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.

Early ficolin-1 is a sensitive prognostic marker for functional outcome in ischemic stroke.

BACKGROUND: Several lines of evidence support the involvement of the lectin pathway of complement (LP) in the pathogenesis of acute ischemic stroke. The aim of this multicenter observational study was to assess the prognostic value of different circulating LP initiators in acute stroke. METHODS: Plasma levels of the LP initiators ficolin-1, -2, and -3 and mannose-binding lectin (MBL) were measured in 80 stroke patients at 6 h only and in 85 patients at 48 h and later. Sixty-one age- and sex-matched healthy individuals served as controls. Stroke severity was measured on admission using the National Institutes of Health Stroke Scale (NIHSS). The outcome was measured at 90 days by the modified Rankin Scale (mRS). RESULTS: Ficolin-1 was decreased in patients compared with controls measured at 6 h (median 0.13 vs 0.33 µg/ml, respectively, p < 0.0001). At 48 h, ficolin-1 was significantly higher (0.45 µg/ml, p < 0.0001) compared to the 6 h samples and to controls. Likewise, ficolin-2 was decreased at 6 h (2.70 vs 4.40 µg/ml, p < 0.0001) but not at 48 h. Ficolin-3 was decreased both at 6 and 48 h (17.3 and 18.23 vs 21.5 µg/ml, p < 0.001 and <0.05, respectively). For MBL no difference was detected between patients and controls or within patients at the different time points. In multivariate analysis, early ficolin-1 was independently associated with unfavorable mRS outcome (adjusted odds ratio (OR): 2.21, confidence interval (CI) 95 % 1.11-4.39, p = 0.023). Early ficolin-1 improved the discriminating ability of an outcome model including NIHSS and age (area under the curve (AUC) 0.95, CI 95 % 0.90-0.99, p = 0.0001). CONCLUSIONS: The ficolins are consumed within 6 h after stroke implicating activation of the LP. Early ficolin-1 is selectively related to 3-month unfavorable outcome.

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.

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.

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.

The role of ultrasonic instruments in pharyngolaryngeal endoscopic surgery.

The purpose of this study was to assess the applicability and efficacy of ultrasonic instruments in laryngeal and pharyngeal endoscopic surgery. This article describes three cases of supraglottic laryngopharyngeal carcinoma transorally treated with the Harmonic forceps, which are indicative of our preliminary experience in this field. Based on our preliminary experience, we believe that the use of the ACE Harmonic forceps opens up very encouraging prospects in transoral endoscopic surgery of pharyngolaryngeal tumors and can potentially become a key instrument in this area. Given their different characteristics, we believe that ultrasonic instruments should be used not so much as an alternative to, but rather in addition to those traditionally used in pharyngolaryngeal endoscopic surgery and laser in particular. Finally, we hope that a more widespread use of these instruments in this surgical field may encourage manufacturers to solve the current technical limitations of miniaturization, thus designing and developing more precise and accurate instruments for this type of surgery.

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.

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.

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.

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.

Applause sign: is it really specific for Parkinsonian disorders? Evidence from cortical dementias.

OBJECTIVE: The applause sign, originally reported as a specific sign of progressive supranuclear palsy (PSP), has recently been found in several parkinsonian disorders. Its nature is still uncertain. It has been interpreted as a motor perseveration or a form of apraxia. The present study aims to: (a) verify the specificity of the applause sign for parkinsonian disorders, examining the presence of the applause sign in cortical dementias which should be error free and (b) clarify the nature of the applause sign (resulting or not from apraxia). METHODS: 77 subjects were included: 10 PSP, 15 frontotemporal dementia (FTD), 29 Alzheimer's disease (AD) and 23 normal controls. The presence of apraxia was an exclusion criterion. All patients underwent a detailed neuropsychological examination, and cognitive performance was correlated to the applause sign. RESULTS: All patient groups showed the applause sign and differed significantly from normal subjects who were error free. No difference was found when comparing PSP with FTD and FTD with AD. AD differed significantly from PSP but they were not error free (31% of patients with AD showed the applause sign). The only correlation with background neuropsychology was found for measures of executive functions. CONCLUSIONS: The presence of the applause sign in cortical dementia does not confirm the specificity of the applause sign for parkinsonian disorders. The applause sign should be interpreted as a sign of frontal lobe dysfunction rather than a form of apraxia, and can likely be detected in any kind of disease which involves frontal lobe structures to some extent.

Identification of the prion protein allotypes which accumulate in the brain of sporadic and familial Creutzfeldt-Jakob disease patients.

A characteristic feature of Creutzfeldt-Jakob disease (CJD) is the accumulation in the brain of the amyloid protease-resistant protein PrPres. PrPres derives from a host-encoded, protease-sensitive isoform, PrPsen. Mutations of this protein are linked to familial variants of the disease, and the presence of a methionine or valine residue at the polymorphic position 129 may be critical in sporadic CJD cases. We found that in the brain of patients heterozygous for the mutation in which isoleucine is substituted for valine at codon 210 (Val21Olle), the PrPres is formed by both the wild-type and mutant PrPsen. We also found that in a sporadic CJD patient, who was heterozygous (Met/Val) at position 129, PrPres is also formed by both allotypes. These data associate transmissible spongiform encephalopathies with other amyloidosis, although the nature of the transmissible agent remains unsettled.

The role of instrumental examinations in delayed migraine diagnosis.

Patients affected by migraine without aura very often consult different specialists who, misunderstanding the correct diagnosis, submit them to different instrumental examinations. The objective of the study was to assess if each instrumental examination was really useful for a faster migraine definition, or on the contrary, it increased the time delay for a correct diagnosis. We enrolled 300 consecutive patients referring to our Headache Center with a first diagnosis of migraine without aura and submitted them to a face-to-face interview about time from disease's onset to a correct diagnosis. In each patient, the first instrumental examination performed to specifically investigate migraine-related symptoms was defined. Brain MRI, brain CT, sinus CT, sinus X-rays, cervical spine X-rays and EEG were the most often performed examinations. All the exams, with the exception of brain CT, determined a significant increase of time delay in migraine diagnosis (p < 0.05). Brain CT was significantly associated with a higher probability to obtain a correct diagnosis in less than 1 year. Migraine without aura patients are usually addressed to perform radiological and other instrumental examinations. This attitude may increase the risk of time delay to obtain a correct diagnosis. The performance of a careful clinical history evaluation and neurological examination, with the addition of a brain CT when appropriate, is the best approach for a rapid and correct diagnosis of migraine without aura.

Instrumental investigations and migraine diagnosis.

Migraine diagnosis is based on clinical parameters. Before reaching a correct diagnosis, patients usually consult a large number of specialists and perform unhelpful exams. This represents a significant problem for an optimization of healthy resources. Our aim in this study was to evaluate the relationship between time interval from symptoms' onset to a correct diagnosis and number and type of clinical and instrumental investigations. We considered 180 consecutive patients referred to our Headache Center who obtained the first diagnosis of migraine without aura. Most patients were referred to our center by general practitioners (80%). Previously, about half of patients consulted a specialist not involved in migraine management. In 68% of cases, patients performed radiological and/or laboratory exams. Time from symptom onset to a correct diagnosis of migraine was less than 1 year in only 16.7% of the cases. In 83.3% of patients, the time delay overcame 1 year. In 53.3%, it reached 5 or more years. The time interval to obtain a correct diagnosis significantly influenced the number of specialists consulted and the number of radiological and laboratory investigations performed. Our findings confirm the presence of problems in migraine management. In particular, expensive and unnecessary visits and exams are very often prescribed. This inappropriate procedure could be easily counteracted by a correct application of diagnostic criteria for migraine.

Functional transcranial Doppler assessment of cerebral blood flow velocities changes during attention tasks.

BACKGROUND AND PURPOSE: Aim of our study was to evaluate cerebral hemodynamic changes during performance of attention tasks and to correlate them with reaction time (RT) and percentage of right answers. METHODS: Mean flow velocity (MFV) in middle cerebral arteries was monitored in 30 subjects by transcranial Doppler during tonic alertness, phasic alertness, focused and divided attention tasks. RESULTS: Mean flow velocity increase was significantly higher during divided attention with respect to other tasks (P < .001). MFV increase was higher in the right than in the left side (P < .001). Asymmetry during attention tasks resulted significantly higher than that observed in tonic alertness condition. RT was increased during focused attention tasks (P < .001 vs. both alert tasks), with further increase during divided attention tasks (P < .001 vs. focused attention task). RT was inversely related to MFV increase only during tonic alertness (P = 0.012 for left side; P = 0.008 for right side). During the divided attention tasks, an association was found between MFV increase and correct answers (r = 0.39, P = 0.033). CONCLUSIONS: These data show a relationship between RT, correct answers and changes in blood flow velocity and suggest that this method of cerebral blood flow investigation could be a useful approach during assessment of patients with attention deficit.

Cognitive and cerebral hemodynamic impairment in scleroderma patients.

BACKGROUND AND PURPOSES: Neurological involvement in systemic sclerosis is unusual despite the possible cerebral localization of vascular lesions. The aim of this study was to evaluate cognitive performances and cerebral vasoreactivity in young scleroderma patients without any signs or symptoms of nervous system involvement. METHODS: Sixteen scleroderma patients and 16 sex- and age-matched healthy subjects without vascular risk factors were included. A neuropsychological assessment for the evaluation of different areas of cognition was performed. For an assessment of cerebrovascular reactivity (CVR), each subject was submitted to hypercapnia with transcranial Doppler ultrasonography using the Breath-Holding Index (BHI). RESULTS: Patients had significantly lower adjusted mean levels of performance with respect to controls in the Modified Card Sorting Test (P < 0.001) and in the Trail Making Test Parts A and B (P < 0.001 and P < 0.05 respectively). Regarding CVR, BHI values were significantly lower in patients with respect to controls: 0.82 +/- 0.44 vs. 1.34 +/- 0.18, P < 0.0001. CONCLUSIONS: These findings show the presence of reduced performances of executive functions in scleroderma patients. The associated alteration of CVR in the absence of other apparent causes of cerebrovascular impairment suggests that cognitive problems may be related to an alteration in cerebral perfusion regulation specifically linked to the disease. Further studies are needed to evaluate whether cognitive changes may be positively influenced by treatments aimed to improve vessels functionality in scleroderma patients.

Cannabidiol as adjunctive treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome.

Epilepsy is one of the most common chronic disorders of the brain affecting around 70 million people worldwide. Treatment is mainly symptomatic, and most patients achieve long-term seizure control. Up to one-third of the affected subjects, however, are resistant to anticonvulsant therapy. Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) are severe, refractory epilepsy syndromes with onset in early childhood. Currently available interventions fail to control seizures in most cases, and there remains the need to identify new treatments. Cannabidiol (CBD) is the first in a new class of antiepileptic drugs. It is a major chemical of the cannabis plant, which has antiseizure properties in absence of psychoactive effects. This article provides a critical review of the pharmacology of CBD and the most recent clinical studies that evaluated its efficacy and safety as adjunctive treatment of seizures associated with LGS and DS.