Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human status epilepticus (SE) is consistently associated with cognitive problems, and with widespread neuronal necrosis in hippocampus and other brain regions. In animal models, convulsive SE causes extensive neuronal necrosis. Nonconvulsive SE in adult animals also leads to widespread neuronal necrosis in vulnerable regions, although lesions develop more slowly than they would in the presence of convulsions or anoxia. In very young rats, nonconvulsive normoxic SE spares hippocampal pyramidal cells, but other types of neurons may not show the same resistance, and inhibition of brain growth, DNA and protein synthesis, and of myelin formation and of synaptogenesis may lead to altered brain development. Lesions induced by SE may be epileptogenic by leading to misdirected regeneration. In SE, glutamate, aspartate, and acetylcholine play major roles as excitatory neurotransmitters, and GABA is the dominant inhibitory neurotransmitter. GABA metabolism in substantia nigra (SN) plays a key role in seizure arrest. When seizures stop, a major increase in GABA synthesis is seen in SN postictally. GABA synthesis in SN may fail in SE. Extrasynaptic factors may also play an important role in seizure spread and in maintaining SE. Glial immaturity, increased electronic coupling, and SN immaturity facilitate SE development in the immature brain. Major increases in cerebral blood flow (CBF) protect the brain in early SE, but CBF falls in late SE as blood pressure falters. At the same time, large increases in cerebral metabolic rate for glucose and oxygen continue throughout SE. Adenosine triphosphate (ATP) depletion and lactate accumulation are associated with hypermetabolic neuronal necrosis. Excitotoxic mechanisms mediated by both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors open ionic channels permeable to calcium and play a major role in neuronal injury from SE. Hypoxia, systemic lactic acidosis, CO2 narcosis, hyperkalemia, hypoglycemia, shock, cardiac arrhythmias, pulmonary edema, acute renal tubular necrosis, high output failure, aspiration pneumonia, hyperpyrexia, blood leukocytosis and CSF pleocytosis are common and potentially serious complications of SE. Our improved understanding of the pathophysiology of brain damage in SE should lead to further improvement in treatment and outcome.
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PMID:Pathophysiological mechanisms of brain damage from status epilepticus. 838 2

Two brothers, aged 27 and 20 months, born from consanguineous healthy parents, presented with cardiomyopathy, lactic acidosis and carnitine abnormalities in serum and muscle, without clinical evidence of muscle involvement. The histochemical reaction for cytochrome c oxidase (COX) activity was negative in all muscle fibres, although the holoenzyme and subunits were present at a normal level, as shown by immunocytochemistry. The COX activity was, respectively, 5 and 25% of control values, in muscle biopsies. Partial deficiency of complex IV was confirmed in fresh isolated muscle mitochondria from patient 2 and was associated with a defect of complex I. Patient 1 died at age 3 yr 6 months. Partial improvement of cardiomyopathy in patient 2 was obtained under carnitine therapy, but seizures occurred and CT scan and magnetic resonance imaging (MRI) revealed thalamic hypodensity. Thus, the disorder appears to be progressive despite the clinical stabilization of the cardiomyopathy. This further demonstrates the complexity and clinical heterogeneity of combined respiratory chain complex deficiencies.
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PMID:Infantile familial cardiomyopathy due to mitochondrial complex I and IV associated deficiency. 839 9

MELAS, a syndrome characterized by Myopathy, Encephalopathy, Lactic Acidosis and Stroke-like episodes, is one of a group of diseases known as mitochondrial encephalopathies. These genetically-transmitted diseases result in metabolic abnormalities associated with mitochondrial dysfunction, which contribute to neuronal destruction. Clinical manifestations include dementia, seizures, muscle weakness and stroke-like episodes. Accurate diagnosis is difficult to make and effective treatment is nonexistent at this time. The focus of care is supportive and the nurse's role centers on identification of deficits and maintenance of existing function.
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PMID:MELAS: a mitochondrial encephalomyopathy syndrome. 856 43

Alpers' syndrome is a progressive neurodegenerative disorder with liver disease that usually presents in the first few years of life. Only rarely have patients presented later in life with delayed onset of Alpers' syndrome. Herein we present a case of a 17-year-old male with a progressive 8-month course of severe headaches, multiple stroke-like episodes with visual deficits, and seizures that concluded with acute hemorrhagic pancreatitis. Neuropathological findings were characteristic for Alpers' syndrome: neurodegeneration and astrogliosis of the occipital cortices including the striate cortices, similar but less advanced changes in the parietal cortices, right Ammons horn sclerosis, degeneration of the posterior columns, and mild cerebellar Purkinje cell loss. Examination of the liver revealed extensive centrilobular hepatocyte necrosis. Skeletal muscle did not contain ragged red fibers, nor were there mitochondrial DNA point mutations characteristic for mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS).
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PMID:Alpers' syndrome presenting with seizures and multiple stroke-like episodes in a 17-year-old male. 860 37

The clinical course of MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes) is described in five cases. The age of onset was 9.2 years on average. Cerebral symptoms occurred at an age of 24.6 years on average. The diagnosis was only made later. Three patients died during the follow-up period. The mean age at death was 33.3 years, the average duration of the disease, 19.6 years. All patients suffered from progressive hearing loss, multiple strokes, and complex-partial and generalized seizures. They all had short stature, normal early development and 'ragged red fibers' in the muscle biopsy. Imaging studies (CT and MRI) showed bilateral calcification of basal ganglia and multiple strokes. One patient, admitted with epileptic status as initial symptom, showed lymphocytic pleocytosis in the cerebrospinal fluid; thus, in her case the differential diagnosis included encephalitis. Four patients were studied by dynamic endocrinological testing. Endocrinological disturbances were detected in three patients. Two of them suffered from hypothalamic-pituitary failure and one patient exhibited hyperprolactinemia. Endocrinological disturbances were considered an expression of the underlying cytopathy. Cerebral symptoms occurred rather late in the course of the disease and indicated poor prognosis.
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PMID:[Follow-up studies and disorders of endocrinologic function in MELAS syndrome]. 876 1

Idiopathic localization-related epilepsies are summarized according to the current classification of the International League Against Epilepsy. The recognition of a distinctive idiopathic epileptic syndrome occurring in children and featuring ictal vomiting, partial motor seizures, and occipital spikes is emphasized. Atypical evolutions of benign partial epilepsy of childhood and status of BPECS. Acquired epileptic aphasia has also been correlated to BPECS, and all these syndrome (CSWS). Childhood epilepsy with occipital paroxysms may also evolve into CSWS and into clinical and EEG status. Differential diagnosis of BPECS includes children with fortuitous associations of BPECS with cerebral palsy and the occurrence of a clinicoelectroencephalographic phenotype of BPECS in children with progressive and nonprogressive structural brain pathologies. Childhood epilepsy with occipital paroxysms should be differentiated from cerebrovascular abnormalities mitochondrial myophathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), and the syndrome of posterior cerebral calcifications, epilepsy, and celiac disease.
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PMID:[Atypical evolution of benign partial epilepsy in children]. 897 48

Coenzyme Q10 (CoQ10) transfers electrons from complexes I and II of the mitochondrial respiratory chain to complex III. There is one published report of human CoQ10 deficiency describing two sisters with encephalopathy, proximal weakness, myoglobinuria, and lactic acidosis. We report a patient who had delayed motor milestones, proximal weakness, premature exertional fatigue, and episodes of exercise-induced pigmenturia. She also developed partial-complex seizures. Serum creatine kinase was approximately four times the upper limit of normal and venous lactate was mildly elevated. Skeletal muscle biopsy revealed many ragged-red fibers, cytochrome c oxidase-deficient fibers, and excess lipid. In isolated muscle mitochondria, impaired oxygen consumption was corrected by the addition of decylubiquinone. During standardized exercise, ventilatory and circulatory responses were compatible with a defect of oxidation-phosphorylation, which was confirmed by near-infrared spectroscopy analysis. Biochemical analysis of muscle extracts revealed decreased activities of complexes I+II and I+III, while CoQ10 concentration was less than 25% of normal. With a brief course of CoQ10 (150 mg daily), the patient reported subjective improvement. The triad of CNS involvement, recurrent myoglobinuria, and ragged-red fibers should alert clinicians to the possibility of CoQ10 deficiency.
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PMID:Mitochondrial encephalomyopathy with coenzyme Q10 deficiency. 915 50

We describe a childhood mitochondrial disorder in which the clinical symptoms began and remained confined to the gastrointestinal (GI) system during the first 4 y. Seizures heralded the onset of progressive encephalopathy at age 7. Peripheral neuropathy, retinitis pigmentosa, and neural deafness developed subsequently. Laboratory investigations disclosed elevated levels of plasma lactate, and a muscle biopsy revealed ragged red fibers lacking cytochrome c oxidase activity and diminished levels of respiratory chain enzyme complexes. Molecular genetic tests failed to show any of the previously reported pathogenic mitochondrial DNA (mtDNA) mutations. We therefore screened the whole mitochondrial genome by coupling restriction digestions with single-strand conformational polymorphism (SSCP) patterns. We identified a unique SSCP in the segment that encompassed the tRNA(Lys) gene, and direct sequencing of this segment revealed a G-->A transition at an evolutionarily conserved nucleotide at mtDNA position 8313. This G8313A transition was heteroplasmic in muscle and fibroblasts of the patient, but was absent in the white blood cells and platelets from his maternal relatives. This report illustrates how GI symptoms can be the initial manifestation in a mitochondrial disorder and suggests that mitochondrial dysfunction should be considered in differentials of unexplained chronic GI symptoms, especially when lactic acidosis or other unrelated clinical signs or symptoms are present.
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PMID:A novel mitochondrial G8313A mutation associated with prominent initial gastrointestinal symptoms and progressive encephaloneuropathy. 938 Apr 35

A 32-year-old woman developed chronic progressive hearing impairment, trunkal ataxia, bilateral ptosis and external ophthalmoplegia. She also showed slowly progressive mild to moderate proximal dominant muscle weakness and atrophy. ECG showed incomplete right bundle branch block. An aerobic exercise test showed abnormal blood lactate elevation and muscle biopsy revealed ragged-red fibers in addition to the myopathic change. Analysis of mitochondrial DNA extracted from biopsied muscle and fibroblast samples revealed a 1,758bp deletion from the cytochrome b to ND6 coding regions. Common mutations in tRNALeu(UUR) coding region to the mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) were not present. She was diagnosed as having incomplete Kearns-Sayre syndrome (KSS). Since the age of 35, she developed complex partial seizure attacks with secondary generalization frequently and at the age of 42, she had a severe generalized seizure with delayed consciousness loss followed by left hemiplegia. MRI showed wide T2-high signal lesions in the right temporo-parieto-occipital area. The proton MR-spectroscopy showed prominent increase of lactate beyond the lesions detected by MRI, indicating diffuse aerobic metabolic dysfunction in the central nervous system. We reviewed two other KSS cases with a stroke like episode, who also had epilepsy and large deletion but no tRNALeu(UUR) mutation, in mitochondrial DNA. Patients with KSS who have seizure may develop the stroke-like episode as seen in MELAS patients.
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PMID:[A case of incomplete Kearns-Sayre syndrome with a stroke like episode]. 940 43

Administration of endogenous corticosterone to intact animals induces calbindin-D28k protein in the hippocampal CA1-CA2 subfields. The fact that this effect on calbindin-D28k was shown to be specific for the hippocampus argues for a receptor-mediated effect on gene expression. In addition, chronic pretreatment with corticosterone aggravates ischemia-induced neuronal damage in the CA3-CA4 subfields. This effect is similar to that of preischemic hyperglycemia, which also induces postischemic seizures and aggravates brain damage, since corticosterone raises blood glucose level and enhances tissue lactic acidosis during ischemia. The energetically compromising qualities of corticosterone indicates that it is a key factor in hippocampal vulnerability. We assume that the increase of calbindin-D28k expression in the CA1-CA2 subfields in corticosterone-treated animals is an adaptive response to the exogenous stress. The lack of adaptive response in CA3-CA4 neurons endangers them by impairing the ability of these neurons to counteract the deleterious effects of calcium. This finding, supports: (1) the hypothesis that corticosterone treatment, when paired with an ischemic insult, causes a prolonged elevation of neuronal [Ca2+]i, in an energy dependent manner, probably through the reduction of calcium efflux and (2) that neurons which do contain calbindin-D28k are particularly predisposed to ischemic insults. The CA1-CA2 neurons express high amounts of calbindin-D28k under stress conditions because their activity may involve a high rate of calcium buffering.
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PMID:Synergy between chronic corticosterone treatment and cerebral ischemia in producing damage in noncalbindinergic neurons. 950 Sep 60


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