ppt

1. MANAGEMENT SESSION ON
NEUROLOGIC DISEASE IN RVI
PATEINTS
BY : DrAbduA
January 11 /2011

2. NEUROLOGIC DISEASES IN RVI Pts
 Virtually all RVI pts have some degree of NS involvement. 90% pt
have CSF abnormality even during the asymptomatic phase :
Pleocytosis – 50-65%
Viral RNA – 75%
↑protein – 35%
Intrathecal anti HIV Ab – 90%.
But the neurologic function of RVI pts should be considered
NORMAL unless clinically manifest
 CNS disorders accounts for a significant degree of morbidity &
mortality.
 Primary - results from viral infection of CNS
macrophages/ glial cells, or release of
neurotoxins & toxic cytokines (IL-1β,TNF-α,IL-6,TGF-β)
 Secondary - due to OIs & Neoplasms ;&ART drug S/E
-Occur in 1/3 pts & decrease withART

3. Neurologic diseases in RVI pts
OIs Myelopathy
 Toxoplasmosis
 Cryptococcosis
 PML
 CMV
 Syphilis
 TB
 HTLV-1
Neoplasms
 PCNSL
 KS
Result of HIV infection
 Aseptic meningitis
 HIV encephalopathy
 Vacuolar myelopathy
 Pure sensory ataxia
 Parasthesia/ dysesthesia
Peripheral neuropathy
 AIDP/ GBS
 CIDP
 Mononeuritis multiplex
 Distal symmetric
polyneuropathy
Myopathy

4. Approach to HIV pts with CNS
lesions
 Evaluation & Mx is challenging (vast DDx,
overlapping CF, drug interactions & S/E)
 Degree of immunosupression is the most
important factor in determining the DDx
CD4 count (/μlit) DDx
>500 Benign & malignant
brain tumors,
metastases
200-500 HIV associated cognitive
& motor disorders
<200 CNS mass lesions (OIs &
Neoplasms)

5.  Clinical feature & Dx remains similar to those in
Pre-ART era. ButTMP-SMX prophylaxis & ART
alter clinical spectrum of disease & Diagnostic
considerations E.g.
TE showed ↓from 72.2 to 18.6% in 1991 to 1996 in
those receiving Bactrim
 ART ↓incidence of HE, PCNSL,??PML, systemic
lymphoma
 Radiologic evaluation
 With or w/out contrast
 Enhancement  inflammation
 Steroid -↓inflammation non enhancing

6. Approach ctd
CT MRI
 Cheaper & readily
available
 Less time
consuming
 Less sensitive for
solitary, white
matter & posterior
fossa lesions
 Expensive
 Time consuming
 Claustrophobia
 Much more sensitive
to determine if the
lesion is truly solitary,
white matter &
posterior fossa
lesions

7. With mass effect - swelling, edema
-Usually enhance
- Headache, N/V,
confusion, lethargy
Tuberculoma,TE ,PCNSL,
Neurocysticercosis
CNS mass lesions - Brain abscess,
Cryptoccocoma,
syphilitic gummas
W/out mass effect -usually don’t enhance
-Don’t cause hernation
-PML,HE

8. Characteri
stics
Tuberculo
ma
TE PCNSL PML
№ Single,Multipl
e
Multiple(70-
80%);single
rarely (<4cm)
Multiple,Solitary
(50%each)
Multiple
Location Parietal/frontal
lobe,thalamus,b
asal
ganglia,cortico
medullary
junction
Corpus
callosum,periven
tricular/periepen
dymal area
White
matter,cerebral
hemispheres,cer
ebellum,brain
stem
Enhance
ment
+ + in 90% +
(patchy,
irregular)
_
Remark Nodular lesion Uncommonly as
diffuse
encephalitis;
Eccentric target
sign is typical
Solitary lesion
>4cm is 70%
more likely to be
PCNSL
Continues to
occur despite
widespread use
of ART

9.  Ancillary imaging studies
 Very limited access
 More sensitive & specific than clinical, CT or MRI
evaluation
E.g. thallium SPECT scan, perfusion MRI,MR
spectroscopy, PET (positron emission tomography)
 CSF analysis
 PCR – DNA of JC virus, EBV,T.gondii
 Empiric toxoplasma therapy
- alternative to brain biopsy
-Usually 1-2wks
Mini mental state examination (MMSE)
Algorithm for the Mx of RVI pts with CNS lesion :
see fig below

11. Indications for corticosteroids :
 Substantial mass effect on imaging studies &
depressed mental status
 Established Dx of PCNSL (b/c steroids can cause
false negative brain biopsy results)
Regimen (preferred)
 Dexamethasone 10mg IV LD ff by 4mg QID
 DISCONTINUE as soon as possible
 ↓brain swelling regardless of cause (mass,
infection); so clinical improvement is of no value
in Dx

12. TOXOPLASMOSIS
 Caused by intracellular protozoan parasite -
T.gondii
 In immuncompitent pts, it is asymptomatic &
latent infection persists for life
 In immunosupressed pts,toxo represent a
reactivation syndrome as evidenced by 10x ↑ risk
among seropositives as compared to
seronegatives. In seronegatives, the likelihood
of a mass lesion to be toxo is <10%.

15. Epidemiology
 Worldwide distribution, but variable seroprevalence
USA – 15%
Europe (esp. France) – 50%
Ethiopia - 80%
 RVI pts with CD4<100 ,seropositives & not on prophylaxis have 30%
chance of reactivation disease.
 CNS toxo is the most common parasitic CNS OI in pts not on
prophylaxis
 TMP-SMX prophylaxis & HAART has significantly ↓the incidence of
toxo. E.g. in one study, incidence of CNS toxo ↓from 5.4 in 1990-
1992 to 3.8 in 1993-1995 to 2.2% in 1996-1998/1000
Site of reactivation
 CNS – commonest(89%)
 Heart , lungs, pancreas, occular,BM,bladder,pharynyx,skin ,liver,LND
 Wide spread distribution is more common pathologically than is
clinically appreciated – Autopsy study
 The most prominent RF for extra cerebral toxo is advanced
immunosupression (CD4 < 57)

16. Clinical features
TE
-commonly seen in severe immunosupression
-typically present with headache
-in one study:
headache(55%),confusion(52%),fever(47%)
-focal neurological deficits (50-75%)& seizure(15-30%)
-dull affect, mental status change, nausea/vomiting
Pneumonitis
-fever,dyspnea,non productive cough
-Reticulonodular infiltrates on CXR
-CF indistinguishable from PCP
-Trophoziotes can be identified in BAL fluid
-LDH >600 U/L is more likely to beTOXO associated
than PCP,but no agreement

17. Diagnosis
Serology
-Majority are +ve (80-90%) for IgG but
quantitative titers are not useful
-IgM may be absent, if present indicates recent
infection
-The absence of Ab makes the Dx less likely, but
doesn’t exclude the possibility ofTE (b/c 5%
seronegatives haveTE)

18. Dx ctd
MRI/CT – multiple(70-
80%),hypodense, ring
enhancing lesions
often with edema with
predilection to basal
ganglia

19. Dx ctd

20. Dx ctd
 Definitive Dx of extra cerebralToxo is made by the
demonstration of tacchyzoites in tissue or fluid
Brain Biopsy
 Definitive Dx
 Open / sterotactic approach
 Hematoxylin/Eosin & immunoperoxide stain
 Assd with ↑morbidity (12%) & mortality(2%)
 Indications : failed empiric therapy
Unmet CDC criteria
CDC criteria : 90% PPV
 Presumptive Dx of CNS toxo is made & Rx should be started in
RVI pts if CD4 <100cells &
 IgG +ve
 Not receiving effective prophylaxis
 Suggestive brain imaging

21. Dx ctd
 PCR – in seronegatives & pts on prophylaxis to
exclude others (MTB,EBV,JC,C.neoformans)
 CSF analysis – mild mononuclear pleocytosis
&↑ protein
-DNA amplification – can detect
T.gondii tacchyzoites

22. TREATMENT
Similar for both CNS & extra cerebral toxo
Response is prompt (10-14days)
1st line Rx – for pregnant & non pregnant
A.Pyrimethamine 200mg po
LD ff by 75mg/d +
sulphadiazine 6-8g/d po in
four divided doses
+leucovorin Ca 10-25mg
po/d
-High incidence of cutaneous
hypersensitivity rxn
-Lower incidence of relapse
-No need of additionalTMP-
SMX for PCP
B.Pyrimethamine (as in A) +
clindamycin 600-
1200mg IV or 450mg
po QID
-If intolerant or allergy
to sulphadiazine

23. Alternative regimen
 Is indicated for those intolerant to sulphadiazine or
clindamycin
A.Pyrimethamine (as above) + Azithromycin 1200-1500mg po
once/day + leucovorin OR
B.Pyrimethamine (as above) + Atovaquone 750mg po QID +
leucovorin OR
C. Sulphadiazine 1500mg QID + Atovaquone 1500mg BID
OR
D.TMP-SMX
 10mg/kg/dTMP & 50mg/kg/d SMX x4wks then ½ dose x 3mo
 Pilot study showed no statistically significant Difference in efficacy as 1st
line Rx
 Even More SE in standard Rx
 Effective alternative esp. in resource limited areas
 Can be given IV in critically ill pts but less effective

24. In Ethiopia
1. Sulfadoxine /Pyrimethamine (Fansidar) :
500/25mg po BIDX2days followed by once daily +
folinic acid 10mg po/d X 4wks
 S/E : anemia, pancytopenia, hepatitis, GI
intolerance
 C/I : foliate deficiency
2 . Alternative Rx :
 When Fansidar contraindicated
 Cotrimoxazole 15mg/kg+ trimethoprim 10mg/kg
in 3 divided doss
 Dexamethasone 4mg IVQID used if indicated &
should be discontinued as soon clinically as
feasible

25. Duration of Rx
 4-6 wks followed by chronic suppressive Rx
Steroids
 Adjunctive – midline shift,↑ICP, or clinical
deterioration w/in 1st 48 hrs of Rx
 Dexamethasone 4mg IV QID tapered over several
days
 Makes clinical & radiological response to Rx difficult
 Monitor for development of other OIs
Anticonvulsants
 Prophylaxis is not recommended
 Should only be given for Rx of Seizure
 Drug interaction is a concern

26. Monitoring to Rx
 Clinical evaluation
 Serial brain imaging
 Adverse effects medications
Pyrimethamine -rash,nausea,BM supression
-Wkly CBC
-Leucovorin 50-100mg po/d
Sulphadiazine-
rash,fever,leucopenia,hepatitis,N/V,diarrhea,
crystaluria
Clindamycin-fever,rash,N/diarrhea
 No need to do serial IgG

27. Response to Rx
 ~80-90 % pts respond well
 50% cases don’t tolerate
 Clinical improvement is earlier than
radiologic one daily neurologic assessment
 Radiologic asst if no clinical improvement ,or
clinical worsening w/in the 1st wk of Rx
 Early neurologic deterioration or lack of
improvement (except headache & SZ) by day
10-14 should raise the possibility of
alternative Dx

28. Prophylaxis
 All RVI pts should be screened for anti toxo
Ab,& prophylaxis be given to seropositives
Primary prophylaxis
 CD4 < 200 & sero+ve
 TMP-SMX in doses given for PCP is the usual
choice
 Seronegatives :
counseling to avoid under cooked meat, use
gloves when handling cat litter boxes

29. Prophylaxis ctd
Secondary prophylaxis
 Following six wks of Rx
 1st choice
Sulphadiazine 2-4gm/d in 4divided doses +
Pyrimethamine 25-50mg/d +leucovorin
 Alternative
A. clindamycin 300mg po QID or 450mg poTID +
Pyrimethamine 25-50mg/d + leucovorin
B. Atovaquone 750mg po 2-4x/d w/w/out
Pyrimethamine 25mg/d + leucovorin
C. Atovaquone 750mg po QID monotherapy can be
considered in pts intolerant to Pyrimethamine
but there is risk of relapse (26%)

30. WHEN TO DISCONTINUE PROPHYLAXIS?
 BOTH PRIMARY & SECONDARY PROPHYLAXIS CAN
BE DICONTINUED IN PTs WHO ACHIEVE IMMUNE
RECONSTITUTION WITH HAART
 Primary or secondary prophylaxis should be re
initiated if CD count decline <200
If CD4 rise >200 for ≥3mo, primary prophylaxis for
both PCP & toxo can be D/C
Secondary prophylaxis D/C :
 Low risk pts for recurrentTE
Completed Rx
Remain asymptomatic
Sustained ↑ in CD4 >200 for >6m0
 But pts should be educated about SSn ofTE

31. CRYPTOCOCCAL MENINGOENCEPHALITIS
 Is the most common manifestation of
Cryptococcosis
 Meningoencephalitis is more appropriate than
meningitis as there is brain parenchymal
involvement almost always on pathologic human
brain studies. Localized infection (cryptoccocoma )
is rare.
Etopathogenesis & epidemiology
 Cryptococcos neoformans (var neoformans &
gatti),the latter being rare in RVI pts
 C.neoformans : 2 serotypes A(80%), B(20%)
 Typically, burden of organism is higher in RVI pts
but much lesser inflammatory response as
compared to other groups

32.  Respiratory inhalation from pigeon dropping lung disseminated with
greaterTROPISM to CNS (periventricular area, basal ganglia) due may be
to:
 CSF is a good media for growth (low complement activity)
 High dopamine level in CSF promoting its virulence
 Local production of mannitol by the organism may inhibit phagocyte
function & contribute to brain edema
 Common in immunosupressed pts :
RVI Sarcoidosis
Hematologic malignancies Chronic steroid Rx
Solid organ transplantation Hepatic failure
 It is the Leading infectious cause of meningitis in RVI pts. In pre ART era,5-
8% RVI pts in developed world acquire disseminated cryptococcal infection.
Incidence has dramatically decreased with HAART but remains a leading
cause of mortality in developing world, particularly in Africa (20%)
 Is an initial AIDS defining illness in ~2%, & generally occur in pts with
CD4 <100

33. Clinical features
 Indolent, usually 1-2wks of Meningoencephalitis
SSn. High index of suspicion is important!!
 3 most common : fever, headache & malaise
 Neck stiffness, photophobia & vomiting : ¼-1/3
 Seizure & focal neurologic deficit – uncommon
Px- unimpressive
 Altered mentation (24%)
 Focal neurologic deficit (6%)
 Tachypnea
 Papilledema : 1/3
 Visual & hearing loss, CN palsy (due to ↑ICP)

34. Cf ctd
Disseminated disease :
 Pulmonary
- 1/3pts
-Chest pain (40%),cough (20%),↑RR
-CXR - infiltration,mass,no cavity; LAP, effusion
 Skin -10%pts
-Molluscum contagiosum like lesion
 Bone – osteolytic, cold abscess
 Palatal/ glossal ulcers, arthritis,GE,myocarditis
 Prostatitis –prostate serve as a reservoir for
recurrent disease

35. Diagnosis
CSF analysis
 Opening pressure -↑in 70 %pts (>200mmH20)
 WBC – low(<50) with mononuclear predominance
 Protein –slightly ↑, or normal
 Glucose- usually normal in RVI but low in non RVI
 Cryptococcal Ag
- latex agglutination
- Confirm Dx & prognosticator
-Very sensitive (93-100%) &specific(93-98%)
-High titers  higher burden but not helpful in Mx or f/up as changes don’t
correlate with clinical response
-False +ve – Trichosporum Beigelii
 Normal CSF profile – in 25-30%pts
 Serum Ag
-Fungemia in10-30% RVI pts
- comparable sensitivity & specificity as CSF
-Important in those contraindication to LP & as screening test in endemic areas
to identify earlier disease

36. Dx ctd
 India ink
(Pelikan drawing ink)
- +ve in 75%
-encapsulated yeast
forms

37. Dx ctd
 CSF culture
- usually +ve
-definitive Dx
-with saboraud agar

38. Dx ctd
Extra neural culture
 Blood (+ve in 2/3) , urine (with prostatic
massage) , sputum
 All pts with +ve serum Ag or +ve extra neural
culture should have neuroimaging prior to LP
Neuroimaging
 When LP is considered in pts with focal deficit
 Detect Hydrcephalus,cryptococcoma,or to
R/O other OIs
Brain biopsy – Dx of cryptoccocoma

39. TREATMENT
 3 phases : induction ,consolidation ,& maintenance
INDUCTION
1. Standard Rx
 Amphotericin B 0.7mg/kg/d IV + Flucytocin 25mg/kg po QID
X2wks
 Flucytocin ↑ absorption of Amphotericin B & ↓relapse rate
 Dose adjustment is needed for Flucytocin in renal insufficiency
 The most fungicidal regimen
 Can be extended >2wks in pts presenting poor prognostic signs
 SE- infusional toxities (fever, chills, hypokalemia,orthostatic
hypotension, tachycardia, N/V ,headache, phlebitis),or RF
Rx – acetaminophen,Diphenhydramine,Steroids 30min
before administration
-LiposomalAmphotericin B 4mg/kg/d
-Effective, even faster sterilization of CSF, less
toxic but expensive
-Test dose 0.1mg/kg to avoid anaphylactic rxn

40. Rx ctd
 2. Alternative Rx
 Fluconazole 400-800mg/d po X2wks ±
Flucytocin
 Can be used in resource limited settings & when
the standard Rx is problematic
 Large clinical trial showed equivalent effectiveness
as induction Rx . But Rx Amphotericin B result in
rapid CSF sterilization, & there is ↑mortality w/in
1st 2wks of Rx with Fluconazole

41. Rx ctd
CONSOLIDATION
 Fluconazole 400mg/d po for normal LFT &
RFT X 8wks
MAINTENANCE (SECONDARY PREVENTION)
 Fluconazole 200mg/d po until CD4 >200 for
≥6mo in response to ART
 Fluconazole is superior to Itraconazole for
preventing relapse

42. Rx ctd
↑ICP
 Is due to ↑vascular permeability & impaired CSF absorption
 Should be aggressively managed to ↓ mortality &morbidity
 Check Opening pressure in pts neurologic deterioration or
who fail to improve on induction Rx
 No role for acetazolamide & corticosteroids (fungal flare-up)
 Daily LP to ↓OP to <200mmH20 or to ↓ by 50% from initial
value
 Neuroimaging is needed prior to LP to R/o ICSOL
 Pts with continued requirement of serial LP after 4wks of
appropriate Rx may need permanent ventricular shunt
 Among pts with normal baseline OP (<200) , repeat LP should
be done 2wks latter to exclude development of ↑ICP &also to
determine sterilization

43. When to start or re initiate
ART??
 Optimal timing is imprecise
 Due to concerns of IRIS, most clinicians restart
OR start ART at end of consolidation phase

44. When to discontinue
maintenance Rx??
Some pts achieving immune reconstitution on
HAART may be able to discontinue
maintenance Rx :
 Successfully completed the initial Rx
 Remain asymptomatic
 Sustained↑ CD4 >100-200 for ≥6mo-1yr
 But maintenance Rx should be reinstituted if
CD4 count falls to <100-200

45. Monitoring during Rx
 Repeat LP if only new Sxs after 2wks of Rx
(e.g. Headache) to R/o ↑ICP
 Not recommended in pts with clinical
improvement
 Monitoring for side effects of Rx
Serum levels of Flucytocin 2hrs after po (NV
<100µg),or CBC
LFT during maintenance Rx though hepatic toxicity
is UNCOMMON

46. PRIMARY PREVNTION
A. In resource rich setting
 Antifungal prophylaxis should not be used routinely
due to relative infrequency of cryptococcal disease,
lack of survival benefits, drug interaction, potential
drug resistance,& cost ineffectiveness. If used,
Fluconazole 100-200mg/d po for pts with CD4 <50
B. Resource limited setting
 DespiteART, cryptococcal disease remains a
significant cause of morbidity & mortality
 Fluconazole 200mg 3x/wk
 Prospective double blind randomized controlled
trial in Uganda showed ↓cryptococcal disease &
esophageal candidiasis but no difference in mortality

47. PROGNOSIS
 UNIFORMLY FATAL IF UNTREATED
 Prognosis improved with ART & antifungal Rx
 Despite ,Acute mortality remains 6-15%
 Predictors of death during initial Rx are
 Abnormal mental status at presentation
 CSF Ag titer >1:1024
 CSFWBC count <20/μL
 Diastolic HTN ( due to ↑ICP)

48. HIV ENCEPHALOPATHY
 HIV ASSOCIATED DEMENTIA
 AIDS DEMENTIACOMPLEX
 An initial AIDS defining illness in 3% pts, but clinically
significant encephalopathy eventually develops in 25% of RVI
pts with ↑ risk & severity in advanced immunosupression
 Is late manifestation progressing over mos, but can occur in CD4
>350
 “Sub cortical dementia “
- aphsia,apraxia,agnosia are uncommon
-pathologic changes occur in sub cortical areas of brain involved
in motor ,language & judgment
 Defined as constellation of SSn (dementia, motor ,behavioral)
Dementia- major feature
 Decline in cognitive function from previous level !!
 E. g. impaired concentration,↑forgetfullness,difficulty reading
& performing complex tasks

49. Motor problems
 Unsteady gait, poor balance,tremor,difficult
RAM,↑DTR & tone
 Bowel & bladder incontinence,paraplegia
(lately)
Behavioral abnormalities
 Apathy , lack of initiation
 Agitation, mild mania
 Alertness not affected
 Vegetative state
Clinical staging :

50. Stage Definition
Stage 0 (normal) Normal mental and motor function
Stage 0.5
(equivocal/subclin
ical)
Absent, minimal, or equivocal symptoms without impairment of work
or capacity to perform activities of daily living. Mild signs (snout
response, slowed ocular or extremity movements) may be present.
Gait and strength are normal.
Stage 1 (mild) Able to perform all but the more demanding aspects of work or
activities of daily living but with unequivocal evidence (signs or
symptoms that may include performance on neuropsychological
testing) of functional, intellectual, or motor impairment. Can walk
without assistance.
Stage 2
(moderate)
Able to perform basic activities of self-care but cannot work or
maintain the more demanding aspects of daily life. Ambulatory, but
may require a single prop.
Stage 3 (severe) Major intellectual incapacity (cannot follow news or personal events,
cannot sustain complex conversation, considerable slowing of all
output) or motor disability (cannot walk unassisted, usually with
slowing and clumsiness of arms as well).
Stage 4 (end-
stage)
Nearly vegetative. Intellectual and social comprehension and output
are at a rudimentary level. Nearly or absolutely mute. Paraparetic or
paraplegic with urinary and fecal incontinence

51. pathogenesis
 Unclear
 Direct effect of HIV on CNS & immune response
(inflammatory cytokines)
 HIV found in brain
 Cytokines (see below)
 Rapid improvement in cognitive function for ART
 Pallor,gliosis,vacuolar myelopathy, diffuse spongiform
changes in sub cortical areas

52. Diagnosis
 No criteria
 Depends on OBJECTIVE DEMONSTRATION OF ↓COGNITIVE FUNCTION
USING MMSE in pts with prior scores all RVI pts should have baseline
MMSE score !!
 The most widely used test
 takes ~ 7mins (see table below )
 Tests broad ranges of cognitive functions
 Max score is 30
 Score < 24 is suggestive of dementia or delirium
 Changes in scores may be absent in mild encephalopathy
 Scores are influenced by age , education ,language, motor & visual
impairment
 Changes ≤2pts over time are of uncertain significance as may represent
measurement error, regression to mean or practice effect
 Using cutoff pt of 24 MMSE has:
Sensitivity = 87%
Specificity = 82%
 Higher cutoff pts - improves sensitivity but↓ specificity
-For research purpose
 Low cutoff pts – in populations where prevalence of dementia is low

53. Points
Orientation
Name: season/date/day/month/year 5 (1 for each name)
Name: hospital/floor/town/state/country 5 (1 for each name)
Registration
Identify three objects by name and ask patient to repeat 3 (1 for each object)
Attention and calculation
Serial 7s; subtract from 100 (e.g., 93–86–79–72–65) 5 (1 for each subtraction)
Recall
Recall the three objects presented earlier 3 (1 for each object)
Language
Name pencil and watch 2 (1 for each object)
Repeat "No ifs, ands, or buts" 1
Follow a 3-step command (e.g., "Take this paper, fold it in half, and
place it on the table")
3 (1 for each command)
Write "close your eyes" and ask patient to obey written command 1
Ask patient to write a sentence 1
Ask patient to copy a design (e.g., intersecting pentagons) 1
Total 30

54. Dx ctd
 MRI/CT – cerebral
atrophy

55. Dx ctd
LP
 R/O other OIs
 ↑cell & protein
 HIV RNA
 MCP-1,β2 microglobulin,Neoptrin,Quinolinic acid
 non specific
Treatment
 ART – rapid improvement in cognitive function
 Pts have ↑ sensitivity & extra pyramidal SE of
neuroleptic drugs

56. Lymphoma
 ~6% RVI pts develop lymphoma at sometime in the course of the
disease , which is 120x ↑incidence as compared to general population.
 ART ↓ incidence of PCNSL but not systemic lymphoma
Risk groups :
severe immunodeficiency
Prolonged duration of HIV
Hemophiliacs
E.g. At 3yrs 0.8%
At 8yrs2.6%
 Rate ↑ exponentially with immunodeficiency & duration
 Generally is late manifestation occurring at CD4< 200
 Incidence is thus expected to ↑as life expectancy RVI pts has been
improved with use of HAART
 90% are B cell phenotype
 Mono/polyclonal which may be related to polyclonal B cell activation
seen in RVI pts

57. Clinical features
 Variable
 80% have extra nodal disease (e.g. CNS)
 80% B Sxs : fever,wt loss, night sweating
 CNS - the most common extra nodal site (1/3
pts)
-60% are PCNSL
PCNSL
 Focal neurologic deficit,CN
palsy,headache,Seizure

58. PCNSL :1-3 of 3-5cm ring enhancing (less pronounced
than TE) in any location deep in the white matter
-

59. CF CTD
Systemic lymphoma
 Seen at earlier stages than PCNSL (mean CD4 189)
 20 % pts have CNS disease in the form of
leptomeningeal involvement
 LND
 GIT (25%)- any site
-Dysphgia, abdominal pain, mass in oral
cavity
-Dx-CT/MRI of abdomen
 Bone marrow(25%) - Pancytopenia
 Liver (10)
 Lung (10%) – mass, multiple nodules, Interstitial
infiltrates

60. summary of Lymphomas in RVI pts
Lympho
ma
% CD4
at
Dx
Comm
on age
(yrs)
affecte
d
EBV
DNA
+vity
(%)
Remark Rx &
Prognosis
gradeIII/IV
immunobl
astic
60 <200 Elderly HHV-8 Body cavity lymphoma
(pleura,pericardium,peri
toneum) in absence
nodal/extra nodal
disease Combined
chemotherapy ;
Has been
improving with
the use of ART &
chemotherapy
Burkitt’s
(SNCCL)
20 <200 10-19 50 1000X↑higher
incidence in RVI pts&
not seen in other
immunosupression
states
C-myc
translocation(812/22)
PCNSL 20 50 All ages Up to
100
Occurs late in the
disease as compared to
others
Supportive/pall
iative
Poor with
median survival
of <1yr

61. seizure
 RVI pts have lower seizure threshold due to
electrolyte abnormalities
 Seizure may be the presenting Sx of HIV
 Etiology : mainly mass lesions
DISEASE %
HE 7-50
TE 15-40
Cryptococcal
Meningoencephalitis
8
PCNSL 15-40
TB,Aseptic meningitis,PML

62. Sz ctd
Rx
 Anticonvulsants are indicated in ALL RVI pts
with SZ (as it tends to be recurrent in most
pts ) unless rapidly correctable cause is found
 Phenytoin – drug of choice
S/E – hypersensitivity rxn in >10% pts
 Phenobarbitone,valproic acid - alternatives

63. Stoke in RVI pts
 Similar clinical Fx as in non RVI
Etiology
 Vasculitis :VZV,Neurosyphilis,fungal septic
emboli,
 Atherosclerotic cerebllar vascular disease
 TTP
 Cocaine, Amphetamine

64. RECOMMENDATIONS
 RVI pts with CNS disease deserve
Daily neurologic asst to see
improvement, deterioration or to
detect other OIs !!
 MMSE better be done as a
BASELINE for every RVI pt at 1st
entry to care !!

65. References sited
 Harrison principles of internal medicine,17th
edition
 Uptodate 17.1
 emedicine
 National HIV/ART guideline,2008
 internet

66. E
S
P
A
R
E
N
Z
A