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)

Epilepsy is a common comorbidity among developmentally disabled (DD) patients, and special considerations apply to its treatment. In particular, clinicians should try to avoid antiepileptic drugs (AEDs) with sedating properties or adverse cognitive effects that might further diminish quality of life for DD patients. Behavioral changes due to medication and significant pharmacokinetic interactions with other medications are also concerns. The newer AEDs, approved in the 1990s, offer new options for the treatment of individuals with developmental disability and epilepsy. Gabapentin does not interact with the hepatic metabolism of other AEDs or psychotropic agents, results in a statistically significant reduction in seizure frequency in mentally retarded children, and is generally well tolerated. Felbamate is an effective broad-spectrum AED, but has serious toxicity issues limiting its use. Lamotrigine has been extensively studied in the DD population, achieving seizure reduction rates of up to 50% in some trials. Although it is usually well tolerated in this population, its pharmacokinetic profile is influenced by concomitant medications. Levetiracetam has been found to be effective against kindled seizures and has been approved as adjunctive therapy for partial epilepsies. It does not cause any pharmacokinetic interactions, but may have behavioral side effects. Oxcarbazepine is a homologue of carbamazepine that has fewer drug interactions. It is approved for mono- or adjunctive therapy in patients with partial seizures, and its use in DD individuals appears to be worthwhile. Tiagabine is extensively bound to plasma proteins and is therefore subject to protein-binding displacement interactions by other highly protein-bound drugs, such as sodium valproate. While there are trial data showing its efficacy as adjunctive therapy in partial epilepsy in adults and children, there is a paucity of data specific to the DD population. Common side effects include sedation. Topiramate is a broad-spectrum AED approved as adjunctive therapy for partial and primary generalized tonic-clonic seizures. It appears to be particularly effective in patients with Lennox-Gastaut syndrome and those with cognitive disabilities. It appears to be better tolerated in the DD population than in the general population. Zonisamide has been effective in the DD population, yielding a seizure reduction of 50% in 41% of children in 1 trial. It has been associated with renal stone formation, sedation, and cognitive effects, however. The new AEDs have a role in treating seizures in the DD. Side effects that limit their use include anorexia, behavioral changes, and sedation. Seizure exacerbation can occur with the new AEDs and success is defined empirically and by improvements in quality of life.
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PMID:Antiepileptic drug treatment in the developmentally disabled: treatment considerations with the newer antiepileptic drugs. 1260 9

A one-year-old, neutered female Skye terrier presented with anorexia, vomiting, seizures and ascites. Portal venography demonstrated the presence of multiple acquired portosystemic shunts. Hepatic biopsy confirmed the presence of copper accumulation and fibrosis. Treatment included ursodeoxycholic acid therapy, colchicine and oral zinc. To the authors' knowledge, this is the first case report detailing successful management of Skye terrier hepatopathy.
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PMID:Diagnosis and management of hepatic copper accumulation in a Skye terrier. 1262 74

A family of three white-faced saki monkeys (Pithecia pithecia pithecia) died 48-96 hours after the onset of anorexia, nasal discharge, pyrexia and oral ulceration. One animal also had clonic seizures. Lesions found post-mortem consisted of oral and esophageal ulcers, hepatic and intestinal necrosis, meningoencephalitis and sporadic neuronal necrosis. Intranuclear inclusion bodies and syncytial cells were present in oral lesions and affected areas of liver. Herpes simplex virus 1 (HSV-1) was identified as the etiology of disease by virus isolation, polymerase chain reaction, or in situ hybridization in all three animals. Immunohistochemistry for detection of apoptotic DNA and activated caspase-3 showed significant levels of apoptosis in oral and liver lesions and occasional apoptotic neurons in the brain. These findings demonstrate the vulnerability of white-faced saki monkeys to HSV-1 and provide initial insight into the pathogenesis of fatal HSV-1-induced disease, indicating that apoptosis plays a significant role in cell death.
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PMID:Naturally occurring fatal herpes simplex virus 1 infection in a family of white-faced saki monkeys (Pithecia pithecia pithecia). 1273 97

Neuropeptide Y (NPY), the most abundant peptide present in the mammalian brain, exhibits a wide spectrum of central and peripheral activities mediated by at least six G-protein coupled receptors. The latter observation, and the implication of NPY in the pathophysiology of feeding, seizures, diabetes, intestinal dysfunction, cardiovascular diseases and respiratory disorders, have led to vigorous efforts to dissociate various effects of NPY and develop receptor selective ligands required for fundamental investigations, and possible clinical utility. These efforts have made significant advancement in the development of antagonists, especially for Y(1) and Y(5) receptors mediating NPY effects on feeding and/or thermogenesis. However, only a limited progress has been made in the case of Y(2) ligands, and none in the case of Y(4) ligands. Moreover, most of the nonpeptidic ligands developed to date have little use clinically because of their solubility and toxicity problems and their limited passage through blood-brain barrier. Furthermore, no progress has been made in developing lower molecular weight agonists, which may also have clinical potential in treating seizures, intestinal dysfunction, respiratory disorders, cachexia and anorexia. Thus, despite significant advances, NPY research is expected to attract scientists for years to come in the pursuit to develop clinically useful ligands. The recent advances in the peptide drug delivery techniques have given added impetus for these efforts. This article reviews the usefulness of widely used ligands as well as those developed more recently.
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PMID:Neuropeptide Y (NPY) family of hormones: progress in the development of receptor selective agonists and antagonists. 1276 44

Although the incidence of lead toxicosis in small animals continues to decrease, it remains a significant malady. We have reviewed the literature of the past 45 years, which revealed 70 cases involving cats. Sources, signs, diagnosis, pathology and treatment of feline lead toxicosis are reviewed. In 84% of these cases the source of lead was old paint usually from home renovation. The most common signs in cats are anorexia, vomiting, and seizures. The younger individuals seem more likely to show CNS signs. Since signs are often vague, lead toxicosis may be significantly under diagnosed in cats. The gold standard of diagnostic tests is blood lead concentration, although it does not necessarily correlate with total body burden of lead or with metabolic effects including clinical signs. Diagnostic tests including erythropoietic protoporphyrin (EPP), urine aminolevulinic acid, and others are discussed. Gross findings on necropsy are few and include a yellow-brown discoloration of the liver often with a nutmeg-like appearance. Histological examination may reveal pathognomonic inclusion bodies in liver and renal tissues. Characteristic histological changes in the CNS include neuronal necrosis and demyelination. Treatment of lead toxicosis in cats, as in any species, involves removing the exposure, decontaminating the individual and the environment, supportive care and chelation therapy. The most recently available chelator is succimer (meso 2,3-dimercaptosuccinic acid). Succimer given orally is well tolerated and has a wide margin of safety. A high index of suspicion of lead toxicosis is warranted in cats since they often present with vague and non-specific signs. With any consistent history owners need to be asked about home renovation. Early diagnosis and treatment affords a good prognosis.
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PMID:Lead toxicosis in cats-a review. 1294 99

To study the functions of 5-HT4 receptors, a null mutation was engineered in the corresponding gene. 5-HT4 receptor knock-out mice displayed normal feeding and motor behaviors in baseline conditions but abnormal feeding and locomotor behavior in response to stress and novelty. Specifically, stress-induced hypophagia and novelty-induced exploratory activity were attenuated in the knock-out mice. In addition, pentylenetetrazol-induced convulsive responses were enhanced in the knock-out mice, suggesting an increase in neuronal network excitability. These results provide the first example of a genetic deficit that disrupts the ability of stress to reduce feeding and body weight and suggest that 5-HT4 receptors may be involved in stress-induced anorexia and seizure susceptibility.
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PMID:Attenuated response to stress and novelty and hypersensitivity to seizures in 5-HT4 receptor knock-out mice. 1472 39

This study examined the efficacy and safety of zonisamide as monotherapy in pediatric patients with epilepsy. Seventy-seven children with epilepsy (ages 8 months-15 years) were treated with zonisamide. Nine patients were withdrawn early because of side effects; these patients were included in side effect but not efficacy analyses. Zonisamide dosages were initiated at approximately 2 mg/kg per day and adjusted for each patient individually to a maximum of 12 mg/kg per day. Among 44 patients with cryptogenic/symptomatic partial epilepsy, 36 (82%) became seizure free; 4 (9%) had a > or =50% reduction in seizure frequency; and 4 (9%) had no change in seizures with zonisamide treatment. Of 11 patients with cryptogenic/symptomatic generalized epilepsy, 10 (91%) became seizure free, and 1 experienced no change with zonisamide treatment. Similarly, 4 patients (100%) with idiopathic partial epilepsy, and 8 of 9 patients (89%) with idiopathic generalized epilepsy became seizure free with zonisamide treatment; in the last group, 1 experienced no change. Thirty patients (39%) reported side effects, including somnolence (11.7%), decreased spontaneity (7.8%), anorexia (6.5%), and rash (6.5%). Thus, zonisamide is effective for partial seizures with or without secondarily generalized seizures in children and should be considered a broad-spectrum antiepilepsy agent.
Seizure 2004 Dec
PMID:Effects of zonisamide monotherapy in children with epilepsy. 1551 85

Zonisamide is an antiepilepsy drug (AED) with both sodium and calcium channel-blocking properties. This dual mechanism may predict efficacy in some refractory patients, and a broad spectrum of action against different seizure types. Zonisamide has been commercially available in Japan since 1989, and became available in the United States for treatment of adults over the age of 12 with partial-onset seizures in March 2000. Several multicenter clinical trials have been conducted in the United States over the past 15 years. These have included three double-blind, placebo-controlled trials as well as long-term open-label studies. Zonisamide was characterized in these studies as a safe and effective adjunctive treatment for partial-onset seizures. Zonisamide has not yet been studied in the United States as an initial monotherapy, but in one long-term study, some patients were able to discontinue other AEDs and successfully transition to monotherapy. The most frequently reported adverse events were somnolence, dizziness, and anorexia. Current United States labeling states that 12 patients with epilepsy receiving zonisamide had symptomatic kidney stones; however, after more than a dozen years of zonisamide use in Japan, the incidence of kidney stones associated with zonisamide remains low.
Seizure 2004 Dec
PMID:Review of United States and European clinical trials of zonisamide in the treatment of refractory partial-onset seizures. 1551 95

European clinical trials of zonisamide as adjunctive therapy for refractory partial seizures included a 12-week double-blind, placebo-controlled study and a 15-month open-label extension study. In the double-blind study, patients (n = 144) were randomized to placebo or zonisamide (400 mg QD) after baseline evaluation. Patients completing the double-bind study (n = 115) continued on open-label zonisamide for up to 18 months. Median percent reduction in partial seizures from baseline was significantly greater in zonisamide-treated patients compared to those receiving placebo (31.6% versus 3.3%, respectively; P = 0.008). Additionally, more zonisamide-treated patients achieved > or = 50% reduction in seizure frequency relative to baseline than did placebo patients (30.4% versus 14.7%, respectively; P = 0.03). The extension study showed that zonisamide efficacy was maintained or improved over time. Patient and physician assessments favored zonisamide over placebo in terms of patient improvement with treatment. Median zonisamide maintenance dosage was 400mg/day, and the average therapeutic blood level was 16.9 microg/mL. Both studies showed that zonisamide was well tolerated; adverse events were generally mild to moderate and most frequently included fatigue, dizziness, somnolence, and anorexia. Collectively, these findings corroborate those of US and Asian clinical trials, which also show that zonisamide is safe and effective for adjunctive therapy of partial seizures.
Seizure 2004 Dec
PMID:Zonisamide clinical trials: European experience. 1551 96

Topiramate is an effective treatment for several types of seizures. The aim of this study is to assess the efficacy and tolerability of slow topiramate dose titration as add-on therapy in childhood epilepsy. This investigation is a prospective open-label, single-center, add-on study in 22 children with a diagnosis of refractory epilepsy. Topiramate (dose 0.5-2 mg/kg/day) was titrated at 2-week intervals up to the recommended dose of 6-12 mg/kg/day. Seizure frequency rate reduction was significant, declining from 23 +/- 5.1 seizures/week (mean +/- S.E.M.) at baseline phase to 3.5 +/- 1.2 seizures/week at the end of the 16-week stabilization phase (P < 0.001). After 16 weeks of stabilization, 19 patients (86%) had more than 50% seizure reduction. Seven patients (31%) were 100% seizure-free. Two patients (9%) manifested no improvement; only one patient (5%) did not tolerate the added drug and discontinued topiramate. One patient manifested severe side effects, whereas 21 patients experienced mild to moderate side effects mostly represented by somnolence, nervousness, and anorexia with or without weight loss. We conclude that slow dose titration improves efficacy and tolerability of topiramate as add-on therapy in the treatment in refractory epilepsy.
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PMID:Topiramate slow dose titration: improved efficacy and tolerability. 1551 17


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