (on autopsy)

Lancet Infect Dis 2010;10: 803

Probable TB meningi+s
Clinical entry criteria + a total diagnos>c score 10 points (cerebral imaging is not available) or 12 points (cerebral imaging is available) plus exclusion of alterna+ve diagnoses At least 2 points should either come from CSF or cerebral imaging criteria

Lancet Infect Dis 2010;10: 803

Possible TB meningi+s
Clinical entry criteria + total diagnos>c score 69 points (cerebral imaging is not available) or 611 points (cerebral imaging is available) Plus exclusion of alterna+ve diagnoses Possible tuberculosis cannot be diagnosed or excluded without doing a lumbar puncture or cerebral imaging

Lancet Infect Dis 2010;10: 803

Diagnos+c score

Lancet Infect Dis 2010;10: 803

Lancet Infect Dis 2010;10: 803

Clinical stages
For prognosis and therapy Stage I : no focal neurologic signs or evidence of hydrocephalus Stage II : exhibit lethargy, confusion; may have mild focal signs, such as cranial nerve palsy or hemiparesis Stage III : advanced illness with delirium, stupor, coma, seizures, mul+ple cranial nerve palsies, and/or dense hemiplegia
Bri/sh Medical Research Council, Lancet 1948; 1:582

Recommended regimen
Intensive phase INH, RIF, PZA, and EMB or STM for 2 months Con>nua>on phase INH and RIF for 7- 10 months 9- 12 months in drug-sensi>ve infec>ons Tuberculoma is extended to 18 months
Am J Respir Crit Care Med 2003; 167:603

Glucocor+coid in TBM
Indica>ons for adjunc>ve therapy 1. Progressing stage before Rx 2. Acute encephali+s, open pressure 400cmH2O 3. Therapeu+c paradox,"clinical signs (eg, fever, change in menta+on) post Rx 4. Spinal block (CSF protein > 500 mg/dL) 5. CT brain : marked basal enhancement and hydrocephalus (mod-severe) 6. Tuberculoma with marked perilesional edema

N Engl J Med 2004; 351:1741

Glucocor+coid in TBM
Dexamethasone 12 mg/day for adults for 3 weeks, then tapered o gradually over 3 - 4 weeks Prednisolone 60 mg/day for adults, for 3 weeks, then tapered o gradually over 3 weeks

N Engl J Med 2004; 351:1741

Encephali+s
Presence of an inammatory process of the brain in associa+on with clinical evidence of neurologic dysfunc>on fever , headache, altera>on of cons. Pathogens reported to cause encephali+s, the majority are viruses The e+ology of encephali+s remains unknown in most pa+ents
IDSA Guidelines for Management of Encephali/s CID 2008:47 (1 August) 303

Viral encephali+s
1. Epidemiologic clues and assessment of risk factors to iden+fy poten+al e+ologic agents 2. General and specic neurologic ndings 3. History of recent illness or vaccina+on 4. Specic diagnos+c studies 5. Empirical Therapy 6. Specic Therapy
IDSA Guidelines for Management of Encephali/s CID 2008:47 (1 August) 303

Viral encephali+s
Risk factor Elderly persons
Possible infec>ous agent(s)

Immunocompromised

IDSA Guidelines for Management of Encephali/s CID 2008:47 (1 August) 303

Eastern equine encephali+s virus L. monocytogenes VZV, CMV, HHV 6, West Nile virus, HIV, JC virus, L. monocytogenes, TB, C. neoformans, Coccidioides species, Histoplasma capsulatum, T. gondii

Viral encephali+s
Risk factors Exposure to animals Exposure to horses Agammaglobulinemia Unvaccinated status Unpasteurized milk Possible infec>ous agent Rabies virus, C. burne0i, Bartonella species Hendra virus Enteroviruses, Mycoplasma pneumoniae VZV, JE virus, poliovirus, measles, mumps , rubella
Tickborne encephali+s virus, L. monocytogenes, C. burne0i

IDSA Guidelines for Management of Encephali/s CID 2008:47 (1 August) 303

Viral encephali+s
Risk factors Possible infec>ous agents Physicians and health care VZV, HIV, inuenza virus, Worker measles virus, TB Winter Inuenza virus Transfusion and CMV , EBV, West Nile transplanta+on virus, HIV, +ckborne, rabies , iatrogenic CJD, T. pallidum,C. neoformans, Coccidioides species, H. capsulatum, T. gondii

IDSA Guidelines for Management of Encephali/s CID 2008:47 (1 August) 303

Viral encephali+s
Clinical presenta>on Hepa++s Paro++s Re+ni+s Urinary symptoms Lymphadenopathy Skin rash Possible infec>ous agent Coxiella burne0i Mumps virus CMV , West Nile virus, B. henselae, T. pallidum St. Louis encephali+s virus HIV, EBV, CMV , measles virus, rubella virus Many viruses

IDSA Guidelines for Management of Encephali/s CID 2008:47 (1 August) 303

Viral encephali+s
Neurologic ndings Cerebellar ataxia Cranial n. abnormali+es Demen+a Parkinsonism Possible infec>ous agent VZV(children), EBV, mumps
HSV,EBV L.monocytogenes,

TB ,SY, Crypto, Histo. caps HIV, sCJD and vCJD, measles virus, T. pallidum

JE virus, St. Louis,West Nile Nipah, T. gondii JE, +ckborne encephali+s; enterovirus-71, coxsackie, poliovirus

Poliomyeli+s-like accid paralysis

IDSA Guidelines for Management of Encephali/s CID 2008:47 (1 August) 303

Viral encephali+s
Diagnosis CT, MRI, EEG Note: EEG is abnormal in viral encephali+s LP ndings : asep+c meningi+s Laboratory tes+ng

IDSA Guidelines for Management of Encephali/s CID 2008:47 (1 August) 303

First-line tes+ng
If immunocompetent Rou0ne CSF PCR tes0ng HSV 1&2, VZV Enterovirus, Adenovirus Human herpes-6/7 (<30 years) Rou0ne serology If increased ac+vity Mumps or measles Inuenza A or B Human herpesvirus-6/7 (<30 years) If immunocompromised As forimmunocompetent Cytomegalovirus Epstein-Barr virus Human herpesvirus-6/7 JC virus Lymphocy+c choriomeningi+s virus Serology JC virus

Lancet Infect Dis 2010; 10: 835

Lancet Infect Dis 2010; 10: 835

IDSA Guidelines for Management of Encephali+s

Empirical Therapy Acyclovir should be ini+ated in all pa>ents with suspected encephali+s, pending results of diagnos+c studies (AIII) Other empirical an>microbial agents for presumed bacterial meningi+s, if clinically indicated (A-III) Clinical clues sugges+ve of rickehsial during appropriate season, doxycycline should be added (A-III)

IDSA Guidelines for Management of Encephali/s CID 2008:47 (1 August) 303

IDSA Guidelines for Management of Encephali+s

Specic Therapy HSV : acyclovir is recommended (AI) VZV : acyclovir is recommended (BIII) ganciclovir can be an alterna+ve (C-III) cor+costeroids can be considered (C-III) CMV: combina+on of ganciclovir plus foscarnet is recommended (B-III) Inuenza virus: oseltamivir considered (C-III)
IDSA Guidelines for Management of Encephali/s CID 2008:47 (1 August) 303

IDSA Guidelines for Management of Encephali+s

Specic therapy HIV: HAART is recommended (A-II). JC virus: reversal of immunosuppression (AIII) HAART in HIV (A-II) is recommended EBV : acyclovir is not recommended cor+costeroids may benecial (C-III)

IDSA Guidelines for Management of Encephali/s CID 2008:47 (1 August) 303

HSV ENCEPHALITIS
General Mortality 70% untreated Severe neurodefects in > 50% Pathophysiology Predilec+on for temporal lobes and frontal lobes (limbic system) producing new psychiatric features such as memory loss, aphasia,strange behaviour CT may show hypodense lesions in temporal lobe 1/3 primary infec+on 2/3 Direct transmission from CN I or V to brain

Lancet Infect Dis 2010; 10: 835

HSV ENCEPHALITIS
History Fever 90% Headache 81% Psych symptoms 70% Seizure 67% Vomi+ng 46% Focal weakness 33% Memory loss 24% Physical Altered LOC 97% Fever 90% Dysphasia 76% Ataxia 40% Seizure 38% Hemiparesis 38% CN defect 32% Papilledema 15%

Lancet Infect Dis 2010; 10: 835

HSV ENCEPHALITIS
Lumbar Puncture Increased wbc and rbc Increased red cells characteris+c (due to small hemorrhages) Treatment: acyclovir 10 mg/kg iv q8hr un>ll clinical improve

Lancet Infect Dis 2010; 10: 835

Brain abscesses
3 routes Result of spread of infec+on from oropharynx, middle ear, and paranasal sinuses APer penetra+ng trauma or neurosurgical procedures ranges from 2% -14% Hematogenous : chronic pyogenic lung disease, endocardi+s, intra-abdominal abscess, and urinary tract infec+ons Infect Dis Clin N Am 23 (2009) 609623

Brain abscess

Infect Dis Clin N Am 23 (2009) 609623

Brain abscesses
Organisms : depends on ini>al site of infec>on H&N : Streptococcus spp and anaerobic Lung abscess : Strep spp and anaerobic IE : Staphylococcus aureus or viridians strep Intraabdominal or genitourinary Enteric Gram-nega+ve bacill O//s media or o//s extrena : Pseudomonas Surgical : Staphylococcus aureus
Infect Dis Clin N Am 23 (2009) 609623

Brain abscesses
Opportunis/c pathogens Nocardia spp: dissemina+on or pulmonary TB and NTM : in pa+ents with HIV infec+on L monocytogenes : in immunosuppressed Fungal brain abscesses : in immunosuppressed yeast (Candida spp, Cryptococcus spp) dimorphic fungi ( Histoplasma spp,) molds (Aspergillus spp, Rhizopus) Zygomycosis : poorly controlled diabetes Toxoplasma gondii, and neurocystcercosis

Infect Dis Clin N Am 23 (2009) 609623

single- or mul+ple-ring enhancing lesions

MRI sensi+vity and specicity >> CT CT-guided stereotac+c biopsy with aspira+on

Treatment
An>microbial therapy based on predisposing factors frequently polymicrobial, empiric should cover Gram-posi+ve, nega+ve, and anaerobic : 3rd -4th gen. cephalosporin + metronidazole (carbapenem) and vancomycin denite organism should considered Infect Dis Clin N Am 23 (2009) 609623

Treatment
Dura>on of therapy is inuenced by causa+ve microorganisms and reduc+on in the size of the abscess Least 6 - 8 weeks of IV tradi>onally Surgical therapy 2.5 cm in diameter should be surgically treated ventriculostomy placement is indicated for signicantly elevated intracranial pressure
Infect Dis Clin N Am 23 (2009) 609623

Treatment
Adjuvant therapy Dexamethasone : reducing ICP , especially in impending brain hernia+on Seizure is common complica+on(13% -25%) An+convulsant should be prescribed to prevent seizure in early course of therapy

Infect Dis Clin N Am 23 (2009) 609623

SUBDURAL EMPYEMA
Purulent infec+on of space between the cranial dura and arachnoid membrane Neurosurgical emergency (10%-13% mortality) Major symptoms include headache, altered mental status, and focal signs, depending on the extent of empyema CT scan: shows a hypodense subdural lesion with medial membrane enhancement 23 (2009) 609623 Infect Dis Clin N Am

SUBDURAL EMPYEMA
MRI may be more sensi>ve to visualize subdural lesions Combina>on of an>microbial therapy and adequate surgical irriga+on of subdural space via burr hole or craniotomy is a mainstay

Infect Dis Clin N Am 23 (2009) 609623

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