Neurological Manifestations of HIV Infection: A Practical ...Neurological Manifestations of HIV infection Directly due to HIV ±Sensory neuropathy ±Vacuolar myelopathy ±Dementia
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AnxietyDepressionAlcoholRecreational drugsMedication side effectsMetabolic encephalopathyHypothyroidismVitamin B12 deficiency
Drug interactions with protease inhibitors
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Pathology of HAND
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Productive Infection in
perivascular macrophages
Jones et al., 2000; Kruman et al., 1998
Tat
gp120
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Dentate Gyrus
normal HIV no encephalitis
HIVE HIVE + drug abuse
Jones, Bell and Nath (unpublished)
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virotoxinsCellular toxins
chemokines
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Principles of Therapy for HIV CNS infection
Maximize antiretrovirals to suppress CSF HIV RNA
Preferably use CNS-
Construct simplified regime - BD or QD
Supervised therapy:Int
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stavudine (D4T) zidovudine (ZDV)abacavir (ABV)
NNRTIefavirenz (EFV) nevirapine (NVP)
Protease Inhibitorsindinavir (IDV)
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Poor penetration across BBBP-glycoproteinorganic transporters
Drug resistanceNo effect post viral integration
viral reservoirs sparedearly viral proteins still producedInt
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HIV infection andCerebellar degeneration
(Tagliati et al., Neurology 1998;50:244-51)
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HIV+ Cocaine(Meltzer et al., AJNR 1998;19:83-9)
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8yr old with congenital HIV infection with microcephaly and developmental delay developed sudden onset of hemiparesis. CT showed subarachanoid hemorrhage
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Riedel et al., Nature Neurol 2006
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methylprednisone 1g/day x 5 days
Dramatic improvement in mental status
Discharged on prednisone 60mg/day
tenofovir, lopinavir/ritonavir, zidovudine
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worseningclinical condition that is paradoxicallyattributable to the recovery of the immune system after initiation of ART
Immune Reconstitution Inflammatory Syndrome
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15-25%
Patients on HAART
20-45%
Patients with OI on HAART
Shelburne et al., 2006
EPIDEMIOLOGY of IRIS
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0 10 20 30 40 50 60 70 800
25
50
75
100
Patients with IRIS (%)
Tim
e in
terv
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ays)
Shelburne et al., AIDS, 2005 Johnson and Nath NYAS 2010
Time between of Initiation of HAART and IRIS
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Steroids:
Risks from immune suppression
Interruption of HAART/immune restorative therapy:
Risk for resistance to therapy
Re-emegence of IRIS upon restarting HAART/ immune restorative therapy
Treatment options for IRIS are not ideal
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Recommendation for use of steroids in IRIS
Catastrophic IRIS: high dose steroids taper with oral steroids x 1 month (with OI prophylaxis)
Symptomatic IRIS: high dose steroids taper with oral steroids (debatable)
Asymptomatic IRIS: wait and see (debatable)
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Peripheral Nervous System with HIV
RadiculopathyGBSMononeuritis multiplexSensory motor neuropathy
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CMV PolyradiculitisOccurs late in HIV infection; CD4 usually < 100; concurrent CMV infection in >60%Cauda equina syndrome: asymmetric motor, perineal sensory, back pain, sphincter CSF: poly pleocytosis, protein, glucose, + CMV PCR+ in 95%
Increased frequency of GBS relative to general populationSimilar presentation to HIV neg, except that CSF usually cellularUsually presents early in HIV infectionPresumably an immune-mediated phenomenon