Neuropsychological profile of children with subcortical band heterotopia

Aim  Subcortical band heterotopia (SBH) or 'double cortex' is a malformation of cortical development resulting from impaired neuronal migration. So far, research has focused on the neurological, neuroimaging, and genetic correlates of SBH. More recently, clinical reports and small sample studies have documented neuropsychological dysfunction in patients with this malformation. This study aimed to characterize further the phenotype of patients with SBH by describing the neuropsychological profiles of children.
Method  Seven children (six females) aged 4 to 15 years were assessed for cognitive functioning (intellectual ability, processing speed, attention, working memory) and academic achievement (reading, spelling, arithmetic). Parents completed questionnaires examining their child's social skills and problem behaviours. Magnetic resonance images (MRI) conducted for routine clinical follow-up were coded by a paediatric neurologist. Genetic and seizure history were obtained from medical records.
Results  There was variation in the neurological, neuroimaging, and genetic presentation of children in the sample. Impairments were observed in all areas of neuropsychological functioning examined. Intellectual ability was generally within the 'extremely low' range (full-scale IQ 44–74; performance IQ 45–72; verbal IQ 57–80). Generalized impairments in cognitive skills were typical, with severe impairments (scores greater than 2SD below the test mean) reported in processing speed, working memory, and arithmetic. Impairments in academic, social, and behavioural functioning were less generalized. No clear relationship between neuroimaging and neuropsychological impairments was found.
Interpretation  Children with SBH demonstrate cognitive, academic, social, and behavioural problems, with the greatest difficulties in processing speed and complex cognitive skills.     

Evaluating MRI‐Compatible Pacemakers: Patient Data Now Paves the Way to Widespread Clinical Application?

The worldwide use of both magnetic resonance imaging (MRI) and pacing devices has vastly increased in recent years and an important number of implanted patients likely will need an MRI over the course of the lifetime of their device. Although some studies have demonstrated that, given appropriate precautions, MRI can be safely performed in patients with selected implantable pacemakers, MRI in pacemaker patients is still contraindicated. Recently, new pacing systems have been specifically designed for safe use in the MRI environment and the first experience reported suggests that the technology is safe and may allow patients to undergo MRI. This review will describe the outstanding issues and controversies surrounding the safety of MRI imaging in pacemaker patients and the potential benefits of the new MRI‐conditional technology. We will also discuss how to approach the decision whether or not an MRI‐conditional system should be implanted and highlight key issues that warrant further studies.     

Familial adult-onset Pompe disease associated with unusual clinical and histological features

The adult-onset form of Pompe disease had a wide clinical spectrum, ranging from asymptomatic patients with increased CK to muscle cramps and pain syndrome or rigid-spine syndrome. In addition clinical severity and disease progression are greatly variable. We report on a family with 3 siblings characterized by an unusual adult-onset Pompe disease including dysphagia and weakness of tongue, axial and limb-girdle muscles, in association with atypical globular inclusions in muscle fibres. Our study confirms the great clinical and histological variability of adult-onset Pompe disease and further supports the need of careful evaluation of bulbar function in patients affected by this pathology.Key words: Pompe disease, globular inclusions, bulbar symptomsGlycogen storage disease type II (Pompe disease or acid maltase deficiency) is a rare autosomal recessive muscular disorder characterized by deficiency of acidalfa glucosidase (GAA), determining accumulation of glycogen in the lysosomes, mainly in cardiac and skeletal muscle cells. Typical phenotypes of glycogenosis type II include the severe classic infantile form, characterized by severe muscle weakness and hypertrophic cardiomyopathy, almost invariably fatal by 12 months, a "non-classic" form presenting between 1 and 2 years of age and the lateonset form, presenting at any time after the age of 1 year, including juvenile and adult-onset subtypes, which are considered as part of a continuous clinical spectrum (1). In particular the adult-onset form presents with slowly progressive proximal lower limb and/or paraspinal muscle weakness, often followed by restrictive respiratory failure, which could be life-threatening, as it is in infants and children (2). However the clinical spectrum of adultonset form is wide, ranging from asymptomatic patients with increased CK to muscle cramps and pain syndrome or rigid-spine syndrome (2, 3). Furthermore clinical severity and disease progression is greatly variable.We report on a family with 3 siblings with an unusual adult-onset Pompe disease clinically characterized by weakness of bulbar, axial and limb-girdle muscles in association with atypical histopathological changes.     

Angiotensin-Converting Enzyme and Endothelial Nitric Oxide Synthase Polymorphisms in Patients with Atrial Fibrillation

GENSINI, F., et al. ; Angiotensin-Converting Enzyme and Endothelial Nitric Oxide Synthase Polymorphisms in Patients with Atrial Fibrillation. Experimental studies have shown a significant increase in angiotensin-converting enzyme (ACE) expression in atrial tissue of AF patients. ACE regulates the synthesis of endothelial nitric oxide (NO), which modulates autonomic nervous activity involved in the development of AF. The aim of the study was to evaluate the prevalence of ACE insertion/deletion and endothelial NO synthase (eNOS) T-786C, G894T, and 4a/4b polymorphisms in 148 patients with persistent AF, compared with 210 control subjects. ACE insertion/deletion polymorphism genotype distribution and allele frequency were significantly different between patients and controls (   P < 0.0001   and   P < 0.0001   , respectively). ACE DD genotype was significantly associated with the risk of AF   (OR DD/ID + II = 3.24, P < 0.0001)   . Analysis of eNOS polymorphisms showed no significant difference in genotype distribution and allele frequency between patients and controls. The results suggest a possible role of ACE DD genotype as a predisposing factor to AF and a pathophysiological mechanism of ACE inhibition in reducing the incidence of AF in patients with left ventricular dysfunction. (PACE 2003; 26[Pt. II]:295–298)     

Hydrolytic conditions for the formation of open-chain oligopeptides from cyclosporin A

In this work we report data on the hydrolysis of CsA, allowing interpretation on the formation of previously identified open chain oligopeptides from CsA. © Munksgaard 1997.     

Effect of inhaled histamine on occlusion pressure and breathing pattern in asthmatic patients

In animals, histamine inhalation is known to increase either respiratory frequency or respiratory drive by stimulation of airway vagal sensitive endings. However, it is not well known whether these changes are concomitant in man. In order to elucidate this point, we carried out the present investigation in thirty-five asthmatic patients who underwent bronchial provocation test by progressively doubling the dose of inhaled histamine. Bronchial reactivity to histamine allowed two populations of patients to be defined: group I with moderate and group II with mild, increased reactivity. In the twenty-three group I patients, neuromuscular inspiratory drive, assessed by mouth occlusion pressure (P_0.1), was found to be significantly increased while no significant changes in breathing pattern were noted. In the twelve group II patients histamine did not modify P_0.1 or breathing pattern. However, we were able to separate in group I a sub-group of ten patients, as with atopic asthma, in which histamine-induced increase in P_0.1 was paralleled by rapid and shallow breathing (RSB). Changes in P_0.1 and breathing pattern did not depend on baseline airway calibre. In group I, after bronchoconstriction had been reversed by inhaling a β₂-agonist bronchodilator agent (fenoterol), P_0.1 decreased significantly and RSB was found to be reversed; however, these changes were not interrelated. We concluded that: (i) in asthmatics, histamine-induced increase in P_0.1 is not necessarily paralleled by, nor related with, change in breathing pattern and (ii) in atopics a 'sensitization' of vagal receptors could account for the concomitance of enhanced P_0.1 with RSB.     

Effects of Hydrophilic and Lipophilic β-Blockers on Heart Rate Variability and Baroreflex Sensitivity in Normal Subjects

To evaluate the effect of a hydrophilic and a lipophilic β- blocker on the autonomic nervous system, 20 normal subjects were studied under baseline conditions and 7 days after being randomly assigned to metoprolol (200 mg/day), nadolol (80 mg/day), and placebo. Under each condition, the time-domain parameters were analyzed by means of 24-hour ECG monitoring and the frequency-domain parameters by means of the autoregressive method using 10-minute ECGs during rest, controlled respiration, and after a head-up tilt test. The alpha index (the gain in the relationship between the RR period and systolic arterial pressure variability) was also calculated. Both nadolol and metoprolol significantly increased all of the time-domain parameters except the standard deviation of the RR intervals; they also modified the frequency-domain parameters. Both blunted the significant reduction in the high frequency (HF) component and alpha index during tilt. In normal subjects, hydrophilic and lipophilic β-blockers similarly modify the time- and frequency-domain parameters that are particularly evident when high sympathetic tone is present (during daytime and tilt). The value of the alpha index was increased by both β-blockers in the HF, but not in the low frequency band; this difference might be due to the fact that the former is a measure of the vagal component of the baroreflex control and the latter a measure of the sympathethic component. The effects of hydrophilic and lipophilic β-blockers on the time- and frequency-domain parameters of heart rate variability are similar.