Neonatal diabetes mellitus due to pancreatic agenesis and pervasive developmental disorder

Recent studies suggested a link between type 1 diabetes mellitus and pervasive developmental disorder. Moreover, permanent neonatal diabetes mellitus due to pancreatic agenesis can be associated with neurological deficit involving cerebellar functions, but no association with pervasive developmental disorder has been described so far. Clinical and neuropsychological evaluation of a child with pancreatic agenesis, mental retardation and pervasive developmental disorder is reported

Alternating Hemiplegia of Childhood: Pharmacological treatment of 30 Italian patients

Background Alternating Hemiplegia of Childhood (AHC) is a severe disorder. Several drugs have been administered as prophylaxis for paroxysmal attacks, however, no therapy is completely effective. Methods Our aim is to review the pharmacological data related to the prophylactic and acute treatment of a cohort of 30 patients (16 M, 14 F, age range 5\u201342 years) and to correlate them with the clinical and genetic data collected through the Italian Biobank and Clinical Registry for AHC. Results Flunarizine was the most commonly used long-term treatment in the cohort; it reduced duration and frequency of attacks in 50% of patients and decreased intensity in 32.1%. In younger patients, flunarizine seemed significantly more effective in reducing intensity. We found no correlation between the effectiveness of flunarizine and genotype, or between developmental outcome and duration of treatment. In particular, 3 of our patients affected by E815K mutation presented rapid neurological deterioration despite ongoing treatment. Among the other administered prophylactic therapies, few proved to be effective (benzodiazepines, niaprazine, acetazolamide, melatonin, olanzapine, ketogenic diet). No clear rationale exists regarding their use, but these therapies may work by reducing the triggering factors. Conclusions The presented data are retrospective, but they are aimed at filling a gap given the rarity of the disease and the lack of randomized and controlled studies. Besides their usefulness in clarifying the pathophysiology of the disease, prospective studies involving larger cohorts of ATP1A3 mutated AHC patients are needed to provide a rationale for testing other molecules

Analysis of the phenotypes in the Rett Networked Database

Rett spectrum disorder is a progressive neurological disease and the most common genetic cause of intellectual disability in females. MECP2 is the major causative gene. In addition, CDKL5 and FOXG1 mutations have been reported in Rett patients, especially with the atypical presentation. Each gene and different mutations within each gene contribute to variability in clinical presentation, and several groups worldwide performed genotype-phenotype correlation studies using cohorts of patients with classic and atypical forms of Rett spectrum disorder. The Rett Networked Database is a unified registry of clinical and molecular data of Rett patients, and it is currently one of the largest Rett registries worldwide with several hundred records provided by Rett expert clinicians from 13 countries. Collected data revealed that the majority of MECP2-mutated patients present with the classic form, the majority of CDKL5-mutated patients with the early-onset seizure variant, and the majority of FOXG1-mutated patients with the congenital form. A computation of severity scores further revealed significant differences between groups of patients and correlation with mutation types. The highly detailed phenotypic information contained in the Rett Networked Database allows the grouping of patients presenting specific clinical and genetic characteristics for studies by the Rett community and beyond. These data will also serve for the development of clinical trials involving homogeneous groups of patient

One hand, two hands, two people: Prospective sensorimotor control in children with autism

Where grasps are made reveals how grasps are planned. The grasp height effect predicts that, when people take hold of an object to move it to a new position, the grasp height on the object is inversely related to the height of the target position. In the present study, we used this effect as a window into the prospective sensorimotor control of children with autism spectrum disorders without accompanying intellectual impairment. Participants were instructed to grasp a vertical cylinder and move it from a table (home position) to a shelf of varying height (target position). Depending on the conditions, they performed the task using only one hand (unimanual), two hands (bimanual), or with the help of a co-actor (joint). Comparison between the performance of typically developing children and children with autism revealed no group difference across tasks. We found, however, a significant influence of IQ on grasp height modulation in both groups. These results provide clear evidence against a general prospective sensorimotor planning deficit and suggest that at least some form of higher order planning is present in autism without accompanying intellectual impairment. Keywords: Autism, Prospective control, Grasp height effect, Sensorimotor, Kinematics, Joint actio

MR imaging findings in 2 cases of late infantile GM1 gangliosidosis.

Late infantile GM1 gangliosidosis is a rare lysosomal disorder characterized by mental deterioration and progressive spastic, cerebellar, and extrapyramidal signs, without facial dysmorphisms and organomegaly. Neuroimaging findings have been reported in only a few cases. Here we report on predominant globus pallidus MR signal-intensity abnormalities in 2 patients with the late infantile form of GM1 gangliosidosis. GM1 gangliosidosis is a rare metabolic disorder due to deficiency of the lysosomal enzyme \u3b2-galactosidase, resulting in accumulation of GM1 gangliosides and other glycoconjugates in the brain and visceral organs. There are 3 clinical forms correlating with the degree of residual activity of the mutant enzyme. The infantile form (type 1) is a severe degenerative encephalopathy presenting between birth and 6 months with coarse facial features, skeletal dysostosis, and hepatosplenomegaly, leading to death within the first 2 years of life. Patients with the late infantile or juvenile form (type 2) present after 1 year of age with motor delay in the absence of dysmorphisms and organomegaly; later, mental deterioration and spastic, cerebellar, and extrapyramidal signs dominate the neurologic picture, probably as a consequence of predominant basal ganglia storage of gangliosides.1 The adult form (type 3) has a slowly progressive course and predominant extrapyramidal features without visceral or skeletal changes.2 Reports on the neuroimaging features of the very rare late infantile GM1 gangliosidosis are scant and have mainly included brain atrophy and white matter and basal ganglia abnormalities.3,4 We report 2 young patients in whom MR imaging predominantly showed evidence of globus pallidum paramagnetic ion accumulation

CC and CXC chemokines are pivotal mediators of cerebral injury in ischaemic stroke.

The definition of ischaemic stroke has been recently updated as an acute episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischaemia in the presence of a cerebral infarction. This "tissular" definition has highlighted the importance of pathophysiological processes underlying cerebral damage. In particular, post- ischaemic inflammation in the brain and in the blood stream could influence crucial steps of the tissue injury/repair cascade. CC and CXC chemokines orchestrate the inflammatory response in atherosclerotic plaque vulnerability and cerebral infarction. These molecules exert their activities through the binding to selective transmembrane receptors. CC and CXC chemokines modulate crucial processes (such as inflammatory cell recruitment and activation, neuronal survival, neoangiogenesis). On the other hand, CXC chemokines could also modulate stem cell homing, thus favouring tissue repair. Given this evidence, both CC and CXC chemokines could represent promising therapeutic targets in primary and secondary prevention of ischaemic stroke. Only preliminary studies have been performed investigating treatments with selective chemokine agonists/antagonists. In this review, we will update evidence on the role and the potential therapeutic strategies targeting CC and CXC chemokines in the pathophysiology of ischaemic stroke

Pathophysiological role of inflammatory molecules in paediatric ischaemic brain injury.

Ischaemic stroke is one of the major causes of death and lifelong disability also in the paediatric population. Strong scientific effort has been put to clarify the pathophysiology of this disease in adults. However, only few studies have been performed in children. Preliminary results indicate that pathophysiological processes might differently affect the poststroke neuronal injury in neonates as compared to children. During the neural development, selective molecular mechanisms might be differently triggered by an ischaemic insult, thus potentially resulting in defined postischaemic clinical outcomes. Basic research studies in neonatal animal models of cerebral ischaemia have recently shown a potential role of soluble inflammatory molecules (such as cytokines, chemokines and oxidants) as pivotal players of neuronal injury in both perinatal and childhood ischaemic stroke. Although larger clinical trials are still needed to confirm these preliminary results, the potential benefits of selective treatments targeting inflammation in perinatal asphyxia encephalopathy might represent a promising investigation field in the near future. In this review, we will update evidence on the pathophysiological role of soluble inflammatory mediators in neonatal and childhood ischaemic stroke. Recent evidence on potential anti-inflammatory treatments to improve paediatric stroke prognosis will be discussed