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When the immune system attacks the brain: anti-GAD 65
When the immune system attacks the brain: anti-GAD 65

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When the immune system attacks the brain: anti-GAD 65 - Description

spectrum of imaging findings Remy R Lobo MD Edward P Quigley III MD PhD Scott McNally MD PhD EE03 Electronic Excerpta Disclosures None Purpose Limbic encephalitis is becoming more commonly recognized in a wide patient population ID: 541773 Download Presentation

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anti negative mri gad negative anti gad mri flair left encephalitis temporal gad65 case immune 2015 auto shown pcr

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Presentation on theme: "When the immune system attacks the brain: anti-GAD 65"— Presentation transcript

Slide1

When the immune system attacks the brain: anti-GAD 65spectrum of imaging findings

Remy R. Lobo, MDEdward P. Quigley III, MD, PhDScott McNally, MD, PhD

EE-03Electronic ExcerptaSlide2

DisclosuresNoneSlide3

Purpose

Limbic encephalitis is becoming more commonly recognized in a wide patient populationOncologic and non cancer patients alikeDiagnosis is often difficult to make, and neuroimaging plays a critical roleThis presentation describes findings in a perplexing case of anti-GAD 65 auto-immune encephalitisSlide4

Case report71 year old man with one month gradual onset of aphasia and a single

seizurePast medical history: hypertension No surgical or oncologic history

Social/family history noncontributoryPresents for neuroimagingSlide5

Left temporal lobe hypoattenuationNonspecific features, warrants additional evaluation with MRI

Presentation NECTSlide6

MRI same day:

Mass like T2 and FLAIR hyperintensity

in the left temporal lobeSlide7

MRI, continued

Areas of DTI hyperintensity with ADC

correlateNo significant enhancement on T1+C Slide8

MRI, continued. CTA

No susceptibility on

SWINo attributable vascular abnormality on CTAMultifocal atherosclerotic narrowing (not shown)

Initially presumed strokeArea is hypovascularAdjacent vein of

Labbe

is

patentSlide9

Hospital Day 5

Repeated seizures, worsening aphasiaRepeated lumbar punctureRepeated MRIEnlarging left temporal lobe lesion on FLAIR

New FLAIR lesions bilaterallySlide10

Spectroscopy

135 msec, single voxel study

Low NAADepressed choline and creatine peaksLarge lactate doublet

No other findings on MRI (no T2* or enhancement)Slide11

Proceeded to angiography (HD 7)

Severe right sided stenosis (contralateral to the primary lesion)Left ICA injection, AP, cross filling of the right sided systemNo local vascular abnormalitySlide12

HD 9, MR perfusion

Aphasic, still seizingHas failed steroids, plasmapheresisDifferential of ADEM, tumor, infection or other cause of demyelinationPerfusion showed slightly increased peak

enhancementSlide13

HD 10, repeat MRI / MRACervical/thoracic/lumbar negative (not shown)

MRA using 3D TOF, and vessel wall sequencesNo abnormal vessel wall enhancementSelected black blood pre/post contrast images shown(note intrinsic

T1 signal in the left temporal lobe)

Pre contrast DANTE sequence

Post contrast DANTE sequenceSlide14

HD 11, biopsy

Lack of response to therapy, unknown etiology, family elected for biopsyNECT post biopsy shows that 2 cm segment of temporal lesion takenBut

new lesions continue to appear (even on NECT)Slide15

HD 14, what we (don’t) know

HHV-6 PCR negativeCMV PCR negativeHSV PCR

negativeVZV IgG and IgM negativeVZV PCR negativeEnterovirus PCR

negativeWest Nile IgG and IgM negativeHIV-1,2 negativeHepatitis B and C negativeFungal antibodies (Histoplasma,

Coccidiomycosis

,

Blastomycosis

,

H.

mycelia

, A

spergillus

)

negative

Gram

stain

negative

JC

virus

negative

RPR and

Quantiferon

TB negative

.

ANA, ANCA, SSA/SSB negative

ESR, CRP both normal

CSF

ACE normal, negative OCB

LDH - 269

(upper

normal

253). Repeat LDH elevated at

1800s

Flow

cytometry

negative

Paraneoplastic

Abs (PCCA/ANNA IgG CSF)

negative. LGI-1/

Caspr

Ab

negative

Apolipoprotein

A-1

negative

Prothrombin

G20210A mutation

negative. Lupus

anticoagulant

negative

Protein

C and

S, homocysteine, and

antithrombin

all normal

CJD negativeSlide16

HD 15 repeat MRI (path not back)

Redemonstrated multiple nonenhancing lesions, all continue to increase in size (as shown on FLAIR)Slide17

HD 16, skull-thigh FDG/PET

Areas of T2/FLAIR signal abnormality show

increased

FDG avidity. No other lesions foundSlide18

Follow up MRI, HD 27FLAIR signal continues to

expandNo significant enhancement (not shown)Slide19

Day 35Plasmapheresis, steroids, IVIG all proved ineffective

Extensive CSF and hematologic work up failed to reveal etiology/causative agentBiopsy showed reactive gliosis, no neoplasmAll subsequent stains were negativeSend out CSF panel returned anti-GAD65 antibodies

Despite extensive intervention, family elected to withdraw care, patient passedSlide20

anti-GAD 65GAD65 is a GABA synthesizer in neurons

GABA = γ-aminobutyric acidGABA is important for neuron inhibitionGAD65 starts as an intracellular proteinCan be

displayed on surfaces during exocytosisExpressed in hippocampi (HF), cerebellum (Cbll)Antigen can be a target in patients with diabetes, thyroiditis, and (rarely) tumors (e.g. lung)Slide21

anti-GAD 65

Body forms a T cell mediated responseAuto immune etiologies/response variesHF – cancer related, poorly responsive to therapyCbll – less neoplastic related, responds well to therapy

Diagnosis is tricky and is often delayedReliance upon imaging, lumbar puncture, EEGTreatment – immunomodulatory agentsIVIG, plasma exchange, immunosuppressants

Can follow antibody titers, will decrease if effectiveSlide22

anti-GAD 65

Non-neoplastic auto-immune encephalitisTypically present with stiff man syndrome or cerebellar ataxia, but cognitive decline is also possible

Epilepsy is poorly responsive to AED’sSignal abnormality is most commonly in the hippocampus, amygdala, and mesial temporal lobesOur case was a little atypicalSlide23

anti-GAD 65

Imaging shows T2/FLAIR signal

Enhancement on T1+C infrequentWill be FDG avid

Diagnosis usually requires an LPSlide24

Proposed diagnostic approach

A.J. da Rocha, R.H.

Nunes

, A.C.M. Maia Jr,

L.L.F

. do

Amaral

Sept 2015Slide25

anti-GAD 65

anti-GAD65 case example from literatureA. FLAIR signal bilaterallyB.

FDG/PET hypermetabolism (right>left)C. EEG

showing two seizures (left slow wave, right delta), which both generalized late

Aug 2015

G. Widman,

et al.Slide26

SummaryAuto immune encephalitis is becoming more commonly recognized

It may OR may not be associated with cancerWork-up is time consuming and difficultConsider anti-GAD65 and other auto immune etiologies in perplexing casesSlide27

Thank you for your timePlease contact

remy.lobo@hsc.utah.edu with any comments or feedbackSlide28

References

da Rocha AJ, et al. Recognizing Autoimmune-Mediated Encephalitis in the Differential Diagnosis of Limbic Disorders. AJNR. ePub Sep 2015.

p1-10Saiz A, et al. Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain

(2008), 131, p2553-2563Fauser S, et al. Long latency between GAD-antibody detection and development of limbic encephalitis - a case report. BMC Neurol 2015 30;15(1):177. Epub

2015 Sep

30

Ali

F,

et al. Stiff-person syndrome (SPS) and anti-GAD-related CNS degenerations: Protean additions to the autoimmune central neuropathies.

Jrnl

of

Autoim

.

Volume 37, Issue 2,

Sep

2011,

p79–87

Widman G,

et al. Treating a GAD65 antibody-associated limbic encephalitis with

basiliximab

: a case study. Front. Neurol.,

August 2015,

Volume 6 Article

167, p1-11