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Background Parkinson's disease (PD) is the second most common progressive neurodegenerative disease. In the advanced stages, the continuous delivery of levodopa (LD) as levodopa-carbidopa intestinal gel (LCIG) has demonstrated significant improvement of motor and nonmotor complications and improvement of the patients' quality of life (QoL). Despite the growing global experience with this treatment, anumber of unsolved practical issues remain, and currently, the data on the reasons that can lead to the discontinuation of LCIG are scarce. Objective In the present study, we aimed to analyze the causes that led to the discontinuation of LCIG therapy. Methods In this retrospective study, after 10 years of experience with LCIG as a therapeutic option in advanced PD, we analyzed the data of all dropout cases among the 204 patients that initiated LCIG therapy in two Romanian centers. Results Of the 204 patients enrolled, 43 patients dropped out. Disease duration until LCIG infusion was significantly longer (11.67±4.98 vs 9.44±3.44) and the overall clinical picture more sever (both regarding motor symptoms and cognitive decline) in dropout patients (compared to patients who continued treatment). The dropout patients also presented significant differences regarding the incidence of polyneuropathy (32.5% vs 11.18%). The main cause of discontinuation was death. Conclusion The causes of discontinuation from LCIG therapy in Romanian patients are similar to those from other centers; however, the rate of dropouts is somewhat lower. The clinician's experience in selecting and treating the patients in advanced stages of PD can increase therapeutic adherence. Also, the presence of a well-trained caregiver along with the availability of a proper aftercare system is mandatory for maintaining the long-term benefits of the therapy and the overall best outcome possible. Targeted prospective studies are needed to confirm whether a more severe stage of the disease and cognitive impairment at the time of initiation, respectively, the association of polyneuropathy can be considered as predictive factors for dropout.

ObjectiveTo assess the association of baseline imaging markers of cerebral small vessel disease (SVD) and brain frailty with clinical outcome after acute stroke in the Efficacy of Nitric Oxide in Stroke (ENOS) trial.MethodsENOS randomized 4,011 patients with acute stroke (ResultsIn all participants and those with lacunar syndrome (LACS; 1,397, 34.8%), baseline CT imaging features of SVD and brain frailty were common and independently associated with unfavorable shifts in mRS score at day 90 (all participants: SVD score odds ratio [OR] 1.15, 95% confidence interval [CI] 1.07–1.24; brain frailty score OR 1.25, 95% CI 1.17–1.34; those with LACS: SVD score OR 1.30, 95% CI 1.15–1.47, brain frailty score OR 1.28, 95% CI 1.14–1.44). Brain frailty was associated with worse cognitive scores at 90 days in all participants and in those with LACS.ConclusionsBaseline imaging features of SVD and brain frailty were common in lacunar stroke and all stroke, predicted worse prognosis after all acute stroke with a stronger effect in lacunar stroke, and may aid future clinical decision-making.IdentifierISRCTN99414122.

Background There is insufficient data in the literature regarding the real-life, daily clinical practice evaluation of patients with advanced Parkinson's disease (APD). We are not sure what is the upper limit of dopaminergic medication, especially the levodopa (LD) dosage, and how it is influenced by access and suitability to the various add-on and device-aided therapies (DAT). Objective This retrospective study explored the profile of APD patients that were considered and systematically evaluated regarding the suitability for DAT. Methods We analyzed the data from 311 consecutive patients with APD hospitalized between 2011 and 2017 that 1) described at least 2 hrs/day off periods divided into at least two instances/day (except early morning akinesia), 2) were in stage 3 or above on the Hoehn and Yahr scale, 3) were with or without dyskinesia, and 4) received at least four levodopa doses/day combined with adjuvant therapy. Results Of the 311 patients enrolled initially, 286 patients showed up for the second visit, of which in 125 cases we assessed that DAT would be necessary. Finally, 107 patients were tested in our clinic to confirm the efficacy of LCIG. Patients selected for DAT had significantly longer off periods, more frequent dyskinesia, early morning akinesia, and freezing despite having significantly higher LD doses than those with an improved conservative therapy. Conclusion Patients with APD can have a variety of symptoms, and because symptoms and therapeutical efficacy can be manifested in many different combinations, it is not possible to decide using a single, rigid set of criteria which APD patient is eligible for DAT. Nevertheless, treating physicians should refer APD patients to a specialized movement disorder center when patients with an average daily dose of LD of at least 750-1000 mg and maximal complementary therapies present daily motor complications that significantly reduce the quality of life.

Depressive disorders are among the most important health problems and are predicted to constitute the leading cause of disease burden by the year 2030. Aside significant impact on quality of life, psychosocial well-being and socioeconomic status of affected patients, depression is associated with impaired cardiovascular health and increased mortality. The link between affective and cardiovascular disease has largely been attributed to dysregulation of the autonomic nervous system resulting in a chronic shift toward increased sympathetic and decreased parasympathetic activity and, consecutively, cardiac dysautonomia. Among proposed surrogate parameters to capture and quantitatively analyze this shift, heart rate variability (HRV) and baroreflex sensitivity have emerged as reliable tools. Attenuation of these parameters is frequently seen in patients suffering from depression and is closely linked to cardiovascular morbidity and mortality. Therefore, diagnostic and therapeutic strategies were designed to assess and counteract cardiac dysautonomia. While psychopharmacological treatment can effectively improve affective symptoms of depression, its effect on cardiac dysautonomia is limited. HRV biofeedback is a non-invasive technique which is based on a metronomic breathing technique to increase parasympathetic tone. While some small studies observed beneficial effects of HRV biofeedback on dysautonomia in patients with depressive disorders, larger confirmatory trials are lacking. We reviewed the current literature on cardiac dysautonomia in patients suffering from depression with a focus on the underlying pathophysiology as well as diagnostic workup and treatment.

Abstract: Introduction: The motor and non-motor complications of Parkinson’s disease impair the patients’ quality of life and limit therapeutical options. There are no clear criteria for ‘advanced’ Parkinson’s disease or for the optimal moment for invasive therapies. There is little evidence regarding the upper limits of levodopa doses, and how these may be influenced by the availability of device-aided therapies. Aim: To analyze substitution therapy in patients with advanced Parkinson’s disease. Method: In our retrospective study, we analyzed the data from all patients with advanced Parkinson’s disease hospitalized between 1st June 2011 and 31st May 2017, receiving combined levodopa treatment at least 4×/day, reporting a minimum of 2 hours off periods, with or without dyskinesia. We analyzed levodopa therapy for patients who were recommended either device-aided or conservative therapy. Results: Out of 311 patients with advanced Parkinson’s disease, for 125 we proposed device-aided therapies whereas in 42 patients we increased the levodopa dose. The average levodopa doses and the administration rate were higher for the 107 patients tested for levodopa-carbidopa intestinal gel. Disease duration, mean levodopa doses and frequency of dosing were all higher in patients proposed for device-aided therapies versus patients with continued conservative treatment. Conclusion: Our patients were on lower levodopa doses (compared to literature), but the combinations were used more often. Device-aided therapies should be considered in patients with severe motor complications who receive at least 750–1000 mg levodopa daily, divided minimum 5×/day. These patients need to be tested in specialized centers by multidisciplinary teams in order to make the best decision for further action. Orv Hetil. 2019; 160(17): 662–669.

Background: In the advanced stages of Parkinson’s disease (APD), complex forms of dyskinesia may severely impair the patient’s quality of life. Objective: In the present study, we aimed to analyze the evolution under LCIG therapy of the most important motor fluctuations and complex disabling dyskinesias, including diphasic dyskinesia. Methods: In this retrospective study, we analyzed the characteristics of patients with APD who had at least 30 min of diphasic dyskinesia (DID) in 3 consecutive days, were considered responders and were treated with LCIG in our clinic. Patients were evaluated before and after PEG and at 6, 12 and 18 months, when the changes in the therapy were recorded, and they completed a 7-point Global Patient Impression of Improvement (PGI-I) scale. Results: Forty patients fulfilled the inclusion criteria—out of which, 34 performed all visits. There was a substantial difference between the calculated and real LCIG (1232 ± 337 mg vs. 1823 ± 728 mg). The motor fluctuations and most dyskinesias improved significantly after starting LCIG, but an increasing number of patients needed longer daily administrations of LCIG (24 instead of 16 h). Conclusions: Patients with APD with complex dyskinesias must be tested in dedicated hospitals, and they need a special therapeutic approach. The properly adapted LCIG treatment regarding the dose and time of administration completed with well-selected add-on medication should offer improvement for patients who want to or can only choose this DAT vs. others.

Creutzfeldt–Jacob disease is a progressive and ultimately fatal disease, representing one of the most common forms of prion diseases. It is a rare pathology presenting with various symptomatology, and the fact that a definite diagnosis can be obtained solely by neuropathological techniques makes it hard to recognize and diagnose. Here we present the clinical and neuropathological features of a 72-year-old woman, who originally presented in a county hospital, then, along with the disease progression, got transferred to a university center in Romania, where CJD-specific tests are rarely performed, and ultimately was diagnosed with the help of international collaboration. The purpose of this case report and review is to summarize the Romanian CJD situation until the present day, to place the Romanian CJD epidemiology in an Eastern European context, and to highlight the diagnostic options and possibilities for clinical practitioners. We would also like to draw attention to the need for a national surveillance system. By presenting the patient’s route in Romania from the first presentation to diagnosis, we would like to emphasize the importance of interdisciplinary and international collaboration, by which we managed to cross the regional diagnostic boundaries and create a possible diagnostic pathway for future cases.

IntroductionNitrate-induced headache is common and may signify responsive cerebral vasculature. We assessed the relationship between nitrate headache and outcome in patients with acute stroke.Materials and methodsPatients were those randomised to glyceryl trinitrate (GTN) versus no GTN in the efficacy of nitric oxide in stroke trial. Development of headache by end of treatment (day 7), and functional outcome (modified Rankin Scale, primary outcome) at day 90, were assessed. Analyses are adjusted for baseline prognostic factors and give OR and mean difference (MD) with 95% CI.ResultsIn 4011 patients, headache was more common in GTN than control (360, 18.0% vs 170, 8.5%; pDiscussion and conclusionDevelopment of a nitrate headache by day 7 after stroke may be associated with improved activities of daily living and cognitive impairment at day 90, which was not seen with non-nitrate headache.

WOS: 000469346800032, PubMed: 30626285, Background and Purpose-Increased blood pressure (BP), heart rate, and their derivatives (variability, pulse pressure, rate-pressure product) are associated with poor clinical outcome in acute stroke. We assessed the effects of glyceryl trinitrate (GTN) on hemodynamic parameters and these on outcome in participants in the ENOS trial (Efficacy of Nitric Oxide in Stroke). Methods-Four thousand and eleven patients with acute stroke and raised BP were randomized within 48 hours of onset to transdermal GTN or no GTN for 7 days. Peripheral hemodynamics were measured at baseline (3 measures) and daily (2 measures) during treatment. Between-visit BP variability over days 1 to 7 (as SD) was assessed in quintiles. Functional outcome was assessed as modified Rankin Scale and cognition as telephone mini-mental state examination at day 90. Analyses were adjusted for baseline prognostic variables. Data are mean difference or odds ratios with 95% CI. Results-Increased baseline BP (diastolic, variability), heart rate, and rate-pressure product were each associated with unfavorable functional outcome at day 90. Increased between-visit systolic BP variability was associated with an unfavourable shift in modified Rankin Scale (highest quintile adjusted odds ratio, 1.65; 95% CI, 1.37-1.99), worse cognitive scores (telephone mini-mental state examination: highest quintile adjusted mean difference, -2.03; 95% CI, -2.84 to -1.22), and increased odds of death at day 90 (highest quintile adjusted odds ratio, 1.57; 95% CI, 1.12-2.19). GTN lowered BP and rate-pressure product and increased heart rate at day 1 and reduced between-visit systolic BP variability. Conclusions-Increased between-visit BP variability was associated with poor functional and cognitive outcomes and increased death 90 days after acute stroke. In addition to lowering BP and rate-pressure product, GTN reduced betweenvisit systolic BP variability. Agents that lower BP variability in acute stroke require further study., British United Provident Association UK Foundation; National Institute for Health Research TARDIS [10/104/24]; British Heart Foundation RIGHT-2 (Rapid Intervention With Glyceryl Trinitrate in Hypertensive Stroke Trial 2) [CS/14/4/30972]; Medical Research CouncilMedical Research Council UK (MRC) [G0501797], ENOS (Efficacy of Nitric Oxide in Stroke) was funded by the British United Provident Association UK Foundation and Medical Research Council (G0501797). J.P. Appleton is funded by National Institute for Health Research TARDIS (10/104/24) trial (Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke) and British Heart Foundation RIGHT-2 (Rapid Intervention With Glyceryl Trinitrate in Hypertensive Stroke Trial 2; CS/14/4/30972).

Background Parkinson’s disease (PD) is the second most common progressive neurodegenerative disease. In the advanced stages, the continuous delivery of levodopa (LD) as levodopa-carbidopa intestinal gel (LCIG) has demonstrated significant improvement of motor and nonmotor complications and improvement of the patients’ quality of life (QoL). Despite the growing global experience with this treatment, anumber of unsolved practical issues remain, and currently, the data on the reasons that can lead to the discontinuation of LCIG are scarce. Objective In the present study, we aimed to analyze the causes that led to the discontinuation of LCIG therapy. Methods In this retrospective study, after 10 years of experience with LCIG as a therapeutic option in advanced PD, we analyzed the data of all dropout cases among the 204 patients that initiated LCIG therapy in two Romanian centers. Results Of the 204 patients enrolled, 43 patients dropped out. Disease duration until LCIG infusion was significantly longer (11.67±4.98 vs 9.44±3.44) and the overall clinical picture more sever (both regarding motor symptoms and cognitive decline) in dropout patients (compared to patients who continued treatment). The dropout patients also presented significant differences regarding the incidence of polyneuropathy (32.5% vs 11.18%). The main cause of discontinuation was death. Conclusion The causes of discontinuation from LCIG therapy in Romanian patients are similar to those from other centers; however, the rate of dropouts is somewhat lower. The clinician’s experience in selecting and treating the patients in advanced stages of PD can increase therapeutic adherence. Also, the presence of a well-trained caregiver along with the availability of a proper aftercare system is mandatory for maintaining the long-term benefits of the therapy and the overall best outcome possible. Targeted prospective studies are needed to confirm whether a more severe stage of the disease and cognitive impairment at the time of initiation, respectively, the association of polyneuropathy can be considered as predictive factors for dropout.

Abstract: Introduction: Selective monoamine oxidase B inhibitors have an accurate place in therapeutical strategy of Parkinsons’s disease. In the early stages of the disease, especially in younger patients with milder symptoms, the introduction of levodopa substitution could be efficacious in delaying; in advanced stages they are mainly used to treat motor complications, as an adjunct to levodopa. Aim: The evaluation of therapeutical strategies used in the neurology clinics of Tirgu Mures County Emergency Clinical Hospital in order to define the role of monoamine oxidase B inhibitors. Method: This retrospective study includes all records of patients with Parkinson’s disease hospitalized between 1 January 2003 and 31 December 2016. From the 2194 reports we used data focusing on the therapeutic recommendations. Regarding disease duration, we divided the patients in two groups: less than or equal to 5 years and more than 5 years. Results: From the 1183 patients in first group, 243 received monoamine oxidase inhibitors: 12 as monotherapy, 52 together with dopamine agonists, in 61 cases combined with levodopa. In 118 cases monoamine oxidase inhibitors were combined with levodopa and dopamine agonists. From 582 cases whith Parkinson’s disease for more than 5 years, 195 received monoamine oxidase B inhibitors (selegiline: 10 cases, rasagiline: 185 cases). In 429 cases we did not find accurate data regarding disease duration (selegiline: 5 cases, rasagiline: 93 cases). Conclusion: The use of monoamine oxidase B inhibitors was similar to those found in literature. The treating physicians should utilise more confidently the available therapeutical combinations. Orv Hetil. 2017; 158(51): 2023–2028.

Introduction In patients older than 70 years there is no valid alternative to progressively introduced substitution therapy. The antiparkinsonian drugs introduced in the last decade to treat Parkinson’s disease, especially in its early phases, promised a comparable efficacy in reducing symptoms to levodopa. In younger patients and/or patients with mild symptoms we hoped to delay the motor complications by postponing the start of levodopa therapy. While these assumptions may not be true for all patients, probably the most important current challenge is the optimal starting moment of levodopa therapy. The aim of the study was to analyze the therapeutical choices during the early phase of Parkinson’s disease in the Neurological Departments of Târgu Mures¸ County Hospital. Materials and methods We examined data obtained from hospitalized Parkinson’s disease patients during a 15-year period. According to the duration of the disease we split the patients into two groups, patients with Parkinson’s disease for less than or equal to 5 years and patients with disease duration longer than 5 years, and then analyzed only the former group. Results During the examined period, 2,379 patients with Parkinson’s disease were hospitalized, and 1,237 patients had a disease duration shorter than 5 years. In this group, 18 patients had monoamine oxidase inhibitor monotherapy. Also, 665 patients received dopamine agonists, in 120 cases as monotherapy and in 83 patients associated with monoamine oxidase inhibitors. In 521 patients we found only levodopa treatment. A further 481 patients received combined therapy (levodopa with dopamine agonists and/or monoamine oxidase inhibitors). Conclusion Treatment strategies for the early stages of Parkinson’s disease in our group were comparable to results from other studies. However, the authors feel that neurologists should use levodopa-sparing drugs with greater courage. Furthermore, if the clinical context is appropriate, physicians should combine substitution therapy with other antiparkinsonian drugs in order to reduce levodopa doses.

Neuropsychiatric and cognitive symptoms are common in Parkinson’s disease (PD) and may precede and exceed motor symptoms as major factors impacting disease course and quality of life. Neuropsychiatric symptoms (NPS) in PD are various and are attributed to pathologic changes within multiple brain regions, to psychological stress, and to adverse effects of dopamine replacement therapy. Sleep disorders and mood symptoms such as apathy, depression, and anxiety may antedate the development of motor symptoms by years, while other NPS such as impulse control disorders, psychosis, and cognitive impairment are more common in later stages of the disease. Few studies report on NPS in the early, untreated phase of PD. We reviewed the current literature on NPS in PD with a focus on the early, drug-naive stages of PD. Among these early disease stages, premotor and early motor phases were separately addressed in our review, highlighting the underlying pathophysiological mechanisms as well as epidemiological characteristics, clinical features, risk factors, and available techniques of clinical assessment.

WOS: 000367136500008, PubMed: 26645254, Background and Purpose The Efficacy of Nitric Oxide in Stroke (ENOS) trial found that transdermal glyceryl trinitrate (GTN, a nitric oxide donor) lowered blood pressure but did not improve functional outcome in patients with acute stroke. However, GTN was associated with improved outcome if patients were randomized within 6 hours of stroke onset. Methods In this prespecified subgroup analysis, the effect of GTN (5 mg/d for 7 days) versus no GTN was studied in 629 patients with intracerebral hemorrhage presenting within 48 hours and with systolic blood pressure 140 mm Hg. The primary outcome was the modified Rankin Scale at 90 days. Results Mean blood pressure at baseline was 172/93 mm Hg and significantly lower (difference -7.5/-4.2 mm Hg; both P0.05) on day 1 in 310 patients allocated to GTN when compared with 319 randomized to no GTN. No difference in the modified Rankin Scale was observed between those receiving GTN versus no GTN (adjusted odds ratio for worse outcome with GTN, 1.04; 95% confidence interval, 0.78-1.37; P=0.84). In the subgroup of 61 patients randomized within 6 hours, GTN improved functional outcome with a shift in the modified Rankin Scale (odds ratio, 0.22; 95% confidence interval, 0.07-0.69; P=0.001). There was no significant difference in the rates of serious adverse events between GTN and no GTN. Conclusions In patients with intracerebral hemorrhage within 48 hours of onset, GTN lowered blood pressure was safe but did not improve functional outcome. Very early treatment might be beneficial but needs assessment in further studies., Bupa UK Foundation; Medical Research CouncilMedical Research Council UK (MRC) [G0501797]; Agency for Science, Technology and Research (Singapore)Agency for Science Technology & Research (ASTAR); Hypertension Trust (United Kingdom); Queen Elizabeth II Health Sciences Centre Research Fund (Canada); Reichstadt family (United Kingdom); Medical Research CouncilMedical Research Council UK (MRC) [MR/K026992/1]; National Institute for Health ResearchNational Institute for Health Research (NIHR) [NF-SI-0611-10003], Efficacy of Nitric Oxide in Stroke (ENOS) was funded by the Bupa UK Foundation and Medical Research Council (G0501797). Other funders, who supported the trial, were the Agency for Science, Technology and Research (Singapore), Hypertension Trust (United Kingdom), Queen Elizabeth II Health Sciences Centre Research Fund (Canada), and Reichstadt family (United Kingdom).

WOS: 000427517600005, PubMed: 28770403, at day Post-stroke dysphagia is common, associated with poor outcome and often requires non-oral feeding/fluids. The relationship between route of feeding and outcome, as well as treatment with glyceryl trinitrate (GTN), was studied prospectively. The Efficacy of Nitric Oxide in Stroke (ENOS) trial assessed transdermal GTN (5 mg versus none for 7 days) in 4011 patients with acute stroke and high blood pressure. Feeding route (oral = normal or soft diet; non-oral = nasogastric tube, percutaneous endoscopic gastrostomy tube, parenteral fluids, no fluids) was assessed at baseline and day 7. The primary outcome was the modified Rankin Scale (mRS) measured 90. At baseline, 1331 (33.2%) patients had non-oral feeding, were older, had more severe stroke and more were female, than 2680 (66.8%) patients with oral feeding. By day 7, 756 patients had improved from non-oral to oral feeding, and 119 had deteriorated. Non-oral feeding at baseline was associated with more impairment at day 7 (Scandinavian Stroke Scale 29.0 versus 43.7; 2p < 0.001), and worse mRS (4.0 versus 2.7; 2p < 0.001) and death (23.6 versus 6.8%; 2p = 0.014) at day 90. Although GTN did not modify route of feeding overall, randomisation ae6 h of stroke was associated with a move to more oral feeding at day 7 (odds ratio = 0.61, 95% confidence intervals 0.38, 0.98; 2p = 0.040). As a proxy for dysphagia, non-oral feeding is present in 33% of patients with acute stroke and associated with more impairment, dependency and death. GTN moved feeding route towards oral intake if given very early after stroke., Medical Research CouncilMedical Research Council UK (MRC) [G0501797]; Bupa Foundation; Medical Research CouncilMedical Research Council UK (MRC); Stroke Association, This work was supported by the Medical Research Council [grant number G0501797]. ENOS was funded by the Bupa Foundation and Medical Research Council, and supported by the Stroke Association. PMB is a Stroke Association Professor of Stroke Medicine, and a NIHR Senior Investigator. No GTN manufacturer was involved in the trial.

Author(s): Szatmari, Szabolcs; Bereczki, Daniel; Fornadi, Katalin; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P; Molnar, Miklos Z | Abstract: Study objectivesThe association between restless legs syndrome (RLS) and Parkinson's disease (PD) has been extensively studied with inconclusive results; therefore, we prospectively examined the associations of the presence of RLS with development of incident PD.MethodsFrom a nationally representative prospective cohort of almost 3.5 million US veterans (age: 60 ± 14 years, 93% male, median follow-up time of 7.8 years [interquartile range: 6.4-8.4 years]), we created a propensity-matched cohort of 100882 PD-free patients and examined the association between prevalent RLS and incident PD. This association was also assessed in the entire cohort. Associations were examined using Cox models.ResultsThere were 68 incident PD events (0.13%, incidence rate 1.87 [1.48-2.37]/10000 patient-years) in the RLS-negative group, and 185 incident PD events (0.37%, incidence rate 4.72 [4.09-5.45]/10000 patient-years) in the RLS-positive group in the propensity-matched cohort. Prevalent RLS was associated with more than twofold higher risk of incident PD (hazard ratio [HR]: 2.57, 95% confidence interval [CI]: 1.95-3.39) compared to RLS-negative patients. Qualitatively similar results were found when we examined the entire 3.5 million cohort: Prevalent RLS was associated with more than twofold higher risk of incident PD (multivariable adjusted HR: 2.81, 95%CI: 2.41-3.27).ConclusionRLS and PD share common risk factors. In this large cohort of US veterans, we found that prevalent RLS is associated with higher risk of incident PD during 8 years of follow-up, suggesting that RLS could be an early clinical feature of incident PD.

Background and Purpose— Mannitol is used worldwide to treat acute stroke, although its efficacy and safety have not been proven by randomized trials. Methods— In a tricenter, prospective study, we analyzed the 30-day and 1-year case fatality with respect to mannitol treatment status in 805 patients consecutively admitted within 72 hours of stroke onset. Confounding factors were compared between treated and nontreated patients. Results— Two thirds of the patients received intravenous mannitol as part of their routine treatment (mean dose, 47±22 g/d; mean duration, 6±3 days). The case fatality was 25% versus 16% ( P =0.006) at 30 days and 38% versus 25% ( P P =0.044). Although the prognostic scores of the Scandinavian Neurological Stroke Scale were similar in treated and nontreated patients, both in ischemic and hemorrhagic strokes, the patient groups differed in several factors that might also have influenced survival. Conclusions— Based on the results of this study, no recommendations can be made on the use of mannitol in acute stroke, and properly randomized, controlled trials should be performed to come to a final conclusion.

Temporal arteritis (TA), also known as giant cell arteritis, is a chronic vasculitis of medium and large-sized blood vessels, in particular the main cervical branches of the aorta, with particular affinity to the temporal arteries and eye-supplying arteries. Temporal artery biopsy is still a gold standard for diagnosis, however in recent years colour duplex ultrasound examination has been proposed as a useful diagnostic screening tool in cases of TA suspicion. We report three cases of TA in which the ultrasonographical examination of the temporal arteries had a decisive role in the diagnosis.

Background Vinpocetine is a synthetic ethyl ester of apovincamine, a vinca alkaloid obtained from the leaves of the Lesser Periwinkle (Vinca minor) and discovered in the late 1960s. Although used in human treatment for over twenty years, it has not been approved by any regulatory body for the treatment of cognitive impairment. Basic sciences studies have been used to claim a variety of potentially important effects in the brain. However, despite these many proposed mechanisms and targets, the relevance of this basic science to clinical studies is unclear. Objectives To assess the efficacy and safety of vinpocetine in the treatment of patients with cognitive impairment due to vascular disease, Alzheimer's disease, mixed (vascular and Alzheimer's disease) and other dementias. Search methods The Cochrane Dementia and Cognitive Improvement Group's Specialized Register was searched on 23 March 2009 using the terms vinpocetin*, cavinton, kavinton, Rgh-4405, Tcv-3B, "ethyl apovincaminate", vinRx, periwinkle, "myrtle vincapervinc" and cezayirmeneksesi. This register contains up to date references from major health care databases like MEDLINE and EMBASE as well as records from trials databases in the field of dementia.The manufacturers of vinpocetine were asked for information on trials of vinpocetine for dementia. In addition we tried to collect articles not listed in MEDLINE or other sources on the Internet (e.g. articles in Hungarian and Romanian). Selection criteria All human, unconfounded, double-blind, randomized trials in which treatment with vinpocetine was administered for more than a day and compared to control in patients with vascular dementia, Alzheimer's dementia or mixed Alzheimer's and vascular dementia and other dementias. Non-randomized trials were excluded. Data collection and analysis Data were independently extracted by the two reviewers (SzSz and PW) and cross-checked. Data from "washout" periods were not used for the analysis. For continuous or ordinal variables, such as cognitive test results, the main outcomes of interest were the change in score from baseline. The categorical outcome of global impression was transformed to binary data (improved or not improved) as was the occurrence of adverse effects; here the endpoint itself was of interest and the Peto method of the "typical odds ratio" was used. A test for heterogeneity of treatment effects between the trials was made if appropriate. Data synthesis and analysis were performed using the Cochrane Review Manager software (RevMan version 4.1). Main results All identified studies were performed before and in the early 1990s and used various terms and criteria for cognitive decline and dementia. The three studies included in the review involved a total of 583 people with dementia treated with vinpocetine or placebo. The reports of these studies did not make possible any differentiation of effects for degenerative or vascular dementia. The results show benefit associated with treatment with vinpocetine 30 mg/day and 60 mg/day compared with placebo, but the number of patients treated for six months or more was small. Only one study extended treatment to one year. Adverse effects were inconsistently reported and without regard for relationship to dose. The available data do not demonstrate many problems of adverse effects but intention-to-treat data were not available for any of the trials. Authors' conclusions Although the basic science is interesting, the evidence for beneficial effect of vinpocetine on patients with dementia is inconclusive and does not support clinical use. The drug seems to have few adverse effects at the doses used in the studies. Large studies evaluating the use of vinpocetine for people suffering from well defined types of cognitive impairment are needed to explore possible efficacy of this treatment.

Cerebrovascular disease is a major public health problem in Eastern European countries. A Hungarian post-stroke population was examined to estimate the rate of dementia, the risk factors for cognitive impairment, and the applicability of a recently established Canadian diagnostic checklist in this cohort. Chronic cerebrovascular outpatients were screened for cognitive impairment with a combined checklist: the Diagnostic Checklist for Vascular Dementia established by the Consortium of Canadian Centres for Clinical Cognitive Research using the Mini Mental State Examination instead of the detailed neuropsychological part of the Checklist. Of the 247 consecutive patients at a cerebrovascular outpatient unit, 176 had cerebrovascular disorder diagnosed either by computed tomography (CT; n = 126) or by the clinical signs. Of these, 15% were cognitively impaired and 5% fulfilled the criteria of dementia. The mean age of the patients with cognitive impairment was significantly higher than that of patients with normal cognition (68.2 ± 10.2 and 60.5 ± 10.5 years, P < 0.001). The Barthel index was significantly lower in the cognitively affected group than in non-affected patients (92.4 ± 16.0 and 97.1 ± 8.7, P = 0.027). Diabetes and more than two subcortical infarcts on CT or magnetic resonance imaging were more frequent in patients with cognitive loss (P = 0.043 and P = 0.013, respectively). Cognitive performance was also influenced by the level of education. Higher age, diabetes, motor deficits, and multiple subcortical infarcts are risk factors for cognitive impairment after stroke. The combined checklist appears to be a practical screening test for cognitive impairment in patients with chronic cerebrovascular diseases.