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

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

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-1 alpha, 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

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

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

Assessment of brain tissue viability under clinical circumstances

The growing body of clinical and instrumental information that can be gathered from the earliest phases of stroke has radically modified the way in which neurologists tackle the treatment of stroke patients. It is now theoretically possible to tailor therapeutic choices on the basis of prognostic estimates made within a few hours of stroke onset, that is at a time when numerous options to limit the ischemic insult are still open. However, once many hours or even days have passed, all one can do is witness the effects of a natural course which by then is virtually unmodifiable. This applies not only to stroke patients being treated within the context of pharmacological trials, but also to those in daily clinical management, since some choices, such as when and how to treat brain oedema and give thrombolytics, may now be made earlier and more accurately than in the past. Emergency CT in particular discloses important indices of subsequent clinical evolution and outcome, thus adding to already well-known predictors such as age and severity of neurological status at hospital admission [20]. CT does have the aforementioned limitations regarding inter-observer agreement, which may, however, be minimised by an appropriate training of observers. Moreover it has intrinsic limitations regarding the visualisation of the actual brain tissue damage, since up to one fifth of patients with no or very limited early CT signs may present symptomatic hemorrhagic transformation after thrombolysis [23] and approximately one sixth of early deteriorating patients do not show early CT signs [52]. Other techniques, such as positron and single photon emission tomography and in particular MR imaging, which may shed light on tissue viability and perfusion as well as arterial patency simultaneously, might be able to provide more accurate information [19] Nevertheless, CT is still the most widely used tool in clinical centres which hospitalise stroke patients, and is unlikely to be routinely replaced by the other imaging devices in the foreseeable future. Consequently, there is an urgent need both for a general consensus on the identification criteria of early CT signs and for the widest possible awareness of knowledge regarding CT capabilities among neurologists [47], waiting for the wide applicability of newer technologies

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

Pharmacological Neuroprotection in Stroke: Rationale, State of the art and Future Directions

Pharmacological Neuroprotection in Stroke: Rationale, State-of-the-art and Future Directions Ischemic brain damage develops at a pace slower than previously believed. In the penumbral area of the ischemic territory after focal ischemia, or in selectively vulnerable regions following transient global ischemia, cell death occurs hours or days following the acute insult. The process is the result of a complex cascade of pathogenic events, in which local and systemic factors play a role. Early and late excitotoxicity, apoptosis and inflammation have been found to contribute to the maturation of the damage. Mechanisms include calcium overload, oxidative stress, mitochondrial dysfunction, as well as damage to DNA, structural proteins and enzymes. Systemic factors include also inflammation and body temperature, as hypothermia has been shown to constitute a powerful neuroprotectant factor in experimental models of brain ischemia. Ischemic brain injury can be counteracted, totally or in part, by appropriate therapeutic interventions, resulting in varying degrees of neuroprotection in animal models. Although clinical trials based on neuroprotective agents have been disappointing, therapeutic strategies targeting recently identified pathogenic processes offer new hope. These approaches, alone or in combination with therapies based on early reperfusion of the ischemic brain, are likely to provide powerful tools for the treatment of human stroke

ERGOTAMINE-INDUCED HEADACHE CAN BE SUSTAINED BY SUMATRIPTAN DAILY INTAKE

We describe the case report of a migraine sufferer who developed ergotamine-induced headache and subsequently replaced ergotamine with daily sumatriptan (100 mg p.o.). The features of the headache were unchanged except for the presence of superimposed migraine-like headaches that occurred every 24 h