Treatment Practices and Outcomes in Continuous Spike and Wave during Slow Wave Sleep: A Multicenter Collaboration

Bäumer, F; McNamara, Nancy; Fine, Anthony L.; Pestana-Knight, Elia M.; Shellhaas, Renée A.; He, Zihuai; Arndt, Daniel H.; Gaillard, William D.; Kelley, Sarah A.; Nagan, Margot R.; Ostendorf, Adam P.; Singhal, Nilika Shah; Speltz, Laura; Chapman, Kevin

doi:10.1016/j.jpeds.2021.01.032

Cited by 17 publications

(13 citation statements)

References 40 publications

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“…57 To categorize clinical outcomes here, we relied on the long-term qualitative assessments of the treating providers, consistent with current clinical practice in this ultra-rare epilepsy syndrome. 58 That the subjects included here had clinical responses determined by six separate attending neurologists before the conception of this study increases the generalizability and rigor of our findings. As benzodiazepines can also introduce side effects of sedation and psychomotor impairment, it will be important to evaluate for improved cognitive function alongside the improvements in sleep spindles when used in treatment.…”

Section: Discussionmentioning

confidence: 87%

“…We also recognize that the appropriate quantitative measure for cognitive response related to sleep spindles is a measure of sleep‐dependent memory consolidation 16,54,55,56 which are not available in routine neuropsychological assessments or standard clinical exams, but long‐term assessments that include periods of sleep are more likely to capture these improvements 57 . To categorize clinical outcomes here, we relied on the long‐term qualitative assessments of the treating providers, consistent with current clinical practice in this ultra‐rare epilepsy syndrome 58 . That the subjects included here had clinical responses determined by six separate attending neurologists before the conception of this study increases the generalizability and rigor of our findings.…”

Section: Discussionmentioning

confidence: 99%

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Preliminary evidence of a relationship between sleep spindles and treatment response in epileptic encephalopathy

McLaren

Luo

Kwon

et al. 2023

Ann Clin Transl Neurol

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ObjectiveEpileptic encephalopathy with spike‐wave activation in sleep (EE‐SWAS) is a challenging neurodevelopmental disease characterized by abundant epileptiform spikes during non‐rapid eye movement (NREM) sleep accompanied by cognitive dysfunction. The mechanism of cognitive dysfunction is unknown, but treatment with high‐dose diazepam may improve symptoms. Spike rate does not predict treatment response, but spikes may disrupt sleep spindles. We hypothesized that in patients with EE‐SWAS: (1) spikes and spindles would be anti‐correlated, (2) high‐dose diazepam would increase spindles and decrease spikes, and (3) spindle response would be greater in those with cognitive improvement.MethodsConsecutive EE‐SWAS patients treated with high‐dose diazepam that met the criteria were included. Using a validated automated spindle detector, spindle rate, duration, and percentage were computed in pre‐ and post‐treatment NREM sleep. Spikes were quantified using a validated automated spike detector. The cognitive response was determined from a chart review.ResultsSpindle rate was anti‐correlated with the spike rate in the channel with the maximal spike rate (p = 0.002) and averaged across all channels (p = 0.0005). Spindle rate, duration, and percentage each increased, and spike rate decreased, after high‐dose diazepam treatment (p ≤ 2e‐5, all tests). Spindle rate, duration, and percentage (p ≤ 0.004, all tests) were increased in patients with cognitive improvement after treatment, but not those without. Changes in spindle rate but not changes in spike rate distinguished between groups.InterpretationThese findings confirm thalamocortical disruption in EE‐SWAS, identify a mechanism through which benzodiazepines may support cognitive recovery, and introduce sleep spindles as a promising mechanistic biomarker to detect treatment response in severe epileptic encephalopathies.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Preliminary evidence of a relationship between sleep spindles and treatment response in epileptic encephalopathy

McLaren

Luo

Kwon

et al. 2023

Ann Clin Transl Neurol

View full text Add to dashboard Cite

show abstract

“…We also recognize that the appropriate quantitative measure for cognitive response related to sleep spindles is a measure of sleep dependent memory consolidation 16,[53][54][55] which are not available in routine neuropsychological assessments or standard clinical exams, but long-term assessments that include periods of sleep are more likely to capture these improvements. 56 To categorize clinical outcome here, we relied on the long-term qualitative assessments of the treating providers, consistent with current clinical practice in this ultra-rare epilepsy syndrome 57 . That the subjects included here had clinical responses determined by six separate attending neurologists before the conception of this study increases the generalizability and rigor of our findings.…”

Section: Discussionmentioning

confidence: 99%

Preliminary evidence of a relationship between sleep spindles and treatment response in epileptic encephalopathy

McLaren

Luo

Kwon

et al. 2023

Preprint

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Objective: Epileptic encephalopathy with spike wave activation in sleep (EE-SWAS) is a challenging neurodevelopmental disease characterized by abundant epileptiform spikes during non-rapid eye movement (NREM) sleep accompanied by cognitive dysfunction. The mechanism of cognitive dysfunction is unknown, but treatment with high-dose diazepam may improve symptoms. Spike rate does not predict treatment response, but spikes may disrupt sleep spindles. We hypothesized that in patients with EE-SWAS: 1) spikes and spindles would be anticorrelated, 2) high-dose diazepam would increase spindles and decrease spikes, and 3) spindle response would be greater in those with cognitive improvement. Methods: Consecutive EE-SWAS patients treated with high-dose diazepam that met criteria were included. Using a validated automated spindle detector, spindle rate, duration, and percentage were computed in pre- and post-treatment NREM sleep. Spikes were quantified using a validated automated spike detector. Cognitive response was determined from chart review. Results: Spindle rate was anticorrelated with spike rate in the channel with the maximal spike rate (p=0.002) and averaged across all channels (p=0.0005). Spindle rate, duration, and percentage each increased, and spike rate decreased, after high-dose diazepam treatment (p≤2e-5, all tests). Spindle rate, duration, and percentage (p≤0.004, all tests) were increased in patients with cognitive improvement after treatment, but not those without. Changes in spike rate did not distinguish between groups. Interpretation: These findings confirm thalamocortical disruption in EE-SWAS, identify a mechanism through which benzodiazepines may support cognitive recovery, and introduce sleep spindles as a promising mechanistic biomarker to detect treatment response in severe epileptic encephalopathies.

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“…31 We followed the traditional non-benzodiazepine ASMs as the first treatment choice, resulting in an EEG improvement rate of 5.5%, similar to the results of previous studies. 32,33 The EEG improvement rates were 30.9% for ASMs with benzodiazepine, and 37% for ASMs, benzodiazepines and steroids. As ASMs are the first choice for children with ESES in our center, those who did not respond would consider adding benzodiazepines or steroids, the actual effectiveness of benzodiazepines and steroids may be higher.…”

Section: Treatment and Prognosis Of Children With Esesmentioning

confidence: 98%

“…34 A study from 11 pediatric epilepsy centers in the US found that ASMs are less effective, but did not not find strong evidence for superiority of steroids over benzodiazepines. 33 It is possible that patients who are most likely to recover respond to whichever treatment they receive first. To develop evidence-based treatment protocols for children with ESES, we must first work to standardize assessments, treatment protocols, and clinically relevant outcome measures.…”

Section: Treatment and Prognosis Of Children With Esesmentioning

confidence: 99%

The prospective study of 54 children with electrical status epilepticus during sleep: How to simplify the electroencephalogram diagnosis and guide the treatment

Zhang

Yan

Peng

et al. 2023

Epileptic Disorders

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ObjectiveTo simplify the electroencephalogram (EEG) diagnosis and guide the treatment of electrical status epilepticus during sleep (ESES).MethodsWe recruited 54 children with ESES from December 2019 to December 2020 and compared various spike–wave index (SWI) calculation methods. Time‐frequency analysis assessed the correlation between high‐frequency oscillations energy and the SWI. We divided 42 children into responder and non‐responder treatment groups based on the observations made during a 12‐month follow‐up period and evaluate different treatment and the independent risk factors of refractory ESES.ResultsThe SWI of 5 min before the second sleep cycle of non‐rapid eye movement (NREM; long method II) and that of all NREM sleep (total method) were not significantly different (p = .06). The average energy of γ (r = .288, p = .002) and ripple (r = .203, p = .04) oscillations were correlated with the SWI. Multivariable logistic regression analysis showed that encephalomalacia was an independent risk factor for refractory ESES (OR: 10.48, 95% CI: 1.62–67.63). The clinical seizure improvement rates of anti‐seizure medications (ASMs), ASMs with benzodiazepines, and ASMs with benzodiazepines and steroids after 12 months were 9.3%, 42.8%, and 53.8%, EEG improvement rate were 5.5%, 30.9% and 37%, respectively. The intelligence of the children in the responder treatment group has improved during the 1‐year follow‐up.SignificanceThese findings demonstrate EEG and clinical features of ESES and may provide basis for simplifying diagnosis and guiding the treatment of children with ESES.

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Treatment Practices and Outcomes in Continuous Spike and Wave during Slow Wave Sleep: A Multicenter Collaboration

Cited by 17 publications

References 40 publications

Preliminary evidence of a relationship between sleep spindles and treatment response in epileptic encephalopathy

Preliminary evidence of a relationship between sleep spindles and treatment response in epileptic encephalopathy

Preliminary evidence of a relationship between sleep spindles and treatment response in epileptic encephalopathy

The prospective study of 54 children with electrical status epilepticus during sleep: How to simplify the electroencephalogram diagnosis and guide the treatment

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