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MRgFUS Vim thalamotomy is a novel, effective, minimally invasive therapeutic option for patients with essential tremor (ET). Among the selection criteria, some parameters related to the patient's anatomy, such as the skull density ratio (SDR), are well recognized. The role of brain tissue interposed between the target and the ultrasound transducers has never been explored. Therefore, the purpose of our study was to evaluate the correlation and the possible predictive value between brain tissue volumes (grey matter - GM, white matter - WM, and cerebrospinal fluid - CSF) and several treatment-related variables (periprocedural parameters, MRI imaging findings, and the clinical outcome). We analysed data from thirty ET patients previously submitted to MRgFUS thalamotomy. Pre-treatment images were automatically segmented in sopra-tentorial (ST) WM, GM, and CSF using SPM 12. The most significant findings were a positive correlation of the ST-GM with the Accumulated Thermal Dose (ATD) (p 0,001) and a negative correlation of the ATD temperature with ST-CSF and ST-TIV (p 0,001). Ultrasound propagation speed is lower in fluids than brain tissues. Also, WM has an attenuation rate of 1.5 higher than the GM. Therefore, the difference in the ATD may be explained by the different acoustic properties of normal brain tissues interposed between the transducers and the VIM.

To analyze and compare direct and indirect targeting of the Vim for MRgFUS thalamotomy. We retrospectively evaluated 21 patients who underwent unilateral MRgFUS Vim ablation and required targeting repositioning during the procedures. For each patient, in the three spatial coordinates, we recorded: (i) indirect coordinates; (ii) the coordinates where we clinically observed tremor reduction during the verification stage sonications; (iii) direct coordinates, measured on the dentatorubrothalamic tract (DRTT) at the after postprocessing of DTI data. The agreement between direct and indirect coordinates compared to clinically effective coordinates was evaluated through the Bland–Altman test and intraclass correlation coefficient. The median absolute percentage error was also calculated. Compared to indirect targeting, direct targeting showed inferior error values on the RL and AP coordinates (0.019 vs. 0.079 and 0.207 vs. 0.221, respectively) and higher error values on the SI coordinates (0.263 vs. 0.021). The agreement between measurements was higher for tractography along the AP and SI planes and lower along the RL planes. Indirect atlas-based targeting represents a valid approach for MRgFUS thalamotomy. The direct tractography approach is a valuable aid in assessing the possible deviation of the error in cases where no immediate clinical response is achieved.

Tremor is a common and very disabling symptom in patients with essential tremor and Parkinson's disease. In the recent years, transcranial ablation of thalamic nuclei using magnetic resonance guided high-intensity focused ultrasound has emerged as a minimally invasive treatment for tremor. The aim of this review is to discuss, in the light of our single-center experience, the technique, current applications, results, and future perspectives of this novel technology.

Background Treatment with onabotulinumtoxin A (BT-A) is safe and effective for chronic migraine (CM). Several studies assessed possible predictors of response to treatment with BT-A, but there is little knowledge on the frequency and predictors of sustained response. The aim of this study was to evaluate sustained response to BT-A in patients with CM. Main body In this prospective open-label study, 115 patients with CM and treated with BT-A were consecutively enrolled in two Italian headache centers and followed up for 15 months. Anytime responders were defined as those patients who achieved a ≥ 50% reduction in headache days during any three-month treatment cycle compared with the 3 months prior to initiation of BT-A treatment. Sustained responders were defined as those who achieved a ≥ 50% reduction in headache days within the third treatment cycle and maintained response until the end of follow-up. Non-responders were defined as those patients who never achieved a ≥ 50% reduction in headache days during the follow-up. Headache characteristics prior to BT-A treatment were assessed in order to evaluate their ability in predicting treatment response. The 115 enrolled patients (84.3% female; median age 50 years) had a median migraine duration of 30 years (interquartile range 22–38). At the end of follow-up, 66 patients (57.4%) were classified as anytime responders. Among the 51 patients who achieved a clinical response within the third month of treatment, 33 (64.7%) were sustained responders. Patients with sustained response had a lower CM duration (median 31 vs 65 months; P = 0.030) and a lower number of headache days (median 25 vs 30; P = 0.013) at baseline compared with non-responders. Conclusions About two thirds of patients who gain ≥50% response to BT-A within the third cycle of treatment maintain this positive response over time. More recent onset of CM and more headache-free days at baseline are associated with sustained response. We suggest not to delay preventive treatment of CM with BT-A, in order to increase the likelihood to achieve sustained clinical response.

Objective: To identify possible relevant factors contributing to tremor relapse after MRgFUS thalamotomy in patients with essential tremor (ET) and Parkinson’s disease (PD). Methods: We identified patients with tremor relapse from a series of 79 treatments in a single institution. The demographic and clinical characteristics of the study group patients were compared to those of patients who did not relapse in the same follow-up period. Imaging and procedural factors were compared using a control group matched for clinical and demographic characteristics. Results: Concerning clinical and demographic characteristics, we did not find statistically significant differences in gender and age. Seventy-three percent of patients with tremor relapse were Parkinson’s disease patients. Using MRI, we found larger thalamotomy lesions at the 1-year follow-up in the control group with stable outcomes, compared to patients with tremor relapse. In the tractography evaluation, we found a more frequent eccentric position of the DRTt in patients with tremor relapse. Conclusions: The most relevant determining factors for tremor relapse after MRgFUS thalamotomy appear to be tremor from Parkinson’s disease and inaccurate thalamic targeting. Size of the thalamotomy lesion can also influence the outcome of treatment.

Background There are few large population-based studies of outcomes after subarachnoid hemorrhage (SAH) than other stroke types. Methods We pooled data from 13 population-based stroke incidence studies (10 studies from the INternational STRroke oUtComes sTudy (INSTRUCT) and 3 new studies; N=657). Primary outcomes were case-fatality and functional outcome (modified Rankin scale score 3-5 [poor] vs. 0-2 [good]). Harmonized patient-level factors included age, sex, health behaviours (e.g. current smoking at baseline), comorbidities (e.g.history of hypertension), baseline stroke severity (e.g. NIHSS >7) and year of stroke. We estimated predictors of case-fatality and functional outcome using Poisson regression and generalized estimating equations using log-binomial models respectively at multiple timepoints. Results Case-fatality rate was 33% at 1 month, 43% at 1 year, and 47% at 5 years. Poor functional outcome was present in 27% of survivors at 1 month and 15% at 1 year. In multivariable analysis, predictors of death at 1-month were age (per decade increase MRR 1.14 [1.07-1.22]) and SAH severity (MRR 1.87 [1.50-2.33]); at 1 year were age (MRR 1.53 [1.34-1.56]), current smoking (MRR 1.82 [1.20-2.72]) and SAH severity (MRR 3.00 [2.06-4.33]) and; at 5 years were age (MRR 1.63 [1.45-1.84]), current smoking (MRR 2.29 [1.54-3.46]) and severity of SAH (MRR 2.10 [1.44-3.05]). Predictors of poor functional outcome at 1 month were age (per decade increase RR 1.32 [1.11-1.56]) and SAH severity (RR 1.85 [1.06-3.23]), and SAH severity (RR 7.09 [3.17-15.85]) at 1 year. Conclusion Although age is a non-modifiable risk factor for poor outcomes after SAH, however, severity of SAH and smoking are potential targets to improve the outcomes.

Aim Emotional reactivity (ER) and neuropsychological (Np) status were investigated in a case series of patients that underwent a surgical ablation of temporal lobe tumors (TLT). Methods Ten patients (6 females, 4 males) who had undergone surgical ablation of TLT and 10 controls matched for age and gender were recruited. ER was tested using International Affective Picture System (IAPS); Clinical Global Impression evaluated behavioral disturbances, affective symptoms and emotional involvement/reaction to the pathological condition. Np assessment was carried out using well established measures; anatomopathological, neuroradiological and clinical data were also collected. Results Patients showed more positive valence and higher arousal upon viewing neutral images compared to controls. To a lesser extent, the same pattern was observed with socially pleasant images. No affective symptoms were observed at CGI-BP evaluation. Arousal to negative images, with or without social involvement, revealed a moderately strong relationship with the patient’s subjective emotional appraisal of the consequences of the illness. Conclusion We observed an optimistic emotional environment perception and a detachment from the pathological condition related to lowered emotional involvement and reactivity to negative emotional cues. This pattern of emotional reactivity leads to the hypothesis of an effective coping strategy development to a severe pathological condition.

We evaluated the predictive value of several clinical, radiological and laboratory parameters on the risk of predict intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF). We conducted a case-control study on a consecutive hospital based series of patients with AF and ICH. A random sample of subjects with AF without ischemic or hemorrhagic stroke was selected from the same hospital in the same period to perform as the control group, with a ratio of two controls per case. All patients underwent the same evaluation protocol. Patients without neuroimaging exams were excluded. During the study period we identified 37 subjects with AF and ICH. 74 subjects without stroke events were randomly chosen among subjects with AF. Among cases 56.8% were female; mean age was 83.1 years. Patients with ICH were more often on anticoagulant therapy (75.7%), compared with controls (45.9%; p = 0.0002). On CT scans, cases had a greater severity of leukoaraiosis at the Blennow scale (p

Background: Patients who are in a coma, a vegetative state or a minimally conscious state present a clinical challenge for neurological assessment, which is a prerequisite for establishing a prognosis and planning management. Several scales have been developed to evaluate these patients. The Wessex Head Injury Matrix is a comprehensive tool but is currently available only in the French and English languages. The aim of this study was to translate and evaluate the reliability of the Italian version of the scale. Methods: The original scale was translated according to a standard protocol: three separate translations were made, and a selected version was back-translated to check for any errors in order to obtain the most accurate Italian translation. A final back translation of the agreed version was made as a further check. The final version was then administered blind to a consecutive series of patients with severe acquired brain injury by two examiners. Inter-rater and test-retest reliability were assessed using a weighted Cohen’s kappa (Kw). Concurrent validity of the WHIM was evaluated by ρ Spearman’s correlation coefficient using the Glasgow Coma Scale (GCS) and the Coma Recovery Scale Revised (CRS-R) as the available gold standard. Results: Twenty-four patients (12 males and 12 females; mean age 59.9 ± 20.1; mean duration from index event 17.7 ± 20.0 days) with stroke (n = 15), traumatic brain injury (n = 7) and anoxic encephalopathy (n = 2) were included. Inter-rater [Kw 0.80 (95% CI 0.75–0.84)] and test-retest reliability [Kw 0.77 (95% CI 0.72–0.81)] showed good values. WHIM total scores correlated significantly with total scores on the GCS (ρ = 0.776; p < 0.001) and the CRS-R (ρ = 0.881; p < 0.001) demonstrating concurrent validity; Conclusion: The Italian version of the scale is now available for clinical practice and research.

Background: Outcomes after subarachnoid hemorrhage (SAH) have been rarely examined in large cohorts. Methods: This is an extension of the International Stroke Outcomes Study (INSTRUCT) pooling 13 ‘ideal’ stroke incidence studies (n=657 with SAH from 1993-2017, median age 56 years; 46% men). The primary outcomes were mortality and functional outcome (mRS score 3-5). Harmonized study factors included age, sex, behaviors (current smoking, alcohol intake), comorbidities (history of hypertension, ischemic heart disease, atrial fibrillation), stroke severity (e.g. NIHSS score) and year of stroke. In the pooled dataset, we estimated predictors of mortality using Poisson regression, to estimate incidence rate ratio (IRR) at 1 month (11 studies), 1 year (12 studies) and 5 years (7 studies). Generalized equation estimates in the log-binomial family were used to calculate risk ratios (RRs) for predictors of poor functional outcome at 1 month (5 studies) and 1 year (8 studies). Results: Mortality was 33% at 1 month, 43% at 1 year, and 47% at 5 years (Fig 1). Poor functional outcome was 25% at 1 month and 15% at 1 year (Fig 1). In multivariable analysis, age and stroke severity were associated with mortality at all time points, together with current smoking at 1 and 5 years, and history of hypertension at 5 years (Fig 2). Poor functional outcome was predicted by age (RR 1.03; 95% CI 1.01-1.04) at 1 month and by age (RR 1.04; 95% CI 1.00-1.08) and stroke severity (RR 1.94; 95% CI 1.02-2.87) at 1 year. Conclusion: Risk factors that predict SAH incidence including hypertension and smoking make outcomes worse. Better management of older patients and those with severe strokes could improve outcomes after SAH.

Background Triptans and erenumab are both migraine-specific agents acting on the calcitonin gene-related peptide pathway. Therefore, response to triptans might be associated with response to erenumab. Main body In our study, consecutive patients referring to the Headache Centers of the Abruzzo region from January 2019 to March 2020 and treated with erenumab were interviewed about past use and efficacy of triptans. Triptan users were classified as ‘triptan responders’ if they were headache-free 2 h after treating ≥3 migraine attacks with ≥1 triptan. We considered patients as ‘erenumab responders’, if they had a ≥ 50% mean reduction in monthly migraine days between the 4th and the 6th month from treatment start compared with baseline. Of 91 triptan users, 73 (80.2%) were triptan responders and 58 (63.7%) were erenumab responders. The odds ratio of being erenumab responder was 3.64 (95% CI, 1.25–10.64) for triptan users as compared to non-users. (P = 0.014). Besides, starting erenumab improved triptan response in both erenumab responders and non-responders. Conclusions Our data of an association between response to triptans and response to erenumab can be useful for patient advice and to improve the understanding of migraine pathophysiology and treatment.

BackgroundMost patients treated with erenumab in clinical practice have chronic migraine (CM). We assessed the rate and possible predictors of conversion from CM to episodic migraine (EM) in a real-life study.Main bodyWe performed a subgroup analysis of patients treated with erenumab from January 2019 to February 2020 in the Abruzzo region, central Italy. Treatment was provided according to current clinical practice. For the purpose of the present study, we included patients fulfilling the definition of CM for the three months preceding erenumab treatment and with at least 6 months of follow-up after treatment. We assessed the rate of conversion to EM from baseline to Months 4–6 of treatment and during each month of treatment. To test the clinical validity of conversion to EM, we also assessed the decrease in monthly headache days (MHDs), acute medication days, and median headache intensity on a Numerical Rating Scale (NRS). We included in our study 91 patients with CM. At Months 4–6, 62 patients (68.1%) converted from CM to EM; the proportion of converters increased from Month 1 to Month 5. In the overall group of patients, median MHDs decreased from 26.5 (IQR 20–30) to 7.5 (IQR 5–16;P P P ConclusionsIn our study, two thirds of patients with CM converted to EM during 6 months of treatment with erenumab. MHDs, acute medication use, and headache intensity decreased regardless of conversion from CM to EM.

Background Identifying the cause of intracerebral hemorrhage (ICH) is relevant to optimize its management. We aimed to assess the applicability and utility of the Edinburgh CT criteria for cerebral amyloid angiopathy (CAA) in an unselected cohort of hospitalized patients. Patients and Methods We retrospectively applied the Edinburgh criteria to the first available brain CTs of patients hospitalized for a first-ever lobar ICH in the district of L’Aquila from 2011 to 2017. ICH characteristics and outcomes were compared according to the presence of the Edinburgh CT criteria, including associated subarachnoid hemorrhage (aSAH) and finger-like projections (FLPs). The outcome of ICH in-hospital mortality was assessed with multivariate logistic regression analysis. We adopted the Edinburgh criteria, age, NIHSS and Glasgow Coma Scale scores, systolic blood pressure, antiplatelet treatment, ICH volume, and intraventricular extension on admission as covariates. Results Of 178 patients with lobar ICH, 52 (29.2%) had aSAH+FLPs, 60 (33.7%) aSAH only, 1 (0.6%) FLPs, and 65 (36.5%) none. Patients with aSAH+FLPs were older (79.0 ± 9.2 years) than those with only one criterion or none (74.0 ± 15.3 and 72.2 ± 13.8 years, respectively; P = 0.020). Patients with aSAH+FLPs also had more severe ICH at onset, higher in-hospital case-fatality (log rank test P = 0.003) and higher mRS scores at discharge (P Discussion Our data suggest the applicability of the Edinburgh CT criteria in a hospital setting. The presence of those criteria reflects ICH clinical severity. Conclusions Applying the Edinburgh CT criteria might help refining the diagnosis and improving the management of patients with lobar ICH.

Background We aimed to assess the efficacy and safety of erenumab, a fully human monoclonal antibody inhibiting the calcitonin gene-related peptide receptor (CGRPr), for the prevention of migraine in a real-life setting. Main body We included in our observational study all patients with episodic or chronic migraine treated with erenumab during the year 2019 in the Abruzzo region, central Italy, and with a 6-month follow-up. We included 89 patients; 76 (85.4%) received 6 doses of erenumab, 11 (12.4%) autonomously withdrew the drug due to perceived inefficacy, and 2 (2.2%) due to adverse events. Seventy-eight patients (87.6%) were female, with a mean age of 46.8 ± 11.2 years; 84 (94.4%) had chronic migraine, and 64 (71.9%) medication overuse. All patients had ≥2 prior preventive treatment failures. Fifty-three patients (69.7%) had a 50% decrease in monthly migraine days (MMDs) within the first three doses; 46 (71.9%) of 64 patients withdrew medication overuse. In the 76 patients who completed a 6-dose treatment, erenumab decreased median MMDs from 19 (interquartile range [IQR] 12–27.5) to 4 (IQR 2–9.5; P Conclusions Our real-life data confirm the efficacy and tolerability of erenumab for the prevention of migraine in a difficult-to-treat population of patients with a high prevalence of chronic migraine and medication overuse.

Objectives: To examine sex differences in disease profiles, management, and survival at 1 and 5 years after ischemic stroke (IS) among people with atrial fibrillation (AF). Methods: We performed a systematic literature search of reports of AF at IS onset according to sex. We undertook an individual participant data meta-analysis (IPDMA) of nine population-based stroke incidence studies conducted in Australasia, Europe, and South America (1993–2014). Poisson regression was used to estimate women:men mortality rate ratios (MRRs). Study-specific MRRs were combined using random effects meta-analysis. Results: In our meta-analysis based on aggregated data from 101 studies, the pooled AF prevalence was 23% (95% confidence interval [CI]: 22%–25%) in women and 17% (15%–18%) in men. Our IPDMA is of 1,862 IS-AF cases, with women (79.2 ± 9.1, years) being older than men (76.5 ± 9.5, years). Crude pooled mortality rate was greater for women than for men (1-year MRR 1.24; 1.01–1.51; 5-year 1.12; 1.03–1.22). However, the sex difference was greatly attenuated after accounting for age, prestroke function, and stroke severity (1-year 1.09; 0.97–1.22; 5-year 0.98; 0.84–1.16). Women were less likely to have anticoagulant prescription at discharge (odds ratio [OR] 0.94; 95% CI: 0.89–0.98) than men when pooling IPDMA and aggregated data. Conclusions: AF was more prevalent after IS among women than among men. Among IS-AF cases, women were less likely to receive anticoagulant agents at discharge; however, greater mortality rate in women was mostly attributable to prestroke factors. Further information needs to be collected in population-based studies to understand the reasons for lower treatment of AF in women.

IgG4-related disease is a recently discovered pathological entity, histologically characterised by fibrosis and IgG4-positive plasma cell infiltration. This condition may virtually involve every site of the organism, with a various range of clinical presentations. The most commonly affected organ is the pancreatic gland, but it can also involve the biliary tract, salivary and lacrimal glands, kidneys, orbital tissues, lymph nodes, lungs and many others. More recently, IgG4-related disease has been demonstrated to involve, in rare cases, also the central nervous system, with a pattern mainly characterised by hypertrophic pachymeningitis. In this paper we evaluated the clinical and magnetic resonance imaging features of the IgG4-related disease in the central nervous system, reporting a case of brain and spinal cord involvement. In our case, in fact, a 62-year-old man complaining of paresthesia, burning dysesthesia and severe hyposthenia in the lower limbs presented with inflammatory pseudotumour with orbital involvement and focal dural and spinal root thickening.

Background Erenumab, a fully human monoclonal antibody directed against the calcitonin gene-related peptide receptor, was approved for the prevention of episodic (EM) or chronic migraine (CM) at the monthly dose of 70 mg or 140 mg. We reviewed the available literature to understand if patients with prior preventive treatment failures benefit more from the 140 mg dose than the 70 mg. Main body We searched papers indexed in PubMed and conference abstracts published in the last 2 years which assessed the safety and efficacy of erenumab in patients with prior preventive treatment failures. We reviewed the results of 3 randomized controlled trials and their subgroup analyses and open-label extensions. The 140 mg monthly dose of erenumab had a numerical advantage over the 70 mg monthly dose in patients with prior preventive treatment failures, both in EM and CM (with or without medication overuse) during the double blind phases of the trials and their open-label extensions. The numerical difference between the two doses increased with the increase in the number of prior preventive treatment failures. Conclusions The available data suggest that erenumab 140 mg monthly might be preferred over the 70 mg monthly dose in patients with EM or CM and prior preventive treatment failures. Further data are needed to assess the long-term efficacy in clinical practice of the two doses of erenumab, while their safety profile is comparable.

Increasing evidence suggests that uric acid (UA) is a relevant risk factor for arteriolosclerosis and recent studies have demonstrated the positive relationship between UA concentrations and the severity of leukoaraiosis. However, the association between lacunar infarcts (LI) and UA levels has seldom been reported in the literature. The aim of our study was to assess whether serum UA levels may be related to the presence of LI. We recruited 242 patients (113 males and 129 females, aged 82.83 ± 6.49 years) from our Geriatric Department for whom CAT scans (CT) were available. Clinical and laboratory data was collected. Patients CT images were examined to identify the presence, the size, the number, and the location of LI. LI without neurological symptoms were considered silent LI. Serum UA levels were found to be positively associated with the presence (p = 0.0001), the number (p = 0.001), the size (p = 0.001), and the location of LI in the basal ganglia (p = 0.0038), the deep white matter (DWM) (p

Background. We investigated low-dose aspirin (ASA) efficacy and safety in subjects with silent brain infarcts (SBIs) in preventing new cerebrovascular (CVD) events as well as cognitive impairment.Methods. We included subjects aged ≥45 years, with at least one SBI and no previous CVD. Subjects were followed up to 4 years assessing CVD and SBI incidence as primary endpoint and as secondary endpoints: (a) cardiovascular and adverse events and (b) cognitive impairment.Results. Thirty-six subjects received ASA while 47 were untreated. Primary endpoint occurred in 9 controls (19.1%) versus 2 (5.6%) in the ASA group (p=0.10). Secondary endpoints did not differ in the two groups. Only baseline leukoaraiosis predicts primary [OR 5.4 (95%CI 1.3-22.9, p=0.022)] and secondary endpoint-a [3.2 (95%CI 1.1-9.6, p=0.040)] occurrence.Conclusions. These data show an increase of new CVD events in the untreated group. Despite the study limitations, SBI seems to be a negative prognostic factor and ASA preventive treatment might improve SBI prognosis.EU Clinical trialis registered with EudraCT Number:2005-000996-16; Sponsor Protocol Number: 694/30.06.04.

Background. Posterior reversible encephalopathy syndrome (PRES) is characterized by a variable association of symptoms including headache, consciousness impairment, visual disturbances, seizures, and focal neurological signs. Treating the underlying cause usually leads to partial or complete resolution of symptoms within days or weeks. Brain MRI findings include hyperintensities on T2-weighted sequences and their reversibility on follow-up exams. We describe two patients, one with an atypical clinical presentation characterized by a severe and prolonged impairment of consciousness and the other with atypical neuroimaging findings. Case Presentation. The first patient was a 42-year-old woman, with a negative medical history, presenting with seizures, lethargy, and left hemiparesis, 60 hours after uncomplicated delivery. Brain MRI showed an atypical pattern of alterations, with patchy asymmetric distribution in all lobes. Symptoms completely resolved after twelve days. The second patient was a 59-year-old woman with a history of hypertension, presenting with severe impairment of consciousness, vision loss, and seizures. Symptoms partially resolved after three weeks. Conclusion. PRES is characterized by reversible symptoms and radiological findings. Brain MRI usually shows widespread oedema in white matter with typical patterns. The cases we described suggest that PRES may presents with atypical symptoms and radiological manifestations, mimicking other neurological conditions.

Objective. The aim of this prospective observational multicenter postmarketing study was to evaluate fingolimod efficacy in a real world clinical setting.Methods. One hundred forty-two subjects with relapsing-remitting multiple sclerosis (RRMS) were enrolled in three multiple sclerosis centers throughout Central and Southern Italy between January 2011 and September 2013. After enrollment, regular visits and EDSS assessment were scheduled every 3 months, and MRI scan was obtained every 12 months. Patients were followed up from 1 to 33 months (mean 14.95 ± 9.15 months). The main efficacy endpoints included the proportion of patients free from clinical relapses, from disability progression, from magnetic resonance imaging activity, and from any disease activity.Results. Out of 142 patients enrolled in the study, 88.1% were free from clinical relapse and 69.0% were free from disability progression; 68.5% of patients remained free from new or newly enlarging T2 lesions and 81.7% of patients were free from gadolinium enhancing lesions. Overall the proportion of patients free from any disease activity was 41.9%.Conclusions. Our data in a real world cohort are consistent with previous findings that yield convincing evidence for the efficacy of fingolimod in patients with RRMS.

An association of obstructive sleep apnea syndrome (OSAS) and other sleep-disordered breathing (SDB) with Parkinson's disease (PD) has been reported in some small studies. In the present study we investigated the occurrence of SDB in a large consecutive outpatient series. This is a case-control study in subjects attending a neurological clinic where all patients were screened for SDB by means of sleep-wake history, Epworth Sleepiness Scale, and full-night polysomnography, when indicated. 3194 patients were recruited. Of these, 194 were affected by PD and 77 by other parkinsonisms. Snoring, excessive daytime sleepiness and OSAS were more common in patients with PD or parkinsonisms (40.59, 5.9, and 4.06%) than in controls (35.58, 2.19, and 2.09%). Our study suggests an increased frequency of OSAS and other SDB in PD and parkinsonisms. Early detection and management of these disorders may have a substantial impact on quality of life and survival in these patients.

Progressive multifocal leukoencephalopathy (PML) is a rare rapidly progressive demyelinating disease of the central nervous system caused by reactivation of latent John Cunningham (JC) polyomavirus (JCV) infection. We describe an unusual case of PML in a 54-year-old patient with follicular non-Hodgkin lymphoma who received rituximab plus cyclophosphamide, hydroxydaunorubicin, oncovicin and prednisolone (R-CHOP) therapy. She started to notice gradual progressive neurological symptoms about two months after completion of rituximab treatment and was therefore admitted to hospital. On admission, brain CT and MRI showed widespread lesions consistent with a demyelinating process involving the subcortical and deep white matter of the cerebral and cerebellar hemispheres. CT and MRI findings were suggestive of PML, and JC virus DNA was detected by polymerase chain reaction assay of the cerebrospinal fluid and serum. The patient was treated supportively but reported a progressive worsening of the clinical and radiological findings. Our report emphasizes the role of CT and MRI findings in the diagnosis of PML and suggests that PML should be considered in patients with progressive neurological disorders involving the entire nervous system and mainly the white matter, especially in the presence of previous immunomodulatory treatment or immunosuppression.

Our aim was to evaluate the reproducibility of the Functional Independence Measure (FIM) scale when assessed by physical therapists in the routine setting of a Rehabilitation Hospital. We included a consecutive series of patients with spinal cord or cerebral lesions. Each of the 50 selected patients was evaluated by two of the 5 experienced physical therapists participating in the study. The degree of inter-rater and intrarater agreement was measured by a weighted k statistic, k for perfect agreement, and k for the agreement with tolerance. The weighted k index for inter-rater agreement on the FIM score was in the almost perfect range (k 0.87; 95% CI = 0.79 - 0.95), but a 20-point tolerance was necessary to reach a k value of 0.81 (95% CI = 0.66 - 0.95). Agreement was substantial or almost perfect for most subscales, but the k index with 1-point tolerance reached the almost perfect rating for comprehension only. For intra-rater agreement, weighted k index was in the almost perfect range for the FIM score and for all subscales; kappa index reached the almost perfect range with a 4-point tolerance for FIM score and with 1-point of tolerance for all subscales except interpersonal relations. FIM is useful to monitor patient improvement during rehabilitation treatment, mostly when assessed by the same physical therapist.

Although tumefactive multiple sclerosis is a well recognized variant of multiple sclerosis, prognostic uncertainty still exists about long term prognosis. The aim of this study was to estimate the occurrence and long term outcome of tumefactive demyelinating lesions (TDLs) in a cohort of multiple sclerosis patients. We reviewed brain MRI of 443 patients referred to our MS clinic. All patients meeting the McDonald criteria for multiple sclerosis and showing at least one TDL were included. Kaplan–Meier estimates of disease-free survival in patient cohort were compared with control group without TDLs using a log-rank test. Seven cases with TDLs were identified (occurrence 1.58 %). Tumefactive demyelinating lesion recurrence was 16.6 %. Cumulative proportion of patients free from clinical relapse and from new T2 lesions was lower in the control group although not reaching statistical significance (30 vs 50 %; P = 0.666 and 21.7 vs 33.3 %; P = 0.761, respectively). Disability progression analysis showed a not significant trend towards lower probability of remaining progression free for TDL patients (50 vs 61 %; P = 0.295). Occurrence of tumefactive demyelinating lesions in our cohort was higher than those reported in other studies. Overall, TDLs were not predictive of poor outcome in terms of disability progression.

Continuous duodenal infusion of levodopa/carbidopa intestinal gel (LCIG) is an established treatment to control motor fluctuations in Parkinson's disease. Duodenal infusion allows a steady absorption of the drug in the small bowel, reducing plasmatic fluctuations of levodopa. Some complications may occur during the treatment, often related to intrajejunal percutaneous endoscopic gastrostomy (PEG-J). We report a case of duodenal ulcer associated with a phytobezoar involving the end of jejunal probe, in a patient who underwent PEG-J for LCIG infusion. In the last 2 weeks, the patient suffered from abdominal pain and dyspepsia. Oesophagogastroduodenoscopy showed an ulcerative lesion of the duodenum due to traction of the jejunal tube; the end of the jejunal tube was wrapped in a phytobezoar. This case is interesting because of the extension of the ulcerative lesion due to PEG-J dislocation and because of the subtle symptoms associated with it.

Objective: To evaluate incidence, case fatalities and prognosis of subarachnoid hemorrhage (SAH). Subjects and Methods: Prospective population-based registry (1994–1998) including patients with a first-ever stroke followed up to 10 years. Results: In a 5-year period we included 118 patients (55 men and 63 women; mean age ± SD 60.7 ± 15.9 years) with an SAH. The crude annual incidence rate was 7.93 cases per 100,000 inhabitants (95% CI 6.46–9.63), 7.60 per 100,000 when standardized to the 2006 European population and 5.27 per 100,000 when standardized to the 2005 world population. The 7-day case-fatality rate was 16.1% (95% CI 9.5–22.7), 30-day case-fatality rate was 34.7% (95% CI 21.2–43.3), and 1-year case-fatality rate was 44.9% (95% CI 35.9–53.9). At the end of the 1-year follow-up, 53 patients (44.9%) had a good recovery [modified Rankin scale (mRS) 0–2] and 12 (10.2%) had a severe disability (mRS 3–5). The 10-year survival rate was 46.4% (95% CI 36.0–57.8). Conclusion: In our district, the SAH incidence rate was similar to what is reported in most European countries. Since more than half of the patients with SAH remained severely disabled or died, results from our population-based study strongly support the notion that the most appropriate treatments should be made available for all patients in comprehensive centers and the call for an urgent implementation of telemedicine in the rural areas of our district.

Background. Cerebral amyloid angiopathy-related inflammation (CAA-ri) results from autoimmune response to beta-amyloid deposits in cerebral vessels. Its clinical course and complications have seldom been described in literature.Case Report. In a patient presenting with delirium and left hemiparesis the diagnosis of CAA-ri was supported by the finding of elevated anti-amyloid autoantibodies in the cerebrospinal fluid (CSF). Steroid therapy produced significant improvements in clinical and investigational assessments, but after two months, it caused Acute Respiratory Distress Syndrome. After steroid therapy discontinuation the patient presented a rapidly progressive dementia, Guillain-Barré syndrome, new cerebral ischemic lesions, and thrombosis of the right cephalic and subclavian veins that were treated with subcutaneous heparin. After a week the patient died because of brain hemorrhage.Conclusion. This case suggests caution in steroid therapy discontinuation and antithrombotic therapy administration in patients with CAA-ri. The CSF search of anti-amyloid autoantibodies could be helpful to support the diagnosis.

Background: Endovascular treatment plays a continuously expanding role in the treatment of acute ischemic stroke. Several randomized controlled clinical trials evaluating possible benefits of endovascular therapy were conducted. From these trials emerged conflicting results. The aim of this study was to evaluate the efficacy of endovascular treatment over standard therapy in acute ischemic stroke. Methods: We searched in PubMed and EMBASE databases from the date of inception until 2015/07/31. The primary outcome was the functional neurological outcome at 90 days measured with modified Rankin Score ≤ 2. Secondary outcomes were partial or complete recanalization, assessed with modified arterial occlusive lesion, thrombolysis in myocardial infarction or thrombolysis in cerebral infarction scores of 2-3 and mortality. Safety outcome was Symptomatic Intracranial Hemorrhage (SICH). Data were pooled in the control and intervention groups, and odds ratios were calculated with 95% interval confidence. Statistical heterogeneity was evaluated with the χ2 Mantel-Haenszel method and I₂ method. A p value

Objective: The aim of this study was to compare the efficacy of natalizumab and fingolimod in relapsing-remitting multiple sclerosis patients in real-world clinical setting. Methods: We enrolled 391 patients starting either natalizumab or fingolimod for relapsing-remitting multiple sclerosis, referred to four multiple sclerosis centers between March 2007 and July 2013. Cumulative proportion of patients free from any disease activity, as defined by freedom from relapse, Expanded Disability Status Scale (EDSS) progression, new or newly enlarging T2 lesions, and gadolinium enhancing lesions at magnetic resonance imaging (MRI) was assessed at 12-month follow-up. Results: Out of 391 patients, 197 were treated with natalizumab and 194 with fingolimod. The cumulative proportion of patients free from any disease activity was 72.0% in the natalizumab and 59.1% in the fingolimod group (P=0.014). This proportion was lower in fingolimod patients with prior natalizumab exposure compared to those without (51.7% vs. 61.8%; P=0.008). Moreover, the cumulative proportion of patients free from new MRI lesions was 87.5% in the natalizumab vs. 70.0% in the fingolimod group (P

Background: Recent evidence has indicated that flavanol consumption may have many health benefits in humans, including improved cognitive activities. Objective: The aim was to evaluate the effect of flavanol consumption on cognitive performance in cognitively intact elderly subjects. Design: This was a double-blind, controlled, parallel-arm study conducted in 90 elderly individuals without clinical evidence of cognitive dysfunction who were randomly assigned to consume daily for 8 wk a drink containing 993 mg [high flavanol (HF)], 520 mg [intermediate flavanol (IF)], or 48 mg [low flavanol (LF)] cocoa flavanols (CFs). Cognitive function was assessed at baseline and after 8 wk by using the Mini-Mental State Examination (MMSE), the Trail Making Test (TMT) A and B, and the Verbal Fluency Test (VFT). Results: The changes in MMSE score in response to the 3 different treatments were not different. In contrast, there was a positive impact of the intervention on specific aspects of cognitive function. Mean changes (±SEs) in the time required to complete the TMT A and B after consumption of the HF (−8.6 ± 0.4 and −16.5 ± 0.8 s, respectively) and IF (−6.7 ± 0.5 and −14.2 ± 0.5 s, respectively) drinks significantly (P < 0.0001) differed from that after consumption of the LF drinks (−0.8 ± 1.6 and −1.1 ± 0.7 s, respectively). Similarly, VFT scores significantly improved among all treatment groups, but the magnitude of improvement in the VFT score was significantly (P < 0.0001) greater in the HF group (7.7 ± 1.1 words/60 s) than in the IF (3.6 ± 1.2 words/60 s) and LF (1.3 ± 0.5 words/60 s) groups. Significantly different improvements in insulin resistance (P < 0.0001), blood pressure (P < 0.0001), and lipid peroxidation (P = 0.001) were also observed for the HF and IF groups in comparison with the LF group. Changes in insulin resistance explained ∼17% of changes in composite z score (partial r2 = 0.1703, P < 0.0001). Conclusions: This dietary intervention study provides evidence that regular CF consumption can reduce some measures of age-related cognitive dysfunction, possibly through an improvement in insulin sensitivity. These data suggest that the habitual intake of flavanols can support healthy cognitive function with age. This trial was registered at www.controlled-trials.com as ISRCTN68970511.

We assessed the in vitro effects of interferon beta-1b (IFNbeta-1b), cyclophosphamide (CY), and azathioprine (AZA) alone and of the combination of IFNbeta-1b with CY or AZA on the production of Th1 and Th2 cytokines in 10 patients with multiple sclerosis. Cytokine levels were determined at baseline and after stimulation with IFNbeta-1b, CY, and AZA alone or with the combination of IFNbeta-1b with CY or AZA. The combination of IFNbeta-1b with CY resulted in a statistically significant decrease in the production of interleukin-2 (IL-2) (P=0.003) and tumor necrosis factor alpha (TNF-alpha) (P=0.03). An additive effect on the production of interferon gamma (IFN-gamma) (P=0.2) and interleukin-10 (IL-10) (P=0.6), and a positive interaction on the production of interleukin-4 (IL-4) (P=0.08) were observed although the findings were not statistically significant. The combination of IFNbeta-1b with AZA resulted in a significant negative effect on the production of IL-2 (P=0.006), whereas TNF-alpha (P=0.02), IFN-gamma (P=0.03), IL-4 (P=0.2), and IL-10 (P=0.3) were not statistically impacted. Our data show that CY was able to improve the effects of IFNbeta-1b on the ratio of Th1/Th2 cytokines.

Prophylactic activity of flunarizine in migraine is attributed to its antioxidant properties and to the relief of cerebral vasospasm in which nitric oxide (NO) is involved. We investigated the antimigraine activity of flunarizine and its influence on NO and oxidative marker bioavailability in 25 subjects suffering from migraine without aura and in 25 healthy controls. Urinary samples collected before and after treatment with flunarizine (5 mg orally per day for 6 months) were assayed for NO stable metabolites (NOx) and thiobarbituric acid reactive substances (TBARS). Urinary levels of NOx and TBARS were higher in migraine sufferers before treatment than in healthy controls. No differences were observed in NOx levels in migraine sufferers, before and after flunarizine treatment; urinary TBARS levels were decreased after flunarizine treatment ( P < 0.05) and remained persistently higher than in healthy controls ( P < 0.05). Our results suggest that flunarizine did not prevent NO-mediated vasodilatation, while it proved effective in limiting the oxidative reactions occurring in migraine sufferers.

Intracerebral hemorrhage (ICH) occurs as a result of bleeding into the brain parenchyma and formation of a focal hematoma. Treatment for ICH is primarily supportive, and outcome remains poor. Initial management is directed toward stabilizing breathing and circulation. Increased intracranial pressure is currently managed with osmotic agents (mannitol and glycerol); steroids, hypovolemia, controlled hyperventilation, and barbiturate coma can also be employed. Arterial blood pressure control is useful and requires adequate compliance to specific guidelines. Ultra-early hemostatic therapy may represent a promising tool to reduce early hematoma enlargement and to improve outcome.

Type 1A, the most common form of Charcot-Marie-Tooth (CMT1A) disease, is characterized by demyelination of the peripheral nervous system. So far, only a few cases of the disease with concomitant brain white matter lesions have been described. We report an Italian family with CMT1A disease, consisting of the proband and 4 affected members, presenting with concomitant brain white matter lesions at magnetic resonance imaging. The association is particularly fascinating and might depend on an autoimmune mechanism, not yet clarified.

Stroke is the most common neurologic disease and the leading cause of adult disability in Western countries. The number of patients affected by stroke will increase by the effect of aging. Mainly due to increased life expectancy, the proportion of individuals over 65 years in the L'Aquila district showed an increase of 18.3% in a 10 years period (1981-1991). Among the resident population, in a five-year period (1994-1998) we collected all the patients with a first-ever stroke, and we found high crude and standardized (European population 1996) incidence rates. There was a significant correlation between crude and standardized incidence rates and proportion of individuals aged 65 and over, suggesting that the high incidence was due to an increased stroke risk linked to aging. As a cosequence, the number of subjects with atherosclerotic comorbidity will increase and the quality of life will worsen.

Objective—To estimate the prevalence of multiple sclerosis in the L’Aquila district, central Italy. Methods—All available case sources were screened. Definite and probable cases of multiple sclerosis, classified according to the Poser criteria, were considered as prevalent cases. Results—On the prevalence day, 31 December 1996, 158 patients (105 women and 53 men; ratio 2:1) aVected by definite (n=131) or probable (n=27) multiple sclerosis were alive and resident in the L’Aquila district. Mean (SD) age was 38.4 (11.9) years (38.9 (11.7) years for women and 38.5 (12.3) years for men, p=0.9). The overall crude prevalence was 53.0/100 000 (95% confidence interval (95% CI)=45.4‐ 62.0); 68.4/100 000 (95% CI=56.5‐82.8) in women, and 36.7/100 000 (95% CI=28.1‐ 48.0) in men. The prevalence was similar (55.9/100 000) when standardised to the 1996 European population. Mean (SD) age at onset of multiple sclerosis was 29.4 (9.6) years and mean (SD) duration of the disease was 9.4 (7.4) years, without any significant diVerence between sexes. Mean age at onset was significantly higher in patients with the primary progressive than in those with the relapsing-remitting course (p=0.0002, ScheVe’s test). Conclusions—The prevalence found in the L’Aquila district gives support to the consideration of Italy as an area in which multiple sclerosis has been shown to have high prevalence at least in the populations that were surveyed recently. (J Neurol Neurosurg Psychiatry 2000;68:349‐352)

Background and Purpose —Prognosis of ischemic stroke in young adults is reported as favorable, and transient ischemic attack (TIA) is commonly considered a benign event. We investigated long-term outcome and prognostic predictors of cerebral ischemia in patients under 45 years of age. Methods —Three hundred thirty-three patients aged 15 to 44 years who suffered from a first-ever TIA or ischemic stroke were prospectively followed up with annual clinical evaluation or complete phone interview. End points were the composite outcome event of stroke, myocardial infarction, and vascular or nonvascular death and death from all causes. The probability of event-free survival was estimated by the Kaplan-Meier method. Univariate and multivariate estimates of hazard ratios were calculated according to the Cox proportional hazards analysis. Results —An average follow-up of 96 months was available in 330 patients (99.1%). Survival was worse in patients with stroke at entry (86.5%) than in those with TIA (97.1%). Mortality in both groups was significantly higher than in the general population (standardized mortality ratio [SMR] 14.5, P P =0.002). The average annual mortality rate was higher during the first (3.94%, 95% CI 1.84 to 6.04) than in the subsequent years. The average annual incidence rate of new stroke was higher in patients with stroke than in those with TIA at entry, and it declined from 1.56% (95% CI 0.21 to 2.91) during the first year to 0.06% (95% CI 0.04 to 0.08) at the end of the follow-up. Myocardial infarction occurred later, after the first year, with similar rates in patients with stroke and TIA at entry. The average annual rates of new stroke (2.36%), myocardial infarction (1.68%), and death (3.05%) were higher in patients with the mixed atherothrombotic and cardioembolic etiology than in the remaining patients. Male gender, age >35 years, stroke at entry, and cardiac diseases were independent predictors of the composite outcome event at the Cox regression analysis, whereas only stroke at entry and cardiac diseases predicted death from all causes. Conclusions —Stroke and TIA in young adults have severe prognostic implications, because the mortality risk was highly increased with respect to the general population. Preventive measures are strongly recommended in the presence of any unfavorable prognostic profile.

Transcranial Doppler is routinely used to assess the cerebrovascular reactivity, despite scarce information on its reproducibility. We evaluated the reproducibility of cerebrovascular reactivity measurements by this method utilizing different vasodilatory and vasoconstrictor stimuli. The cerebrovascular reactivity was measured in 45 healthy volunteers during hypercapnia induced by inhalation of a mixture of 5% CO2 and 95% O2, breath holding and rebreathing, and during hypocapnia induced by voluntary hyperventilation. Three sets of measurements were performed at times 0, 1, and 24 h to assess the within-observer short- and long-term reproducibility. The reproducibility was analyzed using the intraclass correlation coefficient. For the CO2 inhalation method, a good short-term (rI = 0.55; 95% CI = 0.39–0.68) and a good long-term (rI = 0.43; 95% CI = 0.25–0.59) reproducibility was found. For the breath-holding method a good short-term agreement was found (rI = 0.41; 95% CI = 0.22–0.57), while the long-term reproducibility was poor (rI = 0.17; 95% CI = –0.03–0.36). Rebreathing showed a fair (rI = 0.31; 95% CI = 0.11–0.48) short-term and a poor (rI = 0.17; 95% CI = –0.03–0.36) long-term reproducibility. For voluntary hyperventilation, the short-term reproducibility was good (rI = 0.53; 95% CI = 0.36–0.66), and the long- term reproducibility was fair (rI = 0.31; 95% CI = 0.11–0.48). In our study, CO2 inhalation and voluntary hyperventilation had the highest reproducibility and should be preferred when assessing cerebral vasoreactivity, especially in follow-up studies.

Although a considerable body of scientific data is now available on neuroprotection in acute ischaemic stroke, this field is not yet established in clinical practice. At its third meeting, the European Ad Hoc Consensus Group considered the potential for neuroprotection in acute stroke and the practical problems attendant on the existence of a very limited therapeutic window before irreversible brain damage occurs, and came to the following conclusions. Neuroprotectants in Clinical Development: Convincing clinical evidence for an efficacious neuroprotective treatment in acute stroke is still required. Caution should be exercised in interpreting and extrapolating experimental results to stroke patients, who are a very heterogeneous group. The limitations of the time windows and the outcome measures chosen in trials of acute stroke therapy have an important influence on the results. The overall distribution of functional outcomes provides more statistical information than the proportion above a threshold outcome value. Neurological outcome should also be assessed. Neuroprotectants should not be tested clinically in phase II or phase III trials in a time window that exceeds those determined in experimental studies. The harmful effects of a drug in humans may override its neuroprotective potential determined in animals. Agents that act at several different levels in the ischaemic cascade may be more effective than those with a single mechanism of action. Current In-Hospital Management of Acute Stroke: The four major physiological variables that must be monitored and managed are blood pressure, arterial blood gas levels, body temperature, and glycaemia. The effects of controlling these physiological variables have not been studied in prospective trials, though they may all contribute to the outcome of acute ischaemic stroke and affect the duration of the therapeutic window. Optimal physiological parameters are inherently neuroprotective. Trials of new agents for the treatment of acute stroke should aim to maintain these physiological variables as close to normal as possible, and certainly within strictly defined limits. The Place of Neuroprotectants in Acute Stroke Management: Stroke patients are a very heterogeneous group with respect to stroke mechanisms and severity, general condition, age and co-morbidities. At the present time, the only firm guideline than can be proposed for patient selection is the need for early admission to enable neuroprotectant and/or thrombolytic treatment to be started as soon as possible within the therapeutic window. The severity of potential side-effects will largely determine who should assess a patient with suspected stroke and initiate treatment. There is little information on which to base the duration of neuroprotectant therapy, and more experimental data are needed. Even if prehospital treatment proves to be feasible, it should not replace comprehensive stroke management in a specialist hospital unit. Clinical trials of neuroprotectants should only be performed in stroke units. The combined approach of restoring blood flow and providing neuroprotection may be the most productive in human stroke, but current clinical trial design will have to change in order to test combination therapy. Important side-effects are those that interfere with any possible benefit or increase mortality. Pharmaco-Economic Aspects of Neuroprotectants: The early increase in hospital costs associated with neuroprotectant therapy may be balanced by the shorter length of hospital stay and lesser degree of disability of the surviving patients. The overall direct financial cost is highly dependent on the number of patients eligible for neuroprotectant therapy, which is itself dependent on the length of the therapeutic window and the severity of potential side-effects. A treatment that achieves a good functional outcome is the most cost-effective approach.

The type of small-vessel disease in small deep (lacunar) infarcts (SDIs) remains contentious as opposed to that in primary intracerebral haemorrhage (PICH), which is lipohyalinosis in most cases. Therefore, we compared risk factor profiles as indicators of underlying vessel pathology, between patients with SDI and patients with PICH, and those with a non-cardio-embolic infarct involving the cortex (CORTI). Multivariate regression analysis showed that diabetes mellitus [odds ratio (OR) 0.56; 95% confidence interval (CI) 0.34–0.90] and hypercholesterolaemia (OR 0.63; 95% CI 0.40–0.99) were more strongly associated with CORTI than with SDI. Carotid stenosis was associated with SDI in comparison with PICH (OR 7.5; 95% CI 1.02–54.94). Compared with PICH, CORTI was more strongly associated with diabetes mellitus (OR 3.27; 95% CI 1.38–7.76), carotid stenosis (OR 24.42; 95% CI 4.99–119.45), and hypercholesterolaemia (OR 3.12; 95% CI 1.47–6.65), whereas hypertension was associated with PICH (OR 0.37; 95% CI 0.18–0.79). These data support the hypothesis that small-vessel atheromatosis rather than small-vessel lipohyalinosis underlies lacunar infarcts in most cases.

Neuroinflammation is believed to be involved in the pathophysiological mechanisms of silent brain infarcts (SBI). However, the immunological profile of SBI has been scarcely investigated. In the context of a national research project named SILENCE, aimed at investigating clinical, biochemical and pathogenic features of SBI, we have measured the plasma profile of some inflammatory-related molecules in SBI patients (n = 21), patients with recent lacunar infarcts (LI, n = 28) and healthy controls (n = 31), consecutively enrolled in four Italian centres. A panel of chemokines (MIG, CTACK, IL16, SDF1a, MCP1), growth factors (SCF, SCGFb, HGF, IL3), immunoglobulin-type adhesion molecules (ICAM1, VCAM1), proinflammatory cytokines (IL18, INFa2, MIF, IL12p40), cell surface receptors on T-cells (IL2Ra), and inductors of apoptosis (TRAIL) was assessed in plasma samples by Luminex xMAP™ technology. Immunological parameters were compared using non-parametric statistics and performance to distinguish SBI and LI was evaluated by receiver operating characteristic (ROC) analysis. Plasma levels of ICAM1 were significantly higher in both SBI and LI patients as compared to controls (SBI≥LI>Ctrl). A different trend was observed for IL16 (SBICtrl), SCF (LICtrl) and SCGFb (SBI>LICtrl) and IL18 when compared to LI patients (Ctrl≤SBI>LI). All the other immunological markers did not significantly differ among groups. According to ROC analysis, the best predictor for SBI condition was the chemokine MIG (AUC = 0.84, sensitivity 86%, specificity 77%), while SCF had the best performance in distinguishing LI patients (AUC = 0.84, sensitivity 86%, specificity 68%). These results confirm the involvement of inflammatory processes in cerebrovascular disorders, particularly in SBI, a very common age-related condition. The differences in plasma profile of inflammatory molecules may underlie different pathological mechanisms in SBI and LI patients.

Objective: To estimate the prevalence and outcome of symptomatic internal carotid artery lesions in young adults. Design: Multicentre hospital based observational study with five year follow up. Setting: Seven neurological departments in northern and central Italy. Subjects: 240 patients (115 men) aged 15-44 with a recent transient ischaemic attack or stroke in the carotid territory. Main outcome measures: (a) Prevalence of symptomatic internal carotid artery stenosis or occlusion detected by continuous wave Doppler ultrasonography at entry; (b) incidence rates of cerebral, cardiac, and non-vascular death; non-fatal stroke; and non-fatal myocardial infarction. Results: Carotid stenoses of 50-99% and occlusions were found in 38 patients (15.8%). Both conditions were significantly more frequent in patients aged over 35 and in those with hypertension, diabetes mellitus, and stroke at entry. The standardised mortality ratio at five years was 10.5 (95% confidence interval 5.0 to 19.3). Survival of patients with stenoses of 0-49% and occlusions was significantly better than that of patients with stenoses of 50-99%. Carotid stenosis of 50-99% was an independent predictor of death (hazard ratio 7.9; 95% confidence interval 2.2 to 29) and non-fatal stroke (hazard ratio 7.4; 1.5 to 37.4). Conclusions: The prevalence of carotid stenosis or occlusion in young adults after a cerebrovascular event is low. Though patients with high grade symptomatic carotid stenosis are at risk of non-fatal and fatal events, patients with internal artery occlusion apparently have a benign prognosis. Key messages Key messages Young adults with a history of transient ischaemic attack and stroke have a low prevalence of high grade symptomatic carotid artery stenosis and occlusion The five year prognosis is apparently benign in patients aged 15-44 with internal carotid artery occlusion but poor (in terms of fatal and non-fatal events) in the presence of high grade carotid stenosis Primary and secondary medical prevention of cerebral ischaemia based on routine Doppler examinations should be initiated early in subjects at risk Endarterectomy should be considered even in young adults with ipsilateral carotid artery stenosis of 70-99% to halt the progression of arterial lesions and improve prognosis

Flavanol consumption is favorably associated with cognitive function. We tested the hypothesis that dietary flavanols might improve cognitive function in subjects with mild cognitive impairment. We conducted a double-blind, parallel arm study in 90 elderly individuals with mild cognitive impairment randomized to consume once daily for 8 weeks a drink containing ≈990 mg (high flavanols), ≈520 mg (intermediate flavanols), or ≈45 mg (low flavanols) of cocoa flavanols per day. Cognitive function was assessed by Mini Mental State Examination, Trail Making Test A and B, and verbal fluency test. At the end of the follow-up period, Mini Mental State Examination was similar in the 3 treatment groups ( P =0.13). The time required to complete Trail Making Test A and Trail Making Test B was significantly ( P P z score variability through the study period (partial r 2 =0.4013; P

Background and Purpose. Stroke incidence increases with age and is likely to increase in the aging populations. We investigated incidence, outcome, and resource use in very old subjects with stroke.Methods. We performed a systematic review of available data through electronic search of the literature databases and manual search of reference lists. Data were extracted for the age groups of over 80, 80 to 84 years old, and over 85. Overall incidence rates, expressed as the number of first strokes per 1000 person-years, were estimated using Poisson regression analysis. Odds ratios for the comparisons between subjects over and under 80 were calculated with the Mantel-Haenszel method.Results. We found a high incidence of stroke in the very old. The estimated incidence rates were 20.78 (95% CI 19.69 to 21.87) in subjects over 80, 17.23 (95% CI 15.97 to 18.49) for those 80 to 85 years old, and 20.78 (95% CI 16.74 to 23.78) for those over 85. Subjects over 80 contributed 29.95% of strokes; rates were similar among genders. Thirty-day case fatality rate and occurrence of dependency were higher in subjects over 80, although associated with less frequent hospital and stroke unit admission and less diagnostic resource use.Conclusions. The contribution of very old subjects to the global burden of stroke is relevant and may require efficient dedicated stroke services.