Yao Ding

Objective: Epilepsy manifesting as sleep‐related seizures (EpSRS) represents a common but heterogeneous group. This study aimed to identify distinct clinical subtypes of EpSRS and explore alterations in sleep–wake seizure rhythms over the disease course. Methods: EpSRS is defined by seizures occurring ≥80% during sleep. We conducted a cross‐sectional study of 550 patients with EpSRS. Patients were classified as current EpSRS if ≥80% of their seizures occurred during sleep over the past year, or as previous EpSRS if they had a prior history of EpSRS but no longer met this 80% threshold during the past year. A two‐step cluster analysis was applied to the current EpSRS cohort, and disease trajectories were evaluated across both cohorts. Results: Cluster analysis classified the current EpSRS cohort ( n = 447) into two distinct subtypes. The sleep tonic–clonic seizure (TCS) subtype ( n = 218) featured later onset (18.0 years), infrequent (n = 229) featured early onset (11.0 years), frequent (≥1 seizure/month, 52.0%) focal preserved/impaired consciousness seizures (FPCSs/FICSs, 96.9%), an association with etiology of malformations of cortical development (27.9%), and a high rate of DRE (62.9%). Furthermore, an evolution pattern was found in the previous EpSRS cohort ( n = 103), marked by a transition from the sleep TCS subtype into awake FPCS/FICS pattern (52.5% were diagnosed as temporal lobe epilepsy), with the DRE proportion surging from 5.2% to 39.0%. This phenotypic evolution could be predicted by later age at epilepsy onset, female sex, and a history of febrile seizures. Significance: This study establishes a practical framework for classifying EpSRS, which is useful for predicting prognosis and evaluating etiology. It should be noted that among patients with the sleep TCS subtype, a transition into an awake FPCS/FICS pattern is associated with an increased risk of DRE.

Background: Myoclonus has become one of the neurological manifestations associated with coronavirus disease 2019 (COVID-19); however, the origin and pathophysiological mechanism remained uncertain. Case presentation: A rare case of myoclonus-ataxia syndrome associated with COVID-19 was presented . A 52-year-old Asian woman exhibited generalized myoclonus, ataxia, nystagmus, and dysarthria two weeks after a fever episode, which deteriorated rapidly within a few days. Electromyography (EMG) revealed synchronized bursts in both hands concurrent with myoclonic jerks. The absence of somatosensory evoked potential and lack of correlation between electromyography (EEG) and EMG suggested a subcortical origin of the myoclonus. A post-infectious immune-mediated process was considered the most likely mechanism, given the latency from fever to myoclonus onset, and the absence of other possible etiologies. Treatment with intravenous methylprednisolone led to notable improvement and a good outcome at the two-month follow-up. Conclusion: Myoclonus arising from subcortical structures can be associated with COVID-19. Early aggressive immunotherapy is important for a favorable outcome. Review of similar cases along with our report suggests COVID-19-associated myoclonus-ataxia as a distinct syndrome warranting prompt diagnosis and treatment.

Objective: This study aims to evaluate the glymphatic system (GS) in different temporal lobe epilepsy (TLE) subtypes using diffusion tensor imaging analysis along the perivascular space (DTI‐ALPS) and to explore its correlation with clinical factors and memory performance. Methods: The study encompassed 112 TLE patients with hippocampal sclerosis (TLE‐HS), 73 TLE patients with no lesions on magnetic resonance imaging (TLE‐NL), and 55 healthy controls. The DTI‐ALPS index was calculated based on 3.0T diffusion tensor image sequences, and the memory performance was assessed using the Wechsler Memory Scale‐Revised. The DTI‐ALPS index was compared among the three groups, and its relationships with clinical characteristics and memory performance were explored. Results: TLE‐HS group showed a significantly lower DTI‐ALPS index compared with healthy controls in both hemispheres (ipsilateral: p < 0.001; contralateral: p = 0.002). By contrast, TLE‐NL group exhibited a reduced DTI‐ALPS index solely in the ipsilateral hemisphere ( p < 0.001). Within TLE‐NL cohort, those with a history of focal to bilateral tonic–clonic seizures showed reduced DTI‐ALPS indices in both hemispheres (ipsilateral: p = 0.037; contralateral: p = 0.004). In the TLE‐HS group, DTI‐ALPS index positively correlated with memory performance ( p s < 0.05). A multiple regression analysis indicated that the average DTI‐ALPS index was significantly associated with memory quotient ( β = 0.309, p < 0.001; R ² = 0.226), independent of the ipsilateral hippocampal volume. Significance: The patterns of reduced DTI‐ALPS index differed between TLE‐HS and TLE‐NL patients. The extent of GS impairment in TLE‐HS patients correlated with memory decline, suggesting its potential as a therapeutic target for memory enhancement. Plain Language Summary: This study employed the DTI‐ALPS index, a neuroimaging marker, to assess glymphatic system function in distinct subtypes of temporal lobe epilepsy (TLE). Glymphatic impairment was observed in both TLE with hippocampal sclerosis (TLE‐HS) and nonlesional TLE (TLE‐NL), exhibiting distinct patterns. Notably, this dysfunction was associated with memory deficits, suggesting that targeting glymphatic clearance may represent a novel therapeutic strategy for memory improvement in epilepsy.

Familial adult myoclonus epilepsy (FAME) is a genetic neurological disorder characterized by cortical myoclonus and epileptic seizures with clinical features that overlap with other movement disorders and epileptic syndromes, particularly essential tremor (ET), progressive myoclonic epilepsy (PME), and juvenile myoclonic epilepsy (JME). The key clinical manifestations include an autosomal dominant family history, tremorlike cortical myoclonus, generalized tonic–clonic seizures, photosensitivity, mild cognitive impairment, and other associated symptoms. Electrophysiological examinations are essential in demonstrating cortical hyperexcitability and confirming the cortical origin of myoclonus. Neuroimaging studies typically show mild cerebellar atrophy or nonspecific structural changes on magnetic resonance imaging. Notably, photosensitivity is confirmed by clinical, electrophysiological, and neuroimaging evidence, highlighting its significant yet underestimated role in the underlying etiology of FAME. Genetic analysis, particularly long‐read genome sequencing, is recognized as the gold standard for definitive diagnosis. We propose an integrated and clinically oriented diagnostic approach for FAME, including clinical assessment, electrophysiological tests, neuroimaging studies, and genetic analysis. The differential diagnosis of FAME, ET, PME, and JME is also thoroughly discussed. Antiseizure medications are the cornerstone of FAME treatment, with a combination of valproate or levetiracetam with benzodiazepines serving as the first‐line therapy. A detailed review and a well‐established diagnostic workflow for FAME can enhance the understanding of FAME; the identification of specific biomarkers for FAME requires further investigation.

Objective: This study evaluated the association between temporal piriform cortex (tPC) resection and long‐term postoperative outcomes in temporal lobe epilepsy (TLE). Methods: We conducted a retrospective analysis of patients with TLE undergoing surgery between 2012 and 2022, with a minimum follow‐up of 2 years. The extent of resection, including the tPC, hippocampal head/body, and amygdala, was assessed using magnetic resonance imaging scans. These measurements, along with demographic data and other presurgical evaluations, were analyzed for their associations with Engel class postoperative outcomes and antiseizure medications (ASMs) withdrawal across different TLE subtypes. Results: Among 216 included patients, 158 had mesial TLE (MTLE). At the final follow‐up, 131 MTLE and 35 neocortical TLE (NTLE) patients were seizure‐free. Multivariable logistic regression revealed that unresected tPC significantly predicted seizure recurrence ( p < .001, odds ratio [OR] = 4.415, 95% confidence interval [CI] = 2.032–9.594), along with older age at surgery ( p = .018, OR = 1.034, 95% CI = 1.006–1.063) and nonspecific pathology ( p = .017, OR = 3.899, 95% CI = 1.278–11.894). In NTLE, tPC resection did not significantly affect outcomes. However, in MTLE, unresected tPC was strongly associated with poorer seizure outcomes at both 2‐year ( p = .012, OR = 3.362, 95% CI = 1.311–8.621) and 5‐year ( p = .014, OR = 5.750, 95% CI = 1.423–23.242) follow‐ups. Among seizure‐free MTLE patients, those with tPC resection had higher rates of ASMs reduction and withdrawal after 5 years ( p < .05). In hippocampal sclerosis (HS) patients, unresected tPC correlated with seizure recurrence ( p < .05), whereas no such association was observed in non‐HS cases. Significance: Our findings suggest that tPC involvement in the epileptogenic zone varies by TLE subtype, with tPC resection strongly linked to favorable outcomes in MTLE, particularly in HS patients. These results reinforce the understanding of the hippocampus–amygdala–piriform complex as crucial to the epileptogenic zone in MTLE.

Objective: Ketogenic diet therapy (KDT) is a safe and effective intervention for drug‐resistant epilepsy (DRE), yet its neural mechanisms remain unclear. This study aimed to explore how KDT‐induced changes in brain network dynamics relate to its therapeutic efficacy.Methods: Resting‐state functional magnetic resonance imaging was performed on 38 DRE patients at both pre‐ and post‐KDT stages, alongside 35 healthy controls. Using energy landscape analysis, we assessed individualized brain network dynamics, including brain states and transitions. Patients were categorized as responders or nonresponders based on seizure reduction rates following KDT. A subset of 14 follow‐up patients completed an auditory reaction time (ART) task to evaluate information processing speed. Exploratory analyses examined associations between brain dynamics and KDT outcomes.Results: Six consistent brain states were identified across healthy controls and patients, categorized into two major states and one intermediate state. KDT normalized abnormal brain dynamics in DRE by reducing the frequency and duration of major states and direct transitions between major states, and by increasing the frequency and duration of the intermediate state and indirect transitions between major states. Notably, the altered frequency of direct transitions was correlated with the rate of seizure reduction. Whereas ART was correlated with rigid dynamics at the pre‐KDT stage, post‐KDT improvements in ART showed an association with enhanced dynamic flexibility. The pre‐KDT frequency of direct transitions emerged as a potential biomarker for predicting KDT responsiveness.Significance: This study provides novel insights into the neural mechanisms underlying KDT in DRE, highlighting the significance of monitoring network dynamics and its normalization effects on the brain. The identified biomarker holds promise for facilitating personalized treatment strategies, thereby optimizing therapeutic outcomes for patients with DRE.

Objective: To investigate how etiology and seizure localization influence ictal scalp electroencephalographic (EEG) patterns in temporal lobe epilepsy (TLE).Methods: We retrospectively analyzed ictal EEG features from 504 focal seizures recorded in 189 TLE patients with various etiologies who underwent resective surgery.Results: For seizure onset patterns (SOPs), α/β onset was more common in the low‐grade tumor group (38.4%) than in the hippocampal sclerosis (HS) group (14.1%, p < 0.001). The ictal EEG duration was shorter in the tumor group compared to the focal cortical dysplasia (FCD), HS, and non‐specific groups (p < 0.05). Among mesial TLE patients, SOPs varied depending on the etiology. Within both the tumor and non‐specific groups, SOPs and the spreading time to the contralateral hemisphere differed between mesial and neocortical origins. Ictal pattern (87.7%) and ictal theta activity (83.9%) correctly lateralized the seizure in most cases.Significance: The ictal scalp pattern in TLE is influenced by both etiology and seizure localization. TLE associated with low‐grade tumors exhibits distinct ictal EEG characteristics. Furthermore, ictal pattern and ictal theta activity are equally effective in lateralizing seizures, regardless of etiology.Plain Language Summary: This research examined how brain activity during seizures in people with temporal lobe epilepsy can be different based on what caused the epilepsy and where in the brain the seizure starts. We found that seizures caused by brain tumors have unique patterns in the brain's electrical activity. Additionally, we discovered that specific patterns and types of brain waves can help determine which side of the brain the seizure is occurring on, regardless of its cause.

Objectives: This study aims to investigate whether alterations in white matter topological networks are associated with focal to bilateral tonic–clonic seizures (FBTCS) in temporal lobe epilepsy (TLE). Additionally, we investigated the variables contributing to memory impairment in TLE.Methods: This cross‐sectional study included 88 unilateral people with TLE (45 left/43 right), and 42 healthy controls. Graph theory analysis was employed to compare the FBTCS (+) group (n = 51) with the FBTCS (−) group (n = 37). The FBTCS (+) group was subcategorized into current‐FBTCS (n = 31) and remote‐FBTCS (n = 20), based on the history of FBTCS within 1 year or longer than 1 year before scanning, respectively. We evaluated the discriminatory power of topological network properties by receiver operating characteristic (ROC) analysis. Generalized linear models (GLMs) were employed to investigate variables associated with memory impairment in TLE.Results: Global efficiency (Eg) was significantly reduced in the FBTCS (+) group, especially in the current‐FBTCS subgroup. Greater disruption of regional properties in the ipsilateral occipital and temporal association cortices was observed in the FBTCS (+) group. ROC analysis revealed that Eg, normalized characteristic shortest path length, and nodal efficiency of the ipsilateral middle temporal gyrus could distinguish between FBTCS (+) and FBTCS (−) groups. Additionally, GLMs linked the occurrence of current FBTCS with poorer verbal memory outcomes in TLE.Interpretation: Our study suggests that abnormal networks could be the structural basis of seizure propagation in FBTCS. Strategies aimed at reducing the occurrence of FBTCS could potentially improve the memory outcomes in people with TLE.

Objectives: To investigate and characterize epileptic seizures and electrophysiological features of familial cortical myoclonic tremor with epilepsy (FCMTE) type 1 patients in a large Chinese cohort.Methods: We systematically evaluated 125 FCMTEtype 1 patients carrying the pentanucleotide (TTTCA) repeat expansion in the SAMD12 gene in China.Results: Among the 28 probands, epileptic seizures (96.4%, 27/28) were the most common reason for an initial clinic visit. Ninety‐seven (77.6%, 97/125) patients had experienced seizures. The seizures onset age was 36.5 ± 9.0 years, which was 6.9 years later than cortical tremors. The seizures were largely rare (<1/year, 58.8%) and occasional (1–6/year, 37.1%). Prolonged prodromes were reported in 57.7% (56/97). Thirty‐one patients (24.8%, 31/125) reported photosensitivity history, and 79.5% (31/39) had a photoparoxysmal response. Interictal epileptiform discharges (IEDs) were recorded in 69.1% (56/81) of patients. Thirty‐three patients showed generalized IEDs and 72.7% (24/33) were occipitally dominant, while 23 patients presented with focal IEDs with 65.2% (15/23) taking place over the occipital lobe. Overnight EEG of FCMTE patients displayed paradoxical sleep–wake fluctuation, with a higher average IED index of 0.82 ± 0.88/min during wakefulness and a lower IED index of 0.04 ± 0.06/min during non‐rapid eye movement sleep stages I–II.Interpretation: FCMTE type 1 has a benign course of epilepsy and distinct clinical and electrophysiological features. In addition to a positive family history and cortical myoclonus tremor, the seizure prodromes, specific seizure triggers, photosensitivity, distribution of IEDs, and unique fluctuations during sleep–wake cycle are cues for proper genetic testing and an early diagnosis of FCMTE.

Objectives: Analysis of FDG‐PET imaging commonly shows that hypometabolism extends into extra‐epileptogenic zones (extra‐EZ). This study investigates the distribution patterns of hypometabolism in frontal lobe epilepsy (FLE) originating in different frontal regions.Methods: Sixty‐four patients with FLE were grouped by EZ localization according to Brodmann areas (BAs): Group 1 (the frontal motor and premotor area), BAs 4, 6, and 8; Group 2 (the inferior frontal gyrus and opercular area), BAs 44, 45, and 47; Group 3 (the dorsal prefrontal area), BAs 9, 10, 11, and 46; and Group 4 (the medial frontal and anterior cingulate gyrus), BAs 32 and 24. Regions of extra‐EZ hypometabolism were statistically analyzed between FLE groups and healthy controls. Correlation analysis was performed to identify relationships between the intensity of hypometabolism and clinical characteristics.Results: Significant hypometabolism in the ipsilateral (Groups 1 and 4) or bilateral (Groups 2 and 3) anterior insulae was found. Groups 1 and 4 presented with limited distribution of extra‐EZ hypometabolism, whereas Groups 2 and 3 showed widely distributed extra‐EZ hypometabolism in the rectus gyrus, cingulate gyrus, and other regions. Additionally, the intensity of hypometabolism was correlated with epilepsy duration in Groups 2 and 3.Conclusions: All FLE groups showed hypometabolism in the anterior insula. In addition, distinct patterns of extra‐EZ hypometabolism were identified for each FLE group. This quantitative FDG‐PET analysis expanded our understanding of the topography of epileptic networks and can guide EZ localization in the future.