Hoerth, Matthew T.

Background: Catamenial epilepsy refers to cyclic seizure exacerbation in relation to the menstrual cycle. Three distinct patterns have been described: C1-perimenstrual, C2-periovulatory, and C3-inadequate luteal. There is experimental and clinical evidence that gonadal steroid hormones affect neuronal excitability with estrogens being mainly proconvulsant and progesterone anticonvulsant. If reproductive steroids have a role in seizure occurrence, they may also have a role in treatment. Objective: The objective of this study was to critically assess current evidence regarding the efficacy of progesterone as adjunctive therapy in women with intractable catamenial epilepsy. Methods: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, medical librarian, and content experts in the fields of epilepsy and gynecology. Results: A randomized, placebo-controlled clinical trial was selected for critical appraisal. This trial compared the efficacy of adjunctive cyclic natural progesterone therapy versus placebo for seizures in women with intractable partial epilepsy, stratified by catamenial and noncatamenial status. There was no significant difference in proportions of responders between progesterone and placebo in the catamenial and noncatamenial strata. Prespecified secondary analysis showed that the level of perimenstrual seizure exacerbation is a significant predictor of the responder rate for progesterone therapy. Conclusions: Cyclic natural progesterone is not superior to placebo in reducing seizure frequency in women with intractable partial epilepsy. Posthoc findings suggest that progesterone may benefit a subset of women with perimenstrually exacerbated seizures.

Summary Objective To validate predictive models for neural antibody positivity and immunotherapy response in epilepsy. Methods We conducted a retrospective study of epilepsy cases at Mayo Clinic (Rochester‐ MN ; Scottsdale‐ AZ , and Jacksonville‐ FL ) in whom autoimmune encephalopathy/epilepsy/dementia autoantibody testing profiles were requested (06/30/2014‐06/30/2016). An Antibody Prevalence in Epilepsy ( APE ) score, based on clinical characteristics, was assigned to each patient. Among patients who received immunotherapy, a Response to Immunotherapy in Epilepsy ( RITE ) score was assigned. Favorable seizure outcome was defined as >50% reduction of seizure frequency at the first follow‐up . Results Serum and cerebrospinal fluid (CSF) from 1,736 patients were sent to the Mayo Clinic Neuroimmunology Laboratory for neural autoantibody evaluation. Three hundred eighty‐seven of these patients met the diagnostic criteria for epilepsy. Central nervous system (CNS)–specific antibodies were detected in 44 patients. Certain clinical features such as new‐onset epilepsy, autonomic dysfunction, viral prodrome, faciobrachial dystonic seizures/oral dyskinesia, inflammatory CSF profile, and mesial temporal magnetic resonance imaging (MRI) abnormalities had a significant association with positive antibody results. A significantly higher proportion of antibody‐positive patients had an APE score ≥4 (97.7% vs. 21.6%, p < 0.01). Sensitivity and specificity of an APE score ≥4 to predict presence of specific neural auto‐antibody were 97.7% and 77.9%, respectively. In the subset of patients who received immunotherapy (77), autonomic dysfunction, faciobrachial dystonic seizures/oral dyskinesia, early initiation of immunotherapy, and presence of antibodies targeting plasma membrane proteins (cell‐surface antigens) were associated with favorable seizure outcome. Sensitivity and specificity of a RITE score ≥7 to predict favorable seizure outcome were 87.5% and 83.8%, respectively. Significance APE and RITE scores can aid diagnosis, treatment, and prognostication of autoimmune epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here .