Alla Guekht

Long-term efficacy and safety of eslicarbazepine acetate: results of a 1-year open-label extension study in partial-onset seizures in adults with epilepsy.

Purpose:  To evaluate the long‐term efficacy and safety of once daily eslicarbazepine acetate (ESL) as adjunctive therapy for partial‐onset seizures in adults with epilepsy.

Factors influencing on quality of life in people with epilepsy

OBJECTIVES To assess the influence of different factors on health-related QOL in adults with epilepsy in Moscow, Russia. METHOD We evaluated quality of life in 242 patients (98 de novo and 144 previously inadequately treated) by using QOLIE-31. Partial cryptogenic or symptomatic epilepsy was diagnosed in 214 patients, in 28-idiopathic generalized epilepsy. Stepwise regression analysis was performed to assess the influence of different factors on QOL. RESULTS In patients with epilepsy in Russia the total score of QOLIE-31 was rather low-42.13+/-4.14. Relationship of quality of life (total score) and frequency of seizures and duration of disease was analyzed. Frequency of seizures was the most significant parameter related to QOL (R=0.46 with total score). Duration of disease also correlated with QOL score (R=0.24 with total score). Significant but rather weak association (link) between frequency of seizures and almost all of subscales of quality of life was noticed. Duration of epilepsy correlated with less number of subscales: Energy/fatigue, Medication effects, Social functioning, Overall QOL subscales. When factors influencing on QOL were separately analyzed in newly diagnosed and previously treated patients frequency of seizures was the most important parameter in both groups. CONCLUSIONS Frequency of seizures is the most important factor influencing on QOL in adults with epilepsy (newly diagnosed and previously treated).

Post-stroke cognitive decline: an update and perspectives for clinical research

The close relationship between stroke and dementia is an important health issue. Ischaemic stroke can facilitate the onset of vascular dementia as well as aggravate pre‐existing cognitive decline. The onset of cognitive decline may become manifest immediately following the onset of ischaemic stroke, but often there is a delay in the development of cognitive decline after a stroke. This delay can be seen as a therapeutic time window allowing interventions to be applied to preserve cognition following stroke. Both neurodegenerative and vascular mechanisms are activated and probably result in overlapping processes within the neurovascular unit. This review focuses on the incidence and prevalence of cognitive decline following stroke, predisposing stroke aetiologies, pre‐stroke decline, imaging factors and biomarkers. Outcomes are discussed in relation to timing of assessment and neuropsychological tests used for evaluation of cognitive decline in ischaemic stroke patients. Including such tests in routine evaluations of stroke patients after some weeks or months is recommended. Finally, an outlook on ongoing and planned intervention trials is added and some recommendations for future research are proposed.

Costs of illness and care in Parkinson's disease: an evaluation in six countries.

We investigated the costs of Parkinsons Disease (PD) in 486 patients based on a survey conducted in six countries. Economic data were collected over a 6-month period and presented from the societal perspective. The total mean costs per patient ranged from EUR 2620 to EUR 9820. Direct costs totalled about 60% to 70% and indirect costs about 30% to 40% of total costs. The proportions of costs components of PD vary notably; variations were due to differences in country-specific health system characteristics, macro economic conditions, as well as frequencies of resource use and price differences. However, inpatient care, long-term care and medication were identified as the major expenditures in the investigated countries.

Social and clinical determinants of quality of life in Parkinson's disease in a Russian cohort study

Parkinsons disease (PD) is a chronic neurodegenerative disorder that has a major impact on health and longevity in Eastern countries. Studies investigating health-related quality of life (HRQoL) in Eastern European and Asian countries are scarce. The objective of this cross-sectional survey was to assess HRQoL in Russian patients with PD and identify its social and clinical determinants. The study included 100 outpatients with idiopathic PD and 100 controls. Patients were consecutively recruited from the neurological department of the Russian Medical State University in Moscow between October 2004 and December 2005. Regional healthy controls were matched for age and sex. The evaluation of HRQoL was performed using the EuroQol instrument (EQ-5D and EQ VAS). Disease severity was assessed using the Unified Parkinsons Disease Rating Scale (UPDRS). Multivariate regression analyses were used to identify independent determinants of HRQoL. HRQoL was more notably decreased in PD patients than in controls (98% versus 74% of individuals with moderate or severe problems in at least one dimension of the EQ-5D (p < 0.001), respectively). As compared to patients, the controls reported a higher mean EQ VAS score (74.0 +/- 16.0 versus 47.7 +/- 16.7, p < 0.001). Social and clinical determinants of HRQoL were age, disease severity, dystonia, depression, dementia and social support. While the HRQoL of patients with PD in Western countries is predominately affected by clinical parameters, social factors play an important role in Eastern countries. Our data should be considered in the development of national healthcare programs that seek to provide better social services support for patients with PD.

Costs of Illness in a Russian Cohort of Patients with Parkinson's Disease

AbstractBackground: The economic burden associated with Parkinson’s disease (PD) is increasing as the worldwide population ages. While cost-of-illness studies for PD from developed countries have recently been published, data for Eastern Europe and Asia are still lacking. Objective: To prospectively evaluate direct and indirect costs in a cohort of Russian patients with PD in order to identify cost-driving factors. Methods and Patients: We recruited 100 patients with idiopathic PD who visited the outpatient department for movement disorders of the Russian Medical State University in Moscow between October 2004 and December 2005. The Unified Parkinson’s Disease Rating Scale was used to evaluate clinical status. Economic data were collected in a ‘bottom-up’ approach and evaluated from the societal perspective. Indirect costs were estimated using a human capital approach. Russian currency was converted into €, year 2005 values, using the purchasing power parity. All costs were then inflated to €, year 2008 values, using the Medical Care Component of the Consumer Price Index. Independent cost predictors were identified by means of multivariate regression analyses. Results: From the societal perspective, total costs per patient over 6 months amounted to h2620 (95%CI 2050, 3200), with direct costs accounting for 67% and indirect costs for 33% of the total. Patients’ expenditures accounted for 43% of their private income. The primary burden on patients was due to informal care and drugs. Only 10% of home care was provided by the formal service sector. Costs for the nation are estimated at €1.1 billion per year. Conclusion: The economic burden of PD in Russia is considerable, especially when taking into account low private incomes. Further development of a formal care system and better reimbursement systems for drugs are necessary in Russia.

Diabetes and the brain: issues and unmet needs.

Abstract Diabetes mellitus (DM) is associated with an increased risk of mild cognitive impairment, dementia and stroke. The association between DM and dementia appears to be stronger for vascular cognitive impairment than for Alzheimer’s disease, suggesting cerebrovascular disease may be an important factor in cognitive impairment in DM. Although the exact mechanisms by which DM affects the brain remain unclear, changes to brain vasculature, disturbances of cerebral insulin signaling, insulin resistance, glucose toxicity, oxidative stress, accumulation of advanced glycation end products, hypoglycemic episodes, and alterations in amyloid metabolism may all be involved. Cognitive impairment and dementia associated with DM may also be mediated via vascular risk factors, in particular brain ischemia, the occurrence of which can have an additive or synergistic effect with concomitant neurodegenerative processes. To date, no drug has been approved for the treatment of vascular dementia and there are no specific pharmacological treatments for preventing or reducing cognitive decline in patients with DM. Most focus has been on tighter management of vascular risk factors, although evidence of reduced cognitive decline through reducing blood pressure, lipid-lowering or tighter glycemic control is inconclusive. Tailored, multimodal therapies may be required to reduce the risk of cognitive dysfunction and decline in patients with DM. The use of pleiotropic drugs with multimodal mechanisms of action (e.g., cerebrolysin, Actovegin) may have a role in the treatment of cognitive dysfunction and their use may warrant further investigation in diabetic populations.

Pleiotropic neuroprotective and metabolic effects of Actovegin's mode of action.

This article reviews the mechanisms of action of Actovegin in the context of its preclinical effects and new concepts in the pharmacological treatment of neurological disorders. Actovegin is an ultrafiltrate of calf blood, composed of more than 200 biological substances. The drug is used for a broad spectrum of diseases, including disturbances of peripheral and cerebral blood circulation, burns, impaired wound healing, radiation-induced damage and diabetic polyneuropathy. Actovegin is composed of small molecules present under normal physiological conditions, therefore pharmacokinetic and pharmacodynamic studies to determine its active substance are not feasible. Preclinical data have revealed that it improves metabolic balance by increasing glucose uptake and improving oxygen uptake under conditions of ischemia. Actovegin also resists the effects of gamma-irradiation and stimulates wound healing. More recent preclinical studies have suggested that anti-oxidative and anti-apoptotic mechanisms of action specifically underlie the neuroprotective properties of Actovegin. The drug has been found to exert these beneficial effects experimentally, in primary rat hippocampal neurons and in an STZ-rat model of diabetic polyneuropathy, while also providing evidence that it positively affects the functional recovery of neurons. Latest data suggest that Actovegin also has a positive influence on the NF-κB pathway, but many molecular and cellular pathways remain unexplored. In particular, Actovegins influence on neuroplasticity, neurogenesis and neurotrophicity are questions that ideally should be answered by future research. Nevertheless, it is clear that the multifactorial and complex nature of Actovegin underlies its pleiotropic neuroprotective mechanisms of action and positive effect on clinical outcomes.

Cerebrolysin in Vascular Dementia: Improvement of Clinical Outcome in a Randomized, Double-Blind, Placebo-Controlled Multicenter Trial

No drug to treat vascular dementia (VaD) has yet been approved by the American or European authorities, leaving a large population of patients without effective therapy. Cerebrolysin has a long record of safety and might be efficacious in this condition. We conducted a large, multicenter, double-blind, placebo-controlled study in 242 patients meeting the criteria for VaD. The primary endpoint was the combined outcome of cognition (based on Alzheimers Disease Assessment Scale Cognitive Subpart, Extended Version [ADAS-cog+] score) and overall clinical functioning (based on Clinicians Interview-Based Impression of Change plus Caregiver Input [CIBIC+] score) assessed after 24 weeks of treatment. Intravenous Cerebrolysin 20 mL was administered once daily over the course of 2 treatment cycles as add-on therapy to basic treatment with acetylsalicylic acid. The addition of Cerebrolysin was associated with significant improvement in both primary parameters. At week 24, ADAS-cog+ score improved by 10.6 points in the Cerebrolysin group, compared with 4.4 points in the placebo group (least squares mean difference, -6.17; P < .0001 vs placebo). CIBIC+ showed a mean improvement of 2.84 in the treatment arm and 3.68 in the placebo arm, a treatment difference of 0.84 (P < .0001 vs placebo). These findings were confirmed by responder analyses demonstrating higher rates in the Cerebrolysin group (ADAS-cog+ improvement of ≥4 points from baseline, 82.1% vs 52.2%; CIBIC+ score of <4 at week 24, 75.3% vs 37.4%; combined response in ADAS-cog+ and CIBIC+, 67.5% vs 27.0%). For Cerebrolysin, the odds ratio for achieving a favorable CIBIC+ response was 5.08 (P < .05), and that for achieving a favorable combined response was 5.63 (P < .05). Our data indicate that the addition of Cerebrolysin significantly improved clinical outcome, and that the benefits persisted for at least 24 weeks. Cerebrolysin was safe and well tolerated.

The epidemiology of epilepsy in the Russian Federation

UNLABELLED This study is the first analysis of the epidemiology of epilepsy in the Russian Federation (RF), in the English medical literature. The RF is geographically the largest territory in the world with a population of 142 million. The study evaluated prevalence of epilepsy in older teenagers and adults in 14 regions of the RF with total population of 517,624 persons (about 0.34% of all the population of the RF). Study sites were located in both European (Western population) and Siberian (Eastern population) regions of Russia. We identified 1753 patients with established epilepsy (1033 men, 720 women) from available medical information sources. Epilepsy cases were evaluated by study neurologists or epileptologists; all the patients underwent EEG, one third - neuroimaging. The age adjusted prevalence of epilepsy, standardized to the European Standard Million was 3.40 (95%CI: 3.26-3.55) per 1000. Prevalence was higher among men-4.50 (95%CI: 4.25-4.76) than among women-2.52 (95%CI: 2.35-2.69) (p < 0.0001). Prevalence in the Eastern population was significantly higher than in the Western population. The highest prevalence was found in the age group 50-59 years. Localization-related (focal) epilepsies/epilepsy syndromes were diagnosed in the majority (81.6%). In about one-third of those with localization-related epilepsies etiology remained undetermined. Head injury was the main identified cause of epilepsy, followed by cerebrovascular disorders. CONCLUSION The prevalence of epilepsy in the population ≥ 14 y.o. in Russia is consistent with results of the studies in adults in other European countries, although at lower end of the range. Age and gender trends are similar.