Low penetrance, broad resistance, and favorable outcome of interleukin 12 receptor beta1 deficiency: medical and immunological implications.

The clinical phenotype of interleukin 12 receptor beta1 chain (IL-12Rbeta1) deficiency and the function of human IL-12 in host defense remain largely unknown, due to the small number of patients reported. We now report 41 patients with complete IL-12Rbeta1 deficiency from 17 countries. The only opportunistic infections observed, in 34 patients, were of childhood onset and caused by weakly virulent Salmonella or Mycobacteria (Bacille Calmette-Guérin -BCG- and environmental Mycobacteria). Three patients had clinical tuberculosis, one of whom also had salmonellosis. Unlike salmonellosis, mycobacterial infections did not recur. BCG inoculation and BCG disease were both effective against subsequent environmental mycobacteriosis, but not against salmonellosis. Excluding the probands, seven of the 12 affected siblings have remained free of case-definition opportunistic infection. Finally, only five deaths occurred in childhood, and the remaining 36 patients are alive and well. Thus, a diagnosis of IL-12Rbeta1 deficiency should be considered in children with opportunistic mycobacteriosis or salmonellosis; healthy siblings of probands and selected cases of tuberculosis should also be investigated. The overall prognosis is good due to broad resistance to infection and the low penetrance and favorable outcome of infections. Unexpectedly, human IL-12 is redundant in protective immunity against most microorganisms other than Mycobacteria and Salmonella. Moreover, IL-12 is redundant for primary immunity to Mycobacteria and Salmonella in many individuals and for secondary immunity to Mycobacteria but not to Salmonella in most.

Effects of Levetiracetam and Sulthiame on EEG in benign epilepsy with centrotemporal spikes: A randomized controlled trial.

PURPOSE: BECTS (benign childhood epilepsy with centrotemporal spikes) is associated with characteristic EEG findings. This study examines the influence of anti-convulsive treatment on the EEG. METHODS: In a randomized controlled trial including 43 children with BECTS, EEGs were performed prior to treatment with either Sulthiame or Levetiracetam as well as three times under treatment. Using the spike-wave-index, the degree of EEG pathology was quantified. The EEG before and after initiation of treatment was analyzed. Both treatment arms were compared and the EEG of the children that were to develop recurrent seizures was compared with those that were successfully treated. RESULTS: Regardless of the treatment agent, the spike-wave-index was reduced significantly under treatment. There were no differences between the two treatment groups. In an additional analysis, the EEG characteristics of the children with recurrent seizures differed statistically significant from those that did not have any further seizures. CONCLUSION: Both Sulthiame and Levetiracetam influence the EEG of children with BECTS. Persistent EEG pathologies are associated with treatment failures.

Mitotic impairment by doublecortin is diminished by doublecortin mutations found in patients.

Mutations in doublecortin ( DCX) affect the migration of neuronal precursor cells and cause subcortical band heterotopia and lissencephaly. DCX is known to bind and bundle microtubules; however, the impact of mutation on DCX function and its relation to the manifestation of DCX-associated disorders is still unclear. We analyzed the impact of DCX mutants on COS7 cell microtubule networks. We found that both mutant and wild type DCX are able to bind and bundle microtubules; however, mutants possess a decreased ability to perturb the mitotic machinery, to cause abnormal spindle orientation, and to impair mitotic progression. The magnitude of this decrease is proportional to the severity of the mutation-associated clinical symptoms, thereby providing a cell-based assay for the prognosis of DCX-associated neuronal migration disorders.