Topical Cellular/Tissue and Molecular Aspects Regarding Nonpharmacological Interventions in Alzheimer's Disease-A Systematic Review.

One of the most complex and challenging developments at the beginning of the third millennium is the alarming increase in demographic aging, mainly-but not exclusively-affecting developed countries. This reality results in one of the harsh medical, social, and economic consequences: the continuously increasing number of people with dementia, including Alzheimer's disease (AD), which accounts for up to 80% of all such types of pathology. Its large and progressive disabling potential, which eventually leads to death, therefore represents an important public health matter, especially because there is no known cure for this disease. Consequently, periodic reappraisals of different therapeutic possibilities are necessary. For this purpose, we conducted this systematic literature review investigating nonpharmacological interventions for AD, including their currently known cellular and molecular action bases. This endeavor was based on the PRISMA method, by which we selected 116 eligible articles published during the last year. Because of the unfortunate lack of effective treatments for AD, it is necessary to enhance efforts toward identifying and improving various therapeutic and rehabilitative approaches, as well as related prophylactic measures.

PRISMA Systematic Literature Review, including with Meta-Analysis vs. Chatbot/GPT (AI) regarding Current Scientific Data on the Main Effects of the Calf Blood Deproteinized Hemoderivative Medicine (Actovegin) in Ischemic Stroke.

BACKGROUND: Stroke is a significant public health problem and a leading cause of death and long-term disability worldwide. Several treatments for ischemic stroke have been developed, but these treatments have limited effectiveness. One potential treatment for this condition is Actovegin®/AODEJIN, a calf blood deproteinized hemodialysate/ultrafiltrate that has been shown to have pleiotropic/multifactorial and possibly multimodal effects. The actual actions of this medicine are thought to be mediated by its ability to reduce oxidative stress, inflammation, and apoptosis and to enhance neuronal survival and plasticity. METHODS: To obtain the most up-to-date information on the effects of Actovegin®/AODEJIN in ischemic stroke, we systematically reviewed the literature published in the last two years. This review builds upon our previous systematic literature review published in 2020, which used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method to search for and select related articles over almost two decades, between 1 January 2001 and 31 December 2019. Additionally, we compared the results of our PRISMA search (human intelligence-based) with those obtained from an interrogation of a GPT-based chatbot (ChatGPT) in order to ensure comprehensive coverage of potentially relevant studies. RESULTS: Our updated review found limited new evidence on the use of Actovegin®/AODEJIN in ischemic stroke, although the number of articles on this subject consistently increased compared to that from our initial systematic literature review. Specifically, we found five articles up to 2020 and eight more until December 2022. While these studies suggest that Actovegin®/AODEJIN may have neuroprotective effects in ischemic stroke, further clinical trials are needed to confirm these findings. Consequently, we performed a funnel analysis to evaluate the potential for publication bias. DISCUSSION: Our funnel analysis showed no evidence of publication bias, suggesting that the limited number of studies identified was not due to publication bias but rather due to a lack of research in this area. However, there are limitations when using ChatGPT, particularly in distinguishing between truth and falsehood and determining the appropriateness of interpolation. Nevertheless, AI can provide valuable support in conducting PRISMA-type systematic literature reviews, including meta-analyses. CONCLUSIONS: The limited number of studies identified in our review highlights the need for additional research in this area, especially as no available therapeutic agents are capable of curing central nervous system lesions. Any contribution, including that of Actovegin (with consideration of a positive balance between benefits and risks), is worthy of further study and periodic reappraisal. The evolving advancements in AI may play a role in the near future.

Molecular Aspects of Hypoxic Stress Effects in Chronic Ethanol Exposure of Neuronal Cells.

Experimental models of a clinical, pathophysiological context are used to understand molecular mechanisms and develop novel therapies. Previous studies revealed better outcomes for spinal cord injury chronic ethanol-consuming patients. This study evaluated cellular and molecular changes in a model mimicking spinal cord injury (hypoxic stress induced by treatment with deferoxamine or cobalt chloride) in chronic ethanol-consuming patients (ethanol-exposed neural cultures (SK-N-SH)) in order to explain the clinical paradigm of better outcomes for spinal cord injury chronic ethanol-consuming patients. The results show that long-term ethanol exposure has a cytotoxic effect, inducing apoptosis. At 24 h after the induction of hypoxic stress (by deferoxamine or cobalt chloride treatments), reduced ROS in long-term ethanol-exposed SK-N-SH cells was observed, which might be due to an adaptation to stressful conditions. In addition, the HIF-1α protein level was increased after hypoxic treatment of long-term ethanol-exposed cells, inducing fluctuations in its target metabolic enzymes proportionally with treatment intensity. The wound healing assay demonstrated that the cells recovered after stress conditions, showing that the ethanol-exposed cells that passed the acute step had the same proliferation profile as the cells unexposed to ethanol. Deferoxamine-treated cells displayed higher proliferative activity than the control cells in the proliferation-migration assay, emphasizing the neuroprotective effect. Cells have overcome the critical point of the alcohol-induced traumatic impact and adapted to ethanol (a chronic phenomenon), sustaining the regeneration process. However, further experiments are needed to ensure recovery efficiency is more effective in chronic ethanol exposure.

Telerehabilitation: A Practical Remote Alternative for Coaching and Monitoring Physical Kinetic Therapy in Patients with Mild and Moderate Disabling Parkinson's Disease during the COVID-19 Pandemic.

Background: The COVID-19 pandemic imposed social/physical distancing, lockdown measures, and forced reorientation of the rehabilitation programs for people with Parkinson's disease (PD). Epidemiologic safety measures boosted remote exercise-based treatment. Objectives: Remote delivery of rehabilitation care services is not typically used in our department. Therefore, this study aimed to assess and implement a telehealth physical rehabilitation program tailored for outpatients with idiopathic PD and slight or medium functional limitations. Methods: A prospective study was performed on a group of outpatients with idiopathic PD, selected from the database of the neurorehabilitation clinic of the Emergency Teaching Hospital "Bagdasar-Arseni." We studied 17 patients (5 women and 12 men), aged between 54-70 years (average 65.9 ± 4.87), with a disease history of 7.3 ± 3.6 (years), with mild or moderate disabling clinical forms, quantified by an average Hoehn and Yahr score of 2.3 ± 0.35 (limits 1.5-3). All patients underwent pharmacologic treatment with unchanged doses throughout the study. No patients had disabling osteoarticular problems (all could walk independently) and had no significant psycho-cognitive dysfunction. Patients were supervised and coached online in tandem by the therapist and physician. In addition, a family member assisted and supervised the patient's performance and coordinated the technical electronic procedures. Walking biodynamics was assessed by timing "6-meters walking" and "Get up and walk 3 meters" (TUG) tests. Each person attended ten sessions of motor telerehabilitation procedures (2 per week) lasting 50 minutes each during social distancing (October-December 2021). Results: None of the patients was at increased risk of falling. They all improved their locomotor performance, reflected in a significant decrease in TUG duration (the initial average time improved from 13.50 seconds to 10.57). The telerehabilitation program also significantly improved the average walking speed (initially, 44.5 cm/sec and finally, it raised to 56.8 cm/sec). Discussion. The TUG and "6-meters walking" tests are helpful tools for a global biodynamic remote assessment of PD patients. Limitations of the study: a small group of selected patients, restrictive working conditions (due to epidemiological social/physical restrictions and no direct physiotherapist-patient contact), and need for supervision by an attendant to assist the subject and perform the audio-video transmission. Further studies are necessary to identify the optimal web-based model of care and boost the implementation of this modern neurorehabilitation concept. Conclusions: Telemedicine turned the virtual space into a new reality and may compensate for the restrictions imposed on face-to-face meetings in pandemic conditions. Moreover, with modern telecommunication techniques, a regular and individualized physical kinetic rehabilitation program can be performed even in pandemic conditions. Remote delivery of kinetic motor programs was appropriate for selected groups of PD patients.

Topical Reappraisal of Molecular Pharmacological Approaches to Endothelial Dysfunction in Diabetes Mellitus Angiopathy.

Diabetes mellitus (DM) is a frequent medical problem, affecting more than 4% of the population in most countries. In the context of diabetes, the vascular endothelium can play a crucial pathophysiological role. If a healthy endothelium-which is a dynamic endocrine organ with autocrine and paracrine activity-regulates vascular tone and permeability and assures a proper balance between coagulation and fibrinolysis, and vasodilation and vasoconstriction, then, in contrast, a dysfunctional endothelium has received increasing attention as a potential contributor to the pathogenesis of vascular disease in diabetes. Hyperglycemia is indicated to be the major causative factor in the development of endothelial dysfunction. Furthermore, many shreds of evidence suggest that the progression of insulin resistance in type 2 diabetes is parallel to the advancement of endothelial dysfunction in atherosclerosis. To present the state-of-the-art data regarding endothelial dysfunction in diabetic micro- and macroangiopathy, we constructed this literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We interrogated five medical databases: Elsevier, PubMed, PMC, PEDro, and ISI Web of Science.

Parkinson's Disease and SARS-CoV-2 Infection: Particularities of Molecular and Cellular Mechanisms Regarding Pathogenesis and Treatment.

Accumulating data suggest that chronic neuroinflammation-mediated neurodegeneration is a significant contributing factor for progressive neuronal and glial cell death in age-related neurodegenerative pathology. Furthermore, it could be encountered as long-term consequences in some viral infections, including post-COVID-19 Parkinsonism-related chronic sequelae. The current systematic review is focused on a recent question aroused during the pandemic's successive waves: are there post-SARS-CoV-2 immune-mediated reactions responsible for promoting neurodegeneration? Does the host's dysregulated immune counter-offensive contribute to the pathogenesis of neurodegenerative diseases, emerging as Parkinson's disease, in a complex interrelation between genetic and epigenetic risk factors? A synthetic and systematic literature review was accomplished based on the "Preferred Reporting Items for Systematic Principles Reviews and Meta-Analyses" (PRISMA) methodology, including registration on the specific online platform: International prospective register of systematic reviews-PROSPERO, no. 312183. Initially, 1894 articles were detected. After fulfilling the five steps of the selection methodology, 104 papers were selected for this synthetic review. Documentation was enhanced with a supplementary 47 bibliographic resources identified in the literature within a non-standardized search connected to the subject. As a final step of the PRISMA method, we have fulfilled a Population-Intervention-Comparison-Outcome-Time (PICOT)/Population-Intervention-Comparison-Outcome-Study type (PICOS)-based metanalysis of clinical trials identified as connected to our search, targeting the outcomes of rehabilitative kinesitherapeutic interventions compared to clinical approaches lacking such kind of treatment. Accordingly, we identified 10 clinical trials related to our article. The multi/interdisciplinary conventional therapy of Parkinson's disease and non-conventional multitarget approach to an integrative treatment was briefly analyzed. This article synthesizes the current findings on the pathogenic interference between the dysregulated complex mechanisms involved in aging, neuroinflammation, and neurodegeneration, focusing on Parkinson's disease and the acute and chronic repercussions of COVID-19. Time will tell whether COVID-19 neuroinflammatory events could trigger long-term neurodegenerative effects and contribute to the worsening and/or explosion of new cases of PD. The extent of the interrelated neuropathogenic phenomenon remains obscure, so further clinical observations and prospective longitudinal cohort studies are needed.

Cellular and Molecular Targets for Non-Invasive, Non-Pharmacological Therapeutic/Rehabilitative Interventions in Acute Ischemic Stroke.

BACKGROUND: Cerebral circulation delivers the blood flow to the brain through a dedicated network of sanguine vessels. A healthy human brain can regulate cerebral blood flow (CBF) according to any physiological or pathological challenges. The brain is protected by its self-regulatory mechanisms, which are dependent on neuronal and support cellular populations, including endothelial ones, as well as metabolic, and even myogenic factors. OBJECTIVES: Accumulating data suggest that "non-pharmacological" approaches might provide new opportunities for stroke therapy, such as electro-/acupuncture, hyperbaric oxygen therapy, hypothermia/cooling, photobiomodulation, therapeutic gases, transcranial direct current stimulations, or transcranial magnetic stimulations. We reviewed the recent data on the mechanisms and clinical implications of these non-pharmaceutical treatments. METHODS: To present the state-of-the-art for currently available non-invasive, non-pharmacological-related interventions in acute ischemic stroke, we accomplished this synthetic and systematic literature review based on the Preferred Reporting Items for Systematic Principles Reviews and Meta-Analyses (PRISMA). RESULTS: The initial number of obtained articles was 313. After fulfilling the five steps in the filtering/selection methodology, 54 fully eligible papers were selected for synthetic review. We enhanced our documentation with other bibliographic resources connected to our subject, identified in the literature within a non-standardized search, to fill the knowledge gaps. Fifteen clinical trials were also identified. DISCUSSION: Non-invasive, non-pharmacological therapeutic/rehabilitative interventions for acute ischemic stroke are mainly holistic therapies. Therefore, most of them are not yet routinely used in clinical practice, despite some possible beneficial effects, which have yet to be supplementarily proven in more related studies. Moreover, few of the identified clinical trials are already completed and most do not have final results. CONCLUSIONS: This review synthesizes the current findings on acute ischemic stroke therapeutic/rehabilitative interventions, described as non-invasive and non-pharmacological.

Translation of the Fugl-Meyer assessment into Romanian: Transcultural and semantic-linguistic adaptations and clinical validation.

Purpose: The Fugl-Meyer Assessment (FMA) scale, which is widely used and highly recommended, is an appropriate tool for evaluating poststroke sensorimotor and other possible somatic deficits. It is also well-suited for capturing a dynamic rehabilitation process. The aim of this study was to first translate the entire sensorimotor FMA scale into Romanian using the transcultural and semantic-linguistic adaptations of its official afferent protocols and to then validate it using the preliminary clinical evaluation of inter- and intra-rater reliability and relevant concurrent validity. Methods: Through three main steps, we completed a standardized procedure for translating FMA's official afferent evaluation protocols into Romanian and their transcultural and semantic-linguistic adaptation for both the upper and lower extremities. For relevant clinical validation, we evaluated 10 patients after a stroke two times: on days 1 and 2. All patients were evaluated simultaneously by two kinesi-physiotherapists (generically referred to as KFT1 and KFT2) over the course of 2 consecutive days, taking turns in the roles of an examiner and observer, and vice versa (inter-rater). Two scores were therefore obtained and compared for the same patient, i.e., being afferent to an inter-rater assay by comparing the assessment outcomes obtained by the two kinesi-physiotherapists, in between, and respectively, to the intra-rater assay: based on the evaluations of the same kinesi-physiotherapist, in two consecutive days, using a rank-based method (Svensson) for statistical analysis. We also compared our final Romanian version of FMA's official protocols for concurrent validity (Spearman's rank correlation statistical method) to both of the widely available assessment instruments: the Barthel Index (BI) and the modified Rankin scale (mRS). Results: Svensson's method confirmed overall good inter- and intra-rater results for the main parts of the final Romanian version of FMA's evaluation protocols, regarding the percentage of agreement (≥80% on average) and for disagreement: relative position [RP; values outside the interval of (-0.1, 0.1) in only two measurements out of the 56 comparisons we did], relative concentration [RC; values outside the interval of (-0.1, 0.1) in only nine measurements out of the same 56 comparisons done], and relative rank variation [RV; all values within an interval of (0, 0.1) in only five measurements out of the 56 comparisons done]. High correlation values were obtained between the final Romanian version of FMA's evaluation protocols and the BI (ρ = 0.9167; p = 0.0002) for FMA-upper extremity (FMA-UE) total A-D (motor function) with ρ = 0.6319 and for FMA-lower extremity (FMA-LE) total E-F (motor function) with p = 0.0499, and close to the limit, with the mRS (ρ = -0.5937; p = 0.0704) for FMA-UE total A-D (motor function) and (ρ = -0.6615; p = 0.0372) for FMA-LE total E-F (motor function). Conclusions: The final Romanian version of FMA's official evaluation protocols showed good preliminary reliability and validity, which could be thus recommended for use and expected to help improve the standardization of this assessment scale for patients after a stroke in Romania. Furthermore, this endeavor could be added to similar international translation and cross-cultural adaptations, thereby facilitating a more appropriate comparison of the evaluation and outcomes in the management of stroke worldwide.

Non-invasive, non-pharmacological/bio-technological interventions towards neurorestoration upshot after ischemic stroke, in adults-systematic, synthetic, literature review.

Considering its marked life-threatening and (not seldom: severe and/or permanent) disabling, potential, plus the overall medico-psycho-socio-economic tough burden it represents for the affected persons, their families and the community, the cerebrovascular accident (CVA)-including with the, by far more frequent, ischemic type-is subject to considerable scientific research efforts that aim (if possible) at eliminating the stroke induced lesions, and consist, as well, in ambitious-but still poorly transferable into medical practice-goals such as brain neuroregeneration and/or repair, within related corollary/upshot of neurorestoration. We have conducted, in this respect, a systematic and synthetic literature review, following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)" concept. Accordingly, we have interrogated five internationally renowned medical data bases: Elsevier, NCBI/PubMed, NCBI/PMC, PEDro, and ISI Web of Knowledge/Science (the last one to check whether the initially identified articles are published in ISI indexed journals), based on a large (details in the body text) number of most appropriate, to our knowledge, key word combinations/"syntaxes"-used contextually-and subsequently fulfilling the related, on five steps, filtering/selection methodology. We have thereby selected 114 fully eligible (of which contributive: 83-see further) papers; at the same time, additionally, we have enhanced our documentation-basically, but not exclusively, for the introductive part of this work (see further)-with bibliographic resources, overall connected to our subject, identified in the literature within a non-standardized search. It appears that the opportunity window for morph-functional recovery after stroke is larger than previously thought, actually being considered that brain neurorestoration/repair could occur, and therefore be expected, in later stages than in earlier ones, although, in this context, the number of cases possibly benefitting (for instance after physical and/or cognitive rehabilitation-including with magnetic or direct current transcranial stimulation) is quite small and with more or less conflicting, related outcomes, in the literature. Moreover, applying especially high intense, solicitating, rehabilitation interventions, in early stages post (including ischemic) stroke could even worsen the functional evolution. Accordingly, for clarifications and validation of more unitary points of view, continuing and boosting research efforts in this complex, interdisciplinary domain, is necessary. Until finding (if ever) effective modalities to cure the lesions of the central nervous system (CNS)-including post ischemic stroke-it is reasonable and recommendable-based on rigorous methodologies-the avail of combined ways: physiatric, pharmacologic, possibly also bio-technologic. On a different note, but however connected to our subject: periodic related systematic, synthetic literature reviews reappraisals are warranted and welcome.

Uncommon Association of Two Anatomical Variants of Cerebral Circulation: A Fetal-Type Posterior Cerebral Artery and Inferred Artery of Percheron, Complicated with Paramedian Thalamomesencephalic Stroke-Case Presentation and Literature Review.

BACKGROUND: The unilateral fetal variant of the posterior cerebral artery (FPCA) is characterized by the congenital absence of the P1 arterial segment. The artery of Percheron (AOP) is an uncommon vascular variant, in which a single dominant thalamoperforating arterial trunk arises from one P1 segment, bifurcates, and provides bilateral supply to the paramedian thalami and rostral midbrain. CASE PRESENTATION: This is a retrospective case study of a 37-year-old man with multiple lifestyle risk factors (chronic marijuana and tobacco abuse), who suffered a thalamomesencephalic stroke, rapidly worsening to comatose state. After restoration of consciousness, he clinically manifested with left paramedian midbrain syndrome. Imaging demonstrated an asymmetric paramedian thalamic infarction with mesencephalon extension, patency of the basilar, vertebral arteries, and left PCA and right-sided FPCA, respectively. Left-sided thalamoperforating arterioles were not differentiated; AOP was inferred. Neither evident clinical source of embolus nor prothrombotic states were found. Mobile cardiac telemetry and transesophageal echocardiography were not available. The diagnosis was established too late for thrombolytic treatment. Anticoagulation was indicated during the acute and subacute stages, followed by low dose of antiplatelet. DISCUSSION: This uncommon cerebrovascular configuration (FPCA+AOP) might be the fourth case described in the literature. Sustained rehabilitation and abstinence from tobacco and cannabis led to favorable outcomes.

Prevention of diving-induced spinal cord injuries-preliminary results of the first Romanian mass media prophylactic educational intervention.

STUDY DESIGN: The study was an observational study of the seasonal incidence of diving accidents, according to the summer weather pattern and the influence of an educative prophylactic intervention. OBJECTIVES: The study analyzed the preliminary results of a national project, disseminated on social networking (Facebook) and broadcasted on main national and international Romanian TV channels. SETTING: The study was conducted at the Neurorehabilitation, Teaching Emergency Hospital 'Bagdasar-Arseni.' METHODS: The study had a dichotomous design (a retrospective review and a prospective component), and it analyzed the evolution trends of diving accidents, before and after the prophylactic intervention. The retrospective review analyzed 41 diving accidents, registered during 2011-2015. The prospective component focused on cases registered in 2016. Spearman's Rho non-parametric test was used to evaluate the association between two variables (the air temperature and the number of diving accidents). RESULTS: The study involved 46 males and 1 female, with a mean age (at the time of injury) 26.4±7.02 (median 25, mode 23), admitted to rehabilitation in an early post-acute status after surgical intervention. Male youths and young adults <35 years old represented 83% of all cases. During 2011-2015, a monotonic association between the summer climate and the incidence of diving-induced tetraplegia (R=0.97468; P=0.00482) was noticed. Analyzing the evolutionary trends of similar cases registered in 2016, variables did not increase in value together (R=0.73561; P=0.09561). In 2016, the number of diving-induced quadriplegics was reduced on average by 26.8%. CONCLUSIONS: One year is not enough for a successful, durable educative intervention. It is compulsory to continue, extend and intensively promote this program.

European core curriculum in neurorehabilitation.

To date, medical education lacks Europe-wide standards on neurorehabilitation. To address this, the European Federation of NeuroRehabilitation Societies (EFNR) here proposes a postgraduate neurorehabilitation training scheme. In particular, the European medical core curriculum in neurorehabilitation should include a two-year residency in a neurorehabilitation setting where trainees can gain practical experience. Furthermore, it should comprise six modules of classroom training organized as weekend seminars or summer/winter schools. In conclusion, after defining the European medical core curriculum in neurorehabilitation, the next activities of the EFNR will be to try and reach the largest possible consensus on its content among all national societies across Europe in order to further validate it and try to extend it to the other, non-medical, professionals on the neurorehabilitation team in line with their core curricula defined by each professional association.

Acute spontaneous thoracic epidural hematoma, triggered by weight-lifting training, in a retired sportsman: case report and literature review.

INTRODUCTION: Spontaneous spinal epidural hematoma (SSEH) is a rare clinical entity, most often with acute symptomatic spinal cord compression and potentially permanent neurologic deficits. SSEH usually has surgical solutions and a good outcome after hematoma evacuation. CASE PRESENTATION: A 61-year-old professional weight-lifting coach presented to the emergency department with sudden back pain, rapidly progressive paraparesis, and neurogenic bladder, after an intense training, 5 h previously. Magnetic resonance imaging revealed a ventral thoracic epidural hematoma with significant compression at Th3-Th6. Surgical procedure was performed within the first 12 h: decompressive laminectomy from Th3 to Th7 vertebral levels and near total epidural hematoma removal. The patient improved rapidly from Th5 AIS-C to Th7 AIS-D paraplegia with independent ambulation, after the intervention. The rehabilitation program led to further improvement of the neurologic deficits and a favorable outcome, to AIS-E. DISCUSSION: Weightlifting has been reported as SSEH precipitating factor in young athletes. Our case is unique however, because the athlete was older. The underlying pathophysiological mechanism is represented by intravenous pressure changes and bleeding of the epidural venous plexus during a prolonged Valsalva maneuver, induced by strenuous, repeated efforts. Spondylosis, hypertension, and low doses of aspirin were incriminated as risk factors for SSEH. Prompt diagnosis, emergent decompressive intervention, early rehabilitation, and secondary prophylaxis were essential for a good outcome.

Evolution of traumatic spinal cord injury in patients with ankylosing spondylitis, in a Romanian rehabilitation clinic.

The ankylosing spondylitis (AS) is a systemic, multi-factorial, chronic rheumatic disease. Patients are highly susceptible to vertebral fractures with or without spinal cord injury (AS-SCI), even after a minor trauma. The study is a retrospective descriptive survey of post-acute, traumatic AS-SCI patients, transferred from the neurosurgical department and admitted in a Romanian Neurorehabilitation Clinic, during 2010-2014. There were 11 males associating AS-SCI (0.90% of all consecutive SCI admitted cases), with an average age of 54.6 years (median 56, limits 42-73 years). The average duration between the medically diagnosed AS and the actual associated spinal fracture(-s) moment was 21.4 years (median 23; limits 10-34 years). Low-energy trauma was incriminated in 54.5% cases. The spinal level of fracture was: cervical (four cases), thoracic (three), lumbar (four), assessed at admission as: American Spinal Injury Association (ASIA) Impairment Scale (AIS) A (four subjects), C (five) and D (two). By the time of discharge, neither patient has neurologically deteriorated; five patients (45.5%) improved of at least grade 1 (AIS). The overall complications were mainly infections: symptomatic urinary tract infections (seven patients; 63.6%), pulmonary (three subjects; 27.3%) and spondylodiscitis (one case; 9%). The average follow-up period was 15.3 months (median 12; limits 1-48 months) after discharge; three subjects gained functional improvement to AIS-E. The clinical profile (different risk factors, mechanisms, types and levels of spinal fractures, additional encephalic and/or cord lesions, co-morbidities), different post-surgical and/or general complications acquired during admission in our rehabilitation ward, served us for future prevention strategies and a better therapeutic management.

A retrospective, multi-center cohort study evaluating the severity- related effects of cerebrolysin treatment on clinical outcomes in traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of death and disability for which there is currently no effective drug therapy available. Because drugs targeting a single TBI pathological pathway have failed to show clinical efficacy to date, pleiotropic agents with effects on multiple mechanisms of secondary brain damage could represent an effective option to improve brain recovery and clinical outcome in TBI patients. In this multicenter retrospective study, we investigated severity-related efficacy and safety of the add-on therapy with two concentrations (20 ml/day or 30 ml/day) of Cerebrolysin (EVER Neuro Pharma, Austria) in TBI patients. Adjunctive treatment with Cerrebrolysin started within 48 hours after TBI and clinical outcomes were ranked according to the Glasgow Outcome Scale and the Modified Rankin Disability Score at 10 and 30 days post-TBI. Analyses of efficacy were performed separately for subgroups of patients with mild, moderate or severe TBI according to Glasgow Coma Scale scores at admission. Compared to standard medical care alone (control group), both doses of Cerebrolysin were associated with improved clinical outcome scores at 10 days post-TBI in mild patients and at 10 and 30 days in moderate and severe cases. A dose-dependent effect of Cerebrolysin on TBI recovery was supported by the dose-related differences and the significant correlations with treatment duration observed for outcome measures. The safety and tolerability of Cerebrolysin in TBI patients was very good. In conclusion, the results of this large retrospective study revealed that early Cerebrolysin treatment is safe and is associated to improved TBI outcome.