Sharp Waves Research Articles

Amyotrophic lateral sclerosis mimicking radiculopathy: a case series.

ABSTRACTThe clinical findings of early stage amyotrophic lateral sclerosis (ALS) are similar to those of cervical or lumbar radiculopathy. In the current study, we describe 3 cases of ALS that were misdiagnosed as cervical or lumbar radiculopathy. Three patients (a 48-, a 52-, and an 80-year-old) visited our clinic due to motor weakness on either the upper or lower extremities. At other clinics or hospitals, they were diagnosed with radiculopathy due to herniated lumbar disc or cervical foraminal stenosis. The motor weakness in these patients was ipsilateral or bilateral but dominant on one side. Sensory deficits or bulbar symptoms were not observed. Of the 3 patients, 2 had neuropathic pain, but it was not dermatome related. We conducted an electrodiagnostic test and observed a low amplitude of compound motor action potential on the affected nerve and positive sharp waves on muscles of involved segments, including thoracic paraspinalis. All the patients were diagnosed with probable laboratory-supported ALS or possible ALS based on the established diagnostic criteria (El Escorial Criteria). In the present study, we showed three cases of ALS that were misdiagnosed as radiculopathy. Our study would be helpful for early and accurate diagnosis of patients with ALS.

Migratory Rolandic Encephalopathy Caused by the Mitochondrial ND3 Variant.

An 18-year-old woman was admitted to the hospital with focal seizures. Serial MRI studies showed migratory rolandic lesions (Figure, A–D) and the EEG showed sharp waves when the lesion appeared. The initial differential diagnosis included cerebral venous thrombosis, myelin oligodendrocyte glycoprotein antibody-associated disease, and metabolic disorders. Magnetic resonance venography, serum, and CSF analyses were unrevealing. An analysis of the entire mtDNA of urine sediment by next-generation sequencing showed a pathogenic m.10191T>C variant in the mt-ND3 gene (degree of heteroplasmy, 87%). Further analysis revealed the m.10191T>C variant was heteroplasmic in blood (24%) and oral mucosal (86%) cells. This case illustrates that m.10191T>C variant may present with migratory rolandic encephalopathy.1

A Long Time Constant May Endorse Sharp Waves and Spikes Over Sharp Transients in Scalp Electroencephalography: A Comparison of After-Slow Among Different Time Constants Concordant With High-Frequency Activity Analysis.

Objective: To clarify whether long time constant (TC) is useful for detecting the after-slow activity of epileptiform discharges (EDs): sharp waves and spikes and for differentiating EDs from sharp transients (Sts).Methods: We employed 68 after-slow activities preceded by 32 EDs (26 sharp waves and six spikes) and 36 Sts from 52 patients with partial and generalized epilepsy (22 men, 30 women; mean age 39.08 ± 13.13 years) defined by visual inspection. High-frequency activity (HFA) associated with the apical component of EDs and Sts was also investigated to endorse two groups. After separating nine Sts that were labeled by visual inspection but did not fulfill the amplitude criteria for after-slow of Sts, 59 activities (32 EDs and 27 Sts) were analyzed about the total area of after-slow under three TCs (long: 2 s; conventional: 0.3 s; and short: 0.1 s).Results: Compared to Sts, HFA was found significantly more with the apical component of EDs (p < 0.05). The total area of after-slow in all 32 EDs under TC 2 s was significantly larger than those under TC 0.3 s and 0.1 s (p < 0.001). Conversely, no significant differences were observed in the same parameter of 27 Sts among the three different TCs. Regarding separated nine Sts, the total area of after-slow showed a similar tendency to that of 27 Sts under three different TCs.Significance: These results suggest that long TC could be useful for selectively endorsing after-slow of EDs and differentiating EDs from Sts. These findings are concordant with the results of the HFA analysis. Visual inspection is also equally good as the total area of after-slow analysis.

Abdominal Segmental Myoclonus Mimicking Belly Dancer Dyskinesias in CASPR2 Antibody Encephalomyelitis.

An 86-year-old man presented with continuous movements of the abdominal wall (abdominal segmental myoclonus mimicking a belly dancer), gait unsteadiness, progressive cognitive deficit, episodic symptomatic hypotension, and diaphoresis for 2 months. Clinical examination confirmed cognitive dysfunction, and showed bilateral proximal muscle weakness of the upper and lower limbs and absent deep tendon reflexes. The Video shows the presence of spontaneous rhythmic, continuous, sinuous movements involving the abdominal muscles (Video 1). MRI of the spinal cord and the brain were normal. Electroencephalography showed generalized background slowing in the absence of epileptiform discharges. Polymyographic studies revealed rhythmic (about 2 Hz) electromyography bursts with variable duration of 500 to 1000 ms present with synchronous onset in the rectus abdominis and paravertebral muscles (Fig. 1). Detailed blood analysis was normal except for the presence of contactin-associated protein-like 2 (CASPR2) antibodies (IgG ≥1:40960). Cerebrospinal fluid analyses showed the presence of oligoclonal bands and CASPR2 antibody (IgG ≥1:160). Other anti-neuronal antibodies were absent, both on blood and cerebrospinal fluid analyses. Thoraco-abdominal-pelvic CT and whole-body FDG-PET did not show thymoma or other neoplasia. A diagnosis of CASPR2 antibody-related encephalomyelitis was made. Treatment with intravenous immunoglobulin and oral corticosteroids was started. Because of the absence of clinical improvement, plasma exchange and rituximab treatment were started leading to dramatic improvement of abdominal myoclonus but moderate effect on gait unsteadiness and cognitive deficit. CASPR2 is a membrane protein expressed in the central and peripheral nervous system, with its cytoplasmic domain essential for the function of potassium channel Kv1.1 clustering at the juxtaparanodes of myelinated axons. It is involved in neuronal excitability (i.e., stabilize conduction at nodes of Ranvier, and maintain resting potential) and synaptic transmission.1 CASPR2 antibodies induce a functional blocking of the potassium channel. CASPR2 antibody–associated disorders include acquired neuromyotonia, Morvan syndrome, limbic encephalitis, seizures and cerebellar ataxia. Diagnosis of CASPR2-related nervous system disorders is based on the clinical presentation and the presence of specific autoantibodies. Based on the earlier reported cases of CASPR2-associated encephalomyelitis, cerebral and spinal MRI is unremarkable in the majority of cases.2 T2/FLAIR hyperintensities can be observed in the medial temporal lobes especially in patients with cognitive deficit and seizures, and brainstem hyperintensities or cerebellar atrophy in patients presenting with ataxia. Focal (especially in the temporal regions) or diffuse slowing and sharp waves may be observed on electroencephalography. CASPR2 antibody-related encephalomyelitis are frequently associated with other autoimmune affections (including thyroiditis or myasthenia gravis), and paraneoplastic in a minority of cases (mainly related to thymoma).2 The most striking clinical feature in our case was the presence of rhythmic abdominal myoclonus resembling belly dance. Belly dancer myoclonus is a segmental myoclonus considered to be of spinal origin involving sometimes also diaphragm muscles. Lower limb myoclonus while standing or walking has been earlier reported as a movement disorder phenotype in CASPR2 antibody-related encephalomyelitis.3, 4 One patient with spinal myoclonus has been reported with clinical lower limb myoclonus associated with abdominal myoclonus only observed by electromyography.5 To the best of our knowledge, this is the first case of clinical abdominal myoclonus associated with CASPR2 antibodies. We would like to thank Drs Anne-Laurie Pinto and Sergio Muniz-Castrillo for the analysis of CSF samples. We would like to thank Dr Sarah Coudray for the attainment and interpretation of the electrophysiological data. (1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript: A. Writing of the first draft, B. Review and Critique. L.K.: 1A, 2C, 3A D.R.: 2C, 3B J.H.: 1C, 2B G.C.: 1A, 2C, 3A, 3B The present work respects ethical guidelines. The authors confirm that the approval of an institutional review board was not required for this work. Written consent was obtained for showing the patients' video. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. The authors declare that there are no funding sources or conflicts of interest relevant to this work. The authors declare that there are no additional disclosures to report.

Antibiotic-induced gut dysbiosis leads to activation of microglia and impairment of cholinergic gamma oscillations in the hippocampus

Antibiotics are widely applied for the treatment of bacterial infections, but their long-term use may lead to gut flora dysbiosis and detrimental effects on brain physiology, behavior as well as cognitive performance. Still, a striking lack of knowledge exists concerning electrophysiological correlates of antibiotic-induced changes in gut microbiota and behavior. Here, we investigated changes in the synaptic transmission and plasticity together with behaviorally-relevant network activities from the hippocampus of antibiotic-treated mice. Prolonged antibiotic treatment led to a reduction of myeloid cell pools in bone marrow, circulation and those surveilling the brain. Circulating Ly6Chi inflammatory monocytes adopted a proinflammatory phenotype with increased expression of CD40 and MHC II. In the central nervous system, microglia displayed a subtle activated phenotype with elevated CD40 and MHC II expression, increased IL-6 and TNF production as well as with an increased number of Iba1 + cells in the hippocampal CA3 and CA1 subregions. Concomitantly, we detected a substantial reduction in the synaptic transmission in the hippocampal CA1 after antibiotic treatment. In line, carbachol-induced cholinergic gamma oscillation were reduced upon antibiotic treatment while the incidence of hippocampal sharp waves was elevated. These alterations were associated with the global changes in the expression of neurotrophin nerve growth factor and inducible nitric oxide synthase, both of which have been shown to influence cholinergic system in the hippocampus. Overall, our study demonstrates that antibiotic-induced dysbiosis of the gut microbiome and subsequent alteration of the immune cell function are associated with reduced synaptic transmission and gamma oscillations in the hippocampus, a brain region that is critically involved in mediation of innate and cognitive behavior.

Sharp-Wave Ripple Frequency and Interictal Epileptic Discharges Increase in Tandem During Thermal Induction of Seizures in a Mouse Model of Genetic Epilepsy.

Dravet Syndrome (DS) is a genetic, infantile-onset epilepsy with refractory seizures and severe cognitive impairment. While network level pathophysiology is poorly understood, work in genetic mouse models of DS reveals selective reduction of inhibitory interneuron excitability, a likely mechanism of seizures and comorbidities. Consistent with the critical role of interneurons in timing and recruitment of network activity, hippocampal sharp wave ripples (SPW-R)—interneuron dependent compound brain rhythms essential for spatial learning and memory—are less frequent and ripple frequency is slower in DS mice, both likely to impair cognitive performance. Febrile seizures are characteristic of DS, reflecting a temperature-dependent shift in excitation–inhibition balance. DS interneurons are sensitive to depolarization block and may fall silent with increased excitation precipitating epileptic transformation of ripples. To determine the temperature dependence of SWP-R features and relationship of SPW-R to hippocampal interictal activity, we recorded hippocampal local field potentials in a DS mouse model and wildtype littermate controls while increasing core body temperature. In both genotypes, temperature elevation speeds ripple frequency, although DS ripples remain consistently slower. The rate of SPW-R also increases in both genotypes but subsequently falls in DS mice as interictal epileptic activity simultaneously increases preceding a thermally-evoked seizure. Epileptic events occur intermixed with SPW-R, some during SPW-R burst complexes, and transiently suppress SPW-R occurrence suggesting shared network elements. Together these data demonstrate a temperature dependence of SPW-R rate and ripple frequency and suggest a pathophysiologic mechanism by which elevated temperature transforms a normal brain rhythm into epileptic event.

Electromyographic findings in primary lateral sclerosis during disease progression

ObjectiveTo characterize electromyographic (EMG) findings in patients with primary lateral sclerosis (PLS) during the disease course. MethodsIn PLS patients we scored spontaneous activity and motor unit action potential (MUP) pattern on EMG. We compared patients according to lower (group A) and higher (group B) EMG scores. EMG studies were repeated at intervals longer than 11 months; two or three repeat studies were required for inclusion in the analysis. ResultsWe studied 22 patients. Fasciculation potentials were found in 13 and fibrillations/positive sharp waves (fibs/sw) in 3 patients. Both were stable over time. Most patients had MUP abnormalities (n = 17), with worsening in the lower limbs in patients with three evaluations (p = 0.010). Compared to group A (n = 12), patients of group B (n = 10) had a significant shorter disease duration (median 10.9 vs 15.2 years, p < 0.001), lower functional score at both first (39 vs 45, p = 0.034) and last (29 vs 38, p = 0.003) evaluations, and had a faster functional decline (0.19 vs 0.08, p = 0.004). ConclusionsMost PLS patients showed minor and stable EMG abnormalities, without progression to ALS. Patients with more EMG abnormalities have a faster progression. SignificanceEMG abnormalities in most PLS patients are minor and stable.

Epidemiological and Clinical Characteristics of Sporadic Creutzfeldt-Jakob Disease: A Retrospective Study in Eastern China.

Objective: We aimed to characterize the epidemiological and clinical characteristics of sporadic Creutzfeldt–Jakob disease (sCJD) in eastern China in this retrospective study.Methods: This study enrolled 67 patients with sCJD hospitalized in a grade-A tertiary hospital in eastern China from January 2010 to January 2020. Demographic data, clinical symptoms, brain magnetic resonance imaging (MRI), electroencephalogram (EEG), cerebrospinal fluid (CSF) 14-3-3 protein test, polymerase chain reaction (PCR), and DNA sequence determination of genes were collected and analyzed.Results: There were 62 patients with probable sCJD and 5 patients with possible sCJD. Male (28 cases) to female (39 cases) ratio was 1:1.39. Mean age at disease onset was 64.42 ± 9.00 years (range: 29–88 years), and mean survival time was 9.39 ± 12.58 months (range: 1–60 months for patients who received the follow-ups). The most common onset symptoms were dementia (49.25%), movement disorder (44.78%), and visual disturbance (22.39%), while the most frequent clinical manifestations were language disorders (74.63%), ataxia (70.15%), and myoclonus (70.15%). The positive rates of brain MRI abnormalities, 14-3-3 protein in CSF, and periodic sharp wave complexes (PSWCs) on EEG were 84.90, 68.00, and 46.03%, respectively. The 14-3-3 protein positive (p = 0.033) and PSWCs on EEG (p = 0.020) acted as the favorable and unfavorable factor for over 1 year of survival time, respectively.Conclusions: There were some differences in epidemiological and clinical characteristics among patients in China and those of other countries. The prognosis and its influencing factors were relatively unexplored in China. The mean survival time of Chinese patients was longer than that of Caucasian patients but shorter than that of Japanese patients. The 14-3-3 protein in CSF and PSWCs on EEG were both closely related to the survival time. It is necessary to promote autopsy or biopsy to better understand sCJD in China.

Observation of nearshore crescentic sandbar formation during storm wave conditions using satellite images and video monitoring data

Crescentic nearshore sandbars (CNSBs) that are observed in the shallow waters (< 10 m) of sandy beaches are important for understanding coastal dynamics because of their strong interaction with nearshore circulation. However, their formation, originating from shore-parallel straight nearshore sandbars (SNSBs), has rarely been observed in the field because their occurrence is typically short (less than a week). In this study, a process in which a nearly SNSB changed into a fully developed CNSB was observed using satellite images, field surveys, and video monitoring data at a sandy beach in South Korea. Freely available Sentinel-2 satellite images and the bathymetry data measured by echosounders were used to find out formation of an SNSB system after attack of Typhoon Tapah in September 2019 and that the SNSB changed to a CNSB in February 2020. The process was narrowed down using video monitoring data and hydrodynamic measurements, observing that two storm waves with maximum wave heights of >3 m developed in the site over a one-month period in January 2020 when the CNSB formed. The first storm wave had a sharp peak wave height that reached ~5 m and lasted ~2 days. The second storm wave had lower wave energy but several peak waves of ~4 m height and a total storm period of ~6 days. During both storm periods, the infragravity wave energy increased and strong (>0.5 m/s) offshore and longshore (northwest) currents developed for ~1 day and ~ 3 days for the first and second storm respectively. The results from video monitoring data show that a nearly developed SNSB system transformed into a weakly developed CNSB system after the first storm when alongshore variability on the nearly SNSB was intensified to become horns and bays of the weak CNSB. During the second storm, the CNSB system fully developed as the horns moved further onshore and the bays further offshore shaping the clear horn and bay pattern. This indicates that positive feedback between the flows and sediments played a key role for the formation of the CNSB and, therefore, the self-organization mechanism might be appropriate to describe the process during the two storm periods. Specifically, the high infragravity wave energy and strong quasi-steady currents were important because they could trigger the development of rip channels during the first storm whereas the channels were further strengthened by the long consistency of currents during the second storm.

Disorganization of Oscillatory Activity in Animal Models of Schizophrenia.

Schizophrenia is a chronic, debilitating disorder with diverse symptomatology, including disorganized cognition and behavior. Despite considerable research effort, we have only a limited understanding of the underlying brain dysfunction. In this article, we review the potential role of oscillatory circuits in the disorder with a particular focus on the hippocampus, a region that encodes sequential information across time and space, as well as the frontal cortex. Several mechanistic explanations of schizophrenia propose that a loss of oscillatory synchrony between and within these brain regions may underlie some of the symptoms of the disorder. We describe how these oscillations are affected in several animal models of schizophrenia, including models of genetic risk, maternal immune activation (MIA) models, and models of NMDA receptor hypofunction. We then critically discuss the evidence for disorganized oscillatory activity in these models, with a focus on gamma, sharp wave ripple, and theta activity, including the role of cross-frequency coupling as a synchronizing mechanism. Finally, we focus on phase precession, which is an oscillatory phenomenon whereby individual hippocampal place cells systematically advance their firing phase against the background theta oscillation. Phase precession is important because it allows sequential experience to be compressed into a single 120 ms theta cycle (known as a ‘theta sequence’). This time window is appropriate for the induction of synaptic plasticity. We describe how disruption of phase precession could disorganize sequential processing, and thereby disrupt the ordered storage of information. A similar dysfunction in schizophrenia may contribute to cognitive symptoms, including deficits in episodic memory, working memory, and future planning.

Correlation between the occurrence of seizures and EEG results

Epilepsy is a state of electrical signal disturbance in the brain that manifests as seizures. Diagnosis of epilepsy with history, physical examination, and investigations. One of the investigations that help diagnose epilepsy is electroencephalography (EEG). The EEG result is abnormal if there are epileptogenic and non-epileptogenic waves such as sharp waves, spike waves, and amplitude abnormalities. This study aims to determine the relationship between seizure frequency and EEG result.

Effects of River-Ice Breakup on Sediment Transport and Implications to Stream Environments: A Review

During the breakup of river ice covers, a greater potential for erosion occurs due to rising discharge and moving ice and the highly dynamic waves that form upon ice-jam release. Consequently, suspended-sediment concentrations can increase sharply and peak before the arrival of the peak flow. Large spikes in sediment concentrations occasionally occur during the passage of sharp waves resulting from releases of upstream ice jams and the ensuing ice runs. This is important, as river form and function (both geomorphologic and ecological) depend upon sediment erosion and deposition. Yet, sediment monitoring programs often overlook the higher suspended-sediment concentrations and loads that occur during the breakup period owing to data-collection difficulties in the presence of moving ice and ice jams. In this review paper, we introduce basics of river sediment erosion and transport and of relevant phenomena that occur during the breakup of river ice. Datasets of varying volume and detail on measured and inferred suspended-sediment concentrations during the breakup period on different rivers are reviewed and compared. Possible effects of river characteristics on seasonal sediment supply are discussed, and the implications of increased sediment supply are reviewed based on seasonal comparisons. The paper also reviews the environmental significance of increased sediment supply both on water quality and ecosystem functionality.

Multiple ictal onset patterns underlie seizure generation in seizure-free patients with temporal lobe epilepsy surgery: an SEEG study

PurposeSeizure originates from different pathological substrate; however, the same pathologies may have distinct mechanisms underlying seizure generation. We aimed to improve the understanding of such mechanisms in patients with temporal lobe epilepsy (TLE) by investigating the stereoelectroencephalography (SEEG) ictal onset patterns (IOPs).MethodsWe analyzed data from a cohort of 19 consecutive patients explored by SEEG and had 1–3-year seizure-freedom following temporal lobe resection.ResultsSix IOPs were identified. They were low voltage fast activity (LVFA) (36.5%), rhythmic spikes or spike-waves at low frequency and with high amplitude (34.1%), runs of spikes (10.6%), rhythmic sharp waves (8.2%), low frequency high amplitude repetitive spiking (LFRS) (7.1%), and delta activity (3.5%). All six patterns were found in patients with mesial temporal onset and only two patterns were found in patients with temporal neocortical onset. The most prevalent patterns for patients with mesial temporal onset were rhythmic spikes or spike-waves, followed by LVFA with a mean discharge rate 74 Hz. For patients with temporal neocortical onset, the most prevalent IOP pattern was LVFA with a mean discharge rate 35 Hz, followed by runs of spikes. Compared with Lateral TLE (LTLE), the duration between the onset of the IOPs to the onset of the symptom was longer for patients with MTLE (Mesial TLE) (MTLE:55.7 ± 50.6 s vs LTLE:19.5 ± 16.4 s).ConclusionMultiple IOPs underlie seizure generation in patients with TLE. However, the mesial and lateral temporal lobes share distinct IOPs.

EEG patterns and their correlations with short- and long-term mortality in patients with hypoxic encephalopathy

ObjectiveTo analyze the association between electroencephalographic (EEG) patterns and overall, short- and long-term mortality in patients with hypoxic encephalopathy (HE). MethodsRetrospective, mono-center analysis of 199 patients using univariate log-rank tests (LR) and multivariate cox regression (MCR). ResultsShort-term mortality, defined as death within 30-days post-discharge was 54.8%. Long-term mortality rates were 69.8%, 71.9%, and 72.9%, at 12-, 24-, and 36-months post-HE, respectively. LR revealed a significant association between EEG suppression (SUP) and short-term mortality, and identified low voltage EEG (LV), burst suppression (BSP), periodic discharges (PD) and post-hypoxic status epilepticus (PSE) as well as missing (aBA) or non-reactive background activity (nrBA) as predictors for overall, short- and long-term mortality. MCR indicated SUP, LV, BSP, PD, aBA and nrBA as significantly associated with overall and short-term mortality to varying extents. LV and BSP were significant predictors for long-term mortality in short-term survivors. Rhythmic delta activity, stimulus induced rhythmic, periodic or ictal discharges and sharp waves were not significantly associated with a higher mortality. ConclusionThe presence of several specific EEG patterns can help to predict overall, short- and long-term mortality in HE patients. SignificanceThe present findings may help to improve the challenging prognosis estimation in HE patients.

The essential role of hippocampo-cortical connections in temporal coordination of spindles and ripples

The predominant activity of slow wave sleep is cortical slow oscillations (SOs), thalamic spindles and hippocampal sharp wave ripples. While the precise temporal nesting of these rhythms was shown to be essential for memory consolidation, the coordination mechanism is poorly understood. Here we develop a minimal hippocampo-cortico-thalamic network that can explain the mechanism underlying the SO-spindle-ripple coupling indicating of the succession of regional neuronal interactions. Further we verify the model predictions experimentally in naturally sleeping rodents showing our simple model provides a quantitative match to several experimental observations including the nesting of ripples in the spindle troughs and larger duration but lower amplitude of the ripples co-occurring with spindles or SOs compared to the isolated ripples. The model also predicts that the coupling of ripples to SOs and spindles monotonically enhances by increasing the strength of hippocampo-cortical connections while it is stronger at intermediate values of the cortico-hippocampal projections.

Common Peroneal Nerve Injury in a Patient with COVID-19 Infection

This report described a 46-year man with the characteristic Computerized Tomography (CT) scan findings of Corona Virus Disease Infection 19 (COVID-19) who presented to the hospital with right ankle weakness three weeks after the pneumonitis. He had been initially hospitalized, complaining of fever, myalgia, cough, and dyspnea. Electromyogram (EMG) revealed obvious evidence of increased insertional activity (IA) and significant denervation potentials, including positive sharp waves (PSW) and fibrillation potentials, particularly in ankle dorsiflexor muscles. Moreover, no voluntary motor unit action potential (MUAP) was observed. Eventually, the patient was diagnosed with severe axonal mononeuropathy of the right CPN, which could be considered a rare complication of COVID-19.

Sleep Deprivation Impairs Learning-Induced Increase in Hippocampal Sharp Wave Ripples and Associated Spike Dynamics during Recovery Sleep.

Sleep deprivation (SD) causes deficits in off-line memory consolidation, but the underlying network oscillation mechanisms remain unclear. Hippocampal sharp wave ripple (SWR) oscillations play a critical role in off-line memory consolidation. Therefore, we trained mice to learn a hippocampus-dependent trace eyeblink conditioning (tEBC) task and explored the influence of 1.5-h postlearning SD on hippocampal SWRs and related spike dynamics during recovery sleep. We found an increase in hippocampal SWRs during postlearning sleep, which predicted the consolidation of tEBC in conditioned mice. In contrast, sleep-deprived mice showed a loss of tEBC learning-induced increase in hippocampal SWRs during recovery sleep. Moreover, the sleep-deprived mice exhibited weaker reactivation of tEBC learning-associated pyramidal cells in hippocampal SWRs during recovery sleep. In line with these findings, tEBC consolidation was impaired in sleep-deprived mice. Furthermore, sleep-deprived mice showed augmented fast excitation from pyramidal cells to interneurons and enhanced participation of interneurons in hippocampal SWRs during recovery sleep. Among various interneurons, parvalbumin-expressing interneurons specifically exhibited overexcitation during hippocampal SWRs. Our findings suggest that altered hippocampal SWRs and associated spike dynamics during recovery sleep may be candidate network oscillation mechanisms underlying SD-induced memory deficits.

A de novo nonsense mutation of STXBP1 causes early-onset epileptic encephalopathy

Mutations in syntaxin-binding protein 1, STXBP1 (also known as MUNC18-1), are linked to multiple neurodevelopmental disorders, including severe early-onset epileptic encephalopathies (EOEEs). A de novo nonsense mutation of STXBP1 (c. 863G > A, p. W288X) was found in a patient diagnosed with EOEE at the age of 17 days. The electroencephalogram (EEG) showed sharp waves and spikes, while brain magnetic resonance imaging was normal. We generated a zebrafish EOEE model by overexpressing mutant STXBP1(W288X) and studied the behavioral changes further to understand the mechanism of W288X mutation in epileptogenesis. In addition, effective antiepileptic drugs were screened in the zebrafish model. Zebrafish STXBP1 homologs were highly conserved and prominently expressed in the larval zebrafish brain. The Tg(hSTXBP1W288X) zebrafish larvae exhibited hyperactivity compared with the wild-type (WT) controls. The expression of STXBP1 decreased during the development course from 1 to 5 days post fertilization. Spontaneous seizures and increased c-fos expression were observed in the mutant zebrafish larvae. The susceptibility of Tg(hSTXBP1W288X) zebrafish to pentylenetetrazol challenge also dramatically increased. Levetiracetam, clonazepam, and topiramate showed antiepileptic effects in the Tg(hSTXBP1W288X) larvae to different extents. Our findings in the newly generated mutant line of zebrafish suggested that zebrafish recapitulated clinical phenotypes associated with human STXBP1 mutation, which provided an appropriate in vivo model for epilepsy research.

Neuroprotective Effect of Ganoderma lucidum Polysaccharides in an Epileptic Rat Model

We have previously shown the antiepileptic effects of Ganoderma lucidum polysaccharides in in vitro studies; however, so far there is no such study reported in an in vivo model. In this study, the status epilepticus was induced in rats by kainic acid injection followed by G. lucidum polysaccharides treatment once a day for 7 days. Their epileptic behavior, electroencephalograph, along with the expression of caveolin-1, brain derived neurotrophic factor, nuclear factor kappa B, and hippocampal neuronal survival were assessed. Results showed that the epileptic behavior was improved significantly after G. lucidum polysaccharides treatments by a significant reduction of both the epileptic score and the duration of a heavy seizure attack while increasing both the epileptic latency and the time to heavy seizure attack. The epileptic electroencephalograph was ameliorated from previous sharp waves and frequent high amplitudes spikes to a group of scattering waves with lower frequency and small spikes. Furthermore, G. lucidum polysaccharides treatments enhanced the expression of caveolin-1, brain derived neurotrophic factor, and survivin, but decreased nuclear factor kappa B expression. These changes indicate that G. lucidum polysaccharides can alleviate epileptic seizure and this neuroprotective effect may be via increasing the expression of caveolin-1, brain derived neurotrophic factor, and survivin and decreasing the expression of nuclear factor kappa B in the hippocampal neurons.

High-Frequency Oscillations on Interictal Epileptiform Discharges in Routinely Acquired Scalp EEG: Can It Be Used as a Prognostic Marker?

IntroductionDespite all the efforts for optimizing epilepsy management in children over the past decades, there is no clear consensus regarding whether to treat or not to treat epileptiform discharges (EDs) after a first unprovoked seizure or the optimal duration of therapy with anti-seizure medication (ASM). It is therefore highly needed to find markers on scalp electroencephalogram (EEG) that can help identify pathological EEG discharges that require treatment.Aim of the studyThis retrospective study aimed to identify whether the coexistence of ripples/high-frequency oscillations (HFOs) with interictal EDs (IEDs) in routinely acquired scalp EEG is associated with a higher risk of seizure recurrence and could be used as a prognostic marker.Methods100 children presenting with new onset seizure to Children’s Medical Center- Dallas during 2015–2016, who were not on ASM and had focal EDs on an awake and sleep EEG recorded with sample frequency of 500 HZ, were randomly identified by database review. EEGs were analyzed blinded to the data of the patients. HFOs were visually identified using review parameters including expanded time base and adjusted filter settings.ResultsThe average age of patients was 6.3 years (±4.35 SD). HFOs were visually identified in 19% of the studied patients with an inter-rater reliability of 99% for HFO negative discharges and 78% agreement for identification of HFOs. HFOs were identified more often in the younger age group; however, they were identified in 11% of patients >5 years old. They were more frequently associated with spikes than with sharp waves and more often with higher amplitude EDs. Patients with HFOs were more likely to have a recurrence of seizures in the year after the first seizure (P < 0.05) and to continue to have seizures after 2 years (P < 0.0001). There was no statistically significant difference between the two groups with regards to continuing ASM after 2 years.ConclusionIncluding analysis for HFOs in routine EEG interpretation may increase the yield of the study and help guide the decision to either start or discontinue ASM. In the future, this may also help to identify pathological discharges with deleterious effects on the growing brain and set a new target for the management of epilepsy.