HIV Neurology

Neurologic Manifestations
of HIV
Yidnekachew, Final Year Medical Resident
Moderator: Dr Selam Kifelew, Consultant Neurologist
November 2021
12/10/2021 HIV Neurology 1

Outlines
 Introduction
 Principles
 Meningeal syndromes
 Cognitive problems
 Mass lesions
 Seizure

Introduction
 So far- 77.3M infections and 35.4M deaths
 38M cases WW,1.8M new cases & 1M deaths
 SSA- 50% of burden (6.2% of world population)
 Ethiopia- 0.9% (690,000 people)
 Emerging issues- epidemiologic shift, effects beyond the immunity

Neuropathogenesis

NeuroAIDS Facts
 Before era of ART

 An initial presentation in 10%
 30-50% over the course
 Autopsy- 80%
 Contributes to morbidity and mortality
 Impaired CMI, Direct infection, autoimmunity or inflammation and drugs
 Decreased incidence with ART (10 fold) ± Prophylaxis
 2nd most commonly affected system

Principles
1. CD4 is the most important
2. More than one pathology can exist
3. Any neuraxis can be affected
4. Most infections are reactivation
5. Can have non HIV related disease
6. OIs first and ART ASAP

Classification
 Pathophysiologic
 Anatomical
 Temporal

Classification

HIV Neurology

Temporal

Clinical Approach
1. Meningitis ± Encephalitis
2. Cognitive Impairment
3. Mass Lesions (FND)
4. Seizure
5. IRIS

Meningitis
 Cryptococcal- 52-62.3%
 Tuberculous- 19.6-24.6%
 ABM- 10.1-14.2%
 Syphilitic
 Listeria species
 Lymphomatous
 Aseptic

Aseptic Meningitis
 Acute and chronic forms
 During seroconversion
 Headache, stiff neck and fever with systemic symptoms
 Mod pleo and inc prot with normal gluc
 Diagnosis of exclusion
 Symptomatic tx and ART

Fiebig Staging of Acute HIV

Syphilitic Meningitis
 Accelerated course
 Bidirectional relationship
 Complex diagnosis and management
 All patients should have CSF evaluation
 IV penicillin

Tuberculous Meningitis
 The most common form of CNS TB
 Second most common cause of meningitis
 Subacute to chronic meningitis
 Headache, fever, nausea, vomiting, seizure, AMS, FND
 Systemic TB is more common
 CSF- GeneXpert/AFB/Culture/LAM

Diagnosis

Treatment
 Same as non HIV
 Add steroid to be tapered over 6-8 weeks
 Delay ART for 4-6 weeks
 Delay in treatment is poor prognostic marker
 Prognosis- MASH-P
 Monitor- IRIS/Paradoxical worsening

Cryptococcal Meningitis
 The most common CNS OI in Africa
 7% in Ethiopia
 Very high mortality
 15-20% of deaths in HIV
 Meningoencepahlitis
 Stabilized at a higher level in SSA

Clinical Features
 Slowly progressive headache with fever- median 14 days
 Meningismus (1/4 to 1/3)
 Altered mentation
 Evidence of disseminated disease
 Complications
 Early detection- serum CrAg (8% in Ethiopia)

Brian Imaging

CSF or Serum (for Ag)
PCR

Prognostic Factors
 Abnormal mental status
 High burden of yeast
 CSF WBC <20/microL
 Raise ICP
 Low body weight/hypoalbuminemia
 Delayed and sub optimal treatment

Management
 Antifungal, Management of ICP and ART
 ICP- serial LP, shunt or catheter
 Avoid steroid, acetazolamide or mannitol
 Anticipate IRIS
 Outcomes- Response, Failure(SX or ASX), Relapse, IRIS

Management
Consolidation
Induction Maintenance
Fluconazole 400-
AmB + 5-FC Fluconazole 200mgs
800 mgs daily, 8 daily
2 weeks
weeks

FMOH Ethiopia

Primary Prevention

Meningitis Differential Diagnosis

HIV Associated Neurocognitive Disorders
 One of the most common (up to 50%)
 Direct infection, toxic signaling pathways, inflammation, comorbidities
 Changing pattern with ART- severity and domains
 RF- CVD RFs, CKD, duration of HIV, educational status, age, HCV
 Behavioral, cognitive and motor
 Diagnosis of exclusion, Screening
 CSF VL ≥ Plasma VL

Pre and Post ART Era
HAND
70% ANI
26% MND
4% HAD

Diagnosis

Frascati Criteria

Screening Tools

Differential Diagnosis
 OIs and OMs
 Degenerative diseases
 Vascular dementia
 Nutritional/Endocrine
 Psychiatric
 Polypharmacy

Treatment
 ART is the most important (simple regimen)
 Treat comorbidities (CV, Psychiatric)
 Social support, exercise and physiotherapy
 Methylphenidate for fatigue and psychomotor slowing
 Consider CSF viral load and DST
 Outcome- stable(61%), improve(16%), worsen(23%)
 Three fold increased mortality

CSF Viral Escape
 Undetectable plasma HIV RNA with detectable CSF HIV RNA
 Phylogenetically different or unique resistance mutations
 Not common (7-18%)
 RF- low nadir CD4, poor adherence
 Symptomatic, asymptomatic or secondary
 Symptomatic- optimize ART (DST or CPE)
 IRIS- CD8 encephalitis, diffuse GM &WM lesions and CD8 pleocytosis

CNS Escape

CPE Rank 2010
Dolutegravir

Focal CNS Lesions in HIV

Toxoplasma Encephalitis
 The most common CNS OI in HICs
 Zoonotic disease
 CD4<200 and seropositive (80% in Ethiopia)
 Etiology- Toxoplasma Gondi
 Usually reactivation
 Most in CNS(89%), rarely- pul(6%), ocular(3.5%) and diss(1.7%)

Clinical Features
 Headache, fever, focal neurologic deficits, and seizures
 Cerebral edema: confusion, dementia, and lethargy, and coma
 Predilection for the BG, G-WM junction
 LP is often contraindicated because of the mass effect
 CSF- PCR for Toxoplasma(50% sen and 96-100% spe)
 Presumptive diagnosis- CD4, CP, Imaging, and Serology

Diagnosis

Treatment
 First line: pyrimethamine, sulfadiazine, and leucovorin for 6 weeks or until

enhancement resolves
 Empiric treatment- AIDS with ring-enhancing lesions
 Improvement- Clinical(50% in 3 days and 90% in 2 weeks) and radiologic(2-3
weeks)
 Sulfa allergy- atovaquone
 Steroid- with indications
 Prevention- 1o and 2o

TE Vs. PCNSL

For our setting

For the Developed Cxs
Predictors
Mass effect
Toxo serology
Prophylaxis
Response to Cotri
CSF PCR/Cytology
Imaging features
CD4
Biopsy

PCNSL
 1000-4000 fold increased risk
 Unregulated proliferation of EBV
 ~10-20% of the cases of lymphoma in HIV patients (most DLBCL)
 RF- low CD4(<50), high VL, Hep B/C coinfection
 Confusion, lethargy, memory loss, hemiparesis, aphasia cranial nerve deficits,

headaches, and/or seizures- acute to subacute
 Constitutional symptoms are variable

Diagnosis
 Single heterogeneously enhancing lesion (50%)
 Deep WM and peri-ventricular regions
 CSF- Cytology and flow-cytometry, EBV PCR
 Brain biopsy- for a definitive diagnosis
 Thallium 201 SPECT and FDG PET
 Radiation and methotrexate, steroid

Diagnosis

PML
 Etiologic agent- JC virus
 Lytic infection of oligodendrocytes
 Demyelination (leukocortical and intracortical)
 CD4+ < 100 cells/mm3
 Slowly progressive FND- hemiparesis, aphasia, ataxia, visual deficits, and cognitive
impairment
 Spares SC and ON

Diagnosis
 Definitive: clinical, radiographic, and virologic evidence
 MRI- multifocal lesions in the subcortical and periventricular WM (U fibers)
 Basal ganglia, brainstem, and cerebellum can be involved
 Hyperintense on T2 and hypointense on T1
 No mass effect or enhancement (Classical Vs. Inflammatory)
 CSF- PCR (74-93% sen and 92-100% spe), Biopsy

Differential Diagnosis

Diagnosis

Treatment
 No specific treatment
 ART is the main stay of treatment
 Investigational treatments
 Steroid for IRIS
 Prognosis- age, CD4, ART, AIDS, neurologic impairment, JC VL, Imaging
 One year survival- 50% vs. 10% with or with out ART (no remyelination)

CMV Encephalitis
 CD4+ T<50 cells/mm3
 Ventriculoencephalitis, micro nodular encephalitis, retinitis, or polyradiculitis
 Often in the presence of a concurrent CMV-related systemic infection
 CSF- pleocytosis, elevated protein, and low glucose
 CSF- PCR(80&90% sen and spe)

 Treatment- ganciclovir and foscarnet for at least 2 to 3 weeks
 Valganciclovir until the CD4+>100 cells/mm3 for at least 3 to 6 months

Diagnosis

IRIS
 Clinical deterioration in the setting of immune recovery
 Risk factors- Lower CD4+and faster immune recovery with rapid decline of VL, early initiation
of ART
 Paradoxical or unmasking
 Systemic much more common than CNS
 Most in CM, TBM and PML
 Fulminant encephalitis

IRIS
 Diagnosis of exclusion
 Prevention is the most important
 Work up for OI, appropriate Tx and delay ART
 Treatment of underlying infection
 Steroids- severe cases with slow tapering over 4-6 weeks
 Pulse for risk of herination

Stroke
 An independent RF
 Both hemorrhagic and ischemic
 More with low CD4
 Aggressive control of RFs
 Cause for cryptogenic stroke

Seizure
• More common with advanced disease
• GTCSZ is the most common
• 5-10% incidence
• EEG- diffuse slowing
• High risk of status/recurrence
• Up to 50%- no cause identified
• AEDs

Cause of Seizure in HIV

Approach to New Onset Seizure in HIV Patients

Summary of Neurological Diseases in HIV

Summary of Neurological Diseases in HIV

Approach

References
 Bradley's Neurology in Clinical Practice, 8th edition, 2021

 Mendel's Principles and Practice of Infectious Diseases, 9th edition, 2020
 National Consolidated Guideline for HIV, FMOH, Ethiopia, 2018
 Review articles, NeuroAIDS
 Neurology in Africa, William Hewlett, 2012
 Continuum Neuroinfectious Disease Guest Editor: Joseph R. Zunt, MD,
MPH,OCTOBER 2018 VOL. 24 NO. 5
 Harrison's Principles of internal Medicine, 20th edition, 2018
 Uptodate online

THANK YOU

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Neurologic Manifestations

Moderator: Dr Selam Kifelew, Consultant Neurologist

12/10/2021 HIV Neurology 1

12/10/2021 HIV Neurology 2

 So far- 77.3M infections and 35.4M deaths

 38M cases WW,1.8M new cases & 1M deaths

 SSA- 50% of burden (6.2% of world population)

 Ethiopia- 0.9% (690,000 people)

 Emerging issues- epidemiologic shift, effects beyond the immunity

12/10/2021 HIV Neurology 3

12/10/2021 HIV Neurology 4

 Before era of ART

 30-50% over the course

 Contributes to morbidity and mortality

 Impaired CMI, Direct infection, autoimmunity or inflammation and drugs

 Decreased incidence with ART (10 fold) ± Prophylaxis

 2nd most commonly affected system

12/10/2021 HIV Neurology 5

1. CD4 is the most important

2. More than one pathology can exist

3. Any neuraxis can be affected

4. Most infections are reactivation

5. Can have non HIV related disease

6. OIs first and ART ASAP

12/10/2021 HIV Neurology 6

12/10/2021 HIV Neurology 7

12/10/2021 HIV Neurology 8

12/10/2021 HIV Neurology 9

12/10/2021 HIV Neurology 10

3. Mass Lesions (FND)

12/10/2021 HIV Neurology 11

12/10/2021 HIV Neurology 12

 Acute and chronic forms

 Headache, stiff neck and fever with systemic symptoms

 Mod pleo and inc prot with normal gluc

 Symptomatic tx and ART

12/10/2021 HIV Neurology 13

12/10/2021 HIV Neurology 14

 Complex diagnosis and management

 All patients should have CSF evaluation

12/10/2021 HIV Neurology 15

 The most common form of CNS TB

 Second most common cause of meningitis

 Subacute to chronic meningitis

 Headache, fever, nausea, vomiting, seizure, AMS, FND

 Systemic TB is more common

12/10/2021 HIV Neurology 16

12/10/2021 HIV Neurology 17

 Same as non HIV

 Add steroid to be tapered over 6-8 weeks

 Delay ART for 4-6 weeks

 Delay in treatment is poor prognostic marker

 Monitor- IRIS/Paradoxical worsening

12/10/2021 HIV Neurology 18

 The most common CNS OI in Africa

 Very high mortality

 15-20% of deaths in HIV

 Stabilized at a higher level in SSA

12/10/2021 HIV Neurology 19

 Slowly progressive headache with fever- median 14 days

 Meningismus (1/4 to 1/3)

 Evidence of disseminated disease

 Early detection- serum CrAg (8% in Ethiopia)

12/10/2021 HIV Neurology 20