CNS infection in HIV patients Int.Naruenont Dolsaritchaiya 24 th June 2013

CNS infectionCNS infectioninin

HIV patientsHIV patients

Int.Naruenont Dolsaritchaiya Int.Naruenont Dolsaritchaiya 2424thth June 2013 June 2013

OutlineOutline

ApproachApproach Common diseasesCommon diseases

- - basic knowledgesbasic knowledges

- medical treatmentmedical treatment

- surgical indication- surgical indication Take home messagesTake home messages

How to approachHow to approach

HIV patients can acquire both opportunistic HIV patients can acquire both opportunistic infections and others found in normal hostinfections and others found in normal host

Work up should be extensive due to the Work up should be extensive due to the possibility of multiple infectionspossibility of multiple infections

HoweverHowever, , opportunistic infection should opportunistic infection should draw attention firstly draw attention firstly


AlgorithmAlgorithm


Source : Source :

HIV-associatedHIV-associated

OpportunisticOpportunistic

infections of the CNSinfections of the CNS

Lancet Neurol 2012;Lancet Neurol 2012;

11: 605-1711: 605-17


Lesions can be categorized into 3 types Lesions can be categorized into 3 types based on radiological appearance : based on radiological appearance :

1.Focal mass1.Focal mass

2.White matter disease2.White matter disease

3.Meningeal disease3.Meningeal disease


Focal masses Focal masses Focal masses with rim-enhancementFocal masses with rim-enhancement 1.Toxoplasmosis1.Toxoplasmosis 2.Tuberculoma2.Tuberculoma 3.Cryptococcoma3.Cryptococcoma 4.Primary CNS lymphoma 4.Primary CNS lymphoma ((not infectionnot infection)) 5.Bacterial and fungal abscesses5.Bacterial and fungal abscesses 6.CMV encephalitis6.CMV encephalitis ( (rarelyrarely))


Focal masses Focal masses Focal masses without rim-enhancementFocal masses without rim-enhancement

1.Toxoplasmosis1.Toxoplasmosis

2.Cryptococcoma2.Cryptococcoma

3.Atypical primary CNS lymphoma3.Atypical primary CNS lymphoma


White matter disease White matter disease

1.HIV encephalopathy 1.HIV encephalopathy ((HIVEHIVE))

2.CMV encephalitis2.CMV encephalitis

3.Progressive multifocal 3.Progressive multifocal leukoencephalopathy leukoencephalopathy ((PMLPML))


Meningeal diseaseMeningeal disease

1.HIV meningoencephalitis1.HIV meningoencephalitis

2.Cryptococcal meningitis2.Cryptococcal meningitis

3.Tuberculous meningitis3.Tuberculous meningitis

4.Other bacterial/viral meningitis 4.Other bacterial/viral meningitis

Common diseasesCommon diseases

ToxoplasmosisToxoplasmosis

Principal OI in HIV patientsPrincipal OI in HIV patients 15-40% of AIDS patients15-40% of AIDS patients Usually occurs when CD4 < 100Usually occurs when CD4 < 100 Almost always a reactivation and serology is Almost always a reactivation and serology is

positive in 85%positive in 85% Seronegative cases occur as a result Seronegative cases occur as a result

immunosuppression or rarely a primary immunosuppression or rarely a primary infectioninfection


Common sites : Common sites : 1.Basal ganglia1.Basal ganglia 2.Cortico-medullary junction 2.Cortico-medullary junction usually frontal and parietal lobe usually frontal and parietal lobe 3.Brainstem3.Brainstem

Meningeal involvement uncommonMeningeal involvement uncommon


Diagnosis Diagnosis 1. Imaging : CT/MRI1. Imaging : CT/MRI - rim-enhancing lesion- rim-enhancing lesion - typically 1-2 cm - typically 1-2 cm - < 20- < 20%% solitary solitary 2.Serology : IgG2.Serology : IgG,, IgM IgM 3.PCR 3.PCR



Treatment : Treatment :

Pyrimethamine + Sulfadiazine 6 weeksPyrimethamine + Sulfadiazine 6 weeks In cases of failure to diagnose or respond to In cases of failure to diagnose or respond to

medical treatmentmedical treatment within 7 dayswithin 7 days, , biopsy is biopsy is needed for tissue pathological diagnosisneeded for tissue pathological diagnosis

Secondary prophylaxis until CD4 > 200 for Secondary prophylaxis until CD4 > 200 for 6 months6 months

TuberculosisTuberculosis

Found in both immunocompromised and Found in both immunocompromised and immunocompetent hostimmunocompetent host

HIV patients are prone to develop HIV patients are prone to develop reactivation and extrapulmonary infectionreactivation and extrapulmonary infection

Tuberculous meningitis and Tuberculous meningitis and tuberculoma/TB abscess tuberculoma/TB abscess ((uncommonuncommon))


CN III palsy CN III palsy Involves cerebral artery which can produce Involves cerebral artery which can produce

focal ischemiafocal ischemia


Diagnosis Diagnosis

1.CSF profile : mainstay for Dx 1.CSF profile : mainstay for Dx

***AFB +ve in 1***AFB +ve in 1//3 3

2.Imaging : CT/MRI2.Imaging : CT/MRI


Diagnosis : CSF profileDiagnosis : CSF profile


Imaging : CT/MRI Imaging : CT/MRI

- Leptomeningeal enhancement mainly at - Leptomeningeal enhancement mainly at the base of skullthe base of skull

- tuberculoma at basal ganglia- tuberculoma at basal ganglia

- communicating/noncommunicating - communicating/noncommunicating hydrocephalus hydrocephalus




Treatment : HRZE x 9 months or moreTreatment : HRZE x 9 months or more

***Steroid reduces morbidity***Steroid reduces morbidity In case of hydrocephalusIn case of hydrocephalus, , extraventricular extraventricular

drainage or shunt is required to reduce ICPdrainage or shunt is required to reduce ICP

CryptococcosisCryptococcosis

Usually develops whenUsually develops when CD4 < 100CD4 < 100 Forms : meningitis/cryptococcomaForms : meningitis/cryptococcoma

pulmonarypulmonary

skin and soft tissueskin and soft tissue Meningismus may be absentMeningismus may be absent Complication : CN deficitComplication : CN deficit, , visual lossvisual loss, ,

cognitive impairmentcognitive impairment

CryptococcosisCryptococcosis Poor prognosis : Poor prognosis : - +ve Indian ink- +ve Indian ink - high CSF pressure- high CSF pressure - low glucose- low glucose - low pleocytosis < 2 cells- low pleocytosis < 2 cells//mm3 mm3 - extraneural yeast cell- extraneural yeast cell - absence of Ab- absence of Ab - CSF or serum crypto. Ag > 1:32- CSF or serum crypto. Ag > 1:32 - steroid use- steroid use - hematologic malignacy - hematologic malignacy


Diagnosis Diagnosis

1.Indian ink1.Indian ink

2.Cryptococcal Ag in CSF/serum 2.Cryptococcal Ag in CSF/serum




Imaging : CT/MRIImaging : CT/MRI

- hydrocephalus- hydrocephalus

- meningeal enhancement- meningeal enhancement

- cryptococcomas at basal ganglion- cryptococcomas at basal ganglion

- punched-out cystic lesion- punched-out cystic lesion




Treatment : Treatment :

Amp. B 0.7-1.0 mg/kg/day 2 weeks and then Amp. B 0.7-1.0 mg/kg/day 2 weeks and then fluconazole 400 mg/day for 10 weeksfluconazole 400 mg/day for 10 weeks

Repeated LP or shunt is necessary to relieve Repeated LP or shunt is necessary to relieve increased ICPincreased ICP


Primary CNS lymphomaPrimary CNS lymphoma

Frequently occurs in severe Frequently occurs in severe immunosuppression or AIDSimmunosuppression or AIDS

High grade B-cell lymphomaHigh grade B-cell lymphoma Strongly associated with EBV Strongly associated with EBV Poor prognosis compared to similar Poor prognosis compared to similar

lymphoma outside CNSlymphoma outside CNS



- rim-enhancing or heterogeneously - rim-enhancing or heterogeneously enhancing enhancing

- usually > 3 cm- usually > 3 cm

- periventricular- periventricular, , frontalfrontal, , temporaltemporal Difficult to distinguish from toxoplasmosis Difficult to distinguish from toxoplasmosis

or metastasis or metastasis


Diagnosis usually made after failure to Diagnosis usually made after failure to respond to toxoplasmosis Rxrespond to toxoplasmosis Rx

Brain biopsy is mandatory to obtain tissue Brain biopsy is mandatory to obtain tissue pathologypathology

If safe to LPIf safe to LP, , CSF for EBV DNA help to CSF for EBV DNA help to diagnose with no need to perform biopsydiagnose with no need to perform biopsy




Treatment : CMT + WBRTTreatment : CMT + WBRT > 90> 90% % have a recurrence diseasehave a recurrence disease Surgical resection : for immediate Surgical resection : for immediate

decompresion of life-threatening mass effectdecompresion of life-threatening mass effect

HIV encephalopathyHIV encephalopathy

HIV-associated dementiaHIV-associated dementia Symptoms : progressive dementiaSymptoms : progressive dementia,, cognitive cognitive

impairmentimpairment, , motor symptomsmotor symptoms, , gait gait disturbancedisturbance, , tremortremor

Subcortical dementia : no aphasiaSubcortical dementia : no aphasia, , apraxia apraxia or agnosiaor agnosia

Alertness is minimally perturbedAlertness is minimally perturbed


Diagnosis Diagnosis


2.CSF profile2.CSF profile




CSF profileCSF profile

- - non specific increased in cells and proteinnon specific increased in cells and protein

- helpful in diagnosing or ruling out OI- helpful in diagnosing or ruling out OI

- - HIV RNA not correlate with HIV HIV RNA not correlate with HIV encephalopathyencephalopathy


Treatment : HAARTTreatment : HAART CNS resistance may occurCNS resistance may occur

CMV encephalitisCMV encephalitis

Usually occurs when CD4 < 50Usually occurs when CD4 < 50 Reactivation of latent infectionReactivation of latent infection Two forms : Two forms :

1.Encephalitis : progressive dementia1.Encephalitis : progressive dementia

2.Ventriculoencephalitis2.Ventriculoencephalitis : CN deficit: CN deficit, , alteration of consciousnessalteration of consciousness, , nystagmusnystagmus, , disorientationdisorientation, , ventriculomegalyventriculomegaly


Diagnosis Diagnosis 1.CSF : PCR for CMV DNA1.CSF : PCR for CMV DNA cultureculture 2.Imaging : CT/MRI2.Imaging : CT/MRI - periventricular enhancement - periventricular enhancement ***no calcification like congenital CMV***no calcification like congenital CMV - subependymal enhancement- subependymal enhancement - 50- 50% % normal imagingnormal imaging




Treatment : GanciclovirTreatment : Ganciclovir,, Valganciclovir Valganciclovir

induction of 14-21 days followed by induction of 14-21 days followed by prolonged maintenance therapyprolonged maintenance therapy


PMLPML

Caused by the reactivation of the Caused by the reactivation of the

Jamestown Canyon Jamestown Canyon ((JCJC) ) virusvirus

CD4 counts usually below 100/mm3CD4 counts usually below 100/mm3

Multiple areas of demyelination throughout Multiple areas of demyelination throughout

the brain sparing cord and optic nervethe brain sparing cord and optic nerve

PMLPML

Symptoms : visual lossSymptoms : visual loss

mental impairmentmental impairment

weakness weakness

ataxiaataxia

PMLPML

Diagnosis :Diagnosis :

1. MRI1. MRI

- multifocal asymmetric white matter - multifocal asymmetric white matter lesionslesions

- subcortical white matter- subcortical white matter, , cerebellumcerebellum

- low signal on T1 weighted images and - low signal on T1 weighted images and hyperintense on T2 weighted/FLAIRhyperintense on T2 weighted/FLAIR

PMLPML

Diagnosis : MRIDiagnosis : MRI

PMLPML


2.CSF : PCR for JCV DNA2.CSF : PCR for JCV DNA

normal cells and proteinnormal cells and protein

HSV encephalitisHSV encephalitis

HSV produces necrotizing encephalitis in HSV produces necrotizing encephalitis in

HIV patientsHIV patients

Predilection for the medial temporal and Predilection for the medial temporal and

inferior frontal lobesinferior frontal lobes


Diagnosis : Diagnosis :

1.CSF : PCR for HSV DNA1.CSF : PCR for HSV DNA

- sens. 96- sens. 96% % and spec. 99and spec. 99% %

((equivalent or exceed brain biopsyequivalent or exceed brain biopsy) )

- - maybe negative if too early maybe negative if too early ((< 72 hr< 72 hr) ) or or

more than 14 daysmore than 14 days



2.Imaging : CT/MRI 2.Imaging : CT/MRI

- area of low absorption- area of low absorption, , mass effect or mass effect or

hemorrhage on CT hemorrhage on CT

- hyperintensity signal on T2/FLAIR or - hyperintensity signal on T2/FLAIR or

diffuse-weighteddiffuse-weighted




Treatment : IV acyclovir 10 mg/kg q 8 hr Treatment : IV acyclovir 10 mg/kg q 8 hr

for 14 days and repeat CSF profilefor 14 days and repeat CSF profile

*** Dilute < 7mg/ml and infused slowly *** Dilute < 7mg/ml and infused slowly

over 1 hr to minimize renal dysfunctionover 1 hr to minimize renal dysfunction

Take home messagesTake home messages

Neurological manifestations in HIV/AIDS Neurological manifestations in HIV/AIDS

patients have a wide spectrumpatients have a wide spectrum

Clinicians must consider multiple causes Clinicians must consider multiple causes

which share similar clinical and which share similar clinical and

radiographic patternsradiographic patterns

Neurosurgery carry an important role for Neurosurgery carry an important role for

diagnosis and treatment diagnosis and treatment

ReferencesReferences

Youman textbook of neurosurgery 6Youman textbook of neurosurgery 6thth ed. ed.

Harrison textbook of internal medicine 17Harrison textbook of internal medicine 17thth

ed.ed.

Lancet neurology 2012Lancet neurology 2012

THANK YOUTHANK YOU

Documents

CNS infection in HIV patients Int.Naruenont Dolsaritchaiya 24 th June 2013