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Alfonso C.,U.O. Ortopedia e Traumatologia | Jann S.,U.O. Neurologia | Massa R.,University of Rome Tor Vergata
Neurological Sciences | Year: 2010

The carpal tunnel syndrome is a compressive neuropathy with high incidence rates, and its correct diagnosis, treatment and follow-up may lead to significant benefits in healthcare, social and economic terms. In this review, based on systematic review databases and guidelines, we summarise the appropriate indications for the diagnosis, treatment and follow-up, accompanied, whenever possible, by the levels of evidence and strength of recommendations.© Springer-Verlag 2010.


Chieffi S.,The Second University of Naples | Iavarone A.,UO Neurologia | Iavarone A.,University of Naples Federico II | Carlomagno S.,University of Trieste
International Journal of Geriatric Psychiatry | Year: 2011

Objective to investigate patterns of anosognosia for memory deficit in subjects with amnestic mild cognitive impairment (MCI) and Alzheimer's disease (AD). Methods the study involved twenty-five subjects with MCI, 15 with mild AD and 21 normal controls (NC). Subjective rating of memory functioning was assessed with a six-items questionnaire that was administered before and after memory testing; an informant version from caregivers gave a discrepancy score (SRD). In the Objective Judgement (OJ) task, aiming to evaluate memory-monitoring abilities, subjects were requested three times to predict their memory performance in recalling words from a list of ten. Then they had to recall the words. Prediction accuracy was computed by subtracting the predicted performance from the actual performance. Results MCI and AD showed reduced awareness of memory difficulties at the SRD and did not change their rating of these difficulties after memory testing. At the OJ task, MCI and AD consistently overestimated their memory performances as compared with NC. The SRD and OJ measures were not correlated with some patients being impaired on only one measure. Only the OJ measure was significantly related to executive functioning. Conclusions AD and MCI subjects show unawareness for memory deficit and significant memory-monitoring disorder. This confirms that anosognosia is an important symptom of MCI. Similarities of patterns of impaired awareness between AD and MCI supports the view of a continuum of the anosognosia phenomenon in MCI and AD. Copyright © 2010 John Wiley & Sons, Ltd.


Ferrucci R.,Centro Clinico per la Neurostimolazione | Brunoni A.R.,University of Sao Paulo | Parazzini M.,CNR Institute of Biomedical Engineering | Vergari M.,U.O. Neurofisiopatologia | And 8 more authors.
Cerebellum | Year: 2013

Neuroimaging studies suggest that the cerebellum contributes to human cognitive processing, particularly procedural learning. This type of learning is often described as implicit learning and involves automatic, associative, and unintentional learning processes. Our aim was to investigate whether cerebellar transcranial direct current stimulation (tDCS) influences procedural learning as measured by the serial reaction time task (SRTT), in which subjects make speeded key press responses to visual cues. A preliminary modeling study demonstrated that our electrode montage (active electrode over the cerebellum with an extra-cephalic reference) generated the maximum electric field amplitude in the cerebellum. We enrolled 21 healthy subjects (aged 20-49 years). Participants did the SRTT, a visual analogue scale and a visual attention task, before and 35 min after receiving 20-min anodal and sham cerebellar tDCS in a randomized order. To avoid carry-over effects, experimental sessions were held at least 1 week apart. For our primary outcome measure (difference in RTs for random and repeated blocks) anodal versus sham tDCS, RTs were significantly slower for sham tDCS than for anodal cerebellar tDCS (p=0.04), demonstrating that anodal tDCS influenced implicit learning processes. When we assessed RTs for procedural learning across the one to eight blocks, we found that RTs changed significantly after anodal stimulation (interaction time×blocks 1/8: anodal, p=0.006), but after sham tDCS, they remained unchanged (p=0.094). No significant changes were found in the other variables assessed. Our finding that anodal cerebellar tDCS improves an implicit learning type essential to the development of several motor skills or cognitive activity suggests that the cerebellum has a critical role in procedural learning. tDCS could be a new tool for improving procedural learning in daily life in healthy subjects and for correcting abnormal learning in neuropsychiatric disorders.


Verrotti A.,University of Perugia | Loiacono G.,University of Chieti Pescara | Rossi A.,University of Chieti Pescara | Zaccara G.,U.O. Neurologia
Epilepsy Research | Year: 2014

Epilepsy is a common neurological disorder. Despite a broad range of commonly used antiepileptic drugs, approximately 30% of patients with epilepsy have drug resistance or encounter significant adverse effects. Eslicarbazepine acetate is a new central nervous system-active compound with anticonvulsant activity whose mechanism of action is by blocking the voltage-gated sodium channel. Eslicarbazepine acetate was approved by the European Medicines Agency and launched onto the European market in 2009 for adjunctive treatment in adult subjects of partial-onset seizures, with or without secondary generalization. This article provides an overview on the recent studies on eslicarbazepine acetate in the treatment of drug-resistant partial epilepsy. Efficacy and safety of this drug for partial-onset seizures were assessed in four randomized clinical trials with responder rates ranged between 17% and 43%. Adverse events were usually mild to moderate in intensity and the most common were dizziness, somnolence, nausea, diplopia, headache, vomiting, abnormal coordination, blurred vision, vertigo and fatigue. Eslicarbazepine acetate is not recommended below 18 years, but a published phase II trial had the main goal to evaluate the pharmacokinetics, efficacy and safety of this drug in pediatric population. Eslicarbazepine acetate appears to be a safe and effective drug with a linear pharmacokinetics, very low potential for drug-drug interactions and therefore it can offer a valid alternative to current antiepileptic drugs. Additionally, it is undergoing investigation for monotherapy in subjects with partial epilepsy, and other neurological and psychiatric disorders. © 2013 Elsevier B.V.


Verrotti A.,University of Chieti Pescara | Loiacono G.,University of Chieti Pescara | Di Sabatino F.,University of Chieti Pescara | Zaccara G.,U.O. Neurologia
Acta Neurologica Scandinavica | Year: 2013

The first aim of our study was to analyze the adverse events statistically significantly associated with zonisamide, through a systematic review and meta-analysis of available randomized placebo-controlled trials (RCTs). The second aim was to compare these results with those obtained from an analysis of non-RCTs and observational studies. Randomized controlled trials were identified using Medline (PubMed), EMBASE (Ovid), and Cochrane CENTRAL, from 1990 to September 2012. RevMan version 5.1 and OpenMeta[Analyst] were used for analyses of RCT and non-RCTs, respectively. Six eligible studies with 1184 patients between 12 and 80 years of age were included in RCTs analysis. Fifteen adverse events were investigated. In this first part of the analysis, no adverse events were statistically significantly associated with zonisamide. In the non-RCT analysis, a high incidence of weight loss and headache was found. In RCTs, zonisamide was statistically significantly associated with an increased risk of adverse event-related study withdrawals [RR (99% CI) = 1.81 (1.07-3.08)]. Although our study revealed no statistically significantly associated adverse effects (AEs) with zonisamide, this is very likely a consequence of the small numbers in the RCTs available. The limited data available from the studies appear to reveal no major safety concerns related to zonisamide. However, the high incidence of weight loss and headache in the non-RCTs suggests that these AEs could be of clinical significance. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Zaccara G.,U.O. Neurologia | Zaccara G.,San Giovanni Of Dio Hospital | Gangemi P.,Anffas Rehabilitation Institute | Perucca P.,University of Pavia | Specchio L.,University of Foggia
Epilepsia | Year: 2011

Purpose: Despite the widespread use of antiepileptic drugs (AEDs) across different neurologic and psychiatric disorders, no study has systematically reviewed all available randomized controlled trials (RCTs) of a given AED to fully uncover its tolerability profile. We aimed at identifying treatment emergent adverse events (AEs) associated with pregabalin through a systematic review and meta-analysis of all available RCTs. We also assessed the association between serious AEs and pregabalin, and investigated whether pregabalin AEs display a dose-response relationship. Methods: We searched MEDLINE, EMBASE, and Cochrane CENTRAL to February 2010 for RCTs. Additional studies were identified from reference lists of retrieved papers and from online clinical databases. We selected placebo-controlled, double-blind RCTs investigating the therapeutic effects of pregabalin in adults with any condition. Studies had to include at least 20 subjects per arm and have a duration of at least 4 weeks. AEs were assessed for their association with pregabalin after identification/exclusion of synonyms, rare AEs, and nonassessable AEs due to methodologic limitations. We used relative risks (RRs) to assess the association of any [99% confidence intervals (CIs)] or serious AEs (95% CIs) with pregabalin, and risk differences (RDs, 95% CIs) to investigate dose-response relationships of pregabalin AEs. Key findings: Thirty-eight RCTs were included in our study. Of 39 AEs, 20 (51%) were significantly associated with pregabalin (dizziness, vertigo, incoordination, balance disorder, ataxia, diplopia, blurred vision, amblyopia, tremor, somnolence, confusional state, disturbance in attention, thinking abnormal, euphoria, asthenia, fatigue, edema, peripheral edema, dry mouth, constipation). The highest RRs were found for cognition/coordination AEs. There was no significant association between serious AEs and pregabalin. There was a selective dose-response pattern in the onset of pregabalin AEs, with certain AEs appearing at lower doses than others. Significance: Individuals starting treatment with pregabalin are at increased risk for several AEs, particularly those affecting cognition/coordination. Pregabalin AEs appear according to a selective dose-response pattern, possibly reflecting the severity of dysfunction of distinct anatomic structures. These findings may aid clinicians in providing better patient management, and support the value of including in meta-analyses of AED tolerability profiles RCTs performed in different conditions. © Wiley Periodicals, Inc. 2011 International League Against Epilepsy.


Van Zuuren E.J.,Leiden University | Fedorowicz Z.,Cochrane Collaboration | Pucci E.,U.O. Neurologia | Jagannath V.,American Mission Hospital
Journal of Neurology, Neurosurgery and Psychiatry | Year: 2014

Background: It has been recently hypothesised that chronic cerebrospinal venous insuf ficiency (CCSVI) may be an important factor in the pathogenesis of multiple sclerosis (MS). The proposed treatment for CCSVI is percutaneous transluminal angioplasty, also known as the 'liberation procedure', which is claimed to improve the blood flow in the brain, thereby alleviating some of the symptoms of MS. Our objective was to determine the effects of percutaneous transluminal angioplasty used for the treatment of CCSVI in people with MS. Methods: We searched the following databases up to June 2012 for randomised controlled trials: The Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register, CENTRAL, in The Cochrane Library 2012, Issue 5, MEDLINE (from 1946), EMBASE (from 1974) and reference lists of articles. We also searched several online trials registries for ongoing trials. Results: Our searches retrieved 159 references, six of which were related to ongoing trials. No randomised controlled trials met our inclusion criteria. Conclusions: There is currently no high level evidence to support or refute the efficacy or safety of percutaneous transluminal angioplasty for treatment of CCSVI in people with MS. Clinical practice should be guided by evidence supported by well-designed randomised controlled trials: closure of some of the gaps in the evidence may be feasible at completion of the six ongoing clinical trials.


Falace A.,University of Genoa | Filipello F.,University of Genoa | La Padula V.,Italian Institute of Technology | Vanni N.,University of Genoa | And 10 more authors.
American Journal of Human Genetics | Year: 2010

Idiopathic epilepsies (IEs) are a group of disorders characterized by recurrent seizures in the absence of detectable brain lesions or metabolic abnormalities. IEs include common disorders with a complex mode of inheritance and rare Mendelian traits suggesting the occurrence of several alleles with variable penetrance. We previously described a large family with a recessive form of idiopathic epilepsy, named familial infantile myoclonic epilepsy (FIME), and mapped the disease locus on chromosome 16p13.3 by linkage analysis. In the present study, we found that two compound heterozygous missense mutations (D147H and A509V) in TBC1D24, a gene of unknown function, are responsible for FIME. In situ hybridization analysis revealed that Tbc1d24 is mainly expressed at the level of the cerebral cortex and the hippocampus. By coimmunoprecipitation assay we found that TBC1D24 binds ARF6, a Ras-related family of small GTPases regulating exo-endocytosis dynamics. The main recognized function of ARF6 in the nervous system is the regulation of dendritic branching, spine formation, and axonal extension. TBC1D24 overexpression resulted in a significant increase in neurite length and arborization and the FIME mutations significantly reverted this phenotype. In this study we identified a gene mutation involved in autosomal-recessive idiopathic epilepsy, unveiled the involvement of ARF6-dependent molecular pathway in brain hyperexcitability and seizures, and confirmed the emerging role of subtle cytoarchitectural alterations in the etiology of this group of common epileptic disorders. © 2010 The American Society of Human Genetics.


Mioni G.,University of Padua | Meligrana L.,U.O. Neurologia | Grondin S.,Laval University | Perini F.,U.O. Neurologia | And 2 more authors.
Journal of the International Neuropsychological Society | Year: 2015

Previous studies have demonstrated that emotional facial expressions alter temporal judgments. Moreover, while some studies conducted with Parkinson's disease (PD) patients suggest dysfunction in the recognition of emotional facial expression, others have shown a dysfunction in time perception. In the present study, we investigate the magnitude of temporal distortions caused by the presentation of emotional facial expressions (anger, shame, and neutral) in PD patients and controls. Twenty-five older adults with PD and 17 healthy older adults took part in the present study. PD patients were divided into two sub-groups, with and without mild cognitive impairment (MCI), based on their neuropsychological performance. Participants were tested with a time bisection task with standard intervals lasting 400 ms and 1600 ms. The effect of facial emotional stimuli on time perception was evident in all participants, yet the effect was greater for PD-MCI patients. Furthermore, PD-MCI patients were more likely to underestimate long and overestimate short temporal intervals than PD-non-MCI patients and controls. Temporal impairment in PD-MCI patients seem to be mainly caused by a memory dysfunction. (JINS, 2015, 21, 1–10) Copyright © The International Neuropsychological Society 2015


Voltage computed analysis of spikes (S) and the average amplitude of spike and wave complexes (SW) were evaluated in three adult patients with frontal pseudo-absence seizures in order to identify the origins of the abnormalities related to this type of seizures. Interhemispheric phase shift delays of S were detected in all cases. In two patients with frontal lobe damage, the average amplitude of SW was asymmetric and the phase shift analysis of S showed constant delays on one side of the brain. In one of these cases with unilateral cerebral damage, the average amplitude of SW was reduced on the damaged side, while S originated in the contralateral frontal region. In another patient with no evidence of cerebral lesions, the analysis of S indicated a bilateral independent origin of the epileptic abnormalities in homologue frontal regions, suggesting a potential pathogenic role of mirror foci in pseudo-absence seizures. Voltage computed analysis of S and SW should be considered in the diagnostic work-up of patients with generalised epileptic discharges. It should be noted that, in pseudo-absence seizures, the origin of the epileptic abnormalities may not be related to evident parenchymal damage.

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