Eslicarbazepine acetate as adjunctive treatment in partial-onset epilepsy.

OBJECTIVE: The aim of the study was to assess the clinical response to eslicarbazepine acetate (ESL) as add-on therapy in adult patients with partial-onset epilepsy by means of the time-to-baseline seizure count method. METHODS: We retrospectively identified consecutive patients with partial-onset seizures, with or without secondary generalization, prescribed to ESL add-on therapy. The primary endpoint was the time-to-baseline monthly seizure count. Subgroup analysis was performed according to carbamazepine (CBZ)/oxcarbazepine (OXC) status (prior vs never use). Secondary outcomes were the rate of treatment-related adverse events (AEs) and the AEs affecting ≥5% of patients. RESULTS: One-hundred and eighteen patients were included. The median time-to-baseline monthly seizure count was 46 (35-101) days in the overall study cohort. The number of concomitant anti-epileptic drugs (AEDs) was associated with the time-to-endpoint (adjusted hazard ratio [adj HR]=2.22, 95% CI 1.18-4.14, P=.013 for two AEDs vs one; adj HR=3.65, 95% CI 1.66-8.06, P=.001 for three or more AEDs vs one). Groupwise, the median times-to-baseline seizure count were 47 (35-97) and 43 (34-103) in patients with prior and never exposure to CBZ/OXC, respectively (P for log-rank test=.807). Adverse events occurred in 53.4% (63 of 118) of patients; the most frequently reported were dizziness (13.6%), somnolence (11.9%), nausea (6.8%), and fatigue (5.1%). CONCLUSIONS: Add-on ESL improved seizure control and was overall well-tolerated in adult patients with partial-onset epilepsy.

The organisation of the acute ischemic stroke management: key notes of the Italian Neurological Society and of the Italian Stroke Organization.

The main aim of acute ischemic stroke treatment is the as much possible prompt, safe and effective arterial recanalisation, in order to restore reperfusion into the ischemic brain area. The procedures obtaining this result are rapidly evolving and in the last years, we observed new evidences that affirmed the therapeutical benefit of the concomitant treatment using endovenous thrombolysis and mechanical thrombectomy in selected patients with ischemic stroke. However, all treatments are time-sensitive and the main limitation for their application is represented by the time. For this reason, the optimisation of the acute stroke management that includes a pre-hospital and an in-hospital phase is essential to reduce the avoidable delay, increasing the number of patients potentially treatable. The purpose of this document is to define the main elements and to suggest the principal key points constituting the optimal pathway of stroke management in Italian care settings, in line with the recommendations coming from the current national and international guidelines.

Prevalence of obstructive sleep apnea syndrome in a population of patients with transient global amnesia.

OBJECTIVE: The etiology of transient global amnesia (TGA) is largely undetermined. The aim of this study was to investigate whether the prevalence of obstructive sleep apnea syndrome (OSAS), a condition associated with subtle changes in brain structures involved in memory processes, increases in subjects who have previously experienced a TGA episode. METHODS: Twenty-nine patients who had had a TGA episode were included. A case-control model was used, matching cases with controls by sex, age, and body mass index category. Diagnosis of OSAS was based on the results of the Berlin Questionnaire, which was later confirmed by means of an all-night polysomnography recording. RESULTS: The prevalence of OSAS among TGA patients was significantly higher with respect to that in controls (44.8% vs 13.8%, p = 0.020, χ2 test). At logistic regression model, subjects with TGA had an odds ratio of 8.409 (95% confidence interval = 1.674-42.243; p = 0.010) of having OSAS when compared with controls. CONCLUSIONS: According to our findings, an accurate investigation of sleep disturbances could be considered for a complete assessment of patients with TGA. The subtle cerebral anatomo-functional damage induced by the repeated nocturnal apneic episodes may be a pathophysiologic link between OSAS and TGA.

Diagnostic delay and prognosis in primary central nervous system lymphoma compared with glioblastoma multiforme.

Glioblastoma multiforme (GBM) and primary central nervous system lymphoma (PCNSL) are malignant cerebral neoplasms associated with poor prognosis. Early diagnosis and subsequent planning of adequate treatment strategy are relevant to improve survival and reduce neurological deficit. Two groups of patients affected by GBM and PCNSL were compared to identify: (1) factors influencing the time necessary to obtain a correct diagnosis; (2) the influence of the interval time from clinical onset to diagnosis on the prognosis. Fifty-six patients (28 PCNSL and 28 GBM, 23 females and 33 males) referred to the same hospital setting were retrospectively evaluated. The mean age at diagnosis was 61 years. The two groups were comparable in terms of age, sex, clinical symptoms at onset and performance status. There was no relevant difference in time span from clinical onset to first neuroimaging examination, while time span from first neuroimaging to final morphological diagnosis was much longer in PCNSL patients (p = 0.008). Multivariate Cox regression analysis, including both PCNSL and GBM cases, showed a significant association of the overall survival with: time to diagnosis (HR 0.06), age at onset (HR 1.04). Our results show a significant diagnostic delay in PCNSL cases. Age at onset of disease and time to diagnosis emerge as clinical factors affecting overall survival in both groups. Stereotactic-guided biopsy should be chosen as routine method to early diagnose PCNSL. The clinical relevance of early diagnosis in GBM and PCNSL needs to be emphasized to maximize the overall survival in both neoplasms.

Triptan use among hospital workers affected by migraine.

Triptans represent the most specific and effective treatment for migraine attacks. Nevertheless, in clinical practice, they are often underused. Hospital workers, in particular physicians, are expected to be more aware of the correct use of specific drugs, especially for a very common disease such as migraine. Aim of this study was to evaluate whether different hospital workers affected by migraine are able to correctly manage the most suitable therapy for their migraine attacks. During a 1-year period, we submitted hospital employees to a structured interview with a questionnaire to investigate the presence of headache and its characteristics. In particular, in the subpopulation of subjects affected by migraine, we took information regarding their usual treatment for the control of attacks. The type of drug and the category of the working activity were synthesized as two different ordinal variables. Difference in the distribution of the different drug categories was evaluated with Chi squared test. Statistics was performed with SPSS 13.0 for Windows systems. We enrolled 1250 consecutive subjects: 20.3 % of the population (254 patients) was affected by migraine. Triptans use was significantly lower than that of non-steroidal anti-inflammatory drugs. The distribution of the use of the drugs was significantly different (p < 0.0001) at Chi squared test. Among migraineur physicians, only 10.7 % used triptans. Even in this subgroup, we observed a significant difference (p < 0.0001) in the distribution of the use of the drugs at Chi squared test. Our findings show a reduced use of triptans among hospital workers. These data reflect the unsatisfactory dissemination of knowledge regarding the correct management of migraine attacks and the advantages of treatment with triptans. An incorrect therapeutic approach to migraine contributes to the risk of the most important complications, such as drugs abuse or illness chronicization. These findings suggest that an insufficient awareness of migraine-related therapeutic options also involves hospital workers, including physicians.

Skin features in myotonic dystrophy type 1: an observational study.

Poor data regarding skin involvement in Myotonic Dystrophy, also named Dystrophia Myotonica type 1, have been reported. This study aimed to investigate the prevalence and types of skin disorders in adult patients with Myotonic Dystrophy type 1. Fifty-five patients and one hundred age- and sex-matched healthy subjects were referred to a trained dermatologist for a complete skin examination to check for potential cutaneous hallmarks of disease. No difference in prevalence of preneoplastic, neoplastic, and cutaneous lesions was detected between the two groups. Among morphofunctional, proliferative and inflammatory lesions, focal hyperhidrosis (p < 0.0001), follicular hyperkeratosis (p = 0.0003), early androgenic alopecia (p = 0.01), nail pitting (p = 0.003), pedunculus fibromas (p = 0. 01), twisted hair (p = 0.01), seborrheic dermatitis (p = 0.02), macules of hyperpigmentation (p = 0.03) were significantly more frequent in patients compared with controls. In patients with Myotonic Dystrophy type 1 significant differences according to sex were found for: early androgenic alopecia, twisted hair and seborrheic dermatitis, whose prevalence was higher in males (p < 0.0001). Our preliminary results seem to rule out an increased prevalence of pre-neoplastic, and neoplastic skin lesions in Myotonic Dystrophy type 1. On the other hand, an increased prevalence of morphofunctional, inflammatory, and proliferative diseases involving adnexal structures seems to characterize adult patients with Myotonic Dystrophy type 1.

Features and predictors of activity limitations and participation restriction 2 years after intensive rehabilitation following first-ever stroke.

BACKGROUND: Although stroke-related disability has been extensively studied, only few studies have investigated Participation restriction in chronic stroke survivors. AIM: To identify features and predictors of Activity limitation and Participation restriction in the chronic phase of a first-ever stroke. DESIGN: Cross-sectional observational study. SETTING: Comprehensive stroke unit with outpatient rehabilitation facility. POPULATION: Subjects submitted to intensive rehabilitation after first-ever stroke, from 1st January 2009 to 31st December 2010. METHODS: Participation was investigated through the Frenchay Activity Index (FAI) and the Functional Status Questionnaire (FSQ) at 2.4±0.5 years after the event. Basic activities of daily living (ADL) and mood were also assessed through the Modified Barthel Index (MBI) and the Beck Depression Inventory (BDI). A retrospective search of the medical records looked for: type/side of brain lesion, stroke clinical syndromes, comorbidities and functional condition at discharge from intensive rehabilitation (upper limb motricity index-ULMI-, Functional Ambulation Category-FAC, MBI, cognitive deficits). RESULTS: Forty-five subjects (17 female, age 70.1±11.5 years) were enrolled. They showed a striking restriction in their Participation, mainly for FAI-outdoor activities (median FAI score was <50% of the theoretical maximum). A poor gait function (FAC) and an impaired mood (BDI) were the only independent predictors of FAI indoor (F=6.1; p=,005; R^2= 64%) and outdoor activities (F=4.1; P=0.01; R^2=48%), respectively. The univariate analysis showed a strong dependence of all FSQ scores from global disability (MBI), motor function impairment (ULMI and FAC) and cognitive deficits. Depression influenced "psychological function" score, whereas gait capacity was the only factor significantly associated with the "work performance" score. The gait function level, achieved after intensive rehabilitation, was extrapolated by the multivariate analysis, as the most powerful independent predictor of the chronic activity limitations, as measured by MBI (F=33.8, P<0.0001, R2=0.539). CONCLUSION: Gait dysfunction is the main factor of Activity limitations and Participation restriction in chronic stroke. Participation is restricted by global disability, depression, older age and dementia. More than 50% variance of Participation measures cannot be explained by the quoted factors. CLINICAL REHABILITATION IMPACT: The study results support the need to integrate the standard rehabilitation approach with vocational rehabilitation in order to reduce Participation restriction.

The neural correlates of road sign knowledge and route learning in semantic dementia and Alzheimer's disease.

BACKGROUND: Although there is a growing body of research on driving and Alzheimer's disease (AD), focal dementias have been understudied. Moreover, driving has never been explored in semantic dementia (SD). METHODS: An experimental battery exploring road sign knowledge and route learning was applied to patients with SD and AD selected in the early-moderate stage of disease and to a group of healthy participants. Neuropsychological data were correlated to cerebral hypometabolism distribution, investigated by means of positron emission tomography. RESULTS: The two dementias showed opposite profiles. Patients with SD showed poor road sign knowledge and normal performance in route learning. By contrast, patients with AD showed low performance in route learning test with preservation of semantic knowledge of road signs. In SD, there was a correlation of semantic knowledge impairment with hypometabolism in the left temporolateral cortex. No correlation between the AD region of interests (ROIs) and the relevant behavioural indices was found, while in the whole-brain analysis there was a significant correlation between route learning and the superior frontal gyrus. DISCUSSION AND CONCLUSIONS: For the first time, driving skills were explored in SD, and it is showed a differential profile from the one detected in AD. We demonstrate that the left anterior temporal cortex is implicated in road sign knowledge, while a distributed cortical network, including the frontal cortex, is likely to process route learning.

[Topical pharmacologic approach with 5% lidocaine medicated plaster in the treatment of localized neuropathic pain]. / Approccio farmacologico topico con lidocaina cerotto 5% nel trattamento del dolore neuropatico localizzato.

The treatment of neuropathic pain is a medical challenge. The responsiveness to the different classes of drugs is often unsatisfactory and frequently associated to a wide range of side effects. International guidelines suggest for the "localized" neuropathic pain the topical treatment with 5% lidocaine medicated plaster, alone or associated to systemic drugs, as the first choice since its favorable efficacy and tolerability profile. Many clinical experiences support the rationale for using 5% lidocaine medicated plaster in different kinds of localized neuropathic pain, such as postherpetic and trigeminal neuralgia, compressive syndromes, painful diabetic polyneuropathy and pain secondary to trauma or surgical interventions. This paper reports a series of clinical cases whose heterogeneity suggests the wide burden of applicability of the topical 5% lidocaine, either alone and associated to systemic drugs. All the described conditions were characterized by a highly intense pain, not adequately controlled by actual medications, which improved after the use of topical lidocaine. The good response to lidocaine allowed the reduction, of even the withdrawal, of concurrent drugs and improved the patients' quality of life.

Natalizumab treatment in multiple sclerosis patients: a multicenter experience in clinical practice in Italy.

We evaluated efficacy of natalizumab in relapsing-remitting multiple sclerosis patients in a clinical practice setting. We report data on the first consecutive 343 patients receiving natalizumab in 12 multiple sclerosis (MS) Italian centers enrolled between April 2007 and November 2010. The main efficacy endpoints were the proportion of patients free from relapses, disease progression, combined clinical activity, defined as presence of relapse or disease progression, from MRI activity, and from any disease activity defined as the absence of any single or combined activity. At the end of follow-up, the cumulative proportion of patients free from relapses was 68%; the proportion of patients free from Expanded Disability Status Scale (EDSS) progression was 93%; the proportion of patients free from combined clinical activity was 65%; the proportion of patients free from MRI activity was 77%; and the proportion of patients free from any disease activity was 53%. Natalizumab was effective in reducing clinical and neuroradiological disease activity. Its effectiveness in clinical practice is higher than that reported in pivotal trials and was maintained over time.

Migraine in health workers: working in a hospital can be considered an advantage?

Migraine is the most common form of headache, and is one of the most diffused pathologies in the world. Moreover, patients often lose years before obtaining a correct diagnosis. The aim of this study was to evaluate whether diagnostic delay differs between hospital workers, in theory more sensible to health problems, and common people. We compared our cohort of patients attending the headache center on which we put a diagnosis of migraine with and without aura with a sample of hospital workers investigated about headache presence and characteristics. Particularly, hospital workers were evaluated by ID-migraine test, a three-question test validated to formulate a migraine diagnosis. Continuous variables (age and diagnostic delay) were compared with t test for independent samples. Dichotomous and categorical variables were compared with Chi squared test. The mean difference between in-hospital workers and outpatients was analyzed with a GLM/multivariate model accounting for age and sex. The difference between the single subcategory of workers affected by migraine was explored with a GLM/multivariate model accounting of age and sex. Five hundred and ninety-nine patients affected by migraine with and without aura were enrolled. Demographical characteristics were comparable in the two study populations. In-hospital workers (99 patients) had a mean longer diagnostic delay (14.89 years; 95 % CI: 7.85-21.93 years) with respect to the outpatients (12.13 years; 95 % CI: 5.37-18.89 years). The difference resulted statistically significant at the multivariate model (p < 0.05). Single subpopulations of in-hospital workers did not have a statistically significant different delay in diagnosing migraine. Diagnostic delay was significantly longer in hospital workers with respect to outpatients. Then, we can conclude that our population of hospital workers did not present a particular attention to their headache, probably because of a tendency to self-treating. Moreover, we did not find differences among different typology of workers, underlining that different job experience and education did not contribute to a best management of headache. More information and informative initiatives are necessary to sensitize people about migraine, especially among hospital workers.

Headache in a population of hospital workers.

Headache prevalence is very high, especially during working life. Hospital workers are expected to be particularly careful with health problems. Few data are available about the dimension of the headache-related problems among hospital workers, including disease awareness and diagnostic delay. 502 subjects employed in our hospital (doctors, nurses, technicians, administrative employees) were enrolled over a 3-month period and submitted to a questionnaire about the presence of headache, its characteristics and time spent from disease onset to diagnosis. We used the ID-migraine test, a validated tool, to obtain a correct migraine diagnosis based on a three-question test. Age and education were collected as continuous variables while the other variables (sex, presence of headache, presence of migraine, diagnosis put by the general practitioners) were encoded as binary. The difference of the distribution of the analyzed variables in tables was evaluated with χ (2) test. The data were analyzed with SPSS 13.0 for Windows systems. In the analyzed population (mean age 40.15 ± 11.0 years; males 60.7 %), 216 patients complained of headache (43.1 %) and 77 (15.4 %) were diagnosed as migraineous at the in-hospital evaluation. Among the 216 cephalalgic patients, the majority (59.7 %, p < 0.0001 at χ (2) test) did not refer to their general practitioner. Of the 77 patients affected by migraine, 55.8 % referred to their general practitioner, but only 27 (35.1 %) received a definite migraine diagnosis. Fifty subjects (64.9 %) were still undiagnosed and unevaluated at the moment of our survey (p < 0.0001 at χ (2) test). Headache prevalence was very high in this population of hospital workers. Diagnostic errors and delays were frequent. Unexpectedly, self-awareness of the headache was very low. Headache, particularly migraine, is a relevant cause of loss of working days and low productivity. Our findings suggest the necessity to program initiatives aimed to raise the awareness of headache in order to improve diagnostic and therapeutic possibilities.

Emergency room access for recurring seizures: when and why.

BACKGROUND AND PURPOSE: To develop a hypothetical model identifying potentially modifiable predictive factors of Emergency Room (ER) visits by patients suffering from drug resistant epilepsy. METHODS: During a 1-year period, all adult drug resistant patients followed by the same epileptologist were recruited after the occurrence of one or more epileptic attacks. They were divided into two groups based on whether they went to the ER after seizures. A prospective comparative analysis of the clinical and social characteristics of the two groups was performed in order to identify independent predictors of ER visits. Logistic regression analysis was used to confirm the potential predictive role of the evaluated variables. RESULTS: Logistic regression analysis confirmed the potential role in predicting ER visits for these variables: foreign nationality, current psychiatric therapy, current antiepileptic drug polytherapy, comorbidities, more than one episode in the same day and changes in usual seizure pattern. A relevant association was also found between the frequency of ER neuroimaging use and the following variables: occurrence of episodes on holidays or weekends, current antiepileptic drug monotherapy, multiple comorbidities and brain injury after seizure. CONCLUSIONS: The present study evaluated factors, some potentially amenable to change, related to drug resistant epileptic patients' ER visits following a seizure. This information may serve to improve the clinical and therapeutic management of patients, decrease the need for urgent care and reduce subsequent patient stress and related costs.

Diagnostic delay in migraine with aura.

Migraine with aura (MWA) is a common headache, characterized by short-lasting neurological signs preceding an headache attack with migraine characteristics. We have recently performed several investigations about time-delay for migraine without aura diagnosis (MWoA). Aim of this study was to compare the time necessary to obtain a correct diagnosis in MWA and MWoA patients. We enrolled 31 consecutive patients affected by MWA and 62 age- and sex-matched patients affected by MWoA. All subjects were submitted to a face-to-face interview about the time-delay from symptoms' onset and a correct migraine typology diagnosis, the number of specialists consulted and the instrumental examinations performed. Independent samples and repeated measures t test, Mann-Whitney U were performed to compare the variables of the cases with the matched controls. No significant differences were found among the collected variables. Diagnostic delay was significantly different (p < 0.05), resulting lower in patients affected by MWA than in those with MWoA. In fact, subjects affected by MWA had a mean diagnostic delay of 6.70 years (SE ± 1.5), while patients affected by MWoA had a mean interval of 10.7 years (SE ± 1.20). Patients affected by MWA present a significant lower delay for the formulation of a correct diagnosis with respect to subjects with MWoA. This could be probably due to the fact that MWA patients develop major alarm reactions related to visual symptoms and look for an earlier appointment with a specialist medical center.

Action observation as a useful approach for enhancing recovery of verb production: new evidence from aphasia.

BACKGROUNDS: Evidence exists that the observation of actions performed by others enhance word retrieval and can be used in aphasia rehabilitation to treat naming impairments. AIM: The aim of the present study was to assess to what extent action observation treatment may improve verb retrieval in chronic aphasics. DESIGN: This was an observational study. SETTING: Patients were recruited from the Neurorehabilitation Centre of Ancona Hospital. POPULATION: Six aphasic patients underwent an intensive language training to improve verb naming. METHODS: Language evaluation was carried out before and after the treatment. A rehabilitation therapy based on observation of actions was administered daily to each patient for two consecutive weeks. Four different rehabilitation procedures were adopted: 1) "observation of action performed by the examiner"; 2) "observation and then execution of action"; 3) "observation of videoclips of actions"; and, as a control condition; 4) "observation of action and execution of meaningless movement". RESULTS: In four participants, a significant improvement in verb retrieval was found for the three experimental procedures (χ² (3)=75.212, P<0.0001), with respect to the control condition. No significant improvement was observed in the two patients with severe deficits in verb semantics (χ² (3)=0.592, P=0.892). CONCLUSIONS: Action observation therapy may become a useful intervention strategy to promote verb retrieval in aphasic patients. CLINICAL REHABILITATION IMPACT: The observation of videoclips of actions may be an efficacious alternative approach to traditional rehabilitation programs for lexical deficits. This finding endorses the planning of innovative low-cost interventions in language rehabilitation.

Endovascular treatment of CCSVI in patients with multiple sclerosis: clinical outcome of 462 cases.

Although it is still debated whether chronic cerebro-spinal venous insufficiency (CCSVI) plays a role in multiple sclerosis (MS) development, many patients underwent endovascular treatment (ET) of CCSVI. The objective of the study is to evaluate the outcome and safety of ET in Italian MS patients. Italian MS centers that are part of the Italian MS Study Group were all invited to participate to this retrospective study. A structured questionnaire was used to collect detailed clinical data before and after the ET. Data from 462 patients were collected in 33 centers. ET consisted of balloon dilatation (93 % of cases) or stent application. The mean follow-up duration after ET was 31 weeks. Mean EDSS remained unchanged after ET (5.2 vs. 4.9), 144 relapses occurred in 98/462 cases (21 %), mainly in RR-MS patients. Fifteen severe adverse events were recorded in 3.2 % of cases. Given the risk of severe adverse events and the lack of objective beneficial effects, our findings confirm that at present ET should not be recommended to patients with MS.

The real usefulness and indication for migraine diagnosis of neurophysiologic evaluation.

According to IHS criteria, a correct clinical history is fully adequate for a diagnosis of migraine. Patients usually perform many useless instrumental and laboratoristic exams and specialistic evaluations. In particular, electroencephalogram (EEG) is often prescribed as a first-line study in migraine patients. The objective is to analyze the indications of EEG in migraine and to evaluate whether its performance may negatively influence the time necessary to obtain a correct diagnosis. In particular, we compared the effects of EEG performance with those related to neuroradiological examinations in terms of time necessary to obtain a migraine diagnosis. 400 consecutive patients affected by migraine without aura were enrolled. Demographic and clinical data were collected. We used an ordinal regression model considering diagnostic delay as the main outcome and EEG and radiological examinations (in particular brain CT) as predictors. Delay was defined as a time to diagnosis greater than 1-year. Age, sex, number of specialists and examinations were included in the model as covariates. EEG represented the most often performed non-radiologic examination in our sample (20 %). It was associated with a significant risk of diagnostic delay [OR 1.66 (95 % CI 1.65-1.66, p < 0.001)]. An appropriate workup, including CT scan and early referral to a headache center was the most time-saving approach, being associated to the lowest probability of diagnostic delay [OR 0.72 (95 % CI 0.63-0.82, p < 0.001)]. EEG is a frequently prescribed exam in migraine. Our data show that it can contribute to diagnostic delay, highlighting only uncertain and unspecific elements. These data confirm the usefulness of a wide application of IHS guidelines, not recommending this exam for migraine detection.