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

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Presentation on theme: "CNS infection in HIV patients Int.Naruenont Dolsaritchaiya 24 th June 2013."— Presentation transcript:

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

2 Outline Approach Approach Common diseases Common diseases - basic knowledges - basic knowledges - medical treatment - medical treatment - surgical indication - surgical indication Take home messages Take home messages

3 How to approach HIV patients can acquire both opportunistic infections and others found in normal host HIV patients can acquire both opportunistic infections and others found in normal host Work up should be extensive due to the possibility of multiple infections Work up should be extensive due to the possibility of multiple infections However, opportunistic infection should draw attention firstly However, opportunistic infection should draw attention firstly

4 How to approach Algorithm

5 Source : HIV-associatedOpportunistic infections of the CNS Lancet Neurol 2012; 11:

6 How to approach Lesions can be categorized into 3 types based on radiological appearance : Lesions can be categorized into 3 types based on radiological appearance : 1.Focal mass 1.Focal mass 2.White matter disease 2.White matter disease 3.Meningeal disease 3.Meningeal disease

7 How to approach Focal masses Focal masses Focal masses with rim-enhancement Focal masses with rim-enhancement 1.Toxoplasmosis 1.Toxoplasmosis 2.Tuberculoma 2.Tuberculoma 3.Cryptococcoma 3.Cryptococcoma 4.Primary CNS lymphoma (not infection) 4.Primary CNS lymphoma (not infection) 5.Bacterial and fungal abscesses 5.Bacterial and fungal abscesses 6.CMV encephalitis (rarely) 6.CMV encephalitis (rarely)

8 How to approach Focal masses Focal masses Focal masses without rim-enhancement Focal masses without rim-enhancement 1.Toxoplasmosis 1.Toxoplasmosis 2.Cryptococcoma 2.Cryptococcoma 3.Atypical primary CNS lymphoma 3.Atypical primary CNS lymphoma

9 How to approach White matter disease White matter disease 1.HIV encephalopathy (HIVE) 1.HIV encephalopathy (HIVE) 2.CMV encephalitis 2.CMV encephalitis 3.Progressive multifocal leukoencephalopathy (PML) 3.Progressive multifocal leukoencephalopathy (PML)

10 How to approach Meningeal disease Meningeal disease 1.HIV meningoencephalitis 1.HIV meningoencephalitis 2.Cryptococcal meningitis 2.Cryptococcal meningitis 3.Tuberculous meningitis 3.Tuberculous meningitis 4.Other bacterial/viral meningitis 4.Other bacterial/viral meningitis

11 Common diseases Common diseases

12 Toxoplasmosis Principal OI in HIV patients Principal OI in HIV patients 15-40% of AIDS patients 15-40% of AIDS patients Usually occurs when CD4 < 100 Usually occurs when CD4 < 100 Almost always a reactivation and serology is positive in 85% Almost always a reactivation and serology is positive in 85% Seronegative cases occur as a result immunosuppression or rarely a primary infection Seronegative cases occur as a result immunosuppression or rarely a primary infection

13 Toxoplasmosis Common sites : Common sites : 1.Basal ganglia 1.Basal ganglia 2.Cortico-medullary junction 2.Cortico-medullary junction usually frontal and parietal lobe usually frontal and parietal lobe 3.Brainstem 3.Brainstem Meningeal involvement uncommon Meningeal involvement uncommon

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

15 Toxoplasmosis

16 Toxoplasmosis Treatment : Treatment : Pyrimethamine + Sulfadiazine 6 weeks Pyrimethamine + Sulfadiazine 6 weeks In cases of failure to diagnose or respond to medical treatment within 7 days, biopsy is needed for tissue pathological diagnosis In cases of failure to diagnose or respond to medical treatment within 7 days, biopsy is needed for tissue pathological diagnosis Secondary prophylaxis until CD4 > 200 for 6 months Secondary prophylaxis until CD4 > 200 for 6 months

17 Tuberculosis Found in both immunocompromised and immunocompetent host Found in both immunocompromised and immunocompetent host HIV patients are prone to develop reactivation and extrapulmonary infection HIV patients are prone to develop reactivation and extrapulmonary infection Tuberculous meningitis and tuberculoma/TB abscess (uncommon) Tuberculous meningitis and tuberculoma/TB abscess (uncommon)

18 Tuberculosis CN III palsy CN III palsy Involves cerebral artery which can produce focal ischemia Involves cerebral artery which can produce focal ischemia

19 Tuberculosis Diagnosis Diagnosis 1.CSF profile : mainstay for Dx 1.CSF profile : mainstay for Dx ***AFB +ve in 1/3 ***AFB +ve in 1/3 2.Imaging : CT/MRI 2.Imaging : CT/MRI

20 Tuberculosis Diagnosis : CSF profile Diagnosis : CSF profile

21 Tuberculosis Imaging : CT/MRI Imaging : CT/MRI - Leptomeningeal enhancement mainly at the base of skull - Leptomeningeal enhancement mainly at the base of skull - tuberculoma at basal ganglia - tuberculoma at basal ganglia - communicating/noncommunicating hydrocephalus - communicating/noncommunicating hydrocephalus

22 Tuberculosis Imaging : CT/MRI Imaging : CT/MRI

23 Tuberculosis Treatment : HRZE x 9 months or more Treatment : HRZE x 9 months or more ***Steroid reduces morbidity ***Steroid reduces morbidity In case of hydrocephalus, extraventricular drainage or shunt is required to reduce ICP In case of hydrocephalus, extraventricular drainage or shunt is required to reduce ICP

24 Cryptococcosis Usually develops when CD4 < 100 Usually develops when CD4 < 100 Forms : meningitis/cryptococcoma Forms : meningitis/cryptococcoma pulmonary pulmonary skin and soft tissue skin and soft tissue Meningismus may be absent Meningismus may be absent Complication : CN deficit, visual loss, cognitive impairment Complication : CN deficit, visual loss, cognitive impairment

25 Cryptococcosis Poor prognosis : Poor prognosis : - +ve Indian ink - +ve Indian ink - high CSF pressure - high CSF pressure - low glucose - low glucose - low pleocytosis < 2 cells/mm3 - low pleocytosis < 2 cells/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

26 Cryptococcosis Diagnosis Diagnosis 1.Indian ink 1.Indian ink 2.Cryptococcal Ag in CSF/serum 2.Cryptococcal Ag in CSF/serum 3.Imaging : CT/MRI 3.Imaging : CT/MRI

27 Cryptococcosis

28 Cryptococcosis Imaging : CT/MRI Imaging : CT/MRI - hydrocephalus - hydrocephalus - meningeal enhancement - meningeal enhancement - cryptococcomas at basal ganglion - cryptococcomas at basal ganglion - punched-out cystic lesion - punched-out cystic lesion

29 Cryptococcosis Imaging : CT/MRI Imaging : CT/MRI

30 Cryptococcosis Treatment : Treatment : Amp. B mg/kg/day 2 weeks and then fluconazole 400 mg/day for 10 weeks Amp. B mg/kg/day 2 weeks and then fluconazole 400 mg/day for 10 weeks Repeated LP or shunt is necessary to relieve increased ICP Repeated LP or shunt is necessary to relieve increased ICP Secondary prophylaxis until CD4 > 200 for 6 months Secondary prophylaxis until CD4 > 200 for 6 months

31 Primary CNS lymphoma Frequently occurs in severe immunosuppression or AIDS Frequently occurs in severe immunosuppression or AIDS High grade B-cell lymphoma High grade B-cell lymphoma Strongly associated with EBV Strongly associated with EBV Poor prognosis compared to similar lymphoma outside CNS Poor prognosis compared to similar lymphoma outside CNS

32 Primary CNS lymphoma Imaging : CT/MRI Imaging : CT/MRI - rim-enhancing or heterogeneously enhancing - rim-enhancing or heterogeneously enhancing - usually > 3 cm - usually > 3 cm - periventricular, frontal, temporal - periventricular, frontal, temporal Difficult to distinguish from toxoplasmosis or metastasis Difficult to distinguish from toxoplasmosis or metastasis

33 Primary CNS lymphoma Diagnosis usually made after failure to respond to toxoplasmosis Rx Diagnosis usually made after failure to respond to toxoplasmosis Rx Brain biopsy is mandatory to obtain tissue pathology Brain biopsy is mandatory to obtain tissue pathology If safe to LP, CSF for EBV DNA help to diagnose with no need to perform biopsy If safe to LP, CSF for EBV DNA help to diagnose with no need to perform biopsy

34 Primary CNS lymphoma Imaging : CT/MRI Imaging : CT/MRI

35 Primary CNS lymphoma Treatment : CMT + WBRT Treatment : CMT + WBRT > 90% have a recurrence disease > 90% have a recurrence disease Surgical resection : for immediate decompresion of life-threatening mass effect Surgical resection : for immediate decompresion of life-threatening mass effect

36 HIV encephalopathy HIV-associated dementia HIV-associated dementia Symptoms : progressive dementia, cognitive impairment, motor symptoms, gait disturbance, tremor Symptoms : progressive dementia, cognitive impairment, motor symptoms, gait disturbance, tremor Subcortical dementia : no aphasia, apraxia or agnosia Subcortical dementia : no aphasia, apraxia or agnosia Alertness is minimally perturbed Alertness is minimally perturbed

37 HIV encephalopathy Diagnosis Diagnosis 1.Imaging : CT/MRI 1.Imaging : CT/MRI 2.CSF profile 2.CSF profile

38 HIV encephalopathy Imaging : CT/MRI Imaging : CT/MRI

39 HIV encephalopathy CSF profile CSF profile - non specific increased in cells and protein - non 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 encephalopathy - HIV RNA not correlate with HIV encephalopathy

40 HIV encephalopathy Treatment : HAART Treatment : HAART CNS resistance may occur CNS resistance may occur

41 CMV encephalitis Usually occurs when CD4 < 50 Usually occurs when CD4 < 50 Reactivation of latent infection Reactivation of latent infection Two forms : Two forms : 1.Encephalitis : progressive dementia 1.Encephalitis : progressive dementia 2.Ventriculoencephalitis : CN deficit, alteration of consciousness, nystagmus, disorientation, ventriculomegaly 2.Ventriculoencephalitis : CN deficit, alteration of consciousness, nystagmus, disorientation, ventriculomegaly

42 CMV encephalitis Diagnosis Diagnosis 1.CSF : PCR for CMV DNA 1.CSF : PCR for CMV DNA culture culture 2.Imaging : CT/MRI 2.Imaging : CT/MRI - periventricular enhancement - periventricular enhancement ***no calcification like congenital CMV ***no calcification like congenital CMV - subependymal enhancement - subependymal enhancement - 50% normal imaging - 50% normal imaging

43 CMV encephalitis Imaging : CT/MRI Imaging : CT/MRI

44 CMV encephalitis Treatment : Ganciclovir, Valganciclovir Treatment : Ganciclovir, Valganciclovir induction of days followed by prolonged maintenance therapy induction of days followed by prolonged maintenance therapy Secondary prophylaxis until CD4 > 100 for 3 months Secondary prophylaxis until CD4 > 100 for 3 months

45 PML Caused by the reactivation of the Jamestown Canyon (JC) virus Caused by the reactivation of the Jamestown Canyon (JC) virus CD4 counts usually below 100/mm3 CD4 counts usually below 100/mm3 Multiple areas of demyelination throughout the brain sparing cord and optic nerve Multiple areas of demyelination throughout the brain sparing cord and optic nerve

46 PML Symptoms : visual loss Symptoms : visual loss mental impairment mental impairment weakness weakness ataxia ataxia

47 PML Diagnosis : Diagnosis : 1. MRI 1. MRI - multifocal asymmetric white matter lesions - multifocal asymmetric white matter lesions - subcortical white matter, cerebellum - subcortical white matter, cerebellum - low signal on T1 weighted images and hyperintense on T2 weighted/FLAIR - low signal on T1 weighted images and hyperintense on T2 weighted/FLAIR

48 PML Diagnosis : MRI Diagnosis : MRI

49 PML Diagnosis : Diagnosis : 2.CSF : PCR for JCV DNA 2.CSF : PCR for JCV DNA normal cells and protein normal cells and protein

50 HSV encephalitis HSV produces necrotizing encephalitis in HIV patients HSV produces necrotizing encephalitis in HIV patients Predilection for the medial temporal and inferior frontal lobes Predilection for the medial temporal and inferior frontal lobes

51 HSV encephalitis Diagnosis : Diagnosis : 1.CSF : PCR for HSV DNA 1.CSF : PCR for HSV DNA - sens. 96% and spec. 99% - sens. 96% and spec. 99% (equivalent or exceed brain biopsy) (equivalent or exceed brain biopsy) - maybe negative if too early (< 72 hr) or more than 14 days - maybe negative if too early (< 72 hr) or more than 14 days

52 HSV encephalitis Diagnosis : Diagnosis : 2.Imaging : CT/MRI 2.Imaging : CT/MRI - area of low absorption, mass effect or hemorrhage on CT - area of low absorption, mass effect or hemorrhage on CT - hyperintensity signal on T2/FLAIR or diffuse-weighted - hyperintensity signal on T2/FLAIR or diffuse-weighted

53 HSV encephalitis Imaging : CT/MRI Imaging : CT/MRI

54 HSV encephalitis Treatment : IV acyclovir 10 mg/kg q 8 hr for 14 days and repeat CSF profile Treatment : IV acyclovir 10 mg/kg q 8 hr for 14 days and repeat CSF profile *** Dilute < 7mg/ml and infused slowly over 1 hr to minimize renal dysfunction *** Dilute < 7mg/ml and infused slowly over 1 hr to minimize renal dysfunction

55 Take home messages Neurological manifestations in HIV/AIDS patients have a wide spectrum Neurological manifestations in HIV/AIDS patients have a wide spectrum Clinicians must consider multiple causes which share similar clinical and radiographic patterns Clinicians must consider multiple causes which share similar clinical and radiographic patterns Neurosurgery carry an important role for diagnosis and treatment Neurosurgery carry an important role for diagnosis and treatment

56 References Youman textbook of neurosurgery 6 th ed. Youman textbook of neurosurgery 6 th ed. Harrison textbook of internal medicine 17 th ed. Harrison textbook of internal medicine 17 th ed. Lancet neurology 2012 Lancet neurology 2012

57 THANK YOU THANK YOU


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