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
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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