1/3. Widespread upregulation of drug-resistance proteins in fatal human status epilepticus.PURPOSE: Accumulating evidence implicates drug-transporter proteins ABCB1 and ABCC1 in resistance to multiple antiepileptic drugs (AEDs) in refractory epilepsy. These proteins are upregulated in surgically resected human brain tissue containing epileptogenic pathologies, including cortical dysplasia. In surgically resected cases, no upregulation is seen in normal adjacent tissue, suggesting that neither seizures nor prolonged exposure to AEDs need induce ABCB1 or ABCC1 expression. We wished to determine if status epilepticus might cause upregulation of these proteins. methods: immunohistochemistry was performed for ABCB1 and ABCC1 in postmortem human brain tissue from a patient who died in status epilepticus and was found to have unihemispheric cortical dysplasia. RESULTS: There was upregulation of both proteins, as expected, in the hemisphere containing dysplasia. There also was widespread upregulation of both proteins in glia from the normal hemisphere. Previous work shows that drug treatment does not cause such upregulation. CONCLUSIONS: Upregulation of these proteins in histologically normal brain tissue is most likely the result of seizures in status, as seen in animal models. The findings provide a possible explanation for the appearance of AED resistance in prolonged status and emphasise the importance of prompt treatment of status epilepticus.- - - - - - - - - - ranking = 1keywords = upregulation (Clic here for more details about this article) |
2/3. Evidence for S284L mutation of the CHRNA4 in a white family with autosomal dominant nocturnal frontal lobe epilepsy.PURPOSE: To identify mutations of the neuronal nicotinic acetylcholine receptor alpha4 subunit gene (CHRNA4) responsible for autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) in a group of white patients. methods: A group of 47 patients from 21 unrelated families with ADNFLE were screened for mutations in CHRNA4. Clinical features and EEG findings in the patients were consistent with those reported in the literature for other affected families. The entire gene was amplified from genomic dna by polymerase chain reaction (PCR) followed by multitemperature single-strand conformation polymorphism analysis (MSSCP) and sequencing. RESULTS: A c.851C>T transition in exon 5 of CHRNA4 was identified in three affected individuals from two generations of the same family, but not in the remaining patients or in 100 healthy volunteers. This mutation caused an S284L substitution in the transmembrane domain M2 segment of the alpha4 subunit of the neuronal nicotinic acetylcholine receptor. The same mutation had previously been detected in a single Japanese family with ADNFLE, and in an Australian woman with a sporadic form of NFLE. CONCLUSIONS: This is the first report of an occurrence of c.851C>T transition in a white family with ADNFLE.- - - - - - - - - - ranking = 7.2608631689932E-7keywords = receptor (Clic here for more details about this article) |
3/3. hypertensive encephalopathy after bilateral carotid endarterectomy.BACKGROUND: hypertension occurs frequently after carotid endarterectomy and may lead to cerebral vascular complications and myocardial infarction. Its pathophysiology has recently been related to surgically induced damage of carotid baroreceptors. CASE DESCRIPTION: A 45-year-old normotensive man with no history of epilepsy was admitted 3 weeks after bilateral carotid endarterectomy for severe repetitive paroxysmal headaches, vomiting, and agitation that were closely associated with attacks of marked hypertension. During one of these attacks, he had a grand mal seizure. plasma catecholamine levels during hypertensive attacks were highly elevated despite the absence of pheochromocytoma, reflecting abnormalities in baroreceptor sensitivity that lead to unrestrained activation of the central sympathetic nervous system. heart rate response to valsalva maneuver showed suppression of the usual tachycardia, indicating baroreceptor reflex insensitivity. CONCLUSIONS: We report the first case of hypertensive encephalopathy associated with baroreflex failure syndrome after bilateral carotid endarterectomy. The role of blood pressure monitoring may be critical in revealing carotid baroreceptor insensitivity in such clinical settings.- - - - - - - - - - ranking = 1.4521726337986E-6keywords = receptor (Clic here for more details about this article) |