Secretin and autism: a two-part clinical investigation.

Recent anecdotal reports have touted the gastrointestinal (GI) hormone secretin as a treatment modality for autism, though there is little clinical evidence or literature to support its viability. We undertook a two-part clinical trial to investigate these claims. Fifty-six patients (49 boys, 7 girls, mean age = 6.4 years, SD = 2.7) enrolled in an open-label trial of secretin, during which they received one injection of the hormone (2 IU/kg). All subjects were evaluated by their parents at baseline and follow-up visits (3-6 weeks later, M = 3.7, SD = 1.4 weeks) with Childhood Autism Rating Scales (CARS). Thirty-four patients were labeled with Pervasive Developmental Disorder Not Otherwise Specified, and 22 met diagnostic criteria for Autistic Disorder. Forty-five patients were concurrently on other drug treatments. At follow-up, some reported minimal but potentially significant improvements including changes in GI symptoms, expressive and/or receptive language function, and improved awareness and social interactions. No adverse effects were reported or observed. Subsequently, 17 of the most responsive patients from Study 1 began a double-blind trial that also included 8 newly enrolled patients. Patients in this second study were alternatively entered into one of two groups and received injections of secretin or placebo with crossover at 4 weeks. Patients from Study 1 entered into Study 2 at an average of 6.5 (SD = 0.8) weeks after beginning Study 1. Results of both inquiries indicate that although treatment with secretin was reported to cause transient changes in speech and behavior in some children, overall it produced few clinically meaningful changes when compared to children given placebo injections.

Serum autoantibodies to brain in Landau-Kleffner variant, autism, and other neurologic disorders.

OBJECTIVE: Etiologically unexplained disorders of language and social development have often been reported to improve in patients treated with immune-modulating regimens. Here we determined the frequency of autoantibodies to brain among such children. DESIGN: We collected sera from a cohort of children with (1) pure Landau-Kleffner syndrome (n = 2), (2) Landau-Kleffner syndrome variant (LKSV, n = 11), and (3) autistic spectrum disorder (ASD, n = 11). None had received immune-modulating treatment before the serum sample was obtained. Control sera (n = 71) were from 29 healthy children, 22 with non-neurologic illnesses (NNIs), and 20 children with other neurologic disorders (ONDs). We identified brain autoantibodies by immunostaining of human temporal cortex and antinuclear autoantibodies using commercially available kits. RESULTS: IgG anti-brain autoantibodies were present in 45% of sera from children with LKSV, 27% with ASD, and 10% with ONDs compared with 2% from healthy children and control children with NNIs. IgM autoantibodies were present in 36% of sera from children with ASD, 9% with LKSV, and 15% with ONDs compared with 0% of control sera. Labeling studies identified one antigenic target to be endothelial cells. Antinuclear antibodies with titers >/=1:80 were more common in children with ASD and control children with ONDs. CONCLUSION: Children with LKSV and ASD have a greater frequency of serum antibodies to brain endothelial cells and to nuclei than children with NNIs or healthy children. The presence of these antibodies raises the possibility that autoimmunity plays a role in the pathogenesis of language and social developmental abnormalities in a subset of children with these disorders.

Clinical experience of three pediatric and one adult case of spike-and-wave status epilepticus treated with injectable valproic acid.

Subclinical or nonconvulsive status epilepticus may cause severe postmorbid neurologic dysfunction. It is, therefore, critical to rapidly identify and treat these cases. The recent availability of injectable valproic acid (Depacon) provides an additional method for treatment of status epilepticus, although studies concerning its effectiveness are not widely available in the literature. We report four cases (three pediatric, one adult) of patients who presented to us in status epilepticus. All had previously failed more than one other common method of treatment for this condition. Treatment with injectable valproic acid resulted in the elimination of all clinical indications of status epilepticus as well as a return to the baseline EEG condition in all four cases. Seizure types included focal, multifocal, and generalized spike and wave forms, suggesting potential benefit from injectable valproic acid treatment in a wide range of status epilepticus patients. We present these cases for review.

Pharmacodynamic interactions between phenytoin and valproate: individual and combined antiepileptic and neurotoxic actions in mice.

Although the current trend is to use monotherapy in the treatment of epilepsy, combination therapy is still employed in patients who have failed to respond to monotherapy. There is little clinical or experimental documentation of evidence against or in favor of anticonvulsant combination therapy. In this context, anticonvulsant and neurotoxic pharmacodynamic interactions between phenytoin (PHT) and valproate (VPA) were assessed in an experimental model in mice. All results were expressed in terms of brain drug concentrations for eliminating any pharmacokinetic interaction from the analysis. Both the median neurotoxic and the median anticonvulsant brain concentrations were determined for each drug used alone and for the combination. The interaction for the combination of PHT and VPA was shown to be supraadditive for the anticonvulsant activity, indicating an antiepileptic potentiation, whereas neurotoxicity was simply additive. These results suggest a potential benefit in terms of overall efficacy versus toxicity for the combination of PHT and VPA, as compared with PHT or VPA used alone.

Acute septic arthritis due to Acremonium.

A case of Acremonium species arthritis in a previously healthy child is reported. This fungus has frequently been implicated in cases of mycetoma and keratomycosis in the tropics, and invasive disease has occurred almost exclusively in immunocompromised patients. The acute presentation of this illness and its successful treatment with IV amphotericin-B are highlighted to alert physicians to this pathogen.

Altered metabolic incorporation of fucose and leucine into PNS myelin of 25-week-old diabetic (C57BL/Ks [db/db]) mice: effects of untreated diabetes on nerve metabolism.

Sciatic nerves of 25-week-old genetically diabetic (C57BL/Ks [db/db]) mice and their litter-mate controls were removed, and their metabolic incorporation of [3H]fucose and [14C]leucine into myelin was studied in vitro. Untreated diabetic animals showed significant increases (p less than 0.05) in the fucose/leucine incorporation into myelin when compared to values found for their litter-mates. These results correlated well with previous experiments performed on alloxan or streptozotocin-diabetic rats and thus show the in vitro incubation procedure to be a good indicator of altered metabolic conditions in peripheral nerves due to diabetes mellitus. The resulting ratio increases seen in diabetic animals is at variance with the decrease in ratios found in animals undergoing typical Wallerian degeneration. These results suggest that different metabolic processes operate in untreated diabetics than in normals or in those undergoing other degenerative nerve processes.