The imaging features of - PowerPoint Presentation

Slide1

The imaging features of

acute HIV encephalitis -characteristics and pitfalls

Paramesh, KAMazumder, AAHolmes, PSiddiqui, ASlide2

Disclosures

None Slide3

Aims

PurposeTo describe and demonstrate the imaging features of HIV encephalitis.MethodReview of imaging findings of a series of patients with likely or confirmed HIV encephalitisFindingsAcute HIV encephalitis can cause diffuse white and grey matter patients, of which white matter changes takes longer to resolve

DiscussionTo consider other differentials such as PML, and other causes of encephalitis Slide4

Epidemiology

65 million people affected by HIV worldwide HIV-1 subtype predominant subtypeNeurological disorders affects 40-70%Treated with cART (combination Anti-Retroviral Therapy) also called HAART (Highly Active Anti-Retroviral Therapy)

Genederedinnovations.stanford.edu, map reproduced from UNAIDS dataSlide5

HIV and the brain

The effect of HIV on the CNS can be divided into three ways:Primary HIV neurological disease- in which HIV in itself is sufficient to cause neurological disease

Secondary or opportunistic neurological diseaseopportunistic infections and tumoursTreatment related neurological diseaseSlide6

Primary HIV infection

Nature Reviews Microbiology 11, 877–883 (2013) doi:10.1038/nrmicro3132Slide7

Acute HIV Infection

Acute HIV infection is the period from initial infection to seroconversionEarly CNS infection can be

asymptomatic although CSF and imaging can detect abnormalities that predate the clinical symptomsGendersexualityhealth.orgSlide8

Acute HIV infection

Common CNS manifestations include aseptic meningitis or meningoencephalitis, Bell’s palsyInflammatory neuropathyThese individuals tend to have A higher CSF viral load

Mild lymphocytosis in CSF, Increased proteinNormal glucose

Natural history after sexual violence

(via presentation Prof Furrer, AIDS focus conference, Bern)Slide9

Acute HIV infection

This is important to recognise because:Neurological symptoms occur before seroconversion Therefore HIV tests can be equivocal or negative (PCR needed for diagnosis)

Initiating treatment with cART, or changing and intensifying the regimen to include more CNS penetrating disease may suppress symptoms Slide10

Other HIV infection

HIV also causes a chronic neurodegenerative condition: HAND (HIV-associated neurocognitive disorder)Same as AIDS dementia complex, HIV-associated dementiaSecondary infection – opportunistic infection and tumoursSlide11

Treatment related neurological disease

Nature Reviews Microbiology 12, 772–780 (2014) doi:10.1038/nrmicro3351Slide12

IRIS (immune

reconstititution inflammatory syndrome)Serious problem complicating the treatment of HIV/AIDSCharacterised by paradoxical clinical worsening that usually occurs within the first 4-8 weeks after starting cARTMassive inflammatory response - resulting in either worsening of the known infection or unmasking a subclinical infection

This inflammatory response is characterised by a massive infiltration of CD8+ T-cells Slide13

IRIS

Among the most common CNS infections known to be involved in IRIS is HIV encephalitis, PML (as shown), crytococcusRisk factors for IRIS are

Taking cART for the first timeActive or subclinical opportunistic infectionCD4 counts <50High CD8+ countAnaemia

Rapid decline in viral load

Treatment

with corticosteroids

has been advocated

especially in

the clinical context of

raised

intracranial

pressure

Martin-Blondell, Mars, Brain 2011Slide14

Pathogenesis of HIV encephalitis

HIV is neuroinvasive (can enter the CNS), neurotrophic (can live in neural tissues) and

neurovirulent (causes disease of the nervous system). The mechanism of neuroinvasion includes the:

‘Trojan horse hypothesis

’

Neuropathogenesis of AIDS, Martin-Garcia, Nature reviews immunology 5, 69-81 2005Slide15

Trojan Horse Hypothesis

HIV infected monocytes are admitted through the blood brain barrierThese monocytes then mature into persistently infected perivascular macrophages

There is direct infection of the choroid plexus, capillary endothelial cells, astrocytes, microgliaPerivascular and parenchymal macrophages fuse with microglia to form giant cellsPathological signs of giant cell encephalitis can be found in the cortex, but preferentially affects the

subcortical white matter, deep white matter tracts

and

basal ganglia

This correlates closely with the imaging findings Slide16

Case study 1

Patient 1

Age

Sex

Clinical presentation

HIV RNA load

CSF findings

CSF PCR

Other results

 47

 M

HIV, CD4<500, presenting with frontal headache and fevers.

57680

Lymphocytosis, raised protein (0.74)

Negative

HepBsAg 459

A) T2 axial imaging showing diffuse signal abnormality within the right caudate and lentiform nuclei (yellow arrows) with extension into the adjacent white matter, and (B) also extending rostrally into the right coronal radiata (green arrows).

A

BSlide17

Case study 1: Imaging findings

Imaging

Follow-up imaging

Initial scan

Subtle T2 hyperintensity within  the  right  corpus

striatum,  thalamus  and  adjacent  deep  white  matter  without

mass  effect  or  pathological  enhancement

8 days later

Diffuse high signal and mild swelling in the right corpus striatum, corpus callosum and right corona radiata and deep frontal white matter, High signal in right cerebral peduncle and pons.

1 month later

Clear progression with diffuse white mater signal abnormality in both cerebral hemispheres, subcortical whit matter, temporal stem, both middle cerebral peduncles

4 months after initial study

 Marked improvement of diffuse white matter signal change in the cerebral white matter. Minimal residual signal change in periventricular regions ad right subinsular region

Resolution of the grey matter changes (yellow arrows) occurred on the follow up study (C)

CSlide18

Case study 2

Patient 2

Age

Sex

Clinical presentation

HIV RNA load

CSF findings

CSF PCR

Other results

 40

 M

New diagnosis of HIV,  CMV,   CD4 12, poor memory, no focal neurology 

733010, 16 days later, 879265

Raised protein (0.97)

Normal glucose

CMV positive with viral load of 12537

nil

T2 axial imaging: On the presentation study there is signal abnormality within the (A) deep grey structures (yellow arrows), and (B) deep white matter and (C) extending rostrally into the corona radiata

A

B

CSlide19

Case study 2: Imaging findings

Imaging

Follow-up imaging

Initial scan

Widespread patchy to confluent signal change in cerebral white matter in both hemispheres, caudate and lentiform nuclei, dorsal pons, middle cerebellar peduncles and deep cerebellar white matter. No restricted diffusion or contrast enhancement.

4 months later

Improvement in the signal change in basal ganglia and thalami. Progressive signal abnormality in deep cerebral white matter, especially the frontal lobes and periventricular parietal matter

D) Follow up T2 axial imaging showing resolution of grey matter changes (yellow arrows), with persistent white matter changes, although reduced in extent in comparison to the presentation imaging (green arrows).

DSlide20

Case study 3

Hospital no

Age

Sex

Clinical presentation

HIV RNA load

CSF findings

CSF PCR

Other results

Patient 3

 50

 M

HIV, intermittent headaches, dizziness, poor vision, confusion

.

12062

Nil

nil

nil

A) T2 axial imaging - diffuse grey and white matter signal abnormality is shown on the initial imaging within involvement of deep grey structures, white matter, pons, brachia pontis and cerebellum. B) Early resolution of grey matter changes (compare regions highlighted by arrows)

B

ASlide21

Imaging findings

Imaging

Follow-up imaging

Initial scan

Extensive abnormality in cerebral hemispheres, brainstem, basal ganglia and cerebellum with swelling

9 days later

Slight progression with T2 signal abnormality in white matter in cerebellar hemispheres with enhancement

3 months later

Marked improvement in extensive cerebral and brainstem signal change, although widespread frontal and parietal white matter change persists.

C) Follow up imaging. Compared to the previous imaging we note the persistence of white matter signal change in the frontal lobes (green arrows) with resolution of the deep grey, cerebellar and pontine changes (yellow arrows)

CSlide22

Summary of imaging findings

Widespread subcortical white matter and grey matter changesImprovement in grey matter changes initially with signal change in white matter taking longer to resolveThe extent of signal change may not necessarily correlate with the clinical pictureSlide23

Summary of imaging findings 2

Resolution often takes weeks to months with grey matter changes resolving first and white matter changes taking much longerNot all of the patients we studied had imaging follow-up until resolutionTherefore difficult to determine whether all changes completely resolved

Often on a background of MRI changes associated with HANDSlide24

Pitfalls

It is important to consider other differentials such asPML, lymphoma, IRIS Other causes of encephalitisHence correlation with history, clinical exam and pathology crucial

PML (radiopedia)HSV encephalitis radiopedia

CNS lymphoma

radiopediaSlide25

References

Acute encephalitis as initial presentation of primary HIV infection Nzwalo, anon, aguas, BMJ case reports 2012HIV related neuropathology, 1985-1999: Rising prevalence of HIV encephalotpathy in the era or HAART Neuenburg, Scholte JAIDS 31:171-177, 2002 Neuropathogenesis of HIV-1 infecton Zink, Gendelman FEMS 26(1999)233-241HIV infection of the CNS: Clinical features and neuropathogenesis Boisse, Power Neurol Clin (2008) 799-819Neurologic Presentations of AIDS Singer, Levine Neurol Clin 28 (2010) 253-275CD8 encephalitsis in HIV-infected patients receiving cART: A treatable entity Lescure, Gray CID 2013:57Trojan horse hypothesis – Neuropathogenesis of AIDS, Martin-Garcia, Nature reviews immunology 5, 69-81 2005

MRI images for other differential diagnoses from radiopedia,com HIV epidemiology –Genederedinnovations.stanford.edu, map reproduced from UNAIDS dataAcute HIV infection – gendersexualityhealth.orgNatural history after sexual violence – Prof Furrer, AIDS focus conference, BernPML and IRIS - Pathogenesis of the immune reconstitution inflammatory syndrome affecting the central nervous system in patients infected with HIV Brain 2011 Martin-Blondell and Mars