Neurological Manifestations Associated with HIVAIDS : Indian Scenario

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Neurotuberculosis associated with HIV/ AIDS-
Limited resource settings

• P.Satishchandra
• Department of Neurology
• National Institute of Mental Health Neuro
  Sciences (NIMHANS),Bangalore, India

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Nervous System and HIV Infection

• Initial manifestation - 10
• Symptomatic Neurological - 40-70
  disorders and HIV
• Autopsy evidence of nervous - 90
  system involvement

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Neurological Manifestations Associated with
HIV/AIDSNIMHANS Experience (1989-2001) (n430 )

• Opportunistic CNS Injections (Group I) 368
  (85.6)
• Non-Infections (Group II) 62 (14.4)
• P.Satishchandra,A.Nalini,M.Gourie-Devi et al
• Indian J Med Res 2000 11114-23

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Opportunistic Infections Associated with HIV/AIDS
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Opportunistic Infections of Nervous System
Associated with HIV/AIDS

• Virus Bacteria
  Fungi Parasite
• Herpes M.Tuberculosis Cryptococcal CNS
  Toxoplasmosis
• CMV Atypical Mycobacteria Coccidiodomycosis
  Acanthamoeba
• HSV Syphilis Histoplasmosis
  Trypanosoma C
• VZV Bartonella Blastomycosis
  S.Stercoralis
• JC Virus Nocardia Aspergillosis
  Cysticercosis
• Candida Albicans
• Mucormycosis
• Sporotrichosis

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Neuro Infections associated with HIV/AIDS
(1989-2000)
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Opportunistic Infections Associated with HIV/AIDS

• Nature of Infection
  NIMHANS RR Hospital Ruby Hall
  
  Bangalore New Delhi
  Pune
  
• 
  n () n
  () n ()
• Tuberculous Meningitis 120 (32.6) 40 (42.1)
  16 (11.2)
• Cryptococcal Meningitis 100 (27.2) 24 (25.3)
  58 (40.5)
• TBM Crypto. Meningitis 45 (12.2) 4
  (4.2) 01 ( 0.7)
• Toxoplasmosis 36 (9.9) 7 (7.4)
  41 (28.7)
• Tuberculoma / Toxoplasma 22 (5.9) 8 (8.4)
  20 (13.9)
• Crypto TB Mixed infections 18 (4.9) 5
  (5.3) -
• Crypto Toxo 13 (3.5) 2 (2.1)
  -
• Herpes Infection 7 (1.9)
  - -
• Neurosyphilis 5 (1.3) -
  2 ( 1.4)
• TBM Polymicrobial infection -
  3 (3.1) -
• Acute Pyogenic Meningitis 2 (0.6) 2 (2.1)
  5 ( 3.5)
• Total
  368 95
  143

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Diagnosis of CNS Tuberculosis
Neuroimaging
Systemic Screening
CSF Examination
FNAC Lym. Node
USG abdomen
X-ray Chest
MRI Brain
CT Scan
Immunological Tests
PCR for Myco. DNA
CSF Smear For AFB
Routine

• Cytology
• Cell count
• Protein

AFB C/S
Anti bodies
Antigen
Immune Complex
Conventional LJ Slopes
BACTEC Rapid
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Neuro imaging in CNS Tuberculosis

• CT Scan No. of cases MRI
  No. of cases
• findings N111
  Findings N4
• Normal 5 Tuberculoma 3
• Hydrocephalus 32 Hydrocephalus 1
• Basal exudates 17
• Arteritis infarction 21
• Diffuse oedema 7
• Tuberculoma 29

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HIV TBM
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T1
T1 C
HIV TBM
T2
T2
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TBM with and without HIV Infection NIMHANS Study

• Clinical Features
• P lt 0.05 Kawre KK,
  Satishchandra P. 2001

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TBM with and without HIV Infection NIMHANS Study

• Clinical Features HIV Positive HIV
  Negative TBM (n32) TBM (n35)
• Extra CNS TB 15 (46.9) 6 (17.1)
• Oral candidasis 07 (21.9) 3 ( 5.7)
• Focal neurological deficits 11 (34.4) 14 (40
  .0)
• Cranial nerve deficits 06 (18.8) 16 (45.7)
• ESR (mm/hr) 78.7 42.0
• Mean CD4 count 196.4 587.2
• Mean CD4 / CD8 -0.63 1.16
• Significant Kawre KK,
  Satishchandra P. 2001

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TBM with or without HIV Co-infection NIMHANS Study

• Parameters HIV Positive HIV Negative
• TBM TBM
• CSF Cell count 274 (7-1925) 209 (14-1200)
• Protein / mg 158.9 183.4
• AFB Positivity 5 (15.6) 9 (25.7)
• Mycobacterial 12 (37.5) 18 (51.4)
• Antibody (ve)
• Kawre KK, Satishchandra P. 2001

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TBM with and without immuno deficiency Imaging
CT Scan

• Significant
  Kawre KK, Satishchandra P. 2001

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Mortality in TBM with and without immuno
deficiency (meta analysis)
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Kawre KK, Satishchandra P, 2001
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TUBERCULOUS BASAL MENINGITIS
AFB POSITIVE
HIV POSITIVE
HIV NEGATIVE
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HIV Positive TBM No exudate
Basal Smear AFB POSITIVE
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TB phlebitis
TB arteritis
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Treatment for CNS - Tuberculosis

• Treatment
  No. of cases
  N120
• ATT only 110
• ATT Steroids 9
• No. specific treatment 1

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Drug resistance pattern of M.Tuberculosis
isolates to four primary anti-tuberculosis drugs
Pereira M et al. IJMR 121, April, 2005, pp 235-239
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Preventive Therapy for TB in HIV Infected
Individuals

• Co-infection of HIV TB
• 68 in Sub-Saharan Africa
• 22 in South East Asia.
• Intervention Strategies for Developing Countries
• Case finding Treatment
• Provision of BCG vaccination during infancy
• Preventive therapy chemoprophylaxis
• Enviornmental Measures

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Atypical Mycobacteria

• Mycobacterium Avium intracellulare (MAI)
• Single or multiple mass lesions
• Atypical meningitis
• Imaging similar to MTB
• Four drug regimenAzithromycin 500 1000
  mg/dayClarithromycin 500 1000
  mg/dayEthambutol 15 mg/kg/dayClofazamine 100
  mg/day
• In general response is disappointing

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Differential Diagnosis of Nodular lesions in HIV

• --------------------------------------------------
  ---------------------------------------
• Parameters Toxoplasmosis CNS Lymph
  PML Tuberculosis
• --------------------------------------------------
  ---------------------------------------
• Duration Days Days-Weeks Weeks
  Weeks
• Fever
  -
• No.of lesions Variable Multiple
  Few Variable
• Enhancement
  Nil
• Site BG, Cerebellum
  Periventricular White Disseminated
• brain stem
  subcortical matter
• CD4 Low Very
  low Very low 150-300
• --------------------------------------------------
  ---------------------------------------

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HIV AUTOPSY DATA (1990-2004)Department of
Neuropathology(N134)

• Crypto meningitis (CM) 42 (31.3)
• Toxo encephalitis (TE) 28 (20.8)
• TB meningitis (TBM) 27
  (20.1)
• CM TBM
  06 (4.4)
• CM TE 06 (4.4)
• CM TE TBM 02 (1.5)
• TBMTE 05 (3.7)
• TE Acanthameba encep 01 (0.7)
• CM CMV encephalitis 01
  (0.7)
• Santosh V, Yasha T C ,Panda, KM, Das S,
  Satishchandra P,, Shankar SK
• Annals of Indian Academy of Neurology, 1998,Vol
  1,71-82

Herpes encephalitis 01 (0.7) Pyogenic mening 02
(1.5) HIV leukoenceph 03 (2.2) Lymphoma 1
(0.7) Lymphomatoid granul 1 (0.7) PML (Biopsy-
3) 5 (3.7) Cerebral malaria 1 (0.7) Stroke
(VZV) 1 (0.7) AIDP 1 (0.7)
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Natural History of HIV Infection Without the Use
of Antiretroviral Therapy
Primary Infection
Death
Acute HIV syndrome Wide dissemination of
virus Seeding of lymphoid organs
1200 1100 1000 900 800 700 600 500 400 30
0 200 100 0
OpportunisticDiseases
Clinical latency
HIV/RNA Copies per ml Plasma
Constitutional Symptoms
CD4 T Lymphocyte Count (cells/mmm3)
0 3 6 9 12
1 2 3 4 5 6
7 8 9 10 11
Years
Weeks
Source Fauci et al 1996.
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Benefits of ARV Therapy

• Prevents opportunistic infections
• Alters/reverses course of existing opportunistic
  infections
• Decreases hospitalizations
• Increases survival
• Improves quality of life
• Restores hope
• Reduces HIV transmission
• Benefits both adults and children

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QUALITY OF LIFE AT LAST FOLLOWUP
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Conclusion

• Effective interventions against opportunistic
  infection require not only appropriate medication
  for a given OI, but also necessary infrastructure
  to diagnose the condition/ and monitor the
  intervention
• These interventions would definitely improve
  quality of life of the people living with HIV /
  AIDS and prolong life

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Co-Investigators

• A. Nalini Dept of Neurology
• M. Gourie-Devi
• A. Chandramuki Dept of Neuromicrobiology
• S. Nagarathna
• V. Ravi Dept of Neurovirology
• Anitha Desai
• S.K Shankar Dept of Neuropathology
• Anitha Mahadevan
• P.N. Jayakumar Dept of Neuroradiology
• S. Srikanth
• D.K. Subbakrishna Dept of Biostatistics

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• As it takes two to make quarrel,so it takes
  two to make a disease,the microbes and its host
• Charles V Chapin (1856-1941)

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Thank You
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Neurological Manifestations of HIV infection

• Neurological manifestations No. of cases ()
• 
  
• HIV associated dementia 21 (4.3)
• Cranial neuropathy 14 (2.9)
• Stroke like presentation 27 (5.6)
• Meningitis 86 (17.8)
• Mass lesions 77 (16.0)
• Seizures/Headache 21 (4.3)
• Myelopathy 136 (28.3)
• Retinopathy 43 (8.9
• Psychiatric 24 (4.9)
• Others 27 (5.6)
• Total 481
• 
  Wadia et al JAPI
  2001 49343-348.

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Nervous System Manifestations of HIV Infections

• AIDS Dementia Myelitis OIs Peripheral
  Neuropathy
• Primary HIV Infection AIDP Malignancy Myopathy
• Vacuolar Myelopathy CIDP Lymphoma
• Ch.Sensory Neuropathy Muscle Disorders Plasmacyto
  ma Kaposi Sarcoma
• PML
• Metabolic

Primary HIV Virus involvement
Latent phase CD4 200-500
Advanced phase CD4 lt 200
Due to ART
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HIV infection in children

• --------------------------------------------------
  -----------------------
• Parameters Adults
  Children
• --------------------------------------------------
  -----------------------
• Mode of transmission Sexual
  Vertical
• IV drug
  Blood
• Common complaint Headache,
  Failure to thrive Fever
  Recurrent infections
• Mass-common Toxoplasmosis Lymphoma
• Tuberculoma
• OIs Crypto, Toxo CMV, Rubella
• TB TB
• --------------------------------------------------
  ---------------------------------------

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Neuro AIDS ART

• At NIMHANS, only few patients could afford ART
  and hence this preliminary report.
• Experience with the use of ART in 37 NEUROAIDS
• Side effects noted

Nausea,vomiting 12
patients Bone marrow suppression 1
patient Peripheral neuropathy 1 patient
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FLAIR
T2
HIV TBM
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Diagnosis of CNS Tuberculosis

• Diagnosis No. of cases
  age
• N120
• Tuberculous Meningitis 51 40.5
• TBM Arteritis 12 10.0
• TBM Hydrocephalus 10 8.3
• Tuberculoma 22 18.3
• TBM Tuberculoma 11 9.2
• TBM Spinal. Arach. 9 7.5
• Other combinations 5
  4.2

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CNS Tuberculosis and Systemic Infections

• Associated Systemic No. of
  casesTuberculosis
• Lymphnodes 8
• Pulmonary 47
• Abdominal 3
• Disseminated 5
• Associated Sys.Syphilis 2
• Associated Sys.Herpes 3

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HIV WITH TBM