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

The homozygous knockout mouse for the beta3 subunit of the GABAA receptor has been proposed as a model for the neurodevelopmental disorder, Angelman syndrome, based on phenotypic similarities of craniofacial abnormalities, cognitive defects, hyperactivity, motor incoordination, disturbed rest-activity cycles, and epilepsy. Since most children with Angelman syndrome are autosomal heterozygotes of maternal origin, apparently through genomic imprinting, we used gabrb3-deficient heterozygote mice of defined parental origin to investigate whether this phenotype is also maternally imprinted in mouse. Whole brain extracts showed greatly reduced beta3 subunit levels in male mice of maternal origin but not in male mice of paternal origin. Females of both parental origin showed greatly reduced beta3 subunit levels. Heterozygotes did not exhibit hyperactive circling behavior, convulsions, or electrographically recorded seizures. EEGs showed qualitative differences among heterozygotes, with male mice of maternal origin demonstrating more abnormalities including increased theta activity. Ethosuximide inhibited theta bursts, suggesting an alteration in the thalamocortical relay. Carbamazepine induced EEG slowing in males and EEG acceleration in females, with a larger effect in paternal-origin heterozygotes. Evidence thus suggests both parent-of-origin and gender-related components in developmental regulation of beta3 expression, in particular, that the maternally-derived male heterozygote may carry a developmental modification resulting in less beta3 protein, which may reflect partial genomic imprinting of the gabrb3 gene in mice.
 ...
PMID:GABAA receptor beta3 subunit gene-deficient heterozygous mice show parent-of-origin and gender-related differences in beta3 subunit levels, EEG, and behavior. 1587 4

The ceroid-lipofuscinoses comprise a group of inherited storage diseases of human beings and animals that are characterised by progressive neurodegenerative disease and the accumulation within cells of a fluorescent lipopigment. A distinct syndrome occurs in Cocker spaniel dogs in which there is a generalised accumulation of a lipofuscin-like pigment, with such a heavy accumulation in smooth muscle that the intestine and other organs have a brown discolouration. Such discolouration is not observed in other forms of ceroid-lipofuscinosis. Dogs are clinically affected in adulthood and show progressive hind limb paresis, incoordination, and deficient postural reactions and proprioception. Spinal reflexes may be exaggerated. Behavioural or temperament changes, seizures or blindness may occur.
 ...
PMID:Generalised ceroid-lipofuscinosis and brown bowel syndrome in Cocker spaniel dogs. 1603 90

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL), or Batten disease, is a childhood neurodegenerative disease that is characterized clinically by progressive visual loss, seizures, dementia, and motor incoordination. Children affected with this disease tend to develop normally for the first 5 years of life. However, once disease onset occurs, they decline rapidly and die in their late 20s to early 30s. Though this represents the typical disease course, the onset and severity of disease symptoms can vary. This variability is presumed to be the result of both differences in the causative genetic mutation in the CLN3 gene as well as environmental influences. Most cases of JNCL are caused by a 1 kb deletion in the CLN3 gene, resulting in a frameshift mutation predicted to leave the first 153 amino acids of the CLN3 protein intact, followed by the addition of 28 novel amino acids. Here we report the discovery of a novel mutation identified as a G to T transversion at nucleotide 49 (G49T) in exon 2 of CLN3, introducing a premature stop codon (E17X) near the N-terminus. This mutation represents the most 5' mutation described to date. The patient examined in this study was heterozygous for the common 1 kb deletion and E17X. She had classical disease progression, suggesting that this mutation in CLN3 mimics the more prevalent 1 kb deletion and that progression of JNCL is predominantly the result of loss of CLN3 function.
 ...
PMID:Novel CLN3 mutation predicted to cause complete loss of protein function does not modify the classical JNCL phenotype. 1608 92

Glut-1 deficiency syndrome (Glut-1 DS, OMIM #606777) is characterized by infantile seizures, developmental delay, acquired microcephaly and hypoglycorrhachia. It is caused by haploinsufficiency of the blood-brain barrier hexose carrier. Heterozygous mutations or hemizygosity of the GLUT-1 gene cause Glut-1 DS. We generated a heterozygous haploinsufficient mouse model by targeted disruption of the promoter and exon 1 regions of the mouse GLUT-1 gene. GLUT-1+/- mice have epileptiform discharges on electroencephalography (EEG), impaired motor activity, incoordination, hypoglycorrhachia, microencephaly, decreased brain glucose uptake as measured by positron emission tomography (PET) scan and decreased brain Glut-1 expression by western blot (66%). The GLUT-1+/- murine phenotype mimics the classical human presentation of Glut-1 DS. This GLUT-1+/- mouse model creates an opportunity to investigate Glut-1 function, to examine the pathophysiology of Glut-1 DS in vivo and to evaluate new treatment strategies.
 ...
PMID:A mouse model for Glut-1 haploinsufficiency. 1649 25

We report the case of a 32-month-old female patient presenting with cerebellar pilocytic astrocytoma with epileptic seizures, psychomotor delay, and severe language delay. Usually, the typical onset of cerebellar tumor is characterized by raised intracranial pressure and cerebellar incoordination. A review of the few cases reported in the literature evidencing epileptic seizures symptomatic of a focal, nondegenerative mass limited to the cerebellum is included. Moreover, a discussion about the cerebellar contribution to nonmotor functions in children is presented, in particular following tumor resection.
 ...
PMID:Epilepsy and neuropsychologic deficit in a child with cerebellar astrocytoma. 1697 Aug 95

This study was undertaken to explore the perceived impact of having a seizure (SZ) compared with having an adverse effect (AE). Patients (N=201) with partial-onset epilepsy taking two or more antiepileptic drugs (AEDs) rated their health state from 0 to100 based on their health today, hypothetical health if experiencing a SZ today, and hypothetical health if experiencing an AE today. Overall health status ratings (HLTH) declined as SZ frequency increased (P=0.01). Perceived decrements in HLTH with SZs were greatest for patients with the least frequent SZs (P=0.001) and the most recent SZs (P=0.004). Perceived decrements in HLTH with SZs compared with AEs (SZ-AE) differed across SZ recency groups (P<0.05 except for muscle incoordination and weakness). Patients with the more remote SZs were most concerned with SZ control; patients with more recent SZs were more sensitive to AED side effects. These data provide insight into the risk-benefit concerns of patients at equipoise when addressing the efficacy and AEs of AEDs.
 ...
PMID:The impact of seizures and adverse effects on global health ratings. 1768 63

Guanosine, a purine nucleotide, promotes the reuptake of l-glutamate by astrocytes; astrocytic reuptake of glutamate is a major mechanism of its synaptic inactivation. The current experiments showed that guanosine reduced the ability of MK-801 (dizocilpine), a noncompetitive NMDA receptor "open-channel" blocker, to raise the threshold voltage for electrically-precipitated tonic hindlimb extension in unstressed intact mice. This modulatory effect may be due to guanosine's removal of glutamate from the synaptic cleft, resulting in a reduced proportion of NMDA receptor-associated ion channels in the open configuration. The modulatory effect of guanosine on MK-801's ability to disrupt rotorod performance in unstressed mice or antagonize electrically-precipitated seizures in stressed mice was not seen. The inability to demonstrate modulation in the rotorod paradigm may reflect the sensitivity of this measure of motor incoordination to MK-801's disruptive effects. Whereas failure to see this effect in our incremental electroconvulsive shock paradigm in stressed mice may be due to the fact that stress and guanosine act in the same direction to reduce MK-801's antiseizure efficacy. Given the phencyclidine model of schizophrenia and its pharmacological actions as a noncompetitive NMDA receptor "open-channel" blocker and guanosine's antagonistic effect on MK-801's antiseizure efficacy in unstressed mice, the current data support development of guanine-based purines for the treatment of at least some aspects of schizophrenia.
 ...
PMID:Guanosine possesses specific modulatory effects on NMDA receptor-mediated neurotransmission in intact mice. 1832 59

The ongoing H5N1 Asian epidemic is currently affecting a number of avian species including ducks. These birds are an important part of the poultry industry in the affected countries, and it is likely that they are acting as a reservoir of infection. Ten Pekin ducks were challenged with 100 microl containing 10(7) 50% egg infective dose of the highly pathogenic avian influenza virus (HPAIV) A/Duck/Vietnam/12/05 (H5N1), administered by an intra-nasal and oral route. Clinical symptoms were recorded twice a day up to 14 days postinfection (dpi). Clinical signs were first noted at 2 dpi, with conjunctivitis and slight depression, and progressed over a period of 1-3 days to severe neurologic signs consisting of torticollis, incoordination, tremors, and seizures. Survival times varied from 3 to 7 dpi. On postmortem examination, hemorrhages were observed in the duodenum, ceca, proventriculus, ventriculus, trachea, pancreas, and brain. Histologic lesions, as well as immunohistochemistry positivity, were recorded in the pancreas and brain. In situ hybridization revealed viral antigen associated with acinar pancreatic cells, bronchial epithelial cells, and with cells of the central nervous system as well as neurons of the submucosal plexus of the duodenum. Our experimental findings agree with those previously observed in ducks naturally infected with HPAIV H5N1 viruses, confirming the acquired viral neurotropism and pancreatotropism, as previously noted in other avian species, as well as in humans.
 ...
PMID:Pathologic findings of highly pathogenic avian influenza virus A/Duck/Vietnam/12/05 (H5N1) in experimentally infected pekin ducks, based on immunohistochemistry and in situ hybridization. 1784 35

Huntington's disease is an incurable, adult-onset, dominantly inherited neurodegenerative disease. The clinical symptoms of the disease are primarily related to the progressive death of medium spiny gamma-amino butyric acid (GABAergic) neurons in the striatum and the deep layers of the cortex. Further in the later stage of life, the degeneration extends to a variety of brain regions, including the hypothalamus and hippocampus. Various GABAergic agents are being attempted for the treatment of Huntington's disease. Tiagabine [(R)-N-(4, 4-di-(3-methylthien-2-yl) but-3-enyl) nipecotic acid], a GABA uptake inhibitor, widely used in the treatment of seizures, is suggested to have neuroprotective properties. However, none of the study has elucidated its effect in the treatment of Huntington's disease and related pathologies. We explored whether tiagabine may attenuate various behavioral and biochemical alterations induced by systemic administration of 3-nitropropionic acid (an inhibitor of complex II of the electron transport chain), an accepted experimental animal model of Huntington's disease phenotype. Intraperitoneal administration of 3-nitropropionic acid (20 mg/kg., i.p.) for 4 days produced hypolocomotion, muscle incoordination and memory deficit. Daily treatment with tiagabine (5 and 10 mg/kg., i.p.) 30 min prior to 3-nitropropionic acid administration for a total of 4 days, significantly improved the 3-nitropropionic acid-induced motor and cognitive impairment. Biochemical analysis of the whole brain revealed that systemic 3-nitropropionic acid administration significantly increased lipid peroxidation, nitrite levels, total RNA levels and decreased reduced glutathione and succinate dehydrogenase activity which was reversed by daily treatment with tiagabine. Further, there was a decrease in adrenal ascorbic acid levels following daily administration of 3-nitropropionic acid, which was reversed by administration of tiagabine. The results of the present study indicate that tiagabine (5 and 10 mg/kg., i.p.) significantly reversed 3-nitropropionic acid-induced alterations in various behavioral and biochemical parameters and it could be a therapeutic agent for the treatment of Huntington's disease.
 ...
PMID:Tiagabine, a GABA uptake inhibitor, attenuates 3-nitropropionic acid-induced alterations in various behavioral and biochemical parameters in rats. 1823 12

Unverricht-Lundborg disease (ULD), progressive myoclonic epilepsy type 1 (EPM1, OMIM254800), is an autosomal recessively inherited neurodegenerative disorder characterized by age of onset from 6 to 16 years, stimulus-sensitive myoclonus, and tonic-clonic epileptic seizures. Some years after the onset ataxia, incoordination, intentional tremor, and dysarthria develop. Individuals with EPM1 are mentally alert but show emotional lability, depression, and mild decline in intellectual performance over time. The diagnosis of EPM1 can be confirmed by identifying disease-causing mutations in a cysteine protease inhibitor cystatin B (CSTB) gene. Symptomatic pharmacologic and rehabilitative management, including psychosocial support, are the mainstay of EPM1 patients' care. Valproic acid, the first drug of choice, diminishes myoclonus and the frequency of generalized seizures. Clonazepam and high-dose piracetam are used to treat myoclonus, whereas levetiracetam seems to be effective for both myoclonus and generalized seizures. There are a number of agents that aggravate clinical course of EPM1 such as phenytoin aggravating the associated neurologic symptoms or even accelerating cerebellar degeneration. Sodium channel blockers (carbamazepine, oxcarbazepine) and GABAergic drugs (tiagabine, vigabatrin) as well as gabapentin and pregabalin may aggravate myoclonus and myoclonic seizures. EPM1 patients need lifelong clinical follow-up, including evaluation of the drug-treatment and comprehensive rehabilitation.
 ...
PMID:Clinical picture of EPM1-Unverricht-Lundborg disease. 1832 13


<< Previous 1 2 3 4 5 6 7 Next >>