The role of EEG and neuroimaging in the diagnosis of non-convulsive status epilepticus in Subacute Encephalopathy with Seizures in Alcoholics (SESA syndrome): a case report and overview of the literature.

Epileptic seizures are frequently associated with liver dysfunction and alcoholism. Subacute encephalopathy with seizures in chronic alcoholics (SESA) is an underrecognized condition with peculiar clinical, EEG and neuroradiological features.We report the case of a 58-year-old man with previous alcohol use disorder (AUD) and acute-on chronic liver failure on alcohol-related cirrhosis, referred for urgent Orthotopic Liver Transplantation evaluation. The patient presented with delirium, aphasia and progressive deterioration of consciousness leading to intensive care unit admission. EEG showed slow activity with superimposed lateralized periodic discharges (LPDs) over the left temporo-occipital regions and ictal discharges with focal motor phenomena, consistent with focal status epilepticus. Antiseizure treatment with lacosamide and levetiracetam was administered with progressive improvement of consciousness.Brain MRI disclosed T2/FLAIR areas of hyperintensity in the left pulvinar and T2/FLAIR hyperintensity with corresponding DWI hyperintensity in the left hippocampal cortex, suggestive of post/peri-ictal excitotoxic changes with anatomical correspondence to focal LPDs distribution. SWI demonstrated decreased prominence of cortical veins in the left temporo-occipital region consistent with increased venous blood oxygenation in compensatory hyperperfusion.In conclusion, SESA should be suspected in the differential diagnosis of patients with AUD presenting with focal neurological deficits, seizures and focal EEG abnormalities. In this context, EEG and brain MRI represent useful tools with both diagnostic and prognostic value.

The role of the amygdala in ictal central apnea: insights from brain MRI morphometry.

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.

Tagging EEG features within exam reports to quickly generate databases for research purposes.

OBJECTIVE: assess the effectiveness of a new method for classifying EEG recording features through the use of tags within reports. We present feature prevalence in a sample of patients with toxic-metabolic encephalopathy and discuss the advantages of this approach over existing classification systems. METHODS: during EEG report creation, tags reflecting background activity, epileptiform features and periodic discharges were selected according to the findings of each recording. Reports including the tags have been collected and processed by the EEG report parser script written in PHP language. The resulting spreadsheet was analysed to calculate the prevalence and type of EEG features in a sample group of patients with toxic-metabolic encephalopathy. RESULTS: tag checking and extraction were very little time-consuming processes. Considering 5784 EEG recordings performed either in inpatients or outpatients over 2 years, toxic-metabolic aetiology was tagged in 218 (3.8 %). The most frequent background feature was severe slowing (5-6 Hz frequency), occurring in 79 (36.2 %). Epileptiform abnormalities were rare, reaching a maximum of 10 (4.6 %). Triphasic waves were tagged in 43 (19.7 %) recordings. CONCLUSIONS: tagging and parsing processes are very fast and integrated into the daily routine. Sample analysis in patients with toxic-metabolic encephalopathies showed EEG slowing as the prevalent feature, while triphasic waves occurred in a minority of recordings. Existing software such as "SCORE" (Holberg EEG) requires the replacement of the currently used software for EEG reporting, minimizing additional costs and training. EEG Report Parser is free and open-source software, so it can be freely adopted, modified and redistributed, allowing further improvement and adaptability.

Exploring the relationship between amygdala subnuclei volumes and cognitive performance in left-lateralized temporal lobe epilepsy with and without hippocampal sclerosis.

Cognitive disruption is a debilitating comorbidity in Temporal Lobe Epilepsy (TLE). Despite recent advances, the amygdala is often neglected in studies that explore cognition in TLE. Amygdala subnuclei are differently engaged in TLE with hippocampal sclerosis (TLE-HS) compared to non-lesional TLE (TLE-MRIneg), with predominant atrophy in the first and increased volume in the latter. Herein, we aim to explore the relationship between the volumes of the amygdala and its substructures with respect to cognitive performances in a population of left-lateralized TLE with and without HS. Twenty-nine TLEs were recruited (14 TLE-HS; 15 TLE-MRIneg). After investigating the differences in the subcortical amygdalae and hippocampal volumes compared to a matched healthy control population, we explored the associations between the subnuclei of the amygdala and the hippocampal subfields with the cognitive scores in TLE patients, according to their etiology. In TLE-HS, a reduced volume of the basolateral and cortical amygdala complexes joined with whole hippocampal atrophy, was related to poorer scores in verbal memory tasks, while in TLE-MRIneg, poorer performances in attention and processing speed tasks were associated with a generalized amygdala enlargement, particularly of the basolateral and central complexes. The present findings extend our knowledge of amygdala involvement in cognition and suggest structural amygdala abnormalities as useful disease biomarkers in TLE.

Impact of an optimized epilepsy surgery imaging protocol for focal epilepsy: A monocentric prospective study.

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.

Amygdala subnuclear volumes in temporal lobe epilepsy with hippocampal sclerosis and in non-lesional patients.

Together with hippocampus, the amygdala is important in the epileptogenic network of patients with temporal lobe epilepsy. Recently, an increase in amygdala volumes (i.e. amygdala enlargement) has been proposed as morphological biomarker of a subtype of temporal lobe epilepsy patients without MRI abnormalities, although other data suggest that this finding might be unspecific and not exclusive to temporal lobe epilepsy. In these studies, the amygdala is treated as a single entity, while instead it is composed of different nuclei, each with peculiar function and connection. By adopting a recently developed methodology of amygdala's subnuclei parcellation based of high-resolution T1-weighted image, this study aims to map specific amygdalar subnuclei participation in temporal lobe epilepsy due to hippocampal sclerosis (n = 24) and non-lesional temporal lobe epilepsy (n = 24) with respect to patients with focal extratemporal lobe epilepsies (n = 20) and healthy controls (n = 30). The volumes of amygdala subnuclei were compared between groups adopting multivariate analyses of covariance and correlated with clinical variables. Additionally, a logistic regression analysis on the nuclei resulting statistically different across groups was performed. Compared with other populations, temporal lobe epilepsy with hippocampal sclerosis showed a significant atrophy of the whole amygdala (p Bonferroni = 0.040), particularly the basolateral complex (p Bonferroni = 0.033), while the non-lesional temporal lobe epilepsy group demonstrated an isolated hypertrophy of the medial nucleus (p Bonferroni = 0.012). In both scenarios, the involved amygdala was ipsilateral to the epileptic focus. The medial nucleus demonstrated a volume increase even in extratemporal lobe epilepsies although contralateral to the seizure onset hemisphere (p Bonferroni = 0.037). Non-lesional patients with psychiatric comorbidities showed a larger ipsilateral lateral nucleus compared with those without psychiatric disorders. This exploratory study corroborates the involvement of the amygdala in temporal lobe epilepsy, particularly in mesial temporal lobe epilepsy and suggests a different amygdala subnuclei engagement depending on the aetiology and lateralization of epilepsy. Furthermore, the logistic regression analysis indicated that the basolateral complex and the medial nucleus of amygdala can be helpful to differentiate temporal lobe epilepsy with hippocampal sclerosis and with MRI negative, respectively, versus controls with a consequent potential clinical yield. Finally, the present results contribute to the literature about the amygdala enlargement in temporal lobe epilepsy, suggesting that the increased volume of amygdala can be regarded as epilepsy-related structural changes common across different syndromes whose meaning should be clarified.

Ictal apnea: A prospective monocentric study in patients with epilepsy.

BACKGROUND AND PURPOSE: Ictal respiratory disturbances have increasingly been reported, in both generalized and focal seizures, especially involving the temporal lobe. Recognition of ictal breathing impairment has gained importance for the risk of sudden unexpected death in epilepsy (SUDEP). The aim of this study was to evaluate the incidence of ictal apnea (IA) and related hypoxemia during seizures. METHODS: We collected and analyzed electroclinical data from consecutive patients undergoing long-term video-electroencephalographic (video-EEG) monitoring with cardiorespiratory polygraphy. Patients were recruited at the epilepsy monitoring unit of the Civil Hospital of Baggiovara, Modena Academic Hospital, from April 2020 to February 2022. RESULTS: A total of 552 seizures were recorded in 63 patients. IA was observed in 57 of 552 (10.3%) seizures in 16 of 63 (25.4%) patients. Thirteen (81.2%) patients had focal seizures, and 11 of 16 patients showing IA had a diagnosis of temporal lobe epilepsy; two had a diagnosis of frontal lobe epilepsy and three of epileptic encephalopathy. Apnea agnosia was reported in all seizure types. Hypoxemia was observed in 25 of 57 (43.9%) seizures with IA, and the severity of hypoxemia was related to apnea duration. Apnea duration was significantly associated with epilepsy of unknown etiology (magnetic resonance imaging negative) and with older age at epilepsy onset (p < 0.001). CONCLUSIONS: Ictal respiratory changes are a frequent clinical phenomenon, more likely to occur in focal epilepsies, although detected even in patients with epileptic encephalopathy. Our findings emphasize the need for respiratory polygraphy during long-term video-EEG monitoring for diagnostic and prognostic purposes, as well as in relation to the potential link of ictal apnea with the SUDEP risk.

Late-Onset Focal Epilepsy: Electroclinical Features and Prognostic Role of Leukoaraiosis.

The aim of this study was to describe the electroclinical and prognostic characteristics, and to investigate the role of leukoaraiosis in outpatients with new-onset elderly focal epilepsy aged ≥60 years, referred to a tertiary epilepsy center between 2005 and December 31, 2020. Among the 720 patients who were referred to the center, we retrospectively selected 162 consecutive outpatients, with a first referral for recent-onset focal epilepsy of unknown cause (UC) or structural cause (SC), and collected a clinical and standard-Electroencephalogram (S-EEG), 24-h ambulatory EEG (A-EEG), and neuroimaging data. We also analyzed the seizure prognosis after titration of the first antiseizure medication (ASM). One hundred and four UC and 58 SC patients, followed up for 5.8 ± 5.3 years (mean ± SD), were included. Compared with the SC group, the patients with UC showed a predominance of focal seizures with impaired awareness (51.9% of cases) and focal to bilateral tonic-clonic seizures during sleep (25%); conversely, the SC group, more frequently, had focal to bilateral tonic-clonic seizures during wakefulness (39.6%) and focal aware seizures (25.8%) (p < 0.0001). Oral or gestural automatisms were prevalent in UC epilepsy (20.2 vs. 6.9% in the SC group, p = 0.04). In UC compared to patients with SC, interictal epileptiform discharges showed a preferential temporal lobe localization (p = 0.0007), low expression on S-EEG, and marked activation during deep Non-Rapid Eye Movement (NREM) sleep (p = 0.003). An overall good treatment response was found in the whole sample, with a probability of seizure freedom of 68.9% for 1 year. The cumulative probability of seizure freedom was significantly higher in the UC compared with the SC group (p < 0.0001). The prognosis was worsened by leukoaraiosis (p = 0.012). In the late-onset focal epilepsy of unknown cause, electroclinical findings suggest a temporal lobe origin of the seizures. This group showed a better prognosis compared with the patients with structural epilepsy. Leukoaraiosis, per se, negatively impacted on seizure prognosis.

Case Report: Ictal Central Apnea as First and Overlooked Symptom in Temporal Lobe Seizures.

Ictal respiratory changes have been mainly described following generalized tonic-clonic seizures and recently considered to be a biomarker to assess the risk of sudden unexplained death in epilepsy (SUDEP). Nonetheless, modification of respiratory pattern can be related also to focal seizures, especially arising from the temporal lobe. Changes in cardiac function such as tachycardia or bradycardia could be often associated. We report a short case series of four patients with temporal lobe epilepsy admitted to our Epilepsy Monitoring Unit (EMU) presenting with an ictal central apnea as the first clinical manifestation of their seizures. None of these patients was aware of the occurrence of respiratory arrest. Age at onset ranged from 15 to 29 years. One patient had seizures with prolonged central apnea accompanied by a significant decrease in oxygen saturation. Neuroimaging in two patients showed alterations of mesial temporal lobe structures, including the amygdala. Recent neurophysiological studies supported the existence of a cortical network involving the limbic system that modulates downstream brainstem respiratory centers. Monitoring for respiratory changes and oxygen saturation in focal seizures is warranted for their potential value in identifying the epileptogenic zone and for a better understanding of ictal respiratory changes that could potentially define a subgroup of patients with high risk of seizure-related autonomic changes.