Rasmussen encephalitis€¦ · Clinical Epilepsia partialis continua or Progressive unilateral...
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www.laborkrone.de CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019 www.mara.de Rasmussen encephalitis Christian G. Bien Lyon, 26.05.2019
Transcript of Rasmussen encephalitis€¦ · Clinical Epilepsia partialis continua or Progressive unilateral...
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
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Rasmussen encephalitis
Christian G. Bien Lyon, 26.05.2019
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
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Rasmussen encephalitis
Three nagging questions
Does my patient have Rasmussen‘s?
If so: Immunotherapy or surgery?
How does this disease work???
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
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Rasmussen encephalitis
Three theses
2A surgically remediable syndrome.
Immunotherapy: only a stopgap solution
1 RE can be securley diagnosed.
3 RE pathogenesis: T cells and microglia (new!)
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
www.mara.de Steinman L, J Clin Invest 2018;128:1724
Rasmussen encephalitis
Objection
Hemispherectomy=only effective seizure tx, and highly effective!
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
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Rasmussen encephalitis
My background
2001
Since 2000:
Rasmussen
research
with Hans
Lassmann
and Jan
Bauer in
Vienna
2006: Habilitation in Bonn.
„Pathogenesis, diagnosis and
treatment of Rasmussen encephalitis“
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
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Rasmussen encephalitis
Case report
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
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• From Ukraine
• Previously healthy
• December 2018: focal aware seizures (clonic, L side of the body)
• Rapid increase in sz frequency
• March 2019: Family comes to Germany for diagnosis and treatment
• Increasing paresis left upper and lower extremity
• Other hospital: AED switch and IVIG therapy
• Epilepsia partialis continua
• April 2019: Transfer to Epilepsy Center Bethel
Case no. 19804258
T., T. ♂ 6 y
History
19804258
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
www.mara.de Case no. 19804258
T., T. ♂ 6 y
Disease onset: December 2018
+2 months + 4 months+ 1 month
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
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Diagnosis
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
www.mara.de Bien CG, Granata T et al., Brain 2005;128:454
T., T. ♂ 6 y
Checking the diagnostic criteria
Part-A-criteria (cross-sectional): all 3 must be fulfilled1. Clinical Focal seizures (+/- EPC) and Unilateral cortical deficit(s)
2. EEG Unihemispheric slowing+/- ETP and Unilateral seizure onset
3. MRI Unihemispheric focal cortical atrophyand >1 of the following:
(1) Grey or white matter T2/FLAIR hyperintense signal
(2) Hyperintense signal or atrophy of the ipsilateral caudate head
Part-B-criteria (longitudinal/histopathological): 2/3 must be fulfilled
1. Clinical Epilepsia partialis continua or Progressive unilateral cortical deficit(s)
2. MRI Progressive unihemispheric focal cortical atrophy
3. Histopathology T cell dominated encephalitis, activated microglial cells, reactive astrogliosis
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
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H&E
Case no. 19804258. H&E, orig. x400. Dr. Roland Coras, Univ. of Erlangen, Dept. of Neuropathology
T., T. ♂ 6 y
Brain biopsy 06.05.2019 (5 months after onset)
H&ECD68
CD8
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
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T., T. ♂ 6 y
Checking the diagnostic criteria
Part-A-criteria (cross-sectional): all 3 must be fulfilled1. Clinical Focal seizures (+/- EPC) and Unilateral cortical deficit(s)
2. EEG Unihemispheric slowing+/- ETP and Unilateral seizure onset
3. MRI Unihemispheric focal cortical atrophyand >1 of the following:
(1) Grey or white matter T2/FLAIR hyperintense signal
(2) Hyperintense signal or atrophy of the ipsilateral caudate head
Part-B-criteria (longitudinal/histopathological): 2/3 must be fulfilled
1. Clinical Epilepsia partialis continua or Progressive unilateral cortical deficit(s)
2. MRI Progressive unihemispheric focal cortical atrophy
3. Histopathology T cell dominated encephalitis, activated microglial cells, reactive astrogliosis
Olson criterion:
2 part-A-criteria plus B3 (Histopathology)
Bien CG, Granata T et al., Brain 2005;128:454 Olson HE et al., Epilepsia 2013;54:1753
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
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Rasmussen encephalitis
Immunotherapy
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
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Tacrolimus
Immunotherapy
Effect of immuno-tx on hemispheric volume and motricity
Bien CG et al., Neurology 2004;62:2106
Bien CG et al., Epilepsia 2013;54:543
No reduction of seizure frequency
Log-rank (Mantel-Cox) Test: P=0.038
Tac or IVIG
Controls
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
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Immunotherapy
Case example: A., N. ♂ disease onset age 5
Case no. 18801367
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
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TreatmentPyrrhic victory by immunotherapy?!
King Pyrrhus of Epirus defeated the Romans in 279 BC at the battle of Asculum in Apulia.
Pyrrhus remarked afterwards: “Another victory like that, and we shall be utterly ruined.”
Preserved motor function (as a result of immuno-tx), but ongoing drug-
resistant seizures. Hemispherectomy can hardly be offered. The patient
remains severely impaired by the ongoing epilepsy.
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
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Rasmussen encephalitis
Hemispherectomy/
hemispherotomy
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
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65%
79% 80% 80% 81%
92%
0%
20%
40%
60%
80%
100%
Kossoff 2003(Baltimore,
N=46)
Schramm 2012(Bonn, N=14)
Honavar 1982(London, N=10)
Delalande 2007(Paris, N=25)
Granata 2014(Mailand, N=16)
Villemure 2006(Lausanne,
N=12)
Hemispherectomy/hemispherotomy
Rasmussen encephalitis sz free outcome rates 1982-2012
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
www.mara.deEpilepsy Center Bethel, Pat.-ID 60356168. - Neurosurgeon: Dr. Thilo Kalbhenn
Hemispherectomy/hemispherotomyBethel: modified periinsular hemispherotomy
Patient O., N. ♂
Onset at age 5
Preoperative MRI:
5 y after onset
MRI 1 mo after surgery
2 y follow-up: Engel IA. No AED. No complication
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
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Hemispherotomy Immunotherapy
Seizures long-term +++ -Sz exacerbation, status +Neurological function ↓↓ ↓↔
Varadkar S et al., Lancet Neurol 2014;13:195
Treatment
Summary
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
www.mara.de Varadkar S, Bien CG et al., Lancet Neurol 2014;13:195
Treatment
Pathway
Are seizures a relevant problem for
the patient?
Yes No
Would the benefit of HE
outweigh its risks and
expected
consequences?
Is there concern about
deterioration of
neurological functions?
No
No
specific
treatment
Yes
Consider trial of
immunotherapy
for prevention
of neurological
deterioration
No
AEDs; consider
trial of
immunotherapy
for
improved
seizure control
Yes
HE
Re-c
he
ck re
gu
larly
Re
-ch
eck r
eg
ula
rly
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
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Rasmussen encephalitis
Bonus Track:
New data on pathogenesis
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
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MAP-2/CD3/GrBGrB/MAP-2
b2-M/MAP-2 Casp-3/MAP-2MHC-I
GrB
Bien CG et al., Ann Neurol 2002;51:311
PathogenesisCytotoxic T cell attack against neurons
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
www.mara.de Tröscher AR et al., Acta Neuropathol 2019;137:619
Pathogenesis
Microglial nodules attract T cells via innate immunity
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
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Rasmussen encephalitis
Summary
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
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Diagnosis: with checklist.
Treatment for szs: Hemispherectomy
Slowing down of neurological deterioration: Long-term immuno-tx
Sz exacerbation: Short-term immuno-tx
Pathogenesis: not antibodies but T cells, attracted by microglial cells
Rasmussen encephalitis
Summary
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CG Bien: Rasmussen encephalitis. Lyon, 26.05.2019
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Antibody diagnostic
laboratory
30 km apart: Bad Salzuflen
Clinical epileptology
130 beds
Bielefeld, Epilepsy Centre Bethel
