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HIV Neurology

HIV Neurology. By:Dawit Ayele - July,2007.

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HIV Neurology

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  1. HIV Neurology By:Dawit Ayele - July,2007

  2. HIV AIDS-Is now second only to the Black Death as the largest epidemic in history. - kills about 2.9 million people a year, or about one person every 11 seconds.-The toll is worst in Africa, where millions of parents have died, leaving children as orphans. -about 1.4% of Ethiopians ages 15 to 49, or one million people, are HIV-positive -nearly 6% of adults in urban areas are HIV-positive, while less than 1% of rural residents age 15 to 49 are HIV-positive. .(eth.demographic & health survey2005/daily HIV/AIDS report sept,2006) By 2015 life expectancy at birth of 7 african countries with prevalence rate >20% will be 32 yrs.lower than in the absence of AIDS

  3. Neurologic diseases in HIV • Neurologic problems occur throughout the course of disease irrespective of the immune status The Brain infected as early as first few weeks, low grade inflammation continues • Virtually all HIV infected patients have some degree of CNS involvement:-evidence ~90%CSF abnormality even during asymptomatic phase. • Affects all levels of the neuraxis • Overall,20 disease of CNS occur in ~1/3 of patients with AIDS.*But this frequency is considerably less in patients receiving ART. • Nature of problem:-inflammatory -demyelinating -degenerative

  4. Neuropathogenesis • Neurologic abnormalities in HIV infected are due to -opportunistic infections & neoplasms. -**direct efffects of HIV & products • HIV is demonstrated in vivo in brain & CSF of infected individuals. • Main cell types infected causing effect in CNS are: -perivascular macrophages & microglial cells. -Monocytes already infected in the blood can migrate & reside in brain or -macrophages can be directly infected in the brain. • No convincing evidence that brain cells other than those of monocyte/macrophage lineage can be productively infected in vivo

  5. Neuropathogenesis:cellular tropism • HIV-1-utilizes 2 coreceptors along CD4 to bind,fuse with and enter target cells:CCR5&CXCR4 -V.Strains that utilize CXCR4X4 viruses -Those that utilize CCR5R5 viruses -Dual usingR5X4 viruses • Early HIV transmitting virus(early stage) is almost invariably an R5virus Note:R5 viruses are more efficient in infecting monocyte/macrophages& microglial cells of the brain.

  6. Neuropathogenesis cont. Eventually 40% of infected individualspredominant X4 associated with rapid progression.(no need of gp120+CD4 interaction& conformational  for co-receptor affinity) 60%maintain R5 virus predominance. • **HIV cytopathicity is low for monocyte lineagecan replicate extensively in cells. • Hence-monocyte/macrophages are normal in number(unlike T-helper cells)&play role in dissemination as reservoir—*represent an obstacle to eradication of HIV by ART.

  7. Neuropathogenesis **Chemotaxis of leucocytes(monocytes) into CNS +endogenous neurotoxins from macrophages & lesser extent astrocytes via indirect pathwaysis responsible for manifestations of white matter lesions +neuronal loss seen in infected individuals. • Development of neuro AIDS depends on: • Immunosuppresion • Neuro-virulence • Genetic factors(E4 allele for apo-lipoproteinE ,CCR5-32) • HAART

  8. Disease Classification • Pathophysiologic (course of the disease) -1ry HIV infection & Seroconversion -sxic/asxic phase(CD4 > 200/mm3) -AIDS defining (late HIV infection) • Neuroanatomic:brain parenchyma(diffuse/focal) meninges(infectious/malignancy) spinal cord(acute/subacute/chronic) peripheral neuropathies(focal/poly) myopathy( +/-inflammatory) • Radiologic appearance of CNS lesions: -lesions with or without mass effect • Etiologic :HIV related Non HIV related(stroke,degenerative dis..) ART related

  9. Approach to HIV infected patients with CNS lesions • **Clinical challenge:-pt with change in mental status or abnormal neurologic exam. • Wide range of presentation:-subtle& non specific to life threatening emergencies. • Most important factor for DDX is degree of immunosuppression: -CD4>500/lBenign& malignant brain tumors with metastasis(as immunocompetent) -CD4 200-500HIV associated cognitive & motor disorders.Usually do not present with focal lesions -CD4<200CNS mass lesions most common.The most likely dxic consideration –OI & AIDS associated tumors. • *Multiple etiologies can coexist:-one study 6%had >1etiology established from histologic sampling.

  10. Epidemiology • Thorough knowledge of the pattern of various etiologies for CNS disease in HIV infected patient in particular area is vital for evaluation&management.(eg-In developed nations tuberculoma is rare) • Patient not taking ART-may present initially with CNS opportunistic infection • Post ART & prophylaxis for PCP-same etiology but different incidence & spectrum Ex-Co-trimoxazole against PCP-effective for TE prevention(72.2%18.6%from1991-1996) -ART markedly HIV encephalopathy,PCNSL,PML or new severe demyelinating leukoencephalopathy

  11. Radiologic appearance of CNS lesions • CT&MRI +/-contrast *Enhancementusually signifies inflammation.(NB-steroid use can enhancement) • MRI advantage Vs CT -much more sensitive in determining truly solitary lesion • sensitive for white matter lesions in posterior fossa • identify peripheral more accessable lesion for biopsy. • Ancillary imaging studies: thallium SPECT,PET,perfusion MRI,MR spectroscopy: more sensitive than specific not readily available

  12. Radiologic appearance of CNS lesions • CNS lesions classified into 2 categories according to +/-mass effect: -CNS lesions with mass effect: Characterized by swelling,edema&mass effect on surrounding structures.In some esp.post fossa cerebral herniation occurs. ass lesions usually enhance a/r the injection of contrast material,indicating local inflammation& breakdown of BBB Presenting feature can be headache,N,V,confusion,lethargy ICP Leading DDX-Toxoencephalitis,tuberculoma,PCNSL -CNS lesions without mass effect Usually do not enhance a/r injection of contrast material & are not associated with risk of herniation. Vast majority:PML or HIV associated encephalopathy

  13. Additional vital diagnostic modalities • In addition to routine laboratory studies: • CD4 count • Serology(for toxo,VDRL…) • CSF analysis(including CSF PCR) • Brain biopsy are very important in reaching specific diagnosis & management

  14. SPECIFIC DISEASES—I)MENINGITIS • 1)Cryptococcal meningitis • Leading infectious cause of meningitis in pts with AIDS ( CD4 < 100/mm3);particularly common in pts with AIDS in Africa occuring in~20% of patients. • AIDS-defining illness for 60 % of the HIV-infected patients in whom it is diagnosed. • In Ethiopia-Medical record review study done at TAH Jan1997-Dec2003(int.conf.of AIDS jul.2004) revealed:-from total 102 microbiologically confirmed crypt.meningitis pts with HIV;median age of 33.5yrs,67%M,in 82.4% it was 1st AIDS defining illness. • C/P: • Subacute meningoencephalitis: • HA, fever, n &v, photophobia ,stiff neck; meningial signs absent in 50%.(Similar figure in Ethiopian studies-HA,f,v present in >90%of cases) • Personality changes, cognitive impairment, altered mentation and coma. • Focal neurologic deficits & Seizure : less frequentCryptococcomas

  15. Cryptococcal meningitis diagnosis • Dx:CSF : Pressure > 200mmhg in 75 % • NL/modest Mononuclear pleocytosis(5-100), prt(50-100) ; low glucose • CSF Culture +ve in > 95%( gold standard) • Indian ink +ve in 60-80% • Crypt Ag +ve > 95% • Biopsy for CNS cryptococcoma • Blood culture +ve in 50-70%, Serum cryp Ag +ve >95% • MRI/CT: • Excludes focal disorders • Cerebral atrophy-related to advanced HIV • Hydrocephalus • Cxn: Hydrocephalus, Gelatinous pseudo-cyst, Infarction, cryptococcoma

  16. Cryptococcal meningitisCont… Treatment: Standard; • Induction: Amp B + 5 FC x 2 wks • Consolidation: Fluconazole 400mg x 8 wks /until CSF sterile • Suppressive phase: Fluconazole 200mg Lower ICP – • LP, V-P shunt, optic nerve sheath fenestration • Repeat LP at 2 wks if no response • Monitor fluconazole level in Renal failure Alternatives: • Fluconazole alone for acute Rx as effective as Amp B –delayed CSF clearancepreserved for mild disease • Fluconazole+ 5 FC x 6-10 wks • Ambisome 4 mg/kg IV x 2wks • Consolidation –iatraconazole *FC combination with AMP B does not improve immediate out come but prevents relapse

  17. Cryptococcal meningitisCont… • Response: • CSF culture –ve at 2wks in 70% • CSF cryp Ag used to follow response • Poor prognostic factors: • Altered level of consciousness • CSF cell < 20/ul • CSF crypt Ag > 1:1024 • High DBP • Treatment failure: **No clinical response at 2 weeks • Continue with same treatment • Higher dose of Fluconazole with FC • Voriconazole  Death inevitable w/o Rx( > 90% in first 2 wks, 40% in wk3-10) (*Even with proper Rx overall mortality is 6-14%.Mortality rate in the Ethiopian study >46% being rxed with amphotericin (45.1%) , Fluconazole(17.6%),no antifungal(39.2%)) • Exclude IRS as a cause of failure • Sxs may recur with HAART initiation as IRIS

  18. Tb meningitis • 1/3 of all AIDS related deaths due to Tb.Untreated universally fatal. • Seropositivity in Zaire study 88% in those with confirmed Tb meningitis. • Accelerates the course of HIV so needs index of suspicion. • *HIV co-infection doesn’t alter c/f,CSF findings,response to therapy • CNS Tb exists in three forms: • Meningitis • Intracranial tuberculoma • Spinal Tb arachinoditis • Inflammation • Proliferative arachinoditis at the base-CN & vessels • Vasculitis-thrombosis & infarction • Hydrocephalus-communicating • Three phases • Prodromal phase-2-3 wks : malaise, fever , HA, personality changes • Meningeal phase: meningismus, confusion, focal signs (CNpalsies or hemiparesis) • Paralytic phase: Stupor, coma, Seizure & dense hemiplegia

  19. Tb meningitis cont…. • CSF - AFB : yield 37% with initial smear, 87% with upto 4 serial specimens examined, • elevated prt & low glucose with a mononuclear pleocytosis Recommended that a minimum 3 LPs be performed at daily intervals . ** Key points to sensitivity of CSF AFB smear: 1-use large volume(10-15ml) &best to use the last fluid removed at LP 2-Smear of clot or sediment most readily demonstrates org.(if no clot; add 2ml of 95%alcohol form heavy protein ppt carrying bacilli) 3-~.02ml of centrifuged slide </=1cm diameter&stain with Ziehl-Neelsen method. 4-200-500 HPF should be observed(2observers)~30minute PCR 60% sensitivity • Radiological clue (CT) -*Communicating hydrocephalus • Basilar arachnoiditis,Cisternal enhancement • Cerebral edema and infarction/ BG infarction • Multiloculated abscess/Tuberculomas ( common in HIV (60 VS 14 %)among pts with TB meningitis)

  20. Treatment of Tb meningitis • Anti TB (HRZ+E/STM)x2 + (HR)x10 months w/o delay • Dexamethasone: -Has no mortality benefit in HIV -Reduces basal inflammation and arteritis • Administration depends on grading • Grade I (GCS 15 , no focal deficit) • Grade II focal deficit, GCS 11-14 • Grade III coma GCS < 10 Gen.Dose recommendation: Dexa-1st 3wks (initially IV 0.4mg/kg/day, tapering to 0.1 mg/kg/day) followed by –PO beginning with 4 mg per day, tapered over 3-4 weeks at the rate of 1 mg decrease in the daily dose each week. Prednisone 60 mg per day tapered gradually over six weeks • Surgery — Patients with hydrocephalus

  21. Neuro syphilis • Share risk factors-coexists: 25 – 70 % • Affects brain, meninges, spinal cord & nerve root • Peculiarity with HIV: - *Manifestations may be altered withrate of early CNS invasion • Multiple neurological relapses after Rx • Serological Rx failure • Slower rate of decline of titer • Two forms • Asymptomatic- • CSF mononuclear pleocytosis, increased protein, reactive VDRL • Probability of progression 20% in 10 years • Symptomatic

  22. Neuro syphilis… • Types:(manifestations may progress fast in HIV!) • Meningeal:onset< 1 year • HA, nausea, vomiting, stiff neck, CN involvement • Seizures, altered mental state • With uveitis & iritis coexist • Meningiovascular :5-10 yrs(more common) • Inflammation of pia & arachnoids with wide spread arterial involvement • Stroke syndrome-MCA in young commonest presentation • Usually follows sub acute encephalitis syndrome (HA, vertigo, insomnia) followed by gradually progressing vascular syndrome • Parenchymatous#:relatively rare • Generalparesis20 yrs? Personality,Affect,Reflexes,Eye(Argyll Robertson pupils),Sensorium,Intellect&Speech • Tabes dorsalis 25-30 yrs? Demyelination of the posterior columns,dorsal roots & ganglia

  23. Neuro syphilis Cont… • Dx: -Serology • Non treponemal test-RPR & VDRL • Treponemal test-FTA-Abs, TPHA for confirmation -CSF: mononuclear pleocytosis >5wbc/mm3, protein >45mg/dl,+VDRL • Reactive VDRL( sensitivity~50%specific)---seen in 40% in 1ry & 2ry • FTA-Abs.(sensitive ) if non reactive excludes -Skin biopsy-silver staining to look for organism(suspicion & -serology) • Rx:-Aqueous penicillin G(18-24mU/dIV,given as 3-4mUq4h or continuous infusion)for 10-14days or -PPF2.4mU/dIM+oral probenecid(500mg qid),both for 10-14days If penicillin allergic patient –Desensitize & treat with penicillin - Response • Dramatic, arrests progression • Relapse –retreatment • Follow up • Regardless of HIV status, patients are considered adequately treated if the non treponemal test antibody titer declines at least four-fold over a specified period of time(a year for early syphilis&2-3yrs a/r latent syphilis) • CSF every 6 months

  24. II)Parenchymal brain disorders • I-Diffuse: IA)Condition with clear level of consciousness a)Minor cognitive motor disorder(MCMD) Clinical diagnosis-at least two of:-Impaired attention or coordination -Mental slowing -Impaired memory -Slowed movements or incoordination *Sxs usually subtle & often overlooked. Clear consciousness,no serious impairment in daily living. Course-Some continue to have only minor problems& others progress to full dementia.*No controlled trial for treatment so far. **Paper published in neurovirology journal(jan2007) by David B.Clifford et.al.-a cross sectional neurological evaluation of cohort of community dwelling Rx naïve HIV infected pts in Ethiopiafinger tapping speed in HIV infected than HIV-ve;correlating wz viral load. Other CNS &/or PNS performance similar with control group. (unanticipated minor evidence of neurocognitive & PN deficit)

  25. b)Dementia • Defn:-combination of acquired limitation in congnitive abilities(attn/concn.,processing,abstraction,memory,speech or visual spatial skills) +abnormalities in motor function or in emotional or behavioral functioning. • AIDS dementia complex:describes the syndrome as a subcortical dementia with a focus on changes in memory,mov’t(motor)&mood. Epidemiology:-Incidence from 20-30%to 10-15%since ART;but overall prevalence same. *ART doesn’t prevent neuropsychological impairment ;it only alter type of impairment & delay onset of dementia Clinical course:-classic triad of sxs-Subcortical dementia(memory & psychomotor speed impairment);depressive sxs& movement disorder. **Absence of higher cortical dysfuncton (aphasia, agnosia, apraxia..) distinguish HAD from classic cortical dementia like alzheimer’s.(*Late& severe HAD may have it)

  26. Clinical staging of HIV encephalopathy(AIDS Dementia Complex)

  27. b)Dementia • Brain imaging -CT/MRI-cerebral atrophy often -used to eliminate other potential diagnosis associated with poor progrosis • DDX-Toxo encephalitis imaging-PML LP -Infections 30 syphilis TFT -Thyroid dysfunction Test -Nutritional deficiencies

  28. b)Dementia • Rx:-Standard optimal HAART cognitive impairment. • ART drugs with est CSF penetration are better-ZDV,d4t,3TC,ABC,NVP,IDV • Aggressive Rx of associated psychiatric problems(such as mood,anxiety,or substance use d/o)

  29. c)Neuropsychiatric disorders • HIV and AIDS can produce a number of psychiatric conditions and exacerbate many others ;some of them: -Major depression -Mania -Schizophrenia -Substance abuse or dependence -Antisocial behavior -Post-traumatic stress disorder (PTSD • The presence of a preexisting psychiatric disorder can increase the risk of HIV acquisition and can also complicate HIV treatment. • Behaviors that are intimately connected with many of these neuropsychiatric conditions actually fuel spread of HIV and thus continuation of the HIV epidemic.

  30. c)Neuropsychiatric disorders • Successful treatment can be achieved with even the most difficult patients by applying a comprehensive diagnostic formulation. • **Each facet of this formulation strategy has the potential to sabotage treatment for all the remaining conditions, and, thus the treatment plan must be comprehensive in scope in order to address the whole person.

  31. IB)Condition with disturbance of consciousness • Delirium -Defn:-Development of disturbance of consciousness with a ability to sustain,focus or shift attention,which occurs over a short period of time. • Is associated with -in cognition & perceptual disturbance - in sleep wake cycle,psychomotor activity( or activity)& emotional state. - mortality,longer hospital stay, care needed upon discharge. Unfortunately still remains underdiagnosed.

  32. Delirium • Careful Hx,P/E&Ix is vital to determine etiology: -Intoxication by drugs & poisons -Withdrawal syndrome -Metabolic encephalopathies -Infections(intracranial or systemic) CMV,PML,cerebral toxo,cryptococcal meningitis,CNS lymphoma. -Neoplasia -Head trauma&space occupying lesions -Epilepsy -Vascular disorders(cardiac& cerebrovascular) - sensitivity reactions -physical agents

  33. Delirium…. • DDx-mental status change in HIV pt— >AIDS mania >major depression >bipolar disorder >schizophrenia *Delirium can usually be distinguished by its rapid onset , fluctuating level of consciousness& link to medical etiology. Rx-General issue:Orienting the patient close & often constant observation(give safety & reassurance to the patient) -information to clinicians -limit restraints provide stable environment-private room, clock, calendar &board that indicates location.

  34. Delirium Rx…. • Controlling symptoms Psychologic behavior-low dose potency neuroleptic agentshaloperidol/CPZ. -don’t use sedating drugs(diazepam)unless they are treating underlying cause of delirirm • Identify & correct cause address potential medical etiologies

  35. Focal parenchymal brain disorders • 1. Cerebral toxoplasmosis • Most common cause of 2ry CNS lesions with AIDS(ART&TE px.era ) • Late complication of HIV (CD4+Tcell<100/l), • ? A reactivation syndrom 10x with Abs to the organism than sero –ve Ethiopian study-Trans R Soc Tropical medicine & hygene(1998jul-Aug).170factory workers (18-45yrs)sera tested for anti-toxo IgG –80.6%+with no sign. difference in prevalence b/n pts infected &not infected by HIV;but ab.titers were higher in HIV+. Previous study~74%seroprevalence from 1010 sera sample from d/t geographic regions. • C/P:Acute/ fulminant OR Insidious ( several weeks) -Patient typically present with headache. -One study –115case review:headache,confusion,fever(55, 52, and 47% respectively) -Focal neurologic deficits & seizure are also common -Dull affect-global encephalitis -More profound mental status(confusion,lethargy,coma)+N,VICP • Dx:-Clinical -Serology (+ >97% for IgG), if –ve likelihood of toxo is < 10% -Radiological -Brain biopsy-definitive Dx(due to risk indications..)

  36. DX of Cerebral toxoplasmosis • Neuro imaging (CT/MRI): Multiple/single, ring enhancement, surrounding edema • Seen in almost all-except diffuse form • False negative-10% • Multiple in 2/3, ring enhancing-90% • Size < 2cm • Site: Parietal/frontal lobes, thalamus , BG, Brainstem, Corticomedulary junction, Pituitary gl DDX:PCNSL,Tb/fungal/bact.abscesses • CSF: +/- mild mononuclear pleocytosis and elevated protein. DNA amplification. Tachyzoites (on cytocentrifuged CSF samples stained with Giemsa) • SPECT /PET : in distinguishing toxoplasmosis or other infections from CNS lymphoma.

  37. DX of Cerebral toxoplasmosis • A presumptive diagnosis of Toxo can be made if the patient has 1. CD4 <100/µL & Sero +ve for T. gondii IgG Ab 2. Not on effective prophylaxis for toxoplasma 3. Brain imaging demonstrates a typical radiographic appearance (eg, multiple ring-enhancing lesions/ “eccentric target sign”) • If these 3 criteria are present, a 90 % probability that Dx is toxo. Brain biopsy is indicated if : -all 3 of the above criteria not met with strong clinical suspicion. - patient doesn’t respond (clinical or radiogr.) to empiric Rx

  38. Treatment of Toxo • Toxoplasmic encephalitis generally responds promptly to treatment. • Lack of either clinical or radiographic improvement within 10 to 14 days of empiric therapy for toxoplasmosis should raise the possibility of an alternative diagnosis • First line therapy 2choces-1-Pyrimethamine(200mg-L/75C) + sulfadiazine(6-8g/d -4d/d) 2-Pyrimethmine+Clindamycine *All pyrimethamine regimens should include folinic acid to prevent drug-induced hematologic toxicity (10 to 25 mg/day PO). • Alternatives: 1. Pyrimethamine+ Azithromycin 2. Pyrimethamine+ Atovaquine 3.Sulfadiazine+ Atovaquone * TMP-SMX-study showed no statistically significant difference with standard Rx.Has side effect profile & can be used as effective alternative Rx regimen esp. in resource poor settings. • Relapses: common(typical 6wks Rx then dosemaintenance Rx is needed!!) • Steroid:- radiographic evidence of midline shift, ICP or clinical deterioration within the first 48 hours of Rx.

  39. Treatment of Toxo • 1ry prophylaxis: CD4 <100/mm3 & +ve toxo IgG Ab • Secondary prophylaxis may be d/c with CD4>200/l for 6mths. • Monitoring of therapy : • Clinical evaluation. :Clinical improvement usually precedes radiographic improvement. Thus, a careful daily neurologic exam. during first 2 wks of treatment. • Serial brain imaging/Radiographic reassessment : should be deferred for 2-3 wks unless no clinical improvement in 1st wk or has shown any worsening. • Rx advrse effects No value to serial assessment of IgG toxoplasma antibody titers.

  40. 2. Primary CNS lymphoma • AIDS defining malignancy (KS, Cervical Ca, NHL) • ~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: • Slowly progressing-weeks • Cognitive impairment • Head ache, confusion, Constitutional symptoms (fever, nights sweats, and weight loss) > 80%. • Focal deficit: CN findings, hemiparesis, aphasia, head ache &/or seizure • Duration <3 months

  41. Dx,Rx&Px of PCNSL • Dx: Neuroimaging (MRI/CT) • Lesion: size 3-5 cm, limited number: 1-3 • 40% multifocal , some degree of ring enhancement –nodular or patchy (less pronounced than toxo) • Location: cortex, corpus callosum, periventricular • <10% posterior fossa CSF cytology not helpful • PCR for EBV-(specif 100%, sensit 90%) - Biopsy Definitive Dx • Rx: • Radiation, steroid: some relief • HAART increases survival > 15 months • Prognosis: Poor - median survival < 1 year • Survival is 1-3 mths from time of presentation in untreated patients • the outcome is not substantially improved by therapy, with reported median survivals of up to 3.5 months

  42. 3. Progressive Multifocal Leukoencephalopathy • Etiology: JC virus(Human polyoma virus), reactivation of prior infection (70% of adult population: Ab to JC virus) • Late manif of AIDS ; in ~4% of pts with AIDS • A demyelinating lesion of sub cortical white matter (Cerebral hemisphere predilection to parieto-occipital area) , cerebellum , BG, thalamus, brainstem & spinal cord • Lesions are usually bilateral, asymmetric, & localized preferentially to periventricular areas & subcortical white matter . • C/P: • Typical patient:-Protracted course +/- Change in mental state,Multifocal deficit: hemiparesis, aphasia, sensory deficit • Ataxia & visual field defect ,aphasia,& sensory deficit may occur

  43. Dx of PML • Dx • CSF: Normal or non specific • PCR for JC :- specific ,if +ve decrease need for biopsy • CT : patchy or confluent hypodense lesions of white matter • MRI: multiple non enhancing white matter lesion (predilection for occipital or parietal lobes). • Brain biopsy-giant astrocytes & altered oligodendrocytes nuclei contains viral inclusions & myelin loss • DDx: HIV encephalopathy and CMV encephalitis

  44. PML Rx, Px... *No specific Rx • HAART –Regression of lesion and -Prolonged survival > 2.5 years • Trial: no clear benefit by cidofovir, IFN , topoisomerase inhibitor, cytosine arabinoside • Prognosis • Median survival in HIV pts + PML ~2.6 months • In patients on HAART 1year survival has increased from10%50% • Paradoxical worsening has been seen with initiation of HAART as IRIS • Spontaneous remission -8% • Favorable out come • Baseline CD4 > 100/ul • Maintenance of Viral load < 500 copies/ml ( baseline doesn’t have independent predictive value of survival) • **One of the few OIs that continues to occur with some frequency despite widespread use of HAART:

  45. Ischemic Bacterial endocard 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 4-Stroke in HIV-Ischemic and hemorrhagic –clinical in 4%, autopsy report 34%.-Sxs-sudden in onset unlike other focal deficits.

  46. 5. Brain abscess (bacterial) • Hematogenous spread (Staphylococcus, Streptococcus, Salmonella, Aspergillus, Nocardia, Rhodococcus, Listeria) • Associated with evidence of disseminated infection • Predilection to MCA territory (posterior frontal & parietal lobe), junction of white-gray • Present as ICSOL than infectious • 11-12 days some times stay months • HA, fever, focal deficit < 50% CT: Multiple hypo dense lesions, ring enhancement -Gm stain & culture –micro.dx • Blood Culture positive~10%, ESR & WBC increases

  47. Brain abscess • Other infections with focal lesionscausing brain abscess – -tuberculose abscess • Syphilitic gumma • Neurocysticercosis • Reactivated trypanosomiasis Rx-Directed towards the identified cause/empirical -Surgical +Medical mgt. -Prophylactic anticonvulsant –for risk patient -Steroids shouldn’t be routine F/up-wz imaging

  48. Algorithm for the management of HIV-infected patients with CNS mass lesions Algorithm for the management of HIV-infected patients with CNS mass lesions Elements in bold represent data which contribute to the decision-making process (see text for details). Toxo: Toxoplasma encephalitis; LP: lumbar puncture; CSF: cerebrospinal fluid; Rx: treatment.

  49. SEIZURE +/- due to OIs, neoplasms, HIVE *Threshold often lower than NL owing to f electrolyte abn. +/- a presenting c/sx Anticonvulsant in all HIV + Sz unless a rapidly correctable cause is found Others: CNS TB, Aseptic meningitis

  50. III)SPINAL CORD DISEASES A.Myelopathy • 20% of pts with AIDS • 90% of HIV myelopathy have some evidence of dementia • *Study published in East Africa Journal of Med.Jan 1995,by Dr.Guta Z.evaluated 130 pts admitted(Dec1990-Dec.1993) with lesion localized to spinal cord at BLH. This accounted for 18% of all neurologic admission to this dept.then. -Commonest presentation-paraparesis/plegia(77%),Quadriparesis/plegia (23%),sensory level,sphinicter dysfunction&bed sores(70%,54%,14%resp.) -Leading cause-Tb spondylitis(26.9%),2nd commonest HIV-1 myelopathy(16.1%). -Restmetastatic cord compression,tropical spastic paraparesis,progressive non-compressive myelopathy,Cx.spondylosis,10cord tumors,TV myelytis

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