High resolution chromosomal microarray in undiagnosed neurological disorders.

AIM: Despite advances in medical investigation, many children with neurological conditions remain without a diagnosis, although a genetic aetiology is often suspected. Chromosomal microarray (CMA) screens for copy number variants (CNVs) and long continuous stretches of homozygosity (LCSH) and may further enhance diagnostic yield. Although recent studies have identified pathogenic CNVs in intellectual disability, autism and epilepsy, the utility of CMA testing in a broader cohort of children with neurologic disorders has not been reported. METHODS: Two hundred fifteen patients with neurological conditions of unknown aetiology were seen over a 6-month period and were prospectively tested by CMA using high-resolution single nucleotide polymorphism (SNP) microarrays (Illumina HumanCytoSNP-12 v2.1 or Affymetrix 2.7M). RESULTS: Thirty of 215 (14%) patients tested had an abnormal CMA. Twenty-nine had CNVs (13%) and one (0.5%) a clinically significant stretch of homozygosity. Twenty (9.3%) had a CMA finding considered to be pathogenic or involved in susceptibility to the condition of interest, and 10 (4.7%) had findings of unknown significance. Their phenotypes included infantile spasms and other epilepsies, neuromuscular conditions, ataxia, movement disorders, microcephaly and malformations of cortical development. At least one third of patients did not meet national funding criteria for CMA at the time of presentation. CONCLUSIONS: CMA detected clinically significant abnormalities in a broad range of neurologic phenotypes of unknown aetiology. This test should be considered a first-tier investigation of children with neurologic disorders in whom the initial clinical assessment does not indicate a likely aetiology, especially those with severe epilepsies and neurologically abnormal neonates.

A biomechanical study of bankart lesion fixation - biodegradable ArthroRivet tack vs. suture repair.

Bioabsorbable fixation is commonly used in soft tissue procedures performed in the shoulder. ArthroRivettrade mark tacks (referred to as rivets here), made from a copolymer of 82% poly-L-lactic acid and 18% polyglycolic acid, were developed for the Bankart procedure. Although a previous in vivo study demonstrated favorable comparison of the fixation strength and absorption characteristics of this device with that of polyglyconate bioabsorbable tacks, there have been no published biomechanical studies of this rivet in the shoulder. Fourteen shoulders were harvested from fresh-frozen cadavers of average age 74 years (46-89). Biomechanical testing was performed by measuring the energy, or work, required to anteriorly displace the humeral head 6 mm from the glenoid. Each shoulder was tested intact, vented, and before and after repair of a simulated Bankart lesion at 0, 45, and 90 degrees of abduction with and without maximal external rotation. Overall, the average work required ranged from 54.7 N-mm to 178.27 N-mm. Although the biomechanical performance of the rivet, based on resistance to anterior displacement of the humeral head, was indistinguishable from that of the suture repair, the statistical power of the test was low due to the large variance in the cadaver specimens. The results, in general, correlated well with those of previously published studies, suggesting the suitability of the bioabsorbable rivet for use in Bankart repair.

Polymicrogyria and deletion 22q11.2 syndrome: window to the etiology of a common cortical malformation.

Several brain malformations have been described in rare patients with the deletion 22q11.2 syndrome (DEL22q11) including agenesis of the corpus callosum, pachygyria or polymicrogyria (PMG), cerebellar anomalies and meningomyelocele, with PMG reported most frequently. In view of our interest in the causes of PMG, we reviewed clinical data including brain-imaging studies on 21 patients with PMG associated with deletion 22q11.2 and another 11 from the literature. We found that the cortical malformation consists of perisylvian PMG of variable severity and frequent asymmetry with a striking predisposition for the right hemisphere (P = 0.008). This and other observations suggest that the PMG may be a sequela of abnormal embryonic vascular development rather than a primary brain malformation. We also noted mild cerebellar hypoplasia or mega-cisterna magna in 8 of 24 patients. Although this was not the focus of the present study, mild cerebellar anomalies are probably the most common brain malformation associated with DEL22q11.

The epidemiology and causes of cerebral palsy.

Cerebral palsy is the commonest physical disability in childhood, occurring in 2.0 to 2.5 per 1000 live births. Although the total number of children with cerebral palsy has remained stable or increased slightly since 1970, there has been a consistent rise in the proportion of cerebral palsy associated with preterm and very preterm births. Known causes of cerebral palsy--whether prenatal, perinatal or postnatal--must be distinguished from risk factors or associations. Much is known about such risk factors which, alone or in combination, may indirectly result in cerebral palsy. Causes and risk factors implicated in cerebral palsy are discussed in detail, together with directions for future research.

Antitumorigenic activity of the prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis on azoxymethane-induced colon carcinogenesis in rats.

Prebiotics such as fructans, and probiotics such as Lactobacilli or Bifidobacteria, or a combination of prebiotics and probiotics (synbiotics) are thought to be protective against colon cancer. Therefore, we studied whether the prebiotic inulin enriched with oligofructose (Raftilose-Synergy1, briefly, Synergy1, 10% of the diet), probiotics [Bifidobacterium lactis (Bb12) and Lactobacillus rhamnosus (LGG), each at 5x10(8) c.f.u./g diet] or synbiotics (a combination of the two) protect rats against azoxymethane (AOM)-induced colon cancer. Male F344 rats were divided into: Controls; PRE, which were fed a diet containing Synergy1; PRO, fed a diet containing LGG and Bb12; PREPRO, fed a diet containing Synergy1, LGG and BB12. Ten days after beginning the diets, rats were treated with AOM (15 mg/kg s.c. two times); dietary treatments were continued for the entire experiment. Thirty-one weeks after AOM, rats treated with Synergy1 (PRE and PREPRO groups) had a significantly lower (P < 0.001) number of tumours (adenomas and cancers) than rats without Synergy1 (colorectal tumours/rat were 1.9 +/- 1.7, 1.1 +/- 1.1, 2.2 +/- 1.4 and 0.9 +/- 1.2 in Controls, PRE, PRO and PREPRO groups, respectively, means +/- SD). A slight, not significant effect of probiotics in reducing malignant tumours was also observed (P = 0.079). Caecal short-chain fatty acids (SCFA) were higher (P < 0.001) in the groups treated with Synergy1. Apoptosis was increased in the normal mucosa of the PRO group, while no variation was observed in the tumours. Colonic proliferation was lower in the PRE group as compared with Controls. Glutathione S-transferase placental enzyme pi type expression, and to a lesser extent, inducible NO synthase were depressed in the tumours from rats in the PRE and PREPRO groups. Cycloxygenase-2 expression was increased in the tumours of control rats but not in those from PRE, PRO or PREPRO rats. In conclusion, prebiotic administration in the diet decreases AOM-induced carcinogenesis in rats.