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This is a short presentation of Neurological manifestation of AIDS specially in India
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NEUROLOGIC MANIFESTATION OF HIV/AIDS (INDIA)
Dr PS Deb, MD, DM
NEURO HIV/AIDS: EPIDEMIOLOGY
Post MortemClinical
First SymptomDeath
0
10
20
30
40
50
60
70
80
HOW DOES HIV AFFECT THE NERVOUS SYSTEM?
NEURO HIV/AIDS CLASSIFICATION: ICD10
B20: Oppor. Infection
• (B20.0) HIV disease resulting in mycobacterial infection
• (B20.1) HIV disease resulting in other bacterial infections
• (B20.2) HIV disease resulting in cytomegaloviral disease
• (B20.3) HIV disease resulting in other viral infections
• (B20.8) HIV disease resulting in other infectious and parasitic diseases
• (B20.9) HIV disease resulting in unspecified infectious or parasitic disease
B23: Other
B21: Neoplasm• (B21.0) HIV disease resulting
in Kaposi's sarcom• (B21.2) HIV disease resulting in other
types of non-Hodgkin's lymphoma• (B21.3) HIV disease resulting in
other malignant neoplasms of lymphoid, haematopoietic and related tissue
• (B21.7) HIV disease resulting in multiple malignant neoplasms
• (B21.8) HIV disease resulting in other malignant neoplasms
• (B21.9) HIV disease resulting in unspecified malignant neoplasm
B22: Specific Syndromes• (B22.0) HIV disease resulting
in encephalopathy
B24: NOS
NEURO HIV/AIDS : PATHO-PHYSIOLOGIC
Primary (caused by HIV alone)• AIDS Dementia Complex (brain)• Vacuolar Myelopathy (spinal cord)• Peripheral Neuropathy (nerve)• Meningitis (acute and chronic)
Secondary (opportunistic infections )• Fungal (Cryptococcal Meningitis)• Parasitic (Toxoplasmosis)• Viral (Progressive Multifocal Leukoencephalopathy, CMV,HSV,VZV)• Bacterial (TB, Syphilis)• HIV-Related Tumors (Primary CNS lymphoma, Kaposi Sarcoma, Multiple
lymphoma)
Tertiary (treatment complications)• Autoimmune (GBS)• Immune Reconstitution Inflammatory Syndrome (IRIS)• “Neuromuscular weakness syndrome”• Drug induced peripheral neuropathy/myopathy
NEURO HIV/AIDS: ANATOMICAL
Brain • Meningitis• Dementia• Stroke• Seizures• Degenerative Disorders
Spinal cord• Transverse myelitis• Progressive Myelopathy
(acute/subacute/chronic)
Peripheral neuropathies• Cranial• Peripheral• Sensory• Motor, • Autonomic
Myopathy( +/-inflammatory)
Parallel Tracking • Existence of multiple
pathologies in different parts of the nervous system (cerebral, spinal cord, peripheral nerves)
Layering • Multiple complications in one
part of the nervous system
Unmasking • Previously compensated
deficits may be unmasked by occurrence of an additional insult
EARLY(CD4 > 500/mm3
MIDSTAGE(CD4 = 200-500/mm3)
ADVANCED(CD4 < 200/mm3)
Seroconversion syndromes
MeningitisMeningoencephalitisMyelitisDemyelinating syndromes
AIDPSensory ganglionopathyBrachial plexopathyRhabdomyolysis
HIV related meningitis: aseptic (acute, recurrent, chronic)Asymptomatic CSF abnormalities: elevated protein, lymphocytic pleocytosis, normal glucose
HIV DementiaCryptococcal meningitisToxoplasmosisPMLVacuolar MyelopathyCMV- encephalitis - polyradiculitis - mononeuritis multiplex
Herpes zoster radiculitis
Distal sensory polyneuropathy
Demyelinating polyneuropathiesMononeuritis multiplex
NRTI neuropathy, AZT myopathyPolymyositis
Immune mediated
Immune compromised
NEURO HIV/AIDS: TEMPORAL
NEURO AIDS IN INDIA: NIMHANS BANGALORE 20Y REGISTRY CASES
HIV 1 C Clad (West B) recombinant strain rare.
Mode of Transmission – Hetero 86%, Blood Transfusion 2.04%, IDU 2.34%
Neuro AIDS – 70-85% OpI
• Cryptococcus - 37.2%• TB - 31.9%• Dementia - 1.4% (west 30-
40%)• PML - Rare • Myelopathy - Rare• Neoplasm -
Infrequent, (PCNL) and (Kaposi
sarcoma)•
Pandey A, Reddy DC, Ghys PD, et al. Improved estimates of India’sHIV burden in 2006. Indian J Med Res 2009; 129: 50–58.
NEUROLOGIC MANIFESTATIONS OF HIV INFECTION: NIMS HYDERABAD
Retrospective survey 1993-2003
Total 7091 (OP 5485 -> IP 1606)
Neurological events 25% (411/1606)
Meningitis: 162
• TBM : 25.06%• CRM : 10.95%• Pyogenic: 1.95%• Aseptic: 1.95%• Syphilis: 0.97%
Mass Lesions: 113• Toxoplasma: 9.25%• Tuberculoma: 10.71%• Lymphoma: 6.08%• PML: 1.70%
Neuoropathy : 84• Mononeuritis multiplex• DSP• Progressive PNP• AIDP• CIDP• Sensory neuropathy• Cranial neuropathy• Toxic Neuropathy
Myelopathy + Dementia: 33
Vijay D. Teja, MD, Sudha Rani Talasila, MSc, Lakshmi Vemu, MD :AIDS Read. 2005;15(3):139-145
NEUROLOGIC MANIFESTATIONS OF THE HIV: MUMBAI
300 cases over 3years ART-naive
67 (22.3%) had neurologic manifestations due to the direct effects of HIV-1
Meningitis: 75
• TBM : 51• CRM : 24• Zoster: 01• Aseptic: 03
CMV Encephalitis 1
Mass Lesions: 137 • Toxoplasma: 61• Tuberculoma: 48• Lymphoma: 08• PML: 20
Myelopathy: 2
Neuoropathy : 24 • Peripheral neuropathy: 15• Cranial neuropathy: 09
Dementia: 4
Myopathy: 1
Stroke: 20
Alaka K. Deshpande, Department of Retroviral Medicine, Grant Medical College & Sir JJ Group of Hospitals, Mumbai, India.
ASEPTIC MENINGITIS
May occur in acute infection or sero-conversion or in the chronic stage of HIV infection
Clinical
• Fever, malaise, stiff neck, and photophobia• Clinical course is self-limited, without sequelae• Cranial neuropathy, typically Bell’s palsy, may co-exist• After recovery, underlying HIV may be asymptomatic
Laboratory evaluation
• CSF: lymphocytic pleocytosis; normal glucose and normal or slightly elevated protein
• HIV serology: may be negative; repeat at 3 and 6 months• HIV antigen and viral determination positive• T cell studies: normal or borderline• EEG, CT or MRI of brain normal or non-diagnostic
SYMPTOMATIC NEURO-COGNITIVE DISORDER ASSOCIATED WITH HIV IN INDIA
Rare – 1-4% in various large studies• Early death due to OIs• Under reporting due to poor
evaluation• HIV clad C • Genetic factor of Host
CMV ENCEPHALITIS
Common (IgM 10%) OpI, HSV5 ubiquitous, (IgG 60-80%) asymptomatic, reactivation in immuno-compromised
Confusion, headache, delirium, focal neurology, cranial nerve deficits
IV ganciclovir, valganciclovir, foscarnet,
cidofovir
CRYPTOCOCCOSIS
•Most cases seen in patients with CD4 count <50 cells/µL•30-40% of Neuro AIDS in Developing countries•5-8% in developed countries before widespread use of effective ART , much lower with use of ART
CRYPTOCOCCAL MENINGITIS
•Fever, malaise, headache
•Neck stiffness, photophobia, or other classic meningeal signs and symptoms in 25-35% of cases
•Lethargy, altered mental status, personality changes (less common)
Subacute or Chronic meningitis
•Lymphocytic with raised protein, low sugar
•India Ink•Cr Ag in CSF•Cr culture in
Blood
CSF
CRYPTOCOCCOSIS: TREATMENT
•Induction (≥2 weeks): •Amphotericin B 0.7 mg/kg IV QD + Flucytosine 25 mg/kg PO QID
•Lipid formulation Amphotericin B 4-6 mg/kg IV QD + Flucytosine 25 mg/kg PO QID
•Consolidation (8 weeks): •Fluconazole 400 mg PO QD
•Chronic maintenance:•Fluconazole 200 mg PO QD
First
•Induction: •Amphotericin (deoxycholate or lipid formulation, dosed as preferred therapy) + fluconazole 400 mg PO or IV QD for 2 weeks
•Amphotericin (deoxycholate or lipid formulation, dosed as preferred therapy) for 2 weeks
•Fluconazole 400-800 mg PO or IV QD + flucytosine 25 mg/kg PO QID for 4-6 weeks (inferior efficacy)
•Consolidation: •Itraconazole 200 mg PO BID for 8 weeks
•iChronic maintenance:• Itraconazole 200 mg PO QD
Alternative
CRYPTOCOCCOSIS: ADVERSE EVENTS
•Up to 30% develop IRIS after initiation of ART
•Management: continue ART and antifungal therapy
•If severe IRIS symptoms, consider short course of corticosteroids
•Consider delaying initiation of ART at least until completion of induction therapy
IRIS
•Lifelong suppressive treatment (after completion of initial therapy), unless immune reconstitution on ART
•Preferred: fluconazole 200 mg QD
•Consider discontinuing maintenance therapy in asymptomatic patients on ART with sustained increase in CD4 count to >200 cells/µL for ≥6 months
•Restart maintenance therapy if CD4 count decreases to <200 cells/µL
Secondary prophylaxis:
TUBERCULOSIS IN HIV
•WHO 2006 9.2millioon TB world and 7.7% were HIV +•TB in normal population 5-10% / 5-15 % in HIV +•Role of HIV epidemic on TB epidemic in India is not clear
CLINICAL AND IMMUNO PATHOLOGICAL COURSE OF HIV ASSOCIATED TUBERCULOSIS (DE COCK ET AL 1992).
HIV AND NS TUBERCULOSIS
1/3 of all AIDS related deaths due to Tb. Untreated universally fatal, with low CD4• HIV accelerates the spread of TB and latent to active by 100
fold• Accelerates the course of HIV so needs index of suspicion.• HAART has reduced TB by 80% in Brazil• India Human Mycobacterium is common not avian
Clinical picture of TBM with/without HIV not much difference• Fever less common• Seizure more common• Hydrocephalus more common• Cerebral infarction more common• No difference in CSF picture• No difference in the response to the treatment
TREATMENT OF TB MENINGITIS
Anti TB (HRZ+E/STM)x2 + (HR)x10 months (12-18months)
Steroid: can be used as in non HIV case• Reduce cerebral edema, ICH,
inflammation• Prevent hydrocephalus, vasculitis• Mortality benefit (41->31%) in Vietnam
study
FOCAL SYNDROMES AND MASS LESIONS
•Herpes simplex; Varicella zoster; progressive multifocal leukoencephalopathy
Viral:
•Abscess due to Cryptococcus, Candida, Zygomycetes, Histoplasma, Aspergillus
Fungal:
•Abscess due to pyogenic bacteria, mycobacteria (tuberculoma), Listeria, Nocardia
Bacterial:
•Trypanosoma cruzei; Taenia solium; toxoplasmosis
Parasitic:
•Primary or metastatic lymphoma; glioma; metastatic Kaposi’s sarcoma
Neoplasm:
TOXOPLASMOSIS
CEREBRAL TOXOPLASMOSIS
20-40% in AIDS with low CD4 (<100)
Reactivation of prior infection
Presentation – Focal mass lesion, altered mentation
Diagnosis• Imaging• Serology (+ >97% for IgG), if –ve likelihood of toxo is <
10%• CSF nonspecific• Biopsy if unresponsive to Rx
CEREBRAL TOXOPLASMOSIS IMAGING
Multiple/single, ring enhancement, surrounding edema• Multiple in 2/3, ring
enhancing-90%• Size < 2cm• Site: Parietal/frontal
lobes, thalamus , BG, Brainstem, Corticomedulary junction, Pituitary
TOXOPLASMOSIS RX
•Pyrimethamine (200mg-L/75C) + Sulfadiazine(6-8g/d -4d/d) till improve CD4 count
•Pyrimethamine + Clindamycine
First Line
•Pyrimethamine+ Azithromycin
•Pyrimethamine+ Atovaquine
•Sulfadiazine+ Atovaquine
Alternative
•Relapse common
•Reduce dose and continue
Maintenance
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)
JC virus(Human polyoma virus), reactivation (70% of adult population: Ab to JC virus)
Late manifestation of AIDS ; in ~4% of pts with AIDS
Bilateral, asymmetric, & localized preferentially to periventricular areas & subcortical white matter .
Protracted course +/- Change in mental state, Multifocal deficit:
Uncommon in India
PRIMARY CNS LYMPHOMA
AIDS defining malignancy ~20% cases of lymphoma in HIV
Usually associated with EBV infection , no age predilection.
Median CD4 ~ 50/ul: at later stage and poorer prognosis than systemic lymphoma
Presentation: Focal deficit with cognitive impairment, sub-acute
Radiotherapy (usually palliative) or high dose methotrexate (chemo)Uncommon in India
STROKE IN HIV
Ischemic and hemorrhagic –clinical in 4%, autopsy report 34%.
Ischemic• Bacterial endocarditis • Non bacterial thrombotic• Infectious vasculitis- (VZV, Tb, syphilis, crypto, angioinvassive fungi-asperg & mucor)
• Granulomatous angitis• Procoagulant state
Hemorrhagic• Thrombocytopenia• Coagulopathy-CLD,DIC• PCNSL, KSa, toxo• Drugs- cocaine, amphetamin• TTP
VACUOLAR MYELOPATHY
Vacuolar Myelopathy• - 1/3 (20-55%) in autopsy series
Clinical manifestation is much smaller• Usually late HIV• Develops slowly (months)• Coexisting neuropathy• Sensory symptoms: loss vibration and joint
position sensation with relatively preserve pain sensation.
• No discrete sensory level
AIDS NEUROPATHY
Distal symmetrical polyneuropathy
Inflammatory demyelinating polyneuropathy
Mononeuritis multiplex
Isolated mononeuropathy
Progressive polyradiculopathy
Autonomic neuropathy
AIDS MYOPATHY
Causes: • Drug treatment (AZT/NRTI);• HIV : AIDS cachexia• Secondary infection – Toxo• Rhabdomyolysis, NHL, myasthenia gravis, nemaline (rod)
Clinical:• Progressive proximal limb weakness
Laboratory:• Elevated creatine kinase; myopathic features on EMG; +/-
myoglobinuria• Muscle biopsy
Treatment:• Discontinue AZT; steroids or plasmapharesis; treat infection