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

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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Single-Epileptic Spasms with or without Hypsarrhythmia: A Study of 16 Patients

Journal of Pediatric Epilepsy ◽

10.1055/s-0037-1603521 ◽

2017 ◽

Vol 06 (03) ◽

pp. 149-155

Author(s):

Raffaele Falsaperla ◽

Robinson Gutierrez ◽

Gabriela Valenzuela ◽

Piero Pavone ◽

Sebastian Fortini ◽

...

Keyword(s):

Antiepileptic Drugs ◽

Ketogenic Diet ◽

Adrenocorticotropic Hormone ◽

Main Type ◽

Epileptic Encephalopathy ◽

Unknown Etiology ◽

Epileptic Spasms ◽

Before And After ◽

Eeg Recordings ◽

Electroencephalogram Eeg

Objective We evaluated the electroclinical features, etiology, treatment, and outcome of 16 patients with single-epileptic spasms (ESs) with or without hypsarrhythmia (WoH). Methods Nine boys and seven girls had single-ESs. ESs were considered as single epileptic spasm variants when no other spasm occurred for 1 minute before and after each spasm. Age at the onset of ESs was between 2 and 84 months, with a mean age of 11 months. Results We recognized a group of 15 patients with single-ESs as the main type of seizure; 6 patients with WoH and 9 patients with hypsarrhythmia, respectively. Nine of these 15 patients had other types of seizures before the onset of single-ESs, and 12 patients had other types of seizures during the period in which the ESs occurred. Nine of 15 patients had a structural and seven had an unknown etiology. In 10 cases, the ESs were refractory to antiepileptic drugs, while 4 patients responded well to adrenocorticotropic hormone (ACTH), 1 to pyridoxine, and 2 to the ketogenic diet (KD). The remaining patient (patient.16) had single-ESs and electroclinical features of Lennox–Gastaut syndrome (LGS). Conclusion In this article, we present a series of infants who had daily single-ESs with or WoH. Those with single-ESs with hypsarrhythmia evolved to an epileptic encephalopathy. Video-electroencephalogram (EEG) and polygraphic-EEG recordings are crucial to identify the single-ESs.

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Efficacy of Tryptophan for the Treatment of Nonketotic Hyperglycinemia: A New Therapeutic Approach for Modulating the N-Methyl-D-aspartate Receptor

PEDIATRICS ◽

10.1542/peds.95.1.142 ◽

1995 ◽

Vol 95 (1) ◽

pp. 142-146

Author(s):

Satoshi Matsuo ◽

Fumio Inoue ◽

Yoshihiro Takeuchi ◽

Hiroshi Yoshioka ◽

Akihiko Kinugasa ◽

...

Keyword(s):

Excitatory Amino Acid ◽

Muscular Hypotonia ◽

Inherited Disease ◽

Excitatory Amino Acid Receptors ◽

Amino Acid Receptors ◽

Aspartate Receptor ◽

Cleavage Enzyme ◽

Glycine Cleavage ◽

Glycine Level ◽

Nonketotic Hyperglycinemia

Nonketotic hyperglycinemia (NKH) is a rare inherited disease caused by a defect of the glycine cleavage enzyme.1 Especially in the neonatal type, neurological symptoms such as muscular hypotonia, seizures, respiratory distress, and lethargy develop rapidly, and the prognosis is unfavorable.1 Elevation of glycine in the cerebrospinal fluid (CSF) is thought to be responsible for these symptoms. However, management is quite difficult, because it is not well understood how elevation of glycine causes these symptoms. Lowering of the glycine level in CSF with sodium benzoate is not enough to avoid severe psychomotor and mental retardation. The N-methyl-D-aspartate (NMDA) receptor, which is one of the excitatory amino acid receptors, has a glycine binding site.2

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

10.21203/rs.3.rs-1112666/v1 ◽

2021 ◽

Author(s):

Liwen Wu ◽

Fang Cai ◽

Siyi Gan ◽

Sai Yang ◽

Xiaofan Yang ◽

...

Keyword(s):

Poor Prognosis ◽

Seizure Control ◽

Epileptic Encephalopathy ◽

Burst Suppression ◽

Unknown Etiology ◽

Focal Seizures ◽

Phenotypic Spectrum ◽

Severe Retardation

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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De Novo KCNQ2 Mutation in One Case of Epilepsy of Infancy With Migrating Focal Seizures That Evolved to Infantile Spasms

Child Neurology Open ◽

10.1177/2329048x18767738 ◽

2018 ◽

Vol 5 ◽

pp. 2329048X1876773 ◽

Cited By ~ 2

Author(s):

Haolin Duan ◽

Jing Peng ◽

Miriam Kessi ◽

Fei Yin

Keyword(s):

Adrenocorticotropic Hormone ◽

De Novo ◽

Epileptic Encephalopathy ◽

Infantile Spasms ◽

Heterozygous Mutation ◽

Interictal Spikes ◽

Rare Type ◽

Focal Seizures ◽

First Case ◽

New Association

Epilepsy of infancy with migrating focal seizures (EIMFS) is a rare type of early-onset epileptic encephalopathy that is characterized by refractory migratory multifocal seizures that migrate between hemispheres. Its etiology is not well known although it is postulated to occur due to channelopathy. The authors report the first case of EIMFS due to a de novo heterozygous mutation in exon 4(c.881C>T missense mutation, p.Ala294Val, NM_172107.2) in KCNQ2 gene which later evolved into infantile spasms. However, it is the second case of EIMFS with KCNQ2 mutation. He presented with multifocal migratory partial seizures which started at the age of 8 days. Electroencephalogram examination revealed multifocal interictal spikes that migrated from one hemisphere to the other within a seizure. It was intractable with antiepileptic drugs and adrenocorticotropic hormone. He later developed spasms from the age of 8 months. Consequently, our case supports the new association between EIMFS and KCNQ2 mutations. Moreover, it enriches the disease phenotype because of transformation.

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Migrating Focal Seizures and Myoclonic Status in ARV1-Related Encephalopathy

Neurology Genetics ◽

10.1212/nxg.0000000000000593 ◽

2021 ◽

Vol 7 (3) ◽

pp. e593

Author(s):

Francesca Darra ◽

Tommaso Lo Barco ◽

Roberta Opri ◽

Elena Parrini ◽

Claudia Bianchini ◽

...

Keyword(s):

Respiratory Infections ◽

Brain Mri ◽

High Amplitude ◽

Epileptic Encephalopathy ◽

Severe Form ◽

Compound Heterozygous ◽

Mri Findings ◽

Eeg Activity ◽

Focal Seizures ◽

Visual Inattention

ObjectiveTo report longitudinal clinical, EEG, and MRI findings in 2 sisters carrying compound heterozygous ARV1 mutations and exhibiting a peculiar form of developmental and epileptic encephalopathy (DEE). Neuropathologic features are also described in one of the sisters.MethodsClinical course description, video-EEG polygraphic recordings, brain MRI, skin and muscle biopsies, whole-exome sequencing (WES), and brain neuropathology.ResultsSince their first months of life, both girls exhibited severe axial hypotonia, visual inattention, dyskinetic movements, severe developmental delay, and slow background EEG activity. Intractable nonmotor seizures started in both at the eighth month of life, exhibiting the electroclinical characteristics of epilepsy of infancy with migrating focal seizures (EIMFS). In the second year of life, continuous epileptiform EEG activity of extremely high amplitude appeared in association with myoclonic status, leading to severely impaired alertness and responsiveness. Repeated brain MRI revealed progressive atrophic changes and severe hypomyelination. WES identified a compound heterozygous in the ARV1 gene [(p.Ser122Glnfs*7) and (p.Trp163*)] in one patient and was subsequently confirmed in the other. Both sisters died prematurely during respiratory infections. Postmortem neuropathologic examination of the brain, performed in one, revealed atrophic brain changes, mainly involving the cerebellum.ConclusionsThis report confirms that biallelic ARV1 mutations cause a severe form of DEE and adds epilepsy with migrating focal seizures and myoclonic status to the spectrum of epilepsy phenotypes. Considering the potential role of human ARV1 in glycosylphosphatidylinositol (GPI) anchor biosynthesis, this severe syndrome can be assigned to the group of inherited GPI deficiency disorders, with which it shares remarkably similar clinical and neuroimaging features. ARV1 should be considered in the genetic screening of individuals with EIMFS.

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The Ketogenic Diet for Seizure Control

Complementary health practice review ◽

10.1177/153321019600200107 ◽

1996 ◽

Vol 2 (1) ◽

pp. 45-48

Author(s):

J. L. Bell

Keyword(s):

Ketogenic Diet ◽

Seizure Control

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Beneficial effects of the ketogenic diet on drug-resistant epileptic encephalopathy associated with a de novo NBEA pathogenic variant

Epileptic Disorders ◽

10.1684/epd.2021.1327 ◽

2021 ◽

Vol 23 (5) ◽

pp. 739-743

Author(s):

Silvia Schiavoni ◽

Carlotta Spagnoli ◽

Susanna Rizzi ◽

Grazia Gabriella Salerno ◽

Daniele Frattini ◽

...

Keyword(s):

Ketogenic Diet ◽

De Novo ◽

Epileptic Encephalopathy ◽

Pathogenic Variant ◽

Drug Resistant ◽

Beneficial Effects

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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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