Paolo Di Bella

Effects of combination of melatonin and dexamethasone on secondary injury in an experimental mice model of spinal cord trauma

Abstract:  This study investigates the effects of combination therapy with melatonin and dexamethasone on the degree of spinal cord injury caused by the application of vascular clip in mice. Spinal cord injury in mice resulted in severe trauma, characterized by edema, neutrophil infiltration, and apoptosis (measured by terminal deoxynucleotidyltransferase‐mediated UTP end labeling staining, and immunoreaction of Bax, Bcl‐2, and Fas Ligand). Infiltration of the spinal cord tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced immuno‐ histochemical and functional alterations revealed, respectively, by an increased of tumor necrosis factor (TNF)‐α immunoreactivity, NOS as well as nitrotyrosine and loss of hind leg movement in spinal cord injury (SCI)‐operated mice. In contrast, the degree of neutrophil infiltration at different time points, cytokine expression, histologic damage iNOS expression, apoptosis, was markedly reduced in the tissues obtained from SCI‐treated mice with the combination therapy, and the motor recovery was also ameliorated. No anti‐inflammatory effect was observed in animals treated with melatonin (10 mg/kg) or with dexamethasone (0.025 mg/kg) alone. This study shows that the combination therapy with melatonin and dexamethasone reduces the degree of secondary damage associated with spinal cord injury in mice, and supports the possible use of melatonin in combination with steroids to reduce the dose and the side effects related with the use of steroids for the management of inflammatory disease.

Role of endogenous glutathione in the secondary damage in experimental spinal cord injury in mice

GSH plays multiple roles in the nervous system including free radical scavenger, redox modulator of ionotropic receptor activity, and possible neurotransmitter. A lot of evidence suggests that GSH is involved in the pathogenesis of neurodegenerative disorders, like spinal cord injury (SCI). This study was undertaken to determine if the inhibition of endogenous glutathione, by L-buthionine-(S,R)-sulfoximine (BSO), affords protection against peroxynitrite-mediated toxicity in response to the spinal cord injury in vivo. The spinal cord of damaged animals showed a significant elevation of biochemical, immunohistochemical and functional parameters, increasing, respectively, neutrophils infiltration, lipid peroxidation, nitrotyrosine formation, PAR expression, apoptosis (measured by TUNEL staining) and loss of hind legs movement in SCI-operated mice. In contrast, the administration of BSO led to worsening of this already compromised setting, increasing the degree of (1) neutrophil infiltration, (2) lipid peroxidation, (3) histological damage, (4) apoptosis, (5) nitrotyrosine formation, (6) PAR expression, (7) apoptosis (measured by TUNEL staining) and (7) loss of hind legs movement. Thus, endogenous glutathione plays an important protective role against secondary damage after SCI.

Quantitative Analysis of Pursuit Ocular Movements in Parkinson’s Disease by Using a Video-Based Eye Tracking System

The purpose of this study is to assess the efficacy and the tolerability of a new vision-based non-intrusive eye tracker in a population composed of normal controls and in patients affected by nonadvanced Parkinson’s disease (PD). PD patients characteristically have difficulty in sustaining repetitive motor actions. Previous studies showed a progressive bradykinesia and hypokinesia of pursuit ocular movements (POM) in advanced PD. We found that the values of POM were lower in PD patients than in normal controls (p < 0.001). In PD patients, the values correlated closely with Hoehn and Yahr stage and Unified Parkinson Disease Rating Scale motor subscore (p < 0.001, for both). Our data suggest that deficit in POM occurs also in nonadvanced PD patients and it is closely correlated with clinical scores. Thus, this vision-based system can be considered a new method to provide, noninvasively, measures of POM dysfunctions and can be used as reliable indices of disease severity in PD patients.

Lennox‐Gastaut syndrome with late‐onset and prominent reflex seizures in trisomy 21 patients

Purpose:  Lennox‐Gastaut syndrome (LGS) is a severe epileptic condition characterized by multiple seizure types including tonic seizures, slow spike‐and‐wave discharges on electroencephalography (EEG), and cognitive impairment. LGS can occur in apparently healthy subjects or in patients with preexisting brain damage. The onset peaks between 3 and 5 years of age and the prognosis is usually poor. Herein we report 13 subjects with trisomy 21 who developed LGS.

Sertraline in the treatment of depressive disorders in patients with Parkinson's disease.

We studied 54 idiopathic Parkinson’s disease (PD) patients with depressive disorders (DD) to compare the efficacy and the effect of treatment with sertraline in the usual formulation and in the liquid oral concentrate (LOC) formulation. After 6 months of sertraline treatment, the Hamilton Depression Rating Scale and the Montgomery and Asberg Depression Rating Scale showed a decrement (p<0.001, for both formulations). Parkinson’s Disease Questionnaire scores improved (p<0.005 for usual formulation and p<0.001 for LOC formulation), as did Clinical Global Impression-Severity of Illness scale and Clinical Global Impression-Global Improvement scale scores (p=0.1, for both formulations). Mini Mental State Examination and Unified Parkinson’s Disease Rating Scale motor subscores did not change. These results suggest that sertraline LOC may also be a useful treatment for DD in PD patients, especially for those with swallowing problems, and have significant benefit for quality of life, without worsening of parkinsonian features.

Volume rendering based on magnetic resonance imaging: advances in understanding the three‐dimensional anatomy of the human knee

The choice of medical imaging techniques, for the purpose of the present work aimed at studying the anatomy of the knee, derives from the increasing use of images in diagnostics, research and teaching, and the subsequent importance that these methods are gaining within the scientific community. Medical systems using virtual reality techniques also offer a good alternative to traditional methods, and are considered among the most important tools in the areas of research and teaching. In our work we have shown some possible uses of three‐dimensional imaging for the study of the morphology of the normal human knee, and its clinical applications. We used the direct volume rendering technique, and created a data set of images and animations to allow us to visualize the single structures of the human knee in three dimensions. Direct volume rendering makes use of specific algorithms to transform conventional two‐dimensional magnetic resonance imaging sets of slices into see‐through volume data set images. It is a technique which does not require the construction of intermediate geometric representations, and has the advantage of allowing the visualization of a single image of the full data set, using semi‐transparent mapping. Digital images of human structures, and in particular of the knee, offer important information about anatomical structures and their relationships, and are of great value in the planning of surgical procedures. On this basis we studied seven volunteers with an average age of 25 years, who underwent magnetic resonance imaging. After elaboration of the data through post‐processing, we analysed the structure of the knee in detail. The aim of our investigation was the three‐dimensional image, in order to comprehend better the interactions between anatomical structures. We believe that these results, applied to living subjects, widen the frontiers in the areas of teaching, diagnostics, therapy and scientific research.

Topiramate modulation of R3 nociceptive reflex in multiple sclerosis patients suffering paroxysmal symptoms

Sirs: Painful paroxysmal symptoms (PS) have been linked with multiple sclerosis (MS) ever since the earliest reports of the disease; they include trigeminal neuralgia, painful tonic spasms and dysesthetic or paresthetic symptoms [7, 14]. Topiramate (TPM) is a third generation, well-tolerated antiepileptic drug [13] found to be effective for refractory intercostal neuralgia [1] and trigeminal neuralgia in MS patients [15]. No neurophysiological evaluation of the effects of TPM on PS in MS has been performed. A close relationship has been found between the subjective sensation of pain, the R3 component of the blink reflex and the pain threshold on electrical stimulation of the supraorbital nerve [9–12]. Not all authors accept this reflex as a measure with which to evaluate pain [5]. However, no neurophysiological test regarding pain measurement is at present accepted by all authors. Previously, we studied this reflex in MS patients and found it to be a good tool for evaluating the nociceptive system in this disease without [3] and with [2] antiepileptic drug therapy. In order to reduce these limitations, we evaluated the effects of TPM on the nociceptive system of MS patients suffering PS, by means of the R3 component of the blink reflex associated with the Visual Analogue Scale (VAS) [4]. A study was performed on 13 clinically diagnosed [8] MS patients (Table 1), 5 males, 8 females (mean age 37.2 years), with Expanded Disability Status Scale (EDSS) score [6] between 1.5 and 7.0 (mean 4,2). All were suffering PS with VAS ≥ 6: 4 had trigeminal neuralgia, 5 painful tonic spasms, and 4 dysesthetic-paresthetic symptoms. All were being followed up as outpatients at the MS Ambulatory of Study and Treatment Center for Long-Stay Neurological Patients (of the Chair of Neurophysiopathology, University of Messina). None of the patients were in relapse at the time of the study, nor had they experienced a relapse for at least one month, nor had they been treated with any drugs for at least one month. R3 reflex and the VAS were performed at TPM therapy onset day (before the first administration) and after 12 weeks’ treatment, all at the same hour. TPM was administered twice daily. The initial dose was 50 mg/day. The daily dose was increased by 50 mg each week until the optimal one was achieved (good response: VAS ≤ 3, no severe and persistent, > 24 hours, side effects). Prior to the R3 reflex recording, the patients were informed about the procedure of the test in order to obtain their maximum collaboration. They were asked to lie supine on a bed in a quiet room with their eyes closed and to relax. The room temperature was maintained between 22–24°C. The skin surface was cleaned carefully prior to application of the surface electrodes, which were tightly fixed to the skin with electrolytic gel. The skin temperature was maintained at 32–34°C. The right supraorbital nerve was transcutaneously stimulated by surface electrodes. The cathode was placed over the supraorbital notch on the right; the anode was placed 2 cm higher and rotated laterally at an oblique angle to avoid spread of current to the controlateral supraorbital nerve. Stimulation consisted of a 300 Hz train of rectangular pulses, 20 ms train duration (6 stimuli), 0.1 ms LETTER TO THE EDITORS

Ictal paresis associated to PLEDS in two children: A video-EEG study

Ictal paresis (IP) is a rare negative motor phenomenon presenting challenging differential diagnostic problems with transient ischemic attacks, post-ictal paralysis, migraine and psychogenic paralysis. Video-EEG undoubtedly represents the essential mean for a proper diagnosis. Periodic lateralised epileptiform discharges (PLEDs) are a distinctive EEG pattern, consisting of periodic spike or sharp wave discharges, often associated with seizures. It is under debate if PLEDs should be considered only a peri-ictal or also an ictal EEG pattern. We describe two children with severe focal epilepsies, who presented IP recorded during video-EEG monitoring, associated to PLEDs. Clinical observation along with interictal and ictal scalp-EEG findings, suggested a fronto-temporal seizure onset in the first, and a temporo-insular onset in the second. We confirm that PLEDs may be an ictal pattern associated with negative motor phenomena.

Description of a family with a novel progressive myoclonus epilepsy and cognitive impairment

We report a family of Algerian origin presenting an unusual, severe form of progressive myoclonus epilepsy characterized by myoclonus, generalized tonic‐clonic seizures and moderate to severe cognitive impairment, with probable autosomal recessive inheritance. Disease onset was between 6 and 16 years of age. The diagnosis of Unverricht‐Lundborg disease and all other known causes of progressive myoclonus epilepsies were excluded by specific laboratory tests and molecular analysis.