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)

A 63-year-old white female who was being treated for hypertension with lisinopril presented with seizures, altered mental status, and a serum sodium of 101 mEq/L. Serum sodium prior to initiation of lisinopril therapy was 137 mEq/L. The hyponatremia was corrected and did not recur after lisinopril was stopped. The hyponatremia may have been a result of polydipsia and inappropriate antidiuresis secondary to ACE-inhibitor therapy.
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PMID:Case report: severe symptomatic hyponatremia associated with lisinopril therapy. 131 75

A 24-year-old woman with overlapping features of sclerodermia sine scleroderma and systemic lupus erythematosus (SLE) presented with rapidly accelerating hypertension accompanied by neuropsychological deficits and tonic-clonic seizures. Kidney biopsy showed severe intimal hyperplasia of small renal arteries but no glomerulonephritis. Following treatment with ACE inhibitor, prednisolone and cyclophosphamide complete remission was achieved with minimal brain damage and normal kidney function. Anti-RNA polymerase I, II and III antibodies have remained positive during follow-up for 2 years, suggesting a linkage with the underlying pathogenetic pathway.
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PMID:Renal crisis in asclerodermic scleroderma--lupus overlap syndrome. 1178 81

Several genes have been implicated as influencing the outcome following traumatic brain injury (TBI). Currently the most extensively studied gene has been APOE. APOE can influence overall and rehabilitation outcome, coma recovery, risk of posttraumatic seizures, as well as cognitive and behavioral functions following TBI. Pathologically, APOE is associated with increased amyloid deposition, amyloid angiopathy, larger intracranial hematomas and more severe contusional injury. The proposed mechanism by which APOE affects the clinicopathological consequences of TBI is multifactorial and includes amyloid deposition, disruption of cytoskeletal stability, cholinergic dysfunction, oxidative stress, neuroprotection and central nervous system plasticity in response to injury. Other putative genes have been less extensively studied and require replication of the clinical findings. The COMT and DRD2 genes may influence dopamine dependent cognitive processes such as executive/frontal lobe functions. Inflammation which is a prominent component in the pathophysiological cascade initiated by TBI, is in part is mediated by the interleukin genes, while apoptosis that occurs as a consequence of TBI may be modulated by polymorphisms of the p53 gene. The ACE gene may affect TBI outcome via mechanisms of cerebral blood flow and/or autoregulation and the CACNA1A gene may exert an influence via the calcium channel and its effect on delayed cerebral edema. Although several potential genes that may influence outcome following TBI have been identified, future investigations are needed to validate these genetic studies and identify new genes that might influence outcome following TBI.
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PMID:Genetic influences on outcome following traumatic brain injury. 1734 13

We report on the clinical and molecular findings of a patient who presented alopecia, epicanthus, micrognathia, retrognathia, high arched palate, hypertelorism, Chiari type I malformation, mixed-type hearing loss but with normal heartbeat Q-T interval, malformed earlobes, down-slanted palpebral fissures, downturned corners of the mouth, syndactyly, atopic eczema, and seizures. The patient was a male adult, 23 years old, with short stature (153 cm) and low weight (50.5 kg), due to severe aortic insufficiency and dilatation of the ascending aorta. Conventional cytogenetic screening did not show any chromosomal gains or losses. Molecular genetic screening was conducted for gene mutations involved in various syndromes; the mutations found included [beta-fibrinogen -455 G>A wt/wt (wt/mut), PAI-1 4G/5G (4G/4G), HPA1 a/b (a/a), MTHFR C677T wt/wt (wt/mut), ACE I/D (I/I), and Apo E E3/E4]. Many clinical and molecular genetics findings overlapped with other conditions associated with arterial tortuosity and arterial aneurysms, including the Marfan, Ehler-Danlos, Shprintzen-Goldberg, and Loeys-Dietz syndromes. Although a diagnosis of Shprintzen-Goldberg syndrome was based on clinical findings and radiographic findings indicate other syndromes, aortic root dilatation seems to be a new symptom, similar to phenotypes of connective tissue disorders. The unique grouping of clinical manifestations in this patient and the molecular genetics findings lead us to suggest that this case could be an example of a previously unrecognized syndrome.
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PMID:A patient with ascending aortic dilatation, similar to phenotypes of connective tissue disorders. 1955 29

The RAS (renin-angiotensin system) is classically involved in BP (blood pressure) regulation and water-electrolyte balance, and in the central nervous system it has been mostly associated with homoeostatic processes, such as thirst, hormone secretion and thermoregulation. Epilepsies are chronic neurological disorders characterized by recurrent epileptic seizures that affect 1-3% of the world's population, and the most commonly used anticonvulsants are described to be effective in approx. 70% of the population with this neurological alteration. Using a rat model of epilepsy, we found that components of the RAS, namely ACE (angiotensin-converting enzyme) and the AT1 receptor (angiotensin II type 1 receptor) are up-regulated in the brain (2.6- and 8.2-fold respectively) following repetitive seizures. Subsequently, epileptic animals were treated with clinically used doses of enalapril, an ACE inhibitor, and losartan, an AT1 receptor blocker, leading to a significant decrease in seizure severities. These results suggest that centrally acting drugs that target the RAS deserve further investigation as possible anticonvulsant agents and may represent an additional strategy in the management of epileptic patients.
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PMID:Inhibition of the renin-angiotensin system prevents seizures in a rat model of epilepsy. 2053 6

The classic renin-angiotensin system (RAS) is described as a circulating hormone system focused on cardiovascular and body water regulation, with angiotensin II as its major effector. Detlef Ganten's discovery some years ago of an independent local brain RAS composed of the necessary functional components (angiotensinogen, peptidases, angiotensins and specific receptor proteins) significantly expanded the possible physiological and pharmacological functions of this system. This review first describes the enzymatic pathways resulting in active angiotensin ligands and their interaction with AT(1), AT(2) and AT(4) receptor proteins. We discuss the characterization and distribution of the AT(1) and AT(2) receptor subtypes and the current controversy over the identity of the AT(4) receptor subtype. Research findings favoring the candidates insulin-regulated aminopeptidase (IRAP) and the type 1 tyrosine kinase receptor c-Met, are presented. Next, we summarize current research efforts directed at the use of angiotensin analogues in the treatment of clinical disorders such as memory dysfunction, cerebral blood flow and cerebroprotection, stress, depression, alcohol consumption, seizure, Alzheimer's and Parkinson's diseases, and diabetes. The use of ACE inhibitors, and AT(1) and/or AT(2) receptor blockers, has shown promise in the treatment of several of these pathologies. The development of blood-brain barrier penetrant AT(4) receptor agonists and antagonists is of major importance regarding the continuing evaluation of the efficacy of new treatment approaches.
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PMID:Brain renin-angiotensin--a new look at an old system. 2177 52

The renin-angiotensin system (RAS) exists in the brain and it may be involved in pathogenesis of neurological and psychiatric disorders including seizures. The aim of the present research was to evaluate the effects of some angiotensin-converting enzyme inhibitors (ACEi; captopril, enalapril, fosinopril and zofenopril), commonly used as antihypertensive agents, in the DBA/2 mice animal model of generalized tonic-clonic seizures. Furthermore, the co-administration of these compounds with some antiepileptic drugs (AEDs; carbamazepine, diazepam, felbamate, gabapentin, lamotrigine, phenobarbital, phenytoin, topiramate and valproate) was studied in order to identify possible positive interactions in the same model. All ACEi were able to decrease the severity of audiogenic seizures with the exception of enalapril up to the dose of 100mg/kg, the rank order of activity was as follows: fosinopril>zofenopril>captopril. The co-administration of ineffective doses of all ACE inhibitors with AEDs, generally increased the potency of the latter. Fosinopril was the most active in potentiating the activity of AEDs and the combination of ACEi with lamotrigine and valproate was the most favorable, whereas, the co-administrations with diazepam and phenobarbital seemed to be neutral. The increase in potency was generally associated with an enhancement of motor impairment, however, the therapeutic index of combined treatment of AEDs with ACEi was predominantly more favorable than control. ACEi administration did not influence plasma and brain concentrations of the AEDs studied excluding pharmacokinetic interactions and concluding that it is of pharmacodynamic nature. In conclusion, fosinopril, zofenopril, enalapril and captopril showed an additive anticonvulsant effect when co-administered with some AEDs, most notably carbamazepine, felbamate, lamotrigine, topiramate and valproate, implicating a possible therapeutic relevance of such drug combinations.
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PMID:Fosinopril and zofenopril, two angiotensin-converting enzyme (ACE) inhibitors, potentiate the anticonvulsant activity of antiepileptic drugs against audiogenic seizures in DBA/2 mice. 2210 91

Many pregnant women drink varying quantities of alcohol, although several guidelines recommend total abstinence. What is known of the dangers of alcohol for the outcome of pregnancy and for the unborn child? To answer this question, we conducted a review of the literature using the standard Prescrire methodology. Fetal alcohol syndrome, which combines facial dysmorphism, growth retardation and intellectual disability, occurs in about 5% of children who are regularly exposed to at least five standard units per day (about 50 g of alcohol per day). Four studies have explored the link between heavy maternal alcohol use over a short period and the risk of cognitive impairment in the child. The results were inconclusive, however, and the authors failed to take concomitant chronic alcohol consumption into account. A methodologically sound study showed an increase in neurological abnormalities (seizures and epilepsy) when the mother drank heavily during short periods between the 11th and 16th weeks of pregnancy. There is a risk of cognitive and behavioural problems in children whose mothers regularly drank more than 2 standard units per day. Studies involving a total of about 150 000 pregnancies sought a link between low-level alcohol consumption and abnormal pregnancy outcomes. Very few showed a statistically significant link, and the results are undermined by the failure to take other risk factors into account. Weekly consumption of 5 standard units or more during pregnancy has been linked to an increased risk of cryptorchidism. Studies in a total of 57 000 pregnancies showed no effect of minimal alcohol consumption on the risk of malformations. A study of 1000 pregnancies showed a statistically significant risk of major malformations, but there were several apparent biases. A link between infant mortality and alcohol consumption during pregnancy was examined in large cohort studies. Consumption of at least 4 standard units per week increased the risk of early neonatal death. Smoking further increased the risk. Daily alcohol consumption should be avoided during pregnancy. A face-to-face interview remains the best way of detecting at-risk drinking during pregnancy. Specific questionnaires (T-ACE and Tweak) can also be helpful. Women often spontaneously cut down on their drinking in early pregnancy. A clinical trial showed that women with at-risk drinking were more likely to reduce their consumption if they were informed of the risks for their pregnancy and their unborn child on several occasions than if they were simply given an information leaflet. In practice, women must be informed of the risks of alcohol consumption during pregnancy, but this must be done tactfully. The risks of minimal alcohol consumption should not be overstated.
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PMID:Pregnancy and alcohol: occasional, light drinking may be safe. 2241 23

We describe a patient with a history of longstanding primary generalised epilepsy, on anticonvulsant therapy, who presented with fever, headache, worsening seizures and hallucinations. Among various investigations, the patient had high CSF protein and ACE levels, leptomeningeal nodular enhancement on MRI brain and non-caseating granulomas in the brain and meninges on the biopsy. The patient was diagnosed with neurosarcoidosis. Subsequently, he was found to be panhypogammaglobulinaemic and was diagnosed with probable common variable immunodeficiency (CVID). The coexistence of common variable immunodeficiency and neurosarcoidosis is rare. Typically, non-caseating granulomas in CVID patients are localised in the lymphatic tissue and solid organs. To our knowledge, there are only five reports of the granulomas of the central nervous system (CNS) in CVID. We discuss the diagnostic difficulties in this case and review the literature.
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PMID:Common variable immunodeficiency with coexisting central nervous system sarcoidosis: case report and literature review with implications for diagnosis and pathogenesis. 2261 19

The polydipsia-hyponatraemia syndrome (PHS) occurs in about 5 to 10% of institutionalised, chronically psychotic patients, 80% of whom have schizophrenia. Major clinical features are polydipsia and dilutional hyponatraemia. Complications of PHS include delirium, generalised seizures, coma and death.Nonpharmacological interventions are fluid restriction, diurnal bodyweight monitoring, behavioural approaches, and supplemental oral sodium chloride administration. These interventions require an experienced and dedicated multidisciplinary staff.A number of pharmacological treatments have been assessed for PHS including the combination of lithium and phenytoin, demeclocycline, propranolol, ACE inhibitors, selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors, typical antipsychotic drugs, clozapine and risperidone. Of these agents, the most promising are the combination of lithium and phenytoin, and clozapine.Integrated treatment requires a highly informed multidisciplinary staff, meticulous monitoring of diurnal weight gain and serum sodium level, and careful record keeping. Acute interventions of observation by trained staff, fluid restriction, water-free areas and supplemental sodium chloride administration are based on diurnal weight gain employing a monthly weight chart and a base weight method. Intravenous hypertonic saline is used briefly and administered in a highly controlled manner when patients with PHS present with generalised seizures and coma. Long term strategies include behavioural interventions and the combination of lithium and phenytoin, and clozapine.
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PMID:Polydipsia-hyponatraemia syndrome : epidemiology, clinical features and treatment. 2333 31


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