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Purpose: The objective of this study is to characterize the electro-clinical phenotype of individuals affected by the rare PPP3CA gene-related developmental and epileptic encephalopathy (DEE)., Methods: We provide a detailed electro-clinical description of four previously unreported subjects, with unremarkable structural brain MRI and a normal screening for inborn errors of metabolism, who carry pathogenic variants within the regulatory domain of the PPP3CA gene, which encodes for calcineurin. We also conducted a literature review via PubMed and SCOPUS (up to December 2023) to collect all the studies reporting clinical details of subjects with PPP3CA pathogenic variants within the regulatory domain., Results: Our in-depth investigation reveals two distinct electro-clinical phenotypes with unique interictal and ictal patterns. Pathogenic variants within the calmodulin-binding domain result in childhood-onset epilepsy with focal and generalized seizures, developmental and intellectual impairments. Pathogenic variants within the regulatory domain lead to early onset drug-resistant severe epilepsy and potentially fatal outcomes. Comparative analysis with existing literature corroborates the notion that truncating mutations, prevalent in the regulatory domain but also possible in the calmodulin-binding domain, consistently associate with more profound disabilities and drug-resistant epilepsy., Conclusion: Our study emphasizes the critical role of pathogenic variants' type and location on the severity of PPP3CA-related DEE. We also speculate, based on peculiar EEG patterns, on potential pathophysiological mechanisms involving calcineurin dysfunction and calcium homeostasis. In order to improve our understanding of this rare DEE, we need both collaborative efforts to gather larger cohorts and further experimental studies., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Epileptic negative myoclonus (ENM), a transient muscular atonic phenomenon time-locked to epileptiform EEG abnormalities, is often observed in children with benign childhood epilepsy with centro-temporal spikes (BECTS). In some, for unknown reasons, ENM can be worsened by carbamazepine (CBZ). We describe two children aged 11 and 15 years, in whom CBZ precipitated seizure worsening and ENM. We investigated the morphological and topographic features of the EEG abnormalities while on CBZ and after CBZ withdrawal and compared them with those from 9 children with classical BECTS. The aim of the study was to identify possible electrophysiological specificities in patients who eventually develop ENM during CBZ treatment., Methods: The characterization of EEG abnormalities, related (R) and unrelated to ENM (U), in patients with ENM and rolandic discharges (RD) and in matched controls with BECTS was performed based on polygraphic digital EEG recordings. Off-line time-domain analysis included correlation coefficient between EEG and EMG channels, quantitative analysis on ENM, and topographic analysis on spike-and-wave complexes. Z-score test and paired t test were used when appropriate for statistical analysis on R, U and RD., Results: Recordings in both children with BECTS and ENM while on CBZ showed frequent R discharges (mean interval between R=19.89+/-9.4 s in patient 1; 2.16+/-1.2 s in patient 2). Withdrawal of CBZ produced abatement of R (no R recorded in patient 1; 5.69+/-7.1 s in patient 2) and reduction of the slow wave component of R (P<0.01). Morphology and topography of R and RD differed in field distribution, amplitude (P<0.01) and duration (P<0.01) of the slow wave component. RD and U did not show a significantly different morphology and field distribution., Conclusions: Our findings suggest that an increased cortical inhibition could be the electrophysiological correlate of CBZ-induced ENM. If confirmed on a larger series, the presence of spike-wave (rather than sharp waves) discharges in children with BECTS might be used as an electrophysiological predictor of an abnormal response to CBZ.

Purpose: To study the neurophysiologic characteristics of epileptic myoclonus in patients with Lennox-Gastaut syndrome (LGS) and myoclonic astatic epilepsy (MAE)., Methods: Three patients with symptomatic LGS (mean age, 15 years +/- 4) and three with cryptogenic MAE (mean age, 9 years +/- 3) were studied. Temporal relationships between electroencephalographic (EEG) and electromyographic activity were studied by analyzing latencies of EEG activity related to the onset of single myoclonic jerks, by using burst-locked EEG averaging where necessary., Results: LGS: neurophysiologic analysis indicated that jerks and the accompanying premyoclonic spikes showed latency differences between sides (mean +/- SD, 18 +/- 5 ms for both) with a constant leading side in each patient. The premyoclonic spike latency was 20 +/- 10 ms (mean +/- SD). Topographic voltage mapping of the premyoclonic spike peak showed a unilateral frontal distribution. MAE: muscles from both sides were activated synchronously, and the EEG correlate was a generalized spike-wave, in which the negative peak of the spike preceded the generalized jerks by 30 +/- 2 ms (mean +/- SD). Topographic voltage mapping of the premyoclonic spike peak showed a diffuse distribution of the electrical field, predominating over the anterior regions, but not lateralized., Conclusions: These neurophysiologic findings indicate that epileptic myoclonus in LGS originates from a stable generator in the frontal cortex, to spread to contralateral and ipsilateral cortical areas, whereas myoclonus in MAE appears to be a primary generalized epileptic phenomenon.

Benign rolandic epilepsy (BRE) and childhood epilepsy with occipital paroxysms (CEOP) are overlapping in age range of presentation. Some children have been reported to manifest occipital and rolandic seizures, as distinct events. However, the presence during the same seizure of rolandic and occipital symptoms is exceptional. We present a 7-year-old boy with BRE in whom we video-EEG recorded two seizures at 4 years of age. The first episode was a classic rolandic seizure during sleep, while the second was prolonged with initial rolandic and late occipital involvement. It is possible that a rolandic seizure, in a child within the age range of both BRE and early onset CEOP, could spread to selectively involve the occipital lobe, because there is susceptibility of cortical neurons of both areas to develop seizures at this age in idiopathic partial epilepsies.

Purpose: We describe 2 girls, aged 19 years, who experienced a rolandic seizure at ages 4 and 5, respectively, together with the interictal EEG features of benign rolandic epilepsy (BRE). In adolescence both patients developed photosensitive occipital seizures accompanied by spontaneous and photic-induced occipital EEG paroxysms., Methods: We have been following 33 patients with a history of BRE, between ages 12 and 28 years (mean 17 years). Twenty-one of these patients had experienced their last rolandic seizure before the age of 10 years and 9 of them had been without treatment since age 11 or earlier. In 2 of these 9 patients, other types of seizures recurred after remission of BRE. Clinical, EEG, and evoked potential findings on these 2 patients are presented., Results: After having experienced BRE, both patients suffered partial seizures from age 12, with elementary visual hallucinations, visual blurring, slow head turning, cephalic pain, epigastric discomfort, unresponsiveness, and vomiting. Seizure onset was related to watching TV or exposure to bright light. EEG showed interictal occipital spikes, and a photoparoxysmal response limited to the occipital lobes. Visual evoked potentials were greatly increased in amplitude. One patient had two visual attacks only and remained seizure free after 4 years of follow-up, while the other had seizures controlled by an association of valproate and carbamazepine., Conclusions: Clinical and neurophysiological characteristics suggest that these two patients may have presented different age-related expressions within the spectrum of a benign seizure susceptibility syndrome rather than sharply distinct epilepsy syndromes.

We collected visual event-related potentials (ERPs) from 6 normal subjects using an "oddball" paradigm. Subjects were required to count the occurrences of matching shapes presented in the left and right visual field. Shapes matched on 20% of trials. ERPs were recorded from 20 or 43 electrodes distributed over the scalp. A multiple spatio-temporal equivalent dipole (ED) model was used to fit the early sensory and P300 component. A latency window to analyze the P300 was determined using the global field power statistic. The spatial topography of the P300 over this window was characterized by a midline positivity that decreased in amplitude with spatial distance from the peak. After sensory components were fit, the source of P300 could be accounted for by 1 or 2 EDs, which were usually located near medial temporal areas. This result is at odds with evidence from depth recordings during the oddball paradigm, showing that multiple regions of the brain are active during this interval.

Objectives: To describe the electroclinical features of typical absences persisting in adult life.Methods: Twelve adult patients (aged 21 to 56 years) with idiopathic generalised epilepsy featuring typical absences as the prominent clinical feature were studied. All patients underwent a full clinical and neurophysiological investigation including ictal documentation of seizures.Results: Neurological examination and neuroradiological investigations were normal in all cases. Clinical findings included a median age at onset of absences of 14 (range 4-32) years, almost constant tonic-clonic seizures (in 83% of patients), frequent episodes of absence status (in 33% of patients), and associated cognitive or psychiatric disturbances. Interictal EEG findings showed normal background activity, generalised paroxysms of spike waves or polyspike waves, and inconstant focal spikes (in five patients); runs of polyspikes were seen during non-REM sleep. Ictal EEG findings showed generalised spike waves at 3 Hz, sometimes preceded by multiple spikes, or more complex EEG patterns with sequences of polyspikes intermingled with spike waves or polyspike waves, showing discharge fragmentation or variation of intradischarge frequency.Conclusion: The results of the present study show that absences persisting in adult life may show particular clinical and EEG patterns, distinct from those in childhood or adolescence. [ABSTRACT FROM AUTHOR]