Epilepsy in children with leukodystrophies

Zhang, Jie; Ban, Takahiko; Zhou, Ling; Ji, Haoran; Yan, Huifang; Shi, Zhen; Cao, Binbin; Jiang, Yuwu; Wang, Jingmin; Wu, Ye

doi:10.1007/s00415-020-09889-y

Cited by 12 publications

(11 citation statements)

References 17 publications

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“…The median age at disease onset was relatively early (5mo), which is consistent with an Iranian study by Ashrafi et al 6 . In the study by Zhang et al., 21 the median age at seizure onset was 20 months. In the current study, the median age at seizure onset was 9 years in patients with leukodystrophy.…”

Section: Discussionsupporting

confidence: 86%

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Epidemiological, clinical, and genetic characteristics of paediatric genetic white matter disorders in Northern Finland

Knuutinen

Oikarainen

Suo‐Palosaari

et al. 2021

Develop Med Child Neuro

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Aim To examine the epidemiological, clinical, and genetic characteristics of paediatric patients with genetic white matter disorders (GWMDs) in Northern Finland. Method A longitudinal population‐based cohort study was conducted in the tertiary catchment area of Oulu University Hospital from 1990 to 2019. Patients were identified retrospectively by International Statistical Classification of Diseases and Related Health Problems codes in hospital records and prospectively by attending physicians. Inclusion criteria were children younger than 18 years with defined GWMDs or genetic disorders associated with white matter abnormalities (WMAs) on brain magnetic resonance imaging. Results Eighty patients (mean age [SD] at the end of the study 11y [8y 6mo], range 0–35y; 45 males, 35 females) were diagnosed with a defined GWMD. The cumulative childhood incidence was 30 per 100 000 live births. Regarding those patients with 49 distinct GWMDs, 20% had classic leukodystrophies and 80% had genetic leukoencephalopathies. The most common leukodystrophies were cerebral adrenoleukodystrophy, Krabbe disease, and Salla disease. Additionally, 29 patients (36%) had genetic aetiologies not previously associated with brain WMAs or they had recently characterised GWMDs, including SAMD9L‐ and NHLRC2‐related neurological disorders. Aetiology was mitochondrial in 21% of patients. The most common clinical findings were motor developmental delay, intellectual disability, hypotonia, and spasticity. Interpretation The cumulative childhood incidence of childhood‐onset GWMDs was higher than previously described. Comprehensive epidemiological and natural history data are needed before future clinical trials are undertaken. Forty‐nine distinct genetic white matter disorders (GWMDs) were identified, with 20% of cases being classic leukodystrophies. The cumulative childhood incidence of GWMDs was higher than described previously. A considerable proportion (36%) of GWMDs were previously undefined or recently characterised GWMDs. Mitochondrial aetiology was more common (21%) than previously reported.

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Section: Discussionsupporting

confidence: 86%

“…This is at the lower end of the incidence noted in previous studies, which reported the incidence of epilepsy as between 31% and 49% in children with leukodystrophy. 6,21 The relatively low incidence of epilepsy could have contributed to the later median onset of seizures in this study.…”

Section: Discussionmentioning

confidence: 85%

Epidemiological, clinical, and genetic characteristics of paediatric genetic white matter disorders in Northern Finland

Knuutinen

Oikarainen

Suo‐Palosaari

et al. 2021

Develop Med Child Neuro

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“…28,29 Moreover, leukodystrophies with early affection of subcortical white matter (eg, MLC, Alexander, and Canavan diseases) are more associated with epilepsy; subcortical white matter changes may affect adjacent cortical neurons, contributing to epilepsy. 30 Patients in the current study had typical brain MRI findings of MLC with diffuse cerebral white matter abnormalities and bilateral subcortical cysts. In patients with classic MLC, white matter signal abnormalities and subcortical cysts generally remain or increase over time.…”

Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Clinicoradiologic Correlation in 22 Egyptian Children With Megalencephalic Leukoencephalopathy With Subcortical Cysts

et al. 2022

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Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare genetic form of cerebral white matter disease whose clinicoradiologic correlation has not been completely understood. In this study, we investigated the association between clinical and brain magnetic resonance imaging (MRI) features in 22 Egyptian children (median age 7 years) with MLC. Gross motor function was assessed using the Gross Motor Function Classification System, and evaluation of brain MRI followed a consistent scoring system. Each parameter of extensive cerebral white matter T2 hyperintensity, moderate-to-severe wide ventricle/enlarged subarachnoid space, and greater than 2 temporal subcortical cysts was significantly associated ( P < .05) with worse Gross Motor Function Classification System score, language abnormality, and ataxia. Having >2 parietal subcortical cysts was significantly related to a worse Gross Motor Function Classification System score ( P = .04). The current study indicates that patients with MLC manifest signification association between certain brain MRI abnormalities and neurologic features, but this should be confirmed in larger studies.

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“…When astrocyte dysfunction occurs, it impairs its extracellular glutamic acid and K + elimination ability leading to extracellular accumulation of glutamic acid and K + , thereby increasing the excitability of neurons and inducing seizures. 16 Zang et al 17 also found leukodystrophies with early subcortical involvement of white matter were more prone to epilepsy than other types of leukodystrophy. This may suggest subcortical white matter involvement is likely to affect neighboring neurons in the cerebral cortex and can lead to epilepsy.…”

Section: Discussionmentioning

confidence: 95%

A rare case of hypomyelinating leukodystrophy-14 benefiting from ketogenic diet therapy

Ünalp¹,

Köse²,

Karaoğlu³

et al. 2022

Turk J Pediatr

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Background. Hypomyelinating leukodystrophy-14 (HLD14) is a rarely seen neurodevelopmental disease caused by homozygous pathogenic ubiquitin-fold modifier 1 gene variants. The disease has an autosomal recessive inheritance. All patients with this condition reported to date have drug-resistant epilepsy. The posttranslational modification of proteins with ubiquitin fold modifier 1 is defective in these patients and is thought to be responsible for severe neurodevelopmental problems. There is no previous report on the effectiveness of the ketogenic diet in the treatment of drug-resistant epileptic seizures in this disease. Therefore, we present a pediatric case diagnosed with HLD14 and whose drug-resistant epileptic seizures were controlled by ketogenic diet therapy. Case. The patient was a three-year-old male with drug-resistant epilepsy and developmental delay. His brain magnetic resonance imaging revealed cerebellar atrophy, periventricular white matter hypomyelination, and ventricular enlargement. Whole-exome sequencing analysis identified a homozygous pathogenic variant in the ubiquitin-fold modifier 1 gene on chromosome 13q13. Ketogenic diet therapy was initiated for his drug-resistant seizures and subsequently reduced seizure frequency by more than 75%. The patient is still on ketogenic diet therapy. Conclusions. Ketogenic diet therapy may be beneficial for seizure control in HLD14 patients with drug-resistant seizures.

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Epilepsy in children with leukodystrophies

Cited by 12 publications

References 17 publications

Epidemiological, clinical, and genetic characteristics of paediatric genetic white matter disorders in Northern Finland

Epidemiological, clinical, and genetic characteristics of paediatric genetic white matter disorders in Northern Finland

Clinicoradiologic Correlation in 22 Egyptian Children With Megalencephalic Leukoencephalopathy With Subcortical Cysts

A rare case of hypomyelinating leukodystrophy-14 benefiting from ketogenic diet therapy

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