Infantile Spasms: Outcome in Clinical Studies

Riikonen, Raili

doi:10.1016/j.pediatrneurol.2020.01.015

Cited by 83 publications

(136 citation statements)

References 104 publications

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“…In a recent review of all clinical studies involving these agents, ACTH seems to be the most effective single treatment, whereas a combination of VGB and ACTH also shows promise. 31 In our cohort ACTH and Pred seemed superior to VGB in both effectiveness and side effects, which is also supported by previous case descriptions. 3,17,18 We therefore suggest that ACTH or Pred to be used as the first-line treatment of ALG13-related ES, possibly with an extended period of weaning as several individuals had seizure recurrence during tapering.…”

Section: Discussionsupporting

confidence: 91%

Predominant and novel de novo variants in 29 individuals with ALG13 deficiency: Clinical description, biomarker status, biochemical analysis, and treatment suggestions

Ng¹,

Eklund²,

Shiryaev³

et al. 2020

J of Inher Metab Disea

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Asparagine-linked glycosylation 13 homolog (ALG13) encodes a nonredundant, highly conserved, X-linked uridine diphosphate (UDP)-Nacetylglucosaminyltransferase required for the synthesis of lipid linked oligosaccharide precursor and proper N-linked glycosylation. De novo variants in ALG13 underlie a form of early infantile epileptic encephalopathy known as EIEE36, but given its essential role in glycosylation, it is also considered a congenital disorder of glycosylation (CDG), ALG13-CDG. Twenty-four previously reported ALG13-CDG cases had de novo variants, but surprisingly, unlike most forms of CDG, ALG13-CDG did not show the anticipated glycosylation defects, typically detected by altered transferrin glycosylation. Structural homology modeling of two recurrent de novo variants, p.A81T and p.N107S, suggests both are likely to impact the function of ALG13. Using a corresponding ALG13-deficient yeast strain, we show that expressing yeast ALG13 with either of the highly conserved hotspot variants rescues the observed growth defect, but not its glycosylation abnormality. We

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Section: Discussionsupporting

confidence: 91%

Predominant and novel de novo variants in 29 individuals with ALG13 deficiency: Clinical description, biomarker status, biochemical analysis, and treatment suggestions

Ng¹,

Eklund²,

Shiryaev³

et al. 2020

J of Inher Metab Disea

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“…ASD was diagnosed in 33 (13%) out 214 subjects with ISs [143]. In the group of 147 subjects a long time follow up 20-35 years after the IS a remission of the seizures was reported in a third of cases, a third had seizures with a daily or monthly frequency, and in the remaining third the seizures occurred with less frequency [140][141][142][143][144]. In a study of Krijgh et al [145], at 8 weeks and 1 year of followup of 162 subjects 64 (40%) were seizure free.…”

Section: Clinical Outcomementioning

confidence: 96%

“…Hypotonia, abnormal archaic reflexes, lethargy, poor reactivity may be clinical signs preceding the onset of IS: all these developmental features are strictly related to the serial epileptic seizures and to background molecular/cellular pathogenic events causing the ISs phenotype. Results of intellectual outcome at adult age in a cohort of 147 subjects affected by ISs according to conventional psychological test or based on educational status gave the following results: 25 children attended school normally with intelligence quotient (IQ) more than 85; 11 were slightly impaired with IQ 68 to 85; 36 with mild learning disability and IQ 40 to 60; 75 with severe impairment with IQ less than 40 [139,140]. Association of ISs and autism spectrum disorder (ASD) has been frequently reported.…”

Section: Clinical Outcomementioning

confidence: 99%

“…In a study of Krijgh et al [145], at 8 weeks and 1 year of followup of 162 subjects 64 (40%) were seizure free. IS tend to disappear within 3 to 4 years of age and transition from IS to Lennox-Gastaut syndrome is reported to occur in 18% of cases [139,140]. Fatal evolution was reported in 13% of the cases by Granstrom [146] and by Riikonen in a series of 214 children with ISs [147].…”

Section: Clinical Outcomementioning

confidence: 99%

“…According to GulMert et al [149], the most relevant prognostic factors are the etiology, the age at the time of presentation, and late and inappropriate treatments. Outcome is usually poor in cases of ISs related to severe brain malformations, post infectious diseases, and primary genetic causes [140]. Until now, the efficacy of treatment in ISs is limited, in most cases, when the pathogenic/etiologic event is severe.…”

Section: Prognosismentioning

confidence: 99%

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West syndrome: a comprehensive review

et al. 2020

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Since its first clinical description (on his son) by William James West (1793-1848) in 1841, and the definition of the classical triad of (1) infantile spasms; (2) hypsarrhythmia, and (3) developmental arrest or regression as "West syndrome", new and relevant advances have been recorded in this uncommon disorder. New approaches include terminology of clinical spasms (e.g., infantile (IS) vs. epileptic spasms (ES)), variety of clinical and electroencephalographic (EEG) features (e.g., typical ictal phenomena without EEG abnormalities), burden of developmental delay, spectrum of associated genetic abnormalities, pathogenesis, treatment options, and related outcome and prognosis. Aside the classical manifestations, IS or ES may present with atypical electroclinical phenotypes (e.g., subtle spasms; modified hypsarrhythmia) and may have their onset outside infancy. An increasing number of genes, proteins, and signaling pathways play crucial roles in the pathogenesis. This condition is currently regarded as a spectrum of disorders: the so-called infantile spasm syndrome (ISs), in association with other causal factors, including structural, infectious, metabolic, syndromic, and immunologic events, all acting on a genetic predisposing background. Hormonal therapy and ketogenic diet are widely used also in combination with (classical and recent) pharmacological drugs. Biologically targeted and gene therapies are increasingly studied. The present narrative review searched in seven electronic databases (primary MeSH terms/keywords included West syndrome, infantile spasms and infantile spasms syndrome and were coupled to 25 secondary clinical, EEG, therapeutic, outcomes, and associated conditions terms) including MEDLINE, Embase, Cochrane Central, Web of Sciences, Pubmed, Scopus, and OMIM to highlight the past knowledge and more recent advances.

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Exhaustive clinical examination of etiology and initial response to first‐line treatment in 577 children with infantile epileptic spasm syndrome children: A 5‐year retrospective observational study

Wan,

Ge,

Liu

et al. 2024

Ann Clin Transl Neurol

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ObjectiveEmploying whole‐exome sequencing (WES) technology to investigate the etiology of infantile epileptic spasm syndrome (IESS), and determining whether different etiologies exhibit phenotypic variations, while elucidating the potential associated factors, might improve short‐term responses to first‐line treatment.MethodsWe retrospectively evaluated patients with IESS admitted for treatment between January 2018 and June 2023. Clinical phenotypic differences among etiological classifications and clinical manifestations were analyzed. Variable selection using the best subset method was performed, followed by logistic regression analysis to identify the factors influencing treatment response.ResultsA total of 577 patients were included; 412 completed trio‐WES. Magnetic resonance imaging abnormalities were detected in 387 patients (67.1%). Patients with etiology as structural abnormalities were likelier to have non‐spasms at the initial seizure onset. A total of 532 patients completed the first‐line treatment; 273 patients received it for the first time at our hospital (initial response rates: 30.1% and 42.1%, respectively). The response group had a lower proportion of early‐onset seizures (≤3 months) than the no‐response group (11.3% vs. 23.7%, p < 0.01 and 11.3% vs. 21.5%, p = 0.03, respectively). Logistic regression analysis indicated that earlier initiation of first‐line treatment was associated with a higher likelihood of an initial response. However, the etiological classification did not have a significant impact on the initial response.InterpretationIESS patients with structural abnormalities are more likely to present with non‐spasm seizures at initial onset. Early initiation of first‐line treatment is crucial; however, initial responses may be less favorable when seizures occur in early infancy.

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Infantile Spasms: Outcome in Clinical Studies

Cited by 83 publications

References 104 publications

Predominant and novel de novo variants in 29 individuals with ALG13 deficiency: Clinical description, biomarker status, biochemical analysis, and treatment suggestions

Predominant and novel de novo variants in 29 individuals with ALG13 deficiency: Clinical description, biomarker status, biochemical analysis, and treatment suggestions

West syndrome: a comprehensive review

Exhaustive clinical examination of etiology and initial response to first‐line treatment in 577 children with infantile epileptic spasm syndrome children: A 5‐year retrospective observational study

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