Vagus nerve stimulation in pediatric epilepsy: a review.

Therapeutic options for intractable epilepsy include new and investigational antiepileptic drugs, ketogenic diet, epilepsy surgery, and, now, vagus nerve stimulation, which is approved by the U.S. Food and Drug Administration for the treatment of refractory partial seizures in adolescents and adults. The exact mechanisms of action are unknown. Although the use of vagus nerve stimulation in children has increased, including those younger than 12 years of age or those with generalized epilepsy, there has been no large controlled pediatric study to date. The identification of favorable prognostic indicators, especially in children, would be useful. Preliminary results suggest that children with Lennox-Gastaut syndrome may have a favorable response, with improvement in both seizure control and global evaluation scores. Improved global evaluation scores have occurred even without an associated improvement in seizure control.

Vagus nerve stimulation therapy in pediatric patients with refractory epilepsy: retrospective study.

This six-center, retrospective study evaluated the effectiveness, tolerability, and safety of vagus nerve stimulation in children. Data were available for 125 patients at baseline, 95 patients at 3 months, 56 patients at 6 months, and 12 patients at 12 months. The typical patient, aged 12 years, had onset of seizures at age 2 years and had tried nine anticonvulsants before implantation. Collected data included preimplant history, seizures, implant, device settings, quality of life, and adverse events. Average seizure reduction was 36.1% at 3 months and 44.7% at 6 months. Common adverse events included voice alteration and coughing during stimulation. Rare adverse events, unique to this age group, included increased drooling and increased hyperactivity. Quality of life improved in alertness, verbal communication, school performance, clustering of seizures, and postictal periods. We concluded that vagus nerve stimulation is an effective treatment for medically refractory epilepsy in children.

[Irritable colon]. / Colon irritabile.

Irritable bowel syndrome is a chronic, relapsing functional bowel disorder of unknown aetiology. Methods of studying intestinal motor function, nociception, and interactions of the central nervous system and enteric nervous system are not applicable for clinical use. The diagnosis is therefore made on the symptoms, but it is necessary to exclude relevant organic disease. Establishment of the diagnosis, information about the disorder, elimination of foods and other factors that provoke the symptoms, and a change in life-style are sufficient in most cases. Treatment is hampered by the lack of effective treatment and the psychological aspects. The therapeutic gain of drug administration is modest and the rate of response to placebo is high. Fibre supplementation, magnesium oxide or cisapride may be tried for constipation, diphenoxylate or loperamide for diarrhoea, and low dose tricyclic antidepressants or serotonin reuptake blockers for severe pain. The introduction of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists seems promising.

Pathophysiology, prevention, and potential treatment of neural tube defects.

Neural tube defects (NTD) remain a major cause of morbidity in spite of the reduction in liveborn incidence with periconceptional folic acid. However, the etiology remains unknown. This article reviews studies that address causation and potential treatment of NTD in humans and in animal models that resemble aspects of the common human NTD. Studies of nutritional markers of vitamin B12 and folic acid support a defect in homocysteine metabolism; a thermolabile variant of methylene tetrahydrofolate reductase, an enzyme that remethylates homocysteine to methionine, correlates with a risk of NTD in some human populations. Numerous mouse mutant models of NTD exist, attesting to the ease of disruption of neurulation, and a genetic basis for this malformation. Of these models, the curly tail mouse mutant most closely resembles the common human NTD. Folic acid does not prevent NTD in this model; however inositol supplementation does result in a significant reduction in incidence. Recent advances in fetal surgery, and evidence from mechanically created myelomeningocele in large animals amenable to surgical intervention suggest that the handicaps associated with myelomeningocele and associated Chiari Type II malformation may be prevented by in utero NTD closure. Success will depend on preservation of neurological tissue until such intervention is possible. Further research in animal models at the genetic and cellular levels, together with technological surgical advances, provide hope that prevention of more NTD and the associated handicaps may be possible. MRDD Research Reviews 6:6-14, 2000.

[Chronic inflammatory bowel disease]. / Kronisk inflammatorisk tarmsygdom.

Chronic inflammatory bowel disease (IBD) encompasses the disease entities, ulcerative colitis (UC) and Crohn's disease (CD). An aetiologic agent has not yet been defined and the diagnosis is based, therefore, on the sum of clinical, paraclinical, radiologic, endoscopic and histopathologic features. In recent years pathogenetic studies have focused on immune mechanisms, transmissible infectious agents, the potential role of the normal intestinal flora, dietary factors, enzymatic alterations and genetic features, in addition to vascular, neuromotor, allergic and psychologic factors. The corner stones in medical therapy of IBD are still corticosteroids and sulphasalazine (SAZ). The new oral salicylates, which are analogues of SAZ or "slow release" preparations of 5-aminosalicylic acid (mesalazine), have provided a therapeutic progress, because they are tolerated better than SAZ. Immunosuppressive agents, such as azathioprine and 6-mercaptopurine, reduce the requirement for corticosteroids and are effective in refractory CD, but the effect is delayed up to several months. The therapeutic action of cyclosporine A is not sustained, but often associated with side effects. Metronidazole has a beneficial effect on perineal disease. The efficacy of antimycobacterial drugs, sodium-cromoglycate, lidocaine, clonidine and sucralfate has been reported only in optimistic case stories and small open trials. A diet, rich in omega-3-fatty acids, modifies leukotriene (LT) production, but its clinical efficacy is insufficient. The first anti-leukotriene-drug, zileuton, has recently been evaluated and a significant, although insufficient, clinical response was obtained by a 70 per cent inhibition of rectal LTB4 synthesis. Dietary therapy may be useful as an adjunct to treatment of local complications in CD.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunoreactivity in pituitary gonadotropes and hypothalamic vasopressinergic neurons for the monoclonal antibody INO.

The monoclonal antibody INO (inhibitor of neurite outgrowth) has been shown to bind to a complex of laminin and a heparan sulfate proteoglycan and to block the action of this complex in promoting neurite outgrowth. We now report that the same antibody binds to cytoplasmic constituents in rat adenohypophyseal gonadotropes, as well as to vasopressinergic neurons in the hypothalamus and their terminals in the neurohypophysis. INO immunoreactivity in fixed sections of pituitary does not colocalize with the immunoreactive laminin in blood vessels and glandular basement membranes, although when unfixed tissue is washed in buffer prior to fixation, the INO immunoreactivity appears in these laminin-rich structures. These observations suggest similarities between the INO hypophyseal antigen and the neurite-promoting proteoglycan complex characterized in conditioned media. Presence of this complex in specific neurosecretory cell types suggests that it is involved with specific secretory products with function yet to be determined.