Clin. Transl. Neurosci., Volume 6, Issue 3 (September 2022) – 8 articles

Female sex has been shown to be associated with an unfavorable outcome after ischemic stroke. In this nationwide analysis, we evaluate a large dataset of patients suffering from acute ischemic stroke to elucidate the factors associated with an increased risk of mortality after stroke in women. We analyzed a nationwide dataset from the German Federal Bureau of Statistics including 1,577,884 (761,537 female sex, 48.3%) in-hospital cases admitted between 1 January 2014 and 31 December 2019 with a primary diagnosis of acute ischemic cerebral infarction. Patients were analyzed regarding morbidity, treatments and in-hospital mortality. A multiple logistic regression analysis was performed, adjusted by patients’ risk profile including age, to evaluate the association of sex and in-hospital mortality. According to the median, women were older than men (79 years vs. 73 years). The multiple logistic regression analysis however revealed female sex remained an independent factor for an increased in-hospital mortality (odds ratio [OR] 1.12; 95% confidence interval [CI] 1.11–1.14; p < 0.001). Women had a higher prevalence of relevant risk factors, namely arterial hypertension (77.0% vs. 74.7%), arterial fibrillation (33.3% vs. 25.6%), chronic heart failure (12.3% vs. 9.7%), chronic kidney disease (15.6% vs. 12.9%) and dementia (6.6% vs. 4.1%), but were less affected with respect to other relevant co-morbidities such as cerebrovascular disease (11.7% vs. 15.1%), coronary heart disease (11.7% vs. 18.8%), diabetes mellitus (26.4% vs. 29.6%), dyslipidemia (38.1% vs. 42.0%), ischemic heart disease (12.3% vs. 19.3%) and previous coronary artery bypass grafting (1.1% vs. 3.2%). Overall, therapeutic interventions were performed less frequently in women such as carotid endarterectomy (1.1% vs. 2.3%), carotid stent (0.7% vs. 1.4%), as well as hematoma drainage (0.1% vs. 0.2%), and renal replacement therapy (0.4% vs. 0.6%). Conclusions: Our nationwide analysis revealed a higher mortality rate after stroke in women. Nevertheless, women had fewer in-hospital complications and were also less likely to experience the severe effects of some important co-morbidities. The dataset, however, showed that women received surgical or interventional carotid treatments after stroke less often. It is important for research on sex disparities in stroke to keep these treatment frequency differences in mind. Full article

On behalf of the SFCNS, Swiss Federation of Clinical Neuro-Societies, we are pleased to present the abstracts of the 5th SFCNS Congress, which is held in Basel, Switzerland, September 28–30, 2022. In total, 169 abstracts were selected for an ePoster, of which 55 were presented as short presentations during the ePoster Sessions and 5 were presented at the YouCliN Research Award Session. We congratulate all the presenters on their research work and contribution. Full article

Importance: The Defense and Veterans Brain Injury Center reported 358,088 mild traumatic brain injury (mTBI) among U.S. service members worldwide between the years 2000 and 2020. Veterans with mTBI have higher rates of Post-Traumatic Stress Disorder (PTSD), depressive disorder, substance use disorder, anxiety disorder, and suicide than their healthy counterparts. Currently, there is no effective treatment for mTBI. Objective: To assess the efficacy of hyperbaric oxygen therapy (HBOT) as a treatment option for mTBI. Design, Setting, Participants: This is a case series of 39 U.S. Veterans diagnosed with mTBI and treated with HBOT. Of these participants, 36 were men and 3 women, and their ages ranged between 28 and 69. The treatment was administered by The 22 Project (a veteran-centered nonprofit organization) using monoplace hyperbaric chambers located in Delray Beach, Florida. Neuroimaging using Single Photon Emission Computer Tomography (SPECT) brain scans performed pre- and post-HBOT were made available for secondary analysis. Nilearn Python Library was utilized to visualize the corresponding neuroimaging data. A two-sided paired t-test in R was used to compare the pre- and post-treatment results. Intervention: A full treatment of HBOT involved 40 sessions. Each session consisted of the administration of 100% oxygen at 1.5 atmospheres for 90 min, twice a day, for 20 days, Mondays to Fridays only. Main Outcome and Measure: Perfusion in the brain’s Brodmann Areas (BA) comparing pre- and post-HBOT using NeuroGam software analysis from brain SPECT scan neuroimaging and multi-symptom self-reports. Results: A comparison between the pre- and post-HBOT brain scans showed significant improvement in the brain perfusion, and the difference was statistically significant (p < 0.001). Separately, participants reported reduced pain, improved mood, and better sleep, an outcome that translated into an average of about 46.6% improvement in the measured symptoms. Conclusions and Relevance: This series demonstrated that HBOT could be a useful treatment for mTBI in U.S. veterans. The participants in the study showed marked improvement in both brain perfusion measured on SPECT scan imaging and measured mTBI symptoms. This is the first study to use brain SPECT scans with quantitative numerical measurements to demonstrate improvement in brain perfusion in veterans with mild TBI treated with HBOT and measured mTBI symptoms. Future research studies are currently being done to validate these important findings. Full article

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia. Various animal models are widely used to investigate its underlying mechanisms, including lipopolysaccharide (LPS)-induced neuroinflammation models. Aim: In this study, we aimed to investigate the effect of different doses (0.25, 0.5, and 0.75 mg/kg) of LPS on short- and long-term spatial memory and hippocampal morphology in an experimental AD mouse model. Materials and methods: Twenty-four adult male Swiss mice (SWR/J) weighing 18–25 g were divided into four groups: control, 0.25 mg/kg LPS, 0.50 mg/kg LPS, and 0.75 mg/kg LPS. All groups were treated with LPS or vehicle for 7 days. Behavioral tests were started (Morris water maze for 6 days and Y maze for 1 day) on the last 2 days of injections. After the behavioral procedures, tissues were collected for further histological investigations. Result: All LPS doses induced significant short- and long-term spatial memory impairment in both the Y maze and Morris water maze compared with the control group. Furthermore, histological examination of the hippocampus indicated degenerating neurons in both the 0.50 mg/kg and 0.75 mg/kg LPS groups, while the 0.25 mg/kg LPS group showed less degeneration. Conclusion: our results showed that 0.75 mg/kg LPS had a greater impact on early-stage spatial learning memory and short-term memory than other doses. Our behavioral and histological findings suggest 0.75 mg/kg LPS as a promising dose for LPS-induced AD models. Full article

Number and picture rapid automatized naming (RAN) tests are useful sideline diagnostic tools. The main outcome measure of these RAN tests is the completion time, which is prolonged with a concussion, yet yields no information about eye movement behavior. We investigated eye movements during a digitized Mobile Universal Lexicon Evaluation System (MULES) test of rapid picture naming. A total of 23 participants with a history of concussion and 50 control participants performed MULES testing with simultaneous eye tracking. The test times were longer in participants with a concussion (32.4 s [95% CI 30.4, 35.8] vs. 26.9 s [95% CI 25.9, 28.0], $t=6.1$). The participants with a concussion made more saccades per picture than the controls (3.6 [95% CI 3.3, 4.1] vs. 2.7 [95% CI 2.5, 3.0]), and this increase was correlated with longer MULES times (r = 0.46, p = 0.026). The inter-saccadic intervals (ISI) did not differ between the groups, nor did they correlate with the test times. Following a concussion, eye movement behavior differs during number versus picture RAN performance. Prior studies have shown that ISI prolongation is the key finding for a number-based RAN test, whereas this study shows a primary finding of an increased saccade number per picture with a picture-based RAN test. Number-based and picture-based RAN tests may be complimentary in concussion detection, as they may detect different injury effects or compensatory strategies. Full article

Primary progressive aphasia (PPA) is a neurodegenerative disorder with a progressive loss of language. Long-term support requires speech therapy but also individually set training programs. Here we propose an 8-month individualized speech-training program which alternates 3-week periods of transcranial direct current stimulation (tDCS) treatment with intensive daily language exercises and a 3-week period without tDCS treatment and a less intensive language exercise from home in a patient with non-fluent variant PPA (nfvPPA). The endpoints were the following: adherence to this program, language data after 8 months, questionnaires related to emotional valence, and brain volume changes. The results showed a persistent adherence after 8 months and a positive compliance reported by both the patient and the partner. The language evaluation showed a clinical stabilization. Moreover, a significant and positive influence of tDCS on mood was observed. This is, to our knowledge, the first ever published report of a combined neuromodulation and language training during the course of 8 months. Our finding suggests the feasibility of programs integrating hospital speech therapy, home training, and tDCS modulation in PPA. Further studies should be conducted in order to disentangle the contextual influences on language performance from the tDCS intervention effects and to address the observation of an initial improvement and a subsequent stabilization effect of language performances. Full article

Background and Objective: Intracranial atherosclerosis (ICAS) is one of the most common causes of stroke worldwide. High-resolution Vessel Wall MR imaging (VW-MR) is commonly used to study ICAS, but in order to accelerate advances in the field of VW-MR ICAS research, the establishment of a multicenter research network is needed. We introduce our experience in establishing a collaborative international VW-MR ICAS research network in China and North America using an innovative, disease-specific ICAS imaging phantom for standardization of VW-MR sequences at the sites. Methods: Both the Medical University of South Carolina and Peking Union Medical College functioned as Central Coordinating Centers in the network. PUMC identified research centers within China that had the potential for collaboration on VW-MR ICAS research based on networking and prior experience. All selected centers refined MRI sequences using an ICAS phantom with study principal investigators virtually present in real-time during scanning. MRI sequences were efficiently calibrated utilizing the broad expertise of all members of the research team. All centers further validated MRI sequences with human subjects. Results: We identified 11 Chinese hospitals as the potential collaborating sites for the network. Of the 11 selected sites, six sites were able to complete the required VW-MR scanning and sequence refinement using the ICAS phantom and subsequent human subjects. Conclusion: The study demonstrated the feasibility of establishing a cross-continent collaborative VW-MR research network and the use of a disease-specific phantom to facilitate convenient and efficient sequence modification for image quality standardization, which is needed for future multicenter VW-MR studies. Full article