Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ohtahara syndrome (OS) is known as an intractable epileptic syndrome in neonatal and early infantile period, differentiated from early myoclonic encephalopathy (EME) in its etiology. We report a patient with OS associated with mitochondrial respiratory chain complex (MRC) I defect. With ketogenic diet and mitochondrial cocktail therapy, seizures were completely controlled and suppression-burst patterns disappeared 3 months after starting treatment. It is suggested that OS could be caused by specific metabolic disorder such as MRC defect and the intensive therapies including ketogenic diet, vitamin and coenzyme therapy and antioxidant treatment might be helpful for some patients.
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PMID:A case of Ohtahara syndrome with mitochondrial respiratory chain complex I deficiency. 2125 94

Convulsions appearing in the neonatal or first year of life can have a very different origin, treatment or prognosis and it shall be up to the neonatologist or neuropediatrician to resolve the problem since they are the ones who know their patients best. There are severe forms of epileptic encephalopathy in the neonatal period such as Ohtahara syndrome or Aicardi myoclonic encephalopathy with poor prognosis and high morbimortality. Furthermore, there are forms of convulsions and epilepsies during the neonatal and infant period which do not respond to AED. In such cases, it is important to initiate as soon as possible another type of treatment to prevent a neurological deterioration due to repeated convulsion crises and thus allow the patients to lead a normal life with the only obligation to take a different medication from AED during their whole life. We discuss the metabolic defects which lead to convulsions and epilepsies and their various treatments. We also include a revision of some forms of convulsions and epilepsies in the infant insisting on treatments with substances completely different from AEDs.
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PMID:[Neonatal refractory seizures]. 1924 1

Aristaless-related homeobox (ARX) gene mutations cause a diverse spectrum of disorders of the human brain, including lissencephaly, various forms of epilepsy and non-syndromic mental retardation. We have identified a novel mutation, c.81C>G (p.Y27X), within the ARX gene in a family with two affected male cousins. One of the boys was diagnosed with an early infantile epileptic encephalopathy also known as Ohtahara syndrome, whereas his cousin had been diagnosed with West syndrome (WS). Both patients have normal genitalia and neither have lissencephaly. The ARX mutation identified is predicted to yield a severely truncated protein of only 26 amino acids and can be considered as a null mutation. Somewhat surprisingly, however, it does not yield the X-linked lissencephaly with ambiguous genitalia (XLAG) syndrome. We proposed that the ARX mRNA translation re-initiated at the next AUG codon at position c.121-123 (aa 41) and, thus, partly rescued these patients from XLAG. Our in vitro studies show that this N-terminally truncated ARX protein (p.M41_C562) is detected by western immunoblot in lysates from cells transiently transfected with an ARX over-expression construct containing the c.81C>G mutation. Although these findings widen the spectrum of clinical phenotypes because of mutations in the ARX gene, they also emphasize the molecular pathogenetic effect of individual mutations as well as the effect of genetic background resulting in intrafamilial clinical heterogeneity for these mutations.
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PMID:Ohtahara syndrome in a family with an ARX protein truncation mutation (c.81C>G/p.Y27X). 1973 37

ARX mutations are associated with variable clinical phenotypes. We report a new neurodegenerative phenotype associated with a known ARX mutation and causing early abnormal neurodevelopment, a complex movement disorder, and early infantile epileptic encephalopathy with a suppression-burst pattern (Ohtahara syndrome). A male infant presented at age 5 months with a dyskinetic movement disorder, which was initially diagnosed as infantile spasms. Clinical deterioration was accompanied by progressive cortical atrophy with a reduction in white matter volume and resulting in death in the first year of life; such a rapidly progressive and severe phenotype has not previously been described. ARX mutation testing should be undertaken in children aged less than 1 year with Ohtahara syndrome and a movement disorder, and in infants with unexplained neurodegeneration, progressive white matter loss, and cortical atrophy.
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PMID:A novel ARX phenotype: rapid neurodegeneration with Ohtahara syndrome and a dyskinetic movement disorder. 1974 3

The authors report the case of an infant suffered from early infantile epileptic encephalopathy with suppression-burst, or Ohtahara syndrome, a severe form of epilepsy in early childhood. The patient was treated with vigabatrin causing a favourable response. This unusual outcome may be related with the normality of neuroimaging and metabolic studies, as happens with idiopathic West syndrome cases.
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PMID:Early infantile epileptic encephalopathy with unusual favourable outcome. 1976 62

The burst suppression (BS) pattern of the EEG was originally described as a response to large dosages of anesthetics and sedatives. It was subsequently found over/in isolated cortex due to surgical procedures or lesions underlying the cortex. Around 1960 with the introduction of modern intensive care treatment (intubation, artificial respiration) the BS pattern has become a typical EEG correlate of cerebral anoxia. These obvious consequences of this therapeutic approach with their impact on the EEG picture are more or less inexplicable. The BS pattern is also typical in two rare and severe central nervous system (CNS) disorders in infants: early infantile myoclonic encephalopathy (EIME) and Ohtahara syndrome.
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PMID:The burst-suppression electroencephalogram. 2007 16

As seizures in the neonatal period have generally been identified only by direct clinical observation, there is frequently a lack of objectivity as to whether seizures are categorized as epilepsies or non-epilepsies. A major characteristic of neonatal seizures is electro-clinical dissociation and some electro-graphic seizures do not produce clinical symptoms. It is difficult to correctly identify real epilepsies or epileptic syndromes in the neonatal period without ictal electroencephalogram (EEG). Some epileptic syndromes starting in the neonatal period such as early myoclonic encephalopathy, Ohtahara syndrome, or migrating partial seizures in infancy are categorized as malignant epilepsies. A suppression-burst EEG pattern (SBP) is usually seen in neonates with serious brain damage, malignant epileptic syndromes or other neurological conditions. However SBP has not been consistently defined in the literature. We review malignant epilepsies and benign familial and non-familial neonatal seizures starting in the neonatal period and propose the characteristics of SBP in Ohtahara syndrome. Epileptic encephalopathies with SBP in the neonatal period are known to evolve into relatively few types of epileptic syndromes. We emphasize the importance of ictal EEG for diagnosis and treatment of malignant epilepsies and epileptic syndromes in the neonatal period.
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PMID:Epilepsies and epileptic syndromes starting in the neonatal period. 2106 77

Recently, it has been reported that longer expansions of the polyalanine tract of the ARX gene could cause an early infantile encephalopathy with suppression burst pattern and that the length of this repeat region could be related to the severity of the electroclinical picture. We describe the history of two male individuals, born from monozygotic twin sisters, with Ohtahara syndrome (OS) that evolved into West syndrome phenotype and epileptic encephalopathy. In both children, we have found a previously unreported missense mutation in exon 5 of ARX gene (c.1604T>A) resulting in the substitution of a leucine with a glutamine in the aminoacid sequence. The two mothers and the maternal grandmother carry the same mutation which segregates with the disease phenotype in the family. This study confirms that ARX is involved in the pathogenesis of cryptogenic early onset epileptic encephalopathy, such as OS, and suggests that the severity of the electroclinical picture is likely to not exclusively correlate with the extent of expansions of the polyalanine tracts, but rather with the functional effect of different pathogenetic mutations.
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PMID:Familial Ohtahara syndrome due to a novel ARX gene mutation. 2110 97

Ohtahara syndrome is a rare epileptic encephalopathy in infants; the underlying etiology is generally thought to be structural brain malformations. The authors present a rare case of this type of epileptic encephalopathy in which a treatable metabolic condition such as biotinidase deficiency was suspected and diagnosed, and early institution of appropriate therapy led to a good clinical outcome.
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PMID:Ohtahara syndrome with biotinidase deficiency. 2111 48

The mitochondrion is a key cellular structure involved in many metabolic functions such as ATP synthesis by oxidative phosphorylation, tricarboxylic acid cycle or fatty acid oxidation. These pathways are fundamental for biological processes such as cell proliferation or death. In the central nervous system, mitochondria dysfunctions have been involved in many neurological diseases and age-related neurodegenerative disorders, including epilepsy, Alzheimer's and Parkinson's diseases. Mitochondrial diseases are frequently caused by a disruption of the respiratory chain. Nevertheless, other mitochondrial functions, including organellar dynamics or metabolite transport, could also be involved in such pathologies. Here we described mitochondrial dysfunctions in a very severe, intractable and relatively rare neonatal epileptic encephalopathy, the Ohtahara syndrome. This condition is characterized by neonatal onset of seizures, interictal electroencephalogram with suppression burst pattern and a very poor outcome with very severe psychomotor retardation or death. The etiology of this disease remains elusive but seems to be very heterogeneous including brain malformations, metabolic errors, transcription factor and synaptic vesicle release defects. In this review, we discuss first the Ohtahara syndrome caused by mitochondrial respiratory chain damages, suggesting that these defects could be more common than previously thought. Then, we will adress the importance of the mitochondrial glutamate carrier SLC25A22 in these pathologies, since mutations of this gene were described in two distinct families. These findings suggest that glutamate metabolism should also be considered as an important cause of the Ohtahara syndrome.
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PMID:Mitochondria and neonatal epileptic encephalopathies with suppression burst. 2116 49


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