scholarly journals Diazepam induced sleep spindle increase correlates with cognitive recovery in a child with epileptic encephalopathy

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
S. M. Stoyell ◽  
B. S. Baxter ◽  
J. McLaren ◽  
H. Kwon ◽  
D. M. Chinappen ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Epileptiform Activity ◽  
Epileptic Encephalopathy ◽  
Sleep Spindles ◽  
High Dose ◽  
Sleep Spindle ◽  
Epileptic Encephalopathies ◽  
Cognitive Improvement ◽  
Epileptiform Discharges ◽  
Neuropsychological Evaluations

Abstract Background Continuous spike and wave of sleep with encephalopathy (CSWS) is a rare and severe developmental electroclinical epileptic encephalopathy characterized by seizures, abundant sleep activated interictal epileptiform discharges, and cognitive regression or deceleration of expected cognitive growth. The cause of the cognitive symptoms is unknown, and efforts to link epileptiform activity to cognitive function have been unrevealing. Converging lines of evidence implicate thalamocortical circuits in these disorders. Sleep spindles are generated and propagated by the same thalamocortical circuits that can generate spikes and, in healthy sleep, support memory consolidation. As such, sleep spindle deficits may provide a physiologically relevant mechanistic biomarker for cognitive dysfunction in epileptic encephalopathies. Case presentation We describe the longitudinal course of a child with CSWS with initial cognitive regression followed by dramatic cognitive improvement after treatment. Using validated automated detection algorithms, we analyzed electroencephalograms for epileptiform discharges and sleep spindles alongside contemporaneous neuropsychological evaluations over the course of the patient’s disease. We found that sleep spindles increased dramatically with high-dose diazepam treatment, corresponding with marked improvements in cognitive performance. We also found that the sleep spindle rate was anticorrelated to spike rate, consistent with a competitively shared underlying thalamocortical circuitry. Conclusions Epileptic encephalopathies are challenging electroclinical syndromes characterized by combined seizures and a deceleration or regression in cognitive skills over childhood. This report identifies thalamocortical circuit dysfunction in a case of epileptic encephalopathy and motivates future investigations of sleep spindles as a biomarker of cognitive function and a potential therapeutic target in this challenging disease.

scholarly journals B.6 High dose diazepam treatment for Electrical Status Epilepticus in Sleep (ESES): Is it effective?

2021 ◽  
Vol 48 (s3) ◽  
pp. S17-S17
Author(s):  
C Gorodetsky ◽  
T Go ◽  
S Weiss
Keyword(s):  
Status Epilepticus ◽  
Epileptiform Activity ◽  
Case Series ◽  
Epileptic Encephalopathy ◽  
Epilepsy Syndrome ◽  
Pediatric Epilepsy ◽  
High Dose ◽  
Retrospective Case ◽  
Cognitive Improvement ◽  
Clinically Significant

Background: Epileptic encephalopathy with electrical status epilepticus in sleep (ESES) is a pediatric epilepsy syndrome with sleep induced epileptic discharges and acquired impairment in cognition, language and/or behavior. Despite the widespread use of high dose diazepam, there is limited research on its efficacy. Methods: Single-center, retrospective case-series of children presenting with cognitive/ language regression and ESES from 2014-2019. All children underwent baseline overnight EEG followed by diazepam (1mg/kg) administered per rectum, and continuation of 0.5 mg/kg of oral diazepam for 3 months. Follow up EEGs were performed following the first dose and after 6-9 weeks of treatment. Results: 23 children were included [male 14 (60%); mean age 7 years (4 -12)]. 10 children (45%) had symptomatic epilepsy (defined by abnormal MRI and/or genetic evaluation). Decrease in more than 25% of the spike activity was seen in 18 (78%). This effect was sustained in 11 children (47%) after 6 weeks. Only 6 (60%) children from the symptomatic group had EEG response, while 11 (91%) responded from the idiopathic group. 5 children (21%) had clinically significant cognitive/ language improvement. Conclusions: Treatment with diazepam reduces epileptiform activity in ESES in majority of children. Despite this reduction only minority of patients experience clinically significant cognitive improvement.

scholarly journals Sleep Spindle Characteristics in Children with Neurodevelopmental Disorders and Their Relation to Cognition

2016 ◽  
Vol 2016 ◽  
pp. 1-27 ◽  
Author(s):  
Reut Gruber ◽  
Merrill S. Wise
Keyword(s):  
Cognitive Function ◽  
Neurodevelopmental Disorders ◽  
Sleep Problems ◽  
Small Sample ◽  
Future Research ◽  
Sleep Spindles ◽  
Sleep Spindle ◽  
High Prevalence ◽  
Future Research Directions ◽  
Small Sample Sizes

Empirical evidence indicates that sleep spindles facilitate neuroplasticity and “off-line” processing during sleep, which supports learning, memory consolidation, and intellectual performance. Children with neurodevelopmental disorders (NDDs) exhibit characteristics that may increase both the risk for and vulnerability to abnormal spindle generation. Despite the high prevalence of sleep problems and cognitive deficits in children with NDD, only a few studies have examined the putative association between spindle characteristics and cognitive function. This paper reviews the literature regarding sleep spindle characteristics in children with NDD and their relation to cognition in light of what is known in typically developing children and based on the available evidence regarding children with NDD. We integrate available data, identify gaps in understanding, and recommend future research directions. Collectively, studies are limited by small sample sizes, heterogeneous populations with multiple comorbidities, and nonstandardized methods for collecting and analyzing findings. These limitations notwithstanding, the evidence suggests that future studies should examine associations between sleep spindle characteristics and cognitive function in children with and without NDD, and preliminary findings raise the intriguing question of whether enhancement or manipulation of sleep spindles could improve sleep-dependent memory and other aspects of cognitive function in this population.

scholarly journals The Epileptic Encephalopathies of Infancy and Childhood

2005 ◽  
Vol 32 (4) ◽  
pp. 409-418 ◽  
Author(s):  
Elaine Wirrell ◽  
Kevin Farrell ◽  
Sharon Whiting
Keyword(s):  
Cognitive Function ◽  
Behavior Disorders ◽  
Intractable Epilepsy ◽  
Epileptic Encephalopathy ◽  
Convulsive Status Epilepticus ◽  
Epileptic Encephalopathies ◽  
Co Morbidity ◽  
Infancy And Childhood ◽  
Infancy And Early Childhood ◽  
Review Current

ABSTRACT:The epileptic encephalopathies comprise a group of devastating seizure syndromes which begin in infancy and early childhood and usually result in intractable epilepsy. While some syndromes are relatively easily diagnosed early in their course, others take time to evolve, hampering an early, confident diagnosis. Epileptic encephalopathies are associated with slowing of cognitive function and evolution of severe behavioral disorders, which are often more distressing to families than the epilepsy. While an underlying etiology may explain some of this co-morbidity, many children have no identifiable etiology found for their seizures. In these “idiopathic” cases, recurrent subtle seizures, frequent epileptiform discharge and non-convulsive status epilepticus probably all play a role in deterioration of cognitive function and evolution of behavior disorders. This paper will review the most common epileptic encephalopathy syndromes, discuss the cognitive and behavioral co-morbidities and review current therapeutic options.

Epileptic Spasms at Muhimbili National Hospital Tanzania, A Retrospective Study.

2020 ◽  
Author(s):  
Joseph Mwalongo ◽  
Edward Kija
Keyword(s):  
Age Of Onset ◽  
Early Recognition ◽  
Epileptic Encephalopathy ◽  
High Dose ◽  
Muhimbili National Hospital ◽  
National Hospital ◽  
Cross Sectional ◽  
Female Ratio ◽  
Epileptiform Discharges ◽  
Epileptic Spasms

Abstract Background; Epileptic spasms (ES) is an epileptic encephalopathy occurring during infancy and early childhood. Early recognition and management is important to prevent severe neurological impairment. This study aimed at describing the clinical presentation, management and outcome of patients with Epileptic Spasms attending Muhimbili National Hospital (MNH), in Dar Es Salaam, Tanzania. Methods; A retrospective cross sectional study of all patients diagnosed with epileptic spasms was conducted at MNH from July 2016 to October 2018. Results; A total of 40 patients diagnosed with epileptic spasms were retrieved with male to female ratio of 3:2. In this study, 17 (42.5%) patients had a documented history of perinatal insult. The median age of onset of spasms was 5 months (IQR 1–12 months). In 14 (80%) out of 17 patients whom electroencephalography ( EEG) findings were retrieved had abnormal EEG findings showing either generalized epileptiform discharges 7(41%), generalized slowing 5(30%), hypsarrthymia 1(6%), or abnormal focal epileptiform discharges 2 (12%). Twenty-nine (73%) received prednisolone, with a median time of spasms subsiding of 1 month with a range of 10 days to 3 months in about 90% of them. Conclusion; The median age of onset of epileptic spasms at MNH is 5 months with the most common cause being perinatal insult in more than 40% of the patients. High dose prednisolone showed a good response in patients with epileptic spasms at MNH.

scholarly journals Continuous Spikes and Waves during Sleep: Electroclinical Presentation and Suggestions for Management

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Iván Sánchez Fernández ◽  
Kevin E. Chapman ◽  
Jurriaan M. Peters ◽  
Chellamani Harini ◽  
Alexander Rotenberg ◽  
...  
Keyword(s):  
Epileptiform Activity ◽  
Epileptic Encephalopathy ◽  
High Dose ◽  
Genetic Associations ◽  
Neurocognitive Deficits ◽  
Eeg Abnormalities ◽  
Electroencephalogram Eeg ◽  
Early Developmental ◽  
Continuous Spikes And Waves ◽  
Eeg Pattern

Continuous spikes and waves during sleep (CSWS) is an epileptic encephalopathy characterized in most patients by (1) difficult to control seizures, (2) interictal epileptiform activity that becomes prominent during sleep leading to an electroencephalogram (EEG) pattern of electrical status epilepticus in sleep (ESES), and (3) neurocognitive regression. In this paper, we will summarize current epidemiological, clinical, and EEG knowledge on CSWS and will provide suggestions for treatment. CSWS typically presents with seizures around 2–4 years of age. Neurocognitive regression occurs around 5-6 years of age, and it is accompanied by subacute worsening of EEG abnormalities and seizures. At approximately 6–9 years of age, there is a gradual resolution of seizures and EEG abnormalities, but the neurocognitive deficits persist in most patients. The cause of CSWS is unknown, but early developmental lesions play a major role in approximately half of the patients, and genetic associations have recently been described. High-dose benzodiazepines and corticosteroids have been successfully used to treat clinical and electroencephalographic features. Corticosteroids are often reserved for refractory disease because of adverse events. Valproate, ethosuximide, levetiracetam, sulthiame, and lamotrigine have been also used with some success. Epilepsy surgery may be considered in a few selected patients.

scholarly journals P110 The association between sleep spindles and cognitive function in middle-aged and older men: A community-based study

2021 ◽  
Vol 2 (Supplement_1) ◽  
pp. A56-A57
Author(s):  
J Parker ◽  
Y Melaku ◽  
A D’Rozario ◽  
G Wittert ◽  
S Martin ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Community Dwelling ◽  
Inspection Time ◽  
Apnea Hypopnea Index ◽  
Sleep Spindles ◽  
Sleep Spindle ◽  
Cross Sectional ◽  
Home Based ◽  
Obstructive Sleep ◽  
Complete Study

Abstract Introduction The association between sleep spindles and cognitive function and the potential confounding influence of obstructive sleep apnea (OSA) remains uncertain. This study examined cross-sectional associations between sleep spindle metrics and cognitive function outcomes in community-dwelling men. Methods Men, Androgen, Inflammation, Lifestyle, Environment, and Stress (MAILES) study participants (n=477) underwent home-based polysomnography between 2010–2011 and completed the inspection time task, trail-making test A (TMT-A) and B (TMT-B), and Fuld object memory evaluation. Frontal spindle metrics derived from sleep electroencephalography included occurrence (total no. of sleep spindle events) and slow (11–13 Hz) and fast (13–16 Hz) spindle density (no./min) during N2 and N3 sleep. Results Men with OSA (any OSA and severe OSA) had significantly impaired sleep spindles (reduced occurrence and densities). In the complete study sample, higher spindle occurrence during N2 sleep was independently associated with faster inspection time (B= -0.44, 95% CI [-0.87, -0.02], p=0.041), whereas higher fast spindle density during N3 sleep was independently associated with worse TMT-B performance (B=20.7, 95% CI [0.55, 40.9], p=0.044). Furthermore, in men with severe OSA (apnea-hypopnea index ≥30/h), higher slow spindle density during N2 sleep was independently associated with worse TMT-A and TMT-B performance, whereas only higher spindle occurrence during N2 sleep was independently associated with worse TMT-A performance (all p<0.05). Discussion Specific spindle metrics during N2 and N3 sleep are independently associated with cognitive function in an unselected population of men and men with undiagnosed severe OSA. The utility of sleep spindles for predicting cognitive dysfunction and decline requires further investigation.

Interstitial Stereotactic Laser Anterior Corpus Callosotomy: A Report of 2 Cases with Operative Technique and Effectiveness

Neurosurgery ◽  
2018 ◽  
Vol 85 (3) ◽  
pp. E569-E574 ◽  
Author(s):  
James X Tao ◽  
Naoum P Issa ◽  
Shasha Wu ◽  
Sandra Rose ◽  
John Collins ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Surgical Complications ◽  
Epileptiform Activity ◽  
Significant Risk ◽  
Invasive Technique ◽  
Corpus Callosotomy ◽  
Cognitive Improvement ◽  
Epileptiform Discharges ◽  
Mri Guided ◽  
Video Eeg

AbstractBACKGROUND AND IMPORTANCECorpus callosotomy is an effective palliative treatment for medically intractable Lennox–Gastaut syndrome (LGS) that disrupts the interhemispheric synchronization of epileptiform discharges. However, traditional open corpus callosotomy carries a significant risk of surgical complications associated with craniotomy and a parafalcine approach to the corpus callosum. Here, we report 2 cases of anterior corpus callosotomy using MRI-guided stereotactic laser interstitial thermal therapy (LITT) as a minimally invasive technique for mitigating the risks of craniotomy while achieving favorable outcomes.CLINICAL PRESENTATIONTwo patients with medically intractable LGS underwent stereotactic laser anterior corpus callosotomy using a 2 laser-fiber approach. Ablation of 70%-80% of the corpus callosum was confirmed by postoperative MRI diffusion tensor imaging and volumetric analysis. Marked reduction of epileptiform activity was observed in both patients during postoperative video-EEG studies as compared to preoperative video-EEG studies. Freedom from disabling seizures including drop attacks was achieved in 1 patient for 18 mo, and more than a 90% reduction of disabling seizures was achieved in the other patient for 7 mo with cognitive improvement and without surgical complications.CONCLUSIONThese early data demonstrate the technical feasibility, safety, and favorable outcomes of MRI-guided stereotactic laser anterior corpus callosotomy in patients with LGS, making it a potentially safe and effective alternative to traditional open corpus callosotomy and other stereotactic methods including radiofrequency ablation and radiosurgery due to the ability to monitor the ablation in real time with MRI.

HIGH DOSE DIAZEPAM (HDD) IN CHILDHOOD-ONSET EPILEPTIC ENCEPHALOPATHIES WITH SLEEP ACTIVATED EEG (EESA_EEG)

2006 ◽  
Vol 37 (S 1) ◽  
Author(s):  
S Hadjiloizou ◽  
B Bourgeois ◽  
F Duffy ◽  
AM Bergin ◽  
M Takeoka ◽  
...  
Keyword(s):  
High Dose ◽  
Childhood Onset ◽  
Epileptic Encephalopathies

scholarly journals Induction of Tertiary Phase Epileptiform Discharges after Postasphyxial Infusion of a Toll-Like Receptor 7 Agonist in Preterm Fetal Sheep

2021 ◽  
Vol 22 (12) ◽  
pp. 6593
Author(s):  
Kenta H.T. Cho ◽  
Mhoyra Fraser ◽  
Bing Xu ◽  
Justin M. Dean ◽  
Alistair J. Gunn ◽  
...  
Keyword(s):  
Moderate Hypertension ◽  
Epileptiform Activity ◽  
Ischemic Brain Injury ◽  
Toll Like Receptor ◽  
Fetal Sheep ◽  
Ischemic Brain ◽  
Tlr Agonists ◽  
Epileptiform Discharges ◽  
Subcortical Regions ◽  
Total Burden

Background: Toll-like receptor (TLR) agonists are key immunomodulatory factors that can markedly ameliorate or exacerbate hypoxic–ischemic brain injury. We recently demonstrated that central infusion of the TLR7 agonist Gardiquimod (GDQ) following asphyxia was highly neuroprotective after 3 days but not 7 days of recovery. We hypothesize that this apparent transient neuroprotection is associated with modulation of seizure-genic processes and hemodynamic control. Methods: Fetuses received sham asphyxia or asphyxia induced by umbilical cord occlusion (20.9 ± 0.5 min) and were monitored continuously for 7 days. GDQ 3.34 mg or vehicle were infused intracerebroventricularly from 1 to 4 h after asphyxia. Results: GDQ infusion was associated with sustained moderate hypertension that resolved after 72 h recovery. Electrophysiologically, GDQ infusion was associated with reduced number and burden of postasphyxial seizures in the first 18 h of recovery (p < 0.05). Subsequently, GDQ was associated with induction of slow rhythmic epileptiform discharges (EDs) from 72 to 96 h of recovery (p < 0.05 vs asphyxia + vehicle). The total burden of EDs was associated with reduced numbers of neurons in the caudate nucleus (r2 = 0.61, p < 0.05) and CA1/2 hippocampal region (r2 = 0.66, p < 0.05). Conclusion: These data demonstrate that TLR7 activation by GDQ modulated blood pressure and suppressed seizures in the early phase of postasphyxial recovery, with subsequent prolonged induction of epileptiform activity. Speculatively, this may reflect delayed loss of early protection or contribute to differential neuronal survival in subcortical regions.

Pharmacologically Increasing Sleep Spindles Enhances Recognition for Negative and High-arousal Memories

2013 ◽  
Vol 25 (10) ◽  
pp. 1597-1610 ◽  
Author(s):  
Erik J. Kaestner ◽  
John T. Wixted ◽  
Sara C. Mednick
Keyword(s):  
Rem Sleep ◽  
Memory Consolidation ◽  
Declarative Memory ◽  
Memory Performance ◽  
Emotional Memory ◽  
Limited Range ◽  
Sleep Spindles ◽  
Sleep Spindle ◽  
Emotional Stimuli ◽  
Valence And Arousal

Sleep affects declarative memory for emotional stimuli differently than it affects declarative memory for nonemotional stimuli. However, the interaction between specific sleep characteristics and emotional memory is not well understood. Recent studies on how sleep affects emotional memory have focused on rapid eye movement sleep (REM) but have not addressed non-REM sleep, particularly sleep spindles. This is despite the fact that sleep spindles are implicated in declarative memory as well as neural models of memory consolidation (e.g., hippocampal neural replay). Additionally, many studies examine a limited range of emotional stimuli and fail to disentangle differences in memory performance because of variance in valence and arousal. Here, we experimentally increase non-REM sleep features, sleep spindle density, and SWS, with pharmacological interventions using zolpidem (Ambien) and sodium oxybate (Xyrem) during daytime naps. We use a full spread of emotional stimuli to test all levels of valence and arousal. We find that increasing sleep spindle density increases memory discrimination (da) for highly arousing and negative stimuli without altering measures of bias (ca). These results indicate a broader role for sleep in the processing of emotional stimuli with differing effects based on arousal and valence, and they raise the possibility that sleep spindles causally facilitate emotional memory consolidation. These findings are discussed in terms of the known use of hypnotics in individuals with emotional mood disorders.

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