Discerning the Role of Autoimmunity and Autoantibodies in Epilepsy

Steriade, Claude; Gillinder, Lisa; Rickett, Kirsty; Härtel, Günter; Higdon, Lindsay; Britton, Jeffrey W.; French, Jacqueline

doi:10.1001/jamaneurol.2021.3113

Cited by 17 publications

(30 citation statements)

References 73 publications

(123 reference statements)

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“…It should be noted that the presence of the anti-NDMAR(GluN1) IgG subclass in CSF is required for the diagnosis of definite anti-NMDAR encephalitis and only positive results in serum can be considered to be unspecified or as false positives [ 7 ]. Thus, the role in the epilepsy of autoantibodies detected only in serum, especially in patients without overt encephalitis (autoimmune-associated epilepsy), should be addressed in future studies [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…We selected patients with concrete epilepsy characteristics and performed a systematic and prospective CSF sampling (in previous published studies with a higher number of patients, a CSF assessment was only usually performed when there is a positive result in serum or when CSF is obtained on a clinical basis from patients with suspected autoimmune encephalitis). The points in our methodology were recently reinforced by members of the ILAE Autoimmune group in a recent review [ 22 ]. An adequate strategy to increase the number of patients would be to perform a multicenter study and that is the next step in our group, supported by the results presented in this paper.…”

Section: Discussionmentioning

confidence: 99%

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Prevalence of Neural Autoantibodies in Paired Serum and Cerebrospinal Fluid in Adult Patients with Drug-Resistant Temporal Lobe Epilepsy of Unknown Etiology

Cabezudo‐García

Ciano-Petersen

Mena-Vázquez

et al. 2021

JCM

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In order to determine the prevalence of neural autoantibodies in adult patients with drug-resistant temporal lobe epilepsy (DRTLE) of unknown etiology, we compared the characteristics of patients with and without autoantibodies and applied antibody predictive scores to the patients. Patients aged ≥18 years with DRTLE of unknown etiology and ≥12 months of evolution were prospectively recruited. Neural autoantibodies in serum and CSF were systematically determined in all patients. We created the ARTE (antibody in drug-resistant temporal lobe epilepsy) score based on the variables associated with the presence of neural autoantibodies. Twenty-seven patients were included. The mean (SD) age in years at the index date was 52 (±14.2) and at epilepsy onset was 32 (±17.1). The mean epilepsy duration was 19 (±12.5) years. Neural autoantibodies were detected in 51.85% (14/27) of patients. The presence of bitemporal, independent, interictal epileptiform discharges (BIIED) had a higher frequency in patients with neural autoantibodies (57.1% vs. 15.4%; p = 0.025) as well as those patients with a previous history of status epilepticus (49.2% vs. 0.0%; p = 0.007). The ARTE score showed an area under the curve (AUC) of 0.854. Using a cut-off point of ≥1, the sensitivity was 100% and the specificity was 46.1%, whereas when using a cut-off point of ≥3, the results were 35.7% and 100%, respectively. We found a high prevalence of neural autoantibodies in patients with DRTLE of unknown etiology, indicating an autoimmune mechanism. The presence of BIIED and a history of SE in DRTLE of unknown etiology are possible markers for autoimmune-associated epilepsy. The proposed ARTE score requires future validation in larger independent cohorts.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prevalence of Neural Autoantibodies in Paired Serum and Cerebrospinal Fluid in Adult Patients with Drug-Resistant Temporal Lobe Epilepsy of Unknown Etiology

Cabezudo‐García

Ciano-Petersen

Mena-Vázquez

et al. 2021

JCM

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“…A "Yes" to one or more items was classified as positive for the ONES checklist, and an APE2 score of ≥4 or an APE2 score of ≤3 followed by a ACES score ≥2 was classified as positive for the APE2/ACES reflex score. 7 Each patient's neural antibody status classification, ONES checklist classification, and APE2/ACES reflex score classification as positive or negative (Figure 1) allowed for sensitivity and specificity calculations.…”

Section: Key Pointsmentioning

confidence: 99%

“…[3][4][5][6] However, the appropriateness of the term "autoimmune epilepsy" has been questioned, and the need for its conceptual distinction from autoimmune encephalitis has been emphasized. [7][8][9] Many clinical and neuroimaging items included in predictive scores that are intended to be applied to patients with epilepsy or seizures of unknown etiology are derived from features of autoimmune encephalitis, for which dedicated diagnostic criteria exist. 8,10 This is reflective of the finding that whereas some patients with neural antibody-associated disease may present with seizures in relative isolation, a substantial proportion ultimately develop broader features of autoimmune encephalitis.…”

Section: Introductionmentioning

confidence: 99%

“…8,10,11 It has recently been suggested that patients who have features that are clearly suspicious for neural antibody positivity, such as those indicative of a broader encephalitis, should be excluded from investigations of neural antibody testing in epilepsy or seizures of unknown etiology. 7 This was attempted in the Antibodies Contributing to Focal Epilepsy Signs and Symptoms (ACES) study, which excluded patients who had features suggesting an immune etiology that were recognized by the referring clinician. 12 Expectedly, the rate of neural antibody positivity in the ACES study was low, at 3.4%, which is in contrast to other studies reporting neural antibody positivity in up to 31.5% of patients with seizures of unknown etiology that did not have this exclusion criterion.…”

Section: Introductionmentioning

confidence: 99%

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“Obvious” indications for Neural antibody testing in Epilepsy or Seizures: The ONES checklist

et al. 2022

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Objective: Numerous predictive scores have been developed to help determine which patients with epilepsy or seizures of unknown etiology should undergo neural antibody testing. However, their diagnostic advantage compared to only performing testing in patients with "obvious" indications (e.g., broader features of autoimmune encephalitis, characteristic seizure semiologies) requires further study. We aimed to develop a checklist that identifies patients who have "obvious" indications for neural antibody testing and to compare its diagnostic performance to predictive scores. Methods: We developed the "Obvious" indications for Neural antibody testing in Epilepsy or Seizures (ONES) checklist through literature review. We then retrospectively reviewed patients who underwent neural antibody testing for epilepsy or seizures at our center between March 2019 and January 2021, to determine and compare the sensitivity and specificity of the ONES checklist to the recently proposed Antibody Prevalence in Epilepsy and Encephalopathy (APE2)/Antibodies Contributing to Focal Epilepsy Signs and Symptoms (ACES) reflex score.Results: One-hundred seventy patients who underwent neural antibody testing for epilepsy or seizures were identified. Seventy-four of 170 (43.5%) with a known etiology were excluded from sensitivity/specificity analyses; none had a true-positive neural antibody. Of the 96 patients with an unknown etiology, 14 (15%) had a true-positive neural antibody. The proportion of false-positives was significantly higher among patients with a known etiology (3/3, 100%) compared to an unknown etiology (2/16, 13%; p = .01). There was no significant difference of the APE2/ACES reflex score compared to the ONES checklist with regard to sensitivity (93% for both, p > .99) or specificity (71% vs. 78%, p = .18) for truepositive neural antibodies. Significance: Compared to only performing neural antibody testing in patients with epilepsy or seizures of unknown etiology who have "obvious" indications, predictive scores confer no clear diagnostic advantage. Prespecified definitions of | 1659 CHANG et al.

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Autoimmune‐associated seizure disorders

Smith,

Budhram,

Geis

et al. 2024

Epileptic Disorders

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With the discovery of an expanding number of neural autoantibodies, autoimmune etiologies of seizures have been increasingly recognized. Clinical phenotypes have been identified in association with specific underlying antibodies, allowing an earlier diagnosis. These phenotypes include faciobrachial dystonic seizures with LGI1 encephalitis, neuropsychiatric presentations associated with movement disorders and seizures in NMDA‐receptor encephalitis, and chronic temporal lobe epilepsy in GAD65 neurologic autoimmunity. Prompt recognition of these disorders is important, as some of them are highly responsive to immunotherapy. The response to immunotherapy is highest in patients with encephalitis secondary to antibodies targeting cell surface synaptic antigens. However, the response is less effective in conditions involving antibodies binding intracellular antigens or in Rasmussen syndrome, which are predominantly mediated by cytotoxic T‐cell processes that are associated with irreversible cellular destruction. Autoimmune encephalitides also may have a paraneoplastic etiology, further emphasizing the importance of recognizing these disorders. Finally, autoimmune processes and responses to novel immunotherapies have been reported in new‐onset refractory status epilepticus (NORSE) and febrile infection‐related epilepsy syndrome (FIRES), warranting their inclusion in any current review of autoimmune‐associated seizure disorders.

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Discerning the Role of Autoimmunity and Autoantibodies in Epilepsy

Cited by 17 publications

References 73 publications

Prevalence of Neural Autoantibodies in Paired Serum and Cerebrospinal Fluid in Adult Patients with Drug-Resistant Temporal Lobe Epilepsy of Unknown Etiology

Prevalence of Neural Autoantibodies in Paired Serum and Cerebrospinal Fluid in Adult Patients with Drug-Resistant Temporal Lobe Epilepsy of Unknown Etiology

“Obvious” indications for Neural antibody testing in Epilepsy or Seizures: The ONES checklist

Autoimmune‐associated seizure disorders

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