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)

Nervous system opportunistic infections are seen in about one fifth of AIDS cases and account for over 40% of the patients with neurological manifestations. Serious infections are seen in severely immunosuppressed patients, usually with CD4 counts of 200 ml-1 or less. The commonest is CMV, which can produce acute encephalitis, sometimes with focal hemisphere or brain-stem signs, dementia, retinitis, optic neuritis and an ascending radiculomyeloencephalitis. Cryptococcal meningitis is the most frequent fungal disease; a high degree of clinical suspicion is required in patients with fever, malaise, headache or seizures. Only CSF cultures are always positive; both serum and CSF cryptococcal antigen tests are highly sensitive and specific. Treatment with amphotericin B and flucytosine is successful in at least 70% of first episodes but side-effects are common. Without maintenance therapy 50% of patients relapse; fluconazole is recommended. Cerebral toxoplasmosis can present with focal cerebral or spinal cord signs but also as a diffuse encephalopathy; negative T. gondii serology is exceptional but positive serum titres are usually unhelpful. Treatment with sulfadiazine, pyrimethamine and folinic acid achieves good results in 90% of the first episodes, but side-effects are common. Appearances on CT scan or MRI may take several weeks to improve. The value of an empirical approach to treatment is well-established; an initial cerebral biopsy is difficult to justify. Without maintenance therapy a relapse rate of 50% can be expected; therapy with sulfadiazine and pyrimethamine may also prevent pneumocystosis. HIV disease appears to increase the likelihood of neurosyphilis, and the risk of relapse after conventional penicillin doses, in patients with syphilis; at least 3-4 weeks of appropriate therapy are recommended. A number of other diseases caused by viruses, fungi, bacteria and parasites are less common; these include progressive multifocal leukoencephalopathy, herpes simplex and zoster infections and tuberculosis.
 ...
PMID:Central nervous system opportunistic infections in HIV disease: clinical aspects. 134 47

Five patients with documented recurrences of glioblastoma multiforme were given continuous infusions of methotrexate delivered intratumorally using implantable catheters and subcutaneous refillable pumps. A continuous infusion of methotrexate (1 mg/d) was begun with concomitant oral administration of folinic acid. The methotrexate dose was increased every 2 weeks to 3, 10, 30, and, ultimately, 75 mg/d in two patients. Samples of serum and ventricular cerebrospinal fluid (CSF) were obtained to determine the levels of methotrexate and total bioactive folates, and brain tissue was obtained from two patients for determination of methotrexate concentration. The patients survived from 7 to 49 weeks after the implantation of the infusion device. Neither the clinical examination nor sequential radiological studies gave clear evidence of reduction in tumor size. Pneumonia developed in one patient, and mild hepatitis and increased seizure frequency in another. Methotrexate was stable in the delivery system over 12 days, and ventricular CSF reached steady-state levels by 5 days. Steady-state ventricular CSF levels of methotrexate were higher than serum levels in some patients, while the reverse was true in others. Levels of total bioactive folates in the CSF did not increase above the normal range. Methotrexate concentrations were highest at the center of the tumor, but measurable amounts of methotrexate were detectable in all areas of the brain. At autopsy in four patients, variable liquefactive necrosis of the brain tumors was seen, and viable tumor was found at the periphery of the tumor bed. These preliminary results suggest that it is technically feasible to infuse methotrexate into brain tumor cavities, and show that little central nervous system or systemic toxicity was encountered in five patients. Better delineation of the safety and efficacy of this therapeutic approach will require further clinical trials.
 ...
PMID:Continuous intratumoral infusion of methotrexate for recurrent glioblastoma: a pilot study. 165 12

There are several protozoan infections that cause relatively benign illness in normal individuals but result in severe disease manifestations in patients with AIDS. These diseases include Pneumocystis carinii pneumonia, CNS toxoplasmosis, cryptosporidiosis, and isosporiasis. Pneumocystis carinii pneumonia (PCP) caused by Pneumocystis carinii, is the most common opportunistic infection in AIDS. It is seen in more than 80% of individuals with this syndrome. Although historically classified as a protozoan, this organism shares many biochemical characteristics with fungi. The onset of PCP may be insidious, and cough and dyspnea are the most common presenting symptoms. Auscultation of the lungs is often unremarkable, but diffuse infiltrates are commonly seen on chest radiographs. The diagnosis of PCP can be confirmed by identifying the organism on specimens obtained by sputum induction or bronchoalveolar lavage. Trimethaprim-sulfamethoxazole is the treatment of choice but is unfortunately associated with leukopenia and rash in many individuals. Both trimethaprim-sulfamethoxazole and aerosolized pentamidine are used prophylactically in patients at high risk for initial or relapsing infection. The appropriate use of these agents has resulted in improved survival for AIDS patients with PCP. Toxoplasmosis, due to Toxoplasma gondii, affects the central nervous system in patients with AIDS. Headache is a common presenting symptom, and both seizures and paresis can occur. A diagnosis of toxoplasmosis is strongly suspected in symptomatic individuals with ringed mass lesions noted on head CT. Patients with this condition are treated with a combination of sulfadiazine, pyrimethamine, and folinic acid. Cryptosporidiosis and isosporiasis are coccidian protozoan diseases that can result in severe, acute, and chronic diarrhea in immunocompromised individuals. Cryptosporidiosis is the more common of the two and is caused by an unknown species of the genus crytosporidium. Isosporiasis is due to infection with Isospora belli. Dehydration and weight loss are a common result of infection with either agent. A definitive diagnosis can be made by examining an acid fast stain of a diarrheal stool specimen and demonstrating oocysts that are specific for each of these organisms. Fluid replacement and general supportive care are essential in the treatment of both of these diseases. Spiramycin is an unproven treatment modality that is often used in patients with cryptosporidiosis. Isosporiasis responds to initial therapy with trimethaprim-sulfamethoxazole, followed by prophylaxis with pyrimethamine. The adoption of safe sexual practices that minimize fecal-oral contamination should decrease the future prevalence of these diseases and other enteric parasitic infections.
 ...
PMID:Parasitic diseases. Diseases associated with acquired immunodeficiency syndrome. 201 33

We conducted a phase II clinical trial of fluorouracil (5FU) and recombinant interferon alfa-2a (rIFN alpha-2a) in 52 previously untreated patients with bidimensionally measurable metastatic colorectal cancer. During week 1, 5FU was administered as a continuous intravenous infusion, 750 mg/m2/d for 5 consecutive days. Intravenous bolus administration of 5FU 750 mg/m2 was given weekly for 7 weeks starting on day 12. rIFN alpha-2a (Roferon; Hoffman-LaRoche, Nutley, NJ), 9 x 10(6) U, was administered subcutaneously three times weekly during weeks 1 to 8. Patients were evaluated for response on week 9. Of 52 patients enrolled in the study, 51 were assessable for toxicity, and 45 were assessable for response. Fifteen patients experienced partial response, and one patient achieved a clinical complete response for an overall response rate of 35% (95% confidence interval [CI], 22%, 50%). Median duration of response is 7.5 months (range, 4 to 11 months). Seventy percent of patients entered on the study are alive with a median follow-up duration of 7 months. Twenty-five percent of patients developed grade 4 toxicity, and 82% developed grade 3 toxicity. One drug-related death in the presence of sepsis was reported, and two treatment-related seizures occurred. Our experience with this schedule produced a lower response rate with greater toxicity than previously reported. Current randomized trials comparing this schedule of 5FU with rIFN alpha-2a to 5FU plus folinic acid (leucovorin) or single-agent 5FU may determine its role in the treatment of advanced colorectal carcinomas.
 ...
PMID:Phase II study of fluorouracil and recombinant interferon alfa-2a in previously untreated advanced colorectal carcinoma. 223 Aug 94

Hyperphenylalaninemia in infants and children may be caused by a deficiency of dihydropteridine reductase (DHPR). Recommended therapy includes folinic acid as a source of tetrahydrofolate, a phenylalanine-restricted diet, and both dopamine and serotonin precursors. We report a child with progressive basal ganglia and other subcortical calcifications prior to the use of folinic acid. Six other reported cases of DHPR deficiency demonstrated similar calcifications prior to folinic acid therapy. Since this pattern of calcification also resembles that seen in CNS folate deficiency caused by both congenital folate deficiency and that which is methotrexate-induced, we propose that intracranial calcification in DHPR deficiency is caused by inadequate CNS tetrahydrofolate and may be prevented by the use of folinic acid. Our patient achieved excellent seizure control following the use of folinic acid, suggesting either a direct or indirect anticonvulsant effect of this compound in patients with DHPR deficiency.
 ...
PMID:Progressive intracranial calcification in dihydropteridine reductase deficiency prior to folinic acid therapy. 278 51

Carbamazepine and valproate each afforded protection against seizures induced by electroshock or by inhalation of hexafluorodiethyl ether (HFDE). After injections of either anticonvulsant for 10 days, plasma folate concentration decreased, but brain folate concentration did not change. Folinic acid administration had no effect on the concentration of either anticonvulsant in plasma or brain. These findings are in contrast with the demonstrated effects of other anticonvulsants on folate biochemistry.
 ...
PMID:Interactions between folates and carbamazepine or valproate in the rat. 681 Feb 6

A 10-year-old girl with aplastic anemia developed seizures and a mild hemiparesis following a bone marrow transplant. Based on serologic evidence and a computed tomography scan, which showed a left parietal lucency with ring enhancement, a diagnosis of toxoplasmosis was considered. A brain biopsy of the lucent area demonstrated the inflammation and necrosis but no organisms were seen. During a six-week course of pyrimethamine, sulfadiazine, and folinic acid therapy there was clinical and neuroradiologic resolution. The short course of therapy as well as the inadvertent substitution of folic acid for folinic acid and trimethoprim-sulfamethoxazole for sulfadiazine resulted in the reappearance of neurologic deficits. Reinstitution of appropriate therapy produced gradual improvement over a nine-month period. Serial computer tomography scans correlated with the clinical course. In the immunologically compromised host CNS toxoplasmosis should be considered in the differential diagnosis of an evolving CNS syndrome. Early detection and prolonged therapy with appropriate drugs can result in a favorable outcome. Computed tomography scanning may be helpful in diagnosis and follow-up.
 ...
PMID:Toxoplasmosis: a treatable neurologic disease in the immunologically compromised patient. 701 42

A nine-week-old Caucasian male presented with right ptosis and right exotropia due to a third cranial nerve palsy. Symmetrical macular lesions and a paramacular hyperpigmented lesion with overlying vitreous cells in the left eye were compatible with congenital toxoplasmosis. Computer tomography demonstrated calcifications in the periventricular and midbrain regions where the oculomotor nerve exits the brainstem. The diagnosis was confirmed by the toxoplasma indirect fluorescent antibody titer greater than 1:2048 for the infant and greater than 1:512 for the mother. Treatment was instituted with pyrimethamine, sulfadiazine and folinic acid. Neurologic sequelae included a right hemiparesis, infantile seizures, and generalized developmental delay. A Mueller's muscle resection (RUL) combined with 9-mm recession of the right lateral rectus and 7-mm resection of the right medial rectus muscles produced minimal ptosis and right exotropia one year later. the child now prefers to fix with the right eye and a vertical nystagmus is evident in the left eye. To our knowledge this is the first reported case of an infant with noncomitant strabismus due to congenital toxoplasma cranial nerve involvement. The finding of an acquired third cranial nerve palsy accompanied by progressive neurologic sequelae warrants consideration of congenital toxoplasmosis.
 ...
PMID:Congenital toxoplasmosis associated with acquired oculomotor nerve (CN III) palsy. 717 24

Congenital errors of folate metabolism can be related either to defective transport of folate through various cells or to defective intracellular utilization of folate due to some enzyme deficiencies. Defective transport of folate across the intestine and the blood-brain barrier was reported in the condition 'Congenital Malabsorption of Folate'. This disease is characterized by a severe megaloblastic anaemia of early appearance associated with mental retardation. Anaemia is folate-responsive, but neurological symptoms are only poorly improved because of the inability to maintain adequate levels of folate in the CSF. A familial defect of cellular uptake was described in a family with a high frequency of aplastic anaemia or leukaemia. An isolated defect in folate transport into CSF was identified in a patient suffering from a cerebellar syndrome and pyramidal tract dysfunction. Among enzyme deficiencies, some are well documented, others still putative. Methylenetetrahydrofolate reductase deficiency is the most common. The main clinical findings are neurological signs (mental retardation, seizures, rarely schizophrenic syndromes) or vascular disease, without any haematological abnormality. Low levels of folate in serum, red blood cells and CSF associated with homocystinuria are constant. Methionine synthase deficiency is characterized by a megaloblastic anaemia occurring early in life that is more or less folate-responsive and associated with mental retardation. Glutamate formiminotransferase-cyclodeaminase deficiency is responsible for massive excretion of formiminoglutamic acid but megaloblastic anaemia is not constant. The clinical findings are a more or less severe mental or physical retardation. Dihydrofolate reductase deficiency was reported in three children presenting with a megaloblastic anaemia a few days or weeks after birth, which responded to folinic acid. The possible relationship between congenital disorders such as neural tube defects or dihydropteridine reductase deficiency and disturbances of folate metabolism are discussed. Neurological symptoms present in most of these congenital disorders highlight the role of folate in the central nervous system.
 ...
PMID:Congenital errors of folate metabolism. 853 63

Careful clinical delineation and advances in analytical methods have opened new possibilities for the detection of inherited neurometabolic disorders, some of which require specific CSF analyses for diagnosis. Although patients suffering from these disorders have recognizable phenotypes, there are strong indications that remain many undiagnosed, leading to a continuation of futile diagnostic searches and, for most disorders, withholding of available rational therapy. As there is still widespread uncertainty about when to perform specialist CSF investigations, it is the aim of this paper to define the place for CSF investigations in the diagnostic work-up of a child with an encephalopathy of unknown origin. Most neurometabolic disorders can be identified through serum, plasma and urine analyses in conjunction with neuroradiological investigations. Whenever CSF investigations are performed, the analysis should include quantitative determination of lactate, pyruvate and amino acids, the latter by methods especially suited for CSF, in addition to cells, glucose, protein, immunoglobulin classes, specific immunoglobulins, and an evaluation of the blood-brain barrier. If the disease course is non-progressive or if extracerebral symptoms are present in addition to an encephalopathy, e.g. endocrinological, hepatic, muscular or renal symptoms, investigations of metabolites in CSF over and above lactate, pyruvate and amino acids are generally noncontributary. Specific CSF investigations, which are discussed in detail, test metabolic pathways of brain metabolism, especially of neurotransmission. For a successful diagnosis of these defects, analyses must be planned individually, before CSF samples are taken, based on family history, clinical findings and disease course. Different determinations require different logistics from taking of the sample to shipment. One indication for specialized CSF analyses including biogenic monoamines and GABA is severe neonatal/infantile epileptic encephalopathy. In addition to a therapeutic trial of B6, folinic acid should be tried empirically for two to three days as the emerging syndrome of folinic acid responsive seizures appears to be the underlying cause in a sizable proportion of patients. In later infancy and childhood, defects in the metabolism of the biogenic monoamines may be suspected in patients with (fluctuating) extrapyramidal disorders, in particular Parkinsonism dystonia or more general "athetoid cerebral palsy", and vegetative disturbances. A severe epileptic encephalopathy and progressive mental retardation may be present. Neuroimaging findings do not show specific lesions. Determinations of folates and organic acids in CSF appear at present only warrantable individually in special constellations, e.g. classical clinical findings and disease course suggestive of glutaryl-CoA dehydrogenase deficiency with repeated negative quantitative analyses of organic acids in urine. The diagnosis of disorders, which require specific analyses of CSF, can only be achieved by conscious diagnostic decisions based on a concept of the respective disease and repeated scrupolous expert clinical evaluation aided by an array of investigations in blood and urine as well as neuroimaging findings. No single one investigation in CSF can serve as a "selective screening" test. A growing awareness of these disorders is needed and should lead to increased and earlier diagnosis of patients through fewer rather than more lumbar punctures.
 ...
PMID:Cerebrospinal fluid investigations for neurometabolic disorders. 963 60


1 2 3 4 5 6 Next >>