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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many conditions in clinical neurology may be responsive to pyridoxine as a therapeutic agent. The current difficulty is in trying to isolate the conditions that are most likely to respond. Treating seizures is a major part of a neurologic practice. Our current therapeutic agents are only partially successful and limited by multiple side effects. One problem is that patients often have to take these agents for an entire lifetime, further raising the risk of toxicity. If pyridoxine supplementation can improve the efficacy of currently used medications, it will be gladly accepted into our therapeutic arsenal. Headache, chronic pain, and depression all appear to run together in many of our patients. The observations that serotonin deficiency is a common thread between them and that pyridoxine can raise serotonin levels open a wide range of therapeutic options. Small studies have been carried out with mixed success. Comparison with amitriptyline in the treatment of headache appears to show about equal efficacy, although side effects would be expected to be more of a problem with the amitriptyline. Behavioral disorders are relatively common and continue to be a major problem, disrupting the lives of the patients and their families. Current treatments are not acceptable to most people because of the risk of side effects with long-term usage. If, as Dr. Feingold suggests, many of these problems are caused by "toxic" exposures to chemicals that are pyridoxine antagonists, supplementation at early ages may reduce the incidence of hyperactivity and aggressive behavior. This raises the question of safety. Is pyridoxine safe for long-term use in large segments of the population, including children? The studies on children with Down's syndrome and autism, utilizing much higher doses than are used for other therapeutic purposes, seem to indicate relative safety if carefully monitored. Studies involving large population groups with carpal tunnel syndrome, all adults, using 100-150 mg/day have shown minimal or no toxicity in five- to 10-year studies. Women self-medicating for PMS taking 500 to 5000 mg/day have shown peripheral neuropathy within one to three years. It would appear from this retrospective analysis that pyridoxine is safe at doses of 100 mg/day or less in adults. In children there is not enough data to make any sort of suggestion. Because the major neurologic complication is a peripheral neuropathy and the causes of this condition are myriad, pyridoxine may cause neuropathy only in patients with a pre-existing susceptibility to this condition.
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PMID:Vitamin B6 in clinical neurology. 216 44

Increasing numbers of reports indicate direct effects of ovarian steroids on the central nervous system. Effects of progesterone and its metabolites on brain excitability in humans and in experimental animals have been studied. Anti-epileptic effects have been shown in cats and in women with partial epilepsy and well-defined epileptic foci. The reduced progesterone metabolite 5 alpha-pregnan-3 alpha-ol-20-one and its 5 beta analogue also decreased the epileptic activity resulting from a penicillin-induced cortical focus in cats. 5 alpha-Pregnan-3 alpha-ol-20-one protected mice against metrazol-, bicuculline- and picrotoxin-induced seizures but not against electroshock-and strychnine-induced seizures. Progesterone, 5 alpha-pregnan-3 alpha-ol-20-one and 5 beta-pregnan-3 alpha-ol-20-one also induce anaesthesia in humans and animals; in a rat model of anaesthesia 5 alpha-pregnan-3 alpha-ol-20-one was eight times more potent than methohexitone (the most potent anaesthetic barbiturate). Anaesthesia with loss of the eyelash reflex was observed in humans 75-90 seconds after the intravenous injection of 5 beta-pregnan-3 alpha-ol-20-one in lipid emulsion. The in vivo production and brain distribution of centrally active steroids has also been studied in relation to the phases of the ovarian and menstrual cycle. A subset of women with epilepsy show changes in seizure frequency in relation to hormonal variations during the menstrual cycle. In the luteal phase when progesterone levels are high the number of generalized seizures is low. It is possible that progesterone and its metabolites play a role in epileptic seizures and also in the premenstrual syndrome.
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PMID:Steroids in relation to epilepsy and anaesthesia. 229 14

Magnesium is an important element for health and disease. Magnesium, the second most abundant intracellular cation, has been identified as a cofactor in over 300 enzymatic reactions involving energy metabolism and protein and nucleic acid synthesis. Approximately half of the total magnesium in the body is present in soft tissue, and the other half in bone. Less than 1% of the total body magnesium is present in blood. Nonetheless, the majority of our experimental information comes from determination of magnesium in serum and red blood cells. At present, we have little information about equilibrium among and state of magnesium within body pools. Magnesium is absorbed uniformly from the small intestine and the serum concentration controlled by excretion from the kidney. The clinical laboratory evaluation of magnesium status is primarily limited to the serum magnesium concentration, 24-hour urinary excretion, and percent retention following parenteral magnesium. However, results for these tests do not necessarily correlate with intracellular magnesium. Thus, there is no readily available test to determine intracellular/total body magnesium status. Magnesium deficiency may cause weakness, tremors, seizures, cardiac arrhythmias, hypokalemia, and hypocalcemia. The causes of hypomagnesemia are reduced intake (poor nutrition or IV fluids without magnesium), reduced absorption (chronic diarrhea, malabsorption, or bypass/resection of bowel), redistribution (exchange transfusion or acute pancreatitis), and increased excretion (medication, alcoholism, diabetes mellitus, renal tubular disorders, hypercalcemia, hyperthyroidism, aldosteronism, stress, or excessive lactation). A large segment of the U.S. population may have an inadequate intake of magnesium and may have a chronic latent magnesium deficiency that has been linked to atherosclerosis, myocardial infarction, hypertension, cancer, kidney stones, premenstrual syndrome, and psychiatric disorders. Hypermagnesemia is primarily seen in acute and chronic renal failure, and is treated effectively by dialysis.
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PMID:Magnesium metabolism in health and disease. 328 51

The hormone progesterone is readily converted to 3alpha-OH-5alpha-pregnan-20-one (3alpha,5alpha-THP) in the brains of males and females. In the brain, 3alpha,5alpha-THP acts like a sedative, decreasing anxiety and reducing seizure activity, by enhancing the function of GABA (gamma-aminobutyric acid), the brain's major inhibitory neurotransmitter. Symptoms of premenstrual syndrome (PMS), such as anxiety and seizure susceptibility, are associated with sharp declines in circulating levels of progesterone and, consequently, of levels of 3alpha,5alpha-THP in the brain. Abrupt discontinuation of use of sedatives such as benzodiazepines and ethanol can also produce PMS-like withdrawal symptoms. Here we report a progesterone-withdrawal paradigm, designed to mimic PMS and post-partum syndrome in a rat model. In this model, withdrawal of progesterone leads to increased seizure susceptibility and insensitivity to benzodiazepine sedatives through an effect on gene transcription. Specifically, this effect was due to reduced levels of 3alpha,5alpha-THP which enhance transcription of the gene encoding the alpha4 subunit of the GABA(A) receptor. We also find that increased susceptibility to seizure after progesferone withdrawal is due to a sixfold decrease in the decay time for GABA currents and consequent decreased inhibitory function. Blockade of the alpha4 gene transcript prevents these withdrawal properties. PMS symptoms may therefore be attributable, in part, to alterations in expression of GABA(A) receptor subunits as a result of progesterone withdrawal.
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PMID:GABA(A) receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid. 979 Jan 85

Previous results from this lab have demonstrated that the GABA-modulatory steroid 3alpha-OH-5alpha-pregnan-20-one (3alpha, 5alpha-THP) exhibits withdrawal properties, increasing anxiety [M.A. Gallo, S.S. Smith, Progesterone withdrawal decreases latency to and increases duration of electrified prod burial: a possible rat model of PMS anxiety, Pharmacol. Biochem. 46 (1993) 897-904.] and seizure susceptibility [S.S. Smith, Q.H. Gong, F.-C. Hsu, R.S. Markowitz, J. M.H. ffrench-Mullen, X. Li, GABAA receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid, Nature 392 (1998) 926-930.] upon abrupt discontinuation after chronic administration of its parent compound, progesterone (P), in a manner similar to other GABA-modulatory drugs. Further, we have demonstrated that withdrawal from P produces insensitivity to the potentiating effects of the benzodiazepine (BDZ) lorazepam (LZM) on GABA-gated Cl- current [A.-M.N. Costa, K.T. Spence, S.S. Smith, J.M. H. ffrench-Mullen, Withdrawal from the endogenous steroid progesterone results in GABAA currents insensitive to BDZ modulation in rats CA1 hippocampus, J. Neurophysiology 74 (1995) 464-469; S.S. Smith, Q.H. Gong, F.-C. Hsu, R.S. Markowitz, J.M.H. ffrench-Mullen, X. Li, GABAA receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid, Nature 392 (1998) 926-930.], assessed using whole cell patch clamp procedures on pyramidal neurons acutely dissociated from CA1 hippocampus. The purpose of the present study was to examine the withdrawal effects of P on the sedative potency of LZM, tested behaviorally as the ability to maintain position on a variable speed treadmill following LZM administration (0.75 mg/kg). Both continuous (continuous release P capsule, single withdrawal) as well as discontinuous (multiple P injection, multiple withdrawal) paradigms were tested. Longer continuous release paradigms were more effective in abolishing the sedative effects of LZM, without producing a change in baseline response. The LZM insensitivity observed following the multiple withdrawal paradigm was prevented by prior intraventricular administration of antisense oligonucleotide against the alpha4 subunit of the GABAA receptor. These results support the hypothesis that withdrawal from P decreases the behavioral response to LZM as a direct result of increases in the alpha4 subunit of the GABAA receptor. Withdrawal from P occurs endogenously during pre-menstrual and post-partum periods, when decreased response to BDZ has been reported.
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PMID:Progesterone withdrawal. II: insensitivity to the sedative effects of a benzodiazepine. 975 6

Some chronic diseases have a favourable course and are cured spontaneously. Allergic diseases such as eczema, hay fever and asthma have a good outcome in more than 75% of cases within 7 to 25 years, depending on the kind of allergy. Migraines have also a good evolution in children and after menopause. Many symptoms due to menstruation such as dysmenorrhea, premenstrual syndrome or anemia, disappear after menopause as well as diseases due to estrogens such as uterine leiomyoma, endometriosis and prolactinoma. The risk of epilepsy relapse after a first seizure is about 40% after 2 years. The risk is lower in children. Attention deficit disorder affects 3 to 5% of children but is present in only 30% of them in adult age. The prevalence of depression decreases in women between 30 and 60 years of age. Functional somatic syndromes such as fibromyalgia, irritable bowel syndrome or dyspepsia decrease in 2/3 of cases within 5 to 10 years if there is no history of anxio-depressive symptoms. However, prognosis is reserved when initial symptoms are severe or if they are connected to sexual abuse, domestic violence or depression. Other diseases have a spontaneous favourable course such as myopia, idiopathic infertility, polycystic ovary disease or ventricular arrhythmia. The knowledge of a good prognosis enables to avoid unnecessary treatments and to reassure many patients.
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PMID:[The benefits of aging. I. Patience and cure: spontaneous beneficial course of certain diseases]. 1172 11

Decisions on ventilatory support (VS) in multiple sclerosis (MS) are complex. All patients with MS requiring mechanical ventilation or tracheostomy since 1969 (22) at Mayo Clinic were reviewed. Seventeen had progressive (PMS; 11 secondary and six primary progressive) and one had relapsing remitting MS (RRMS). Four had neuromyelitis optica (NMO). Of those with PMS, all but two required a wheelchair or were bedbound before VS and survived a median of 22 months; 14 were mechanically ventilated and seven underwent subsequent lifelong tracheostomy; three had tracheostomy only. The indications (usually multiple) for VS in PMS patients were aspiration pneumonia, poor ventilation because of mucous plugging, mechanical failure, and airway control/protection for seizures and coma. The RRMS patient required mechanical ventilation for 10 days, with subsequent short-term tracheostomy during a brainstem exacerbation. Of the four patients with NMO one made a dramatic recovery after plasmapheresis. Compared with PMS, the NMO group had a shorter time from disease onset to VS, a longer duration of ventilation, and the three patients not treated with plasma exchange or steroids did worse. The prognosis for independent ventilation (+/- tracheostomy) was worst for patients with NMO, except for one patient who received plasma exchange, and better then expected for PMS, despite poor preventilation functional status.
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PMID:Mechanical ventilation and tracheostomy in multiple sclerosis. 1531 26

We report herein the case of 32-year-old woman with situs inversus, thrombophilia, antiphospholipid syndrome and severe premenstrual syndrome (PMS) with cerebral edema and epileptic seizures prior to menstruation. Seven days prior to regular menstruation she developed severe PMS, including headache, blurred vision, epileptic seizures, urinary incontinence, craving for food, depression and irritability. Papilledema was detected. Daily hormone analyses prior to and during menstruation confirmed an ovulatory cycle with extremely high progesterone, prolactin and insulin levels in the late luteal phase. From day 29 to day 31, progesterone and insulin decreased sharply and the estradiol/progesterone ratio changed, leading to epileptic seizures and the peak of her symptoms. Diuretic treatment was administered. All symptoms disappeared during the first few days of menstruation. A novel oral contraceptive, containing ethinyl estradiol and drospirenone, an antimineralocorticoid progestogen, was given during the next cycle and hormone analyses were repeated. All symptoms were reduced significantly and no cerebral edema and epileptic seizures occurred. This is the first report of a woman with severe PMS and cerebral edema being treated successfully with an oral contraceptive containing drospirenone.
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PMID:Drospirenone in the treatment of severe premenstrual cerebral edema in a woman with antiphospholipid syndrome, lateral sinus thrombosis, situs inversus and epileptic seizures. 1637 42

Conditions of changing steroid hormone levels are a particularly vulnerable time for the manifestation of neurological disorders, including catamenial epilepsy, premenstrual syndrome (PMS), and postpartum depression. The pathophysiology of these disorders may be related to changes in neurosteroid levels, which can dramatically impact neuronal excitability. Robust changes in neurosteroid levels, such as those that occur following stress, over the ovarian cycle, and throughout pregnancy, profoundly alter GABAA receptor (GABAAR) structure and function and underlie the associated changes in neuronal excitability. A moderate and brief exposure to elevated neurosteroids, such as those that occur over the ovarian cycle and following an acute stressful episode, result in a decrease in GABAAR gamma2 subunit expression and an increase in GABAAR delta subunit expression. These changes are accompanied by a decrease in seizure susceptibility and decreased anxiety-like behavior in mice, demonstrating altered neuronal excitability associated with changes in the receptor composition. More robust changes in steroid hormone levels, such as those that occur throughout pregnancy, result in a decrease in both GABAAR gamma2 and delta subunit expression and are associated with an increase in neuronal excitability evident from the shift in the input-output relationship. Alterations in GABAAR subunit composition may represent a homeostatic mechanism to maintain an ideal level of inhibition in the face of fluctuating neurosteroid levels. Neurosteroids potentiate the effects of GABA on GABAARs, particularly those containing the delta subunit, and reorganization of these receptors may be necessary to prevent sedation and/or anaesthesia in the face of high levels of neurosteroids or to prevent hyperexcitability in the absence of these compounds. Alterations in GABAARs under conditions of altered steroid hormone levels result in measurable changes in neuronal excitability and dysregulation of GABAARs may play a role in steroid hormone-associated neurological disorders.
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PMID:Steroid hormone fluctuations and GABA(A)R plasticity. 1963 51

Some women have negative mood symptoms, caused by progestagens in hormonal contraceptives or sequential hormone therapy or by progesterone in the luteal phase of the menstrual cycle, which may be attributed to metabolites acting on the GABA-A receptor. The GABA system is the major inhibitory system in the adult CNS and most positive modulators of the GABA-A receptor (benzodiazepines, barbiturates, alcohol, GABA steroids), induce inhibitory (e.g. anesthetic, sedative, anticonvulsant, anxiolytic) effects. However, some individuals have adverse effects (seizures, increased pain, anxiety, irritability, aggression) upon exposure. Positive GABA-A receptor modulators induce strong paradoxical effects including negative mood in 3%-8% of those exposed, while up to 25% have moderate symptoms. The effect is biphasic: low concentrations induce an adverse anxiogenic effect while higher concentrations decrease this effect and show inhibitory, calming properties. The prevalence of premenstrual dysphoric disorder (PMDD) is also 3%-8% among women in fertile ages, and up to 25% have more moderate symptoms of premenstrual syndrome (PMS). Patients with PMDD have severe luteal phase-related symptoms and show changes in GABA-A receptor sensitivity and GABA concentrations. Findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor, which may be explained by one or more of three hypotheses regarding the paradoxical effect of GABA steroids on behavior: (1) under certain conditions, such as puberty, the relative fraction of certain GABA-A receptor subtypes may be altered, and at those subtypes the GABA steroids may act as negative modulators in contrast to their usual role as positive modulators; (2) in certain brain areas of vulnerable women the transmembrane Cl(-) gradient may be altered by factors such as estrogens that favor excitability; (3) inhibition of inhibitory neurons may promote disinhibition, and hence excitability. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.
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PMID:Paradoxical effects of GABA-A modulators may explain sex steroid induced negative mood symptoms in some persons. 2160 Feb 69


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