Correction to: Safety and efficacy of Cerebrolysin in acute brain injury and neurorecovery: CAPTAIN I-a randomized, placebo-controlled, double-blind, Asian-Pacific trial.

The above article was published online with incorrect abbreviations in Figures 2 and 3 last sentence of the legend. HDA should be corrected to HADS.

Safety and efficacy of Cerebrolysin in acute brain injury and neurorecovery: CAPTAIN I-a randomized, placebo-controlled, double-blind, Asian-Pacific trial.

OBJECTIVE: To evaluate the safety and efficacy of Cerebrolysin as an add-on therapy to local standard treatment protocol in patients after moderate-to-severe traumatic brain injury. METHODS: The patients received the study medication in addition to standard care (50 mL of Cerebrolysin or physiological saline solution daily for 10 days, followed by two additional treatment cycles with 10 mL daily for 10 days) in a prospective, randomized, double-blind, placebo-controlled, parallel-group, multi-centre phase IIIb/IV trial. The primary endpoint was a multidimensional ensemble of 14 outcome scales pooled to be analyzed by means of the multivariate, correlation-sensitive Wei-Lachin procedure. RESULTS: In 46 enrolled TBI patients (Cerebrolysin 22, placebo 24), three single outcomes showed stand-alone statistically significant superiority of Cerebrolysin [Stroop Word/Dots Interference (p = 0.0415, Mann-Whitney(MW) = 0.6816, 95% CI 0.51-0.86); Color Trails Tests 1 and 2 (p = 0.0223/0.0170, MW = 0.72/0.73, 95% CI 0.53-0.90/0.54-0.91), both effect sizes lying above the benchmark for "large" superiority (MW > 0.71)]. While for the primary multivariate ensemble, statistical significance was just missed in the intention-to-treat population (pWei-Lachin < 0.1, MWcombined = 0.63, 95% CI 0.48-0.77, derived standardized mean difference (SMD) 0.45, 95% CI -0.07 to 1.04, derived OR 2.1, 95% CI 0.89-5.95), the per-protocol analysis showed a statistical significant superiority of Cerebrolysin (pWei-Lachin = 0.0240, MWcombined = 0.69, 95% CI 0.53 to 0.85, derived SMD 0.69, 95% CI 0.09 to 1.47, derived OR 3.2, 95% CI 1.16 to 12.8), with effect sizes of six single outcomes lying above the benchmark for "large" superiority. Safety aspects were comparable to placebo. CONCLUSION: Our trial suggests beneficial effects of Cerebrolysin on outcome after TBI. Results should be confirmed by a larger RCT with a comparable multidimensional approach.

Clinical and Histopathological Assessment on an Animal Model with Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) is a disease of the Central Nervous System (CNS) which alters over 2 million people, and involves an abnormal autoimmune response directed against the brain, nerves and spinal cord. The antigen or the autoimmune target still remains unknown, a fact for which MS is considered to be an immune mediated disease. The pathology involves mainly the white matter, but the gray matter demyelination plays an important role in its pathogenesis. In 80% of the cases with MS, the disease develops relapses. Experimental autoimmune encephalomyelitis (EAE) is the most used model to study MS and for assessing potential treatments. In the present study we report on the histopathological characterization of an EAE model in C57BL/6 mice immunized by injection with myelin oligodendrocyte glycoprotein, MOG35-55 in complete Freud's adjuvant supplemented with pertussis toxin. On a group of 10 immunized animals and on 5 control animals, we followed the development and grading signs of motor deficiency, and after a survival of 34 days, the study aimed to evaluate the histopathological changes in the telencephalon, brainstem, cervical spinal cord, the optic nerve and retina. We utilized histochemistry, immunohistochemistry, and densitometric image analysis methods to assess myelin loss [Luxol fast blue, immunohistochemistry for the presence of microglia (Iba1) and reactive astrocytes (GFAP)]. Moreover, the study includes a first analysis of the detailed histopathological changes of the optic nerve and retina on an EAE model, all of these as the background for testing drugs with potential therapeutic role in MS.

Efficacy and safety of Cerebrolysin treatment in early recovery after acute ischemic stroke: a randomized, placebo-controlled, double-blinded, multicenter clinical trial.

Background and Purpose : The aim of this study was to evaluate the efficacy, safety, and tolerability of cerebrolysin in the early recovery phase after acute ischemic stroke. Methods. This prospective, randomized, double-blinded, placebo-controlled, multicenter, parallel-group study enrolled a total of 100 patients within 18 h after the onset of stroke. The patients were treated with Cerebrolysin (30 mL over seven days followed by 10 mL until day 30) or placebo once daily over a period of four weeks. Efficacy was primarily assessed by the NIH Stroke Scale at day 30, and additional parameters included the modified Rankin Scale, the Clinical Global Impression, the Patient Global Satisfaction (PGS) and the Mini Mental State Examination (MMSE). Nonparametric statistical procedures employing the Wilcoxon-Mann-Whitney test were used for data analysis. Safety and tolerability were assessed by adverse events, vital signs, and laboratory parameters. Results.The estimated effect size on the change from baseline in the NIH Stroke Scale on day 30 indicated a medium to large superiority of cerebrolysin compared to placebo (Mann-Whitney [MW] 0.66; 95% confidence interval [CI] 0.55-0.78, P=0.005). Similar effect sizes were reported for the modified Ranking Scale (MW 0.65; 95% CI 0.54-0.76; P=0.010) and the Clinical Global Impression (MW 0.70; 95% CI 0.55-0.85; P=0.006). Effect sizes in the MMSE and PGS did not reach statistical significance. No significant group differences were seen in any of the safety parameters. Conclusions. Cerebrolysin was effective, safe, and well tolerated in the early recovery phase after acute ischemic stroke and significantly improved neurological and global function outcomes compared to placebo.

The remote effects of intravitreal anti-VEGF therapy.

Objective: To study the effects of intravitreal anti-Vascular Endothelial Growth Factor (VEGF) therapy with Avastin for wet Age-Related Macular Degeneration (AMD) on Benign Prostatic Hyperplasia (BPH)-related symptoms. Methods: An exploratory trial was conducted from August 1, 2013 to February 1, 2014, that included 14 male patients previously diagnosed with BPH, who were aged between 59 and 69 years. The trial was performed in Bucharest and involved two medical institutions: the Clinical Hospital of Eye Emergencies and the "Prof. Dr. Theodor Burghele" Hospital. This prospective study utilized both objective and subjective indicators to analyze the link between intravitreal anti-VEGF therapy for wet AMD and BPH. The evaluations consisted of uroflowmetry and International Prostate Symptom Score (I-PSS) assessments. Results: The maximum flow rate (Qmax) improved by an average of 5.05 ml/ sec in 9 patients, whereas the remaining 5 patients showed a slight decrease in Qmax (mean 1.6 ml/ sec). The I-PSS score improved, with an overall decrease of 1.18 points at follow-up compared to the initial score (mean initial score = 2.42; mean follow-up score = 1.24). Conclusion: The analysis revealed that anti-VEGF therapy for wet AMD had a significant positive effect on all BPH-related symptoms; patients reported improved urinary streams and decreased nocturia. Abbreviations: BPH = benign prostatic hyperplasia, AMD = age-related macular degeneration, VEGF = vascular endothelial growth factor, I-PSS = international prostate symptom score, Qmax = maximum flow rate, TSP-1 = thrombospondin-1, FGF-2 = fibroblast growth factor, mRNA = precursor messenger ribonucleic acid, PSA = prostate-specific antigen, DRE = digital rectal examination, AUR = acute urinary retention, COX2 = cyclooxygenase 2, QoL = quality of life.

Credibility judgments in web page design - a brief review.

Today, more than ever, knowledge that interfaces appearance analysis is a crucial point in human-computer interaction field has been accepted. As nowadays virtually anyone can publish information on the web, the credibility role has grown increasingly important in relation to the web-based content. Areas like trust, credibility, and behavior, doubled by overall impression and user expectation are today in the spotlight of research compared to the last period, when other pragmatic areas such as usability and utility were considered. Credibility has been discussed as a theoretical construct in the field of communication in the past decades and revealed that people tend to evaluate the credibility of communication primarily by the communicator's expertise. Other factors involved in the content communication process are trustworthiness and dynamism as well as various other criteria but to a lower extent. In this brief review, factors like web page aesthetics, browsing experiences and user experience are considered.

Vascular cognitive impairment, dementia, aging and energy demand. A vicious cycle.

To a great extent, cognitive health depends on cerebrovascular health and a deeper understanding of the subtle interactions between cerebrovascular function and cognition is needed to protect humans from one of the most devastating affliction, dementia. However, the underlying biological mechanisms are still not completely clear. Many studies demonstrated that the neurovascular unit is compromised in cerebrovascular diseases and also in other types of dementia. The hemodynamic neurovascular coupling ensures a strong increase of the cerebral blood flow (CBF) and an acute increase in neuronal glucose uptake upon increased neural activity. Dysfunction of cerebral autoregulation with increasing age along with age-related structural and functional alterations in cerebral blood vessels including accumulation of amyloid-beta (Aß) in the media of cortical arterioles, neurovascular uncoupling due to astrocyte endfeet retraction, impairs the CBF and increases the neuronal degeneration and susceptibility to hypoxia and ischemia. A decreased cerebral glucose metabolism is an early event in Alzheimer's disease (AD) pathology and may precede the neuropathological Aß deposition associated with AD. Aß accumulation in turn leads to further decreases in the CBF closing the vicious cycle. Alzheimer, aging and diabetes are also influenced by insulin/insulin-like growth factor-1 signaling, and accumulated evidence indicates sporadic AD is associated with disturbed brain insulin metabolism. Understanding how vascular and metabolic factors interfere with progressive loss of functional neuronal networks becomes essential to develop efficient drugs to prevent cognitive decline in elderly.

Conscience and consciousness: a definition.

While consciousness has been examined extensively in its different aspects, like in philosophy, psychiatry, neurophysiology, neuroplasticity, etc., conscience though it is an equal important aspect of the human existence, which remains an unknown to a great degree as an almost transcendental aspect of the human mind. It has not been examined as thoroughly as consciousness and largely remains a "terra incognita" for its neurophysiology, brain topography, etc. Conscience and consciousness are part of a system of information that governs our experience and decision making process. The intent of this paper is to define these terms, to discuss about consciousness from both neurological and quantum physics point of view, the relationship between the dynamics of consciousness and neuroplasticity and to highlight the relationship between conscience, stress and health.

2nd International Salzburg Conference on Neurorecovery (ISCN 2013) Salzburg/Austria|November 28th-29th, 2013.

The 2nd International Salzburg Conference on Neurorecovery was held on the 28th and 29th of November, 2013, in Salzburg, one of the most beautiful cities in Austria, which is well known for its rich cultural heritage, world-famous music and beautiful surrounding landscapes. The aim of the conference was to discuss the progress in the field of neurorecovery. The conference brought together internationally renowned scientists and clinicians, who described the clinical and therapeutic relevance of translational research and its applications in neurorehabilitation.

Cerebrolysin Accelerates Metamorphosis and Attenuates Aging-Accelerating Effect of High Temperature in Drosophila Melanogaster.

Cerebrolysin® (CBL) is a neuroprotective drug used for the treatment of neurodegenerative diseases. CBL's mechanisms of action remain unclear. Involvement of tryptophan (TRP)-kynurenine (KYN) pathway in neuroprotective effect of CBL might be suggested considering that modulation of KYN pathway of TRP metabolism by CBL, and protection against eclosion defect and prolongation of life span of Drosophila melanogaster with pharmacologically or genetically-induced down-regulation of TRP conversion into KYN. To investigate possible involvement of TRP-KYN pathway in mechanisms of neuroprotective effect of CBL, we evaluated CBL effects on metamorphosis and life span of Drosophila melanogaster maintained at 23 °C and 28 °C ambient temperature. CBL accelerated metamorphosis, exerted strong tendency (p = 0.04) to prolong life span in female but not in male flies, and attenuated aging-accelerating effect of high (28 °C) ambient temperature in both female and male flies. Further research of CBL effects on metamorphosis and resistance to aging-accelerating effect of high temperature might offer new insights in mechanisms of its neuroprotective action and expand its clinical applications.

Clinical improvement and cortical adaptations after functional electrical stimulation in Parkinson's disease patients.

Parkinson's disease (PD) is a neurodegenerative disease of the central nervous system. Although PD is commonly characterized by well-known clinical manifestations, it also involves imbalances in the cortico-subcortical excitation and inhibition processes. Functional electrical stimulation can improve the motor condition of PD patients as a supplement to levodopa therapy. In this study, clinical (using specific tests) and paraclinical (using single-pulse transcranial magnetic stimulation) examinations revealed an improvement in the motor symptoms and the bilateral activation of the primary motor areas of the upper limbs after unilateral functional electrical stimulation in PD patients.

A neuropsychological assessment, using computerized battery tests (CANTAB), in children with benign rolandic epilepsy before AED therapy.

RATIONALE: Benign rolandic epilepsy (BRE) is a form of partial idiopathic epilepsy according to the International League Against Epilepsy (ILAE) syndromes classification (1989). Recent studies have identified cases of BRE that do not meet the initial definition of 'benign'; these included reports of cases with specific cognitive deficits. It is still a matter of debate, whether these deficits are due to epilepsy per se, to treatment or other associated factors. OBJECTIVES: The aim of this study was to evaluate if BRE children have cognitive deficits at the onset of their seizures, prior to their participation in any anti-epileptic drug therapy (AED). METHODS AND RESULTS: We performed a neuropsychological assessment of 18 BRE children compared with a corresponding age-matched control group. We used the Cambridge Neuropsychological Test Automated Battery (CANTAB). Subjects were at their first neurological evaluation, before any AED therapy. We assessed: visual memory, induction and executive functions. In our group, the BRE children performed comparably with the control children for the induction and executive functions. Substantial differences were identified for the visual memory subtests: PRM percent correct (t = -2.58, p = 0.01) and SRM percent correct (t = -2.73, p = 0.01). Age of seizure onset had a negative impact on the visual memory subtest performances (PRM mean correct latency). We found significant correlations between the different CANTAB subtests results and characteristics of the centrotemporal spikes (CTS). DISCUSSION: Our results are consistent with the findings of other similar studies. This form of epilepsy is associated with subtle neuropsychological deficits, present at seizure onset. Neuropsychological deficits identified, suggest a more diffuse brain involvement in the epileptiform process.

Mild traumatic brain injury.

Traumatic Brain Injury (TBI) is among the most frequent neurological disorders. Of all TBIs 90% are considered mild with an annual incidence of 100­300/100.000. Intracranial complications of Mild Traumatic Brain Injury (MTBI) are infrequent (10%), requiring neurosurgical intervention in a minority of cases (1%), but potentially life-threatening (case fatality rate 0,1%). Hence, a true health management problem exists because of the need to exclude the small chance of a life threatening complication in large numbers of individual patients. The 2002 EFNS guidelines used a best evidence approach based on the literature until 2001 to guide initial management with respect to indications for CT, hospital admission, observation and follow up of MTBI patients. This updated EFNS guideline version for initial management inMTBI proposes a more selectively strategy for CT when major (dangerous mechanism, GCS<15, 2 points deterioration on the GCS, clinical signs of (basal) skull fracture, vomiting, anticoagulation therapy, post traumatic seizure) or minor (age, loss of consciousness, persistent anterograde amnesia, focal deficit, skull contusion, deterioration on the GCS) risk factors are present based on published decision rules with a high level of evidence. In addition clinical decision rules for CT now exist for children as well. Since 2001 recommendations, although with a lower level of evidence, have been published for clinical in hospital observation to prevent and treat other potential threads to the patient including behavioral disturbances (amnesia, confusion and agitation) and infection.

Plasmatic markers in hemorrhagic stroke.

Stroke is the third most common cause of death in the United States and it is the leading cause of disability. Early diagnosis and immediate therapeutic interventions are important factors to reduce the extent of brain tissue damage and the risk of stroke-related death. A rapid blood test that can confirm the clinical or imaging diagnosis or that can add to the stratification of the risk would be very useful. Such a test has to be validated in large studies and has to be based on a simple and low-cost technology. Many biological markers were tested for their ability to serve as 'would-be' stroke biological markers; some of them appear to have a place in the diagnostic work-up of stroke patients. These molecules include Glial Fibrillary Acidic Protein (GFAP), the N-methyl-D-aspartate receptor (NMDA), APO C-III, APO C-I, PARK7, nucleoside diphosphate kinase A (NDKA), S100B, B-type neurotrophic growth factor, von Willebrand factor, matrix metalloproteinase-9, and monocyte chemotactic protein-1. There are obvious limitations to this study, among them the fact that disability does not necessarily correlate with the amount of cerebral tissue lost (the site of stroke may be more important) and the role of the blood-brain barrier in delaying the release of the neuronal proteins in the blood stream. Further studies are awaited to confirm the role of these molecules in the management of acute stroke patients.

Efficacy and safety of Cerebrolysin in patients with hemorrhagic stroke.

UNLABELLED: The purpose of the study was to investigate the efficacy and safety of Cerebrolysin in patients with hemorrhagic stroke. The primary objective of this trial was to assess the clinical efficacy and safety of a 10-days course of therapy with a daily administration of Cerebrolysin (50 mL i.v. per day). The trial had to demonstrate that Cerebrolysin treatment is safe in hemorrhagic stroke. METHODS: The study was performed as a prospective, randomized, double blind, placebo-controlled, parallel group study with 2 treatment groups. Efficacy measures were the Unified Neurological Stroke Scale, Barthel Index, and Syndrome Short Test. The duration of the trial was of 21 days for each patient. Out of 100 randomized patients, a total of 96 (96%) completed the study. RESULTS: Overall, no statistically significant group effects were observed based on single average comparisons at the individual visits. It could be shown that the treatment of hemorrhagic stroke with Cerebrolysin is safe and well tolerated. CONCLUSION: In the changes of UNSS, BI and SST from baseline to day 21, the group differences are not statistically significant; however, the use of Cerebrolysin in hemorrhagic stroke is safe and well tolerated and studies with a larger sample size may provide statistical evidence of Cerebrolysin's efficacy in patients with hemorrhagic stroke.

Integrative emphases on intimate, intrinsic propensity/pathological processes--causes of self recovery limits and also, subtle related targets for neuroprotectionl pleiotropicity/multimodal actions, by accessible therapeutic approaches--in spinal cord injuries.

BACKGROUND: The last two decades have come up with some important progresses in the genetic, immune, histochemical and bio (nano)-technological domains, that have provided new insight into cellular/molecular mechanisms, occurring in the central nervous system (CNS)--including in spinal cord-injuries. METHODS: In previous works, emerging from our theoretical and practical endeavors in the field, we have thoroughly described the principal intimate propensity and the pathophysiological processes--representing intrinsic limitations for self-recovery after SCI, and, at the same time, subtle targets for neuroprotection/recovery--and reviewed the main related worldwide-published reports. The aim of this paper is to emphasize the connections between such main aspects and some feasible integrative solutions, including the ones for clinical practice. RESULTS: Consequently, we stress upon some therapeutic suggestions regarding this subject matter by systematizing the most up to date and efficient ones--obviously, within major limits, according to the very low capacities of CNS/ spinal cord (SC) to post-injury self preserve and recover. Moreover, we also talk about accessible drugs, respectively those being already in clinical use (but at present, mainly used to treat other conditions, including the neurological ones) and hence, with relatively well known, determined effects and/or respectively, restrictions. DISCUSSIONS: The recent advances in the knowledge on the basic components of the afore mentioned CNS/ SC propensity for self destroying and inefficient endogenous repair mechanisms in the actual new context, will hopefully be, from now on, more effectively correlated with revolutionary--mostly still experimental--treatments, especially by using stem cells within tissue engineering, including, if needed, more advanced/courageous approaches, based on somatic cell nuclear transfer (SCNT). CONCLUSIONS: This paper contains the scientific motivated highlighting of some already available drugs, "neuroprotective" (and not only) properties too, which enable practitioners with (although not yet capable to cure--but anyway) more efficient therapeutic means, to approach the extremely difficult and still painfully disappointing domain, of spinal cord injury (SCI).

A review of published reports on neuroprotection in spinal cord injury.

STUDY DESIGN: Literature review. OBJECTIVES: To review the main published current neuroprotection research trends and results in spinal cord injury (SCI). SETTING: This paper is the result of a collaboration between a group of European scientists. METHODS: Recent studies, especially in genetic, immune, histochemical and bio (nano)-technological fields, have provided new insight into the cellular and molecular mechanisms occurring within the central nervous system (NS), including SCIs. As a consequence, a new spectrum of therapies aiming to antagonize the 'secondary injury' pathways (that is, to provide neuroprotection) and also to repair such classically irreparable structures is emerging. We reviewed the most significant published works related to such novel, but not yet entirely validated, clinical practice therapies. RESULTS: There have been identified many molecules, primarily expressed by heterogenous glial and neural subpopulations of cells, which are directly or indirectly critical for tissue damaging/sparing/re-growth inhibiting, angiogenesis and neural plasticity, and also various substances/energy vectors with regenerative properties, such as MAG (myelin-associated glycoprotein), Omgp (oligodendrocyte myelin glycoprotein), KDI (synthetic: Lysine-Asparagine-Isoleucine 'gamma-1 of Laminin Kainat Domain'), Nogo (Neurite outgrowth inhibitor), NgR (Nogo protein Receptor), the Rho signaling pathway (superfamily of 'Rho-dopsin gene-including neurotransmitter-receptors'), EphA4 (Ephrine), GFAP (Glial Fibrillary Acidic Protein), different subtypes of serotonergic and glutamatergic receptors, antigens, antibodies, immune modulators, adhesion molecules, scavengers, neurotrophic factors, enzymes, hormones, collagen scar inhibitors, remyelinating agents and neurogenetic/plasticity inducers, all aiming to preserve/re-establish the morphology and functional connections across the lesion site. Accordingly, modern research and experimental SCI therapies focus on several intricate, rather overlapping, therapeutic objectives and means, such as neuroprotective, neurotrophic, neurorestorative, neuroreparative, neuroregenerative, neuro(re)constructive and neurogenetic interventions. CONCLUSION: The first three of these therapeutical directions are generically assimilated as neuroprotective, and are synthetically presented and commented in this paper in an attempt to conceptually systematize them; thus, the aim of this article is, by emphasizing the state-of-the art in the domain, to optimize theoretical support in selecting the most effective pharmacological and physical interventions for preventing, as much as possible, paralysis, and for maximizing recovery chances after SCI.

Neuroprotective and consequent neurorehabilitative clinical outcomes, in patients treated with the pleiotropic drug cerebrolysin.

BACKGROUND: Discovery of neurotrophic factors--emblematic: the nerve growth factor (NGF)--resulted in better approaching central nervous system (CNS) lesions. Recently, another crucial property has been unveiled: their rather unique pleiotropic effect. Cerebrolysin is a peptide mixture that penetrates the blood-brain barrier in significant amounts and mimics the effects of NGF. METHODS: Comparative analysis: Cerebrolysin treated (10 ml x 2/day, i.v. x 3 weeks) vs. non-treated, in patients (all received aside, a rather equivalent complementary, pharmacological and physical, therapy). Two lots of patients, admitted in our Physical & Rehabilitation (neural-muscular) Medical-PR(n-m)M-Clinic Division, during 2007-2009: 69 treated with Cerebrolysin (22 F, 47 M; Average: 59.333; Mean of age: 61.0 Years old; Standard deviation 16.583) and 70 controls (41 F, 29 M; A: 70.014; M.o.a.: 70.5 Y.o.; S.d.: 6.270) were studied. The total number of assessed items was 13: most contributive in relation with the score of Functional Independence Measure at discharge (d FIM), were: admission (a FIM), number of physical therapy days (PT), number of hospitalization days (H), age (A) and--relatively--days until the first knee functional extension (KE). Concomitantly, the main/key, focused on neuro-motor rehabilitative outcomes, functional/analytical parameters, have been assessed regarding the speed in achieving their functional recovery. RESULTS: Concerning d FIM, there have not been objectified significant differences between the two lots (p=0.2453) but regarding key, focused on neuro-motor rehabilitative outcomes, functional/analytical parameters: KE (p=0.0007) and days until the first time recovery of the ability to walk between parallel bars (WPB--p=0.0000)--highly significant differences in favor of Cerebrolysin lot resulted. CONCLUSION: Cerebrolysin administration, as neurorehabilitative outcomes, proved to hasten, statistically significant, especially the recovery of some critical, for standing and walking, parameters. Thus encouraged, we have now initiated a comprehensive national, 5 year retrospective, multi-centre--based on unitary data acquisition frame and mathematical apparatus--study, to evaluate the results of the treatment with Cerebrolysin in traumatic brain injuries (TBI).

A 24-week, double-blind, placebo-controlled study of three dosages of Cerebrolysin in patients with mild to moderate Alzheimer's disease.

Cerebrolysin (Cere) is a compound with neurotrophic activity shown to be effective in Alzheimer's disease in earlier trials. The efficacy and safety of three dosages of Cere were investigated in this randomized, double-blind, placebo-controlled, study. Two hundred and seventy-nine patients were enrolled (69 Cere 10 ml; 70 Cere 30 ml; 71 Cere 60 ml and 69 placebo). Patients received iv infusions of 10, 30, 60 ml Cere or placebo 5 days/week for the first 4 weeks and thereafter, two iv infusions per week for 8 weeks. Effects on cognition and clinical global impressions were evaluated 4, 12 and 24 weeks after the beginning of the infusions using the CIBIC+ and the modified Alzheimer's Disease Assessment Scale (ADAS)-cog. At week 24, significant improvement of cognitive performance on the ADAS-cog (P=0.038) and global function (CIBIC+; P>0.001) was observed for the 10 ml dose. The 30 and 60 ml doses showed significant improvement of the global outcome but failed to show significant improvement of cognition. The results are consistent with a reversed U-shaped dose-response relationship for Cere. The percentage of patients reporting adverse events was similar across all study groups. Cere treatment was well tolerated and led to significant, dose-dependent improvement of cognition and global clinical impression.

Improved global function and activities of daily living in patients with AD: a placebo-controlled clinical study with the neurotrophic agent Cerebrolysin.

BACKGROUND: Cerebrolysin (Cere) is a peptidergic, neurotrophic drug which has been shown to improve cognitive performance and global function of Alzheimer's disease (AD) patients in earlier trials. In this study, we have attempted to replicate this findings with particular emphasis on functional improvement of the patients. PATIENTS AND METHODS: Patients received infusions of 30 ml Cere or placebo five days/week for six consecutive weeks. Patients had to have a diagnosis of AD and a MMSE score of 14-25 inclusive. Effects on cognition, global function, and activities of daily living were evaluated 3, 6, and 18 weeks after the beginning of the infusions. RESULTS: Significant improvement of cognitive function, clinical global impression and activities of daily living were seen after the end of the therapy. The effects were most pronounced in the DAD score, a measure for the capability to perform activities of daily living. Interestingly, and in line with the findings of earlier studies, the treatment effect of Cere was maintained after cessation of treatment up to the week 18 assessment. CONCLUSION: The data confirm the findings of earlier trials and clearly demonstrates that Cere leads to functional improvement of patients with AD. The sustained treatment effect of Cere after withdrawal has been confirmed.