Acute response to cholinergic challenge predicts long-term response to galantamine treatment in patients with Alzheimer's disease.

AIMS: Cholinesterase inhibitors (CEIs) have been shown to improve cognitive functioning in Alzheimer's disease (AD) patients, but are associated with multiple side effects and only 20-40% of the patients clinically improve. In this study, we aimed to investigate the acute pharmacodynamic (PD) effects of administration of a single dose of galantamine on central nervous system (CNS) functioning in mild to moderate AD patients and its potential to predict long-term treatment response. METHODS: This study consisted of a challenge and treatment phase. In the challenge phase, a single dose of 16 mg galantamine was administered to 50 mild to moderate AD patients in a double-blind, placebo-controlled cross-over fashion. Acute PD effects were monitored up to 5 hours after administration with use of the NeuroCart CNS test battery and safety and pharmacokinetics were assessed. In the treatment phase, patients were treated with open-label galantamine according to regular clinical care. After 6 months of galantamine treatment, patients were categorized as either responder or as non-responder based on their minimental state examination (MMSE), neuropsychiatric inventory (NPI) and disability assessment in dementia (DAD) scores. An analysis of covariance was performed to study the difference in acute PD effects during the challenge phase between responders and non-responders. RESULTS: A single dose of galantamine significantly reduced saccadic reaction time (-0.0099; 95% CI = -0.0195, -0.0003; P = .0430), absolute frontal EEG parameters in alpha (-14.9; 95% CI = -21.0, -8.3; P = .0002), beta (-12.6; 95% CI = -19.4, -5.3; P = .0019) and theta (-17.9; 95% CI = -25.0, -10.0; P = .0001) frequencies. Relative frontal (-1.669; 95% CI = -2.999, -0.339; P = .0156) and occipital (-1.856; 95% CI = -3.339, -0.372; P = .0166) EEG power in theta frequency and relative occipital EEG power in the gamma frequency (1.316; 95% CI = 0.158, 2.475; P = .0273) also increased significantly compared to placebo. Acute decreases of absolute frontal alpha (-20.4; 95% CI = -31.6, -7.47; P = .0046), beta (-15.7; 95% CI = -28.3, -0.93; P = .0390) and theta (-25.9; 95% CI = -38.4, -10.9; P = .0024) EEG parameters and of relative frontal theta power (-3.27%; 95% CI = -5.96, -0.58; P = .0187) on EEG significantly distinguished responders (n = 11) from non-responders (n = 32) after 6 months. CONCLUSIONS: This study demonstrates that acute PD effects after single dose of galantamine are correlated with long-term treatment effects and that patients who demonstrate a reduction in EEG power in the alpha and theta frequency after a single administration of galantamine 16 mg will most likely respond to treatment.

Distinctive Under-Expression Profile of Inflammatory and Redox Genes in the Blood of Elderly Patients with Cardiovascular Disease.

PURPOSE: Chronic low-grade inflammation and oxidative stress are present in most of the pathologic mechanisms underlying non-communicable diseases. Inflammation and redox biomarkers might therefore have a value in disease prognosis and therapy response. In this context, we performed a case-control study for assessing in whole blood the expression profile of inflammation and redox-related genes in elderly subjects with various comorbidities. PATIENTS AND METHODS: In the blood of 130 elderly subjects with various pathologies (cardiovascular disease, hypertension, dyslipidemia including hypercholesterolemia, type 2 diabetes mellitus), kept under control by polyvalent disease-specific medication, we investigated by pathway-focused qRT-PCR a panel comprising 84 inflammation-related and 84 redox-related genes. RESULTS: The study highlights a distinctive expression profile of genes critically involved in NF-κB-mediated inflammation and redox signaling in the blood of patients with cardiovascular disease, characterized by significant down-regulation of the genes NFKB2, NFKBIA, RELA, RELB, AKT1, IRF1, STAT1, CD40, LTA, TRAF2, PTGS1, ALOX12, DUOX1, DUOX2, MPO, GSR, TXNRD2, HSPA1A, MSRA, and PDLIM1. This gene expression profile defines the transcriptional status of blood leukocytes in stable disease under medication control, without discriminating between disease- and therapy-related changes. CONCLUSION: The study brings preliminary proof on a minimally invasive strategy for monitoring disease in patients with cardiovascular pathology, from the point of view of inflammation or redox dysregulation in whole blood.

Effectiveness and Safety Profile of Ginkgo biloba Standardized Extract (EGb761®) in Patients with Amnestic Mild Cognitive Impairment.

BACKGROUND: Ginkgo biloba is a common symptomatic treatment for cognitive impairment, although data on its efficacy are controversial. OBJECTIVE: The aim of the current study was to evaluate the effectiveness of standardized Ginkgo biloba extract EGb761® (Tanakan®) for the improvements of cognitive functions over 24 months in a local cohort of patients diagnosed with amnestic mild cognitive impairment (aMCI). METHODS: This multicentre non-interventional study included 500 eligible patients with a MCI treated with 120 mg/day standardized Ginkgo biloba extract EGb761® (Tanakan®). Patients were evaluated using several scales for assessment of cognition, memory, activities of daily living, and depression (MMSE, FAQ, CGI, HAM-D) at baseline and every 6 months after that for a 24-month period. The median change in MMSE at the 24-month follow-up was the primary outcome of the study. RESULTS: A statistically significant increase of 2 points in the median MMSE score was obtained. In patients with other concomitant cognitive disorders, the improvement in MMSE was less significant. Tanakan® improved memory impairment (using the delayed recall test) and the ability to accomplish activities of daily living (mean FAQ score, 1.7); it also decreased the severity of depression (mean HAM-D score, 2.4) at the end of the study. More than 80% of the patients showed minimal improvement of their condition as assessed by the CGI-Improvement Scale. CONCLUSION: The administration of EGb761® (Tanakan®) led to a significant improvement of cognitive decline, memory, activities of daily living, and depression in subjects with aMCI over 24 months.

Characterizing Advanced Parkinson's Disease: Romanian Subanalysis from the OBSERVE-PD Study.

OBSERVE-PD was a cross-sectional, multicountry, observational study conducted in 128 Movement Disorders Centers (MDCs) in 18 countries. Overall, the study enrolled 2615 patients. The aim was to determine the proportion of patients with advanced Parkinson's disease (APD) versus non-APD from MDCs and to uncover the clinical burden of APD, as well as a correlation between overall assessment of APD and several indicators of APD. The advanced stage of the disease and severity were assessed by investigators using their clinical judgement. Data were collected during a single visit between February 2015 and January 2016. Agreement on physician judgement of APD diagnosis and fulfillment of at least one previously established APD indicator was calculated. Motor and nonmotor symptoms (NMSs), activities of daily living, treatment complications, quality of life (QoL), conventional treatments, and device-aided therapy (DAT) eligibility were assessed. Here, country-specific results of 161 Romanian patients with PD are presented. In total, 59.0% of patients were diagnosed with APD and 78.8% met at least one APD indicator. There was only moderate agreement between clinical judgement of APD and overall fulfillment of APD indicators. All scores related to motor symptoms, NMSs, and treatment complications, as well as to QoL, showed a higher disease burden for patients with APD versus non-APD. Physicians considered 73.7% of patients with APD eligible for DAT. The majority of patients eligible for DAT (54.3%) did not receive such treatment. Our results highlight the importance of earlier recognition of APD, by combining clinical judgement with more standardized clinical tools, such as generally recognized APD criteria. However, timely diagnosis of APD alone is not enough to improve patient outcomes. Other critical factors include patient acceptance and access to appropriate treatment.

CACNA1B gene variants in adult-onset isolated focal dystonia.

BACKGROUND: Isolated focal dystonia (IFD) is a heterogeneous group of potentially invalidating movement disorders. The etiopathogenesis is complex, both genetic and environmental factors playing a role, but remains elusive. The CACNA1B gene codes for the N-type neuronal voltage-gated calcium channels CaV2.2, which may play a role in the development of some IFD. METHODS: We analyzed samples from the GENDYS cohort for mutations in CACNA1B gene, using targeted next-generation sequencing (NGS). RESULTS: The GENDYS cohort consists of 120 people with adult-onset IFD (cervical dystonia 47.5%, blepharospasm 47.2%, others 8.3%). Of these, 35% had subsequent topographical extension. Average age at onset was 42 and average disease durations 8 years. Targeted NGS revealed a novel frameshift mutation c.2291AGG > A, in exon 19, and a previously reported variant, c.6834T > G, in exon 47. CONCLUSION: Our findings suggest that disease-causing mutations in CACNA1B gene may be involved in the development of some adult-onset IFD. To our knowledge, this is the first study that identified a disease-causing CACNA1B gene mutation in association with adult-onset IFD.

Application of the '5-2-1' screening criteria in advanced Parkinson's disease: interim analysis of DUOGLOBE.

Aim: A Delphi expert consensus panel proposed that fulfilling ≥1 of the '5-2-1 criteria' (≥five-times daily oral levodopa use, ≥two daily hours with 'Off' symptoms or ≥one daily hour with troublesome dyskinesia) suggests advanced Parkinson's disease (PD). Patients & methods: DUOdopa/Duopa in Patients with Advanced PD - a GLobal OBservational Study Evaluating Long-Term Effectiveness (DUOGLOBE) - is a single-arm, postmarketing, observational, long-term effectiveness study of levodopa-carbidopa intestinal gel (LCIG) for advanced PD. Results: This 6-month interim analysis (n = 139) affirms that most (98%) enrolled patients fulfill ≥1 of the 5-2-1 criteria. These patients responded favorably to LCIG treatment. Safety was consistent with other LCIG studies. Conclusion: In advanced PD patients, the 5-2-1 criteria generally aligns with clinician assessment. Clinical Trial Registration: NCT02611713 (ClinicalTrials.gov).

Moyamoya-like vasculopathy associated to MYH9-related thrombocytopenia manifested by multiple cerebral ischemic lesions: a case report.

BACKGROUND: Moyamoya-like vasculopathy (MMV) and myosin heavy chain 9-related platelet disorders (MYH9-RPDs) or macrothrombocitopenias are rare syndromes. Their association is even more infrequent. CASE PRESENTATION: A 29-year-old female with history of MYH9-RPD, presented to our department for episodes suggesting transient ischemic attacks. Based on the imaging studies that revealed multiple ischemic lesions and stenoses of both distal internal carotid arteries and the arteries of the circle of Willis, the diagnosis of MMV was established. The treatment with Verapamil was initiated, leading to symptom remission. Two months later, the patient presented one episode of dysarthria, followed by involuntary movements of the right upper limb, few days later. Long-term electroencephalogram monitoring depicted epileptiform abnormalities. Resolution of symptoms was obtained after increasing the dose of Verapamil, and initiating Levetiracetam. CONCLUSIONS: This is an interesting case of a patient with two rare pathologies, who presented with cerebral ischemic strokes. To our knowledge there are few cases described in the literature presenting with cerebral hemorrhagic events but none of them with multiple cerebral ischemic lesions. As these cases are very rare, it is important to gather evidence regarding the best approach and treatment strategy.

Clinical Characteristics and Outcomes of Patients with Intracerebral Hemorrhage - A Feasibility Study on Romanian Patients.

Intracerebral hemorrhage is a significant public health problem, as it is a disease associated with overwhelming mortality and disability. We performed a retrospective feasibility study of patients admitted with acute intracerebral hemorrhage in our department for four months. Our aims were to identify peculiarities of the risk factors, demographic and clinical characteristics of intracerebral hemorrhage patients from our population, to estimate a feasible recruitment rate for a larger prospective study of patients with intracerebral hemorrhage and to analyze and correct potential drawbacks in the methodology of a more extensive prospective study of patients with intracerebral hemorrhage hospitalized in our department. During the study period, we admitted 53 patients with intracerebral hemorrhage in our department. The mean age of the patients was 69.1 years, and 53% were men. Arterial hypertension was the most common etiologic factor leading to intracerebral hemorrhage. 50.01% of patients died during hospitalization, 31.19% were discharged with significant disability, and 18.8% had a favorable short-term outcome. Higher hematoma volumes, male sex, deep location of the hemorrhage, and age between 51 and 60 years were factors associated with an unfavorable short-term outcome.

Non-Motor Manifestations in Idiopathic Dystonia with Focal Onset - A Pilot Study.

Recent studies emphasize an increased prevalence of non-motor symptoms in idiopathic dystonia with focal onset (IDFO), but their pathophysiological relationship is not clear. We aimed to identify the prevalence of depression and neurocognitive impairment in a group of patients with idiopathic dystonia with focal onset and their impact on the patients' quality of life. This study represents a component of an ongoing research project - GENDYS. From the database of this project, we selected 48 patients 56.62+/-14.16 years old who have been examined clinically and using specific scales: Patient Health Questionnaire-9 (for depression), Montreal Cognitive Assessment - MoCA (for cognitive impairment), and a 5-degree analog scale for subjective perception of the severity of the disease. We conducted a descriptive cross-sectional study on patients with depression and cognition evaluated by the above-mentioned scales. We also performed a nested case-control analysis on 20 IDFO patients with and without at least moderate depression matched for age and gender; the cut-offs for depression were PHQ-9 score ≥10 and PHQ9 <5, for the depression group and the control group, respectively. The cut-off for MoCA was 26 points. 22 IDFO patients (46%) had depression; 54.5% of IDFO patients with depression had cognitive impairment, indicating a slight trend of increased cognitive impairment in those with depression compared to those without; the perception of the severity of disease was the greatest in patients with depression. Depression is more prevalent in patients with IDFO and is associated with a worse perception of the disease severity.

Cingulate cortex function and multi-modal connectivity mapped using intracranial stimulation.

The cingulate cortex is part of the limbic system. Its function and connectivity are organized in a rostro-caudal and ventral-dorsal manner which was addressed by various other studies using rather coarse cortical parcellations. In this study, we aim at describing its function and connectivity using invasive recordings from patients explored for focal drug-resistant epilepsy. We included patients that underwent stereo-electroencephalographic recordings using intracranial electrodes in the University Emergency Hospital Bucharest between 2012 and 2019. We reviewed all high frequency stimulations (50 â€‹Hz) performed for functional mapping of the cingulate cortex. We used two methods to characterize brain connectivity. Effective connectivity was inferred based on the analysis of cortico-cortical potentials (CCEPs) evoked by single pulse electrical stimulation (SPES) (15 â€‹s inter-pulse interval). Functional connectivity was estimated using the non-linear regression method applied to 60 â€‹s spontaneous electrical brain signal intervals. The effective (stimulation-evoked) and functional (non-evoked) connectivity analyses highlight brain networks in a different way. While non-evoked connectivity evidences areas having related activity, often in close proximity to each other, evoked connectivity highlights spatially extended networks. To highlight in a comprehensive way the cingulate cortex's network, we have performed a bi-modal connectivity analysis that combines the resting-state broadband h2 non-linear correlation with cortico-cortical evoked potentials. We co-registered the patient's anatomy with the fsaverage FreeSurfer template to perform the automatic labeling based on HCP-MMP parcellation. At a group level, connectivity was estimated by averaging responses over stimulated/recorded or recorded sites in each pair of parcels. Finally, for multiple regions that evoked a clinical response during high frequency stimulation, we combined the connectivity of individual pairs using maximum intensity projection. Connectivity was assessed by applying SPES on 2094 contact pairs and recording CCEPs on 3580 contacts out of 8582 contacts of 660 electrodes implanted in 47 patients. Clinical responses elicited by high frequency stimulations in 107 sites (pairs of contacts) located in the cingulate cortex were divided in 10 groups: affective, motor behavior, motor elementary, versive, speech, vestibular, autonomic, somatosensory, visual and changes in body perception. Anterior cingulate cortex was shown to be connected to the mesial temporal, orbitofrontal and prefrontal cortex. In the middle cingulate cortex, we located affective, motor behavior in the anterior region, and elementary motor and somatosensory in the posterior part. This region is connected to the prefrontal, premotor and primary motor network. Finally, the posterior cingulate was shown to be connected with the visual areas, mesial and lateral parietal and temporal cortex.

Update on the Management of Parkinson's Disease for General Neurologists.

Management of Parkinson's disease (PD) is complicated due to its progressive nature, the individual patient heterogeneity, and the wide range of signs, symptoms, and daily activities that are increasingly affected over its course. The last 10-15 years have seen great progress in the identification, evaluation, and management of PD, particularly in the advanced stages. Highly specialized information can be found in the scientific literature, but updates do not always reach general neurologists in a practical and useful way, potentially creating gaps in knowledge of PD between them and neurologists subspecialized in movement disorders, resulting in several unmet patient needs. However, general neurologists remain instrumental in diagnosis and routine management of PD. This review provides updated practical information to identify problems and resolve common issues, particularly when the advanced stage is suspected. Some tips are provided for efficient communication with the members of a healthcare team specialized in movement disorders, in order to find support at any stage of the disease in a given patient, and especially for a well-timed decision on referral.

The Role of Polysomnography in Identifying Sleep Disorders in Children with Migraine.

Migraine pathophysiology and sleep share common neural pathways, and there are clinical as well as paraclinical observations, which lead to the hypothesis of an association between migraine and sleep disorders. The objective of this study consisted of the evaluation of a possible correlation between migraine and sleep disorders in children, as reflected by sleep architecture and electroencephalographic patterns. Eighteen patients aged five to seventeen were recruited for the migraine group, and sixteen age-matched patients with no criteria for migraine or any underlying organic disorder, diagnosed with emotional disorders, were enrolled in the control group. All patients underwent inpatient full night polysomnographic recordings, the results of which were analyzed using appropriate statistical methods. Patients in the migraine group had decreased REM sleep (p = 0.049) and increased N1 sleep (p = 0.018) percentages, compared to the control group. Also, more arousals (p = 0.011) and lower sleep latency (p = 0.029) were noted in the migraine group. A statistically significant association was observed between migraine and sleep disorders when the latter was defined with respect to normal values of polysomnographic parameters published in studies conducted on healthy children. Polysomnography can be a useful tool for studying sleep in pediatric migraine patients. The results of this study can be regarded as a starting point for a better understanding of the complex role of sleep in the developing brain and of eventual intricacies with migraine pathophysiological mechanisms.

Sleep modulates effective connectivity: A study using intracranial stimulation and recording.

OBJECTIVE: Sleep is an active process with an important role in memory. Epilepsy patients often display a disturbed sleep architecture, with consequences on cognition. We aimed to investigate the effect of sleep on cortical networks' organization. METHODS: We analyzed cortico-cortical evoked responses elicited by single pulse electrical stimulation (SPES) using intracranial depth electrodes in 25 patients with drug-resistant focal epilepsy explored using stereo-EEG. We applied the SPES protocol during wakefulness and NREM - N2 sleep. We analyzed 31,710 significant responses elicited by 799 stimulations covering most brain structures, epileptogenic or non-epileptogenic. We analyzed effective connectivity between structures using a graph-theory approach. RESULTS: Sleep increases excitability in the brain, regardless of epileptogenicity. Local and distant connections are differently modulated by sleep, depending on the tissue epileptogenicity. In non-epileptogenic areas, frontal lobe connectivity is enhanced during sleep. There is increased connectivity between the hippocampus and temporal neocortex, while perisylvian structures are disconnected from the temporal lobe. In epileptogenic areas, we found a clear interhemispheric difference, with decreased connectivity in the right hemisphere during sleep. CONCLUSIONS: Sleep modulates brain excitability and reconfigures functional brain networks, depending on tissue epileptogenicity. SIGNIFICANCE: We found specific patterns of information flow during sleep in physiologic and pathologic structures, with possible implications for cognition.

Nociceptive pain unmasking a serious pathology - paraneoplastic hypertrophic osteoarthropathy: A case report.

RATIONALE: Hypertrophic osteoarthropathy, also named Pierre Marie-Bamberger syndrome, represents a rare medical condition that may be considered either a primary or a secondary disease, and lung malignancies are responsible for more than two-thirds of the cases with secondary forms of the disease. PATIENT CONCERNS: We present the case of a 41-year-old man referred to our Neurology Department for pain that was considered secondary to cervical disc protrusions. The neurologic examination was normal. However, the general examination showed digital clubbing, right lateral cervical adenopathy, and pachydermia. The radiographic examinations of the upper and lower limbs depicted osseous abnormalities typical for periostosis, and the computed tomography of the thorax showed the presence of a mass lesion in the right upper pulmonary lobe. High values of vascular endothelial growth factor were also found. The patient was admitted to the Pneumology Clinic, where biopsy was performed from the lateral cervical adenopathy. DIAGNOSES: The anatomopathological examination revealed multiple neoplastic infiltrates suggestive of adenocarcinoma metastasis. Based on the clinical examination and radiological and histologic findings, the diagnosis of pulmonary adenocarcinoma with lymph nodes metastases and paraneoplastic hypertrophic osteoarthropathy was established. INTERVENTIONS: The patient received treatment with nonsteroidal antiinflammatory drugs and opiate analgesics that relieved the pain. OUTCOMES: The patient was referred to the Oncology Department for further treatment of the primary pathology. He received different types of chemotherapeutics, immunotherapy, and radiotherapy. However, despite all therapeutic measures, the disease rapidly progressed and the patient died 9 months later. LESSONS: This is an interesting case of a patient with an overlooked pathology, which was refereed to our clinic for further investigations of a pain that was considered neuropathic, secondary to small cervical protrusions. Conversely, the pain proved to be nociceptive and Pierre Marie-Bamberger syndrome was the positive diagnosis in our patient, as it can be associated with numerous diseases, especially of neoplastic origin.

Illusory own body perceptions mapped in the cingulate cortex-An intracranial stimulation study.

Body awareness is the result of sensory integration in the posterior parietal cortex; however, other brain structures are part of this process. Our goal is to determine how the cingulate cortex is involved in the representation of our body. We retrospectively selected patients with drug-resistant epilepsy, explored by stereo-electroencephalography, that had the cingulate cortex sampled outside the epileptogenic zone. The clinical effects of high-frequency electrical stimulation were reviewed and only those sites that elicited changes related to body perception were included. Connectivity of the cingulate cortex and other cortical structures was assessed using the h2 coefficient, following a nonlinear regression analysis of the broadband EEG signal. Poststimulation changes in connectivity were compared between two sets of stimulations eliciting or not eliciting symptoms related to body awareness (interest and control groups). We included 17 stimulations from 12 patients that reported different types of body perception changes such as sensation of being pushed toward right/left/up, one limb becoming heavier/lighter, illusory sensation of movement, sensation of pressure, sensation of floating or detachment of one hemi-body. High-frequency stimulation in the cingulate cortex (1 anterior, 15 middle, 1 posterior part) elicits body perception changes, associated with a decreased connectivity of the dominant posterior insula and increased coupling between other structures, located particularly in the nondominant hemisphere.

Opsoclonus-Myoclonus Syndrome Associated With West-Nile Virus Infection: Case Report and Review of the Literature.

Opsoclonus-myoclonus syndrome (OMS) is a very rare condition with different autoimmune, infectious and paraneoplastic aetiologies or in most cases idiopathic. We report the case of a 75-year-old woman who was admitted in our department in early fall for altered mental status, opsoclonus, multifocal myoclonus, truncal titubation and generalized tremor, preceded by a 5 day prodrome consisting of malaise, nausea, fever and vomiting. Brain computed tomography and MRI scans showed no significant abnormalities and cerebrospinal fluid changes consisted of mildly increased protein content and number of white cells. Work-up for paraneoplastic and autoimmune causes of OMS was negative but serologic tests identified positive IgM and IgG antibodies against West Nile virus (WNV). The patient was treated with Dexamethasone and Clonazepam with progressive improvement of mental status, myoclonus, opsoclonus and associated neurologic signs. Six months after the acute illness she had complete recovery. To our knowledge this is the 14th case of WNV associated OMS reported in the literature so far. We briefly describe the clinical course of the other reported cases together with the different treatment strategies that have been employed.

Correction: Exploring the reproducibility of functional connectivity alterations in Parkinson's disease.

[This corrects the article DOI: 10.1371/journal.pone.0188196.].

VaD - An Integrated Framework for Cognitive Rehabilitation.

BACKGROUND & OBJECTIVE: Vascular dementia is the second most common cause of dementia, with clinical features that depend on neural substrates affected by the vascular lesions. Like most neurological disorders, it involves alterations that range from the molecular level to neuronal networks. Such alterations begin as compensatory mechanisms that reshape every subsystem involved in the brain's homeostasis. Although there have been recent huge advances in understanding the pathophysiology of cognitive dysfunction, a suitable therapeutic approach to vascular dementia remains elusive. Pharmacological interventions have failed to sustainably improve cognitive function, and it is a well-known fact that there is a need to change the current view for providing neuroprotection and enhancing neurorecovery after stroke. Studies regarding cognitive training are also faced with the difficulty of drawing up protocols that can embrace a holistic approach in cognitively impaired patients. CONCLUSION: This review will present a brief synthesis of current results from basic research data and clinical studies regarding pharmacological and non-pharmacological interventions in vascular dementia and will offer an integrated view from the perspective of systems biology.

Safety and efficacy of Cerebrolysin in early post-stroke recovery: a meta-analysis of nine randomized clinical trials.

This meta-analysis combines the results of nine ischemic stroke trials, assessing efficacy of Cerebrolysin on global neurological improvement during early post-stroke period. Cerebrolysin is a parenterally administered neuropeptide preparation approved for treatment of stroke. All included studies had a prospective, randomized, double-blind, placebo-controlled design. The patients were treated with 30-50 ml Cerebrolysin once daily for 10-21 days, with treatment initiation within 72 h after onset of ischemic stroke. For five studies, original analysis data were available for meta-analysis (individual patient data analysis); for four studies, aggregate data were used. The combination by meta-analytic procedures was pre-planned and the methods of synthesis were pre-defined under blinded conditions. Search deadline for the present meta-analysis was December 31, 2016. The nonparametric Mann-Whitney (MW) effect size for National Institutes of Health Stroke Scale (NIHSS) on day 30 (or 21), combining the results of nine randomized, controlled trials by means of the robust Wei-Lachin pooling procedure (maximin-efficient robust test), indicated superiority of Cerebrolysin as compared with placebo (MW 0.60, P < 0.0001, N = 1879). The combined number needed to treat for clinically relevant changes in early NIHSS was 7.7 (95% CI 5.2 to 15.0). The additional full-scale ordinal analysis of modified Rankin Scale at day 90 in moderate to severe patients resulted in MW 0.61 with statistical significance in favor of Cerebrolysin (95% CI 0.52 to 0.69, P = 0.0118, N = 314). Safety aspects were comparable to placebo. Our meta-analysis confirms previous evidence that Cerebrolysin has a beneficial effect on early global neurological deficits in patients with acute ischemic stroke.

Can suitable candidates for levodopa/carbidopa intestinal gel therapy be identified using current evidence?

Advanced Parkinson's disease (APD) is characterized by increased functional disability, caused by motor complications, the presence of axial symptoms, and emergent disease- and drug-related non-motor symptoms. One of the advanced therapies available is intrajejunal infusion of levodopa/carbidopa intestinal gel (LCIG); however, patient selection for this treatment is sometimes difficult, particularly because of overlapping indications with other alternatives. In recent years, strong evidence has supported the use of LCIG in treating motor fluctuations associated with APD, and several clinical studies provide emerging evidence for additional benefits of LCIG treatment in certain patients. This article provides an overview of the published literature on the benefits, limitations, and drawbacks of LCIG in relation to PD symptoms, the psychosocial impact of the disease, and the quality of life of patients, with the aim of determining candidates for whom treatment with LCIG would be beneficial. According to current evidence, patients with APD (defined as inability to achieve optimal control of the disease with conventional oral treatment), a relatively well-preserved cognitive-behavioral status, and good family/caregiver would count as suitable candidates for LCIG treatment. Contraindications in the opinion of the authors are severe dementia and active psychosis.