Ceroid lipofuscinosis type 2 disease: Effective presymptomatic therapy-Oldest case of a presymptomatic enzyme therapy.

Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a rare, lysosomal storage disorder that causes pediatric onset neurodegenerative disease. It is characterized by mutations in the TPP1 gene. Symptoms begin between 2 and 4 years of age with loss of previously acquired motor, cognitive, and language abilities. Cerliponase alfa, a recombinant human TPP1 enzyme, is the only approved therapy. We report the first presymptomatic cerliponase alfa intraventricular treatment in a familial case of CLN2 related to a classical TPP1 variant. Sister 1 presented with motor, cognitive, and language decline and progressive myoclonic epilepsy since the age of 3 years, evolved with severe diffuse encephalopathy, received no specific treatment, and died at 11 years. Sister 2 had a CLN2 presymptomatic diagnosis and has been treated with cerliponase since she was 12 months old. She is now 6 years 8 months and has no CLN2 symptom except one generalized seizure 1 year ago. No serious adverse event has occurred. Repeated Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition standardized index scores are heterogeneous in the extremely low to low average ranges. Mean length of utterances, a global index of sentence complexity, showed a delay, but a gradual improvement. The reported case enhances the major contribution of presymptomatic diagnosis and significant middle-term treatment benefit for patients with CLN2.

Preoperative Detection of Subtle Focal Cortical Dysplasia in Children by Combined Arterial Spin Labeling, Voxel-Based Morphometry, Electroencephalography-Synchronized Functional MRI, Resting-State Regional Homogeneity, and 18F-fluorodeoxyglucose Positron Emission Tomography.

BACKGROUND: Focal cortical dysplasia (FCD) causes drug-resistant epilepsy in children that can be cured surgically, but the lesions are often unseen by imaging. OBJECTIVE: To assess the efficiency of arterial spin labeling (ASL), voxel-based-morphometry (VBM), fMRI electroencephalography (EEG), resting-state regional homogeneity (ReHo), 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their combination in detecting pediatric FCD. METHODS: We prospectively included 10 children for whom FCD was localized by surgical resection. They underwent 3T MR acquisition with concurrent EEG, including ASL perfusion, resting-state BOLD fMRI (allowing the processing of EEG-fMRI and ReHo), 3D T1-weighted images processed using VBM, and FDG PET-CT coregistered with MRI. Detection was assessed visually and by comparison with healthy controls (for ASL and VBM). RESULTS: Eight children had normal MRI, and 2 had asymmetric sulci. Using MR techniques, FCD was accurately detected by ASL for 6/10, VBM for 5/10, EEG-fMRI for 5/8 (excluding 2 with uninterpretable results), and ReHo for 4/10 patients. The combination of ASL, VBM, and ReHo allowed correct FCD detection for 9/10 patients. FDG PET alone showed higher accuracy than the other techniques (7/9), and its combination with VBM allowed correct FCD detection for 8/9 patients. The detection efficiency was better for patients with asymmetric sulci (2/2 for all techniques), but advanced MR techniques and PET were useful for MR-negative patients (7/8). CONCLUSION: A combination of multiple imaging techniques, including PET, ASL, and VBM analysis of T1-weighted images, is effective in detecting subtle FCD in children.

Abnormal Spontaneous Blood Oxygenation Level Dependent Fluctuations in Children with Focal Cortical Dysplasias: Initial Findings in Surgically Confirmed Cases.

BACKGROUND: Focal cortical dysplasias (FCD) are a frequent cause of drug-resistant epilepsy in children but are often undetected on structural magnetic resonance imaging (MRI). We aimed to measure and validate the variation of resting state functional MRI (rs-fMRI) blood oxygenation level dependent (BOLD) metrics in surgically proven FCDs in children, to assess the potential yield for detecting and understanding these lesions. METHODS: We prospectively included pediatric patients with surgically proven FCD with inconclusive structural MRI and healthy controls, who underwent a ten-minute rs-fMRI acquired at 3T. Rs-fMRI data was pre-processed and maps of values of regional homogeneity (ReHo), degree centrality (DC), amplitude of low frequency fluctuations (ALFF) and fractional ALFF (fALFF) were calculated. The variations of BOLD metrics within the to-be-resected areas were analyzed visually, and quantitatively using lateralization indices. BOLD metrics variations were also analyzed in fluorodeoxyglucose-positron emission tomography (FDG-PET) hypometabolic areas. RESULTS: We included 7 patients (range: 3-15 years) and 6 aged-matched controls (range: 6-17 years). ReHo lateralization indices were positive in the to-be-resected areas in 4/7 patients, and in 6/7 patients in the additional PET hypometabolic areas. These indices were significantly higher compared to controls in 3/7 and 4/7 patients, respectively. Visual analysis revealed a good spatial correlation between high ReHo areas and MRI structural abnormalities (when present) or PET hypometabolic areas. No consistent variation was seen using DC, ALFF, or fALFF. CONCLUSION: Resting-state fMRI metrics, noticeably increase in ReHo, may have potential to help detect MRI-negative FCDs in combination with other morphological and functional techniques, used in clinical practice and epilepsy-surgery screening.

Periodic electroencephalographic discharges and epileptic spasms involve cortico-striatal-thalamic loops on Arterial Spin Labeling Magnetic Resonance Imaging.

Periodic discharges are a rare peculiar electroencephalogram pattern, occasionally associated with motor or other clinical manifestations, usually observed in critically ill patients. Their underlying pathophysiology remains poorly understood. Epileptic spasms in clusters and periodic discharges with motor manifestations share similar electroencephalogram pattern and some aetiologies of unfavourable prognosis such as subacute sclerosing panencephalitis or herpes encephalitis. Arterial spin labelling magnetic resonance imaging identifies localizing ictal and inter-ictal changes in neurovascular coupling, therefore assumed able to reveal concerned cerebral structures. Here, we retrospectively analysed ictal and inter-ictal arterial spin labelling magnetic resonance imaging in patients aged 6 months to 15 years (median 3 years 4 months) with periodic discharges including epileptic spasms, and compared these findings with those of patients with drug-resistant focal epilepsy who never presented periodic discharges nor epileptic spasms as well as to those of age-matched healthy controls. Ictal electroencephalogram was recorded either simultaneously with arterial spin labelling magnetic resonance imaging or during the close time lapse of patients' periodic discharges, whereas inter-ictal examinations were performed during the patients' active epilepsy but without seizures during the arterial spin labelling magnetic resonance imaging. Ictal arterial spin labelling magnetic resonance imaging was acquired in five patients with periodic discharges [subacute sclerosing panencephalitis (1), stroke-like events (3), West syndrome with cortical malformation (1), two of them also had inter-ictal arterial spin labelling magnetic resonance imaging]. Inter-ictal group included patients with drug-resistant epileptic spasms of various aetiologies (14) and structural drug-resistant focal epilepsy (8). Cortex, striatum and thalamus were segmented and divided in six functional subregions: prefrontal, motor (rostral, caudal), parietal, occipital and temporal. Rest cerebral blood flow values, absolute and relative to whole brain, were compared with those of age-matched controls for each subregion. Main findings were diffuse striatal as well as cortical motor cerebral blood flow increase during ictal examinations in generalized periodic discharges with motor manifestations (subacute sclerosing panencephalitis) and focal cerebral blood flow increase in corresponding cortical-striatal-thalamic subdivisions in lateralized periodic discharges with or without motor manifestations (stroke-like events and asymmetrical epileptic spasms) with straight topographical correlation with the electroencephalogram focus. For inter-ictal examinations, patients with epileptic spasms disclosed cerebral blood flow changes in corresponding cortical-striatal-thalamic subdivisions (absolute-cerebral blood flow decrease and relative-cerebral blood flow increase), more frequently when compared with the group of drug-resistant focal epilepsies, and not related to Vigabatrin treatment. Our results suggest that corresponding cortical-striatal-thalamic circuits are involved in periodic discharges with and without motor manifestations, including epileptic spasms, opening new insights in their pathophysiology and new therapeutical perspectives. Based on these findings, we propose a model for the generation of periodic discharges and of epileptic spasms combining existing pathophysiological models of cortical-striatal-thalamic network dynamics.

SYNGAP1-DEE: A visual sensitive epilepsy.

OBJECTIVE: To further delineate the electroclinical features of individuals with SYNGAP1 pathogenic variants. METHODS: Participants with pathogenic SYNGAP1 variants and available video-electroencephalogram (EEG) recordings were recruited within five European epilepsy reference centers. We obtained molecular and clinical data, analyzed EEG recordings and archived video-EEGs of seizures and detailed characteristics of interictal and ictal EEG patterns for every patient. RESULTS: We recruited 15 previously unreported patients and analyzed 72 EEGs. Two distinct EEG patterns emerged, both triggered by eye closure. Pattern 1 (14/15 individuals) consisted of rhythmic posterior/diffuse delta waves appearing with eye-closure and persisting until eye opening (strongly suggestive of fixation-off sensitivity). Pattern 2 (9/15 individuals) consisted of diffuse polyspike-and-wave discharges triggered by eye closure (eye-closure sensitivity). Both patterns presented in 8/15. Including archived video-EEG clips of seizures from 9/15 patients, we analyzed 254 seizures. Of 224 seizures experienced while awake, 161 (72%) occurred at or following eye closure. In 119/161, pattern 1 preceded an atypical absence, myoclonic seizure or myoclonic absence; in 42/161, pattern 2 was associated with eyelid myoclonia, absences and myoclonic or atonic seizures. CONCLUSIONS: Fixation-off and eye closure were the main triggers for seizures in this SYNGAP1 cohort. SIGNIFICANCE: Combining these clinical and electroencephalographic features could help guide genetic diagnosis.

Jerking during absences: video-EEG and polygraphy of epileptic myoclonus associated with two paediatric epilepsy syndromes.

Epileptic myoclonus (EM) is reported in many paediatric epilepsies from neonatal period to adolescence. Myoclonus can be the only seizure type or may occur among others, independently or in combination as a single ictal event. We report two children presenting with absences associated with myoclonus, predominating on one side, in a setting of two different types of absence seizures and two different electro-clinical syndromes. Patients were explored with long-duration video-EEG coupled to surface EMG polygraphy. EEG was visually analysed and complemented by jerk-locked back-averaging. Two types of seizure, encompassing myoclonus and absence, were identified: myoclonic absences in the context of epilepsy with myoclonic absences and atypical absences with atonic component (negative myoclonus) in the context of encephalopathy related to status epilepticus during slow sleep (ESES). In the latter case, rhythmic upper limb jerking, mimicking positive myoclonus, corresponded to recovery of muscular tone after each negative myoclonus. Due to the rhythmic recovery of muscle tone, subsequent rhythmic negative myoclonus may exhibit a similar clinical picture to that of rhythmic positive myoclonus. Video-EEG recording coupled to EMG polygraphy is essential in order to precisely characterize motor manifestations during seizures with myoclonus [Published with video sequences].

Complete hemispherotomy leads to lateralized functional organization and lower level of consciousness in the isolated hemisphere.

OBJECTIVE: To quantify whole-brain functional organization after complete hemispherotomy, characterizing unexplored plasticity pathways and the conscious level of the dissected hemispheres. METHODS: Evaluation with multimodal magnetic resonance imaging in two pediatric patients undergoing right hemispherotomy including complete callosotomy with a perithalamic section. Regional cerebral blood flow and fMRI network connectivity assessed the functional integrity of both hemispheres after surgery. The level of consciousness was tested by means of a support vector machine classifier which compared the intrinsic organization of the dissected hemispheres with those of patients suffering from disorders of consciousness. RESULTS: After hemispherotomy, both patients showed typical daily functionality. We found no interhemispheric transfer of functional connectivity in either patient as predicted by the operation. The healthy left hemispheres displayed focal blood hyperperfusion in motor and limbic areas, with preserved network-level organization. Unexpectedly, the disconnected right hemispheres showed sustained network organization despite low regional cerebral blood flow. Subcortically, functional connectivity was increased in the left thalamo-cortical loop and between the cerebelli. One patient further showed unusual ipsilateral right cerebello-cortical connectivity, which was explained by the mediation of the vascular system. The healthy left hemisphere had higher probability to be classified as in a minimally conscious state compared to the isolated right hemisphere. SIGNIFICANCE: Complete hemispherotomy leads to a lateralized whole-brain organization, with the remaining hemisphere claiming most of the brain's energetic reserves supported by subcortical structures. Our results further underline the contribution of nonneuronal vascular signals on contralateral connectivity, shedding light on the nature of network organization in the isolated tissue. The disconnected hemisphere is characterized by a level of consciousness which is necessary but insufficient for conscious processing, paving the way for more specific inquiries about its role in awareness in the absence of behavioral output.

Neonatal factors related to survival and intellectual and developmental outcome of patients with early-onset urea cycle disorders.

PURPOSE: We aimed to identify prognostic factors for survival and long-term intellectual and developmental outcome in neonatal patients with early-onset urea cycle disorders (UCD) experiencing hyperammonaemic coma. METHODS: We retrospectively analysed ammonia (NH3) and glutamine levels, electroencephalogram and brain images obtained during neonatal coma of UCD patients born between 1995 and 2011 and managed at a single centre and correlated them to survival and intellectual and developmental outcome. RESULTS: We included 38 neonates suffering from deficiencies of argininosuccinate synthetase (ASSD, N = 12), ornithine transcarbamylase (OTCD, N = 10), carbamoylphosphate synthetase 1 (CPSD, N = 7), argininosuccinate lyase (ASLD, N = 7), N-acetylglutamate synthase (NAGS, N = 1) or arginase (ARGD, N = 1). Symptoms occurred earlier in mitochondrial than in cytosolic UCD. Sixty-eight percent of patients survived, with a mean (standard deviation-SD) follow-up of 10.4 (5.3) years. Mortality was mostly observed in OTCD (N = 7/10) and CPSD (N = 4/7) patients. Plasma NH3 level during the neonatal period, expressed as area under the curve, but not glutamine level was associated with mortality (p = .044 and p = .610). 62.1% of the patients had normal intellectual and developmental outcome. Intellectual and developmental outcome tended to correlate with UCD subtype (p = .052). No difference in plasma NH3 or glutamine level during the neonatal period among developmental outcomes was identified. EEG severity was linked to UCD subtypes (p = .004), ammonia levels (p = .037), duration of coma (p = .043), and mortality during the neonatal period (p = .020). Status epilepticus was recorded in 6 patients, 3 of whom died neonatally, 1 developed a severe intellectual disability while the 2 last patients had a normal development. CONCLUSION: UCD subtypes differed by survival rate, intellectual and developmental outcome and EEG features in the neonatal period. Hyperammonaemia expressed as area under the curve was associated with survival but not with intellectual and developmental outcome whereas glutamine was not associated with one of these outcomes. Prognostic value of video-EEG monitoring and the association between status epilepticus and mortality should be assessed in neonatal hyperammonaemic coma in further studies.

Focal seizures with a migrating aspect in infants treated with beta-lactam antibiotics - Report of two cases.

Seizures caused by beta-lactam antibiotics are relatively rare. However, they represent a clinically significant phenomenon and have been widely reported in all age groups. Here we describe two infants presenting subtle multifocal seizures with a migrating aspect on EEG during beta-lactam antibiotic treatment with agents from the carbapenem group (meropenem) and the cephalosporin group (ceftazidime).

How to distinguish seizures from non-epileptic manifestations.

The first and most important step in establishing diagnosis of epilepsy consists of careful history taking from patients and witnesses. The clinical evaluation of the event will lead the indication for further diagnostic tests including e.g. EEG and MRI. Hence, identifying the paroxysmal event as epileptic or non-epileptic is the very first step in the diagnostic process. Paroxysmal events pose a clinical challenge, as these are unpredictable and do not usually occur in the doctor's office. History taking, hunting for witness reports and home-video recordings are the main tools to conclude whether a paroxysmal event is a seizure or not. In this review, we describe the most common differential diagnoses of epileptic seizures, including syncope, psychogenic non-epileptic seizures, as well as a variety of paroxysmal conditions and behaviours of all age groups. Misdiagnosis of non-epileptic events as epilepsy may not only defer the correct diagnosis and treatment but also poses additional risk by prescribing antiepileptic drugs unnecessarily. Moreover, missing the diagnosis of epilepsy implies risk of additional seizures and therefore possibly injuries, sudden death in people with epilepsy, or status epilepticus. Studies have shown that patient and witness accounts are unreliable in a high percentage of cases. Therefore, the core competency of doctors and medical professionals assessing paroxysmal events is knowledge of the clinical features that help define the different aetiologies, thus empowering them to establish the most accurate appraisal of an event. [Published with video sequences].

Epilepsy with migrating focal seizures: KCNT1 mutation hotspots and phenotype variability.

OBJECTIVE: To report new sporadic cases and 1 family with epilepsy of infancy with migrating focal seizures (EIMFSs) due to KCNT1 gain-of-function and to assess therapies' efficacy including quinidine. METHODS: We reviewed the clinical, EEG, and molecular data of 17 new patients with EIMFS and KCNT1 mutations, in collaboration with the network of the French reference center for rare epilepsies. RESULTS: The mean seizure onset age was 1 month (range: 1 hour to 4 months), and all children had focal motor seizures with autonomic signs and migrating ictal pattern on EEG. Three children also had infantile spasms and hypsarrhythmia. The identified KCNT1 variants clustered as "hot spots" on the C-terminal domain, and all mutations occurred de novo except the p.R398Q mutation inherited from the father with nocturnal frontal lobe epilepsy, present in 2 paternal uncles, one being asymptomatic and the other with single tonic-clonic seizure. In 1 patient with EIMFS, we identified the p.R1106Q mutation associated with Brugada syndrome and saw no abnormality in cardiac rhythm. Quinidine was well tolerated when administered to 2 and 4-year-old patients but did not reduce seizure frequency. CONCLUSIONS: The majority of the KCNT1 mutations appear to cluster in hot spots essential for the channel activity. A same mutation can be linked to a spectrum of conditions ranging from EMFSI to asymptomatic carrier, even in the same family. None of the antiepileptic therapies displayed clinical efficacy, including quinidine in 2 patients.

Benign Neonatal Sleep Myoclonus Evokes Somatosensory Responses.

PURPOSE: Benign neonatal sleep myoclonus is a common nonepileptic condition occurring in neurologically normal full-term newborns. During jerks, EEG has always been described as normal. The aim of this study was to describe EEG changes associated with the myoclonic jerks. METHODS: Polygraphic video-EEG recordings of four full-term neonates presenting benign neonatal sleep myoclonus were studied. Myoclonic jerks were analyzed regarding their topography, frequency, propagation pattern, and reflex component. EEG averaging time-locked to myoclonic jerks and to somatosensory stimuli (realized by tapping on palms and feet) was performed to study eventual EEG correlates of myoclonus and to asses somatosensory evoked responses-for the latter, two control newborns were added. RESULTS: Visual analysis of the EEG disclosed theta band slow waves on central and vertex electrodes concomitant to myoclonic jerks and jerk-locked back-averaging disclosed a sequence of deflections, not preceding, but following the myoclonus. This response predominated on the vertex electrode (CZ) and consisted of five components (N1, P1, N2, P2, and N3), with only the three later components being constantly present (at 110, 200, and 350-500 ms, respectively). Back-averaging locked to the tactile stimuli in four subjects and two control newborns showed similar components and were comparable to those described in the literature as late somatosensory evoked responses in full-term newborns. CONCLUSIONS: Myoclonic jerks in benign neonatal sleep myoclonus can evoke visually identifiable EEG potentials on vertex electrodes corresponding to somatosensory responses. This EEG aspect may be misleading and could give rise to an anti-seizure treatment that mostly worsens the condition.

Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy.

Lipoate serves as a cofactor for the glycine cleavage system (GCS) and four 2-oxoacid dehydrogenases functioning in energy metabolism (α-oxoglutarate dehydrogenase [α-KGDHc] and pyruvate dehydrogenase [PDHc]), or amino acid metabolism (branched-chain oxoacid dehydrogenase, 2-oxoadipate dehydrogenase). Mitochondrial lipoate synthesis involves three enzymatic steps catalyzed sequentially by lipoyl(octanoyl) transferase 2 (LIPT2), lipoic acid synthetase (LIAS), and lipoyltransferase 1 (LIPT1). Mutations in LIAS have been associated with nonketotic hyperglycinemia-like early-onset convulsions and encephalopathy combined with a defect in mitochondrial energy metabolism. LIPT1 deficiency spares GCS deficiency and has been associated with a biochemical signature of combined 2-oxoacid dehydrogenase deficiency leading to early death or Leigh-like encephalopathy. We report on the identification of biallelic LIPT2 mutations in three affected individuals from two families with severe neonatal encephalopathy. Brain MRI showed major cortical atrophy with white matter abnormalities and cysts. Plasma glycine was mildly increased. Affected individuals' fibroblasts showed reduced oxygen consumption rates, PDHc, α-KGDHc activities, leucine catabolic flux, and decreased protein lipoylation. A normalization of lipoylation was observed after expression of wild-type LIPT2, arguing for LIPT2 requirement in intramitochondrial lipoate synthesis. Lipoic acid supplementation did not improve clinical condition nor activities of PDHc, α-KGDHc, or leucine metabolism in fibroblasts and was ineffective in yeast deleted for the orthologous LIP2.

Standardized computer-based organized reporting of EEG: SCORE - Second version.

Standardized terminology for computer-based assessment and reporting of EEG has been previously developed in Europe. The International Federation of Clinical Neurophysiology established a taskforce in 2013 to develop this further, and to reach international consensus. This work resulted in the second, revised version of SCORE (Standardized Computer-based Organized Reporting of EEG), which is presented in this paper. The revised terminology was implemented in a software package (SCORE EEG), which was tested in clinical practice on 12,160 EEG recordings. Standardized terms implemented in SCORE are used to report the features of clinical relevance, extracted while assessing the EEGs. Selection of the terms is context sensitive: initial choices determine the subsequently presented sets of additional choices. This process automatically generates a report and feeds these features into a database. In the end, the diagnostic significance is scored, using a standardized list of terms. SCORE has specific modules for scoring seizures (including seizure semiology and ictal EEG patterns), neonatal recordings (including features specific for this age group), and for Critical Care EEG Terminology. SCORE is a useful clinical tool, with potential impact on clinical care, quality assurance, data-sharing, research and education.

Unilateral predominance of abnormal movements: A characteristic feature of the pediatric anti-NMDA receptor encephalitis?

Anti-NMDA receptor encephalitis is a treatable autoimmune disease characterized by cognitive, motor and psychiatric features that primarily affects young adults and children. We present a case of a 7-year-old boy with asymmetrical (mainly right hemibody) and abnormal polymorphic movements without concomitant scalpictal EEG changes but had background slowing predominating over the left hemisphere. This report illustrates previous descriptions of asymmetric presentation of abnormal movements in pediatric anti-NMDA receptor encephalitis and emphasizes the importance of video-EEG interpreted within the overall clinical context, to differentiate epileptic from non-epileptic abnormal movements in patients with autoimmune encephalitis.

Epileptic spasms in congenital disorders of glycosylation.

Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases, characterized by impaired glycosylation. Multisystemic involvement is common and neurological impairment is notably severe and disabling, concerning the central and peripheral nervous system. Epilepsy is frequent, but detailed electroclinical description is rare. We describe, retrospectively, the electroclinical features in five children with CDG and epileptic spasms. Epileptic spasms were observed in patients with ALG1-, ALG6, ALG11-CDG and CDG-Ix, and occurred at an early age, before 6 months in all cases, except one who had spasms that started at 18 months. In this patient, spasms had an unusual aspect; they did not occur in clusters and were immediately preceded by a myoclonus. All but one child also presented rare myoclonias. On EEG, background activity was poorly organized with abundant posterior spike and fast rhythm activity, but without hypsarrhythmia. At the last evaluation (age range: 6-12 years), two patients still presented epileptic spasms and subcortical myoclonias, one showed rare generalized tonic-clonic seizures, and two were seizure-free. CDG disorders can be associated with epileptic spasms showing particular features, such as absence of hypsarrhythmia, posterior EEG anomalies, and an unusual combination of epileptic spasms with myoclonus. These features, associated with pre-existing developmental delay and subcortical myoclonias, may shift toward CDG screening. [Published with video sequence and supplemental EEG plates on www.epilepticdisorders.com].

Epilepsy in young Tsc1(+/-) mice exhibits age-dependent expression that mimics that of human tuberous sclerosis complex.

OBJECTIVE: To describe the epileptic phenotype of Tsc1(+/-) mice pups in comparison with age-related seizures in human tuberous sclerosis complex (TSC). METHODS: Tsc1(+/-) and control mice underwent intracranial electroencephalography (EEG) recording at postnatal ages (P)8 to P33, with linear silicon probe implanted in the somatosensory cortex of one or both hemispheres for 8-24 h. Ictal events were classified visually by independent analyzers; distinct EEG patterns were related to age and analyzed to quantify field potential characteristics and signal dynamics between hemispheres. We collected retrospectively 20 infants with prenatally diagnosed TSC and EEG before seizure onset, and analyzed the electroclinical course of epilepsy, taking into account a first-line treatment by vigabatrin. RESULTS: Spontaneous seizures were disclosed in 55% of Tsc1(+/-) mice at P9-18. Three ictal patterns were identified: from P9 to P12 "spike clusters" consisted of recurring large spikes without clinical correlate; "spasm-like" discharges dominated from P13 to P16 consisting of high amplitude large field potential superimposed with or followed by fast activity repeated every 2-10 s for at least 20 s, accompanied by rhythmic limb contractions; from P14 to P18 a "tonic-clonic like" pattern comprised rhythmic spikes of increasing amplitude with tonic-clonic movements. Early onset "spike clusters" were mainly unilateral, whereas "spasm-like" and "tonic-clonic like" patterns were bilateral. Interhemispheric propagation was significantly faster for "tonic-clonic like" than for "spasm-like" events. In infants diagnosed prenatally with TSC, clusters of sharp waves or spikes preceded the first seizure, and vigabatrin prevented the development of seizures. Patients treated after seizure onset developed spasms or focal seizures that were pharmacoresistant in 66.7% of cases. SIGNIFICANCE: Tsc1(+/-) mice pups exhibit an age-dependent seizure pattern sequence mimicking early human TSC epilepsy features. Spike clusters before seizure onset in TSC should be considered as a first stage of epilepsy reinforcing the concept of preventive antiepileptic therapy.

Early electro-clinical features may contribute to diagnosis of the anti-NMDA receptor encephalitis in children.

OBJECTIVE: To describe initial and follow-up electroencephalographic (EEG) characteristics in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. METHODS: Consecutive polygraphic video-EEG recordings were analyzed in nine pediatric patients with anti-NMDAR encephalitis at the initial stage of the disease and during the intermediate period until motor recovery. EEG characteristics in waking and sleep stages as well as EEG correlates of abnormal movements are described. RESULTS: In six patients, [corrected] the waking EEG showed preserved background activity and either focal or unilateral hemispheric slowing. These children had more favorable outcome than the three children with diffuse slowing. Unilateral [corrected] abnormal movements contra-lateral to hemispheric or focal slowing were also indicative of milder severity when compared to generalized abnormal movements and diffuse slowing. During non-rapid eye movement (NREM) sleep, a decrease in the expected slow waves and unilateral or diffuse theta-alpha band rhythms were observed in six children, not correlated with the outcome, representing a suggestive EEG pattern of anti-NMDAR encephalitis. [corrected]. CONCLUSIONS: In pediatric patients presenting behavioral disorders and abnormal movements, early EEG patterns may be suggestive of anti-NMDAR encephalitis. Moreover early electro-clinical presentation contributes to outcome prediction. SIGNIFICANCE: This case series demonstrates that early EEG patterns may be suggestive of anti-NMDAR encephalitis in pediatric patients with behavioral disorders and abnormal movements.

Children often present with infantile spasms after herpetic encephalitis.

PURPOSE: To determine what epilepsy types occur after herpetic encephalitis and what are the determinant factors for subsequent infantile spasms. METHODS: We analyzed retrospectively the clinical history of 22 patients, referred to Necker and Saint Vincent de Paul Hospitals (Paris) through the French pediatric epilepsy network from March 1986 to April 2010 and who developed epilepsy some months after herpetic encephalitis. We focused on seizure semiology with video-electroencephalography (EEG) recording, and on neuroradiology and epilepsy follow-up. KEY FINDINGS: Fourteen patients developed pharmacoresistant spasms, and eight developed focal epilepsy, but none had both. The patients who developed spasms were more frequently younger than 30 months at age of onset of epilepsy and had herpetic encephalitis earlier (mean 10.6 months of age) than those who developed focal epilepsy (mean 59.7 and 39.6 months, respectively). Epilepsy follow-up was similar in both groups (8.5 and 11 years, respectively). We found 26 affected cerebral areas; none alone was related to the development of epileptic spasms. SIGNIFICANCE: Risk factors to develop epileptic spasms were to have had herpetic encephalitis early (mean 10 months); to be significantly younger at onset of epilepsy (mean 22.1 months); and to have cerebral lesions involving the insula, the hippocampus, and the temporal pole.