Theta-burst stimulation as a therapeutic tool in neurological pathology: a systematic review.

TBS (theta-burst stimulation) is a novel therapeutic approach in a wide range of neurological diseases. The present systematic review aims to identify the various protocols used in the last years, to assess study quality and to offer a general overview of the current state of the literature. The systematic review was conducted according to the Preferred Reporting Item for Systematic Review and Meta-Analyses (PRISMA) guidelines. We applied the following inclusion criteria: (1) population over 18 years old with diagnosed neurological disorders, (2) patients treated with sessions of theta-burst stimulation, (3) randomized-controlled clinical trials, (4) articles in the English language, and (5) studies that report response and score reduction on a validated scale of the investigated disorder or remission rates. We included in the final analysis 56 randomized controlled trials focusing on different neurological pathologies (stroke, Parkinson`s disease, multiple sclerosis, tinnitus, dystonia, chronic pain, essential tremor and tic disorder), and we extracted data regarding study design, groups and comparators, sample sizes, type of coil, stimulation parameters (frequency, number of pulses, intensity, stimulation site etc.), number of sessions, follow-up, assessment through functional connectivity and neurological scales used. We observed a great interstudy heterogenicity that leads to a difficulty in drawing plain conclusions. TBS protocols have shown promising results in improving various symptoms in patients with neurological disorders, but larger and more coherent studies, using similar stimulation protocols and evaluation scales, are needed to establish guideline recommendations.

Cerebrolysin and repetitive transcranial magnetic stimulation (rTMS) in patients with traumatic brain injury: a three-arm randomized trial.

Introduction: Traumatic brain injury (TBI) is a major public health problem affecting millions worldwide. Despite significant advances in medical care, there are limited effective interventions for improving cognitive and functional outcomes in TBI patients. Methods: This randomized controlled trial investigated the safety and efficacy of combining repetitive transcranial magnetic stimulation (rTMS) and Cerebrolysin in improving cognitive and functional outcomes in TBI patients. Ninety-three patients with TBI were randomized to receive either Cerebrolysin and rTMS (CRB + rTMS), Cerebrolysin and sham stimulation (CRB + SHM), or placebo and sham stimulation (PLC + SHM). The primary outcome measures were the composite cognitive outcome scores at 3 and 6 months after TBI. Safety and tolerability were also assessed. Results: The study results demonstrated that the combined intervention of rTMS and Cerebrolysin was safe and well-tolerated by patients with TBI. Although no statistically significant differences were observed in the primary outcome measures, the descriptive trends in the study support existing literature on the efficacy and safety of rTMS and Cerebrolysin. Discussion: The findings of this study suggest that rTMS and Cerebrolysin may be effective interventions for improving cognitive and functional outcomes in TBI patients. However, limitations of the study, such as the small sample size and exclusion of specific patient populations, should be considered when interpreting the results. This study provides preliminary evidence for the safety and potential efficacy of combining rTMS and Cerebrolysin in improving cognitive and functional outcomes in TBI patients. The study highlights the importance of multidisciplinary approaches in TBI rehabilitation and the potential for combining neuropsychological measurements and interventions to optimize patient outcomes. Conclusion: Further research is needed to establish these findings' generalizability and identify the optimal dosages and treatment protocols for rTMS and Cerebrolysin.

Repetitive transcranial magnetic stimulation (rTMS) as a therapeutic option in paraneoplastic cerebellar ataxia - a case report.

Paraneoplastic cerebellar ataxia is a paraneoplastic neurological syndrome (PNS) that can be the first clinical manifestation of underlying cancer. It is usually associated with onco-neuronal antibodies and has no other specific paraclinical feature. After the surgical and oncologic treatment of the primary cancer, the remaining neurological symptoms have limited therapeutic options. We describe a case of severe ataxia as the primary manifestation of ovarian cancer, with a significant clinical and paraclinical improvement of the neurological symptoms after 20 sessions of rTMS intervention.

The Effect of Cerebrolysin on Anxiety, Depression, and Cognition in Moderate and Severe Traumatic Brain Injury Patients: A CAPTAIN II Retrospective Trial Analysis.

Background and Objectives: Traumatic brain injuries represent an important source of disease burden requiring emergency inpatient care and continuous outpatient tailored rehabilitation. Although most TBIs are mild, patients are still developing post-TBI depression, anxiety, and cognitive impairments. Our secondary retrospective trial analysis aimed to (1) analyze correlations between HADS-Anxiety/HADS-Depression and scales that measure cognitive and motor processes in patients treated with Cerebrolysin compared to the placebo group and (2) compare anxiety and depression scores among the two treatment groups. Materials and Methods: Our secondary retrospective analysis focused on TBI patients with moderate and severe disability divided into two groups: Cerebrolysin (treatment) and saline solution (procedural placebo). We analyzed data from 125 patients. We computed descriptive statistics for nominal and continuous variables. We used Spearman's correlation to find associations between HADS and other neuropsychological scales and the Mann-Whitney U test to compare HADS-Anxiety and HADS-Depression scores among the two study arms. Results: Our sample consisted of patients with a mean age of 45.3, primarily men, and with a 24 h GCS (Glasgow Coma Scale) mean of 12.67. We obtained statistically significant differences for HADS-Anxiety during the second and third visits for patients treated with Cerebrolysin. Our results show that Cerebrolysin has a large effect size (0.73) on anxiety levels. In addition, there are positive and negative correlations between HADS-Anxiety and Depression subscales and other neuropsychological scales. Conclusions: Our secondary database analysis supports the existing body of evidence on the positive effect of Cerebrolysin on post-TBI mental health status. Future confirmatory trials are necessary to clarify the link between the intervention and measured outcomes.

Effects of N-Pep-12 dietary supplementation on neurorecovery after ischemic stroke.

BACKGROUND: The aim of the study was to evaluate the effects of N-Pep-12 dietary supplementation on neurorecovery of middle-aged and older adults with cognitive impairment after ischemic stroke, using neuropsychological outcome scales. METHODS: This was a pilot randomized-controlled, phase IV, academic clinical trial that aimed to assess the effect and the safety of a single daily dose of oral 90 mg of N-Pep-12 for 90 days in supporting neurorecovery, as compared with a control group, performed on middle-aged and older adults after supratentorial ischemic stroke. RESULTS: Study group differences in baseline changes at day 90 for Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS) - Anxiety subscale, Color Trails 1 and Symbol Search (number incorrect) were statistically significant (Mann-Whitney U test). For MoCA at day 90, a borderline 'intermediate effect' in favour of N-PEP-12 was observed (dCohen = 0.491, η2 = 0.057, OR = 2.436, p = 0.010). HADS Anxiety and Color Trails 1 at day 90 registered a 'small-to-intermediate' effect in favour of N-PEP-12 (dCohen = 0.424, η2 = 0.043, OR = 2.157, p = 0.026; dCohen = 0.481, η2 = 0.055, OR = 2.3927, p = 0.013, respectively). For symbol search errors, an 'intermediate' effect in favour of the control group was observed (dCohen = 0.501, η2 = 0.059, OR = 2.4811, p = 0.007). CONCLUSION: This exploratory clinical trial indicates a signal for the benefit of dietary supplementation with N-Pep-12 for the enhancement of neurorecovery after supratentorial ischemic stroke.

Biomarkers in traumatic brain injury: new concepts.

Traumatic brain injury is a multifaceted condition that encompasses a spectrum of injuries: contusions, axonal injuries in specific brain regions, edema, and hemorrhage. Brain injury determines a broad clinical and disability spectrum due to the implication of various cellular pathways, genetic phenotypes, and environmental factors. It is challenging to predict patient outcomes, to appropriately evaluate the patients, to determine a suitable treatment strategy and rehabilitation program, and to communicate with patient relatives. Biomarkers detected from body fluids are potential evaluation tools for traumatic brain injury patients. These may serve as internal indicators of cerebral damage, delivering valuable information about the dynamic cellular, biochemical, and molecular environments. The diagnostic and prognostic value of biomarkers tested both in animal models of traumatic brain injury is still under question, despite a considerable scientific literature. Recent publications emphasize that a more realistic approach involves combining multiple types of biomarkers with other investigative tools (imaging, outcome scales, and genetic polymorphisms). Additionally, there is increasing interest in the use of biomarkers as tools for treatment monitoring and as surrogate outcome variables to facilitate the design of distinct randomized controlled trials. This review highlights the latest available evidence regarding biomarkers in adults after traumatic brain injury and discusses new approaches in the evaluation of this patient group.