Enormous bi-atrial enlargement in a persistent idiopathic atrial standstill

A 62-year-old woman came to our clinical attention 21 yearsago for non-cardiac problems. The clinical evaluation discloseda persistent idiopathic atrial standstill (PIAS) with mitralincompetence. The family screening documented a     

The Role of Catheter Ablation Techniques in the Treatment of Classic (Type 1) Atrial Flutter

Several attempts at circuit interruption of type 1 atrial flutter by means of surgical or catheter techniques have been published. We recently reported the results of a series of patients who underwent catheter fulguration of the low septal right atrium, with a mean follow-up of almost 3 years. True electrophysiological success was observed in 7/14 patients (50%). Clinical success, defined as absence of symptoms, was observed in 8/14 (57%) in this patient population. No serious complications were encountered, but the potential risks of DC shock, and the experience that we gained in right atrial mapping using this approach, led us to reconsider the role of atrial DC ablation in these patients. Additional studies assessing the meaning of fragmented electrograms, and identification of one for of severall slow conduction areas of the reentrant circuit are ongoing.     

Abnormal activity of the Na/Ca exchanger enhances glutamate transmission in experimental autoimmune encephalomyelitis

It is increasingly accepted that excessive glutamate release plays a key role in the pathophysiology of grey matter damage in multiple sclerosis (MS). The mechanisms causing abnormal glutamate transmission in this disorder are however largely unexplored. By means of electrophysiological recordings from single striatal neurons in slices, we found that the presymptomatic and acute phases of experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS, are associated with enhanced synaptic release of glutamate. The reverse mode of action of axonal Na⁺/Ca⁺⁺ exchanger, secondary to abnormal functioning of voltage-dependent Na⁺ channels, was identified as a major cause of this alteration. In fact, inhibition of the Na⁺/Ca⁺⁺ exchanger with bepridil or with KB-R7943, which selectively blocks the reverse mode of the exchanger, reduced the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) recorded from striatal neurons in EAE mice but not in control animals. In the presence of tetrodotoxin (TTX), a blocker of voltage-dependent Na⁺ channels, the effect of bepridil was normalized in acute (25 days post-immunization) EAE mice, indicating that axonal accumulation of Na⁺ ions flowing through voltage-dependent Na⁺ channels plays a role in the abnormal activity of the Na⁺/Ca⁺⁺ exchanger in EAE.Our data reveal an important role of Na⁺/Ca⁺⁺ exchanger and of voltage-dependent Na⁺ channels in the pathological process of EAE, and provide a rationale for the use of neuroprotective strategies since the very early stages of MS.     

Synaptic plasticity during recovery from permanent occlusion of the middle cerebral artery

Synaptic rearrangements in the peri-infarct regions are believed to contribute to the partial recovery of function that takes place after stroke. Here, we performed neurophysiological recordings from single neurons of rats with permanent occlusion of the middle cerebral artery (pMCAO) during the resolution of their neurological deficits. Our results show that complex and dynamic changes of glutamate transmission in the peri-infarct area parallel the recovery from brain infarct. We have observed that frequency and duration of spontaneous glutamate-mediated synaptic events were markedly increased in striatal neurons during the early phase of the recovery (3 days after pMCAO), due to potentiation of both NMDA (N-methyl-d-aspartate) and non-NMDA receptor-mediated transmission. In the late phase of recovery (7 days after pMCAO), glutamate transmission was still enhanced because of a selective facilitation of non-NMDA receptor-mediated transmission. Spiny projection neurons but not aspiny interneurons underwent detectable changes of synaptic excitability in the striatum following pMCAO, indicating that the process of neuronal adaptation after focal brain ischemia is cell-type-specific. Our results provide a synaptic correlate of the long-lasting brain hyperexcitability mediating recovery described with noninvasive neurophysiological approaches.     

Mechanisms of disease: basic-research-driven investigations in humans--the case of hyperkinetic disorders

Recent studies have revealed that animal models of Huntington's disease and levodopa-induced dyskinesia show similar changes in corticostriatal transmission. In both conditions, corticostriatal long-term potentiation (LTP) is abnormally stable, causing persistent inhibition of the output nuclei of the basal ganglia, and involuntary movements. This finding has led to speculation that interventions that interfere with the maintenance of corticostriatal LTP might be useful as antidyskinetic treatments. One approach that is known to reduce cortical hyperexcitability in human disorders is the delivery of a long train of low-frequency ( approximately 1 Hz) stimulation using repetitive transcranial magnetic stimulation. This stimulation protocol is remarkably similar to that used in brain slices to reverse previously induced LTP, and consequently it has been used in patients with Huntington's disease or levodopa-induced dyskinesia to try to interfere with the abnormal corticostriatal plasticity postulated to underlie the motor disturbances in these conditions. Clear antidyskinetic effects of stimulation have been obtained in both disorders, without significant side effects. These findings could have implications for the treatment of hyperkinetic disorders in the clinic, and they illustrate how basic neuroscience can generate predictions to be tested in patients.     

A diffusion longitudinal MR imaging study in normal-appearing white matter in untreated relapsing-remitting multiple sclerosis

BACKGROUND AND PURPOSE: Our aim was to evaluate the hypothesis that water diffusion alterations are present in normal-appearing white matter of patients with relapsing-remitting multiple sclerosis (RRMS) and to assess their change with time. MATERIALS AND METHODS: Fifty-four subjects with clinically diagnosed RRMS, with disease duration of less than 12 months and an expanded disability status scale (EDSS) score of <3.5, underwent a diffusion 3T MR imaging study. The apparent diffusion coefficient (ADC) maps generated were compared with those of 18 control subjects. Eighteen of the 54 patients underwent MR imaging assessment at 3 and 6 months after baseline evaluation. Remitting patients were clinically and MR imaging stable for the 2 months before the study. All patients were drug-free for the 3 months before the study, and in the relapsing patients, the MR imaging was always performed before beginning treatment. RESULTS: Mean ADC values showed significant differences when relapsing, remitting, and control patients were compared. The relapsing or remitting phase showed significant difference when compared both with controls (P < .01) and between them (P < .05). Comparing mean ADC values of patients with clinical disability (EDSS <2 versus EDSS >/=2) also provided significant differences with the control group (P < .01). The data of patients showing a relapsing episode during the longitudinal part of the study showed a significant difference compared with data from their remitting phase (P < .01). CONCLUSION: Brain microstructural changes can be detected and correlate with clinical impairment during the stages of MS. These changes modify with time in the relapsing group.     

Exercise attenuates the clinical, synaptic and dendritic abnormalities of experimental autoimmune encephalomyelitis

Voluntary exercise is beneficial in models of primarily neurodegenerative disorders. Whether exercise also affects inflammatory neurodegeneration is unknown. In the present study, we evaluated the clinical, synaptic and neuropathological effects of voluntary wheel running in mice with myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. Exercising EAE mice exhibited less severe neurological deficits compared to control EAE animals. The sensitivity of striatal GABA synapses to the stimulation of cannabinoid CB1 receptors was dramatically downregulated following EAE induction, and was rescued by exercise in EAE mice with access to a running wheel. Finally, we found that exercise was able to contrast dendritic spine loss induced by EAE in striatal neurons, although the degree of inflammatory response was similar in the two experimental groups.Our work suggests that life style and experiences can impact the clinical course of inflammatory neurodegenerative diseases by affecting their synaptic bases.     

Early relapses after the first dose of natalizumab in active multiple sclerosis patients

BackgroundNatalizumab is prescribed in Italy in patients who experienced at least two clinical relapses during a 12-month therapy with other approved immunomodulatory agents.ResultsIn 7 of 35 patients selected on the basis of these recommendations, we have observed clinical relapses occurring within 24 h after the first dose of natalizumab.ConclusionThe mechanism by which a first injection of natalizumab may precipitate a clinical relapse in patients with MS is unknown. We speculate that natalizumab can promote the release of inflammatory mediators from lymphocytes present in the central nervous system at the time of the first infusion, thus favoring the clinical manifestation of a pre-existing active lesion.     

Laparoscopy-assisted orchidopexy: an ideal treatment for children with intra-abdominal testes

BACKGROUND AND PURPOSE: The investigation of a child with a nonpalpable testis is probably the most frequent indication for laparoscopy in pediatric patients. The objective of this study was to evaluate the results and advantages of laparoscopy-assisted orchidopexy performed without dividing the spermatic vessels. PATIENTS AND METHODS: During a 3-year period, 85 boys with nonpalpable testes (NPT) (91 testes overall) underwent laparoscopic diagnostic exploration. Twenty-five patients (27.4%) showed an intra-abdominal testis (IAT): 24 underwent a laparoscopy-assisted orchidopexy (LAO) without sectioning of the spermatic vessels, and one, whose inner spermatic vessels were not adequately long for LAO without tension, underwent a two-step Fowler-Stephens (FS) procedure. The technique consists of dissection and mobilization of the inner spermatic vessels and the vas deferens from the posterior peritoneum, sectioning of the gubernaculum attachments, and bringing down of the testis into the scrotum through the internal inguinal ring, if open, or through a neo-inguinal ring created medial to the epigastric vessels. RESULTS: Surgery lasted between 40 and 80 minutes (median 60 minutes). All the testes were brought down into the scrotum. There was only 1 (4%) intraoperative complication, which occurred in the second patient operated on with this procedure. He experienced an iatrogenic rupture of the spermatic vessels secondary to excessive traction. CONCLUSION: Laparoscopic orchidopexy is the logical extension of diagnostic laparoscopy for the evaluation of NPT. Concerning the technique, we believe that LAO with intact spermatic vessels could be considered the treatment of choice in the patient with IAT, as it does not affect normal testicular vascularization. Alternatively, in the case of very high IAT (more than 3 cm from IIR), an FS procedure may be considered.