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)

Electroencephalographic (EEG) seizures were measured in rats after intrahippocampal injection of 120 nmol quinolinic acid into the stratum radiatum CA1 or 0.19 nmol kainic acid in the dentate gyrus or in the stratum radiatum. Injection of 5 micrograms SMS 201-995, a peptidase-resistant cyclic octapeptide analogue of somatostatin, into the stratum radiatum, 15 min before quinolinic acid, did not significantly modify the number of seizures and the total time in seizures. Five micrograms SMS 201-995 injected into the stratum radiatum reduced the number of seizures induced by kainic acid in the same area and the total time spent in seizures by 58% and 75%, respectively (Student's t-test; P less than 0.01). In both instances the latency to the first ictal episode was not significantly modified. Lesions of the medial septum, which reduced the activity of choline-o-acetyl-transferase (CAT) in the dorsal hippocampus by greater than 90% after one week did not significantly affect seizures induced by quinolinic acid. In rats lesioned in the medial septum, 5 micrograms SMS 201-995 reduced the total time spent in seizures by 43%, without changing the number of ictal episodes and raised the latency to the first quinolinic acid-induced seizure by 53% (ANOVA 2 x 2, P less than 0.05) but had no effect on these measures in the corresponding sham-operated group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A peptidase-resistant cyclic octapeptide analogue of somatostatin (SMS 201-995) modulates seizures induced by quinolinic and kainic acids differently in the rat hippocampus. 183 Jan 35

A large pituitary tumour was discovered in a 20 year old man who came to medical attention because of grand-mal seizures. The tumour produced biologically active LH as demonstrated by supranormal plasma LH and plasma testosterone values. Free alpha-subunit values were also elevated. In contrast, plasma FSH was in the lower normal range. Transsphenoidal operation failed to remove all tumour tissue. Detailed studies were carried out in the postoperative period. TRH and GnRH administration were associated with a rise of plasma LH and alpha-subunit, whereas plasma FSH was low and unresponsive. Bromocriptine treatment was ineffective. In contrast, both during and after treatment with SMS 201-995 for 6 weeks, a decrease of basal plasma LH values was observed. Furthermore, the administration of a single dose of SMS 201-995 reproducibly induced a decrease of plasma LH lasting for a period of about 6 h. The study suggests that SMS 201-995 may be useful in the treatment of patients with gonadotrope cell adenomas.
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PMID:Response of luteinizing hormone secreting pituitary adenoma to a long-acting somatostatin analogue. 289 40

Syncope and epileptic seizures share some common clinical characteristics that may complicate the diagnostic process. In clinical practice, syncope is frequently misdiagnosed as an epileptic seizure and consequently treated with antiepileptic drugs. In this study, we identified 57 patients with syncope (diagnosis based on accepted criteria) who had come to our unit with a previous diagnosis of definite epilepsy in 30 cases (syncope misdiagnosed as epileptic seizures, SMS), or suspected epilepsy in the remaining 27 cases (unrecognized syncope, US). We attempted to identify factors underlying misdiagnosis by reviewing clinical findings, particularly potentially confounding features, and EEG/neuroimaging data. Finally, we compared these two groups of patients to search for crucial elements that had led to misdiagnosis. Although some clinical elements were found to be confounding in both groups, it was the interpretation of the EEG and MRI findings, particularly when combined with the confounding clinical features that constituted the main reasons for misdiagnosis.
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PMID:Over-interpretation of electroclinical and neuroimaging findings in syncopes misdiagnosed as epileptic seizures. 1752 28

The present study has been undertaken in a tertiary care centre of North-west India to know the clinical profile of epilepsy and response to drug therapy with special reference to study the effect of reduction of dosage of anti-epileptic drug after a seizure-free interval of two years. A total of 904 patients were selected during the period January, 2001 to October, 2006 who attended OPD clinic of the department of neurology, SMS Medical College and Hospital, Jaipur. Datailed clinical history was taken, general physical examination, routine blood examination, ECG and CT scan along with MRI (brain) in some cases were carried out. Of all the cases, sex ratio (male : female) was 2:1. A high proportion of cases (62.83%) were from low socio-economic group, 41.15% had normal EEG, 532 patients had normal CT scan (out of 800 cases). Single drug therapy was instituted in 71.67% cases. Patients went follow-up for 3 years. Most of the cases proved to be seizure-free after 2 years. Average maintenance dosage in patients on monotherapy can be reduced after a seizure-free interval of 2 years.
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PMID:Clinical profile of epilepsy, in a tertiary care centre of North-west India. 2188 53

Snyder-Robinson syndrome, also known as spermine synthase deficiency, is an X-linked intellectual disability syndrome (OMIM #390583). First described by Drs. Snyder and Robinson in 1969, this syndrome is characterized by an asthenic body habitus, facial dysmorphism, broad-based gait, and osteoporosis with frequent fractures. We report here a pediatric autopsy of a 4 year old male with a history of intellectual disability, gait abnormalities, multiple fractures, and seizures previously diagnosed with Snyder-Robinson syndrome with an SMS gene mutation (c.831G>T:p.L277F). The cause of death was hypoxic-ischemic encephalopathy secondary to prolonged seizure activity. Although Snyder-Robinson syndrome is rare, the need to recognize clinical findings in order to trigger genetic testing has likely resulted in under diagnosis.
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PMID:Snyder-Robinson syndrome. 3023 87

Loss-of-function mutations of the spermine synthase gene (SMS) result in Snyder-Robinson Syndrome (SRS), a recessive X-linked syndrome characterized by intellectual disability, osteoporosis, hypotonia, speech abnormalities, kyphoscoliosis, and seizures. As SMS catalyzes the biosynthesis of the polyamine spermine from its precursor spermidine, SMS deficiency causes a lack of spermine with an accumulation of spermidine. As polyamines, spermine, and spermidine play essential cellular roles that require tight homeostatic control to ensure normal cell growth, differentiation, and survival. Using patient-derived lymphoblast cell lines, we sought to comprehensively investigate the effects of SMS deficiency on polyamine homeostatic mechanisms including polyamine biosynthetic and catabolic enzymes, derivatives of the natural polyamines, and polyamine transport activity. In addition to decreased spermine and increased spermidine in SRS cells, ornithine decarboxylase activity and its product putrescine were significantly decreased. Treatment of SRS cells with exogenous spermine revealed that polyamine transport was active, as the cells accumulated spermine, decreased their spermidine level, and established a spermidine-to-spermine ratio within the range of wildtype cells. SRS cells also demonstrated elevated levels of tissue transglutaminase, a change associated with certain neurodegenerative diseases. These studies form a basis for further investigations into the leading biochemical changes and properties of SMS-mutant cells that potentially represent therapeutic targets for the treatment of Snyder-Robinson Syndrome.
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PMID:Polyamine Homeostasis in Snyder-Robinson Syndrome. 3054 65

Snyder-Robinson syndrome (SRS) is an X-linked intellectual disability syndrome caused by a loss-of-function mutation in the spermine synthase (SMS) gene. Primarily affecting males, the main manifestations of SRS include osteoporosis, hypotonic stature, seizures, cognitive impairment, and developmental delay. Because there is no cure for SRS, treatment plans focus on alleviating symptoms rather than targeting the underlying causes. Biochemically, the cells of individuals with SRS accumulate excess spermidine, whereas spermine levels are reduced. We recently demonstrated that SRS patient-derived lymphoblastoid cells are capable of transporting exogenous spermine and its analogs into the cell and, in response, decreasing excess spermidine pools to normal levels. However, dietary supplementation of spermine does not appear to benefit SRS patients or mouse models. Here, we investigated the potential use of a metabolically stable spermine mimetic, (R,R)-1,12-dimethylspermine (Me2SPM), to reduce the intracellular spermidine pools of SRS patient-derived cells. Me2SPM can functionally substitute for the native polyamines in supporting cell growth while stimulating polyamine homeostatic control mechanisms. We found that both lymphoblasts and fibroblasts from SRS patients can accumulate Me2SPM, resulting in significantly decreased spermidine levels with no adverse effects on growth. Me2SPM administration to mice revealed that Me2SPM significantly decreases spermidine levels in multiple tissues. Importantly, Me2SPM was detectable in brain tissue, the organ most affected in SRS, and was associated with changes in polyamine metabolic enzymes. These findings indicate that the (R,R)-diastereomer of 1,12-Me2SPM represents a promising lead compound in developing a treatment aimed at targeting the molecular mechanisms underlying SRS pathology.
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PMID:(R,R)-1,12-Dimethylspermine can mitigate abnormal spermidine accumulation in Snyder-Robinson syndrome. 3199 74

Snyder-Robinson syndrome (OMIM #309583) is a rare X-linked condition, caused by mutation in the SMS gene (MIM *300105), characterized by a wide spectrum of clinical signs including developmental delay, epilepsy, asthenic habitus, dysmorphism, osteopenia, and renal or genital anomalies. Here we describe two maternal half-brothers who both presented with severe neurodevelopmental delay, seizures, hearing loss, facial dysmorphism, renal and ophthalmologic anomalies, failure to thrive and premature death. A novel p.(Gly203Asp) variant was found at the hemizygous state in the two boys, and an elevated Spermidine/Spermine ratio confirmed the diagnosis of Snyder-Robinson syndrome. One of the brothers presented with gastrointestinal symptoms, with jejunal stenosis, enteral feeding intolerance, failure to thrive due to a dysfunctional gastrointestinal system, cholestasis and exocrine pancreatic insufficiency. Although more studies will be needed to understand its mechanisms, this observation lends further support to the possibility of severe digestive involvement in Snyder Robinson syndrome.
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PMID:Digestive involvement in a severe form of Snyder-Robinson syndrome: Possible expansion of the phenotype. 3318 60