Antineuronal antibodies and epilepsy:
treat the patient, not the lab
Contributors The author drafted the editorial
commentary.
Stephan Rüegg1,2
Competing interests None declared.
Patient consent for publication Not required.
The study results implicate that starting immunosppressive treatment in newonset epilepsy should be guided by clinics, not simply antibody presence
Epilepsy affects about 70–80 million
people worldwide; about one-
third of
patients cannot become seizure free. New
diagnostic and therapeutic avenues to
improve this situation are welcome. The
impact of autoimmune phenomena on
pathogenesis of some epilepsies increasingly gained attention as these mechanisms open the door for alternative
medical treatments beyond antiseizure
medications, that is, immunosuppressants. Thus, ‘autoimmune’ has become
one of the six aetiologic categories of the
new Intenational League Against Epilepsy
classification of seizures and epilepsies.
Numerous neuronal surface autoantibodies (NSAbs) identified in the past years
cause autoimmune encephalitis (AE),1
often associated with severe seizures and
status epilepticus. Additionally, the prevalence of NSAbs in patients with chronic
epilepsies of unknown aetiology yielded a
prevalence between 3% and 21%, but the
question whether all epilepsy patients with
NSAbs or only those with pharmacoresistant epilepsy (PRE) and/or additional
signs of AE warrant immunosuppressants remained unresolved yet. A study
looking at the presence of NSAbs in PRE
found that 62% of patients responded to
immunotherapy, and 34% even became
seizure free, indicating that a trial may be
justfied.2 But how does this result relate
to patients with new-onset focal epilepsy
(NFE)? The paper by Mc Ginty et al,3
tackles this issue by prospectively looking
at those patients with NFE and a test positive for at least one NSAbs. The authors
established an NSAbs prediction score
based on clinical and paraclinical information and evaluated the value of immunotherapy in patients with NFE. About
1
Medical Faculty, University of Basel, Basel, Switzerland
Neurology, University Hospital Basel, Basel, Switzerland
2
Correspondence to Dr Stephan Rüegg, Medical
Faculty, University of Basel, Basel 4031, Switzerland; S.
Rueegg@unibas.ch
230
Funding The author has not declared a specific grant
for this research from any funding agency in the public,
commercial or not-for-profit sectors.
10% of their cohort was NSAbs positive
and 40% of them were diagnosed with
AE. They identified six features which in
combination were highly predictive for the
presence of NSAbs, that is, age >54 years,
ictal piloerection, self-
reported lowered
mood, MRI changes in the limbic system,
the absence of ‘conventional’ epilepsy risk
factors and intact attention. This ‘NSAbs-
detecting’ Score compared better with the
recently published ‘antibody prevalence
in epilepsy and encephalopathy’ (APE2)
Score4 in terms of forecasting AE, but
worse in predicting presence of NSAbs.
According to the present study (with
an admittedly small sample of patients),
immunotherapy could be omitted in those
patients with NSAbs-
positive new-
onset
epilepsy without signs or symptoms of
AE. Conversely, the study also indicates
that immunosuppressants are warranted
in patients with even subtle AE. This is
in line with another study where patients
with AE even without NSAbs benefitted
from immunosuppressants.5 The authors
conclude that the administration of immunotherapy in NSAbs-
positive patients
should be guided by clinical signs for
(subtle or obvious) AE and not only by
NSAbs positivity per se.
The study did not rely on cerebrospinal
fluid data, probably leading to some missed
cases of NSAbs positivity and AE. It is also
interesting that 5/16 NSAbs positive, but
AE-
negative patients had mRS >0 and,
thus, likely were pharmacoresistant,
although this information was not exactly
verifiable without follow-up phone interview. Statistically, this would exactly fit the
one-
third of patients basically becoming
pharmacoresistant in chronic epilepsy
of various aetiologies. Thus, future trials
should test whether immunotherapy given
to these patients would prevent pharmacoresistancy despite the fact that outcome
without such treatment was mostly promising in this study.
Provenance and peer review Commissioned;
internally peer reviewed.
Open access This is an open access article
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which permits others to distribute, remix, adapt, build
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permitted under CC BY-NC. No commercial re-use. See
rights and permissions. Published by BMJ.
To cite Rüegg S. J Neurol Neurosurg Psychiatry
2021;92:230.
Received 24 November 2020
Accepted 25 November 2020
Published Online First 5 January 2021
►► http://dx.doi.org/10.1136/jnnp-2020-325011
J Neurol Neurosurg Psychiatry 2021;92:230.
doi:10.1136/jnnp-2020-325350
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in new-onset focal epilepsy: implications for
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2021;92:291–4.
4 Dubey D, Alqallaf A, Hays R, et al. Neurological
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Rüegg S. J Neurol Neurosurg Psychiatry March 2021 Vol 92 No 3
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Editorial commentary