RARE DISEASE
Continuous spikes and waves during sleep
Continuous spikes and waves during sleep
Continuous spikes and waves during sleep
Synonyms: CSWS, CSWSS syndrome, Continuous spikes and waves during slow-wave sleep, Epileptic encephalopathy with continuous spike-and-wave during slow sleep
Synonyms: CSWS, CSWSS syndrome, Continuous spikes and waves during slow-wave sleep, Epileptic encephalopathy with continuous spike-and-wave during slow sleep
Synonyms: CSWS, CSWSS syndrome, Continuous spikes and waves during slow-wave sleep, Epileptic encephalopathy with continuous spike-and-wave during slow sleep
Drug discovery
2
drugs
With orphan designations
Overview
Continuous spikes and waves during sleep (CSWS) is a rare childhood-onset epileptic encephalopathy characterized by pharmacoresistant seizures, neurocognitive regression, and an EEG pattern of near-continuous spike-wave discharges occupying ≥25%-85% of non-REM sleep (electrical status epilepticus in sleep/ESES) [1][6][15]. Typically emerging between ages 2-4 years, it causes progressive deficits in language, cognition, and motor skills before partial remission of seizures and EEG abnormalities by adolescence, though neurodevelopmental impairments often persist [1][6][12].
Therapies
First-line: High-dose benzodiazepines (diazepam 1 mg/kg loading), valproate (30-50 mg/kg/day), and corticosteroids (prednisone 2 mg/kg/day) [3][7][9]
Second-line: Levetiracetam, ethosuximide, or epilepsy surgery for refractory cases [7][12][15]
Goal-oriented treatment endpoints: EEG improvement (74% prioritize), cognitive stabilization (52%), and seizure control [3][7]
Categories: rare genetic diseases, rare neurological diseases
Research Papers
173 drug discovery papers about Continuous spikes and waves during sleep, with 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
173 drug discovery papers about Continuous spikes and waves during sleep, with 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-21 | Electrical Status Epilepticus in Sleep (ESES): Evolving Concepts in Etiology, Pathophysiological Mechanisms, Diagnostic Approaches, and Therapeutic Strategies for a Devastating Pediatric Epileptic Encephalopathy
Electrical status epilepticus in sleep (ESES) represents a distinctive and clinically challenging pediatric epileptic encephalopathy characterized by the triad of epilepsy, progressive cognitive regression, and remarkable potentiation of epileptiform activity during non-rapid eye movement sleep, resulting in an electroencephalographic pattern of near-continuous spike-wave discharges. This condition typically emerges during a critical neurodevelopmental window between 2 and 12 years of age, with peak incidence occurring between 3 and 5 years, a period when the developing brain exhibits heightened vulnerability to the disruptive effects of aberrant neural synchronization. The etiological landscape of ESES is remarkably heterogeneous, encompassing both structural brain abnormalities—particularly early developmental lesions involving the thalamus—and an expanding array of genetic etiologies, including monogenic mutations in genes such as GRIN2A, SCN2A, and KCNA2, as well as recurrent copy number variants. The pathophysiological mechanisms underlying the characteristic sleep activation of epileptiform discharges remain incompletely elucidated, though current conceptual frameworks implicate abnormal hyperactivation of thalamocortical oscillatory circuits, potentially driven by a shift from GABAa- to GABAb-mediated postsynaptic inhibition within the reticular thalamic network. Clinically, affected children typically present with infrequent seizures accompanied by developmental stagnation or regression, with behavioral abnormalities—particularly hyperactivity—frequently complicating the clinical picture. The diagnosis rests upon the demonstration of characteristic EEG abnormalities during NREM sleep, with quantitative assessment of the spike-wave index serving as a crucial biomarker for disease severity and treatment response. Management strategies have evolved primarily from retrospective studies and expert consensus, encompassing conventional antiepileptic drugs including levetiracetam, clobazam, and ethosuximide, as well as corticosteroid therapy—which demonstrates superior response rates—and surgical interventions in carefully selected patients with structural pathology. The prognosis is guarded, with spontaneous improvement in seizures and EEG abnormalities typically occurring after puberty, albeit with only partial reversal of cognitive deterioration. Early diagnosis and aggressive intervention are paramount, as delayed treatment may result in irreversible neuropsychological sequelae. This comprehensive review synthesizes current evidence with theoretical frameworks from developmental neurobiology and epileptology, providing a scholarly examination of ESES that informs clinical practice while identifying critical knowledge gaps that merit future investigation.
2026-08-18 | Electrophysiological, neurocognitive, and GFAP biomarker responses to corticosteroid therapy in children with ESES/CSWS.
Developmental and/or epileptic encephalopathy with spike-wave activation during sleep (DE SWAS), including electrical status epilepticus during sleep (ESES/CSWS), is associated with seizures, neurocognitive regression, and characteristic electroencephalographic abnormalities. This study aimed to evaluate the clinical, electrophysiological, neurocognitive, and molecular response to corticosteroid therapy in children diagnosed with DE-SWAS, with a particular focus on serum glial fibrillary acidic protein (GFAP) as a potential biomarker of treatment response. Eleven children aged 6-12 years were retrospectively evaluated using clinical records, sleep electroencephalography with quantification of the spike-wave index (SWI), standardized neuropsychological test results, and serum GFAP measurements obtained before and after corticosteroid treatment. Neurocognitive assessment included the Wechsler Intelligence Scale for Children-Revised (WISC-R), Stroop Color and Word Test, Bender Visual-Motor Gestalt Test, and Turkish Receptive and Expressive Language Test (TIFALDI)High-dose intravenous methylprednisolone was administered monthly for six months. During follow-up, four patients became seizure-free, while the remaining seven demonstrated a reduction in seizure frequency and duration exceeding 50%. Complete normalization of electroencephalographic findings was observed in four patients, and a ≥ 50% reduction in SWI was observed in the remaining seven. Post-treatment neurocognitive evaluations demonstrated overall improvement, particularly in attention, executive functions, and receptive language domains. Mean serum GFAP levels decreased significantly following corticosteroid therapy (p = .017). These findings suggest that corticosteroid therapy is associated with favorable clinical, electrophysiological, and neurocognitive outcomes in children with DE-SWAS and that GFAP may represent a promising biomarker of disease activity and therapeutic response. Larger prospective studies are warranted to validate these results.
2026-07-27 | Developmental and/or Epileptic Encephalopathy with Spike-Wave Activation in Sleep: From Thalamocortical Mechanisms to Precision Therapy
Developmental and/or epileptic encephalopathy with spike-wave activation in sleep (D/EE-SWAS), previously described as continuous spike-wave during slow-wave sleep (CSWS) or electrical status epilepticus in sleep (ESES), is a childhood-onset disorder characterized by cognitive, language, behavioral, and/or motor regression or stagnation associated with marked activation of epileptiform discharges during non-rapid eye movement sleep. Three themes are central to the evolving understanding of D/EE-SWAS. First, it is a network disorder in which thalamocortical dysfunction, impaired sleep-dependent synaptic homeostasis, and potentially neuroinflammatory mechanisms contribute to neurodevelopmental deterioration. Second, increasing recognition of its genetic and structural heterogeneity is reshaping diagnostic evaluation. Monogenic etiologies are identified in up to one-third of cases, with a higher yield in the developmental and epileptic encephalopathy subtype, supporting early genomic testing alongside prolonged sleep EEG, MRI, and serial neuropsychological assessment. Third, treatment remains empiric and constrained by limited comparative evidence. Corticosteroids retain the strongest evidence base for cognitive improvement, although the overall certainty of this evidence remains low to moderate. Benzodiazepines are commonly used alternatives, and epilepsy surgery can provide substantial benefit in appropriately selected patients with focal structural abnormalities. Emerging etiology-directed therapies, including L-serine for selected GRIN loss-of-function variants and primidone for TRPM3-related disease, illustrate a broader transition from syndrome-based to precision management. However, no pharmacological therapy is specifically approved for D/EE-SWAS, long-term neurodevelopmental morbidity remains common, and adequately powered trials using standardized EEG and neurocognitive outcomes are urgently needed.
2026-06-01 | Neurocognitive Trajectories Following Monthly Pulse IV Methylprednisolone in Children with Epileptic Encephalopathy
Background: Pediatric epileptic encephalopathies (EE) are characterized by drug-resistant seizures and cognitive regression. Corticosteroid therapies such as intravenous methylprednisolone (IVMP) have shown variable efficacy. This study evaluates the clinical, neurocognitive, and electrophysiological outcomes of IVMP in children with EE. Methods: A retrospective cohort of 25 children diagnosed with EE (Lennox-Gastaut Syndrome [LGS], CSWS, West Syndrome) received IVMP pulse therapy. Outcomes assessed included seizure response, EEG improvement, cognitive shift, and treatment tolerability. Univariate logistic regression explored predictors of cognitive improvement. Results: Seizure reduction ≥50% was observed in 64.0% overall, significantly higher in CSWS (100%) than LGS (30.8%, P = 0.001). EEG improvement occurred in 60.0%, also favoring CSWS (81.8% vs. 38.5%, P = 0.047). Cognitive improvement was noted in only 16.0% of patients, with no statistically significant predictors. Adverse events were mild and reported in 28.0%. Conclusions: IVMP therapy may effectively reduce seizures and EEG burden in children with EE, particularly in CSWS. However, cognitive gains remain limited, emphasizing the need for adjunctive neurorehabilitative strategies. IVMP appears to be safe and well-tolerated.
2026-01-30 | National consensus on diagnosis and treatment of epilepsy. 2026
Definition. The International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE) define epilepsy as “disorder of the brain characterized by enduring predisposition to generate epileptic seizures and by the neurobiological, cognitive, psychological and social consequences of this condition”.According to the expanded definition of epilepsy of 2014 recommended by ILAE, epilepsy is a disease of the brain defined by any of the following conditions:1. At least 2 unprovoked (or reflex) seizures occurring greater than 24 hours apart.2. One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures (a seizure occurring 30 days after brain stroke in case of established brain structural abnormalities and epileptiform EEG)3. Diagnosis of an epilepsy syndrome (Rolandic epilepsy with low risk of recurring seizures, Landau-Kleffner syndrome, epileptic encephalopathy with continuous spikes and waves during sleep).Epilepsy is considered to be resolved for:- Patients who had an age-dependent epilepsy syndrome but are now past the applicable age,or- Patients who have remained seizure-free for the last 10 years, with no seizure medicines forthe last 5 years.Epilepsy is not diagnosed when seizures occur in case of acute injuries of brain structures (strokes, traumas, encephalitis) or metabolism (hypoglycemia, syncope, intoxication) and fever.2. Epidemiology. Morbidity rate of active epilepsy is similar for the countries with different economic development – 2,3-5,9/1000 for countries with high income economy, 3,7-13,3/1000 for countries with high to moderate income economy, 2,4-22,8/1000 for countries with low to moderate income economy, 3,6-15,4/1000 for countries with low income economy. Morbidity rate is higher for countries with low income and moderate income economy. The average morbidity rate is 45 per 100 000 inhabitants in countries with high income, and 81,7 in the rest of the countries. In Bulgaria individuals suffering epilepsy are about 50 000. In 50 - 60% of the patients, the epilepsy onset occurs earlier than 16 years of age. 2-5% of the children younger than 5 years of age suffer febrile seizures.
proteins
2026-01-24 | ‘Pseudo‐ataxic’ negative myoclonic status in developmental and epileptic encephalopathy with spike‐wave activation in sleep: Utility of ACTH therapy beyond west syndrome
BACKGROUND: Developmental/Epileptic encephalopathy with spike and wave activation in sleep (DEE-SWAS) comprises a spectrum of childhood-onset epilepsies, characterized by near-continuous spike-wave discharges during non-REM sleep which can result in cognitive, behavioral, and motor regression. Negative myoclonic status in the context of DEE-SWAS is extremely rare, and management is difficult as conventional anti-seizure medications (ASM) and immunomodulatory therapies often show limited efficacy. Adrenocorticotropic hormone (ACTH), classically used for infantile spasms, has recently been reported as a potential therapy for refractory DEE-SWAS. CASE PRESENTATION: We report a 7-year-old girl with prior developmental encephalopathy, who experienced recurrent unprovoked seizures from 5 years of age, followed by progressive ataxia and language regression. Clinical examination revealed facial dysmorphism, truncal and gait ataxia, oral apraxia with atonic head drops. Video EEG revealed background slowing with bilateral centro-parieto-temporal spikes markedly activated in sleep, with clusters of atonic neck and truncal drop seizures suggestive of negative myoclonic status leading to 'pseudo-ataxia'. Despite treatment with multiple ASM, intravenous methylprednisolone and immunoglobulin, there was worsening encephalopathy and anterior opercular syndrome. Given therapeutic refractoriness, ACTH was initiated. The patient showed dramatic improvement: resolution of status, a marked reduction in EEG spike-wave burden, recovery of gait and language to baseline, and restoration of social interaction. CONCLUSION: This case demonstrates for the first time the potential of ACTH in refractory DEE-SWAS with negative myoclonic status epilepticus, wherein conventional immunomodulation fails. The sustained clinical and electrographic improvement highlights the broader neuro-modulatory mechanisms of ACTH and supports its consideration in treatment algorithms. Larger prospective studies are warranted to compare the efficacy and safety profile of various corticosteroids in DEE.
2024-06-17 | Successful treatment of epileptic encephalopathy with spike wave activation in sleep with anakinra.
Patients with epileptic encephalopathy with spike wave activation in sleep (EE-SWAS) often display drug-resistant epilepsy. The activation of epileptic activity during sleep is associated temporally with neurocognitive impairment and causes a spectrum of disorders within the epilepsy-aphasia syndrome. The prognosis is dependent on promptness of treatment and etiology. However, there is no clear consensus with regards to the optimal management for patients with EE-SWAS. We queried our Pediatric Epilepsy Outcome-Informatics Project (PEOIP) database for all patients treated with anakinra in our centre. We herein report a case of a female with EE-SWAS, who demonstrated remarkable neurocognitive improvement with anakinra. We suggest that a trial of anakinra may be an option for patients with EE-SWAS due to non-structural and possibly inflammatory etiology.
small molecules
2026-08-21 | Electrical Status Epilepticus in Sleep (ESES): Evolving Concepts in Etiology, Pathophysiological Mechanisms, Diagnostic Approaches, and Therapeutic Strategies for a Devastating Pediatric Epileptic Encephalopathy
Electrical status epilepticus in sleep (ESES) represents a distinctive and clinically challenging pediatric epileptic encephalopathy characterized by the triad of epilepsy, progressive cognitive regression, and remarkable potentiation of epileptiform activity during non-rapid eye movement sleep, resulting in an electroencephalographic pattern of near-continuous spike-wave discharges. This condition typically emerges during a critical neurodevelopmental window between 2 and 12 years of age, with peak incidence occurring between 3 and 5 years, a period when the developing brain exhibits heightened vulnerability to the disruptive effects of aberrant neural synchronization. The etiological landscape of ESES is remarkably heterogeneous, encompassing both structural brain abnormalities—particularly early developmental lesions involving the thalamus—and an expanding array of genetic etiologies, including monogenic mutations in genes such as GRIN2A, SCN2A, and KCNA2, as well as recurrent copy number variants. The pathophysiological mechanisms underlying the characteristic sleep activation of epileptiform discharges remain incompletely elucidated, though current conceptual frameworks implicate abnormal hyperactivation of thalamocortical oscillatory circuits, potentially driven by a shift from GABAa- to GABAb-mediated postsynaptic inhibition within the reticular thalamic network. Clinically, affected children typically present with infrequent seizures accompanied by developmental stagnation or regression, with behavioral abnormalities—particularly hyperactivity—frequently complicating the clinical picture. The diagnosis rests upon the demonstration of characteristic EEG abnormalities during NREM sleep, with quantitative assessment of the spike-wave index serving as a crucial biomarker for disease severity and treatment response. Management strategies have evolved primarily from retrospective studies and expert consensus, encompassing conventional antiepileptic drugs including levetiracetam, clobazam, and ethosuximide, as well as corticosteroid therapy—which demonstrates superior response rates—and surgical interventions in carefully selected patients with structural pathology. The prognosis is guarded, with spontaneous improvement in seizures and EEG abnormalities typically occurring after puberty, albeit with only partial reversal of cognitive deterioration. Early diagnosis and aggressive intervention are paramount, as delayed treatment may result in irreversible neuropsychological sequelae. This comprehensive review synthesizes current evidence with theoretical frameworks from developmental neurobiology and epileptology, providing a scholarly examination of ESES that informs clinical practice while identifying critical knowledge gaps that merit future investigation.
2026-08-18 | Electrophysiological, neurocognitive, and GFAP biomarker responses to corticosteroid therapy in children with ESES/CSWS.
Developmental and/or epileptic encephalopathy with spike-wave activation during sleep (DE SWAS), including electrical status epilepticus during sleep (ESES/CSWS), is associated with seizures, neurocognitive regression, and characteristic electroencephalographic abnormalities. This study aimed to evaluate the clinical, electrophysiological, neurocognitive, and molecular response to corticosteroid therapy in children diagnosed with DE-SWAS, with a particular focus on serum glial fibrillary acidic protein (GFAP) as a potential biomarker of treatment response. Eleven children aged 6-12 years were retrospectively evaluated using clinical records, sleep electroencephalography with quantification of the spike-wave index (SWI), standardized neuropsychological test results, and serum GFAP measurements obtained before and after corticosteroid treatment. Neurocognitive assessment included the Wechsler Intelligence Scale for Children-Revised (WISC-R), Stroop Color and Word Test, Bender Visual-Motor Gestalt Test, and Turkish Receptive and Expressive Language Test (TIFALDI)High-dose intravenous methylprednisolone was administered monthly for six months. During follow-up, four patients became seizure-free, while the remaining seven demonstrated a reduction in seizure frequency and duration exceeding 50%. Complete normalization of electroencephalographic findings was observed in four patients, and a ≥ 50% reduction in SWI was observed in the remaining seven. Post-treatment neurocognitive evaluations demonstrated overall improvement, particularly in attention, executive functions, and receptive language domains. Mean serum GFAP levels decreased significantly following corticosteroid therapy (p = .017). These findings suggest that corticosteroid therapy is associated with favorable clinical, electrophysiological, and neurocognitive outcomes in children with DE-SWAS and that GFAP may represent a promising biomarker of disease activity and therapeutic response. Larger prospective studies are warranted to validate these results.
2026-07-27 | Developmental and/or Epileptic Encephalopathy with Spike-Wave Activation in Sleep: From Thalamocortical Mechanisms to Precision Therapy
Developmental and/or epileptic encephalopathy with spike-wave activation in sleep (D/EE-SWAS), previously described as continuous spike-wave during slow-wave sleep (CSWS) or electrical status epilepticus in sleep (ESES), is a childhood-onset disorder characterized by cognitive, language, behavioral, and/or motor regression or stagnation associated with marked activation of epileptiform discharges during non-rapid eye movement sleep. Three themes are central to the evolving understanding of D/EE-SWAS. First, it is a network disorder in which thalamocortical dysfunction, impaired sleep-dependent synaptic homeostasis, and potentially neuroinflammatory mechanisms contribute to neurodevelopmental deterioration. Second, increasing recognition of its genetic and structural heterogeneity is reshaping diagnostic evaluation. Monogenic etiologies are identified in up to one-third of cases, with a higher yield in the developmental and epileptic encephalopathy subtype, supporting early genomic testing alongside prolonged sleep EEG, MRI, and serial neuropsychological assessment. Third, treatment remains empiric and constrained by limited comparative evidence. Corticosteroids retain the strongest evidence base for cognitive improvement, although the overall certainty of this evidence remains low to moderate. Benzodiazepines are commonly used alternatives, and epilepsy surgery can provide substantial benefit in appropriately selected patients with focal structural abnormalities. Emerging etiology-directed therapies, including L-serine for selected GRIN loss-of-function variants and primidone for TRPM3-related disease, illustrate a broader transition from syndrome-based to precision management. However, no pharmacological therapy is specifically approved for D/EE-SWAS, long-term neurodevelopmental morbidity remains common, and adequately powered trials using standardized EEG and neurocognitive outcomes are urgently needed.
2026-06-01 | Neurocognitive Trajectories Following Monthly Pulse IV Methylprednisolone in Children with Epileptic Encephalopathy
Background: Pediatric epileptic encephalopathies (EE) are characterized by drug-resistant seizures and cognitive regression. Corticosteroid therapies such as intravenous methylprednisolone (IVMP) have shown variable efficacy. This study evaluates the clinical, neurocognitive, and electrophysiological outcomes of IVMP in children with EE. Methods: A retrospective cohort of 25 children diagnosed with EE (Lennox-Gastaut Syndrome [LGS], CSWS, West Syndrome) received IVMP pulse therapy. Outcomes assessed included seizure response, EEG improvement, cognitive shift, and treatment tolerability. Univariate logistic regression explored predictors of cognitive improvement. Results: Seizure reduction ≥50% was observed in 64.0% overall, significantly higher in CSWS (100%) than LGS (30.8%, P = 0.001). EEG improvement occurred in 60.0%, also favoring CSWS (81.8% vs. 38.5%, P = 0.047). Cognitive improvement was noted in only 16.0% of patients, with no statistically significant predictors. Adverse events were mild and reported in 28.0%. Conclusions: IVMP therapy may effectively reduce seizures and EEG burden in children with EE, particularly in CSWS. However, cognitive gains remain limited, emphasizing the need for adjunctive neurorehabilitative strategies. IVMP appears to be safe and well-tolerated.
2026-01-30 | National consensus on diagnosis and treatment of epilepsy. 2026
Definition. The International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE) define epilepsy as “disorder of the brain characterized by enduring predisposition to generate epileptic seizures and by the neurobiological, cognitive, psychological and social consequences of this condition”.According to the expanded definition of epilepsy of 2014 recommended by ILAE, epilepsy is a disease of the brain defined by any of the following conditions:1. At least 2 unprovoked (or reflex) seizures occurring greater than 24 hours apart.2. One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures (a seizure occurring 30 days after brain stroke in case of established brain structural abnormalities and epileptiform EEG)3. Diagnosis of an epilepsy syndrome (Rolandic epilepsy with low risk of recurring seizures, Landau-Kleffner syndrome, epileptic encephalopathy with continuous spikes and waves during sleep).Epilepsy is considered to be resolved for:- Patients who had an age-dependent epilepsy syndrome but are now past the applicable age,or- Patients who have remained seizure-free for the last 10 years, with no seizure medicines forthe last 5 years.Epilepsy is not diagnosed when seizures occur in case of acute injuries of brain structures (strokes, traumas, encephalitis) or metabolism (hypoglycemia, syncope, intoxication) and fever.2. Epidemiology. Morbidity rate of active epilepsy is similar for the countries with different economic development – 2,3-5,9/1000 for countries with high income economy, 3,7-13,3/1000 for countries with high to moderate income economy, 2,4-22,8/1000 for countries with low to moderate income economy, 3,6-15,4/1000 for countries with low income economy. Morbidity rate is higher for countries with low income and moderate income economy. The average morbidity rate is 45 per 100 000 inhabitants in countries with high income, and 81,7 in the rest of the countries. In Bulgaria individuals suffering epilepsy are about 50 000. In 50 - 60% of the patients, the epilepsy onset occurs earlier than 16 years of age. 2-5% of the children younger than 5 years of age suffer febrile seizures.
proteins
2026-01-24 | ‘Pseudo‐ataxic’ negative myoclonic status in developmental and epileptic encephalopathy with spike‐wave activation in sleep: Utility of ACTH therapy beyond west syndrome
BACKGROUND: Developmental/Epileptic encephalopathy with spike and wave activation in sleep (DEE-SWAS) comprises a spectrum of childhood-onset epilepsies, characterized by near-continuous spike-wave discharges during non-REM sleep which can result in cognitive, behavioral, and motor regression. Negative myoclonic status in the context of DEE-SWAS is extremely rare, and management is difficult as conventional anti-seizure medications (ASM) and immunomodulatory therapies often show limited efficacy. Adrenocorticotropic hormone (ACTH), classically used for infantile spasms, has recently been reported as a potential therapy for refractory DEE-SWAS. CASE PRESENTATION: We report a 7-year-old girl with prior developmental encephalopathy, who experienced recurrent unprovoked seizures from 5 years of age, followed by progressive ataxia and language regression. Clinical examination revealed facial dysmorphism, truncal and gait ataxia, oral apraxia with atonic head drops. Video EEG revealed background slowing with bilateral centro-parieto-temporal spikes markedly activated in sleep, with clusters of atonic neck and truncal drop seizures suggestive of negative myoclonic status leading to 'pseudo-ataxia'. Despite treatment with multiple ASM, intravenous methylprednisolone and immunoglobulin, there was worsening encephalopathy and anterior opercular syndrome. Given therapeutic refractoriness, ACTH was initiated. The patient showed dramatic improvement: resolution of status, a marked reduction in EEG spike-wave burden, recovery of gait and language to baseline, and restoration of social interaction. CONCLUSION: This case demonstrates for the first time the potential of ACTH in refractory DEE-SWAS with negative myoclonic status epilepticus, wherein conventional immunomodulation fails. The sustained clinical and electrographic improvement highlights the broader neuro-modulatory mechanisms of ACTH and supports its consideration in treatment algorithms. Larger prospective studies are warranted to compare the efficacy and safety profile of various corticosteroids in DEE.
2024-06-17 | Successful treatment of epileptic encephalopathy with spike wave activation in sleep with anakinra.
Patients with epileptic encephalopathy with spike wave activation in sleep (EE-SWAS) often display drug-resistant epilepsy. The activation of epileptic activity during sleep is associated temporally with neurocognitive impairment and causes a spectrum of disorders within the epilepsy-aphasia syndrome. The prognosis is dependent on promptness of treatment and etiology. However, there is no clear consensus with regards to the optimal management for patients with EE-SWAS. We queried our Pediatric Epilepsy Outcome-Informatics Project (PEOIP) database for all patients treated with anakinra in our centre. We herein report a case of a female with EE-SWAS, who demonstrated remarkable neurocognitive improvement with anakinra. We suggest that a trial of anakinra may be an option for patients with EE-SWAS due to non-structural and possibly inflammatory etiology.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
2 orphan drug designations for Continuous spikes and waves during sleep.
2 orphan drug designations for Continuous spikes and waves during sleep.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
N-[1-((5-cyanopyridin-2-yl)methyl)-1H-pyrazol-3-yl]-2-[4-(1-(trifluoromethyl)cyclopropyl)phenyl]acetamide | small molecules | EMA | Neurocrine Therapeutics Limited | |
N-[1-(5-Cyano-pyridin-2-ylmethyl)-1H-pyrazol-3-yl]-2-[4-(1-trifluoromethyl-cyclopropyl-phenyl]-acetamide | small molecules | FDA | Neurocrine Biosciences Inc. |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI’s forecasts to outperform average preclinical success rates. Whether you’re expanding your R&D pipeline, evaluating a partnership, or simply have a question — we’d love to hear from you.