Efficacy and safety of thalidomide in children and young adults with intractable inflammatory bowel disease: long-term results.

BACKGROUND: Anti-tumour necrosis factor-alpha antibodies are useful for the treatment of refractory Crohn's disease and ulcerative colitis. Thalidomide is another agent with tumour necrosis factor-alpha suppressive properties. AIM: To investigate the long-term efficacy and safety of thalidomide in a group of children and young adults with refractory inflammatory bowel disease. METHODS: Twenty-eight patients with refractory moderate-severe inflammatory bowel disease (19 Crohn's disease, 9 ulcerative colitis) received thalidomide 1.5-2.5 mg/kg/day. Patients were assessed at baseline, at weeks 2, 4, 8 and 12, and then every 12 weeks by patient's diary, physical examinations, laboratory analyses and scoring on activity indexes. Primary outcomes were: (i) efficacy in inducing remission; and (ii) efficacy in maintaining remission. RESULTS: Remission was achieved with thalidomide in 21 of 28 (75%) patients (17 with Crohn's disease, 4 with ulcerative colitis). Mean duration of remission was 34.5 months. Sixteen of 20 (80%) patients suspended steroids. Reversible neuropathy occurred in seven of 28 (25%) patients, but only with cumulative doses over 28 g. Other side effects requiring thalidomide suspension were vertigo/somnolence (one of 28), and agitation/hallucinations (one of 28). CONCLUSIONS: Thalidomide seems to be effective in inducing long-term remission in children and adolescents with intractable inflammatory bowel disease. Neuropathy is the main adverse effect, but appears to be cumulative dose-dependent, thus allowing long-term remission before drug suspension.

Comorbidity of DCD and SLI: Significance of epileptiform activity during sleep.

BACKGROUND: In children affected by specific language impairment (SLI), many authors have investigated a link between language and epileptiform discharges during sleep resembling the focal sharp waves typical of benign epilepsy with centro-temporal spikes (BECTS), the so-called rolandic spikes. On the other hand, the same electroencephalographic trait occurs in more than 50% of children affected by learning or behavioural disabilities without seizures, supporting the hypothesis of a common genetic disposition. The biological background of Developmental Coordination Disorder (DCD) is currently unknown, but a genetic liability may be assumed. The aims of our study were first to estimate the prevalence of sleep-related epileptiform discharges in children affected by DCD and second to investigate the occurrence of DCD in a population of children affected by BECTS. METHODS: We selected a group of eight children with severe DCD. In this group, the presence of epileptiform activity was investigated. We also searched for DCD among a group of 13 children affected by BECTS. RESULTS: We found rolandic spikes in more than 70% of the children with severe DCD and severe DCD in more than 30% of the children with BECTS. CONCLUSIONS: In children with severe DCD other disabilities are frequently associated. In these children, epileptiform activity during sleep is very frequently found and in our opinion, this represents a hallmark of 'Hereditary Impairment of Brain Maturation', a term only partially resembling 'Atypical Brain Development'.

Apparent preferential loss of heterozygosity at TSC2 over TSC1 chromosomal region in tuberous sclerosis hamartomas.

To investigate the molecular mechanisms of tuberous sclerosis (TSC) histopathologic lesions, we have tested for loss of heterozygosity the two TSC loci (TSC1 and TSC2) and seven tumor suppressor gene-containing regions (TP53, NF1, NF2, BRCA1, APC, VHL, and MLM) in 20 hamartomas from 18 TSC patients. Overall, eight angiomyolipomas, eight giant cell astrocytomas, one cortical tuber, and three rhabdomyomas were analyzed. Loss of heterozygosity at either TSC locus was found in a large fraction of the informative patients, both sporadic (7/14) and familial (1/4). Interestingly, a statistically significant preponderance of loss of heterozygosity at TSC2 was observed in the sporadic group (P < 0.01). Among the possible explanations considered, the bias in the selection for TSC patients with the most severe organ impairment seems particularly appealing. According to this view, a TSC2 defect might confer a greater risk for early kidney failure or, possibly, a more rapid growth of a giant cell astrocytoma. None of the seven antioncogenes tested showed loss of heterozygosity, indicating that the loss of either TSC gene product may be sufficient to promote hamartomatous cell growth. Finally, the observation of loss of heterozygosity at different markers in an astrocytoma and in an angiomyolipoma from the same patient might suggest the multifocal origin of the second-hit mutation.