Breaking the cycle: A comparison between intravenous immunoglobulins and high dosage prednisone in the treatment of medically intractable epilepsy in children

Tang-Wai, Richard; Mailo, Janette; Rosenblatt, Bernard

doi:10.1016/j.seizure.2017.03.004

Cited by 12 publications

(5 citation statements)

References 23 publications

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“…Low (green) – moderate (yellow) – serious (orange) – critical (red): estimated risk of bias as compared to a theoretical prospective randomized study on the same intervention (following ROBINS‐I). The only randomized controlled trial 20 was assessed with the ROB‐2 tool 5,20‐57 …”

Section: Resultsmentioning

confidence: 99%

Efficacy and safety of corticosteroids and ACTH in epileptic syndromes beyond Infantile Epileptic Spasms Syndrome (IESS): A systematic review and meta‐analysis

Korinthenberg,

Bast,

Haberlandt

et al. 2024

Epilepsia

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We conducted a systematic review investigating the efficacy and tolerability of adrenocorticotropic hormone (ACTH) and corticosteroids in children with epilepsies other than infantile epileptic spasm syndrome (IESS) that are resistant to anti‐seizure medication (ASM). We included retrospective and prospective studies reporting on more than five patients and with clear case definitions and descriptions of treatment and outcome measures. We searched multiple databases and registries, and we assessed the risk of bias in the selected studies using a questionnaire based on published templates. Results were summarized with meta‐analyses that pooled logit‐transformed proportions or rates. Subgroup analyses and univariable and multivariable meta‐regressions were performed to examine the influence of covariates. We included 38 studies (2 controlled and 5 uncontrolled prospective; 31 retrospective) involving 1152 patients. Meta‐analysis of aggregate data for the primary outcomes of seizure response and reduction of electroencephalography (EEG) spikes at the end of treatment yielded pooled proportions (PPs) of 0.60 (95% confidence interval [CI] 0.52–0.67) and 0.56 (95% CI 0.43–0.68). The relapse rate was high (PP 0.33, 95% CI 0.27–0.40). Group analyses and meta‐regression showed a small benefit of ACTH and no difference between all other corticosteroids, a slightly better effect in electric status epilepticus in slow sleep (ESES) and a weaker effect in patients with cognitive impairment and “symptomatic” etiology. Obesity and Cushing's syndrome were the most common adverse effects, occurring more frequently in trials addressing continuous ACTH (PP 0.73, 95% CI 0.48–0.89) or corticosteroids (PP 0.72, 95% CI 0.54–0.85) than intermittent intravenous or oral corticosteroid administration (PP 0.05, 95% CI 0.02–0.10). The validity of these results is limited by the high risk of bias in most included studies and large heterogeneity among study results. This report was registered under International Prospective Register of Systematic Reviews (PROSPERO) number CRD42022313846. We received no financial support.

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Section: Resultsmentioning

confidence: 99%

Efficacy and safety of corticosteroids and ACTH in epileptic syndromes beyond Infantile Epileptic Spasms Syndrome (IESS): A systematic review and meta‐analysis

Korinthenberg,

Bast,

Haberlandt

et al. 2024

Epilepsia

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“…39 Researchers have studied the advantage of adding intravenous immunoglobulin to steroid in refractory childhood seizures, and have suggested a better seizure control is better with immunoglobulin, especially in children who have underlying immunological disorders. 40…”

Section: Role Of Other Antiepilepticsmentioning

confidence: 99%

Outcome of West Syndrome: A Critical Review

Adhikari

Gautam

2020

J Pediatr Epilepsy

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West syndrome is a genetically heterogeneous electro-clinical syndrome starting in early infancy. Short-term goal of therapy is spasm control and with standard hormonal or vigabatrin treatment, spasms can be controlled in 60 to 80% of patients in 2 weeks to 3 months period. Hormonal treatment with oral steroid is an alternative therapy to injectable adrenocorticotropin hormone, especially in low resource areas. Vigabatrin is preferred in tuberous sclerosis patients. Long-term aim of treatment is sustained remission of seizures and better neurodevelopmental outcome. About 50 to 70% of children are spasm free for prolonged duration, but epilepsy with multiple seizure types including Lennox–Gastaut syndrome is evident in 20 to 40% of children in long-term follow-up. Though hypsarrhythmia is helpful for the diagnosis, prognostic role of the resolution of electroencephalographic abnormalities is still uncertain. Seizures can be controlled in 40 to 60% of the patients, but only 12 to 40% children have normal neurodevelopmental outcome and a third of children are left with severe disabilities. Children with unknown etiology and normal development at spasm onset have better clinical outcome. Young age at onset, nonstandard therapy have less favorable outcome. Surgery is helpful for spasm control in patients with structural lesions and refractory spasms even in the absence of structural lesions.

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“…41 A study comparing IVIg to prednisone for the treatment of intractable pediatric epilepsy arising from a range of etiologies found a significantly greater reduction in seizures in the IVIg group. 42 Contrarily, a retrospective study of 70 patients with West syndrome found poor efficacy, 43 and a recent review of human trials did not find sufficient evidence to draw conclusions regarding the efficacy of IVIg for refractory epilepsy. 44 An in vitro study of human monocytes demonstrated a reduction of IL-6 in response to IVIg treatment.…”

Section: Evidence Of a Neuroinflammatory Contribution To Epilepsy Basmentioning

confidence: 99%

Neuroinflammatory Nexus of Pediatric Epilepsy

Bagla

Dombkowski

2018

J Pediatr Epilepsy

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A rapidly growing body of evidence supports the premise that neuroinflammation plays an important role in initiating and sustaining seizures in a range of pediatric epilepsies. Clinical and experimental evidence indicate that neuroinflammation is both an outcome and a contributor to seizures. In this manner, seizures that arise from an initial insult (e.g. infection, trauma, genetic mutation) contribute to an inflammatory response that subsequently promotes recurrent seizures. This cyclical relationship between seizures and neuroinflammation has been described as a ‘vicious cycle.’ Studies of human tissue resected for surgical treatment of refractory epilepsy have reported activated inflammatory and immune signaling pathways, while animal models have been used to demonstrate that key inflammatory mediators lead to increased seizure susceptibility. Further characterization of the molecular mechanisms involved in this cycle may ultimately enable the development of new therapeutic approaches for the treatment of epilepsy. In this brief review we focus on key inflammatory mediators that have become prominent in recent literature of epilepsy, including newly characterized microRNAs and their potential role in neuroinflammatory signaling.

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Breaking the cycle: A comparison between intravenous immunoglobulins and high dosage prednisone in the treatment of medically intractable epilepsy in children

Abstract: IVIg had greater responders and lower adverse effects and honeymoon effect. This response was independent of epilepsy type, etiology, and duration suggesting different mechanisms of action between prednisone and IVIg and a common, reversible, immune-mediated pathway to intractability.

Cited by 12 publications

References 23 publications

Efficacy and safety of corticosteroids and ACTH in epileptic syndromes beyond Infantile Epileptic Spasms Syndrome (IESS): A systematic review and meta‐analysis

Efficacy and safety of corticosteroids and ACTH in epileptic syndromes beyond Infantile Epileptic Spasms Syndrome (IESS): A systematic review and meta‐analysis

Outcome of West Syndrome: A Critical Review

Neuroinflammatory Nexus of Pediatric Epilepsy

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