TABLE 2.

Guide to operationalization of the ONES checklist

1. The ONES checklist should only be used in patients with epilepsy or seizures of unknown etiology, after appropriate evaluation (e.g., clinical history, physical examination, brain magnetic resonance imaging, electroencephalography) to exclude more likely alternative diagnoses.

2. The ONES checklist restricts anti‐MOG and anti‐GlyR testing to patients with typical disease phenotypes. The tiered approach to the checklist should be followed, with progression from one tier to the next only if the answer is “No” to all preceding items. In the rare patient with seizures and features of both anti‐MOG and anti‐GlyR, panel‐based testing that includes both of these antibodies should be performed, hence their listing as (1a) and (1b) on the ONES checklist.

3. Nervous system dysfunction or neuroimaging findings that are ictal or postictal phenomena should not be the reason for answering “Yes” to relevant items on the ONES checklist. Close clinical and/or neuroimaging follow‐up can aid in making these distinctions and is encouraged.

4. The phrase “in temporal relation to seizure onset” used throughout the ONES checklist emphasizes the importance of evaluating clinical symptoms and neuroimaging findings as they relate to seizure onset, because a temporal relationship supports a shared etiology.

5. The term “distinguishable” and the phrase “of unknown etiology” used throughout the ONES checklist are intended to emphasize the importance of distinguishing dysfunction possibly attributable to neural antibody associated‐disease not only from alternative diagnoses, but also from neuropsychiatric symptoms that are common among patients with epilepsy. Inquiry into the impact of such symptoms on activities of daily living, collection of ancillary clinical history from friends or relatives, and formal cognitive assessment/neuropsychometric testing can help make these determinations and are encouraged.

6. The term “refractory” refers to failure of two or more antiseizure medications (either as monotherapies or in combination). In patients with high seizure frequency, timely identification using the ONES checklist relies on expedient determination of seizure refractoriness.

7. Medial temporal lobe T2‐FLAIR hyperintensity with atrophy suggestive of MTS is not included in the ONES checklist, because of the frequency of MTS in nonimmune temporal lobe epilepsy. In patients with MTS, however, it is critical to review any previously available neuroimaging to look for T2‐FLAIR hyperintensity restricted to the medial temporal lobe(s) without atrophy that is suggestive of autoimmune limbic encephalitis in temporal relation to seizure onset, which is included in the ONES checklist.

8. Where “temporal lobe” seizure localization is specified, review of clinical information (e.g., seizure semiology) and ancillary test data (e.g., electroencephalography) is critical to identify supportive evidence for this localization. Temporal lobe seizures with involvement of adjacent regions (e.g., temporoperisylvian) are included. Thorough review is particularly important for patients with recurrent generalized tonic–clonic seizures, in whom temporal lobe seizure origin may not be immediately apparent.

9. The term “presumed temporal lobe seizures” is intended to identify rare patients with recurrent seizures for whom there are no clinical or ancillary test data that definitively aid in seizure localization. These are patients who could, however, reasonably be presumed to have temporal lobe seizures in the absence of evidence to suggest otherwise. For this reason, patients with non‐temporal lobe symptoms/semiologies, or electroencephalographic findings suggesting exclusively extratemporal/independent extratemporal multifocal spike foci should not be considered to have “presumed temporal lobe seizures.”

10. In patients with seizures and one or more historical features, clinicians are likely to pursue neural antibody testing even prior to definitive determination of seizure localization or refractoriness, so no qualifiers regarding these aspects are included. However, the use of the word “seizures” (plural) should be kept in mind, to avoid incorrect application of these items to single provoked seizures that may occur in this setting. Patients with a single seizure and historical feature(s) may still be considered for neural antibody testing, but often have other items on the checklist that raise suspicion for neural antibody positivity (e.g., other nervous system dysfunction, neuroimaging abnormalities). Thorough review to exclude more likely alternative diagnoses is particularly important in these medically complex patients.

Abbreviations: FLAIR, fluid‐attenuated inversion recovery; GlyR, glycine receptor; MOG, myelin oligodendrocyte glycoprotein; MTS, mesial temporal sclerosis; ONES, “Obvious” indications for Neural antibody testing in Epilepsy or Seizures (ONES).