Cerebral hemodynamics and cognitive functions in the acute and subacute stage of mild ischemic stroke: a longitudinal pilot study.

The association between cerebral hemodynamics and cognitive impairment has been reported in neurodegenerative and cerebrovascular disorders (CVD). However, it is still unclear whether changes occur in the acute phase of CVD. Here we investigated cognitive and hemodynamic parameters and their association in patients with CVD during the acute and subacute phases. Seventy-three patients with mild stroke, not undergoing endovascular treatment, were recruited. All subjects were devoid of intracranial or external carotid stenosis, significant chronic cerebrovascular pathology, dementia or non-compensated cardiovascular diseases. Patients were evaluated within 7 days from symptoms onset (T1) and after 3 months (T2). Clinical and demographic data were collected. NIHSS, MoCA, FAB, and Word-Color Stroop test (WCST) were used to evaluate disease severity and cognitive functions. Basal hemodynamic parameters in the middle cerebral artery were measured with transcranial Doppler. Differences between T2 and T1, correlations between cognitive and hemodynamic variables at T1 and T2, as well as correlations between the T2-T1 variation in cognitive and hemodynamic parameters were assessed. At T1, cognitive performance of MoCA, FAB, and WCST was lower compared with T2; and pulsatility index, a parameter reflecting distal vascular resistance, was higher. However, no correlations between the changes in cognitive and hemodynamic variables were found; therefore, the two seems to be independent phenomena. In the acute phase, the linear association between cerebral blood flow and cognitive performances was lost, probably due to a differential effect of microenvironment changes and vascular-specific phenomena on cognition and cerebral hemodynamics. This relationship was partially restored in the subacute phase.

Early and sustained efficacy of fremanezumab over 24-weeks in migraine patients with multiple preventive treatment failures: the multicenter, prospective, real-life FRIEND2 study.

BACKGROUND: To verify the long-term (24-week) efficacy, safety, and tolerability of fremanezumab in real-life patients with high-frequency episodic migraine (HFEM: ≥ 8 days/month) or chronic migraine (CM: ≥ 15 days/month), and multiple preventive treatment failures. METHODS: This is a prospective, cohort, real-life study at 28 headache centers on consecutive patients affected by HFEM or CM with multiple preventive treatment failures who were prescribed subcutaneous fremanezumab (225 mg monthly/675 mg quarterly) for ≥ 24 weeks. Primary endpoint was the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM at weeks 21-24 compared to baseline. Secondary endpoints encompassed changes in monthly analgesic medications, ≥ 50%, ≥ 75%, and 100% responder rates, and variation in NRS, HIT-6 and MIDAS scores at the same time interval. Changes in MMDs/MHDs, monthly analgesic medications, ≥ 50%, ≥ 75%, and 100% responder rates, and variation in NRS and HIT-6 scores at week 4 were also monitored. RESULTS: Four hundred ten patients who had received ≥ 1 dose of fremanezumab were considered for safety analysis while 148 patients treated for ≥ 24 weeks were included in the efficacy analysis. At weeks 21-24, fremanezumab significantly (p < 0.001) reduced MMDs, MHDs, monthly analgesic medications and NRS, HIT-6, and MIDAS scores in both HFEM and CM compared to baseline. The proportions of ≥ 50%, ≥ 75% and 100% responders at weeks 21-24were 75.0%, 30.8%, 9.6% (HFEM), and 72.9, 44.8 and 1% (CM). A significant (p < 0.001) decrease in MMDs, MHDs, monthly analgesic medications and NRS, HIT-6, and MIDAS scores in both HFEM and CM was already present at week 4. The proportions of ≥ 50%, ≥ 75%, and 100% responders at week 4 were 67.6%, 32.4%, 11.8% (HFEM) and 67.3%, 40%, 1.8% (CM). CM remitted to episodic migraine and medication overuse to no-medication overuse in 83.3 and 75% of patients at week 24, and in 80 and 72.4% at week 4. Adverse events were rare (2.4%), mild and transient. No patient discontinued treatment for any reason. CONCLUSIONS: Fremanezumab is characterized by an early and sustained efficacy in HFEM and CM patients with multiple preventive treatment failures in real-life, revealing an optimal safety and tolerability profile.

The impact of cerebral vasomotor reactivity on cerebrovascular diseases and cognitive impairment.

The regulation of cerebral blood flow (CBF) is a complex and tightly controlled function ensuring delivery of oxygen and nutrients and removal of metabolic wastes from brain tissue. Cerebral vasoreactivity (CVR) refers to the ability of the nervous system to regulate CBF according to metabolic demands or changes in the microenvironment. This can be assessed through a variety of nuclear medicine and imaging techniques and protocols. Several studies have investigated the association of CVR with physiological and pathological conditions, with particular reference to the relationship with cognitive impairment and cerebrovascular disorders (CVD). A better understanding of the interaction between CVR and cognitive dysfunction in chronic and particularly acute CVD could help improving treatment and rehabilitation strategies in these patients. In this paper, we reviewed current knowledge on CVR alterations in the context of acute and chronic CVD and cognitive dysfunction. Alterations in CVR and hemodynamics have been described in patients with both neurodegenerative and vascular cognitive impairment, and the severity of these alterations seems to correlate with CVR derailment. Furthermore, an increased risk of cognitive impairment progression has been associated with alterations in CVR parameters and hemodynamics. Few studies have investigated these associations in acute cerebrovascular disorders and the results are inconsistent; thus, further research on this topic is encouraged.

Neurovascular Dysfunction in Alzheimer Disease: Assessment of Cerebral Vasoreactivity by Ultrasound Techniques and Evaluation of Circulating Progenitor Cells and Inflammatory Markers.

AIMS: The aims of this study were to assess vascular dysfunction in patients with Alzheimer disease (AD) by investigating cerebral vasomotor reactivity using transcranial Doppler ultrasound (TCD) and to evaluate any correlations between cerebral vasoreactivity and endothelium dysfunction. Moreover, the frequency of circulating progenitor cells (CPCs) and the blood concentration of vascular/inflammatory markers were evaluated. MATERIALS AND METHODS: We recruited 35 AD subjects and 17 age-matched, sex-matched, and education-matched healthy control subjects. Cerebral vasomotor reactivity was assessed by means of the TCD-based breath-holding index test (BHI). The level of CPCs was evaluated by means of flow cytometry from venous blood samples, while blood vascular/inflammatory markers were measured by means of enzyme-linked immunosorbent assay. RESULTS: Both cerebral assay blood flow velocity in the middle cerebral artery (MCAFV) and BHI values were significantly lower in AD subjects than in healthy controls (P<0.05). A positive trend was found between MCAFV and BHI values and Mini-Mental State Evaluation (MMSE) scores. Moreover, the hematopoietic progenitor cells' count was found to be lower in patients with AD than in controls (P<0.05). Finally, a significantly higher expression of the plasma chemokine CCL-2 was observed in AD patients than in healthy controls. CONCLUSIONS: Our results confirm that cerebral hemodynamic deterioration may be a critical marker of cognitive decline. Further studies are needed to investigate the role of circulating CPCs and chemokines as potential contributors to neurovascular dysfunction.

Orthostatic hypotension acutely impairs executive functions in Parkinson's disease.

Orthostatic hypotension is a frequent non-motor symptom of Parkinson's disease, with negative prognostic role on cognitive functions. Here we measured the acute effects of orthostatic hypotension on executive functions in Parkinson's disease patients devoid of hypertension, carotid artery stenosis, and significant chronic cerebrovascular pathology. Measurements were carried out during regular visits in outpatient setting. Twenty-eight Parkinson's disease patients were recruited and studied along scheduled outpatient visits. They were divided into two groups (n = 14 each) based on the presence or lack of orthostatic hypotension. This was diagnosed according to international guidelines. All patients were submitted to the Stroop's test and to the phonological and semantic verbal fluency test after 10-min resting in supine position and immediately upon standing in upright position. Testing lasted less than 5 min in either position. In upright position, subjects with orthostatic hypotension displayed significantly worse performances at the Stroop's test word reading time (22.1 ± 4.1 vs. 14.9 ± 4.0 s), interference time (56.1 ± 12.3 vs. 41.4 ± 11.8 s), and number of errors at the interference section (5.8 ± 3.2 vs. 1.3 ± 2.1) as compared to those without orthostatic hypotension. These results demonstrate that worsening of attentive function upon standing can be measured in Parkinson's disease patients with orthostatic hypotension during routine outpatient visits. These findings suggest that clinically asymptomatic orthostatic hypotension in Parkinson's disease patients may acutely worsen neuropsychological performances with possible negative impact on daily functioning.

Single-blind, randomized, pilot study combining shiatsu and amitriptyline in refractory primary headaches.

Complementary alternative medicine, such as shiatsu, can represent a suitable treatment for primary headaches. However, evidence-based data about the effect of combining shiatsu and pharmacological treatments are still not available. Therefore, we tested the efficacy and safety of combining shiatsu and amitriptyline to treat refractory primary headaches in a single-blind, randomized, pilot study. Subjects with a diagnosis of primary headache and who experienced lack of response to ≥2 different prophylactic drugs were randomized in a 1:1:1 ratio to receive shiatsu plus amitriptyline, shiatsu alone, or amitriptyline alone for 3 months. Primary endpoint was the proportion of patients experiencing ≥50%-reduction in headache days. Secondary endpoints were days with headache per month, visual analogue scale, and number of pain killers taken per month. After randomization, 37 subjects were allocated to shiatsu plus amitriptyline (n = 11), shiatsu alone (n = 13), and amitriptyline alone (n = 13). Randomization ensured well-balanced demographic and clinical characteristics at baseline. Although all the three groups improved in terms of headache frequency, visual analogue scale score, and number of pain killers (p < 0.05), there was no between-group difference in primary endpoint (p = ns). Shiatsu (alone or in combination) was superior to amitriptyline in reducing the number of pain killers taken per month (p < 0.05). Seven (19%) subjects reported adverse events, all attributable to amitriptyline, while no side effects were related with shiatsu treatment. Shiatsu is a safe and potentially useful alternative approach for refractory headache. However, there is no evidence of an additive or synergistic effect of combining shiatsu and amitriptyline. These findings are only preliminary and should be interpreted cautiously due to the small sample size of the population included in our study. Trial registration 81/2010 (Ethical Committee, S. Andrea Hospital, Sapienza University, Rome, Italy).

Early (≤ 1-h) vs. late (>1-h) administration of frovatriptan plus dexketoprofen combination vs. frovatriptan monotherapy in the acute treatment of migraine attacks with or without aura: a post hoc analysis of a double-blind, randomized, parallel group study.

The early use of triptan in combination with a nonsteroidal anti-inflammatory drug after headache onset may improve the efficacy of acute migraine treatment. In this retrospective analysis of a randomized, double-blind, parallel group study, we assessed the efficacy of early or late intake of frovatriptan 2.5 mg + dexketoprofen 25 or 37.5 mg (FroDex 25 and FroDex 37.5) vs. frovatriptan 2.5 mg alone (Frova) in the acute treatment of migraine attacks. In this double-blind, randomized parallel group study 314 subjects with acute migraine with or without aura were randomly assigned to Frova, FroDex 25, or FroDex 37.5. Pain free (PF) at 2-h (primary endpoint), PF at 4-h and pain relief (PR) at 2 and 4-h, speed of onset at 60, 90, 120 and 240-min, and sustained pain free (SPF) at 24-h were compared across study groups according to early (≤1-h; n = 220) or late (>1-h; n = 59) intake. PF rates at 2 and 4-h were significantly larger with FroDex 37.5 vs. Frova (early intake, n = 71 FroDex 37.5 and n = 75 Frova: 49 vs. 32 % and 68 vs. 52 %, p < 0.05; late intake, n = 20 Frodex 37.5, and n = 18 Frova: 55 vs. 17 %, p < 0.05 and 85 vs. 28 %, p < 0.01). Also with FroDex 25, in the early intake group (n = 74) PF episodes were significantly higher than Frova. PR at 2 and 4-h was significantly better under FroDex 37.5 than Frova (95 % vs. 50 %, p < 0.001, 100 % vs. 72 %, p < 0.05) in the late intake group (n = 21). SPF episodes at 24-h after early dosing were 25 % (Frova), 45 % (FroDex 25) and 41 % (FroDex 37.5, p < 0.05 combinations vs. monotherapy), whereas they were not significantly different with late intake. All treatments were equally well tolerated. FroDex was similarly effective regardless of intake timing from headache onset.

Comparison of frovatriptan plus dexketoprofen (25 mg or 37.5 mg) with frovatriptan alone in the treatment of migraine attacks with or without aura: a randomized study.

BACKGROUND: Drugs for migraine attacks include triptans and NSAIDs; their combination could provide greater symptom relief. METHODS: A total of 314 subjects with history of migraine, with or without aura, were randomized to frovatriptan 2.5 mg alone (Frova), frovatriptan 2.5 mg + dexketoprofen 25 mg (FroDex25) or frovatriptan 2.5 mg + dexketoprofen 37.5 mg (FroDex37.5) and treated at least one migraine attack. This was a multicenter, randomized, double-blind, parallel-group study. The primary end point was the proportion of pain free (PF) at two hours. Secondary end points were PF at one and four hours, pain relief (PR) at one, two, four hours, sustained PF (SPF) at 24 and 48 hours, recurrence at 48 hours, resolution of nausea, photophobia and phonophobia at two and four hours, the use of rescue medication and the judgment of the treatment. RESULTS: The results were assessed in the full analysis set (FAS) population, which included all subjects randomized and treated for whom at least one post-dose intensity of headache was recorded. The proportions of subjects PF at two hours (primary end point) were 29% (27/93) with Frova compared with 51% (48/95 FroDex25 and 46/91 FroDex37.5) with each combination therapies ( P < 0.05). Proportions of SPF at 24 hours were 24% (22/93) for Frova, 43% (41/95) for FroDex25 ( P < 0.001) and 42% (38/91) for FroDex37.5 ( P < 0.05). SPF at 48 hours was 23% (21/93) with Frova, 36% (34/95) with FroDex25 and 33% (30/91) with FroDex37.5 ( P = NS). Recurrence was similar for Frova (22%, 6/27), FroDex25 (29%, 14/48) and FroDex37.5 (28%, 13/46) ( P = NS), meaning a lack of improvement with the combination therapy. Statistical adjustment for multiple comparisons was not performed. No statistically significant differences were reported in the occurrence of total and drug-related adverse events. FroDex25 and FroDex37.5 showed a similar efficacy both for primary and secondary end points. There did not seem to be a dose response curve for the addition of dexketoprofen. CONCLUSION: FroDex improved initial efficacy at two hours compared to Frova whilst maintaining efficacy at 48 hours in this study. Tolerability profiles were comparable. Intrinsic pharmacokinetic properties of the two single drugs contribute to this improved efficacy profile.

Efficacy of early vs. late use of frovatriptan combined with dexketoprofen vs. frovatriptan alone in the acute treatment of migraine attacks with or without aura.

Early triptan use after headache onset may help improve the efficacy of acute migraine treatment. This may be particularly the case when triptan therapy is combined with a nonsteroidal anti-inflammatory drug (NSAID). The objective of this is to assess whether the combination of frovatriptan 2.5 mg + dexketoprofen 25 or 37.5 mg (FroDex25 and FroDex37.5) is superior to frovatriptan 2.5 mg alone (Frova) in the acute treatment of migraine attacks in patients who took the drug within 30 min from the onset of pain (early use) or after (late use). A total of 314 subjects with a history of migraine with or without aura were randomized into a double-blind, multicenter, parallel group, pilot study to Frova, FroDex25 or FroDex37.5 and were required to treat at least one migraine attack. In the present post hoc analysis, traditional migraine endpoints were compared across study drugs for subgroups of the 279 patients of the full analysis set according to early (n = 172) or late (n = 107) drug use. The proportion of patients pain free at 2 h in the early drug use subgroup was 33 % with Frova, 50 % with FroDex25 and 51 % with FroDex37.5 mg (p = NS combinations vs. monotherapy), while in the late drug use subgroup was 22, 51 and 50 % (p < 0.05 FroDex25 and FroDex37.5 vs. Frova), respectively. Pain-free episodes at 4 h were 54 % for early and 34 % for late use of Frova, 71 and 57 % with FroDex25 and 74 and 68 % with FroDex37.5 (p < 0.05 for early and p < 0.01 for late use vs. Frova). The proportion of sustained pain free at 24 h was 26 % under Frova, 43 % under FroDex25 mg and 40 % under FroDex37.5 mg (p = NS FroDex25 or 37.5 vs. Frova) in the early drug intake subgroup, while it was 19 % under Frova, 43 % under FroDex25 mg and 45 % under FroDex37.5 mg (p < 0.05 FroDex25 and FroDex37.5 vs. Frova) in the late drug intake subgroup. Risk of relapse at 48 h was similar (p = NS) among study drug groups (Frova: 25 %, FroDex25: 21 %, and FroDex37.5: 37 %) for the early as well as for the late drug use subgroup (14, 42 and 32 %). FroDex was found to be more effective than Frova taken either early or late. The intrinsic pharmacokinetic properties of the two single drug components made FroDex combination particularly effective within the 2-48-h window from the onset of the acute migraine attack. The efficacy does not seem to be influenced by the time of drug use relative to the onset of headache.

Assessing the Long-Term (48-Week) Effectiveness, Safety, and Tolerability of Fremanezumab in Migraine in Real Life: Insights from the Multicenter, Prospective, FRIEND3 Study.

INTRODUCTION: Long-term (1-year) fremanezumab treatment proved to be effective, safe, and well tolerated in individuals with migraine and < 2 medication clusters in a randomized controlled trial (RCT). We aimed to assess real-world evidence (RWE), long-term effectiveness, tolerability, and safety of fremanezumab in people with high-frequency episodic migraine (HFEM) or chronic migraine (CM) with > 3 treatment failures and various comorbidities. METHODS: A 48-week, prospective, multicenter (n = 26), cohort study assessed fremanezumab's effectiveness, safety, and tolerability in consecutive adults with HFEM or CM with > 3 treatment failures. Primary endpoint was variation from baseline in monthly migraine days (MMD) in HFEM and monthly headache days (MHD) in CM at weeks 45-48. Secondary endpoints were changes in monthly analgesic medications, Numerical Rating Scale (NRS), Headache Impact Test (HIT-6), and the Migraine Disability Assessment Scale (MIDAS) scores and ≥ 50%, ≥ 75%, and 100% responder rates. RESULTS: Of 533 participants who had received ≥ 1 fremanezumab dose, 130 were treated for ≥ 48 weeks and considered for effectiveness analysis. No participant missed any treatment dosage every other consecutive month during the 12-month period. PRIMARY ENDPOINT: fremanezumab significantly (p < 0.001) reduced both MMD (- 6.4) in HFEM and MHD (- 14.5) in CM. Secondary endpoints: a significant reduction (p < 0.001) was observed in monthly analgesic medications (HFEM - 6.0; CM -16.5), NRS (HFEM - 3.4; CM - 3.4), HIT-6 (HFEM - 16.9; CM - 17.9) and MIDAS score (HFEM - 50.4; CM - 76.6). The ≥ 50%, ≥ 75%, and 100% response rates to fremanezumab were 75.5%, 36.7%, and 2% in HFEM and 71.6%, 44.4%, and 3.7% in CM. Corresponding response rates were 60.5%, 37.2%, and 2.3% in individuals with psychiatric comorbidities, 74.2%, 50%, and 4.8% in CM with medication overuse, and 60.9%, 39.1%, and 4.3% in CM with medication overuse and psychiatric comorbidities. Mild and transient treatment-emergent adverse events occurred in 7.8% of the participants. No subject discontinued the treatment for any reason. CONCLUSION: This RWE study documents that long-term fremanezumab treatment is highly effective and remarkably well tolerated in subjects with HFEM or CM with multiple (> 3) therapeutic failures, even in the presence of concomitant medication overuse, psychiatric comorbidities, or both. The effectiveness-to-tolerability ratio appears to be better in RWE than in RCTs.

The impact of interferon beta and natalizumab on comorbid migraine in multiple sclerosis.

BACKGROUND: Some multiple sclerosis (MS)-specific therapies may exacerbate a comorbid migraine. Whereas data regarding the impact of interferon beta (IFNB) on this comorbidity have been reported, studies on the role of natalizumab (NTZ) are still lacking. PURPOSE: Our aim was to compare the impact of IFNB and NTZ on the frequency and disability of comorbid migraine in MS patients. METHODS: performed a longitudinal evaluation on MS patients with comorbid migraine previously assessed at our center and retested for the present study, by comparing data from 33 patients originally treated with IFNB and thereafter switched to NTZ vs 30 patients continued currently to receive IFNB. RESULTS: Longitudinal analysis showed a significant reduction of migraine frequency (from a mean value of 8.4 to 5.1 days per month; P = .034) and Migraine Disability Assessment Scale (MIDAS) score (from a mean value of 14.2 to 10.5; P = .045) in the subgroup patients switched from IFNB to NTZ but not in those remaining in the IFNB recipient, irrespective of level of fatigue, trait anxiety, depression, alexithymia, or other clinical variables. CONCLUSIONS: Our findings suggest that NTZ did not exacerbate comorbid migraine in MS patients and support the hypothesis that IFNB might represent an important trigger for migraine worsening.

Determinants of the severity of comorbid migraine in multiple sclerosis.

A high co-morbidity between multiple sclerosis (MS) and migraine has been reported, especially in young female patients affected by a relapsing-remitting (RR) course of MS. In this study, we aimed to elucidate the determinants of the severity of comorbid migraine in MS. Demographic, clinical and psychometric variables were collected from a cohort of 205 RR-MS patients regularly attending to an Italian outpatient MS Centre. Of them, 102 (49.8 %) were diagnosed as affected by comorbid migraine. About one-third of MS patients with comorbid migraine have asked the attending neurologist a specific anti-migraine treatment. Despite this, only few MS patients (10.8 %) reported a prior use of prophylactic drugs, and even fewer (2.9 %) took triptans as pain killers; these proportions were significantly lower when compared with those of a control group of 63 migraineurs subjects without MS (p < 0.0001 for both comparison). Factors associated with a moderate or severe disability (MIDAS grades III or IV) due to comorbid migraine in MS patients were the depressive state (OR = 4.294; p = 0.001), the anxiety trait (OR = 5.786; p = 0.004) and an ongoing IFNB treatment (OR = 2.337; p = 0.028). Likewise, depression (OR = 3.453; p = 0.048) and anxiety (OR = 4.582; p = 0.014) were both independent predictors for having a MIDAS grades of III or IV also in migraineurs subjects without MS. Investigating the determinants of migraine severity may allow a better management of MS patients with comorbid migraine. In these patients, a tailored therapeutic approach is warranted to improve their quality of life and reduce the burden of these two chronic and disabling conditions.

Zonisamide for migraine prophylaxis in topiramate-intolerant patients: an observational study.

BACKGROUND: Zonisamide, a sulfonamide analog, is an antiepileptic drug with mechanisms of action similar to topiramate. Because of its pharmacodynamic and pharmacokinetics profiles, zonisamide is also potentially suitable for migraine prevention. METHODS: Tolerability and effectiveness of zonisamide for migraine prophylaxis in patients with a good response to topiramate, but interrupting it for intolerable side effects, were evaluated in 34 patients. After a 1-month period of wash-out, patients were treated with zonisamide (up to a 100 mg/day dosage) for 6 consecutive months. RESULTS: Zonisamide was well tolerated, only 4 (12%) patients reported transient and tolerable side effects. Mean number of days with headache per month was reduced from 14.9 ± 5.3 during the wash-out period to 2.5 ± 0.6 after 6 months of zonisamide (P < .001). We observed a significant reduction in headache severity and disability, as assessed by visual analog scale and migraine disability assessment scale. Finally, when compared with the 1-month period prior to starting zonisamide, a reduced use of analgesics was recorded at the end of the follow-up. CONCLUSION: Our findings support the use of zonisamide as an alternative therapy for migraine prevention in patients with good response, but poor tolerance to topiramate.

The use of ID migraine™ questionnaire in patients with multiple sclerosis.

Primary headaches are underdiagnosed and undertreated in patients with multiple sclerosis (MS). The aim of our study was to investigate the possibility of using the ID migraine™ (ID-M) questionnaire to make a first-line diagnosis of migraine in subjects affected by MS. We consecutively recruited 144 patients regularly attending the MS Centre of S. Andrea Hospital in Rome. Results from ID-M were matched with diagnoses of a blind neurologist. According to the ICHD-II criteria, 77 (53.5%) patients were diagnosed as suffering from migraine. ID-M showed high sensitivity (91%) and specificity (94%) in identifying patients with migraine. ID-M was also able to discriminate patients affected by headache following interferon beta therapy, having only the 10% out of these patients a positive ID-M. The use of the ID-M as a screening test is warranted not only in the epidemiological research, but also to ensure a better clinical management of patients with MS.

Efficacy and tolerability of pregabalin as preventive treatment for migraine: a 3-month follow-up study.

Migraine is a common neurological disorder and epidemiological studies have documented its high social and economic impact. Unfortunately, preventive treatment is often insufficient to substantially reduce migraine frequency or it is not well tolerated. Antiepileptic drugs are increasingly used in migraine prevention. However, data on efficacy and tolerability of pregabalin in patients with migraine are still lacking. Our aim was to evaluate efficacy and tolerability of pregabalin in patients with migraine. We recruited 47 patients who started pregabalin at 75 mg/day, which was titrated to 300 mg/day as tolerated. A total of six patients (13%) reported one or more side effects during the intake of pregabalin; however, three of them discontinued pregabalin, because side effects were intolerable and persistent. Statistically significant reduction in migraine frequency compared to baseline (p < 0.001) was evident after 1 and 3 months of treatment. A greater frequency reduction was observed in those patients who increased the dosage within the first month of therapy. Our data suggest that pregabalin may be well tolerated and may represent an alternative preventive treatment in migraneurs. Limitations of the present study were a small sample size and an uncontrolled, open-label design; further randomized case-control studies are warranted to confirm our findings.

Asymmetric posterior reversible encephalopathy syndrome in patient with hyperplastic anterior choroidal artery.

We describe a case of asymmetric PRES due to the presence of hyperplastic anterior choroidal artery (AChA) in a man affected by sever hypertension. Posterior reversible encephalopathy syndrome (PRES) has become synonymous with a unique pattern of brain vasogenic edema and predominates in the parietal and occipital regions, accompanied by clinical neurological alterations. Sever hypertension is a risk factor that exceeds the limits of brain autoregulation, leading to breakthrough brain edema. In our knowledge this is the first case reported in literature, in which a similar vascular abnormality is linked to a PRES syndrome.

Multi-Center Randomized Phase II Clinical Trial on Remote Ischemic Conditioning in Acute Ischemic Stroke Within 9 Hours of Onset in Patients Ineligible to Recanalization Therapies (TRICS-9): Study Design and Protocol.

Aim: To assess the efficacy of remote ischemic conditioning (RIC) in patients with ischemic stroke within 9 h of onset, that are not candidates for recanalization therapies. Sample Size Estimates: A sample size of 80 patients (40 in each arm) should yield 80% power to detect a 20% difference in early neurological improvement at 72 h at p = 0.05, two sided. Methods and Design: TRICS-9 is a phase II, multicenter, controlled, block randomized, open-label, interventional clinical trial. Patients recruited in Italian academic hospitals will be randomized 1:1 to either RIC plus standard medical therapy or standard medical therapy alone. After randomization, RIC will be applied manually by four alternating cycles of inflation/deflation 5 min each, using a blood pressure cuff around the non-paretic arm. Study Outcomes: The primary efficacy outcome is early neurological improvement, defined as the percent change in the National Institute of Health Stroke Scale (NIHSS) at 72 h in each arm. Secondary outcomes include early neurologic improvement at 24 and 48 h, disability at 3 months, rate of symptomatic intracerebral hemorrhage, feasibility (proportion of patients completing RIC), tolerability after RIC and at 72 h, blood levels of HIF-1α, and HSP27 at 24 h and 72 h. Discussion/Conclusion: RIC in combination with recanalization therapies appears to add no clinical benefit to patients, but whether it is beneficial to those that are not candidates for recanalization therapies is still to be demonstrated. TRICS-9 has been developed to elucidate this issue. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04400981.

Chronic cerebral hypoperfusion: An undefined, relevant entity.

Despite the large body of data available, chronic cerebral hypoperfusion lacks an operative definition. In a tautological way, the term hypoperfusion is being referred to conditions of "inadequate blood flow", "defects of perfusion" or "dysfunction of autoregulation". The chronicity refers to sustained conditions or wavering states characterized by repeated phases of inefficient functional hyperemia. The phenomenon may affect the whole brain or defined areas. A few defined clinical disorders, including heart failure, hypotension, atherosclerosis of large or small vessels and carotid stenosis are thought to cause progressive brain disorders due to chronic hypoperfusion. The clinical relevance manifests mostly as neurocognitive disorders associated with neuroimaging changes.The available data support a conceptual framework that considerschronic cerebral hypoperfusiona likely, relevant pathogenic mechanism for the neurodegeneration-like progression of the neurocognitive disorders. The relationship between neuropathology, cerebral perfusion, and symptoms progression is, however, elusive for several aspects. Typical microangiopathy findings, such as MRI white matter hyperintensities, may appear in individuals without any cerebrovascular risk or vascular lesions. Pathology features of the MRI changes, such as demyelination and gliosis, may result from dysfunction of the neuro-vascular unit not directly associated withvascular mechanisms. In this review, we aim to overview the most common clinical conditions thought to reflect chronic hypoperfusion.

Effect of OSAS on cerebral vasoreactivity and cIMT before and after CPAP treatment.

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) has been shown to be an important risk factor for ischaemic cerebral disease. Specific Doppler parameters may be used to measure cerebral vascular dynamics opening the door to new markers/predictors of risk. The objective of our study was to shed light on how the treatment of OSA with continuous positive airway pressure (CPAP) may have an impact on these parameters and, consequently, lower the risk of cerebral ischemic events in these patients. METHODS: A total of 40 untreated patients diagnosed with moderate to severe obstructive sleep apnoea were submitted to a comprehensive ultrasonographic transcranial Doppler evaluation. The parameters measured were: Breath holding index (BHI), mean blood flow velocity (MBFV) and pulsatility index in middle cerebral artery. Colour Doppler ultrasound was also used to measure carotid intima-media thickness (cIMT). These parameters were compared before and after CPAP treatment. RESULTS: After CPAP treatment, MBFV and BHI were shown to be increased (without statistical significance), while cIMT and polysomnographic parameters were significantly decreased. CONCLUSION: The improvement of cerebral vasoreactivity parameters and cIMT after long-term CPAP treatment suggest that treatment of OSA may influence the cerebral vascular regulation and consequently reduce the risk of stroke.