HIV Neurology, AIDS

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HIV Neurology : 

HIV Neurology Dr Rahul Chakor Lecturer – Dept of Neurology T N Medical College B Y L Nair Hospital Mumbai

Introduction : 

Introduction HIV is neuro-invasive virus (early CNS invasion) HIV is neurovirulent (All areas of the neuro-axis infected) Neurologic complications seen throughout the course of HIV infection Multiform presentation - Multiple simultaneous pathologies (diagnostic law of parsimony/ocams razor does not apply)

Epidemiology : 

Epidemiology Neurologic complications are present in more than 40% of patients with HIV Presenting feature of AIDS in 10-20% Autopsy - prevalence of neuropathologic abnormalities in 80%

Neurologic diseases in patients with HIV infection : 

HIV Infection HIV related Neoplasm's Opportunistic Infections Complications of ART HIV Neurologic diseases in patients with HIV infection

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HIV

HIV Infection : 

HIV Infection Aseptic Meningitis HIV- associated dementia (HIV encephalopathy, AIDS dementia complex) Myelopathy - Vacuolar - Pure sensory ataxia - Paresthesia/dysesthesia

HIV Infection : 

HIV Infection Peripheral Neuropathy - Distal symmetric polyneuropathy - AIDP (GB Syndrome) - CIDP - Mononeuritis multiplex HIV Myopathy

Opportunistic Infections : 

Opportunistic Infections - Cryptococcal meningitis - Toxoplasmosis – granuloma - JC virus - Progressive Multifocal Leukoencephalopathy - CMV – retinitis, encephalitis, lumbosacral polyradiculopathy, vasculitic neuropathy - Syphilis - Tuberculosis – meningitis, abscess, tuberculoma - HTLV

HIV Neoplasm's : 

HIV Neoplasm's - Primary CNS lymphoma - Kaposi’s sarcoma

Related to ART : 

Related to ART - Zidovudine myopathy - NRTI – related neuropathy (Stavudine, Zalcitabine, Didanosine)

Neuroanatomical Classification of HIV neurology : 

Neuroanatomical Classification of HIV neurology Meninges Brain Spinal cord Peripheral nerves Muscle

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Infections Aseptic HIV meningitis Cryptococcal meningitis Tuberculous meningitis Syphilitic meningitis L monocytogenes Neoplasms Lymphomatous meningitis (metastatic) Meninges

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Nonfocal HIV associated dementia CMV encephalitis Herpes encephalitis Toxoplasmic encephalitis Aspergillus encephalitis Focal Toxoplasmosis CNS lymphoma Prog Multi Encephalopathy Tuberculoma VZ encephalitis Cryptococcoma Stroke Brain

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Spinal cord Vacuolar myelopathy CMV myeloradiculopathy VZV myelitis Spinal lymphoma HTLV associated myelopathy

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Early stage AIDP CIDP Vasculitic neuropathy Brachial plexopathy Lumbosacral plexopathy Cranial mononeuropathy Mononeuritis multiplex Mid and late stage Distal sensory polyneuropathy Autonomic neuropathy Peripheral neuropathies

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Late stage CMV polyradiculomyelitis Syphilitic polyradiculomyelitis Tuberculous polyradiculomyelitis Lymphomatous polyradiculoneuropathy Zoster ganglionitis CMV mononeuritis multiplex Nutritional (vit B12, B6) Drug induced NRTI (ddI,ddC,d4T) INH, ETB, Peripheral neuropathies

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Myopathies Polymyositis Pyomyositis Zidovudine myopathy

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EARLY (CD4 > 500/mm3 MIDSTAGE (CD4 = 200-500/mm3) ADVANCED (CD4 < 200/mm3) Seroconversion syndromes Meningitis Meningoencephalitis Myelitis Demyelinating syndromes AIDP Sensory ganglionopathy Brachial plexopathy Rhabdomyolysis HIV related meningitis: aseptic (acute, recurrent, chronic) Asymptomatic CSF abnormalities: elevated protein, lymphocytic pleocytosis, normal glucose HIV Dementia Cryptococcal meningitis Toxoplasmosis PML Vacuolar Myelopathy CMV- encephalitis - polyradiculitis - mononeuritis multiplex Herpes zoster radiculitis Distal sensory polyneuropathy Demyelinating polyneuropathies Mononeuritis multiplex NRTI neuropathy, AZT myopathy Polymyositis Temporal sequence of neurological complications in HIV Immune mediated Immune compromised

Acute HIV Syndrome/ Seroconversion syndrome : 

Acute HIV Syndrome/ Seroconversion syndrome 1-6 weeks after primary infection 80% of pts - Infectious mononucleosis like presentation Fever, headache, arthralgia, anorexia lymphadenopathy, rash, CSF- normal or mild pleocytosis Complete recovery

Acute HIV Syndrome : 

Acute HIV Syndrome 10% of pts – Aseptic meningitis Encephalitis Acute disseminated encephalomyelitis Transverse myelitis Polymyositis Brachial neuritis VII nerve palsy Cauda equina syndrome. Peripheral neuropathy (GB Syndrome)

Acute HIV Syndrome : 

Acute HIV Syndrome CSF pleocytosis, elevated proteins, normal glucose Diagnosis of exclusion No specific treatment Prognosis Resolves spontaneously in 2 -4 weeks

Asymptomatic or latent stage : 

Median 10 years Virus replicates and disease progresses CD4 drop by 50μL/year Opportunistic infections when CD4 reaches < 200 μL Long-term nonprogressors with no decline in CD4 Asymptomatic or latent stage

Common manifestations : 

Common manifestations HIV related HIV associated Dementia Vacuolar Myelopathy Distal sensory polyneuropathy Opportunistic Infections Cryptococcal meningitis Toxoplasmosis Progressive multifocal leukoencephalopathy CMV polyradiculopathy ART related NRTI neuropathy ( stavudine, didanosine zalcitabine

HIV- Associated Dementia/ HIV encephalopathy/ AIDS Dementia Complex : 

HIV- Associated Dementia/ HIV encephalopathy/ AIDS Dementia Complex Late manifestation of AIDS, after other AIDS defining illness AIDS defining illness CD4 count 350 cells/μL or less Progressive cognitive decline Motor symptoms Bowel, bladder incontinence

Clinical staging of AIDS dementia complex : 

Clinical staging of AIDS dementia complex

HIV- Associated Dementia : 

HIV- Associated Dementia Behavioral problems, apathy, slowed thinking, forgetfulness Progressive cognitive decline, motor features, vegetative state, incontinence, paraparetic

HIV- Associated Dementia : 

HIV- Associated Dementia Neuroimaging - To exclude Opportunistic infections and neoplasms - Cerebral atrophy, T2 hyperintensities on MRI CSF - Increase in cells and proteins, to rule out opportunistic infections - HIV PCR, immune activation markers Treatment - HAART

HIV Myelopathy/ Vacuolar Myelopathy : 

HIV Myelopathy/ Vacuolar Myelopathy Late manifestation of HIV Evolves over several months As a part of HAD (similar pathologic process), coexists with DSP Gait difficulty, spasticity, proprioceptive loss, later sphincter disturbance, without back pain Posterior and lateral column degenaration

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Other causes of Myelopathy in AIDS CMV VZV, HSV Neurosyphilis B12 deficiency Lymphoma with epidural metastasis Epidural abscess Tuberculoma or Toxoplasma

HIV Myelopathy : 

HIV Myelopathy

Neuropathy : 

Neuropathy Distal sensory neuropathy Most common neuropathy in HIV Length dependent, axonal, predominantly sensory Mild multimodality stocking sensory loss Subacute onset burning pain and paresthesia in feet, hyperpathia

Neuropathy : 

Other etiologies for neuropathy Didanosine, zalcitabine, stavudine, isoniazid, pyridoxine, dapsone, metronidazole, B12 deficiency, diabetes Treatment Tricyclic antidepressants, anticonvulsants, SSRI Neuropathy

Myopathy : 

Myopathy Presentation like polymyositis During any stage of HIV, immune mediated, immune reconstitution Asymptomatic elevation of CPK Progressive limb girdle syndrome Treatment Steroids, IV globulins

Primary CNS Lymphoma : 

Primary CNS Lymphoma Seen in 5 % AIDS patients Large-cell, B cell, non-Hodgkin lymphoma, affecting brain, rarely spinal cord Opportunistic EB Virus neoplasm Second most common mass lesion (after toxoplasmosis) in AIDS Presentation of late AIDS

Primary CNS Lymphoma : 

Presentation more insidious than toxoplasmosis and faster than PML Presenting symptoms are focal weakness, ataxia, aphasia, lethargy, confusion, impaired memory, headache Funduscopy may reveal ocular involvement Fever is usually absent. Primary CNS Lymphoma

Primary CNS Lymphoma : 

Diagnosis CT scan and MRI of the brain – multicentric mass lesions, periventricular with subependymal extension, white matter. Mass effect, edema contrast enhancement and cystic changes Thallium 201 single photon emission computed tomography (201Tl SPECT) – increased uptake CSF PCR for EBV DNA Stereotactic Brain biopsy ? Trial of Antitoxoplasma therapy Primary CNS Lymphoma

Primary CNS Lymphoma : 

Treatment HAART and cranial radiation increase survival Treatment with ganciclovir was associated with increased survival and undetectable CSF EBV DNA load Use of HAART leads to an increase in CD4+ T cells and increases survival to more than 18 months. Primary CNS Lymphoma

Cryptococcal Meningitis : 

Cryptococcal Meningitis Frequency is 10% in pts with AIDS Encapsulated yeast Cryptococcus neoformans Variable presentation - Headache, photophobia, blurred vision, personality change, cognitive impairmrnt, altered mentation, coma - Headache and papilloedema, pseudotumor syndrome - Fever, neck neck stifness are notably absent

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CSF - Minimal abnormalities - ↑ Pressure, Elevated protiens, pleocytosis, low sugar - India ink preparation for cryptococus - CSF cryptococcal antigen positive in > 90 % patients

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India Ink preparation

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Neuroimaging to exclude focal cerebral disorders and for complications like cryptococcoma, hydrocephalus, infarction Neuroimaging shows cerebral atrophy, no focal lesion

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Management algorithm for Cryptococcal meningitis

Toxoplasmosis : 

Toxoplasmosis Frequency is 10% among AIDS pts T. gondii , recurrence of earlier infection due to immunodeficiency Headache, focal neurodeficit, hemiparesis, aphasia, seizures. Cerebral edema leading to lethargy confusion, stupor and coma

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Thank You

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