Electroencephalographic Abnormalities Research Articles

Effects of Antiepileptic Drugs on Language Abilities in Benign Epilepsy of Childhood with Centrotemporal Spikes.

Background and PurposeThis study is to assess the responsiveness of electroencephalography (EEG) abnormalities and their effects on language ability after initiating different types of antiepileptic therapy in children with newly diagnosed benign epilepsy of childhood with centrotemporal spikes (BECTS).MethodsThe records of patients newly diagnosed with BECTS (n=120; 69 males) were reviewed retrospectively. The patients were randomly treated with lamotrigine, oxcarbazepine, or topiramate monotherapy, and underwent at least two EEG and standardized language tests. Effects were compared using Pearson's chi-square tests and paired t-tests.ResultsThe recurrence rates for seizures in the lamotrigine, topiramate, and oxcarbazepine groups were 19.4%, 21.7%, and 11.4%, respectively, while complete or partial recovery (as indicated by EEG) occurred in 32%, 39%, and 16% of the patients. Patients in the lamotrigine group showed significant improvements in all parameters assessed by the Test of Language Problem Solving Abilities, except for ‘determining cause.’ Patients in the oxcarbazepine group also showed improvements, except for ‘making inferences’ (p<0.05). Most linguistic index scores were worse in the topiramate group except for Mean Length of Utterance in Words. Patients in the lamotrigine and oxcarbazepine groups showed significant improvements in the receptive language test (p<0.05). EEG improvements were not related to language ability.ConclusionsThe improvements in language and problem-solving performance in children with BECTS were greater for lamotrigine and oxcarbazepine than for topiramate. However, EEG remission did not imply that language function would be improved after the treatments.

7q11.23 microduplication syndrome: neurophysiological and neuroradiological insights into a rare chromosomal disorder.

The phenotypical consequence of the heterozygous chromosome 7q11.23 interstitial microdeletion is the Williams-Beuren syndrome, a very well-known genetic multi-systemic disorder. Much less is known about the reverse condition, the heterozygous interstitial microduplication of 7q11.23 region. The first molecular cytogenetic description was published in 2005, and only after several years were the reported patients numerous enough to attempt a description of a common phenotype. By using a broad multidisciplinary approach, we investigated 12 patients with this rare genetic anomaly. Ten of them harboured the duplication of the classical Williams-Beuren syndrome region and two a slightly larger duplication. Upon a detailed description of the clinical and psychological features, we used electroencephalography and magnetic resonance imaging to explore neurophysiological function and brain structures. We analysed the clinical, psychological, neuroradiological and neurophysiological features of 12 yet-unpublished individuals affected by this rare genetic anomaly, focusing specifically on the last two aspects. Several structural abnormalities of the central nervous system were detected, like ventriculomegaly, hypotrophic cerebellum, hypotrophic corpus callosum and hypoplastic temporal lobes. Although only one of 12 individuals suffered from seizures during childhood, three others had abnormal electroencephalography findings prominent in the anterior brain regions, without any visible seizures to date. Taken together, we enlarged the yet-underrepresented cohort in the literature of patients affected by 7q11.23 microduplication syndrome and shed further light on neuroradiological and neurophysiological aspects of this rare genetic syndrome.

Electroencephalographic abnormalities associated to valproate-induced hyperammonemia

Electroencephalographic abnormalities associated to valproate-induced hyperammonemia

Relevance of urinary S100B protein levels as a short-term prognostic biomarker in asphyxiated infants treated with hypothermia.

The initial diagnosis of neonatal hypoxic-ischemic encephalopathy is based on nervous system clinical manifestations. The use of biomarkers to monitor brain injury and evaluate neuroprotective effects allows early intervention and treatment. This study was designed to determine the short-term prognostic significance of urinary S100B calcium-binding protein (S100B) in asphyxiated newborns treated with hypothermia.An observational prospective study was conducted over a period of 5 years in 31 newborns with hypoxic-ischemic encephalopathy who received therapeutic hypothermia. The patients were divided into 2 groups: Group A (13 newborns with a normal neurological examination before discharge) and Group B (18 newborns who died during admission or had an abnormal neurologic examination before discharge). Urinary S100B was the main variable, serum S100B and neuron-specific enolase (NSE) were considered as secondary variables, and all of them were assessed on the first 3 days of life. The newborns were subsequently divided into groups with normal and abnormal electrophysiological and imaging findings.Mean urinary S100B levels were significantly higher in group B than group A on day 1 (10.58 ± 14.82 vs 4.65 ± 9.16 μg/L, P = .031) and day 2 (5.16 ± 7.63 vs 0.88 ± 2.53, P = .002). The optimal cutoff for urinary S100B on day 1 was >1.11 μg/L of (sensitivity, 100%; specificity 60%) for the prediction of neonatal death and < 0.66 μg/L (sensitivity 83% and specificity 70%) for the prediction of a normal neurological examination before discharge. It was not possible to calculate cutoffs with a similar accuracy for serum S100B or NSE. Urinary S100B on day 1 was higher in patients with abnormal magnetic resonance imaging findings (7.89 ± 8.09 vs 4.49 ± 9.14, P = .039) and abnormal positron emission tomography findings (8.60 ± 9.29 vs 4.30 ± 8.28, P = .038). There were no significant differences in S100B levels between patients with normal and abnormal electroencephalography results.Urinary S100B measured in the first days of life can predict neonatal death and short-term prognosis in asphyxiated newborns treated with hypothermia. The method is convenient, noninvasive, and has a higher sensitivity and specificity than measurement of serum S100B or NSE.

Review of Viral Encephalitis Cases Seen at a Tertiary Care Center in Turkey: Focus on Herpes Simplex Type 1.

The objective of this study was to determine the incidence of herpes simplex encephalitis (HSE), known as the most common, potentially mortal, and treatable cause of sporadic encephalitis, in a sample Turkish population. The demographic, clinical, laboratory, imaging, electrophysiology, and polymerase chain reaction (PCR) DNA results of patients examined with a pre-diagnosis of encephalitis were retrospectively examined. A total of 68 patients were included in the study. The most common presenting symptom was altered behavior (67.6%), while temporal T2 hyperintensity was determined in the magnetic resonance imaging (MRI) of 27.9% of the patients and electroencephalography (EEG) abnormalities were determined in 66.2% of the patients. Lymphocytic pleocytosis was determined in the cerebrospinal fluid (CSF) in 35 patients. Fifty-seven patients had been diagnosed with viral encephalitis, 3 with bacterial meningitis, 3 with tuberculous meningitis, 2 with sporadic Creutzfeld-Jakob disease, 2 with acute disseminating encephalomyelitis, and 1 with Brucella encephalitis. Seven (10.2%) cases of viral encephalitis were found to be positive for herpes simplex virus (HSV) DNA by PCR. Viral encephalitis is the most common cause of infectious encephalitis; however, other atypical causes should also be noted. Negative PCR results for HSV DNA should not exclude the need for antiviral therapy in patients with a strong pre-diagnosis of HSE because diagnostic modalities, including PCR, may fail in acute settings and HSE remains the sole treatable cause of infectious encephalitis.

Cerebrospinal Fluid Level of Glutamic Acid Decarboxylase (GAD) Antibody in Patients with Encephalitis

Background: Assaying the Glutamic Acid Decarboxylas( GAD) antibody in patients with encephalitis in cerebrospinal fluid and blood serum and its role in autoimmune encephalitis in children. Objective: This study Aimed at screening for GAD antibody in CSF of children presenting with acute encephalitis with non bacterial cause mostly autoimmune.Participants and methods: study is a pilot prospective study, conducted in the Pediatric department, Children’s Hospital, Ain Shams University.Fifty patients diagnosed with encephalitis exhibited at least one sign of parenchymatous brain dysfunction such as altered consciousness personality or behavior change, seizure, paresis, or ataxia. Encephalitis was defined as the presence of encephalopathy plus at least two of four findings: (1) fever (body temperature>38C); (2) abnormal cerebrospinal fluid examination (pleocytosis>5 white blood cells/mL and/or increased protein content>40 mg/dL) with negative cerebrospinal fluid culture; (3) abnormal electroencephalography findings compatible with encephalitis such as diffuse or focal slow activity, or periodic lateralized epileptiform discharges; and (4)abnormal results of neuroimaging, including computed tomography and magnetic resonance imaging (10), ,with age ranged from 6-144 Months; followed up In the period from September 2014 till March 2016.Basic clinical evaluation and laboratory investigations were done, GAD antibody level was measured in CSF and blood serum. Results: GAD receptor antibody titer was done in CSF which range from (36 -368 ng/l) with median of 64.83 (57.93-74.48), while in serum it range from (42.76-900) ng/l) with median 89.5(58.62-154.5).It was found that 6/50 (12%) patients had high GAD receptor antibody titer were high in CSF. The other 44/50 (88%) patients had low GAD antibody titer. In serum samples of twinty patients we had 8/20 (40%) patients had high GAD antibody titer and the rest were low GAD antibody titer 12/20 (60%).Significant occurrence of DCL, hospitalization plus mechanical ventilation and long term sequel were detected in patients with high GAD antibody titer. EEG findings; Two patients showed generalized epileptogenic activity, one patient had diffuse cortical dysfunction and two patient had multifocal epileptiform discharge and the rest of patients had normal finding. Eighty six precent had normal MRI findings,While 7 patients (14%) had non specific findings;3 patients had transient cortical meningeal enhancment,2 patients had high intensity in medial temporal lobe,one had abnormal signal intensity in medial temporal lobe and one patient had global brain atrophy. Conclusion: GAD Abs are directed against an intracellular antigen. The proposed pathogenic mechanisms of neurological disease in patients with antibodies directed against intracellular proteins is not clear. The present study emphasizes the importance of studying the CSF of patients with encephalitis suspected to be mediated by GAD autoimmunity.Both serum and CSF level must be assessed simultaneously as CSF level may change rapidly with fluctuation of disease. There are great efforts to be done to define the role of these GAD antibodies and to determine how they affect central nervous system function. These studies must be carried out so that appropriate treatments can be provided for the growing number of patients with possible antibody-mediated conditions.

Predictors of electroencephalography abnormalities in generalized epilepsy

Background: There is dearth of data on the pattern and utility of clinical variables that can independently determine EEG abnormalities in Generalized epilepsy (GE).

Electroencephalography in the Diagnosis of Genetic Generalized Epilepsy Syndromes.

Genetic generalized epilepsy (GGE) consists of several syndromes diagnosed and classified on the basis of clinical features and electroencephalographic (EEG) abnormalities. The main EEG feature of GGE is bilateral, synchronous, symmetric, and generalized spike-wave complex. Other classic EEG abnormalities are polyspikes, epileptiform K-complexes and sleep spindles, polyspike-wave discharges, occipital intermittent rhythmic delta activity, eye-closure sensitivity, fixation-off sensitivity, and photoparoxysmal response. However, admixed with typical changes, atypical epileptiform discharges are also commonly seen in GGE. There are circadian variations of generalized epileptiform discharges. Sleep, sleep deprivation, hyperventilation, intermittent photic stimulation, eye closure, and fixation-off are often used as activation techniques to increase the diagnostic yield of EEG recordings. Reflex seizure-related EEG abnormalities can be elicited by the use of triggers such as cognitive tasks and pattern stimulation during the EEG recording in selected patients. Distinct electrographic abnormalities to help classification can be identified among different electroclinical syndromes.

Inhibition of IL-1β Signaling Normalizes NMDA-Dependent Neurotransmission and Reduces Seizure Susceptibility in a Mouse Model of Creutzfeldt-Jakob Disease.

Creutzfeldt-Jakob disease (CJD) is a neurodegenerative disorder caused by prion protein (PrP) misfolding, clinically recognized by cognitive and motor deficits, electroencephalographic abnormalities, and seizures. Its neurophysiological bases are not known. To assess the potential involvement of NMDA receptor (NMDAR) dysfunction, we analyzed NMDA-dependent synaptic plasticity in hippocampal slices from Tg(CJD) mice, which model a genetic form of CJD. Because PrP depletion may result in functional upregulation of NMDARs, we also analyzed PrP knock-out (KO) mice. Long-term potentiation (LTP) at the Schaffer collateral-commissural synapses in the CA1 area of ∼100-d-old Tg(CJD) mice was comparable to that of wild-type (WT) controls, but there was an inversion of metaplasticity, with increased GluN2B phosphorylation, which is indicative of enhanced NMDAR activation. Similar but less marked changes were seen in PrP KO mice. At ∼300 d of age, the magnitude of LTP increased in Tg(CJD) mice but decreased in PrP KO mice, indicating divergent changes in hippocampal synaptic responsiveness. Tg(CJD) but not PrP KO mice were intrinsically more susceptible than WT controls to focal hippocampal seizures induced by kainic acid. IL-1β-positive astrocytes increased in the Tg(CJD) hippocampus, and blocking IL-1 receptor signaling restored normal synaptic responses and reduced seizure susceptibility. These results indicate that alterations in NMDA-dependent glutamatergic transmission in Tg(CJD) mice do not depend solely on PrP functional loss. Moreover, astrocytic IL-1β plays a role in the enhanced synaptic responsiveness and seizure susceptibility, suggesting that targeting IL-1β signaling may offer a novel symptomatic treatment for CJD.SIGNIFICANCE STATEMENT Dementia and myoclonic jerks develop in individuals with Creutzfeldt-Jakob disease (CJD), an incurable brain disorder caused by alterations in prion protein structure. These individuals are prone to seizures and have high brain levels of the inflammatory cytokine IL-1β. Here we show that blocking IL-1β receptors with anakinra, the human recombinant form of the endogenous IL-1 receptor antagonist used to treat rheumatoid arthritis, normalizes hippocampal neurotransmission and reduces seizure susceptibility in a CJD mouse model. These results link neuroinflammation to defective neurotransmission and the enhanced susceptibility to seizures in CJD and raise the possibility that targeting IL-1β with clinically available drugs may be beneficial for symptomatic treatment of the disease.

Seizures, electroencephalographic abnormalities, and outcome of ischemic stroke patients.

SummaryObjectiveSeizures and electroencephalographic (EEG) abnormalities have been associated with unfavorable stroke functional outcome. However, this association may depend on clinical and imaging stroke severity. We set out to analyze whether epileptic seizures and early EEG abnormalities are predictors of stroke outcome after adjustment for age and clinical/imaging infarct severity.MethodsA prospective study was made on consecutive and previously independent acute stroke patients with a National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 on admission and an acute anterior circulation ischemic lesion on brain imaging. All patients underwent standardized clinical and diagnostic assessment during admission and after discharge, and were followed for 12 months. Video‐EEG (<60 min) was performed in the first 72 h. The Alberta Stroke Program Early CT Score quantified middle cerebral artery infarct size. The outcomes in this study were an unfavorable functional outcome (modified Rankin Scale [mRS] ≥ 3) and death (mRS = 6) at discharge and 12 months after stroke.ResultsUnfavorable outcome at discharge was independently associated with NIHSS score (p = 0.001), EEG background activity slowing (p < 0.001), and asymmetry (p < 0.001). Unfavorable outcome 1 year after stroke was independently associated with age (p = 0.001), NIHSS score (p < 0.001), remote symptomatic seizures (p = 0.046), EEG background activity slowing (p < 0.001), and asymmetry (p < 0.001). Death in the first year after stroke was independently associated with age (p = 0.028), NIHSS score (p = 0.001), acute symptomatic seizures (p = 0.015), and EEG suppression (p = 0.019).SignificanceAcute symptomatic seizures were independent predictors of vital outcome and remote symptomatic seizures of functional outcome in the first year after stroke. Therefore, their recognition and prevention strategies may be clinically relevant. Early EEG abnormalities were independent predictors and comparable to age and early clinical/imaging infarct severity in stroke functional outcome discrimination, reflecting the concept that EEG is a sensitive and robust method in the functional assessment of the brain.

Electroencephalographic abnormalities and imaging profile of neurocysticercosis: analysis of 60 cases in children

Background: To study the electroencephalographic abnormalities and imaging profile of 60 children suffering from neurocysticercosis at a tertiary care centre over a period of two years.Methods: A diagnosis of Neurocysticercosis was made mainly on the basis of clinical features, imaging studies and serological tests. Patients were evaluated for different types of abnormalities on electroencephalogram (EEG) of their brains. This study group was subsequently evaluated for nature, type and site of lesion on computed tomographic scan and Magnetic Resonance Imaging of brain.Results: 28 (57.14%) cases had abnormal EEG finding in which nonspecific background changes was the commonest abnormalities. Solitary lesion (71.66%) were most common type of lesion. Parietal lobe was most common affected lobe followed by frontal lobe (18.6%). Transitional lesion (71.66%) in the form of ring enhancement following contrast administration was the prominent nature of lesion.Conclusions: Electroencephalographic abnormalities are not directly related to site and type of involvement. Parietal lobe was the most common affected lobe probably due to middle cerebral artery involvement.

Recent Drug Resistant Epilepsy Spectrum in Eastern India.

Background and PurposeThe Magnitude of Drug-resistant Epilepsy (DRE) in India, being unknown, takes a heavy toll on the patients and society in the form of prolonged dependence, unemployment, morbidity and mortality. We tried to explore the clinical, electro-physiological, neuro-imaging and drug-response spectrum of DRE patients in Eastern India in our study.MethodsDuring the period of January 2014 to December 2015, epilepsy patients were treated and DRE patients were identified according to International League Against Epilepsy criteria. We isolated those patients and studied them in a special clinic.ResultsAmong 2,153 patients treated in Neurology out-patient department, 243 (11.3%) patients were drug-resistant. Among the DRE patients, 63% were male. Age-wise 40%, 30.5% & 18.1% patients were presented in their first, second and third decades respectively. Males were more affected in 0–5 years age group while females in 6–10 years age group. Various seizures types were found alone or in combination. Males were mostly affected by generalized tonic clonic seizure and myoclonus and females by complex partial seizure. Positive family history was higher in partial seizure group. Electroencephalographic (EEG) abnormalities were common with structural lesions in brain. EEG findings in different etiologies were varied with a large number of DRE patients who were found to have normal EEG. Females were higher medicine non-compliant.ConclusionsThe spectrum was pointed towards gender predilection for specific age group and also for seizure types. Idiopathic cases were most common in DRE, pointing towards the need of newer investigations. Normal EEG could be found even in a DRE patient. Non-compliance was more in females.

Clinical profile and neurodevelopmental outcome of new-onset acute symptomatic seizures in children

PurposeTo study clinical profile, neurodevelopmental outcome and its predictors in children with acute symptomatic seizures (ASS). MethodsShort-term neurodevelopmental outcome and predictors of poor outcomes were prospectively assessed in 105 consecutive children with ASS aged 3 months-12 years ResultsMean age was 51.2+42.2months (3–144 months); 67.2% were males. Central nervous system (CNS) infection in 82%, status epilepticus in 15.2%, abnormal neuroimaging in 62.8% and abnormal electroencephalography in 22.3% were noted. At discharge, 27.6% had poor outcome including death (13%); CNS infections were significantly associated with poor outcome compared to ASS of other aetiologies (32.6% vs 5.2%, p=0.02). Low GCS (OR 4.9, 95%CI 1.2–20.7), abnormal electroencephalograph (OR 4.3, 95%CI 1–16.9) and neuroimaging (OR 12.1, 95%CI 1.4–105.2) were independent predictors of poor outcome.After 6 months, 16% children had delayed neurodevelopment and cognition; 6% had seizure recurrences. Abnormal electroencephalograph (p=0.002; OR 6.8, 95%CI 2.0–23.1), abnormal neuroimaging (p=0.015; OR 9.47, 95%CI 1.18–75.8),>1 anti-epileptic (p=0.00; OR 9.9, 95%CI 2.88–33.9), intubation (p=0.004; OR 6.25, 95%CI 1.79–21.7) and poor outcome at discharge (p=0.02; OR 4.44, 95%CI1.38–14.2) predicted abnormal neurodevelopment. ConclusionsCNS infections are the most common cause of ASS in children from developing countries. Abnormal neurodevelopment and seizure recurrences on short-term follow-up are seen in a minority of children.

Preliminary Results of Whole Exome Sequencing in a Cohort of Sicilian Children with Early-Onset Epileptic Encephalopaty

Objective: Early-Onset Epileptic Encephalopathies encompass a group of severe disorders characterized by refractory epilepsy and/or electroencephalographic abnormalities with progressive cerebral dysfunction. The modern technologies of molecular genetics are providing crucial diagnostic insights, however, this is only the tip of the iceberg and a great effort is still necessary to detect new genes, new mutations and define their causative role. We herein present the preliminary results in our cohort with EOEE included into extensive multicenter Whole Exome Sequencing study (SynaPs network). Methods: Twenty-four patients with electroclinical diagnosis of EOEE, no structural abnormalities at brain MRI scans and negative array-CGH were enrolled. Results: A de novo mutation on GRIN1 gene was detected in a 5-years-old girl with EOEE, severe hypotonia, pyramidal and extrapyramidal signs and Rett-like manual stereotypies. GRIN1 mutations impairs functioning of glutamate NMDA receptor. In an 8 years-old male patient with EOEE, hypotonia, ataxia and autism features, a de novo mutation in KCNA2 gene was found. It encodes for potassium channel Kv1.2 and has been associated to inherited episodic ataxia and epilepsy. In a 16 years-old boy with EOEE and subsequent Lennox-Gastaut ’s phenotype, WES analysis evidenced a damaging mutation in the contactin 2 (CNTN2) gene. A pathogenic role of CNTN2 has been hypothesized due to its interaction with Contactin-associated Protein-like 2 which is implicated in several neurological disorders. A SZT2 gene mutation was found in a 7 years-old male with EOEE, microcephaly and severe developmental delay. To date, two clinical reports described few children with SZT2 mutations and heterogeneous clinical phenotypes including epileptic encephalopathy, developmental delay and dysmorphisms. Conclusion: WES analysis may significantly enhance diagnostic chances in patients with EOEE. A synergic work between clinicians and geneticists is mandatory to assess genotype-phenotype correlation and provide proper genetic counseling. Disease- specific treatments could be attempted and taken into account in clinical practice in the future.

Reduced glucose metabolism in neocortical network nodes remote from hypothalamic hamartomas reflects cognitive impairment

The clinical appearance of patients with hypothalamic hamartomas is very heterogeneous, and interindividual variability of intellectual abilities is not completely understood. We retrospectively investigated cerebral dysfunction as indicated by reduced regional glucose metabolism in 29 patients (age range 7-49years) with epilepsy due to hypothalamic hamartomas. Brain metabolism assessed by [18 F]FDG-PET was compared between patients with and without cognitive impairment controlled for unevenly distributed hamartoma lateralization seen on magnetic resonance imaging (MRI). Due to the broad age range, the variable "age" was included in the imaging analyses as a covariate. Additional voxel-wise analysis with hamartoma volume, disease duration, seizure severity, seizure frequency, and antiepileptic drug (AED) load as well as dosage and gender as further covariates was accomplished. Furthermore, global visual ratings on laterality of hypometabolism patterns were assessed according to clinical standards and related to hamartoma lateralization on MRI as well as lateralization of electroencephalography (EEG) abnormalities. Cognitively impaired patients showed significantly reduced glucose metabolism in bilateral frontal as well as right parietal and posterior midline cortices (p<0.005), irrespective of hamartoma lateralization seen on MRI. Additional voxel-wise analysis with the above-mentioned further covariates revealed comparable results. FDG uptake values within the main right frontal cluster obtained from group comparison were not associated with hamartoma volume, disease duration, or AED load. Irrespective of cognitive functioning, lateralization of reduced FDG uptake in global visual ratings was associated with lateralization of hypothalamic hamartomas seen on MRI (p<0.01), but not with EEG abnormalities. We found regions of reduced glucose metabolism in cognitively impaired patients remote from the hypothalamic hamartomas in frontal and parietal regions, which have been identified as important network nodes in the human brain and are linked to higher cognitive functions.

Slow and Fast Neocortical Oscillations in the Senescence-Accelerated Mouse Model SAMP8.

The senescence-accelerated mouse prone 8 (SAMP8) model is characterized by accelerated, progressive cognitive decline as well as Alzheimer’s disease (AD)-like neurodegenerative changes, and resembles the etiology of multicausal, sporadic late-onset/age-related AD in humans. Our aim was to find whether these AD-like pathological features, together with the cognitive deficits present in the SAMP8 strain, are accompanied by disturbances in cortical network activity with respect to control mice (SAM resistance 1, SAMR1) and, if so, how the alterations in cortical activity progress with age. For this purpose, we characterized the extracellular spontaneous oscillatory activity in different regions of the cerebral cortex of SAMP8 and SAMR1 mice under ketamine anesthesia at 5 and 7 months of age. Under these conditions, slow oscillations and fast rhythms generated in the cortical network were recorded and different parameters of these oscillations were quantified and compared between SAMP8 and their control, SAMR1 mice. The average frequency of slow oscillations in SAMP8 mice was decreased with respect to the control mice at both studied ages. An elongation of the silent periods or Down states was behind the decreased slow oscillatory frequency while the duration of active or Up states remained stable. SAMP8 mice also presented increased cycle variability and reduced high frequency components during Down states. During Up states, the power peak in the gamma range was displaced towards lower frequencies in all the cortical areas of SAMP8 with respect to control mice suggesting that the spectral profile of SAMP8 animals is shifted towards lower frequencies. This shift is reminiscent to one of the principal hallmarks of electroencephalography (EEG) abnormalities in patients with Alzheimer’s disease, and adds evidence in support of the suitability of the SAMP8 mouse as a model of this disease. Although some of the differences between SAMP8 and control mice were emphasized with age, the evolution of the studied parameters as SAMR1 mice got older indicates that the SAMR1 phenotype tends to converge with that of SAMP8 animals. To our knowledge, this is the first systematic characterization of the cortical slow and fast rhythms in the SAMP8 strain and it provides useful insights about the cellular and synaptic mechanisms underlying the reported alterations.

Early ictal and interictal patterns in FIRES: The sparks before the blaze.

Febrile infection-related epilepsy syndrome (FIRES) is a catastrophic epileptic encephalopathy described as explosive onset of super refractory status epilepticus (SRSE) in previously healthy children. We describe electroencephalography (EEG) abnormalities in the hyperacute phase of FIRES, with the aim of contributing to the diagnostic characterization of a syndrome otherwise lacking specific biomarkers. This is a retrospective single-center, case series of seven children with FIRES. Cases were identified from a Neurocritical Care database. Patient characteristics and clinical course were obtained from electronic medical records. Electroencephalography recordings were reviewed in two segments: the initial 12 h of recording and the 12 h prior to initiation of a medically induced burst suppression (BS). Fourteen 12-h segments of video-electroencephalography (EEG) recordings were analyzed for commonalities. A beta-delta complex resembling extreme delta brush (EDB) occurred in at least one 12-h segment for all patients. In six patients, seizures were brief and relatively infrequent during the first recording, with a gradual evolution to status epilepticus by the second. We observed a characteristic electrographic seizure pattern in six of seven patients with prolonged focal fast activity at onset. Shifting seizures were seen in four of seven patients. The diagnosis of FIRES is typically assigned late in a patient's clinical course, which has broad implications for clinical care and research. We retrospectively analyzed acute EEG features in seven patients with FIRES and discovered three common features: gradual increase in seizure burden, presence of a recurrent EDB, and a typical seizure pattern. Recognition of this pattern may facilitate early diagnosis and treatment.

Autoimmune encephalitis associated with voltage-gated potassium channels-complex and leucine-rich glioma-inactivated 1 antibodies - a national cohort study.

The aim of this study was to describe clinical and paraclinical characteristics of all Danish patients who tested positive for anti-voltage-gated potassium channels (VGKC)-complex, anti-leucine-rich glioma-inactivated 1 (LGI1) and anti-contactin-associated protein-2 antibodies in the serum/cerebrospinal fluid between 2009 and 2013 with follow-up interviews in 2015 and 2016. We evaluated antibody status, symptoms leading to testing, course of disease, suspected diagnosis and time of admission as well as diagnosis and treatment. All magnetic resonance imaging, electroencephalography and 18 F-fluorodeoxyglucose positron emission tomography scans were re-evaluated by experts in the field. A total of 28/192 patients tested positive for VGKC-complex antibodies by radioimmunoassay and indirect immunofluorescence; 17 had antibodies to LGI1 and 6/7 of the available cerebrospinal fluids from these patients were seropositive. These 17 patients all had a clinical phenotype appropriate to LGI1 antibodies. The remaining 11 were LGI1 negative (n = 4) or not tested (n = 7). Of these, two had a phenotype consistent with limbic encephalitis. The remaining phenotypes were Guillain-Barré syndrome, Creutzfeldt-Jakob disease, neuromyotonia and anti-N-methyl-D-aspartate receptor encephalitis. Magnetic resonance imaging abnormalities were demonstrated in 69% of the LGI1-positive patients. Two patients with normal magnetic resonance imaging demonstrated temporal lobe hypermetabolism using 18 F-fluorodeoxyglucose positron emission tomography. Abnormal electroencephalography recordings were found in 86% of the patients. Upon follow-up (median 3.2 years), the median modified Rankin Scale score of anti-LGI1-positive patients was 2 and only two patients reported seizures in the past year. Patients diagnosed with anti-LGI1 autoimmune encephalitis increased significantly from 2009 to 2014, probably due to increased awareness. In contrast to seropositive anti-VGKC-complex patients, all anti-LGI1-positive patients presented with a classical limbic encephalitis. The majority of patients recovered well.

EEG abnormalities and long term seizure outcome in high functioning autism.

Electroencephalographic abnormalities may occur in autistic spectrum disorders (ASD) even in the absence of clinical seizures. These abnormalities may vary from nonspecific changes to epileptiform abnormalities and are more common compared to the overall population. The level of intelligence is a significant risk factor for epilepsy in ASD. However, the relation between the functionality of the individuals with autism and the electroencephalographic (EEG) abnormalities, and the clinical significance of these abnormalities still remain relatively unclear. In this study we investigated the presence of EEG abnormalities in sixteen children diagnosed with high-functioning ASD. EEG recording was performed for at least 2h and included at least 90min of sleep activity. While none of the patients had clinical seizures, 5 patients (31.3%) were detected to have EEG abnormalities. Four of these were epileptiform (25%), and one patient developed seizure during follow-up. Our results support the fact that EEG abnormalities are observed at a higher rate also in ASD with a better functionality. The potential impact of EEG abnormalities on cognition and behavior, and the risk of epilepsy should be considered during long-term follow-up of these patients.

Age-dependent decrease of GAD65/67 mRNAs but normal densities of GABAergic interneurons in the brain regions of Shank3-overexpressing manic mouse model

Dysfunction of inhibitory GABAergic interneurons is considered a major pathophysiological feature of various neurodevelopmental and neuropsychiatric disorders. The variants of SHANK3 gene, encoding a core scaffold protein of the excitatory postsynapse, have been associated with numerous brain disorders. It has been suggested that abnormalities of GABAergic interneurons could contribute to the SHANK3-related disorders, but the limitation of these studies is that they used mainly Shank3 knock-out mice. Notably, Shank3-overexpressing transgenic mice, modeling human hyperkinetic disorders, also show reduced inhibitory synaptic transmission, abnormal electroencephalography, and spontaneous seizures. However, it has not been investigated whether these phenotypes of Shank3 transgenic mice are associated with GABAergic interneuron dysfunction, or solely due to the cell-autonomous postsynaptic changes of principal neurons. To address this issue, we investigated the densities of parvalbumin- and somatostatin-positive interneurons, and the mRNA and protein levels of GAD65/67 GABA-synthesizing enzymes in the medial prefrontal cortex, striatum, and hippocampus of adult Shank3 transgenic mice. We found no significant difference in the measurements performed on wild-type versus Shank3 transgenic mice, except for the decreased GAD65 or GAD67 mRNAs in these brain regions. Interestingly, only GAD65 mRNA was decreased in the hippocampus, but not mPFC and striatum, of juvenile Shank3 transgenic mice which, unlike the adult mice, did not show behavioral hyperactivity. Together, our results suggest age-dependent decrease of GAD65/67 mRNAs but normal densities of certain GABAergic interneurons in the Shank3 transgenic mice.