Summary
Objective
Pathogenic SLC6A1 variants were recently described in patients with myoclonic atonic epilepsy (MAE) and intellectual disability (ID). We set out to define the phenotypic spectrum in ...a larger cohort of SCL6A1‐mutated patients.
Methods
We collected 24 SLC6A1 probands and 6 affected family members. Four previously published cases were included for further electroclinical description. In total, we reviewed the electroclinical data of 34 subjects.
Results
Cognitive development was impaired in 33/34 (97%) subjects; 28/34 had mild to moderate ID, with language impairment being the most common feature. Epilepsy was diagnosed in 31/34 cases with mean onset at 3.7 years. Cognitive assessment before epilepsy onset was available in 24/31 subjects and was normal in 25% (6/24), and consistent with mild ID in 46% (11/24) or moderate ID in 17% (4/24). Two patients had speech delay only, and 1 had severe ID. After epilepsy onset, cognition deteriorated in 46% (11/24) of cases. The most common seizure types were absence, myoclonic, and atonic seizures. Sixteen cases fulfilled the diagnostic criteria for MAE. Seven further patients had different forms of generalized epilepsy and 2 had focal epilepsy. Twenty of 31 patients became seizure‐free, with valproic acid being the most effective drug. There was no clear‐cut correlation between seizure control and cognitive outcome. Electroencephalography (EEG) findings were available in 27/31 patients showing irregular bursts of diffuse 2.5‐3.5 Hz spikes/polyspikes‐and‐slow waves in 25/31. Two patients developed an EEG pattern resembling electrical status epilepticus during sleep. Ataxia was observed in 7/34 cases. We describe 7 truncating and 18 missense variants, including 4 recurrent variants (Gly232Val, Ala288Val, Val342Met, and Gly362Arg).
Significance
Most patients carrying pathogenic SLC6A1 variants have an MAE phenotype with language delay and mild/moderate ID before epilepsy onset. However, ID alone or associated with focal epilepsy can also be observed.
Summary
Objective
Until now, it has been unclear if the three subsyndromes of adolescent‐onset generalized genetic epilepsy (GGE) differ in long‐term prognosis. Therefore, this study aimed to compare ...long‐term seizure outcome in juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and epilepsy with generalized tonic–clonic seizures alone (EGTCS).
Methods
This retrospective study is based on the archive of an institutional tertiary care outpatient clinic for adult patients with epilepsy. Charts of 870 epilepsy outpatients were reviewed among whom 176 had adolescent‐onset GGE (53 JAE, 66 JME, 57 EGTCS). Median patient age at investigation was 60 years; median follow‐up time was 42.5 years. If possible, GGE patients were additionally interviewed on psychosocial and clinical variables.
Results
Age at first seizure was significantly higher in EGTCS patients (median 18 years) than in patients with JAE or JME (14 years each; p ≤ 0.001). Long‐term seizure outcome hardly differed between the three subsyndromes. At the end of follow‐up, 60% of all patients were in 5‐year terminal seizure remission, and in 14%, epilepsy even had resolved (>10 years without seizures, >5 years without pharmacotherapy). Twenty percent of patients had persistent seizures during the last year of follow‐up. Across all patients, 23% reported a psychiatric comorbidity, 87% had married, and 57% had achieved university entrance qualification.
Significance
Long‐term outcome was shown to be highly similar across all subsyndromes of adolescent‐onset GGE. Even in a selection of difficult‐to‐treat epilepsy patients still attending an adult epilepsy clinic, most become seizure‐free. To confirm these findings, prospective studies are needed.
Objective
Epilepsies are a group of neurological disorders sharing certain core features, but also demonstrate remarkable pathogenic and symptomatic heterogeneities. Various subtypes of epilepsy have ...been identified with abnormal shift in the brain default mode network (DMN). This study aims to evaluate the fine details of shared and distinct alterations in the DMN among epileptic subtypes.
Methods
We collected resting‐state functional magnetic resonance imaging (MRI) data from a large epilepsy sample (n = 371) at a single center, including temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), and genetic generalized epilepsy with generalized tonic‐clonic seizures (GGE‐GTCS), as well as healthy controls (HC, n = 150). We analyzed temporal dynamics profiling of the DMN, including edge‐wise and node‐wise temporal variabilities, and recurrent dynamic states of functional connectivity, to identify abnormalities common to epilepsies as well as those specific to each subtype.
Results
The analyses revealed that hypervariable edges within the specific DMN subsystem were shared by all subtypes (all PNBS < .005), and deficits in node‐wise temporal variability were prominent in TLE (all t(243) ≤ 2.51, PFDR < .05) and FLE (all t(302) ≤ –2.65, PFDR < .05) but relatively weak in GGE‐GTCS. Moreover, dynamic states were generally less stable in patients than controls (all P’s < .001).
Significance
Collectively, these findings demonstrated general DMN abnormalities common to different epilepsies as well as distinct dysfunctions to subtypes, and provided insights into understanding the relationship of pathophysiological mechanisms and brain connectivity.
Summary
Objective
Evaluate the seizure‐reduction response and safety of brain‐responsive stimulation in adults with medically intractable partial‐onset seizures of neocortical origin.
Methods
...Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain‐responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2–6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset.
Results
There were 126 patients with seizures of neocortical onset. The average follow‐up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward LOCF analysis). Twenty‐six percent of patients experienced at least one seizure‐free period of 6 months or longer and 14% experienced at least one seizure‐free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation GEE). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices.
Significance
Brain‐responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.
Functional neuroimaging with PET and SPECT is a commonly used tool in presurgical evaluation. The following article reviews the literature of PET and SPECT in presurgical assessment of epilepsies ...published in the last year.
FDG-PET adds concomitant information in temporal and extratemporal lobe epilepsy in adults and children. The pattern of hypometabolism in FDG-PET is a good additional predictor or seizure outcome in TLE with mesial temporal sclerosis or negative MRI. There is growing evidence that diagnostic value of FDG-PET increases with postprocessing. Although several methods were applied in the reviewed literature, all of them seem to outperform the visual analysis. Imaging of the epileptic focus with ictal SPECT is depending on short injection latencies. It is particularly useful in patients with nonlesional MRI and mostly of extratemporal localization. Areas of hyperperfusion remote of SOZ are reflecting the epileptic network. Combining more concordant investigations including PET and SPECT in MRI-negative evaluation adds to better presurgical stratification and therefore, better postsurgical outcome. FET-PET shows increased uptake in status epilepticus.
PET and SPECT are important investigations to localize the epileptic focus in temporal lobe and nonlesional extratemporal epilepsies. Postprocessing for both modalities is important to increase diagnostic value.
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).
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