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)

We have recently shown that seizures induce significant and sustained elevations of thyrotropin-releasing hormone (TRH) in specific extrahypothalamic rat brain regions associated with epileptic foci including amygdala, hippocampus, pyriform cortex, and anterior cortex. Seizures were induced in dogs to further study the effect on central nervous system TRH in a species known to show epileptiform seizures. Adult mongrel beagles were given pentylenetetrazol (PTZ) to induce generalized tonic-clonic seizures. Two groups of dogs were given either PTZ or saline every other day for four intravenous injections. Major motor seizures were observed visually and by electroencephalography with each PTZ injection, and these lasted from 3 to 10 minutes. Forty-eight hours after the fourth seizure, the dogs were killed and brains were removed, dissected, and stored at -90 degrees. After acetic acid extraction, extracts were assayed for TRH content by specific radioimmunoassay. Significant (P < 0.05) postictal TRH increases were seen in frontal cortex (1.5-fold), dorsal hippocampus (2.2-fold), pyriform cortex (2.5-fold), and amygdala (2.1-fold). Cerebellum, medulla, thalamus, hypothalamus, and septum showed no postictal changes in TRH. This report is the first to demonstrate TRH elevations in specific central nervous system regions associated with epileptic foci in the dog. Our results continue to stress the importance of the pyriform/periamygdaloid region as a key limbic region of endogenous TRH action in response to seizures and provides further evidence that TRH is either directly or indirectly involved in seizure modulation. Additional recent data from our laboratory and others suggest that this modulation is intrinsic to the hippocampus and may be anticonvulsant in nature.
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PMID:Regional changes in central nervous system thyrotropin-releasing hormone after pentylenetetrazol-induced seizures in dogs. 143 20

Sodium diphenylhydantoin (DFH-Na) is the drug of choice to control convulsive seizure disorders. Beneficial as well as adverse effects of DFH-Na have been reported to occur since 1938. Thus, the present article deals with the effect that 2.5, 5, 10, 15, 20 and 100 mg/kg/day (2.5, 5, 10, 15, 20 and 100) might cause on Cerebrum (C), Cerebellum (Cb) and liver (L) DNA [DNA] and Protein [Pr] concentration. Our results showed that: 1) DNA-C-14 (15, 20 and 100) were found decreased when compared to control (p less than 0.001) and [DNA]-C-30 (15, 20 and 100) as well (p less than 0.001). [Pr]-C-7, 14, 30 (2.5, 5, 10, 15, 20 and 100) showed no statistically important differences. 2) [DNA]-Cb-14 (15 and 20) were found lower than control (p less than 0.05) and [DNA]-Cb-30 (15 and 20) as well (p less than 0.05). [Pr]-Cb-14,30 (100) was found decreased (p less than 0.05). 3) [DNA]-L-14 (10, 15, 20 and 100) was found decreased when compared to control (p less than 0.001) and [DNA]-L-30 (10, 15, 20 and 100) as well (p less than 0.001). [Pr]-L-7, 14 and 30 (2.5, 5, 10, 15, 20 and 100) were found lower than control (p less than 0.05). A bimodal pattern of [DNA] of C. Cb and L was demonstrated to occur with i.p. injected DFH-Na.
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PMID:[Sodium diphenylhydantoin changes the concentrations of DNA and proteins in the cerebrum, cerebellum and liver]. 222 13

Mice with the weaver mutation exhibit an uneven weave to their gait, ataxia, mild locomotor hyperactivity and, occasionally, tonic-clonic seizures. A single amino acid mutation in a G-protein coupled, inwardly rectifying K+ channel, GIRK2, gives rise to the symptoms seen in the weaver mice. Two areas of the brain are primarily affected. Cerebellar granule cell neurons die soon after birth and dopaminergic neurons are severely depleted in the substantia nigra. In this article we review recent studies of wild-type and mutant GIRK channels found in native cells or introduced into expression systems. We also review two models that explain some of the details leading to the neuronal cell death observed in weaver mice.
Cerebellum 2002 Jul
PMID:Cell death in weaver mouse cerebellum. 1287 81

The cerebellum is known to have inhibitory effects on seizures. Nevertheless, cerebellar dysplastic lesions can be epileptogenic. We report a patient presenting with epilepsia partialis continua (EPC) following a hemorrhagic cerebellar lesion. Possible pathophysiological mechanisms are discussed.
Cerebellum 2004
PMID:Epilepsia partialis continua possibly caused by cerebellar lesion. 1568 3

The major aim of this study was to elucidate the role of nitric oxide (NO) in the development of pentylenetetrazole (PTZ)-kindling as an animal model of primary generalized epilepsy. The daily administration of PTZ is associated with an increase in the amount of neuronal nitric oxide synthase (nNOS). NO generation was measured directly by in vivo and ex vivo electron paramagnetic resonance on rodents undergoing progressive convulsions. We found that primary generalized epilepsy is caused by NO induction during the persistent up-regulation of nNOS expression, but that NO induction is not associated with severe generalized seizures following long-term kindling phenomena after PTZ withdrawal. Morphological changes in the brain structure of rats were measured by magnetic resonance imaging during epileptic convulsions induced by repetitive administration of PTZ. Cerebellum volume for kindled rats decreased 20% but not in rats treated with the nNOS inhibitor, 3Br-7NI, suggesting that generation of NO in the cerebellum is related to decrease in cerebellum volume following PTZ-kindling.
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PMID:Magnetic resonance and biochemical studies during pentylenetetrazole-kindling development: the relationship between nitric oxide, neuronal nitric oxide synthase and seizures. 1554 97

Progressive myoclonic epilepsies (PMEs) are a group of rare disorders characterized by the occurrence of seizures, myoclonus, and progressive neurological dysfunction. This article discusses epidemiology, genetics, pathology, clinical manifestations, EEG characteristics, methods of diagnosis and treatment of the most common causes of PME, including Unverricht-Lundborg Disease (Baltic Myoclonus), MERRF, neuronal ceroid lipofuscinosis, dentatorubropallidoluysan atrophy, Gaucher disease, Lafora disease, and sialidosis. The aim of this paper is to provide clinicians with useful clinical information in order to facilitate the diagnosis and treatment of these rare diseases.
Cerebellum 2004
PMID:Progressive myoclonic epilepsy. 1554 6

Spinocerebellar ataxias (SCAs) are a clinically heterogeneous group of disorders. Current molecular classification corresponds to the order of gene description (SCA1-SCA 25). The prevalence of SCAs is estimated to be 1-4/100,000. Patients exhibit usually a slowly progressive cerebellar syndrome with various combinations of oculomotor disorders, dysarthria, dysmetria/kinetic tremor, and/or ataxic gait. They can present also with pigmentary retinopathy, extrapyramidal movement disorders (parkinsonism, dyskinesias, dystonia, chorea), pyramidal signs, cortical symptoms (seizures, cognitive impairment/behavioral symptoms), peripheral neuropathy. SCAs are also genetically heterogeneous and the clinical diagnosis of subtypes of SCAs is complicated by the salient overlap of the phenotypes between genetic subtypes. The following clinical features have some specific values for predicting a gene defect: slowing of saccades in SCA2, ophthalmoplegia in SCA1, SCA2 and SCA3, pigmentary retinopathy in SCA7, spasticity in SCA3, dyskinesias associated with a mutation in the fibroblast growth factor 14 (FGF 14) gene, cognitive impairment/behavioral symptoms in SCA17 and DRPLA, seizures in SCA10, SCA17 and DRPLA, peripheral neuropathy in SCA1, SCA2, SCA3, SCA4, SCA8, SCA18 and SCA25. Neurophysiological findings are compatible with a dying-back axonopathy and/or a neuronopathy. Three patterns of atrophy can be identified on brain MRI: a pure cerebellar atrophy, a pattern of olivopontocerebellar atrophy, and a pattern of global brain atrophy. A remarkable observation is the presence of dentate nuclei calcifications in SCA20, resulting in a low signal on brain MRI sequences. Several identified mutations correspond to expansions of repeated trinucleotides (CAG repeats in SCA1, SCA2, SCA3, SCA6, SCA7, SCA17 and DRPLA, CTG repeats in SCA8). A pentanucleotide repeat expansion (ATTCT) is associated with SCA10. Missense mutations have also been found recently. Anticipation is a main feature of SCAs, due to instability of expanded alleles. Anticipation may be particularly prominent in SCA7. It is estimated that extensive genetic testing leads to the identification of the causative gene in about 60-75 % of cases. Our knowledge of the molecular mechanisms of SCAs is rapidly growing, and the development of relevant animal models of SCAs is bringing hope for effective therapies in human.
Cerebellum 2005
PMID:The wide spectrum of spinocerebellar ataxias (SCAs). 1589 52

Spinocerebellar ataxia type 10 (SCA10) is a dominantly inherited ataxia caused by expansion of ATTCT pentanucleotide repeat in intron 9 of a novel gene, E46L, on chromosome 22q13.3. SCA10 is a complex neurodegenerative condition. Initial studies characterized SCA10 as pure cerebellar ataxia associated with seizures. Recent identification of new SCA10 families revealed more diverse phenotypes, including polyneuropathy, pyramidal signs, cognitive and neuropsychiatric impairment. Moreover, several families manifest with ataxia without seizures. Thus a complete clinical spectrum is emerging. Progress has also been made in understanding the molecular and genetic mechanisms of pathogenesis. The length of expanded ATTCT repeats is variable in different tissues and highly unstable during paternal transmission, revealing complex genetic and pathogenetic processes. Under torsional stress, ATTCT repeats form unpaired DNA structure and may serve as an erroneous DNA replication origin, potentially contributing to repeat instability and aberrant cell cycle entry. E46L is a cytoplasmic protein with unknown function. Reduced expression of E46L in primary neuronal cultures from cerebellum and cortex by small interfering RNAs (siRNAs) caused increased apoptosis, raising the possibility that reduced expression of E46L might also play an important role in SCA10 pathogenesis.
Cerebellum 2005
PMID:Recent progress in spinocerebellar ataxia type-10 (SCA10). 1589 57

Autism is a neurodevelopmental disorder that is often comorbid with seizures. Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in brain. GABA(B) receptors play an important role in maintaining excitatory-inhibitory balance in brain and alterations may lead to seizures. We compared levels of GABA(B) receptor subunits GABA(B) receptor 1 (GABBR1) and GABA(B) receptor 2 (GABBR2) in cerebellum, Brodmann's area 9 (BA9), and BA40 of subjects with autism and matched controls. Levels of GABBR1 were significantly decreased in BA9, BA40, and cerebellum, while GABBR2 was significantly reduced in the cerebellum. The presence of seizure disorder did not have a significant impact on the observed reductions in GABA(B) receptor subunit expression. Decreases in GABA(B) receptor subunits may help explain the presence of seizures that are often comorbid with autism, as well as cognitive difficulties prevalent in autism.
Cerebellum 2009 Mar
PMID:Expression of GABA(B) receptors is altered in brains of subjects with autism. 1900 45

Unilateral cerebellar hypoplasia (UCH) is a rare pathological condition characterized by the loss of volume in cerebellar hemispheres ranging from mild asymptomatic to severe symptomatic cases. As the designation of UCH remains problematic, the underlying etiopathogenesis also lacks explanation. We investigated the patients admitted to Departments of Child Neurology, Neurology, and Genetics between the years 1992 and 2010 and detected 12 patients with unilateral cerebellar volume loss, with the exclusion of all other cerebellar pathologies. The ages of patients ranged between 6 months to 55 years. Five patients had a delay in developmental milestones, and one of these was diagnosed with neurofibromatosis type 1. Two patients had epileptic seizures, one patient had peripheral facial paralysis as a component of Moebius syndrome, and four patients were incidentally diagnosed during etiological work-up for headache. The clinical outcomes of patients varied from healthy subjects to marked developmental impairment. Radiologically, five patients had severe disproportionate UCH, six had moderate disproportionate, and one had mild proportionate UCH. Cerebellar peduncles were affected in all, and vermis was partly hypoplastic in eight patients. Brainstem was involved in four patients, and seven patients showed involvement of white matter and/or corpus callosum. Imaging features supported that patients with severe disproportionate UCH also displayed additional cerebral and commissural changes, which were related to ischemic or vascular injuries, implying a prenatally acquired disruption. In the presence of such a wide spectrum of clinical and radiological features, a prenatally acquired lesion and, thus, a disruption seem to be more explanatory rather than a primary developmental process or malformation in the etiopathogenesis of unilateral cerebellar hypoplasia.
Cerebellum 2011 Mar
PMID:Unilateral cerebellar hypoplasia with different clinical features. 2096 75


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