High rates of early remission pattern in adult-onset compared with earlier-onset idiopathic generalized epilepsy: A long-term follow-up study.

OBJECTIVE: To investigate electroclinical characteristics and prognostic patterns of adult-onset vs. younger-onset idiopathic generalized epilepsy (IGE) patients during long-term follow-up. METHODS: In this single-center retrospective cohort comparative study, adult-onset IGE was defined as onset after 20 years of age. Patients with a follow-up duration between 10 and 30 years from epilepsy diagnosis were enrolled. Maximum follow-up duration was limited to 30 years to ensure a better comparison of prognostic data between adult-onset and younger-onset patients. The Benjamini-Hochberg false discovery rate (FDR) method was applied to obtain FDR-adjusted p-values. RESULTS: A total of 177 IGE patients were recruited and 27 adult-onset IGE patients were identified (15.3%). Follow-up duration was similar between younger- and adult-onset IGE patients and 74% of subjects performed at least one 24-hour EEG recording. Of adult-onset IGE patients, 8/27 were diagnosed with juvenile myoclonic epilepsy, while 19/27 were diagnosed with generalized tonic-clonic seizures (GTCS) only. EEG photosensitivity and absence seizures were significantly less frequent among adult-onset IGE patients as compared with younger subjects. When considering prognostic patterns, an early remission pattern was significantly higher among adult-onset IGE patients as compared with younger-onset IGE patients (55.6% vs. 24%, adjusted p value = 0.007). Antiseizure medication withdrawal was attempted in 3/27 adult-onset patients, and all had GTCS relapses. CONCLUSION: Our study contributes to better defining the electroclinical characteristics and long-term follow-up of adult-onset IGE patients. A favorable long-term seizure outcome was found in adult-onset IGE patients, as evidenced by the high rates of early remission pattern when compared with younger onset patients.

Persistent treatment resistance in genetic generalized epilepsy: A long-term outcome study in a tertiary epilepsy center.

OBJECTIVE: To assess prognostic patterns and investigate clinical and electroencephalography (EEG) variables associated with persistent treatment resistance in a population of genetic generalized epilepsy (GGE) patients with a long-term follow-up. METHODS: Data from GGE patients followed from 1975 to 2019 were reviewed retrospectively. Subjects with a follow-up >10 years, starting from epilepsy diagnosis, were included. Persistent treatment resistance was defined as the absence of any period of remission ≥1 year despite treatment with two appropriate and adequate antiepileptic drugs (AEDs). RESULTS: One hundred ninety-nine patients were included. The median age was 39.5 years (interquartile range [IQR] 30-49) and the median follow-up was 27 years (IQR 18-35). The most common syndrome was juvenile myoclonic epilepsy (JME), diagnosed in 44.2% of patients. During follow-up, 163 subjects (81.9%) experienced 3-year remission from any seizure type, whereas 5- and 10-year remission occurred in 141 (70.8%) and 92 (46.2%) cases, respectively. The most common prognostic pattern was a relapsing-remitting course, observed in 80 patients (40.2%), whereas 29 (14.6%) displayed persistent treatment resistance. According to multivariable logistic regression analysis, febrile seizures (FS), specific EEG patterns (namely generalized paroxysmal fast activity, GPFA) and valproate (VPA) resistance were the only variables significantly associated with persistent treatment resistance. JME was the only epilepsy syndrome statistically associated with persistent treatment resistance in univariable logistic regression analysis. SIGNIFICANCE: Persistent treatment resistance was observed in almost 15% of GGE patients followed in a tertiary epilepsy center. A worse outcome was associated with specific clinical variables (JME, FS) and EEG patterns (GPFA).

Seizures in autoimmune encephalitis: Findings from an EEG pooled analysis.

PURPOSE: Seizures are common in autoimmune encephalitis (AE), and an extensive work-up is required to exclude alternative etiologies. The aim of our study was to identify possible clinical/EEG peculiarities suggesting the immune-mediated origin of late-onset seizures. METHODS: Thirty patients diagnosed with AE (19 men, median age 68 years, 18 seronegative) were included. Overall 212 video-electroencephalographic (EEG) and 31 24-h ambulatory EEG (AEEG) recordings were retrospectively reviewed. Posterior dominant rhythm, interictal epileptiform discharges (IEDs), clinical (CSs) and subclinical seizures (SCSs) were analyzed. RESULTS: Six-hundred-nineteen ictal events were recorded in 19/30 subjects, mostly (568/619) during AE acute stage. Among ten patients with CSs other than faciobrachial dystonic seizures, 7 showed prominent autonomic and emotional manifestations. SCSs were detected in 11 subjects, mainly via AEEG (260/287 SCSs vs 150/332 CSs, p < 0.001). Eight patients presented seizures during hyperventilation. IEDs, documented in 21 cases, were bilateral in 14 and focal temporal in 13. Multiple ictal EEG patterns were detected in 9/19 patients, 6 of whom had both CSs and SCSs, bilateral asynchronous seizures and ictal activities arising from temporal and extra-temporal regions. No correlation was found between the lateralization of MRI alterations and that of EEG findings. CONCLUSION: Our study confirms that adult-onset, high frequency focal seizures with prominent autonomic and emotional manifestations should be investigated for AE. Multiple ictal EEG patterns could represent a 'red flag', reflecting a widespread neuronal excitability related to the underlying immune-mediated process. Finally, our work enhances the crucial role of long-lasting EEG monitoring in revealing subclinical and relapsing seizures.

Valproate impact and sex-dependent seizure remission in patients with idiopathic generalized epilepsy.

BACKGROUND: Idiopathic Generalized Epilepsy (IGE) management has become increasingly challenging due to the restricted use of Valproate (VPA) in females. The aim of the study was to assess possible differences in terms of seizure outcome between men and women suffering from IGE. METHODS: A cohort of IGE patients (age range: 13-50 years) followed from 1980 to 2018 were included. Their medical history was retrospectively reviewed to investigate possible factors influencing seizure outcome. Seizure Remission (SR) was defined as the absence of any seizure type over 18 months prior to the last medical observation. The primary outcome was to evaluate sex differences in terms of SR at last observation. A multivariable logistic regression model was elaborated using SR as dependent variable. RESULTS: Three-hundred and sixty patients were included, 204 (56.7%) of whom were women. The median age at the end of follow-up was 30. At last medical observation, fewer women were receiving VPA compared with men (females 39.7% vs males 79.5%, p < .001). Overall SR was 70.6%. SR was significantly different according to sex (females 62.3% vs males 81.4%, p < .001). Multivariable logistic regression model showed that female sex (Odds Ratios [OR] = 0.52, 95% Confidence Interval [CI] = 0.29-0.94; p = .03), VPA treatment at last observation (OR = 0.44, 95% CI = 0.25-0.76; p = .003) and epilepsy syndrome (p < .001) were the factors independently associated with SR. CONCLUSIONS: Recent modifications in VPA prescribing patterns may have determined a worse seizure control among IGE female patients. Comparative clinical trials assessing the best therapeutic options for women with childbearing potential are urgently needed.

Doing without valproate in women of childbearing potential with idiopathic generalized epilepsy: Implications on seizure outcome.

OBJECTIVE: Valproate (VPA) use in women with idiopathic generalized epilepsy (IGE) who are of reproductive age has been a matter of concern and debate, which eventually led to the recent restrictions by regulatory agencies. The aim of our study was to investigate the relationship between VPA avoidance/switch and seizure outcome in women of childbearing potential. METHODS: We retrospectively reviewed data from female patients with IGE, 13-50 years of age, followed since 1980. We evaluated the prescription habits, and the rate of VPA switch for other antiepileptic drugs (AEDs) and its prognostic implications. Seizure remission (SR) was defined as the absence of any seizure type more than 18 months before the last medical observation. The main aim of the study was to assess (a) possible changes in seizure outcome related to VPA switch for other AEDs, especially in patients planning a pregnancy; and (b) possible differences in SR based on the presence/absence of VPA at last observation. RESULTS: One hundred ninety-eight patients were included in the study. Overall SR at last medical observation was 62.7%. SR significantly differed between subjects taking and those not taking VPA (P < .001) at last visit. Multiple regression models showed that taking VPA at last medical observation was strongly associated with SR in both the general population (P < .001) and the juvenile myoclonic epilepsy (JME) group (P < .001). Thirty-six (70.6%) of 51 patients who switched from VPA during follow-up experienced a clinical worsening. Switching back to VPA was more frequently associated with SR at last observation (P < .001). In those patients who substituted VPA in view of a pregnancy, SR and drug burden (monotherapy vs polytherapy) differed significantly before and after the switch. SIGNIFICANCE: Our study suggests that VPA avoidance/switch might be associated with unsatisfactory seizure control in women with IGE who are of childbearing potential. Our findings further highlight the complexity of the therapeutic management of female patients of reproductive age.