Objective: Ictal central apnea (ICA) is a frequent correlate of focal seizures, particularly in temporal lobe epilepsy (TLE), and regarded as a potential electroclinical biomarker of sudden unexpected death in epilepsy (SUDEP). Aims of this study are to investigate morphometric changes of subcortical structures in ICA patients and to find neuroimaging biomarkers of ICA in patients with focal epilepsy.Methods: We prospectively recruited focal epilepsy patients with recorded seizures during a video‐EEG long‐term monitoring with cardiorespiratory polygraphic recordings from April 2020 to September 2022. Participants were accordingly subdivided into two groups: patients with focal seizures with ICA (ICA) and without (noICA). A pool of 30 controls matched by age and sex was collected. All the participants underwent MRI scans with volumetric high‐resolution T1‐weighted images. Post‐processing analyses included a whole‐brain VBM analysis and segmentation algorithms performed with FreeSurfer.Results: Forty‐six patients were recruited (aged 15–60 years): 16 ICA and 30 noICA. The whole‐brain VBM analysis showed an increased gray matter volume of the amygdala ipsilateral to the epileptogenic zone (EZ) in the ICA group compared to the noICA patients. Amygdala sub‐segmentation analysis revealed an increased volume of the whole amygdala, ipsilateral to the EZ compared to controls [F(1, 76) = 5.383, pFDR = 0.042] and to noICA patients ([F(1, 76) = 5.383, pFDR = 0.038], specifically of the basolateral complex (respectively F(1, 76) = 6.160, pFDR = 0.037; F(1, 76) = 5.121, pFDR = 0.034).Interpretation: Our findings, while confirming the key role of the amygdala in participating in ictal respiratory modifications, suggest that structural modifications of the amygdala and its subnuclei may be valuable morphological biomarkers of ICA.

Objective: To evaluate in a real clinical scenario the impact of the ILAE‐recommended “Harmonized neuroimaging of epilepsy structural sequences”‐ HARNESS protocol in patients affected by focal epilepsy.Methods: We prospectively enrolled focal epilepsy patients who underwent a structural brain MRI between 2020 and 2021 at Modena University Hospital. For all patients, MRIs were: (a) acquired according to the HARNESS‐MRI protocol (H‐MRI); (b) reviewed by the same neuroradiology team. MRI outcomes measures were: the number of positive (diagnostic) and negative MRI; the type of radiological diagnosis classified in: (1) Hippocampal Sclerosis; (2) Malformations of cortical development (MCD); (3) Vascular malformations; (4) Glial scars; (5) Low‐grade epilepsy‐associated tumors; (6) Dual pathology. For each patient we verified for previous MRI (without HARNESS protocol, noH‐MRI) and the presence of clinical information in the MRI request form. Then the measured outcomes were reviewed and compared as appropriate.Results: A total of 131 patients with H‐MRI were included in the study. 100 patients out from this cohort had at least one previous noH‐MRI scan. Of those, 92/100 were acquired at the same Hospital than H‐MRI and 71/92 on a 3T scanner. The HARNESS protocol revealed 81 (62%) positive and 50 (38%) negative MRI, and MCD was the most common diagnosis (60%). Among the entire pool of 100 noH‐MRI, 36 resulted positive with a significant difference (p < .001) compared to H‐MRI. Similar findings were observed when accounting for the expert radiologists (H‐MRI = 57 positive; noH‐MRI = 33, p < .001) and the scanner field strength (H‐MRI 43 = positive, noH‐MRI = 23, p < .001), while clinical information were more present in H‐MRI (p < .002).Significance: The adoption of a standardized and optimized MRI acquisition protocol together with adequate clinical information contribute to identify a higher number of potentially epileptogenic lesions (especially FCD) thus impacting concretely on the clinical management of patients with focal epilepsy.

Postconvulsive central apnea has emerged as a contributor to sudden unexplained death in epilepsy. The aim of this study was to evaluate the incidence and characteristics of postictal central apnea (PICA) in focal seizures. The secondary aim was to analyze morphometric features of the amygdala and other subcortical structures involved in autonomic control. We prospectively enrolled consecutive patients admitted to the Epilepsy Monitoring Unit at Modena Academic Hospital (Italy) from April 2020 to December 2023. Inclusion criteria were as follows: (1) age older than 13 years; (2) at least 1 focal-onset seizure recorded during long-term video-EEG monitoring (LTVEM) with cardiorespiratory polygraphy. For each seizure, the presence of ictal central apnea (ICA) and/or PICA and its features were evaluated. Amygdala, hippocampus, thalamus, brainstem, and cerebellum volumetry were compared in patients with ICA/PICA with respect to healthy controls and patients with focal seizures without peri-ictal breathing disorders. A total of 69 patients (mean age 35.7 years; 42% female) with 406 focal-onset seizures were analyzed. ICA was recorded in 71 seizures (17%) in 27 patients. PICA was recorded in 24 seizures in 12 patients (10 with temporal lobe epilepsy) corresponding to 5.9% of all recorded seizures. Notably, PICA was observed only in seizures showing ictal apnea (in 33.8%). In 11 seizures with PICA, a single apneic event starting in the ictal and extending to the postictal period was observed. In 13 seizures, multiple apneic events were present in the postictal period (range 2-8). Seizures with PICA showed a longer peri-ictal apnea time (mean 75 seconds vs 40 seconds; p = 0.007) and a longer time to restore a regular rhythmic breathing after seizure termination (mean 173 seconds vs 42 seconds; p < 0.001) than seizures with self-limiting ictal apnea. Amygdala volumes ipsilateral to the epileptogenic zone were larger in patients with ICA/PICA compared with controls and patients without seizure-related apnea. PICA occurs in approximately 6% of focal seizures and is associated with extended apnea time and an enlarged amygdala ipsilaterally to the epileptogenic zone. Our data support the existence of a continuum from ictal to PICA and highlight the importance of cardiorespiratory recordings in LTVEM.

ObjectivesDEPDC5-related epilepsy carries an increased risk of sudden unexpected death in epilepsy. We evaluated the occurrence and features of ictal central apnea (ICA) in patients with pathogenic sequence variant in DEPDC5.MethodsWe reviewed data of 108 ...

Objective: To characterize the duration of seizures and inter‐seizure intervals in focal status epilepticus (SE).Methods: We reviewed consecutive scalp EEG recordings from adult patients who were admitted for a first episode of focal status epilepticus. We identified electrographic seizure duration and inter‐seizure intervals in the first diagnostic pretreatment EEG. We also reviewed isolated focal self‐limiting seizures in epilepsy patients, as a comparison group for seizure duration.Results: We recorded 307 focal seizures in 100 consecutive focal SE episodes, with a median seizure duration of 107 s (IQR: 54–186), and 134 isolated focal self‐limiting seizures in 42 epilepsy patients, with a median duration of 59 s (IQR: 30–90; p < .001). The only clinical feature of SE that significantly increased seizure duration was acute symptomatic etiology. In SE, 15% and 7% of seizures lasted longer than 300 and 600 s, respectively (t1 of the actual definition for tonic–clonic and focal SE), while only 1% of self‐limiting seizures lasted longer than 300 s, and none lasted longer than 600 s. The analysis of inter‐seizure intervals in SE with multiple seizures showed that 50% of the inter‐seizure periods were shorter than 60 s, and 95% were shorter than 540 s (9 min). Patients who had an increase in seizure duration (last versus first) of at least 1.4 times showed an increased 30‐day mortality.Significance: Focal seizures within a SE episode showed a wide range of duration, partly overlapping with the duration of focal self‐limiting seizures but with a longer median duration. Inter‐seizure intervals within an episode of SE were shorter than 1 min in 50% of the seizures and never lasted more than 10 min. Finally, an increase in seizure duration could represent an “electrophysiological biomarker” of a more severe SE episode, which may require more aggressive and rapid treatment.