Epilepsy of Infancy With Migrating Focal Seizures (EIMFS): Expansion of Clinical Phenotypic And Genotypic Spectra

Abstract EIMFS is a rare early infantile epileptic encephalopathy with unknown etiology and poor prognosis. This study included 36 patients who were diagnosed with EIMFS. 17/36 cases had causative variants across 11 genes, including 6 novel EIMFS genes: PCDH19, ALDH7A1, DOCK6, PRRT2, ALG1 and ATP7A. 13/36 patients had ineffective seizure control, 14/36 patients had severe retardation and 6/36 patients died. Of them, the genes for ineffective seizure control, severe retardation or death include KCNT1, SCN2A, SCN1A, ALG1, ATP7A and WWOX. 17 patients had abnormal MRI, of which 8 had ineffective seizure control, 7 had severe retardation and 4 died. 13 patients had hypsarrhythmia, of which 6 had ineffective seizure control, 6 had severe retardation and 2 died. Also, 7 patients had burst suppression, of which 1 had ineffective seizure control, 3 had severe retardation and 3 died. This study is the first to report that ALDH7A1, ATP7A, DOCK6, PRRT2, ALG1, and PCDH19 mutations cause the phenotypic spectrum of EIMFS to expand the genotypic spectrum. The genes KCNT1, SCN2A, SCN1A, ALG1, ATP7A and WWOX may be associated with poor prognosis. The patients presenting with MRI abnormalities, hypsarrhythmia and burst suppression in EEG may be associated with poor prognosis.

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Malignant Migrating Partial Seizures of Infancy (MMPSI): Expansion of Clinical Phenotypic and Genotypic Spectra

10.21203/rs.3.rs-856006/v1 ◽

2021 ◽

Author(s):

liwen wu ◽

Fang Cai ◽

Siyi Gan ◽

Sai Yang ◽

Xiaofan Yang ◽

...

Keyword(s):

Poor Prognosis ◽

Seizure Control ◽

Treatment Strategies ◽

Epileptic Encephalopathy ◽

Burst Suppression ◽

Unknown Etiology ◽

Pathogenic Genes ◽

Genetic Techniques ◽

Severe Retardation ◽

Free Status

Abstract BackgroundMMPSI is a rare early infantile epileptic encephalopathy with unknown etiology and poor prognosis. With the development of genetic techniques, an increasing number of novel pathogenic genes have been shown to be related to MMSPI. This study included 36 patients who were diagnosed with MMPSI; the clinical features, etiology, treatment strategies and outcomes of these patients were determined to explore new genetic etiology and new precision medicine treatment strategies.Results36 patients were enrolled. The main seizure types were focal, tonic and spasms. The main EEG findings were seizure migration and hypsarrhythmia. 17/36 cases had causative variants across 11 genes, including 6 novel MMPSI genes: PCDH19, ALDH7A1, DOCK6, PRRT2, ALG1 and ATP7A. 13/36 patients had ineffective seizure control, 14/36 patients had severe retardation and 6/36 patients died. Of them, the genes for ineffective seizure control, severe retardation or death include KCNT1, SCN2A, SCN1A, ALG1, ATP7A and WWOX. Genes associated with seizure-free, mild-moderate retardation or normal development included PRRT2, SCN2A, ALDH7A1 and PNPO. Vitamin B6 allowed patients with ALDH7A1 and PNPO mutations to achieve seizure-free status, oxcarbazepine was effective for patients with SCN2A, ATP7A, WWOX, and PRRT2 mutations, and ACTH was partly effective for DOCK6 mutation patients with spasms and hypsarrhythmia. 17 patients had abnormal MRI, of which 8 had ineffective seizure control, 7 had severe retardation and 4 (4/17, 23.5%) died. 13 patients had hypsarrhythmia, of which 6 had ineffective seizure control, 6 had severe retardation and 2 died. Also, 7 patients had burst suppression, of which 1 had ineffective seizure control, 3 had severe retardation and 3 died.ConclusionThis study is the first to report that ALDH7A1, ATP7A, DOCK6, PRRT2, ALG1, and PCDH19 mutations cause the phenotypic spectrum of MMPSI to expand the genotypic spectrum. The genes KCNT1, SCN2A, SCN1A, ALG1, ATP7A and WWOX may be associated with poor prognosis. The patients presenting with MRI abnormalities, hypsarrhythmia and burst suppression in EEG may be associated with poor prognosis. Through early diagnosis with genetic tests and the administration of the corresponding precise treatment, the outcomes of MMPSI can be notably improved.

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Use of Perampanel and a Ketogenic Diet in Nonketotic Hyperglycinemia: A Case Report

Neuropediatrics ◽

10.1055/s-0040-1708536 ◽

2020 ◽

Vol 51 (06) ◽

pp. 417-420

Author(s):

Atsuro Daida ◽

Shin-ichiro Hamano ◽

Satoru Ikemoto ◽

Yuko Hirata ◽

Ryuki Matsuura ◽

...

Keyword(s):

Ketogenic Diet ◽

Adrenocorticotropic Hormone ◽

Seizure Control ◽

Epileptic Encephalopathy ◽

Severe Form ◽

Focal Seizures ◽

Aspartate Receptor ◽

Epileptic Spasms ◽

Glycine Cleavage ◽

Nonketotic Hyperglycinemia

Abstract Background Nonketotic hyperglycinemia is a severe form of early onset epileptic encephalopathy caused by disturbances in the glycine cleavage system; the neurological damage is mainly attributed to overstimulation of the N-methyl-D-aspartate receptor. Case The patient presented with a severe form of nonketotic hyperglycinemia and experienced frequent epileptic spasms and focal seizures, which were resistant to vigabatrin, adrenocorticotropic hormone therapy, and combined dextromethorphan and sodium benzoate treatments. By 9 months of age, perampanel reduced epileptic spasms by >50%. At 14 months of age, the ketogenic diet markedly reduced focal seizures and glycine levels in the cerebrospinal fluid. Conclusion Perampanel reduced fast excitatory neuronal activity, which was induced by an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, followed by prolonged electrical depolarizations due to an N-methyl-D-aspartate receptor. Furthermore, the ketogenic diet may have modulated the excessive neurotoxic cascade through the N-methyl-D-aspartate receptor. Perampanel and ketogenic diet were effective for seizure control in our patient.

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Lymphomatoid Granulomatosis in a Child with Acute Lymphatic Leukemia in Remission

Annals of Otology Rhinology & Laryngology ◽

10.1177/00034894780870s502 ◽

1978 ◽

Vol 87 (5_suppl) ◽

pp. 5-10 ◽

Cited By ~ 7

Author(s):

Seymour R. Cohen ◽

Stuart Siegel ◽

Eva Heuser ◽

Benjamin H. Landing ◽

Susan Shen ◽

...

Keyword(s):

Survival Rate ◽

Poor Prognosis ◽

Lymphoblastic Leukemia ◽

Lymphomatoid Granulomatosis ◽

Unknown Etiology ◽

Acute Lymphatic Leukemia ◽

Clinical Onset ◽

Lymphatic Leukemia ◽

Trachea And Bronchi ◽

Other Neoplasms

Lymphomatoid granulomatosis, a tumor-like process of unknown etiology, produced progressively destructive disease of the larynx, trachea and bronchi in an eight-year-old girl with acute lymphoblastic leukemia of five years duration. The leukemia had been in remission for 4½ years at the clinical onset of the lymphomatoid granulomatosis. Whether this occurrence suggests that lymphomatoid granulomatosis is a type of neoplasm, or is associated with immunologic depression, cannot be stated. Fortunately rare, and of poor prognosis, the disorder may become more frequent with improved survival rate of patients with leukemia and other neoplasms.

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Postanoxic Burst Suppression Electroencephalogram in a Comatose Child Associated with Spontaneous Eyelid Opening

Case Reports in Critical Care ◽

10.1155/2012/760407 ◽

2012 ◽

Vol 2012 ◽

pp. 1-3

Author(s):

John R. Crawford

Keyword(s):

Intensive Care ◽

Poor Prognosis ◽

Burst Suppression ◽

Pathophysiological Mechanism ◽

Rare Phenomenon ◽

Anoxic Injury ◽

Eye Opening ◽

Insight Into

Spontaneous eye opening associated with burst suppression electroencephalogram has been reported in adults following postanoxic injury. Previous reports have correlated the onset of epileptiform bursts with the eye opening and attribute it to a brainstem-release phenomenon associated with poor prognosis. The author presents a case of a 12-year-old boy with burst suppression electroencephalogram following severe anoxic injury where the eye opening occurred at the conclusion of the bursts that has never been previously reported. These electroencephalographic findings are important for intensive care physicians to recognize and may provide further insight into the pathophysiological mechanism of this rare phenomenon.

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A Novel Heterozygous Missense Variant in YWHAG Gene Cause Early-Onset Epilepsy in a Chinese Family

10.21203/rs.3.rs-136482/v1 ◽

2020 ◽

Author(s):

Zhi Yi ◽

Zhenfeng Song ◽

Jiao Xue ◽

Chengqing Yang ◽

Fei Li ◽

...

Keyword(s):

Early Onset ◽

Seizure Control ◽

De Novo ◽

Missense Variant ◽

Epileptic Encephalopathy ◽

Chinese Family ◽

Gene Variants ◽

Case Presentation ◽

Epileptic Encephalopathies ◽

Refractory Seizures

Abstract Background: Developmental and epileptic encephalopathies (DEE) are a heterogeneous group of severe disorders which are characterized by early-onset, refractory seizures and developmental slowing or regression. Genetic variations are significant causes for them. De novo variants in an increasing number of candidate genes have been found to be causal. YWHAG gene variants have been reported to cause developmental and epileptic encephalopathy 56 (DEE56). Case presentation: Here, we report a novel heterozygous missense variant c.170G>A (p.R57H) in YWHAG gene cause early-onset epilepsy in a Chinese family. Both the proband and his mother exhibit early onset seizures, intellectual disability, developmental delay. While the proband achieve seizure control with sodium valproate, his mother's seizures were not well controlled. Conclusions: Our report further confirming the haploinsufficiency of YWHAG results in developmental and epileptic encephalopathies.

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Cerebral Cysticercosis

PEDIATRICS ◽

10.1542/peds.63.5.761 ◽

1979 ◽

Vol 63 (5) ◽

pp. 761-763

Author(s):

William G. Tasker ◽

Stanley A. Plotkin

Keyword(s):

United States ◽

Differential Diagnosis ◽

Seizure Control ◽

Febrile Seizures ◽

The United States ◽

American Child ◽

Focal Seizures ◽

Cerebral Cysticercosis ◽

Csf Pleocytosis

A case of cerebral cysticercosis in an American child is described. The patient was only 2 years old and had never left the United States. Her symptoms began with febrile seizures and progressed to focal motor seizures. Cerebrospinal fuid pleocytosis with eosinophilia, candle-guttering of the walls of the ventricles on pneumoencephalography, and a titer of 1:4,096 against cysticercosis antigen in her blood led to the diagnosis. Over a five-year follow-up period, the patient's course has been one of resolution of her symptoms, improvement in her electroencephalogram, and excellent seizure control with anticonvulsant therapy. cysticercosis should be considered in the differential diagnosis of a child who shows CSF pleocytosis with eosinophilia, particularly if accompanied by focal seizures.

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KCNT1 epilepsy with migrating focal seizures shows a temporal sequence with poor outcome, high mortality and SUDEP

Brain ◽

10.1093/brain/awz240 ◽

2019 ◽

Vol 142 (10) ◽

pp. 2996-3008 ◽

Cited By ~ 6

Author(s):

Mathieu Kuchenbuch ◽

Giulia Barcia ◽

Nicole Chemaly ◽

Emilie Carme ◽

Agathe Roubertie ◽

...

Keyword(s):

Early Diagnosis ◽

High Mortality ◽

Poor Prognosis ◽

Early Mortality ◽

Temporal Sequence ◽

Clinical Spectrum ◽

Neurological Manifestations ◽

Focal Seizures ◽

Poor Outcome ◽

High Prevalence

Data on KCNT1 epilepsy of infancy with migrating focal seizures are heterogeneous and incomplete. Kuchenbuch et al. refine the syndrome phenotype, showing a three-step temporal sequence, poor prognosis with acquired microcephaly, high prevalence of extra-neurological manifestations and early mortality, particularly due to SUDEP. Refining the electro-clinical spectrum should facilitate early diagnosis.

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