Inflammatory biomarkers and intellectual disability in patients with Down syndrome.

BACKGROUND: Intellectual disability (ID) is part of the Down syndrome (DS) phenotypic spectrum, but the exact molecular pathophysiology of ID in individuals with DS is not yet fully understood, with many research hypotheses still unproven. Basing on previous studies (which suggested a possible role of altered inflammatory response in DS-related ID), we assessed the serum levels of a number of inflammatory biomarkers [serum amyloid A (SAA), C-reactive protein (C-RP), high mobility group box-1 (HMGB1)] in a cohort of individuals with DS and healthy controls. METHODS: In total, 24 children diagnosed with DS and 12 healthy controls were enrolled, and all underwent detailed cognitive assessment. Also, serum SAA, C-RP and HMGB1 levels were measured in all recruited subjects and correlated to the severity of ID in the DS group. RESULTS: Serum SAA, C-RP and HMGB1 values were found to be significantly higher in the DS group compared with the healthy subjects (P = 0.001). In addition, serum HMGB1 levels positively correlated with C-RP and SAA in the DS group but not in the healthy controls. Only serum C-RP levels resulted inversely correlated (P < 0.01) with intelligence quotient (IQ); conversely, significant statistical correlations between serum SAA levels and IQ (as well as between HMGB1 and IQ) have been not found (P > 0.05). CONCLUSIONS: The levels of the determined markers were higher in DS individuals compared with (cognitively) healthy subjects, and CRP showed a negative correlation with IQ in children with DS.

PRIMARY NOCTURNAL ENURESIS IN CHILDREN WITH ALLERGIC RHINITIS AND SEVERE ADENOTONSILLAR HYPERTROPHY: A SINGLE CENTER PILOT STUDY.

Nocturnal enuresis is defined as intermittent urinary incontinence during sleep that occurs at least twice a week for three consecutive months. There is no unifying etiology for nocturnal enuresis in the pediatric population and the disorder is likely to be multifactorial. We aimed to investigate the relationship between primary nocturnal enuresis, allergic rhinitis, and related complications in a paediatric case series from a single Center. We retrospectively reviewed and prospectively followed-up at our Institution (i) 32 children (14 females, 18 males; mean age 6.31±1.21 yrs) affected by allergic rhinitis with adenoidal hypertrophygrade I-II (group A) and (ii) 27 children (11 females, 16 males; mean age 6.52±1.33 yrs) affected by allergic rhinitis with adenoidal hypertrophy grade III-IV (group B). Allergic rhinitis was diagnosed on the basis of (a) typical nasal symptoms due to atopic sensitization (e.g., rhinorrhea , itching, sneezing fits, and nasal congestion and obstruction) and (b) positive skin prick testing and/or increased level of total serum IgE. We identified discrepancies between group A and group B in terms of risk of primary nocturnal enuresis. In fact, only 1 child of group A (3.12%) reported uncomplicated primary nocturnal enuresis; conversely, 6 children of group B (22.22%) showed a history of uncomplicated primary nocturnal enuresis (p=0.040). There was no statistically significant difference between the two groups in terms of atopic sensitization and serum total IgE levels (p=0.43). Allergic rhinitis may potentially influence the onset and the natural history of nocturnal enuresis in some children. Children with allergic rhinitis and more severe respiratory manifestations, seem to be more prone to developing primary nocturnal enuresis, likely due to potential multi-factorial causes (e.g., sleep disorders, chronic phlogosis, immune deregulation).

Early-onset epileptic encephalopathy in a girl carrying a truncating mutation of the ARX gene: rethinking the ARX phenotype in females.

Severe early-onset epilepsy is due to a number of known causes, although a clear etiology is not identifiable in up to a third of all the cases. Pathogenic sequence variations in the ARX gene have been described almost exclusively in males, whereas heterozygous female relatives, such as mothers, sisters and even grandmothers have been largely reported as asymptomatic or mildly affected. To investigate the pathogenic role of ARX in refractory epilepsy of early onset even in females, we have screened the ARX sequence in a population of 50 female subjects affected with unexplained epileptic encephalopathy with onset in the first year of life. We report the identification of a novel truncating mutation of the coding region of the ARX gene in a girl with a structurally normal brain. Our findings confirm the role of ARX in the pathogenesis of early epilepsy and underline the importance of screening of the ARX gene in both male and female subjects with otherwise unexplained early onset epileptic encephalopathy.

Visual evoked potentials in succinate semialdehyde dehydrogenase (SSADH) deficiency.

In mammals, increased GABA in the central nervous system has been associated with abnormalities of visual evoked potentials (VEPs), predominantly manifested as increased latency of the major positive component P100. Accordingly, we hypothesized that patients with a defect in GABA metabolism, succinate semialdehyde dehydrogenase (SSADH) deficiency (in whom supraphysiological levels of GABA accumulate), would manifest VEP anomalies. We evaluated VEPs on two patients with confirmed SSADH deficiency. Whereas the P100 latencies and amplitudes for binocular VEP analyses were within normal ranges for both patients, the P100 latencies were markedly delayed for left eye (OS) (and right eye (OD), patient 1) and monocular OS (patient 2): 134-147 ms; normal <118 ms. We hypothesize that elevated GABA in ocular tissue of SSADH patients leads to a use-dependent downregulation of the major GABAergic receptor in eye, GABA(C), and that the VEP recordings' abnormalities, as evidenced by P100 latency and/or amplitude measurements, may be reflective of abnormalities within visual systems. This is a preliminary finding that may suggest the utility of performing VEP analysis in a larger sample of SSADH-deficient patients, and encourage a neurophysiological assessment of GABA(C) receptor function in Aldh5a1(-/-) mice to reveal new pathophysiological mechanisms of this rare disorder of GABA degradation.

Carbon Modular Orthosis (Ca.M.O.): An innovative hybrid modular ankle-foot orthosis to tune the variable rehabilitation needs in hemiplegic cerebral palsy.

BACKGROUND: Hemiplegic Celebral Palsy (CP) children commonly use AFO orthoses as walking aids. It is known that AFOs may have a detrimental effect on gait. To enhance mechanical properties of AFOs we developed an innovative, custom-made, carbon, ankle-foot orthosis (Ca.M.O) which offers the opportunity to tune its response to the patient's gait characteristics and/or functional maturity. OBJECTIVE: To assess the efficacy of Ca.M.O. in improving gait in a group of hemiplegic CP children and to compare its performances with those of commonly prescribed AFO. METHODS: A clinical and instrumental gait analysis was performed on a group of 15 spastic hemiplegic children (WINTERS-GAGE type I-II) walking barefoot, with commonly prescribed AFOs and with Ca.M.O.Temporal, kinematic and kinetic data were collected with an 8 cameras optoelectronic system and 2 force plates. RESULTS: Studied variables were comparable walking with Ca.M.O. and with the commonly prescribed AFO and are significantly different (p < 0.01) with respect to barefoot condition. CONCLUSIONS: Both types of orthoses normalize the kinematics of the first and second ankle rocker. The main advantage of Ca.M.O. is its modularity that allows to tune its effect on gait in relationship with the progress or involution of the child's functional development.

Neuroimaging Changes in Menkes Disease, Part 1.

Menkes disease is a rare multisystem X-linked disorder of copper metabolism. Despite an early, severe, and progressive neurologic involvement, our knowledge of brain involvement remains unsatisfactory. The first part of this retrospective and review MR imaging study aims to define the frequency rate, timing, imaging features, and evolution of intracranial vascular and white matter changes. According to our analysis, striking but also poorly evolutive vascular abnormalities characterize the very early phases of disease. After the first months, myelination delay becomes evident, often in association with protean focal white matter lesions, some of which reveal an age-specific brain vulnerability. In later phases of the disease, concomitant progressive neurodegeneration might hinder the myelination progression. The currently enriched knowledge of neuroradiologic finding evolution provides valuable clues for early diagnosis, identifies possible MR imaging biomarkers of new treatment efficacy, and improves our comprehension of possible mechanisms of brain injury in Menkes disease.

Alpha-synuclein: between synaptic function and dysfunction.

Alpha-synuclein belongs to a family of vertebrate proteins, encoded by three different genes: alpha, ss, and gamma. The protein has become of interest to the neuroscience community in the last few years after the discovery that a mutation in the alpha-synuclein gene is associated with familial autosomal-dominant early-onset forms of Parkinson Disease. However, it is not yet clear how the protein is involved in the disease. Several studies have suggested that alpha-synuclein plays a role in neurotransmitter release and synaptic plasticity. This hypothesis might help elucidate how alpha-synuclein malfunctioning contributes to the development of a series of disorders known as synucleinopathies.

Bulky-pedunculated hemolymphangioma of the esophagus: rare case in a two-years old girl.

Benign esophageal masses are rare. The authors present a rare case of bulky pedunculated hemolymphangioma of the esophagus in a two-year-old female. The symptomatology was characterized by acute episodes of dyspnea associated with the protrusion of the mass from the mouth. The mass was removed endoscopically.

[Essential thrombocythemia in pregnancy. A case report and general considerations]. / Trombocitemia essenziale in gravidanza. Descrizione di un caso clinico e considerazioni generali.

Essential thrombocythemia is a rare disease of unknown etiology characterized by an abnormal increase in the platelet count which cannot be explained by other identifiable causes such as malignancy, infection, chronic inflammatory diseases or other myeloproliferative disorders. It rarely affects people less than 50 years of age and may be associated with hemorrhagic or thrombotic tendencies. A care of pregnancy complicated by essential thrombocythemia treated with aspirin, antiaggregating agent, throughout pregnancy and with hydroxyurea, a platelet lowering drug is reported. Also examine are some pathogenetic and therapeutic aspects of the thrombotic tendency secondary to elevated platelet count in pregnancy.

Abnormal adaptation in children affected by cerebral palsy to robot generated dynamic environment.

This paper aims to investigate how robotic devices can be used to understand the mechanism of sensorimotor adaptation in pediatric subjects affected by hemiparetic cerebral palsy. Previous studies showed how healthy adults, after training in presence of a systematic structured disturbing force field, show an "after effect" and therefore they highly adapt and compensate the external disturbance. An open issue is whether this adaptive capability is preserved or disrupted in pediatric impaired subjects when they experience a robot generated dynamic environment. Fourteen pediatric Cerebral Palsy subjects (CP group), and age-matched control group were exposed to a robot generated speed-dependant force field; during familiarization (no forces generated by the robot) the movement of the CP subjects were more curved, displaying greater and variable directional error; in the force field phase both the groups showed an after-effect, but the CP group had a non significant adaptation rate. This outcome suggests the CP subjects have reduced ability to learn external force and they make greater aiming error because of an inefficient anticipatory strategy during visuomotor task.

The impact of robotic rehabilitation in children with acquired or congenital movement disorders.

AIM: The aim of this study was to evaluate if the robot-mediated therapy (RMT) can yield positive outcomes in children with acquired or congenital upper extremity movement disorders. METHODS: This was an uncontrolled pilot study with pre-post treatment outcome comparison carried out by the Pediatric Rehabilitation Department of a Children's Hospital. The study enrolled 12 children, aged 5 to 15 years, suffering from acquired (at least 12 months post-onset) or congenital upper limb motor impairment. ETIOLOGY: 4 stroke, 6 traumatic brain injuries, and 2 hemiplegic cerebral palsy. RMT was provided 3 times a week for an hour during 6 weeks for a total of 18 robot therapy sessions. The Melbourne Scale (MS) and the upper-extremity subsection of the Fugl-Meyer Assessment (FMA) were used for measurement of impairment. Secondary outcome measurements were made through the Modified Ashworth Scale (MAS); the Reaching Performance Scale (RPS); Parent's Questionnaire, and robot-based evaluation measurements. Specifically, authors compared the smoothness, as measured by the jerk metric, and average speed of unconstrained reaching movements. RESULTS: Pre-post clinical evaluation revealed statistically significant gains for all primary and secondary metrics. In addition, significant improvement of robot-based metrics was observed. The primary outcome measurement mean (SEM) gains were 6.71 (1.29) for MS and 3.33 (0.80) for the FMA. RMT led to spasticity decreases in chronic cases, as shown by the reduction of MAS. It led to improved trunk-upper extremity postural attitude as demonstrated by improved RPS, and it was well accepted by parents and children as observed in the Parent's Questionnaire. CONCLUSIONS: This study suggests that RMT may hold rehabilitative benefits in children suffering from acquired and congenital hemiparesis.

Anoxic brain injury following near-drowning in children. Rehabilitation outcome: three case reports.

PRIMARY OBJECTIVE: To describe the outcome of near-drowning and rehabilitation contexts for recovery. METHODS AND PROCEDURES: Standardized measures were used to emphasize the functional impact of deficits over the first year post-injury in three children <2 years. Multimodal contexts for meaningful interplay were early adapted to the three cases. MAIN OUTCOMES AND RESULTS: The clinical pathways of recovery are identified. Initially all three cases manifested a generalized dystonia. Case 1 exhibited a good outcome with transient dyskinetic-dystonic syndrome; subsequently Bálint's syndrome emerged. In this case, the rehabilitation approach was organized on the pickup of direct perception of task-specific affordances. Cases 2 and 3 had poor outcomes presenting the worsening of torsion dystonia (status dystonicus) that hindered rehabilitation intervention. CONCLUSIONS: The dynamic reaggregation of spatial organization through meaningful interaction in specific ecological contexts is the principal goal of rehabilitation intervention. Status dystonicus represents the worst feature for recovery.

Attempt of Yersinia enterocolitica isolation from human feces in Senegal.

One-hundred-eight stool samples, collected in a fishing village of Senegal from 72 apparently healthy subjects and from 36 patients with gastrointestinal disorders, were examined for the presence of Y. enterocolitica. After 1, 2, 3 weeks of cold enrichment with PBS 1/15M, pH 7.6, plating was performed on MacConkey Agar after use of the alkali method. No Yersinia strains were isolated.

Influence of the temperature of salt brine on salt uptake by Ragusano cheese.

The influence of temperature (12, 15, 18, 21, and 24 degrees C) of saturated brine on salt uptake by 3.8-kg experimental blocks of Ragusano cheese during 24 d of brining was determined. Twenty-six 3.8-kg blocks were made on each of three different days. All blocks were labeled and weighed prior to brining. One block was sampled and analyzed prior to brine salting. Five blocks were placed into each of five different brine tanks at different temperatures. One block was removed from each brine tank after 1, 4, 8, 16, and 24 d of brining, weighed, sampled, and analyzed for salt and moisture content. The weight loss by blocks of cheese after 24 d of brining was higher, with increasing brine temperature, and represented the net effect of moisture loss and salt uptake. The total salt uptake and moisture loss increased with increasing brine temperature. Salt penetrates into cheese through the moisture phase within the pore structure of the cheese. Porosity of the cheese structure and viscosity of the water phase within the pores influenced the rate and extent of salt penetration during 24 d of brining. In a previous study, it was determined that salt uptake at 18 degrees C was faster in 18% brine than in saturated brine due to higher moisture and porosity of the exterior portion of the cheese. In the present study, moisture loss occurred from all cheeses at all temperatures and most of the loss was from the exterior portion of the block during the first 4 d of brining. This loss in moisture would be expected to decrease porosity of the exterior portion and act as a barrier to salt penetration. The moisture loss increased with increasing brine temperature. If this decrease in porosity was the only factor influencing salt uptake, then it would be expected that the cheeses at higher brine temperature would have had lower salt content. However, the opposite was true. Brine temperature must have also impacted the viscosity of the aqueous phase of the cheese. Cheese in lower temperature brine would be expected to have higher viscosity of the aqueous phase and slower salt uptake, even though the cheese at lower brine temperature should have had a more porous structure (favoring faster uptake) than cheese at higher brine temperature. Therefore, changing brine concentration has a greater impact on cheese porosity, while changing brine temperature has a larger impact on viscosity of the aqueous phase of the cheese within the pores in the cheese.