Case presentation

DR MAKAI
• Male 48 RVD R patient presented august 2019 with adult new onset-
seizures (GTC w/ incontinence) for 1 day. Not a known epileptic
• A prior Hx headache and memory lapses .
• Post seizure continued with daily headache, he could not remember
events, was unfamiliar with people and could have tangential
conversations.
• Symptoms have continued to this day except occasionally less
pronounced. But No fits since first presentation.
• Denied fever but admitted to night sweats and weight loss.
• Review of other systems unremarkable.
Past med Hx year Regimen CD4 Viral laod

• Has hx of TB 2014 CXR based. 2004 D4T/3TC/ 8

NVP
• DM⁰ HTN⁰ Asthma⁰ epilepsy⁰ 2009 TDF/3TC/L 150
Drug Hx PV
2010 200
• ATT, Carbamazepine
2011 398 <40
Social Hx
2016 438 54
• Married businessman
2018 604 53.9
• Doesn’t smoke
2019 feb 257 101
• Used to abuse alcohol but stopped in
2005. 2019 nov 265 486
• No animal exposure. 2020 288 212
Fully conscious, oriented in time/?place/person.
obeys commands & speech was normal but couldn’t stay focussed on
one thing.
difficulty naming days of the week both forward and backward.
able to name current president but not former.
Motor-tone/power/reflexes –nml sensation –nml gait-nml
coordination-nml
Vitals –normal
Chest clear CVS-s1s2 regular P/A-soft, non tender no organomegally
Mss-unremarkable.
RVD R on ART since 2004 with low level viremia presenting with
persistent cognitive impairment over the last 11 months.

Differential diagnosis?
Infectious
• PML
• TB meningitis
• HAND
• Neurosyphillis
• Cryptoccocal Meningitis
• CNS toxoplasmosis
• Viral meningitis (HSV/CMV)
• Neurocystercosis.
Non- Infectious
• Other causes of dementia
(vascular,autoimmune,MND)
• Vitamin B12 deficiency
• hypothyroidism
• CNS lymphoma.
• Primary psychiatric disorder.
CSF FBC
Microscopy –1.cell count
Wcc 4.58 Hb 14.4 MCV 93.3 PLT 265
WBC 8 RBC 0
2.indian ink –neg
U/E/Cr
3.gram stain-neg Na 137 K 4.09 sCr 76.3
Biochemistry LFTs
-glu 2.83 Bil 16.7 AST-40.1 Alb 38.6
-protein 0.92
RPR-neg
CAT-neg.
CSF-gene Xpert neg EEG
PCR JC virus –not detected No epileptiform activity seen. Normal
CSF HIV viral load-27268. EEG in the waking and drowsy state.
CT Scan
• Multiple nonenhancing
hypodensities in the cortex and
white matter of bilateral frontal
lobe, right parietal and
periventricular
MRI scan
• Diffuse white matter changes
extending from brainstem to
hemispheres some of which
have correspondingT1
hypointensities. No mass effect.
Impression
CNS-OI,imaging concerning for PML but history concerning for TBM as
well.

Plan.
ATT plus steroids.
Carbamazepine.
 What are the direct effects of HIV on the Central nervous system
(CNS)?
 Image from :Saylor Deanna et al (2016) HIV- associated
neurocognitive disorder- pathogenesis and prospects for
treatment. Nature reviews. Neurology 12 (4), 234-248.
• Areas of the brain most vulnerable to damage include basal ganglia,
frontal cortex and subcortical white matter
• Damage characterised by generalised atrophic changes in the white
matter leading to impaired neurocognition referred to as HIV-
Associated Neurocognitive Disorder (HAND).
• HAND is a spectrum that include asymptomatic neurocognitive
impairment (ANI), mild neurocognitive disorder(MND) and HIV-
associated dementia (HAD).
• Prevalence of HAD has dropped in post CART era.
 Frascati criteria.
Neurocognitive status Functional status
ANI 1 SD below mean, 2 cognitive No impairment in activities of daily living
domains
MND 1 SD below mean, 2 cognitive Impairment in activities of daily living
domains
HAD 2 SD below mean, 2 cognitive Marked impairment in activities of daily living.
domains
Neurocognitive testing should evaluate at least five domains (attention-information processing, language, abstraction-
executive function, complex-perceptual motor skills, memory (learning and recall), simple motor skills & sensory perceptual
skills.
Other etiology of dementia should be ruled out .

Clifford DB & Ances B.M (2013) HIV- associated neurocognitive

disorder. Lancet. Infectious diseases. 13 (1),976-986
• Other diagnostic tests
CSF biomarkers -inflammatory markers (neopterin, IgG-index, IL-6.IL-8), cell stress
marker( CSF sphyngomyelin) and markers of neuronal damage (neurofilament light
protein).
Neuroimaging
- structural (CT/MRI) brain atrophy, some patients will have subcortical white matter
changes on MRI
- metabolic- magnetic resonance spectroscopy, PET
-functional- Magnetic resonance imaging for blood oxygen level dependent imaging
(BOLD).
• No specific treatment of HAND
• Management is geared toward preventing HIV replication in the CNS.
• Variability exists in the penetration and transport of ARVs across the
blood brain barrier.
• CNS viral escape- a form of isolated treatment failure in which local
HIV infection within the CNS compartment is not effectively
suppressed.
• Include two or more agents with high CPE rank in treating CNS HIV
escape.
• CPE ranking does not take into account virological potency, drug
toxities, genetic barrier. Choice of a regimen should not be based on
CPE alone.
• Studies have failed to show benefit of using CPE based strategy for
ART selection particularly in those with milder forms of HAND.
• Quantified HIV-1 RNA in CSF of 97 prospectively enrolled HIV
individuals whose performance on neuropsychological (NP) testing
was noted.
• NP impairment was associated with significantly higher CSF RNA
levels (3.1 vs 1.8 log10 copies/ml) in patients with AIDS (CD4<200)
• Retrospective case series
• At 4 urban medical centers in USA and Europe.
• CSF HIV escape defined as detectable CSF in the setting of treatment
suppressed plasma levels and CSF RNA> 1 log higher than that of plasma RNA.
• 10 patients who presented with neurocognitive symptoms.
• Median HIV RNA 62copies/ml and median CD4 482.
• 8/9 demonstrated clinical improvement following ART regimen optimization.
• 6/7 patients harboured CSF resistant mutations.
• Retrospective study of 11 patients.
• 7/8 had resistant mutations.
• After ART optimization based on CPE and genotypes, all patients
improved.
• Other direct effects of HIV on CNS include increased risk of cerebral
vascular accidents and aseptic meningitis.
conclusion
• Even though the prevalence of the severe form of HAND has dropped
in the post ART era it still occurs.
• Management is tailored towards reducing HIV replication in CNS
• use of CPE based strategy is recommended in patients with HAD and
CNS HIV escape.
Back to our patient
• Current diagnosis
HAND
cant completely exclude - TBM
-PML
• Its clear that he has CNS HIV escape.
patient was switched to DTG/3TC/DRVr
• ordered HIV genotype on CSF
• Plan to repeat CSF after 2months
• He continues ATT
References
1. Clifford DB & Ances B.M (2013) HIV- associated neurocognitive
disorder. Lancet. Infectious diseases. 13 (1),976-986
2. Saylor Deanna et al (2016) HIV- associated neurocognitive disorder-
pathogenesis and prospects for treatment. Nature reviews.
Neurology 12 (4), 234-248.
3. Uptodate.com/contents/HIV associated-neurocognitive-disorder-
management.
4. Medscape.