Brain AbscessBrain Abscess

Dr. Shatdal Dr. Shatdal Chaudhary, M.D.Chaudhary, M.D.Associate ProfessorAssociate Professor

Universal College of Medical Sciences,Universal College of Medical Sciences,Bhairahawa, NepalBhairahawa, Nepal

Email: shatdalchaudhary@yahoo.comEmail: shatdalchaudhary@yahoo.com

Definition

Brain abscess is a focal suppurative infection within the brain parenchyma, typically surrounded by a vascularized capsule.

Cerebritis: is often employed to describe a nonnencapsulated brain abscess.

Epidemiology

Relatively uncommon Incidence~.3-1.3:100000 person per

year

Etiology

Brain abscess may develop by 1. Direct spread from a contiguous cranial site of

infection 2. Head trauma, neurosurgical procedures 3. Hematogenous spread

25% cases : There isno primary source of infection

Predisposing conditions

Otitis media Mastoiditis Paranasal sinusitis Pyogenic infection of chest or any

other part of body Penetrating head injury Neurosurgical procedure Dental infection

In Immunocompetent persons: Streptococcus spp. (aerobic, Anaerobic

and viridans) 40% Enterobacteriaceae (Proteus, E.coli,

Klebsella) 25% Anaerobes (Bacteroides, Fusobacterium)

30% Staphylococci 10% Taenia solium(NCC) Mycobacterial infection (tuberculoma)

In immuno-compromised host Nocardia T gondii Aspergillus Candida C. neoformans

Stages 1. Early Cerebritis: 1-3days

A perivascular infiltration of inflammatory cells around a central core of coagulation necrosis

2. Late Cerebritis: 4-9 days Pus formationin necrotic center which is

surrounded by inflammatory cells and fibroblast 3. Early Capsule Formation: 10-13 days

A capsule that is better develop on corticalthen on ventricle side of lesion

4. Late Capsule Formation: beyond 14 days A well defined necrotic center surrounded by a

dense collageous capsule

Clinical Presentation

Typically presents as an expanding intracranial mass rather than as a infectious process

Symptoms are gradual in onset Patients present weeks to month Usually presents 11-12 days

following onset of symptoms.

Symptoms

Classical triad: seen in <50% patients Headache 75% Fever 50% Focal neurologic deficit 15-35%

Focal neurologic deficit Aphasia Hemiparesis Visual field defect Ataxia Nystagmus Seizures Raised ICP-Papilledema Meningismus Uncommon unless

abscess rupture in ventricle

Investigations

TLC, DLC ESR, CRP Blood cultures Neuroimaging studies:

MRI: better esp can detect early stages of cerebritis

CT Scan: a focal area of hypodensity surrounded by ring enhancementwith surrounding edema (hypodensity)

MRIMRI

CT ScanCT Scan

Microbiological Evaluation

CT-guided stereotactic needle aspiration Gram’s Stain Culture : Aerobic, Anaerobic,

Mycobacterial and fungal cultures

Blood CultureLP: do not perform

D/D

Bacterial Meningitis Meningoencephalitis Acute disseminated

encephalomyelitis Empyema Saggital Sinus Thrombosis Primary or Secondary brain tumor CVA

Treatment Combination of high dose parentral

antibiotics and neurosurgical drainage Third/fourth grneration

cephalosporin+Metronidazole Patients with neurodurgery/Head trauma

Vancomycin+Ceftazidine Meropenem+Vancomycin

Modify antibiotics as per culture results Duration: Min 6-8 weeks

Prophylactic anticonvulsant Should continue atleast 3 months after

resolution of abscess Role of steroids

Not given routinely Usually reserved forof significant

periabscess edema with mass effect and raise ICP

Dexamethasone 10 mg 6 hrly

Aspiration and Drainage of the abscess under stereotactic guidance

Craniotomy and Complete excision of a bacterial abscess: reserved for multiloculated abscess or in those where aspiration is unsucessful.

Prognosis

Mortality rate <15% Neurological sequelae ≥20% of

survivors

Acute Viral MeningitisAcute Viral Meningitis

Enterovirus(coxaschie viruses, Enterovirus(coxaschie viruses, echovirus,human enterovirus68-71echovirus,human enterovirus68-71

HSV 2HSV 2 HIVHIV ArbovirusArbovirus VZVVZV EBVEBV

IntroductionIntroduction Encephalitis is an acute inflammatory process Encephalitis is an acute inflammatory process

affecting the brain parenchymaaffecting the brain parenchyma

MeningoencephalitisMeningoencephalitis EncephalomyelitisEncephalomyelitis EncephalomyeloradiculitisEncephalomyeloradiculitis

Viral infection is the most common and important Viral infection is the most common and important cause, with over 100 viruses implicated worldwidecause, with over 100 viruses implicated worldwide

Incidence of 3.5-7.4 per 100,000 persons per yearIncidence of 3.5-7.4 per 100,000 persons per year ~20,000 cases reported anually in USA~20,000 cases reported anually in USA

Causes of Viral Causes of Viral EncephalitisEncephalitis

Herpes viruses – HSV-1, HSV-2, varicella zoster virus, Herpes viruses – HSV-1, HSV-2, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, human herpes virus 6 cytomegalovirus, Epstein-Barr virus, human herpes virus 6

AdenovirusesAdenoviruses Influenza AInfluenza A Enteroviruses, poliovirusEnteroviruses, poliovirus Measles, mumps, and rubella virusesMeasles, mumps, and rubella viruses RabiesRabies Arboviruses – examples: Japanese encephalitis; St. Louis Arboviruses – examples: Japanese encephalitis; St. Louis

encephalitis virus; West Nile encephalitis virus; Eastern, encephalitis virus; West Nile encephalitis virus; Eastern, Western and Venzuelan equine encephalitis virus; tick borne Western and Venzuelan equine encephalitis virus; tick borne encephalitis virusencephalitis virus

Bunyaviruses – examples: La Crosse strain of California virusBunyaviruses – examples: La Crosse strain of California virus Reoviruses – example: Colorado tick fever virusReoviruses – example: Colorado tick fever virus Arenaviruses – example: lymphocytic choriomeningitis virus Arenaviruses – example: lymphocytic choriomeningitis virus

What Is An Arbovirus?What Is An Arbovirus?

Arboviruses = arthropod-borne viruses Arboviruses = arthropod-borne viruses Arboviruses are maintained in nature Arboviruses are maintained in nature

through biological transmission through biological transmission between susceptible vertebrate hosts between susceptible vertebrate hosts by blood-feeding arthropodsby blood-feeding arthropods

Vertebrate infection occurs when the Vertebrate infection occurs when the infected arthropod takes a blood mealinfected arthropod takes a blood meal

Major Arboviruses That Major Arboviruses That Cause EncephalitisCause Encephalitis

FlaviviridaeFlaviviridae Japanese encephalitisJapanese encephalitis St. Louis encephalitisSt. Louis encephalitis West NileWest Nile

TogaviridaeTogaviridae Eastern equine encephalitisEastern equine encephalitis Western equine encephalitisWestern equine encephalitis

BunyaviridaeBunyaviridae La Crosse encephalitisLa Crosse encephalitis

http://www.cdc.gov/ncidod/dvbid/arbor/worldist.pdf

Japanese Japanese EncephalitisEncephalitis

Japanese EncephalitisJapanese Encephalitis Flavivirus related to St. Louis Flavivirus related to St. Louis

encephalitisencephalitis Most important cause of Most important cause of

arboviral encephalitis arboviral encephalitis worldwide, with over 45,000 worldwide, with over 45,000 cases reported annuallycases reported annually

Transmitted by culex Transmitted by culex mosquito, which breeds in mosquito, which breeds in rice fieldsrice fields Mosquitoes become infected Mosquitoes become infected

by feeding on domestic pigs by feeding on domestic pigs and wild birds infected with and wild birds infected with Japanese encephalitis virus. Japanese encephalitis virus. Infected mosquitoes transmit Infected mosquitoes transmit virus to humans and animals virus to humans and animals during the feeding process.during the feeding process.

History of Japanese History of Japanese EncephalitisEncephalitis

1800s – recognized in Japan1800s – recognized in Japan

1924 – Japan epidemic. 6125 cases, 3797 1924 – Japan epidemic. 6125 cases, 3797 deathsdeaths

1935 – virus isolated in brain of Japanese 1935 – virus isolated in brain of Japanese patient who died of encephalitispatient who died of encephalitis

1938 – virus isolated from Culex mosquitoes in 1938 – virus isolated from Culex mosquitoes in JapanJapan

Today – extremely prevalent in South East Today – extremely prevalent in South East Asia. 30,000-50,000 cases reported each year. Asia. 30,000-50,000 cases reported each year.

Distribution of Japanese Distribution of Japanese Encephalitis in Asia, 1970-Encephalitis in Asia, 1970-

19981998

West Nile VirusWest Nile Virus

West Nile VirusWest Nile Virus FlavivirusFlavivirus Primary host – wild Primary host – wild

birdsbirds Principal arthropod Principal arthropod

vector – mosquitoesvector – mosquitoes Geographic Geographic

distribution - Africa, distribution - Africa, Middle East, Middle East, Western Asia, Western Asia, Europe, Australia, Europe, Australia, North America, North America, Central AmericaCentral America

http://www.walgreens.com/images/library/healthtips/july02/westnilea.jpg

St. Louis St. Louis EncephalitisEncephalitis

St. Louis EncephalitisSt. Louis Encephalitis

FlavivirusFlavivirus Most common Most common

mosquito-mosquito-transmitted human transmitted human pathogen in the USpathogen in the US

Leading cause of Leading cause of epidemic flaviviral epidemic flaviviral encephalitisencephalitis

Eastern Equine Eastern Equine EncephalitisEncephalitis

TogavirusTogavirus Caused by a virus Caused by a virus

transmitted to humans and transmitted to humans and horses by the bite of an horses by the bite of an infected mosquito.infected mosquito.

200 confirmed cases in the 200 confirmed cases in the US 1964-presentUS 1964-present

Human cases occur Human cases occur relatively infrequently, relatively infrequently, largely because the largely because the primary transmission cycle primary transmission cycle takes place in swamp takes place in swamp areas where populations areas where populations tend to be limited. tend to be limited.

Western Equine Western Equine EncephalitisEncephalitis

TogavirusTogavirus Mosquito-borneMosquito-borne 639 confirmed cases 639 confirmed cases

in the US since 1964 in the US since 1964 Important cause of Important cause of

encephalitis in encephalitis in horses and humans horses and humans in North America, in North America, mainly in the mainly in the Western parts of the Western parts of the US and CanadaUS and Canada

La Crosse EncephalitisLa Crosse Encephalitis BunyavirusBunyavirus On average 75 cases per year On average 75 cases per year

reported to the CDCreported to the CDC Most cases occur in children Most cases occur in children

under 16 years oldunder 16 years old Zoonotic pathogen that cycles Zoonotic pathogen that cycles

between the daytime biting between the daytime biting treehole mosquito, and treehole mosquito, and vertebrate amplifier hosts vertebrate amplifier hosts (chipmunk, tree squirrel) in (chipmunk, tree squirrel) in deciduous forest habitatsdeciduous forest habitats

1963 – isolated in La Crosse, 1963 – isolated in La Crosse, WI from the brain of a child WI from the brain of a child who died from encephalitiswho died from encephalitis

Summary – Confirmed and Summary – Confirmed and Probable Human Cases in Probable Human Cases in

the USthe USVirusVirus YearsYears Total casesTotal cases

Eastern Eastern EquineEquine

1964-20001964-2000 182182

Western Western EquineEquine

1964-20001964-2000 649649

La CrosseLa Crosse 1964-20001964-2000 2,7762,776

St. LouisSt. Louis 1964-20001964-2000 4,4824,482

West NileWest Nile 1999-present1999-present > 9,800> 9,800

Clinical Clinical ManifestationsManifestations

Symptoms Symptoms

FeverFever Headache, Headache, Malaise, Anorexia, Nausea and VomitingMalaise, Anorexia, Nausea and Vomiting Abdominal painAbdominal pain Altered level of consciousnessAltered level of consciousness

Mild lethargy to ComaMild lethargy to Coma Behavioral changes, hallucinations, Behavioral changes, hallucinations,

agitations, personality changes, frank agitations, personality changes, frank psychosispsychosis

Focal neurologic deficits: Focal neurologic deficits: Virtually every possible focal neurological Virtually every possible focal neurological

disturbance has been reported.disturbance has been reported.

AphasiaAphasia AtaxiaAtaxia Weakness: Hemiparesis with hyperactive tendon Weakness: Hemiparesis with hyperactive tendon

reflexesreflexes Cranial nerve deficitsCranial nerve deficits Involantary movements- tremors, myoclonic jerksInvolantary movements- tremors, myoclonic jerks Seizures >50% patientsSeizures >50% patients

SIADHSIADH

Patient HistoryPatient History Detailed history critical to determine the likely cause of Detailed history critical to determine the likely cause of

encephalitis. encephalitis. Prodromal illness, recent vaccination, development of few Prodromal illness, recent vaccination, development of few

days → Acute Disseminated Encephalomyelitis (ADEM) .days → Acute Disseminated Encephalomyelitis (ADEM) . Biphasic onset: systemic illness then CNS disease → Biphasic onset: systemic illness then CNS disease →

Enterovirus encephalitis. Enterovirus encephalitis. Abrupt onset, rapid progression over few days → HSE.Abrupt onset, rapid progression over few days → HSE. Recent travel and the geographical context: Recent travel and the geographical context:

Africa → Cerebral malariaAfrica → Cerebral malaria Asia → Japanese encephalitisAsia → Japanese encephalitis High risk regions of Europe and USA → Lyme diseaseHigh risk regions of Europe and USA → Lyme disease

Recent animal bites → Tick borne encephalitis or Rabies.Recent animal bites → Tick borne encephalitis or Rabies. OccupationOccupation

Forest worker, exposed to tick bitesForest worker, exposed to tick bites Medical personnel, possible exposure to infectious diseases. Medical personnel, possible exposure to infectious diseases.

Lab InvestigationLab Investigation CSF examination: Should be performed in all CSF examination: Should be performed in all

the patients until contraindicatedthe patients until contraindicated Diagnosis is usually based on CSF Diagnosis is usually based on CSF

Mild increase in proteinMild increase in protein Inrease cells with predominantly lymphocytesInrease cells with predominantly lymphocytes Normal glucoseNormal glucose Absence of bacteria on culture. Absence of bacteria on culture. Viruses occasionally isolated directly from Viruses occasionally isolated directly from

CSFCSF Less than half are identifiedLess than half are identified

Laboratory DiagnosisLaboratory Diagnosis

CSF PCR techniquesCSF PCR techniques Detect specific viral DNA in CSFDetect specific viral DNA in CSF Usually available for HSVCMV, EBV, Usually available for HSVCMV, EBV,

HHV6, ENTEROVIRUS, VZVHHV6, ENTEROVIRUS, VZV CSF CULTURECSF CULTURE

MRI/ CT ScanMRI/ CT Scan

Can exclude subdural bleeds, tumor, and sinus Can exclude subdural bleeds, tumor, and sinus thrombosis thrombosis

Help byHelp by Focal or diffuse ence4phalitis processFocal or diffuse ence4phalitis process In HSV encephalitis- 80% abnormalities in temporal In HSV encephalitis- 80% abnormalities in temporal

lobe lobe

MRIMRI

MRIMRI

EEGEEG

In HSV: Periodic focal temporal lobe In HSV: Periodic focal temporal lobe spikes on a background of slow or spikes on a background of slow or low amplitude activity.low amplitude activity.

Brain BiopsyBrain Biopsy

Is generally reserved for patients in Is generally reserved for patients in whom CSF PCR fail to lead a specific whom CSF PCR fail to lead a specific diagnosisdiagnosis

Reserved for patients who are worsening, Reserved for patients who are worsening, have an undiagnosed lesion after scan, or have an undiagnosed lesion after scan, or a poor response to acyclovir.a poor response to acyclovir.

D/DD/D Tuberculosis, Fungal, Rickettsia, Mycoplasma, Tuberculosis, Fungal, Rickettsia, Mycoplasma,

Bacterial Bacterial Anoxic/Ischemic conditionsAnoxic/Ischemic conditions Metabolic disordersMetabolic disorders Nutritional deficiencyNutritional deficiency Toxic (Accidental & Intentional)Toxic (Accidental & Intentional) Systemic infectionsSystemic infections Critical illnessCritical illness Malignant hypertensionMalignant hypertension Hashimoto’s encephalopathyHashimoto’s encephalopathy Traumatic brain injuryTraumatic brain injury Epileptic (non-convulsive status)Epileptic (non-convulsive status) CJD (Mad Cow)CJD (Mad Cow)

TreatmentTreatment

SuppportiveSuppportive Vital monitoringVital monitoring ABCABC IVFIVF Treatment of raised ICPTreatment of raised ICP Bed CareBed Care NutritionNutrition DVT prophylaxisDVT prophylaxis

Supportive TherapySupportive Therapy Fever, dehydration, electrolyte imbalances, Fever, dehydration, electrolyte imbalances,

and convulsions require treatment.and convulsions require treatment. For cerebral edema severe enough to For cerebral edema severe enough to

produce herniation, controlled produce herniation, controlled hyperventilation, mannitol, and hyperventilation, mannitol, and dexamethasone.dexamethasone. Patients with cerebral edema must not be Patients with cerebral edema must not be

overhydrated.overhydrated. If these measures are used, monitoring If these measures are used, monitoring

ICP should be considered. ICP should be considered. If there is evidence of ventricular If there is evidence of ventricular

enlargement, intracranial pressure may be enlargement, intracranial pressure may be monitored in conjunction with CSF drainage.monitored in conjunction with CSF drainage.

AcyclovirAcyclovir

Acyclovir is a synthetic purine Acyclovir is a synthetic purine nucleoside analogue with inhibitory nucleoside analogue with inhibitory activity against HSV-1 and HSV-2, activity against HSV-1 and HSV-2, varicella-zoster virus (VZV), Epstein-varicella-zoster virus (VZV), Epstein-Barr virus (EBV) and Barr virus (EBV) and cytomegalovirus (CMV)cytomegalovirus (CMV) In order of decreasing effectivenessIn order of decreasing effectiveness Acyclovir 10 mg/kg 8 hrly 14-21day Acyclovir 10 mg/kg 8 hrly 14-21day

Acyclovir ActionAcyclovir Action Thymidine Kinase (TK) of uninfected cells does not use Thymidine Kinase (TK) of uninfected cells does not use

acyclovir as a substrate.acyclovir as a substrate. TK encoded by HSV, VZV and EBV2 converts acyclovir into TK encoded by HSV, VZV and EBV2 converts acyclovir into

acyclovir monophosphate. acyclovir monophosphate. The monophosphate is further converted into diphosphate by The monophosphate is further converted into diphosphate by

cellular guanylate kinase and into triphosphate by a number cellular guanylate kinase and into triphosphate by a number of cellular enzymes.of cellular enzymes.

Acyclovir triphosphate interferes with Herpes simplex virus Acyclovir triphosphate interferes with Herpes simplex virus DNA polymerase and inhibits viral DNA replication. DNA polymerase and inhibits viral DNA replication.

Acyclovir triphosphate incorporated into growing chains of Acyclovir triphosphate incorporated into growing chains of DNA by viral DNA polymerase.DNA by viral DNA polymerase.

When incorporation occurs, the DNA chain is terminated.When incorporation occurs, the DNA chain is terminated. Acyclovir is preferentially taken up and selectively converted Acyclovir is preferentially taken up and selectively converted

to the active triphosphate form by HSV-infected cells. to the active triphosphate form by HSV-infected cells. Thus, acyclovir is much less toxic Thus, acyclovir is much less toxic in vitroin vitro for normal for normal

uninfected cells because: 1) less is taken up; 2) less is uninfected cells because: 1) less is taken up; 2) less is converted to the active form.converted to the active form.

Ganicyclovir/Foscarnet: For CMV Ganicyclovir/Foscarnet: For CMV related CNS infectionrelated CNS infection Ganicyclovir 5mg/kg (over 1 hr) 12 hrly Ganicyclovir 5mg/kg (over 1 hr) 12 hrly

during induction therapy the od in during induction therapy the od in maintenance therapymaintenance therapy

Foscarnet: 60mg/kg 8hrly during Foscarnet: 60mg/kg 8hrly during induction then maintenance 60-120 induction then maintenance 60-120 mg/kgmg/kg

DexamethasoneDexamethasone

Synthetic adrenocortical steroid Synthetic adrenocortical steroid Potent anti-inflammatory effectsPotent anti-inflammatory effects Dexamethasone injection is Dexamethasone injection is

generally administered initially via generally administered initially via IV then IMIV then IM

Side effects: convulsions; increased Side effects: convulsions; increased ICP after treatment; vertigo; ICP after treatment; vertigo; headache; psychic disturbances headache; psychic disturbances

PrognosisPrognosis The mortality rate varies with etiology, and epidemics The mortality rate varies with etiology, and epidemics

due to the same virus vary in severity in different years. due to the same virus vary in severity in different years. Bad: Eastern equine encephalitis virus infection, nearly 80% of Bad: Eastern equine encephalitis virus infection, nearly 80% of

survivors have severe neurological sequelae. survivors have severe neurological sequelae. Not so Bad: EBV, California encephalitis virus, and Venezuelan Not so Bad: EBV, California encephalitis virus, and Venezuelan

equine encephalitis virus, severe sequelae are unusual. equine encephalitis virus, severe sequelae are unusual. Approximately 5 to 15% of children infected with LaCrosse Approximately 5 to 15% of children infected with LaCrosse

virus have a residual seizure disorder, and 1% have persistent virus have a residual seizure disorder, and 1% have persistent hemiparesis. hemiparesis.

Permanent cerebral sequelae are more likely to occur Permanent cerebral sequelae are more likely to occur in infants, but young children improve for a longer time in infants, but young children improve for a longer time than adults with similar infections. than adults with similar infections. Intellectual impairment, learning disabilities, hearing loss, and Intellectual impairment, learning disabilities, hearing loss, and

other lasting sequelae have been reported in some studies. other lasting sequelae have been reported in some studies.

Prognosis w/ TreatmentPrognosis w/ Treatment Considerable variation in the incidence and severity of Considerable variation in the incidence and severity of

sequelae.sequelae. Hard to assess effects of treatment.Hard to assess effects of treatment.

NIAID-CASG trials: NIAID-CASG trials: The incidence and severity of sequelae were directly related to The incidence and severity of sequelae were directly related to

the age of the patient and the level of consciousness at the time the age of the patient and the level of consciousness at the time of initiation of therapy. of initiation of therapy.

Patients with severe neurological impairment (Glasgow coma Patients with severe neurological impairment (Glasgow coma score 6) at initiation of therapy either died or survived with score 6) at initiation of therapy either died or survived with severe sequelae. severe sequelae.

Young patients (<30 years) with good neurological function at Young patients (<30 years) with good neurological function at initiation of therapy did substantially better (100% survival, initiation of therapy did substantially better (100% survival, 62% with no or mild sequelae) compared with their older 62% with no or mild sequelae) compared with their older counterparts (>30 years); (64% survival, 57% no or mild counterparts (>30 years); (64% survival, 57% no or mild sequelae). sequelae).

Recent studies using quantitative CSF PCR tests for HSV Recent studies using quantitative CSF PCR tests for HSV indicate that clinical outcome following treatment also indicate that clinical outcome following treatment also correlates with the amount of HSV DNA present in CSF at correlates with the amount of HSV DNA present in CSF at the time of presentation. the time of presentation.

VaccinationVaccination None for most EncephalitidesNone for most Encephalitides JEJE

Appears to be 91% effectiveAppears to be 91% effective There is no JE-specific therapy other than supportive There is no JE-specific therapy other than supportive

care care Live-attenuated vaccine developed and tested in Live-attenuated vaccine developed and tested in

China China Appears to be safe and effectiveAppears to be safe and effective Chinese immunization programs involving millions of Chinese immunization programs involving millions of

children children Vero cell-derived inactivated vaccines have been Vero cell-derived inactivated vaccines have been

developed in Chinadeveloped in China 2 millions doses are produced annually in China and Japan2 millions doses are produced annually in China and Japan

Several other JE vaccines under developmentSeveral other JE vaccines under development