Electroclinical Manifestations Research Articles

Frontoparietal 18F-FDG-PET hypo-metabolism in Lennox-Gastaut syndrome: Further evidence highlighting the key network

IntroductionLennox Gastaut syndrome (LGS) can be conceptualised as a “secondary network epilepsy”, in which the shared electroclinical manifestations reflect epileptic recruitment of a common brain network, despite a range of underlying aetiologies. We aimed to identify the key networks recruited by the epileptic process of LGS using interictal 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography (18F-FDG-PET). MethodsGroup analysis of cerebral 18F-FDG-PET, comparing 21 patients with LGS (mean age = 15 years) and 18 pseudo-controls (mean age = 19 years), studied at Austin Health Melbourne, between 2004 and 2015. To minimise the influence of individual patient lesions in the LGS group, we only studied brain hemispheres without structural MRI abnormalities. The pseudo-control group consisted of age- and sex-matched patients with unilateral temporal lobe epilepsy, using only the hemispheres contralateral to the side of epilepsy. Voxel-wise permutation testing compared 18F-FDG-PET uptake between groups. Associations were explored between areas of altered metabolism and clinical variables (age of seizure onset, proportion of life with epilepsy, and verbal/nonverbal ability). Penetrance maps were calculated to explore spatial consistency of altered metabolic patterns across individual patients with LGS. ResultsAlthough not always readily apparent on visual inspection of individual patient scans, group analysis revealed hypometabolism in a network of regions including prefrontal and premotor cortex, anterior and posterior cingulate, inferior parietal lobule, and precuneus (p < 0.05, corrected for family-wise error). These brain regions tended to show a greater reduction in metabolism in non-verbal compared to verbal LGS patients, although this difference was not statistically significant. No areas of hypermetabolism were detected on group analysis, although ∼25 % of individual patients showed increased metabolism (relative to pseudo-controls) in the brainstem, putamen, thalamus, cerebellum, and pericentral cortex. DiscussionInterictal hypometabolism in frontoparietal cortex in LGS is compatible with our previous EEG-fMRI and SPECT studies showing that interictal bursts of generalised paroxysmal fast activity and tonic seizures recruit similar cortical regions. This study provides further evidence that these regions are central to the electroclinical expression of LGS.

Acute to Chronic Electro-Clinical Manifestations of Neuro-COVID and the Long-Haul Consequences in People With Epilepsy: A Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection can involve the central nervous system (CNS). Acute symptomatic seizures or epileptiform discharges have not been commonly reported in patients with altered mental status related to coronavirus disease 2019 (COVID-19) infection. However, long-term neurological symptoms have been reported after COVID-19 infection (i.e., brain fog, cognitive complaints, and confusion), suggesting chronic encephalopathy. People with epilepsy (PWE) have been specifically affected by the COVID-19 pandemic, with changes in their seizure frequency, quality of life, health care accessibility, and medication interactions. This narrative review highlights possible pathophysiological mechanisms of COVID-19 on the brain, related to short- and long-term epileptiform activity and the impact of this infection on PWE.

The Optimal Target and Connectivity for Deep Brain Stimulation in Lennox-Gastaut Syndrome.

ObjectiveDeep brain stimulation (DBS) can reduce seizures in Lennox–Gastaut syndrome (LGS). However, little is known about the optimal target and whether efficacy depends on connectivity of the stimulation site. Using outcome data from the ESTEL trial, we aimed to determine the optimal target and connectivity for DBS in LGS.MethodsA total of 20 patients underwent bilateral DBS of the thalamic centromedian nucleus (CM). Outcome was percentage seizure reduction from baseline after 3 months of DBS, defined using three measures (monthly seizure diaries, 24‐hour scalp electroencephalography [EEG], and a novel diary‐EEG composite). Probabilistic stimulation mapping identified thalamic locations associated with higher/lower efficacy. Two substitute diffusion MRI datasets (a normative dataset from healthy subjects and a “disease‐matched” dataset from a separate group of LGS patients) were used to calculate structural connectivity between DBS sites and a map of areas known to express epileptic activity in LGS, derived from our previous EEG‐fMRI research.ResultsResults were similar across the three outcome measures. Stimulation was most efficacious in the anterior and inferolateral “parvocellular” CM border, extending into the ventral lateral nucleus (posterior subdivision). There was a positive association between diary‐EEG composite seizure reduction and connectivity to areas of a priori EEG‐fMRI activation, including premotor and prefrontal cortex, putamen, and pontine brainstem. In contrast, outcomes were not associated with baseline clinical variables.InterpretationEfficacious CM‐DBS for LGS is linked to stimulation of the parvocellular CM and the adjacent ventral lateral nucleus, and is associated with connectivity to, and thus likely modulation of, the “secondary epileptic network” underlying the shared electroclinical manifestations of LGS. ANN NEUROL 2022;92:61–74

Neonatal seizures: diagnostic updates based on new definition and classification.

Neonatal seizures are the most common neurological symptoms caused by various etiologies in the neonatal period, but their diagnosis and treatment are challenging because their pathophysiology and electroclinical manifestations differ from those of patients in older age groups. Many seizures present as electrographic-only events without clinical signs or as obscure clinical manifestations that are difficult to distinguish from other neonatal behaviors. Accordingly, a new definition and classification of neonatal seizures was recently proposed by the International League Against Epilepsy Task Force on neonatal seizures, highlighting the role of electroencephalography in diagnosing and treating neonatal seizures. Neonatal seizures are defined as electrographic events with sudden, paroxysmal, and abnormal alteration of activity and divided into electroclinical seizures and electrographic-only seizures according to their clinical signs, thus excluding clinical events without an electrographic correlation. Seizure types are described by their predominant clinical features and divided into motor (automatisms, clonic, epileptic spasms, myoclonic, tonic, and sequential), nonmotor (autonomic and behavioral arrest), and unclassified. Although many neonatal seizures are acute reactive events caused by hypoxic-ischemic encephalopathy or vascular insults, structural, genetic, or metabolic etiologies of neonatal-onset epilepsy should also be thoroughly evaluated to determine their appropriate management.

Childhood absence epilepsy: Electro-clinical manifestations, treatment options, and outcome in a tertiary educational center.

Purpose and BackgroundTo evaluate the electro-clinical manifestations and outcomes of children with absence epilepsy at a tertiary center in Saudi Arabia.MethodsThis retrospective study reviewed the medical and EEG records of patients who were diagnosed to have CAE as per the International League Against Epilepsy (ILAE) definition for CAE. The study was conducted in the pediatric neurology clinic of King Khalid University Hospital, King Saud University Medical City, Riyadh, Saudi Arabia, between January 2000 and December 2019. Patients who did not meet (ILAE) criteria, lost follow-up, and those who did not receive treatment at KKUH were excluded. Data regarding the patient's disease, electro-clinical manifestations, anti-seizure medication response, and outcomes were collected.ResultsA total of 35 patients, with an average age at diagnosis of 7 ± 2.1 y, were included in the study; among them, 51.4% were female and approximately 48.6% presented with a family history of epilepsy. Regarding clinical features, all patients experienced staring and altered awareness, 94.2% had less than 20 spells per day at the time of diagnosis, and 65.7% were provoked by the hyperventilation test. Regarding EEG findings, all patients had bilateral, symmetrical, and synchronous discharges in the form of regular 3 Hz spike-and-wave complexes, and 94.3% had a generalized initial ictal discharge. Also, 22.8% had eye fluttering with electrographic seizures. Ethosuximide (ESM) was used as the drug of choice in 45.7% of the patients. Regarding clinical outcomes, 94.3% had their disease clinically controlled, and 80% had a normalized EEG after few months of starting anti-seizure medication. Finally, 37.2% experienced complete remission of epilepsy after 3–5 y; however, one patient developed juvenile myoclonic epilepsy.ConclusionThis study described the electro-clinical manifestations of patients with childhood absence epilepsy and outcomes. Furthermore, early diagnosis and prompt treatment of childhood absence epilepsy improve treatment outcomes.

EEG features of spontaneous recurrent seizures in a mouse model of extended hippocampal kindling

Introduction . Epilepsy is a disease characterized by an enduring predisposition to generate epileptic seizures and by the neurobiological, cognitive, psychological, and social consequences of this condition. Temporal lobe epilepsy (TLE) is the most common and often drug-resistant type of epilepsies in the adult and aging populations and has greatly diverse in etiologies and electro-clinical manifestations. Kindling through repeated brief stimulation of limbic structures has long been used as a model of TLE. While classic kindling in a few weeks does not induce spontaneous recurrent seizures (SRS), extended kindling is able to induce SRS in several animal species. The SRS induction by extended kindling is generally not associated with gross brain injury, but rather a loss of subgroups of GABAergic interneurons in the hippocampal hilar region. The lack of observed gross brain injury in extended kindled animals is different from post status epilepticus models in which SRS emergence is accompanied with pronounced brain damage. As such the extended kindling model may help explore epileptogenesis in the absence of major brain pathology as is seen in many patients with TLE. To data, there is limited insight about EEG characteristics of SRS in rodent models of extended kindling. We therefore attempted to provide more information in this area using a mouse model of extended hippocampal kindling (Song et al., 2018; Liu et al., 2019; Frontier Pharmacology). Methods . Male C57 black mice ages 11–13 months were operated to implant intracranial electrodes. Each mouse was implanted with two pairs of bipolar electrodes, one in the hippocampal CA3 for kindling stimulation and local recordings and another in contralateral/ipsilateral hippocampal CA3, dorsomedial thalamus, parietal cortex or entorhinal cortex. Hippocampal kindling (60 Hz for 2 sec) was applied twice daily, and SRS were detected by 24-hour EEG-video monitoring. Age-match mice that received similar electrode implantation and twice daily handling manipulation but not kindling were used as controls. Brain histological examinations were performed in a subset of mice to verify the location of implanted electrodes and to examine potential gross brain lesion. Results . (1) SRS were observed from 47 mice following 80–140 kindling stimulation; no spontaneous seizure was detected in 12 control mice. (2) SRS remained detectable in individual mice up to 4 months after termination of the kindling stimulation. SRS incidences varied in a range of 2–14 events per day but inter-SRS intervals were ≤2 hours for about 65% of SRS events. (3) Most of SRS were featured with EEG ictal discharges and concurrent motor seizures at the Racine scale 3–5. SRS that presented EEG ictal discharges without or with concurrent motor behaviors at the Racine scale 1–2 were also noticeable, particularly in mice with implanted electrode in the dorsomedial thalamus. (4) In ≥1500 SRS events examined, nearly all EEG ictal discharges presented low-voltage signals at onset and such ictal onset appeared to concur in the kindled CA3 and unkindled site despite the latter targeted to different brain structures. (5) CA3 and cortical EEG ictal discharges were not substantially affected by intra-peritoneal injection of lorazepam (a benzodiazepine positive GABAa receptor modulator) but concurrent severe motor seizures were greatly suppressed. Summary . We suggest that epileptogenic network activity encompassing multiple forebrain areas may be responsible for SRS initiation in the mouse model of extended hippocampal kindling. Subcortical structures involving the dorsomedial thalamic circuitry may play an important role in manifestation and/or control of severe motor seizures in this model. Support . EpLink – The Epilepsy Research Program of the Ontario Brain Institute and Natural Sciences and Engineering Research Council of Canada.

Intracerebral electrical stimulations of the temporal lobe: A stereoelectroencephalography study.

The functional anatomy of the anteromesial portion of the temporal lobe and its involvement in epilepsy can be explored by means of intracerebral electrical stimulations. Here, we aimed to expand the knowledge of its physiological and pathophysiological symptoms by conducting the first large-sample systematic analysis of 1529 electrical stimulations of this anatomical region. We retrospectively analysed all clinical manifestations induced by intracerebral electrical stimulations in 173 patients with drug-resistant focal epilepsy with at least one electrode implanted in this area. We found that high-frequency stimulations were more likely to evoke electroclinical manifestations (p < .0001) and also provoked 'false positive' seizures. Multimodal symptoms were associated with EEG electrical modification (after discharge) (p < .0001). Visual symptoms were not associated with after discharge (p = .0002) and were mainly evoked by stimulation of the hippocampus (p = .009) and of the parahippocampal gyrus (p = .0212). 'False positive seizures' can be evoked by stimulation of the hippocampus, parahippocampal gyrus and amygdala, likely due to their intrinsic low epileptogenic threshold. Visual symptoms evoked in the hippocampus and parahippocampal gyrus, without EEG changes, are physiological symptoms and suggest involvement of these areas in the visual ventral stream. Our findings provide meaningful guidance in the interpretation of intracranial EEG studies of the temporal lobe.

Spontaneous remission of West syndrome associated with acute infection and fever in five patients

ObjectiveWe analyzed the records of 198 patients with West syndrome (WS) seen at a single pediatric neurology center in Argentina between June 2004 and June 2017. Five patients with infection-related spontaneous remission of the electroclinical manifestations were identified. MethodsThe following parameters were investigated: personal and family history, clinical characteristics of the seizures - mainly spasms - and EEG findings, type of treatment, and outcome. The inclusion criteria for WS were epileptic spasms (ES) in clusters, hypsarrhythmia, and mental deterioration. Infants with ES without hypsarrhythmia and other epileptic encephalopathies with ES were excluded. ResultsFive children, four boys and one girl, met the inclusion criteria of WS with spontaneous remission after a viral infection. The etiology of ES was unknown in four patients and one had a structural etiology. All patients had spontaneous remission of the ES and normalization of the EEG following acute upper respiratory infection in four and exanthema subitum in one; all of them had fever between 38.5 and 40 °C. ConclusionWe report five patients with spontaneous remission of WS following acute viral infection, associated with a respiratory virus in four and exanthema subitum in one.

Impaired Spatial Learning and Memory in Middle-Aged Mice with Kindling-Induced Spontaneous Recurrent Seizures.

Temporal lobe epilepsy is the most common and often drug-resistant type of epilepsy in the adult and aging populations and has great diversity in etiology, electro-clinical manifestations, and comorbidities. Kindling through repeated brief stimulation of limbic structures is a commonly used model of temporal lobe epilepsy. Particularly, extended kindling can induce spontaneous recurrent seizures in several animal species. However, kindling studies in middle-aged, aging, or aged animals remain scarce, and currently, little is known about kindling-induced behavioral changes in middle-aged/aging animals. We therefore attempted to provide more information in this area using a mouse model of extended hippocampal kindling. We conducted experiments in middle-aged mice (C57BL/6, male, 12–14 months of age) to model new-onset epilepsy in adult/aging populations. Mice experienced twice daily hippocampal stimulations or handling manipulations for 60–70 days and then underwent continuous electroencephalogram (EEG)-video monitoring to detect spontaneous recurrent seizures. Extended kindled mice consistently exhibited spontaneous recurrent seizures with mean incidences of 6–7 events per day, and these seizures featured EEG discharges and corresponding convulsions. The handling control mice showed neither seizure nor aberrant EEG activity. The two groups of mice underwent the Morris water maze test of spatial learning and memory 1–2 weeks after termination of the kindling stimulation or handling manipulation. During visible platform trials, the kindled mice took a longer distance and required more time than the control mice to find the platform. During hidden platform trials, the kindled mice showed no improvement over 5-day trials in finding the platform whereas the control mice improved significantly. During probe tests in which the hidden platform was removed, the kindled mice spent less time than the controls searching in the correct platform location. There were no significant differences between the kindled and control mice with respect to swim speed or total locomotor activity in an open-field test. Together, these observations indicate that the extended kindled mice with spontaneous recurrent seizures are impaired in spatial learning and memory as assessed by the Morris water maze test. We postulate that the extended hippocampal kindling in middle-aged mice may help explore epileptogenic mechanisms and comorbidities potentially relevant to new-onset temporal lobe epilepsy in adult and aging patients. Limitations and confounds of our present experiments are discussed to improve future examinations of epileptic comorbidities in extended kindled mice.

MEF2C-related epilepsy: Delineating the phenotypic spectrum from a novel mutation and literature review

PurposeMEF2C-related epilepsy has been poorly described in the literature, despite a consistent MEF2C haploinsufficiency phenotype characterized by severe language impairment and motor delay (MIM# 613443). We aimed to delineate the spectrum of electroclinical manifestations of MEF2C-related epilepsy from an illustrative case and literature review. MethodsA retrospective chart review of our case was performed followed by a literature review on PubMed and OMIM. Publications including patients with MEF2C pathogenic, likely pathogenic variants, or microdeletions without involvement of other genes were selected. ResultsThe index case is a 2-year-old male with global developmental delay who presented at 7 months with atypical febrile seizures, generalized myoclonias, and focal impaired awareness seizures. Neuroimaging studies were unremarkable and electroencephalograms showed high voltage 200-400uV, 2–2.5 Hz generalized spike-and-waves and polyspikes with alternating frontal predominance, and multifocal spike-and-slow waves. Whole exome sequencing showed an unreported de novo likely pathogenic variant in the MEF2C gene c.236 G > C (p.Arg79Pro). Data from ten additional publications including 22 patients were gathered. From the 23 patients in total, 19 (82%) had seizures. Febrile seizures were most common, but myoclonic, focal-onset and generalized seizures were also reported. Electroencephalogram findings were described in eleven, and nine (82%) showed epileptiform abnormalities. ConclusionMEF2C-related epilepsy may be described as a spectrum of manifestations including febrile seizures, myoclonia, and focal-onset or generalized seizures. Electroencephalogram is consistently abnormal, showing findings such as background slowing, multifocal and generalized epileptiform discharges and polyspikes. It remains unclear whether most patients are responsive or refractory to treatment with anti-epileptic medications.

Early and long-term electroclinical features of patients with epilepsy and PCDH19 mutation.

Protocadherin 19 (PCDH19) mutations have been identified in epilepsy in females with mental retardation as well as patients with a "Dravet-like" phenotype. We aimed to elucidate the electroclinical phenotype associated with PCDH19 mutation, which is currently difficult to identify at onset leading to a delay in diagnosis. We retrospectively reviewed clinical and EEG data for 13 consecutive patients with PCDH19 mutations or deletions diagnosed at our centers from 2009 to 2011, and followed these patients into adolescence and adulthood. We identified a specific temporal sequence of electroclinical manifestations, identified as three main stages. During the first two years of life, previously healthy girls presented with clusters of afebrile focal seizures. Early seizures were recorded on video-EEG in 10/13 patients, and were focal (n=8) with temporo-occipital and frontal onset. Three patients with strictly stereotyped focal seizures underwent a pre-surgical work-up. Two patients started with generalized seizures, one presenting with early-onset atypical absences and the other generalized tonic-clonic seizures. During the course of the disease, from two to 10 years, seizures became fever-sensitive and continued to recur in clusters, although these were less frequent. Seizures were mainly described by eyewitnesses as generalized tonic-clonic, even though three of five seizures, recorded on EEG, showed a focal onset with fast bilateral spread. Atypical absences and fever-induced tonic-clonic seizures remained frequent in only one patient until the age of 16 years. No specific treatment or combination appeared to be more effective over another. Various degrees of cognitive or behavioural impairment were reported for all patients, but it was in the second decade that behavioural disturbances prevailed with hetero-aggressiveness and behaviour associated with frontal lobe abnormalities leading to psychosis in two. Early recognition of the above features should improve early diagnosis and long-term management of patients with epilepsy and PCDH19 mutations.

F21. Electroclinical manifestations in term newborns with neonatal hypoglycemia

Neonatal hypoglycemia is a relatively common event with a variable clinical presentation, ranging from asymptomatic forms to refractory status epilepticus. It may present as a primary problem or appear in the context of other conditions, such as prematurity or severe systemic disorders (sepsis, hypoxic ischemic encephalopathy, ...), making it difficult to separate its effects on the CNS from those due to the underlying disorder. Aim: To describe the EEG features in term-newborns with primary hypoglycemia admitted to our neonatal unit between 10/2016 and 10/2017. Retrospective review of clinical records of patients fulfilling the following: Inclusion criteria – Term newborns (Gestational age ⩾37 weeks). – Hypoglycemia (plasma glucose ⩽40 mg/dL or ⩽47 mg/dL if symptomatic: CNS dysfunction; dysautonomia). Exclusion criteria – Any antecedent disorder that may explain CNS dysfunction (Primary: e.g. genetic epileptic encephalopathy; Secondary: e.g. cardiorespiratory arrest). We identified 3 patients: 1. Female, presenting with irritability and tremor 48 h. after birth, with plasma glucose of 18 mg/dL, treated with oral glucose with good response. She presented recurrent asymptomatic hypoglycemia, with disproportionately high levels of insulin and C-peptide, and was treated with Cortisone and Diazoxide. Genetic tests confirmed congenital hyperinsulinism (ABCC8-mutation). MR and EEG were normal. At follow-up, 7 months old, she had a normal psychomotor development. 2. Male, presenting with hypoactivity, diaphoresis, and apnea 12 h. after birth, with plasma glucose of 15 mg/dL, metabolic acidosis and high lactate, improving rapidly on i.v. Glucose. His mother had insulin-treated gestational diabetes. He developed focal seizures evolving into status epilepticus, requiring treatment with PB, LEV, MDZ and Lidocaine to achieve control (48 h. after onset). MR showed extensive bilateral cortico-subcortical lesions, predominantly parieto-occipital. Initial EEG showed a discontinuous pattern and 8 focal temporal seizures. Control EEG showed persistent discontinuous pattern (silent periods up to 2 min) and absent cortical reactivity. He died aged 4 days. 3. Male, presenting with hypoactivity with plasma glucose of 16 mg/dL, rapidly improving with i.v. Glucose. He developed focal motor seizures evolving into status epilepticus, requiring PB, LEV and MDZ to achieve control (clinically after 24 h, but seizures persisted on CFM 12 h longer). MR showed bilateral cortico-subcortical lesions, predominantly parieto-occipital. Initial EEG showed normal background with left centro-temporal interictal epileptiform activity. Control EEG showed focal slowing over the same regions. He was discharged on LEV 23 days after onset, with axial hypertonia and brisk reflexes. Neonatal hypoglycemia may present with refractory seizures, which can aggravate CNS damage and impair outcome. EEG monitoring is necessary to identify subclinical seizures and correlates with prognosis.

T05. Pre-surgical assessment of drug-resistant insular and peri insular epilepsy: A single center experience

Epilepsy arising from the insula is widely regarded as a challenging type of seizure, probably owing to the deep-seated location of the insula and the extensive connections it makes with adjacent structures. In recent years, we have rapidly gained insights into insular epilepsy-related obstacles. Here, we describe a detailed analysis of the electro-clinical manifestations of this type of epilepsy using intra-cerebral recordings performed with Stereo-electroencephalography (SEEG). We retrospectively analyzed 12 patients from our epilepsy program who underwent insular exploration using SEEG between June 2013 and June 2017. Patient information reviewed included demographics, clinical history, neurological examination; neuroimaging studies (Brain MRI, PET, Ictal SPECT), Scalp video-EEG, intracranial recordings with SEEG, histopathological findings, and surgical outcomes. 12 patients (M:F = 4:8; mean age, 32.5 years; range, 19–60 years) were found with seizures originating from either the insula alone or simultaneously originating from the insula and adjacent structures. One patient had a family history of epilepsy and another one had previous exposure to viral meningoencephalitis. Six patients had undergone prior surgery for epilepsy treatment. The mean seizure frequency was 4 seizures per week, and one patient experienced seizures daily. The most common aura was somatosensory sensation, followed by cephalic sensation in 4 and 3 patients, respectively. The commonest type of seizure was focal with impaired awareness in 10 patients. 50% of the patients showed a tendency for secondary generalizations, and 25% showed nocturnal predominance. Lesions were observed on brain MRI in 8 cases. Scalp EEG revealed different interictal discharge distributions: 5 patients showed localized frontotemporal spikes, 3 showed bilateral temporal spikes, and no spikes were detected in 4. The location of ictal onset could be localized in only 50% of patients. The most common scalp EEG ictal pattern was rhythmic delta activity (1–3 Hz). Subsequent SEEG showed six patients found to have a combination of clinical and subclinical seizures. SEEG clinical seizure onset from the insula alone was found in 50% of the patients (3 right, 2 left, 1 bilateral). The other patients presented with simultaneous onset from the insula and adjacent structures: 4 from mesial temporal structures, 1 temporal operculum, and 1 frontal operculum. The commonest SEEG ictal pattern was low voltage fast activity in 8 patients. Surgical resections guided by SEEG findings were performed in 5 patients and led to excellent outcomes; all these cases had Engle class 1 outcome at 6–24 months follow up. We observed that it is not uncommon for seizures to simultaneously originate from the insula and adjacent structures. However, non-invasive EEG monitoring tools are likely insufficient to detect such simultaneous seizures. For the given sample, SEEG proved beneficial in providing optimal surgical outcomes.

Chapter 21 - Parietal lobe epilepsy

There are few reports of patients with parietal lobe epilepsy. One of the largest series, from the Montreal Neurological Institute (MNI), reported that patients with epileptogenic areas in the parietal cortex behind the postcentral gyrus comprised 6% of patients with refractory focal epilepsy treated surgically at the MNI between 1929 and 1988. Since then several other institutions have reported their experience with the evaluation and treatment of patients with parietal lobe epilepsy. This chapter reviews the functional anatomy of the parietal lobe, electroclinical manifestations and surgical outcome of parietal lobe epilepsy, and recent advances in the evaluation of patients with refractory focal epilepsy.

Neonatal hypoglycemia: A wide range of electroclinical manifestations and seizure outcomes.

We examined the various types of epilepsy in children with neonatal hypoglycemia in order to define electroclinical and prognostic features of these patients. We retrospectively reviewed the medical records of patients with a history of symptomatic neonatal hypoglycaemia who have been followed at Gazi University Hospital Pediatric Neurology Department between 2006 and 2015. Patients with perinatal asphyxia were excluded. Details of each patient's perinatal history, neurological outcome, epilepsy details, seizure outcome and EEG and brain MRI findings were reviewed. Fourty five patients (range 6mo-15y) with a history of symptomatic neonatal hypoglycaemia were included the study. Epilepsy developed in 36 patients and 23 of them had intractable epilepsy. All patients had occipital brain injury. We observed that most of the patients, either manifesting focal or generalized seizures, further develop intractable epilepsy. This finding establishes neonatal hypoglycemia as a possible cause to be considered in any case of intractable epilepsy.

Anti-NMDA-R encephalitis: Should we consider extreme delta brush as electrical status epilepticus?

Seizures are common clinical manifestations in anti-N-methyl-d-aspartate receptor (anti-NMDA-R) encephalitis, among other neurological and psychiatric symptoms. During the course of the disease, some specific EEG patterns have been described: generalized rhythmic delta activity (GRDA) and extreme delta brush (EDB). In comatose patients, the association of these EEG abnormalities with subtle motor manifestations can suggest ongoing non-convulsive status epilepticus (NCSE). We report the case of a 28-year-old woman admitted for a clinical presentation typical of anti-NMDA-R encephalitis, which was confirmed by CSF analysis. She was rapidly intubated because of severe dysautonomia and disturbed consciousness. Clinical examination revealed subtle paroxysmal and intermittent myoclonic and tonic movements, correlated on video-EEG with GRDA and/or EDB. NCSE was then suspected, but electroclinical manifestations persisted despite many anti-epileptic drugs combinations, or reappeared when barbiturate anesthesia was decreased. In order to confirm or dismiss the diagnosis, intracranial pressure (ICP) and surface video-EEG monitoring were performed simultaneously and revealed no ICP increase, thus being strongly against a diagnosis of seizures. Sedation was progressively weaned, and clinical condition as well as EEG appearance progressively improved. Literature review revealed 11 similar cases, including 2 with focal NCSE. Of the nine other cases, NCSE diagnosis was finally excluded in 5 cases. NCSE diagnosis in association with anti-NMDA-R encephalitis is sometimes very difficult and its occurrence might be overestimated. Video-EEG is highly recommended and more invasive techniques may sometimes be necessary.

The early electroclinical manifestations of infantile spasms: A video EEG study.

Purpose:Infantile spasms are described as flexor extensor and mixed; but more features of their semiology and ictal electroencephalography (EEG) changes are sparse in the literature. The purpose of the study was to describe the clinical and ictal video-EEG characteristics of consecutive cases with infantile spasms and to try to find an association with the etiology.Materials and Methods:The clinical phenomenology and EEG characteristics on video-EEG were analyzed in 16 babies with infantile spasms.Results:A total of 869 spasms were reviewed. Nine (56.3%) showed focal seizures at least once during the recording and 1 (6.3%) had multifocal myoclonus in addition to the spasms. The duration of the cluster and interval between spasms was totally variable in all patients. Lateralizing phenomena were present in at least some of the spasms in all patients. Unilateral manual automatism in the form of holding the pinna was noted in three patients following the spasm. The ictal EEG activity in the majority (75%) was the slow wave. Four (25%) showed fast generalized spindle-like ictal discharges. Spikes, spike and wave activity, or electrodecremental pattern alone during the ictus was seen in none. On bivariate analysis, no factor noted on the video EEG had association with the etiology.Conclusion:Infantile spasms could be associated with focal and other seizures, has unique, non-uniform and variable semiology from patient to patient. The ictal EEG manifestation in the majority (75%) of our patients was the slow wave transient with 25% showing generalized fast spindle-like activity.

A subset of genomic alterations detected in rolandic epilepsies contains candidate or known epilepsy genes including GRIN2A and PRRT2

Rolandic epilepsies (REs) represent the most frequent epilepsy in childhood. Patients may experience cognitive, speech, language, reading, and behavioral issues. The genetic origin of REs has long been debated. The participation of rare copy number variations (CNVs) in the pathophysiology of various human epilepsies has been increasingly recognized. However, no systematic search for microdeletions or microduplications has been reported in RE so far. Array comparative genomic hybridization (aCGH) and quantitative polymerase chain reaction (qPCR) were used to analyze the genomic status of a series of 47 unrelated RE patients who displayed various types of electroclinical manifestations. Thirty rare CNVs were detected in 21 RE patients. Two CNVs were de novo, 12 were inherited, and 16 were of unknown inheritance. Each CNV was unique to one given patient, except for a 16p11.2 duplication found in two patients. The CNVs of highest interest comprised or disrupted strong candidate or confirmed genes for epileptic and other neurodevelopmental disorders, including BRWD3, GRIN2A, KCNC3, PRKCE, PRRT2, SHANK1, and TSPAN7. Patients with REs showed rare microdeletions and microduplications with high frequency and heterogeneity. Whereas only a subset of all genomic alterations found here may actually participate in the phenotype, the novel de novo events as well as several inherited CNVs contain or disrupt genes, some of which are likely to influence the emergence, the presentation, or the comorbidity of RE. The future screening of cohorts of larger size will help in detecting more de novo or recurrent events and in appreciating the possible enrichment of specific CNVs in patients with RE.

Nonlesional atypical mesial temporal epilepsy

Misleading manifestations of common epilepsy syndromes might account for some epilepsy surgery failures, thus we sought to characterize patients with difficult to diagnose (atypical) mesial temporal lobe epilepsy (mTLE). We retrospectively reviewed our surgical database over 12 years to identify patients who underwent a standard anterior temporal lobectomy after undergoing intracranial EEG (ICEEG) evaluation with a combination of depth and subdural electrodes. We carefully studied electroclinical manifestations, neuroimaging data, neuropsychological findings, and indications for ICEEG. Of 835 patients who underwent anterior temporal lobectomy, 55 were investigated with ICEEG. Ten of these had atypical mTLE features and were not considered to have mTLE preoperatively. All of them had Engel class I outcome for 3 to 7 years (median 3.85). Five reported uncommon auras, and 3 had no auras. Scalp-EEG and nuclear imaging studies failed to provide adequate localization. None had MRI evidence of hippocampal sclerosis. However, ICEEG demonstrated exclusive mesial temporal seizure onset in all patients. Clues suggesting the possibility of mTLE were typical auras when present, anterior temporal epileptiform discharges or ictal patterns, small hippocampi, asymmetrical or ipsilateral temporal hypometabolism on PET, anterior temporal hyperperfusion on ictal SPECT, and asymmetry of memory scores. Histopathology revealed hippocampal sclerosis in 6 patients and gliosis in 2. Atypical electroclinical presentation may be deceptive in some patients with mTLE. We emphasize the importance of searching for typical mTLE features to guide ICEEG study of mesial temporal structures in such patients, who may otherwise mistakenly undergo extramesial temporal resections or be denied surgery.

Surgical treatment of hypermotor seizures originating from the temporal lobe

PurposeTo describe the characteristics of electroclinical manifestations in patients with hypermotor seizures (HMSs) originating from the temporal lobe. MethodsWe retrospectively reviewed the data of patients who underwent surgical treatments for seizure to identify patients with HMSs of temporal origin. We systematically reviewed patient seizure histories, imaging reports, video-EEG monitoring data, operative records and pathological findings. ResultsEight of the 9 patients reported auras. The ictal behavior included marked agitation in 5 patients and mild agitation in 4 patients. All of the 9 patients exhibited stiffness or dystonia of the upper limb or contralateral limbs during ictus. Seven of the 9 patients completed intracranial recording and at least 3 seizures were recorded for each patient. The intracranial recordings showed ictal activity originating from mesial temporal lobe in 6 patients and the lateral temporal lobe in 1 patient. The time interval of ictal propagation from the temporal to frontal lobe was 15.0±8.3s. While the time interval from EEG origination to the beginning of hypermotor behavior was 21.0±8.1s. Brain MRIs revealed hippocampal sclerosis in 3, neoplastic lesion in 1, and normal images in the remaining 5 patients. Patients were followed for 1–5 years after the anterior temporal lobectomy; 7 patients remained seizure-free throughout follow-up. ConclusionSome HMSs can originate from the temporal lobe. In carefully selected patients, surgical resection may lead to good outcomes.