Paroxysmal EEG Activity Research Articles

A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study to Evaluate the Safety and Efficacy of XEN1101 as an Adjunctive Therapy in the Treatment of Primary Generalized Tonic-Clonic Seizures (P11-1.012)

A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study to Evaluate the Safety and Efficacy of XEN1101 as an Adjunctive Therapy in the Treatment of Primary Generalized Tonic-Clonic Seizures (P11-1.012)

Kv1.1 channels inhibition in the rat motor cortex recapitulates seizures associated with anti-LGI1 encephalitis.

Autoimmune encephalitis associated with antibodies directed against the leucine-rich glioma inactivated 1 (LGI1) protein is responsible for specific tonic-dystonic motor seizures. Although dysfunctions in neuronal excitability have been associated with anti-LGI1 autoantibodies, their relation to seizures remain inconclusive. We developed a new in vivo experimental rat model to determine whether inhibition of Kv1.1 channels by dentrotoxin-K (DTX) in the primary motor cortex (M1) could recapitulate the human seizures and to elucidate their subtending cortical mechanisms. Comparing electro-clinical features of DTX-induced seizures in rats with those recorded from a cohort of anti-LGI1 encephalitis patients revealed striking similarities in their electroencephalographic (EEG) signature, frequency of recurrence and semiology. By combining multi-site extracellular and intracellular recordings of M1 pyramidal neurons in DTX rats, we demonstrated that the blockade of Kv1.1 channels induced a sequence of changes in neuronal excitability and synaptic activity, leading to massive suprathreshold membrane depolarizations underlying the paroxysmal EEG activity. Our results suggest the central role of Kv1.1 channels disruption in the emergence of anti-LGI1-associated seizures and suggest that this new rodent model could serve future investigations on ictogenesis in autoimmune encephalitis.

Analysis of Clinical Characteristics, Background, and Paroxysmal Activity in EEG of Patients with Juvenile Myoclonic Epilepsy.

Juvenile myoclonic epilepsy (JME) appears in adolescence with myoclonic, absence, and generalized tonic clonic (GTC) seizures with paroxysmal activity of polyspike and slow wave (PSW), or spike and wave (SW) complexes in EEG. Our aim was to analyze the clinical characteristics, background EEG activity, and paroxysmal events in 41 patients with JME. Background EEG activity was analyzed with visual, quantitative (QEEG), and neurometric parameters. Our JME patients started with absence seizures at 11.4 ± 1.5 years old, myoclonic seizures at 13.6 ± 2.5 years, and GTC seizures at 15.1 ± 0.8 years. The seizures presented in awakening at 7:39 h with sleep deprivation, alcoholic beverage intake, and stress as the most frequent precipitant factors. Paroxysmal activity was of PSW and fast SW complexes with 40.5 ± 62.6 events/hour and a duration of 1.7 s. Right asymmetric paroxysmal activity was present in 68.3% of patients. Background EEG activity was abnormal in 31.7% of patients with visual analysis. With QEEG beta AP (absolute power) increase and AP delta decrease were the most frequent abnormalities found. Spectral analysis showed that 48.7% of patients had normal results, and 26.83% and 24.4% had higher and lower frequencies than 10.156 Hz, respectively. We concluded that, with visual analysis, background EEG activity was abnormal in a few patients and the abnormalities increased when QEEG was used.

Automatic detection of generalized paroxysmal fast activity in interictal EEG using time-frequency analysis

ObjectiveMarkup of generalized interictal epileptiform discharges (IEDs) on EEG is an important step in the diagnosis and characterization of epilepsy. However, manual EEG markup is a time-consuming, subjective, and the specialized task where the human reviewer needs to visually inspect a large amount of data to facilitate accurate clinical decisions. In this study, we aimed to develop a framework for automated detection of generalized paroxysmal fast activity (GPFA), a generalized IED seen in scalp EEG recordings of patients with the severe epilepsy of Lennox-Gastaut syndrome (LGS). MethodsWe studied 13 children with LGS who had GPFA events in their interictal EEG recordings. Time-frequency information derived from manually marked IEDs across multiple EEG channels was used to automatically detect similar events in each patient's interictal EEG. We validated true positives and false positives of the proposed spike detection approach using both standalone scalp EEG and simultaneous EEG-functional MRI (EEG-fMRI) recordings. ResultsGPFA events displayed a consistent low-high frequency arrangement in the time-frequency domain. This ‘bimodal’ spectral feature was most prominent over frontal EEG channels. Our automatic detection approach using this feature identified EEG events with similar time-frequency properties to the manually marked GPFAs. Brain maps of EEG-fMRI signal change during these automatically detected IEDs were comparable to the EEG-fMRI brain maps derived from manual IED markup. ConclusionGPFA events have a characteristic bimodal time-frequency feature that can be automatically detected from scalp EEG recordings in patients with LGS. The validity of this time-frequency feature is demonstrated by EEG-fMRI analysis of automatically detected events, which recapitulates the brain maps we have previously shown to underlie generalized IEDs in LGS. SignificanceThis study provides a novel methodology that enables a fast, automated, and objective inspection of generalized IEDs in LGS. The proposed framework may be extendable to a wider range of epilepsy syndromes in which monitoring the burden of epileptic activity can aid clinical decision-making and faster assessment of treatment response and estimation of future seizure risk.

Automated Source Estimation of Scalp EEG Epileptic Activity Using eLORETA Kurtosis Analysis

Objectives: eLORETA (exact low-resolution brain electromagnetic tomography) is a technique created by Pascual-Marqui et al. [Int J Psychophysiol. 1994 Oct; 18(1): 49–65] for the 3-dimensional representation of current source density in the brain by electroencephalography (EEG) data. Kurtosis analysis allows for the identification of spiky activity in the brain. In this study, we focused on the evaluation of the reliability of eLORETA kurtosis analysis. For this purpose, the results of eLORETA kurtosis source localization of paroxysmal activity in EEG were compared with those of eLORETA current source density (CSD) analysis of EEG data in 3 epilepsy patients with partial seizures. Methods: EEG was measured using a digital EEG system with 19 channels. We set the bandpass filter at traditional frequency band settings (1–4, 4–8, 8–15, 15–30, and 30–60 Hz) and 5–10 and 20–70 Hz and performed eLORETA kurtosis to compare the source localization of paroxysmal activity with that of visual interpretation of EEG data and CSD analysis of eLORETA in focal epilepsy patients. Results: The eLORETA kurtosis analysis of EEG data preprocessed by bandpass filtering from 20 to 70 Hz and traditional frequency band settings did not show any discrete paroxysmal source activity compatible with the results of CSD analysis of eLORETA. In all 3 cases, eLORETA kurtosis analysis filtered at 5–10 Hz showed paroxysmal activities in the theta band, which were all consistent with the visual inspection results and the CSD analysis results. Discussion: Our findings suggested that eLORETA kurtosis analysis of EEG data might be useful for the identification of spiky paroxysmal activity sources in epilepsy patients. Since EEG is widely used in the clinical practice of epilepsy, eLORETA kurtosis analysis is a promising method that can be applied to epileptic activity mapping.

Antiepileptics and NO-precursors may be beneficial for stroke-like episodes.

Pathogenesis and management of stroke-like episodes in mitochondrial disorders is under debate and no consensus has been reached thus far how this phenomenon should be managed. Frequently applied are nitric oxide (NO) precursors but a well-designed study confirming the effectiveness of such an approach is lacking. Administration of antiepileptic drugs can be meaningful if there is paroxysmal activity on EEG or if a patient presents with seizures. The case reported by Sakai et al. suggests that administration of antiepileptic drugs for a stroke-like episode may be beneficial even in the absence of seizures or paroxysmal EEG activity.

Early Intervention With Adrenocorticotropin for Acute Encephalopathy-Associated Epileptic Spasms: Report of Two Cases

Acute encephalopathy with biphasic seizures and reduced diffusion (AESD) is a leading cause of childhood-onset encephalopathy in Japan. Children with AESD frequently develop intractable epilepsy, whereas their treatment options remain to be determined. We present 2 unrelated girls, who developed AESD at 25 months (case 1) and 12 months of age (case 2). Both cases underwent intensive cares from the first day of illness, whereas severe neurological impairments were left on discharge. They showed repeated signs of epileptic spasms at 2 months (case 1) and 8 months (case 2) after the onset of AESD. Video-monitoring electroencephalograms (EEG) detected the recurrent attacks accompanying slow-wave bursts and transient suppressions of the precedent epileptiform discharges, as typically observed in epileptic spasms. Intramuscular injection of adrenocorticotropic hormone (ACTH, 0.0125 mg/kg/d) was introduced within 1 month from the onset of epileptic spasms and continued for 2 weeks. The ACTH treatment disrupted the paroxysmal activity in EEG, and it has relieved these patients from epileptic seizures for more than 1 year. This report illustrates the potential efficacy of ACTH for a group of children with epileptic spasms after AESD.

Epileptiform and periodic EEG activities induced by rapid sevoflurane anaesthesia induction

ObjectivesThe aim of the study was to compare the EEG findings and haemodynamic parameters of adult male patients while undergoing mask induction with sevoflurane anaesthesia with either controlled hyperventilation (CH) or spontaneous breathing (SB). MethodsTwenty male patients, aged 23–52 (mean 42) years were anaesthetized randomly with either spontaneous breathing or mild controlled hyperventilation via mask. EEG was recorded using a full 10–20 electrode set. ResultsAnaesthesia induction with high inhaled concentrations of sevoflurane produced several epileptiform and periodic EEG patterns. CH doubled the amount of these EEG patterns compared to SB. Higher heart rate was recorded in the CH group. ConclusionsWe describe a high incidence of paroxysmal EEG activity: epileptiform and generalized periodic discharges (GPDs) during rapid sevoflurane in nitrous oxide-oxygen mask induction in hyperventilated male patients. However these activities have no effect to the heart rate or the mean arterial pressure. SignificanceThe monitoring of GPDs and burst suppression patterns during rapid anaesthesia induction with sevoflurane provides possibility to study the effects of volatile anaesthetics in the healthy brain. In order to analyse the different sources of EEG patterns a wide-band multichannel EEG recording is necessary.

Generalized paroxysmal fast activity in EEG: An unrecognized finding in genetic generalized epilepsy

ObjectiveTo study generalized paroxysmal fast activity (GPFA) in patients with genetic generalized epilepsy (GGE). IntroductionGPFA is an electroencephalographic (EEG) finding in patients with symptomatic generalized epilepsy consisting of 15-25Hz bifrontally predominant generalized fast activity seen predominantly in sleep. Historically GPFA is linked to epileptic encephalopathy with drug resistant epilepsy and intellectual disability. However, GPFA has been rarely described as an atypical finding in patients with GGE without negative prognostic implication. We report cognitive profile and seizure characteristics in seven patients with GGE and GPFA. MethodsThe Vanderbilt EMU and EEG reports were searched for the keywords “idiopathic generalized epilepsy”, “GPFA”and “generalized spike and wave discharges (GSWD)”. We reviewed the EEG tracings and the electronic medical records of patients thus identified. The seizure type, frequency, neurological work-up, clinical profile and imaging data were recorded. ResultsAwake and sleep states were captured on EEGs of all patients. On EEG tracing review six patients were confirmed to have GSWD and GPFA; one patient had GPFA but no GSWD. All patients had normal cognitive function. Four had a normal brain MRI and one a normal head CT (two were never imaged). None of the patients had tonic seizures. The main seizure type was generalized tonic-clonic seizures (GTCS) in five patients, absence in two. Age at onset of epilepsy ranged from 4 to 24years. The mean GTC seizure frequency at the time of EEG was 3; two patients were seizure free on two antiepileptic drugs (AEDs). ConclusionsGPFA can be an unrecognized electrographic finding in patients with genetic generalized epilepsy. While GPFA remains an important diagnostic EEG feature for epileptic encephalopathy (Lennox-Gastaut syndrome) it is not specific for this diagnosis. Thus, GPFA may have a spectrum of variable phenotypic expression. The finding of GPFA is not necessarily indicative of unfavorable outcome.

Generalized Paroxysmal Fast Activity in EEG: not an uncommon finding in genetic generalized epilepsy (P2.226)

Generalized Paroxysmal Fast Activity in EEG: not an uncommon finding in genetic generalized epilepsy (P2.226)

Stroke-like episodes, peri-episodic seizures, and MELAS mutations.

Stroke-like episodes (SLEs) are a hallmark of various mitochondrial disorders, in particular MELAS syndrome. SLEs manifest with vasogenic oedema (DWI and ADC hyperintensity) or partial cytotoxic oedema (DWI hyperintensity, ADC hypointensity) in the acute and subacute stage, and with gyriform T1-hyperintensity (cortical necrosis) in the chronic stage. SLEs must be clearly distinguished from ischaemic stroke, since management of these two entities is different. SLEs may go along with or without seizures or epileptiform discharges on EEG. However, in MELAS syndrome seizures may also occur in the absence of SLEs. Focal and generalised seizures have been reported but it is currently unknown if the one or the other prevail. SLEs with and without seizures may respond to NO-precursors l-arginine, succinate, or citrulline. As a supportive measure a ketogenic diet should be initiated. Seizures prior to or during a SLE or paroxysmal EEG-activity during a SLE should be initially treated with antiepileptic drugs (AEDs) with low mitochondrion-toxicity. Only in case these AEDs are ineffective, AEDs with higher mitochondrion-toxicity should be added. All patients with SLEs need to have an EEG recorded irrespective if they have manifesting seizures or not. There are no mtDNA or nDNA mutations which predispose for SLEs with seizures.

Functional neurotoxicity evaluation of noribogaine using video-EEG in cynomolgus monkeys

IntroductionContinuous video-electroencephalographic (EEG) monitoring remains the gold standard for seizure liability assessments in preclinical drug safety assessments. EEG monitored by telemetry was used to assess the behavioral and EEG effects of noribogaine hydrochloride (noribogaine) in cynomolgus monkeys. Noribogaine is an iboga alkaloid being studied for the treatment of opioid dependence. MethodsSix cynomolgus monkeys (3 per gender) were instrumented with EEG telemetry transmitters. Noribogaine was administered to each monkey at both doses (i.e., 160 and 320mg/kg, PO) with an interval between dosing of at least 6days, and the resulting behavioral and EEG effects were evaluated. IV pentylenetetrazol (PTZ), served as a positive control for induced seizures. ResultsThe administration of noribogaine at either of the doses evaluated was not associated with EEG evidence of seizure or with EEG signals known to be premonitory signs of increased seizure risk (e.g., sharp waves, unusual synchrony, shifts to high-frequency patterns). Noribogaine was associated with a mild reduction in activity levels, increased scratching, licking and chewing, and some degree of poor coordination and related clinical signs. A single monkey exhibited brief myoclonic movements that increased in frequency at the high dose, but which did not appear to generalize, cluster or to be linked with EEG abnormalities. Noribogaine was also associated with emesis and partial anorexia. In contrast, PTZ was associated with substantial pre-ictal EEG patterns including large amplitude, repetitive sharp waves leading to generalized seizures and to typical post-ictal EEG frequency attenuation. InterpretationEEG patterns were within normal limits following administration of noribogaine at doses up to 320mg/kg with concurrent clinical signs that correlated with plasma exposures and resolved by the end of the monitoring period. PTZ was invariably associated with EEG paroxysmal activity leading to ictal EEG. In the current study, a noribogaine dose of 320mg/kg was considered to be the EEG no observed adverse effect level (NOAEL) in conscious freely moving cynomolgus monkeys.

PP13.2 – 3042: Infantile spasms in an infant with anti-NMDA receptor encephalitis secondary to HSV-1 encephalitis

Objective The recent identification of NMDAR antibodies causing choreoatethosis post-herpes simplex encephalitis (HSE) has provided a proof of principle that relapsing symptoms post-HSE are immune mediated. We report the first patient with anti-NMDAR encephalitis post-HSE and infantile spasms. Methods Review of patient's clinical information. Immunological studies as previously reported. Results An 11-month-old boy was admitted to our Pediatric Intensive Care Unit for status epilepticus and fever. The CSF showed 25 WBC/uL and the PCR was positive for HSV1. Intravenous acyclovir was started and over the next days 3 days he developed simple partial seizures that were initially well controlled with valproate (VPA). On day 19th after HSE onset he was readmitted for irritability, impaired interaction, involuntary movements (head shaking and facial twitching), and spasms with EEG hypsarrhythmia. The CSF revealed mild pleocytosis, negative HSV-1 PCR and high titers of NMDAR antibodies. Repeated MRI showed progression of T2/FLAIR abnormalities and intense contrast enhancement that was not present in previous studies. He was treated with midazolam, VPA, vigabatrin and immunotherapy (iv methylprednisolone, IVIg, rituximab, cyclophosphamide) without symptom improvement. Spasms and EEG paroxysmal activity progressively worsened and evolved towards a super-refractory status epilepticus, which was eventually controlled with barbiturate coma, lacosamide and ketogenic diet (KD). Seventy days after HSE onset he underwent plasma exchange for persisting coma and generalized choreoathetosis with partial clinical improvement of symptoms. KD was discontinued after 3 months of seizure control and EEG activity improvement. Conclusion Early onset infantile spasms post-HSE can be caused by anti-NMDAR encephalitis. Recent advances in the genetics of West syndrome (GRIN2B mutations – encoding the NR2B subunit of the NMDA receptor) and the animal model for West syndrome (induced by NMDA) support this hypothesis. Plasma exchange and KD were the most effective treatments in our patient.

Conservative and surgical treatment of patients with resistant epilepsy

To optimize drug treatment in early (6 months) and late (up to 3 years) stages of postoperative period and to study its efficacy. There were selected 72 patients with resistant epilepsy and epileptic encephalopathy symptoms from 467 patients operated for epilepsy. By the end of a 3-year follow-up observation, we found the reduction in seizure frequency and seizure control in 66.3% of patients; regression of EEG paroxysmal activity in 56.8% and reduction in mental disorder symptoms (anxiety and depression) in 12.7%. The data obtained substantiate the necessity to optimize antiepileptic and pathogenetic drug treatment of patients with resistant epilepsy and encephalopathy symptoms during the 3-year postoperative period.

In search of the Rosetta Stone for ESES

We read with interest the report by Sanchez Fernandez et al. (2012) describing a lack of a common language among North-American pediatric epileptologists regarding encephalopathy with electrical status epilepticus during sleep or continuous spike-and-wave during sleep (ESES/CSWS) and related conditions. In this paper, the authors suggested the use of ‘‘ESES’’ when referring to the EEG pattern, and ‘‘CSWS’’ when referring to the epileptic encephalopathy. However this suggestion was not supported by an explanation or by survey results. In our view, there is no reason to consider the term “ESES” as indicative of EEG pattern, or for “CSWS” as the syndrome. Indeed, “CSWS” is

Standardized database development for EEG epileptiform transient detection: EEGnet scoring system and machine learning analysis

The routine scalp electroencephalogram (rsEEG) is the most common clinical neurophysiology procedure. The most important role of rsEEG is to detect evidence of epilepsy, in the form of epileptiform transients (ETs), also known as spike or sharp wave discharges. Due to the wide variety of morphologies of ETs and their similarity to artifacts and waves that are part of the normal background activity, the task of ET detection is difficult and mistakes are frequently made. The development of reliable computerized detection of ETs in the EEG could assist physicians in interpreting rsEEGs. We report progress in developing a standardized database for testing and training ET detection algorithms. We describe a new version of our EEGnet software system for collecting expert opinion on EEG datasets, a completely web-browser based system. We report results of EEG scoring from a group of 11 board-certified academic clinical neurophysiologists who annotated 30-s excepts from rsEEG recordings from 100 different patients. The scorers had moderate inter-scorer reliability and low to moderate intra-scorer reliability. In order to measure the optimal size of this standardized rsEEG database, we used machine learning models to classify paroxysmal EEG activity in our database into ET and non-ET classes. Based on our results, it appears that our database will need to be larger than its current size. Also, our non-parametric classifier, an artificial neural network, performed better than our parametric Bayesian classifier. Of our feature sets, the wavelet feature set proved most useful for classification.

Sleep-disordered breathing in children with congenital muscular dystrophies

ObjectiveMost types of neuromuscular diseases are known to be associated with a high risk of sleep-disordered breathing. We performed a prospective study in a well individualized group of muscular disorders, congenital muscular dystrophies (CMD), to characterize the frequency of sleep-disordered breathing and thereby to determine the potential usefulness of sleep studies in such patients. MethodsTwenty CMD children (12 F, 8 M, aged 4–17 years) were included. Using overnight polysomnography, we determined the following parameters: sleep stages, sleep latency, sleep efficiency index, wake time duration, total sleep time (TST), apnea/hypopnea index (AHI), arterial blood oxygen saturation, and nocturnal paroxysmal EEG activity. ResultsAs compared to healthy controls, we detected in our study group frequent awakenings, a decreased TST (mean 448 ± 44.4 min) and a decreased REM duration (mean 11.5 ± 3.5% of TST). Significant increase in wake time duration (28–90 min) and decrease in REM duration were observed in 12 patients. An apnea/hypopnea syndrome was detected in 13 patients (65%) with central apneas in 8, obstructive apneas in 2 and 3 mixed apneas in 3 patients. AHI was >10 in 3 cases, <10> 5 in 4 cases and were concomitant with blood oxygen de-saturation in four cases. NPA were detected in 10 patients ranging from 10 to 40% of TST. InterpretationOur results confirm the high incidence of sleep disordered breathing in children with CMD, and thereby, the usefulness of overnight polysomnography recordings in such patients.

Cortical hyperexcitability in migraine and aversion to patterns

Patients with migraine are averse to certain visual stimuli, such as flicker and striped patterns that evoke paroxysmal EEG activity in patients with photosensitive epilepsy. Migraineurs demonstrate a hyper-responsiveness to such stimuli, and there is debate as to whether the aversion and hyper-responsiveness are due to a hyperexcitability of the cortex similar to that in patients with photosensitive epilepsy. In these patients grating patterns with certain spatial characteristics can be epileptogenic, depending critically on their movement. If the contours of the grating drift continually, the grating is not epileptogenic, but if the contours are static or if their direction is repeatedly and rapidly reversed so as to vibrate, the grating then becomes highly epileptogenic. We compared aversion to vibrating, drifting and static gratings in migraineurs and controls. The contrast of each grating was gradually increased, but only until the participant felt discomfort, so as to obtain a contrast threshold for aversion with minimal exposure. Migraineurs had lower thresholds than the control group, indicating greater aversion. For both groups the threshold was higher (aversion was lower) for static than for both types of moving gratings. The drifting gratings were more aversive than the vibrating gratings when both groups were combined. The findings suggest that the aversion shown by migraineurs is not attributable to a cortical hyperexcitability similar to that in photosensitive epilepsy.

Epileptic and nonepileptic features in patients with early onset epileptic encephalopathy and STXBP1 mutations

STXBP1 (MUNC18-1) mutations have been associated with various types of epilepsies, mostly beginning early in life. To refine the phenotype associated with STXBP1 aberrations in early onset epileptic syndromes, we studied this gene in a cohort of patients with early onset epileptic encephalopathy. STXBP1 was screened in a multicenter cohort of 52 patients with early onset epilepsy (first seizure observed before the age of 3 months), no cortical malformation on brain magnetic resonance imaging (MRI), and negative metabolic screening. Three groups of patients could be distinguished in this cohort: (1) Ohtahara syndromes (n = 38); (2) early myoclonic encephalopathies (n = 7); and (3) early onset epileptic encephalopathies that did not match any familiar syndrome (n = 7). None of the patients displayed any cortical malformation on brain MRI and all were screened through multiple video-electroencephalography (EEG) recordings for a time period spanning from birth to their sixth postnatal month. Subsequently, patients had standard EEG or video-EEG recordings. We found five novel STXBP1 mutations in patients for whom video-EEG recordings could be sampled from the beginning of the disease. All patients with a mutation displayed Ohtahara syndrome, since most early seizures could be classified as epileptic spasms and since the silent EEG periods were on average shorter than bursts. However, each patient in addition displayed a particular clinical and EEG feature: In two patients, early seizures were clonic, with very early EEG studies exhibiting relatively low amplitude bursts of activity before progressing into a typical suppression-burst pattern, whereas the three other patients displayed epileptic spasms associated with typical suppression-burst patterns starting from the early recordings. Epilepsy dramatically improved after 6 months and finally disappeared before the end of the first year of life for four patients; the remaining one patient had few seizures until 18 months of age. In parallel, EEG paroxysmal abnormalities disappeared in three patients and decreased in two, giving place to continuous activity with fast rhythms. Each patient displayed frequent nonepileptic movement disorders that could easily be mistaken for epileptic seizures. These movements could be observed as early as the neonatal period and, unlike seizures, persisted during all the follow-up period. We confirm that STXBP1 is a major gene to screen in cases of Ohtahara syndrome, since it is mutated in >10% of the Ohtahara patients within our cohort. This gene should particularly be tested in the case of a surprising evolution of the patient condition if epileptic seizures and EEG paroxysmal activity disappear and are replaced by fast rhythms after the end of the first postnatal year.

Sleep disorders in succinic semialdehyde dehydrogenase deficiency: A family report

Background Succinic semialdehyde dehydrogenase deficiency (SSADH) is a rare neurometabolic disorder involving the degradation of γ-aminobutyric acid. Clinically, SSADH deficiency causes progressive or static encephalopathy with late infantile to early childhood onset. It is known that sleep disorders are a common clinical finding in these patients. However, very few studies have investigated sleep disorders with polysomnographies. Aim of the study To analyze sleep disorders breathing, sleep architecture and paroxysmal EEG activity through polysomnographic recordings of two siblings suffering from SSADH deficiency Method Each patient underwent laboratory diurnal and overnight video-polysomnographic recordings in a room specially dedicated to mothers and their children. Results The background EEG activity during quiet wakefulness consisted in abnormal, diffuse, low-voltage, disorganized slow theta waves. In both patients there was a general disorganisation of the sleep architecture with an increase of light sleep and a decrease of REM sleep. In patient 1, during sleep, there were 36 hypopneas, 13 central apneas and one obstructive apnea with a variable duration of 7–30 s. The apnea/hypopnea index (AHI) was 7/h and oxygen saturation dropped to 80% during the respiratory events. In patient 2, the respiratory events consisted in 8 central apneas and 23 hypopneas of 6–20 s; no obstructive apneas or hypopneas were observed. The oxygen saturation dropped to 90% during the apneas and the AHI was 5/h. Conclusion Sleep-disordered breathing (SDB) is a common finding in patients with SSADH deficiency and polysomnography recording is a useful tool for its diagnosis.