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

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

How to approach 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 However, opportunistic infection should draw attention firstly

How to approach Algorithm

How to approach Source : HIV-associated Opportunistic infections of the CNS Lancet Neurol 2012; 11: 605-17

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

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

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

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

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

Common diseases

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

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

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

Toxoplasmosis

Toxoplasmosis Treatment : 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 Secondary prophylaxis until CD4 > 200 for 6 months

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

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

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

Tuberculosis Diagnosis : CSF profile

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

Tuberculosis Imaging : CT/MRI

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

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

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

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

Cryptococcosis

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

Cryptococcosis Imaging : CT/MRI

Cryptococcosis Treatment : Amp. B 0.7-1.0 mg/kg/day 2 weeks and then fluconazole 400 mg/day for 10 weeks Repeated LP or shunt is necessary to relieve increased ICP Secondary prophylaxis until CD4 > 200 for 6 months

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

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

Primary CNS lymphoma Diagnosis usually made after failure to respond to toxoplasmosis Rx 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

Primary CNS lymphoma Imaging : CT/MRI

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

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

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

HIV encephalopathy Imaging : CT/MRI

HIV encephalopathy CSF profile - non specific increased in cells and protein - helpful in diagnosing or ruling out OI - HIV RNA not correlate with HIV encephalopathy

HIV encephalopathy Treatment : HAART CNS resistance may occur

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

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

CMV encephalitis Imaging : CT/MRI

CMV encephalitis Treatment : Ganciclovir, Valganciclovir induction of 14-21 days followed by prolonged maintenance therapy Secondary prophylaxis until CD4 > 100 for 3 months

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

PML Symptoms : visual loss mental impairment weakness ataxia

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

PML Diagnosis : MRI

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

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

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

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

HSV encephalitis Imaging : CT/MRI

HSV encephalitis 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

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

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

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