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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.

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.

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

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 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.

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

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.

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.

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.

Many studies suggest that emotional arousal improves memory storage. The aim of this study was to evaluate the effects of emotional content on explicit memory in untreated cephalalgic patients and in migraineurs treated with the antidepressant amitriptyline. We utilized an adaptation of two versions of the same story, with different arousing properties (neutral or emotional), which have been already employed in experiments involving the enhancing effects of emotions on memory retention. Subjects of the present study were healthy subjects and cephalalgic patients, suffering from migraine headache, which included untreated migraineurs and migraineurs treated with the antidepressant amitriptyline. The findings of our experiments suggest that chronic migraine is related to memory impairment. Taking into account that migraine is associated with major depression, in the present research the effect of the antidepressant amitriptyline was also evaluated. Our results showed that amitriptyline has an impairment effect on memory. In fact, the untreated migraineurs, compared to treated, recalled the most emotional phase of the arousal story significantly better. Then, our data suggest that amitriptyline prevents the enhancing effects of emotional content on memory processes. Moreover, in agreement with our previous data, this study suggests the existence of gender differences in the processing of emotional stimuli and underscores the importance of sex on emotional memory mechanisms.

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.

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)

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.

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.

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

Transcranial Doppler sonography examination was performed on 44 patients with migraine with aura and 88 controls. All patients were investigated in headache-free periods and 10 of them also during a migraine attack. During the headache-free period a not significant increase of mean flow velocity in patients compared to controls was obtained. The pulsatility index (PI) mean values were also higher in patients than in controls and the differences were significant in the MCA (p < 0.05). No difference between right and left side was observed. During the attack the mean flow velocity (MFV) decreased in all arteries but the decrease was significant only in MCA and ACA (p < 0.05). The mean PI increased in all arteries but not significantly. These variations were observed both on the headache and contralateral side. Nevertheless, the MFV decrease in all arteries was observed in four patients only. In four patients the MFV decrease was found in the anterior arteries and the MFV increase in the posterior arteries, while in two patients the MFV increase was observed both in the anterior and posterior arteries. The correlation between the variations of MFV values during the attacks and the time interval from the onset of attacks showed that the PCA and BA flow velocities were increased in patients examined between 0.5 and 3 hours, while an increase in MCA and ACA flow velocities were observed only in patients examined after 1.5 hours.

Transcranial Doppler-sonography (TCD) is a useful noninvasive technique for the measurement of intracranial arterial blood flow velocity. The present study evaluated the reproducibility of this method for repeated measurements of flow velocity in the anterior, middle and posterior cerebral, and basilar arteries. Thirty-six patients (23 males and 13 females) were studied. Three measurements were made by the same examiner on each patient with a time interval of 1 h between the first and the second examination, and about 24 h between the first and the third examination. The statistical evaluation for the reproducibility was performed by calculating the correlation coefficient (r). The results showed good reproducibility of TCD for all arteries both between the first and second and between the first and third measurements (r = 0.78-0.97; p less than 0.001), but when the middle cerebral artery mean velocity is low the posterior cerebral artery reproducibility is poorest (r = 0.42-0.54).

Background and Purpose— The purpose of this study was to evaluate the incidence and prognosis of intracerebral hemorrhage. Methods— We analyzed data referring to our prospective population-based registry, including patients with a first-ever stroke followed up to 10 years. Results— In a 5-year period, we included 549 patients (247 men and 302 women; mean age±SD, 73.6±12.5 years) with an intracerebral hemorrhage. The crude annual incidence rate was 36.9 per 100000 (95% CI, 33.8 to 40.0), 32.9 per 100000 when standardized to the 2006 European population, and 15.9 per 100000 when standardized to the world population. The case-fatality rate was 34.6% (95% CI, 30.6 to 38.6) at 7 days; it increased to 50.3% (95% CI, 46.1 to 54.5) at 30 days and to 59.0% (95% CI, 54.9 to 63.1) at 1 year. Diabetes mellitus and posterior fossa hemorrhage were associated with an increased risk of 7- and 30-day mortality, whereas older age was associated with an increased risk of 30-day mortality only. At the Kaplan-Meier analysis, the 10-year survival rate was 24.1% (95% CI, 20.1 to 28.1). Conclusions— Intracerebral hemorrhage is characterized by a severe prognosis, mostly in the short term. Because of the high proportion of fatal events that occurs early after the stroke, it is mandatory to identify and apply specific therapeutic strategies for patients with intracerebral hemorrhage.

It has been suggested that cerebrovascular factors contribute to Alzheimer's disease. Soluble CD40 ligand (sCD40L) is directly involved in the development of vascular damage. We tested the hypothesis that sCD40L may be enhanced in Alzheimer's disease and predictive of its clinical course. Plasma sCD40L levels were evaluated in three groups of 40 consecutive patients each referring for mild or moderate or severe Alzheimer's disease, as assessed by the Clinical Dementia Rating (CDR), and in 40 healthy subjects. Seventy-seven patients with mild or moderate disease were re-evaluated after 2 years. Cross-sectional comparisons revealed higher plasma sCD40L levels in Alzheimer's disease patients than in controls (9.3+/-4.7 ng/mL versus 3.4+/-1.3 ng/mL, p0.0001). Circulating sCD40L levels significantly increased through the three CDR stages (p=0.0011 or less) and were correlated with MMSE (r=-0.574, p0.0001) and ADAS-cog subscale (r=0.538, p0.0001) scores. Longitudinal evaluation identified sCD40L as an independent predictor of MMSE (beta=-0.157, t=-3.650, p=0.0005) and ADAS-cog subscale (beta=0.484, t=3.890, p=0.0002) score changes after 2 years. Patients with plasma sCD40L levelor=6.0 ng/mL, identified by ROC curve analysis as the best discriminating value for disease progression, had a three-fold increase in the risk of progression toward a worse CDR stage (odd ratio: 3.0, C.I. 95% 1.2-8.1). In conclusion, circulating sCD40L is enhanced in patients with Alzheimer's disease and independently associated with the severity and progression of the disease. These data might suggest a pathogenetic role for sCD40L in Alzheimer's disease.

Background: Only a few non-recent studies assessed the importance of hematocrit (HCT) in patients with ischemic stroke. We evaluated how HCT might affect early mortality after stroke. Methods: We investigated all first-ever ischemic strokes included in the population-based L’Aquila registry. 3,481 patients according to HCT (%) values were included into four categories (≤40, 41–45, 46–50, and >50). Results: There were more men than women with HCT >50 (6.6 vs. 2.8%; p < 0.0001) and more women than men with HCT ≤40 (48.5 vs. 37.9%; p < 0.0001). Proportions of chronic atrial fibrillation (p = 0.0053) increased in women from the lower to the higher HCT categories. 7- and 28-day case-fatality rates were similar in men and women in the lower HCT categories but higher in women than in men in the higher categories. At the 28-day Kaplan-Meier analysis, men had similar survivals in the different categories while women with HCT >50 showed the worst survival (p < 0.0001). At the multivariate Cox regression analysis HCT 46–50 and >50 was an independent predictor of mortality in women within 28 days. Conclusion:High HCT might represent in women a previously underestimated independent predictor of mortality after ischemic stroke. Consideration of HCT in future stroke trials would be useful for ameliorating stroke care, especially in women.

Objective: To evaluate incidence and prognosis of lacunar stroke in a prospective, population-based patient registry. Methods: The authors included first-ever strokes occurring between 1994 and 1998. They assessed incidence, risk factors, mortality, and recurrence in patients with lacunar stroke. Results: The authors identified 491 patients (15.3%) with lacunar stroke (252 men and 239 women) and 2,153 patients (67.3%) with nonlacunar stroke (998 men and 1,155 women). Crude annual incidence rate for a first-ever lacunar stroke was 33.0/100,000 (95% CI 30.2 to 36.0). At the univariate logistic regression analysis among patients with lacunar stroke there was a higher proportion of cigarette smoking and hypercholesterolemia and a lower proportion of chronic atrial fibrillation than in patients with nonlacunar stroke. For lacunar stroke, the 30-day case-fatality rate was 4.3% (95% CI 2.5 to 6.1) and the 1-year case-fatality rate was 13.0% (95% CI 10.0 to 16.0). During the first year of follow-up the average annual stroke recurrence rate was lower in patients with lacunar (2.83%; 95% CI 1.36 to 4.30) than in those with nonlacunar stroke (5.10%; 95% CI 4.17 to 6.03) while from the second year onward, rates were similar in both groups. Conclusion: In the short term, patients with nonlacunar stroke had more vascular events, but in the long term, the risk of death and of stroke recurrence was similar.

Background and Purpose— Atrial fibrillation (AF) is a major risk factor for ischemic stroke and its prevalence increases steeply with age. Population-based data on its influence on stroke outcome are scarce. Methods— We evaluated the prevalence of AF and its influence on prognosis in patients with a first-ever ischemic stroke from a population-based registry. Results— The presence of AF at stroke onset and during the acute phase was confirmed by a standard electrocardiogram in 869 (24.6%) of 3530 patients with ischemic stroke. With respect to patients without the arrhythmia, those with AF were more frequently women, aged 80 years and older, with coronary heart disease and peripheral arterial disease. The presence of AF was associated with high 30-day (32.5%; 95% CI, 29.3 to 35.6) and 1-year case-fatality rates (49.5%; 95% CI, 46.2 to 52.8), with a higher stroke recurrence rate within the first year of follow-up (6.6% versus 4.4%; P =0.046) and with the worst survival after an average follow-up of 45.2 months ( P Conclusions— We found a high prevalence of AF in patients with a first-ever ischemic stroke, especially among elderly women. The overall contribution of AF to stroke mortality was relevant, suggesting that together with new strategies to prevent the development of the arrhythmia more appropriate treatments are needed, mostly in elderly women.

Objective – We estimated the prevalence of Parkinson's disease (PD) in the L'Aquila district. Methods – Cases of PD were identified screening all available case sources including general practitioners and antiparkinsonian drug-users by means of pharmacy records. Prevalence of PD was computed considering the prevalence day of December 31, 2001. Results – On the prevalence day, 682 patients with PD were alive and residing in the L'Aquila district. A total of 354 patients were women and 328 men. The overall crude prevalence rate was 229.3/100,000 (95% CI 212.7–247.1), without any difference between men (227.4/100,000; 95% CI 200.0–257.5) and women (231.1/100,000; 95% CI 202.2–263.1). Prevalence rates increased with age in both sexes and were higher in urban (244.5/100,000; 95% CI 213.7–278.5) than in rural residents (214.7/100,000; 95% CI 189.0–242.9) (SRR = 1.7; 95% CI 1.3–2.1). Conclusions – The prevalence of PD in the L'Aquila district was within the range of prevalence rates found in our country and steeply increased with advancing age in both sexes.

Objective: To evaluate the contribution of subjects 80 years old or older to the burden of ischemic stroke as compared with subjects younger than 80 years. Methods: All first-ever ischemic strokes occurring in a 5-year period (1994 to 1998) in the population-based L’Aquila registry were traced. Incidence, total health care utilization, disability, and mortality were assessed in patients 80 years old or older, and differences with those younger than 80 years were assessed by univariate and survival analyses. Results: One thousand three hundred sixteen of 3,594 first-ever ischemic strokes (36.6%) occurred in patients 80 years old or older, accounting on average for one-third of health care utilization. The crude annual incidence rate was 21.54 per 1,000 (95% CI 20.42 to 22.72). At the 1-year follow-up, 27.7% of patients had mild or no disability, 20.7% had severe disability, and 51.6% had died. With respect to patients under 80 years of age, older patients showed a higher proportion of women (61.3 vs 47.7%), atrial fibrillation (30.2 vs 20.7%), coronary heart disease (31.0 vs 23.4%), and peripheral arterial disease (14.6 vs 10.8%) and a lower proportion of cigarette smoking (15.3 vs 29.2%) and hypercholesterolemia (20.4 vs 29.4%). Thirty-day (34.6 vs 13.4%) and 1-year (51.6 vs 22.3%) mortality were higher in patients 80 years old or older than in those younger than 80, mostly in the presence of atrial fibrillation (hazard ratio [HR] was 1.39 for 30-day mortality and 1.37 for 1-year mortality) and diabetes mellitus (HR was 1.39 for 30-day mortality and 1.31 for 1-year mortality). Conclusion: The burden of ischemic stroke is high in subjects 80 years old or older, contributing about one-third of health care utilization and 59.8% of deaths within 30 days.

Enhanced endothelium nitric oxide (NO) and superoxide anion release may cause migraine through related cerebral blood flow changes. Thirty subjects suffering from migraine with and without aura and 20 healthy controls were investigated. Urine samples collected for 24 h during and after the migraine attack, and during the headache-free period, were assayed for urinary NO stable metabolites (NOx) and thiobarbituric acid reactive substances (TBARS). During the headache-free period urinary NOx and TBARS levels were higher in migraine sufferers than in controls (NOx 0.77 ± 0.14 vs. 0.28 ± 0.15 mmol/mmol creatinine, P < 0.05; TBARS 0.40 ± 0.19 vs. 0.26 ± 0.13 μmol/mol creatinine, P < 0.05). Also, NOx excretion was higher during the headache-free period than during or after the migraine attack ( P < 0.05). Urinary TBARS were increased during the attack with respect to the headache-free period ( P < 0.05). No differences were observed in the same parameters between sufferers of migraine with and without aura. Urinary NOx and TBARS might be promising as markers of their systemic levels to evaluate the increased vulnerability to oxidative stress in migraine sufferers.

To the Editor: We read with interest the article by Jacobs et al1 on stroke in the young. Their epidemiological work was carried out within the frame of the Northern Manhattan Stroke Study, a population-based registry, with comparisons between younger and older patients on demographic characteristics, risk factors, and prognosis, and with computation of the selective contribution of the younger patients to the burden of stroke. We conducted between 1994 and 1998 a similar study on 89 patients under 45 years of age with a first-ever stroke documented by brain neuroimaging, in a defined population of central Italy.2 Despite the inclusion in our study only of white subjects, we would like to make some comments and comparisons between the 2 studies. The overall stroke incidence in the white residents of the Northern Manhattan area was 10/100 000 per year. This figure was identical to that found in our study (10.2/100 000) and within the range of studies on subjects under 45 years of age (8.8 to 15/100 000) quoted by Jacobs et al. However, if we refer to the studies quoted in our article, that were all performed with a comparable methodology, the range …

This study evaluated the effects of two different rates of infusion of echo-contrast agents (ECA) on signal enhancement. A total of 15 patients with insufficient Doppler signal due to inadequate transtemporal acoustic bone window were examined. Signal from the middle cerebral artery was recorded during the IV infusion of Levovist® (300 mg/mL). Increment of signal enhancement in dB, time to signal enhancement appearance, time to clinically useful signal enhancement appearance, and duration of clinically useful signal enhancement were assessed during two infusions at the rate of 1 and 0.66 mL/min, respectively. Increment of signal enhancement was similar at the rate of 1 and 0.66 mL/min (p = 0.4). Mean time to signal enhancement appearance and mean time to clinically useful signal enhancement appearance were not significantly different with the two rates of infusion (p = 0.9 and p = 0.3, respectively). Mean duration of clinically useful signal enhancement was significantly higher with the infusion rate of 0.66 mL/min as compared to 1 mL/min (p < 0.0001). Levovist® injected at the infusion rate of 0.66 mL/min prolonged the mean duration of signal enhancement, maintaining its effectiveness. (E-mail: totaro@cc.univaq.it)

The study is aimed to ascertain whether the Helicobacter pylori ( Hp) infection is responsible for the vulnerability to oxidative stress observed in migraineurs. Hp sero-logical positivity was assessed by ELISA evaluation of specific IgA and IgG antibodies in 30 subjects (11 males and 19 females) suffering from migraine without aura during the headache-free period. The Hp infection was detected in 16.7% of migraineurs. Plasma accumulation of peroxidative substances (TBA-RS), an index of systemic oxidative status, was increased in migraineurs without Hp infection with respect to controls ( P< 0.001), while no significant differences of TBA-RS were found in migraineurs with or without Hp infection. Unmodified values of plasma nitrite/nitrate concentrations, expression of systemic nitric oxide (NO), were obtained in migraineurs in comparison to controls indicating that Hp infection does not modify the plasma oxidative status and the systemic NO bioavailability of migraineurs. In conclusion, our results do not support any specific correlation between Hp infection and migraine.

Objectives: To compare stroke incidence rates among comparable registries and to make correlations with aging of the resident populations. Methods: This correlation study included all comparable stroke registries maintained in industrialized countries (Italy, France, United Kingdom, Denmark, Norway, United States, and Australia). Eleven community-based stroke registries with similar high proportions of radiologically confirmed diagnoses based on standard definitions were identified. Incidence rates of first-ever stroke from the prospective L’Aquila registry and from the other registries were compared after age and sex standardization to the 1996 European population. The rates were then correlated with the proportion of individuals aged 65 and over in the corresponding resident populations by means of the Poisson regression analysis. Results: In the L’Aquila registry, the crude annual incidence of first-ever stroke was 281/100,000 (95% confidence interval 271–293) based on 2,515 patients included during a 3-year period. The rate standardized to the European population was 249/100,000. Standardized incidence ratios indicated a significant excess of first-ever strokes in the L’Aquila registry up to 51% with respect to most of the compared studies. A significant correlation was also found between crude (p < 0.0001) and standardized (p = 0.0012) stroke incidence rates and proportions of individuals aged 65 and over in the different populations. Conclusions: The L’Aquila experience suggests that any further aging of a population will increase the stroke occurrence for both the reasons of a direct and predictable effect of the growing proportion of elderly individuals within that population and a disproportionately increased stroke risk in the older age groups.

Background and Purpose Changes in stroke incidence are likely to occur as a consequence of aging of the population, but evidence for this hypothesis is lacking. Methods A prospective community-based registry of first-ever strokes (1994 to 1998) classified according to the International Classification of Diseases, 9th Revision (ICD-9) was established in the L’Aquila district, central Italy, with a total population of 297 838 (1991 census). Patients were identified by active monitoring of multiple sources, including general practitioners. Results In 1994, 819 patients (398 men and 421 women; mean±SD age, 74.8±11.3 years) suffered from a first-ever stroke. Eighty-nine percent of the patients had neuroimaging studies of the brain and were reclassified with the recent Application of the International Classification of Diseases to Neurology (ICD-10 NA). The occurrence of subarachnoid hemorrhage, intracerebral hemorrhage, cerebral infarction, and ill-defined events was 2.9%, 14.9%, 80.2%, and 2.0%, respectively. Crude annual incidence of first-ever stroke was 2.75/1000 (95% confidence interval [CI], 2.57 to 2.94) and 24.23/1000 (95% CI, 21.65 to 27.10) in patients older than 80 years. Incidence rates were higher in men and steeply increased with age. The standardized rate was 2.37/1000 for the Italian and 2.28/1000 for the European population. The 30-day case-fatality rate was 25.6% (95% CI, 22.8% to 28.7%). The occurrence of death, disability, and full recovery at 1 year was 36.9%, 38.9%, and 24.2%, respectively. No differences were found in stroke incidence and case-fatality according to income and urban or rural residences. Conclusions In our population-based study, we found a high stroke incidence notably in the older age subgroups, suggesting that rather than declining, stroke is only being postponed until later in life.

Transcranial Doppler studies on the effects of sumatriptan on cerebral hemodynamics have shown conflicting results. We evaluated blood flow velocity changes in 21 patients suffering from migraine with (n = 4) or without aura (n = 17) during a spontaneous attack, before and after treatment with sumatriptan. Flow velocity in the internal and external carotid, middle cerebral, and basilar arteries was measured by means of transcranial Doppler. During the attack, measurements were taken before subcutaneous sumatriptan injection, then after 30 minutes, 2 hours, and 24 hours. An additional measurement was taken 1 week later, in a headache-free state. We found a significant reduction of flow velocity during the attack in the middle cerebral artery on both sides (P0.05). After sumatriptan administration, flow velocity increased in the internal carotid artery on both sides (P0.05) and in the middle cerebral artery on the headache side (P = 0.0001), but not in the external carotid and basilar arteries (P0.05). Flow velocity changes may reflect the vasodilation present at the onset of the migraine attack followed by vasoconstriction in the internal carotid and middle cerebral arteries after sumatriptan treatment. Since vasoconstriction occurs in responders and nonresponders to treatment, it is unlikely to be the primary mechanism by which sumatriptan relieves headache.

Alterations of intracranial vessel tone have been implicated in the pathophysiology of migraine. The cerebrovascular reactivity was measured by means of transcranial Doppler in 60 migraine patients with ( n = 30) or without aura ( n = 30) during the headache-free interval and in 30 healthy controls. The vasomotor response was evaluated during hypercapnia induced by inhalation of a mixture of CO2 5% and O2 95% and during hypocapnia obtained after voluntary hyperventilation. To improve the power of the study in detecting possible abnormalities of cerebrovascular reactivity, two different measures were performed at 1 week intervals in migraine patients and controls. Reactivity index values during CO2 inhalation were significantly different ( p=0.01) among the three groups during the first and second measurements; in particular, lower values were found in patients suffering from migraine without aura with respect to controls ( p0.05). Our data suggest a reduced vasodilatory response to hypercapnia of cerebral arterioles in patients suffering from migraine without aura with respect to controls that might be related to baseline arteriolar vasodilation.

Cerebral blood flow was measured by transcranial Doppler sonography (TCD) in 15 patients during and after an attack of paroxysmal atrial fibrillation. During the attack the mean flow velocity (MFV) was reduced significantly in the middle cerebral artery (p < 0.05) and nonsignificantly in the other arteries. The pulsatility index (PI) was reduced in all the arteries but not significantly. During the fibrillation phase the MFV and PI tended to decrease as the heart rate increased. None of the patients showed clinical signs of cerebral ischemia during the attacks. The absence of such signs despite the reduced cerebral blood flow in atrial fibrillation is probably due to the activation of mechanisms of autoregulation.

The etiology of stroke in the young is different from that in older patients and remains unknown in almost one third of the cases. To gain further insight into both pathogenic and etiologic determinants, we prospectively studied a large number of consecutive young adults with focal cerebral ischemia. Three hundred thirty-three patients aged 15-44 years with transient ischemic attack or ischemic stroke within the 8 weeks before hospital admission were recruited and investigated by using a standardized protocol of clinical evaluation, blood tests, electrocardiography, echocardiography, chest roentgenography, and brain computed tomography. Presumed etiology was diagnosed by prospectively applied criteria. Women predominated (61%) among patients under 35 years of age, mainly due to the frequency of cerebral ischemia related to oral contraceptive use, while men outnumbered women (60%) among patients over that age because of a higher prevalence of atherothrombotic disease. Potential cerebral embolism of cardiac origin was the presumed cause of stroke in 23.7%, but conventional sources of emboli were found only in 7.5% of cases. There was a low prevalence of atrial fibrillation among young patients with cerebral ischemia. Mitral valve prolapse was found in 8.4%, as expected, predominantly (71.4%) among the younger patients. The prevalence of stroke over transient ischemic attack was proportional to the likelihood of cardiac embolism. Acute alcohol intoxication was considered a precipitating factor in only three patients. The percentages of cerebral ischemia attributed to arterial dissection (0.3%), oral contraceptive use in women (8.1%), migraine (1.2%), and other associated medical diseases (1.5%) were lower than reported in recent clinical series. Two different groups of pathogenic determinants predominate in younger women and in older men, supporting public health measures aimed at strict medical control of the recognized cerebrovascular risk factors.

7 patients with relapsing-remitting multiple sclerosis (MS) were subjected to an intensive course of intravenous (I.V.) cyclophosphamide (CY) therapy. All patients received induction therapy with 11 daily doses of 300 mg/m2 and then a single dose every six months for three years. After one year of follow-up all patients showed a decrease in relapse rate (0.57.57); in the two subsequent years of follow-up 2 patients showed a mild worsening while the others were clinically stable. As suggested by others, our results indicate that I.V. CY therapy may influence the clinical course of relapsing-remitting MS.

SYNOPSIS In a retrospective survey using a standardized format, 495 patients with “primary headaches” (classic migraine, common migraine, tension headaches, and mixed headaches) were questioned about the role of the seasons and of weather changes in influencing the frequency of their headache attacks. Seasonal influences were more prominent in migraine than in the other headache syndromes, and spring exacerbetions were particularly characteristic of classic migraine. On the other hand, rapid atmospheric variations (quick weather changes) were more potent as headache triggers in mixed headaches than in classic migraine or tension headaches. These differences assist in the delineation of classic migraine as an individual entity.

Background and Purpose —Stroke type in the young may influence the outcome and may have a dramatic impact on the quality of life in survivors. This study aimed to evaluate the incidence and prognosis of first-ever stroke in the young and to make comparisons with older patients within a well-defined population. Methods —All first-ever strokes occurring in the L’Aquila district, central Italy, were traced by active monitoring of inpatient and outpatient health services. Incidence rates were standardized to the 1996 European population according to the direct method. Long-term survival was estimated by the Kaplan-Meier method; outcome in survivors was evaluated by the modified Rankin scale. Results —Of 4353 patients who had a first-ever stroke, 89 patients 45 years of age were 2.4%, 13.3%, and 83.1%. Neuroimaging studies of the brain detected 14 intracranial aneurysms and 6 arteriovenous malformations in 20 of 38 patients (52.6%) with either subarachnoid (n=17) or intracerebral (n=3) hemorrhage. The crude annual incidence rate was 10.18/100 000 (95% CI, 8.14 to 12.57) and 10.23/100 000 when standardized to the 1996 European population. The 30-day case-fatality rate was 11.2% (95% CI, 6.2 to 19.4). Patients with subarachnoid hemorrhage had the highest proportion of good recovery (60%), patients with intracerebral hemorrhage had the highest mortality (44%), and patients with cerebral infarction had the highest proportion of severe disability (47%). Conclusions —Stroke patients