Brain and Behavior

Transcranial magnetic stimulation (TMS) has been evaluated as an effective treatment option for patients with major depressive disorder. However, there are limited studies that have evaluated the efficacy of TMS for other neuropsychiatric disorders such as anxiety and trauma‐related disorders. We reviewed the literature that has evaluated TMS as a treatment for anxiety and trauma‐related disorders.

We searched for articles published up to December 2017 in Embase, Medline, and ISI Web of Science databases, following the Preferred Items for Reporting of Systematic Reviews and Meta‐Analyses (PRISMA) statement. Articles (n = 520) evaluating TMS in anxiety and trauma‐related disorders were screened and a small subset of these that met the eligibility criteria (n = 17) were included in the systematic review, of which nine evaluated TMS in posttraumatic stress disorder (PTSD), four in generalized anxiety disorder (GAD), two in specific phobia (SP), and two in panic disorder (PD). The meta‐analysis was performed with PTSD and GAD since PD and SP had an insufficient number of studies and sample sizes.

Among anxiety and trauma‐related disorders, TMS has been most widely studied as a treatment for PTSD. TMS demonstrated large overall treatment effect for both PTSD (ES = −0.88, 95% CI: −1.42, −0.34) and GAD (ES = −2.06, 95% CI: −2.64, −1.48), including applying high frequency over the right dorsolateral prefrontal cortex. Since few studies have evaluated TMS for SP and PD, few conclusions can be drawn.

Our meta‐analysis suggests that TMS may be an effective treatment for GAD and PTSD.

Mesenchymal stem cell (MSC) transplantation has been reported to improve neurological function following neural injury. Many physiological and molecular mechanisms involving MSC therapy‐related neuroprotection have been identified.

A review is presented of articles that pertain to MSC therapy and diverse brain injuries including stroke, neural trauma, and heat stroke, which were identified using an electronic search (e.g., PubMed), emphasize mechanisms of MSC therapy‐related neuroprotection. We aim to discuss neuroprotective mechanisms that underlie the beneficial effects of MSCs in treating stroke, neural trauma, and heatstroke.

MSC therapy is promising as a means of augmenting brain repair. Cell incorporation into the injured tissue is not a prerequisite for the beneficial effects exerted by MSCs. Paracrine signaling is believed to be the most important mediator of MSC therapy in brain injury. The multiple mechanisms of action of MSCs include enhanced angiogenesis and neurogenesis, immunomodulation, and anti‐inflammatory effects. Microglia are the first source of the inflammatory cascade during brain injury. Cytokines, including tumor necrosis factor‐α, interleukin‐1β, and interleukin‐6, are significantly produced by microglia in the brain after experimental brain injury. The proinflammatory M1 phenotype of microglia is associated with tissue destruction, whereas the anti‐inflammatory M2 phenotype of microglia facilitates repair and regeneration. MSC therapy may improve outcomes of ischemic stroke, neural trauma, and heatstroke by inhibiting the activity of M1 phenotype of microglia but augmenting the activity of M2 phenotype of microglia.

This review offers a testable platform for targeting microglial‐mediated cytokines in clinical trials based upon the rational design of MSC therapy in the future. MSCs that are derived from the placenta provide a great choice for stem cell therapy. Although targeting the microglial activation is an important approach to reduce the burden of the injury, it is not the only one. This review focuses on this specific aspect.

Therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) on motor recovery of Parkinson's disease (PD) have been reported; however, the protocols of these studies varied greatly. The aim of this meta‐analysis was to evaluate the optimal rTMS parameters for motor recovery of PD.

Electronic databases were searched for studies investigating the therapeutic effects of rTMS on motor function in patients with PD. The section III of the Unified Parkinson's Disease Rating Scale (UPDRS) was extracted as the primary outcome, and the standardized mean difference (SMD) with 95% confidence interval (CI) was calculated.

Twenty‐three studies with a total of 646 participants were included. The pooled estimates of rTMS revealed significant short‐term (SMD, 0.37; p < 0.00001) and long‐term (SMD, 0.39; p = 0.005) effects on motor function improvement of PD. Subgroup analysis observed that high‐frequency rTMS (HF‐rTMS) was significant in improving motor function (SMD, 0.48; p < 0.00001), but low‐frequency rTMS (LF‐rTMS) was not. In particular, when HF‐rTMS targeted over the primary motor cortex (M1), in which the bilateral M1 revealed a larger effect size than unilateral M1. Compared to single‐session, multi‐session of HF‐rTMS over the M1 showed significant effect size. In addition, HF‐rTMS over the M1 with a total of 18,000–20,000 stimulation pulses yielded more significant effects (SMD, 0.97; p = 0.01) than other dosages.

In conclusion, multi‐session of HF‐rTMS over the M1 (especially bilateral M1) with a total of 18,000–20,000 pulses appears to be the optimal parameters for motor improvement of PD.

Clinically, Parkinson's disease (PD) presents with asymmetric motor symptoms. The left nigrostriatal system appears more susceptible to early degeneration than the right, and a left‐lateralized pattern of early neuropathological changes is also described in several neurodegenerative conditions, including Alzheimer's disease, frontotemporal dementia, and Huntington's disease. In this study, we evaluated hemispheric differences in estimated rates of atrophy in a large, well‐characterized cohort of PD patients.

Our cohort included 205 PD patients who underwent clinical assessments and T1‐weighted brain MRI's. Patients were classified into Early (n = 109) and Late stage (n = 96) based on disease duration, defined as greater than or less than 10 years of motor symptoms. Cortical thickness was determined using FreeSurfer, and a bootstrapped linear regression model was used to estimate differences in rates of atrophy between Early and Late patients.

Our results show that patients classified as Early stage exhibit a greater estimated rate of cortical atrophy in left frontal regions, especially the left insula and olfactory sulcus. This pattern was replicated in left‐handed patients, and was not influenced by the degree of motor symptom asymmetry (i.e., left‐sided predominant motor symptoms). Patients classified as Late stage exhibited greater atrophy in the bilateral occipital, and right hemisphere‐predominant cortical areas.

We show that cortical degeneration in PD differs between cerebral hemispheres, and findings suggest a pattern of early left, and late right hemisphere with posterior cortical atrophy. Further investigation is warranted to elucidate the underlying mechanisms of this asymmetry and pathologic implications.

To compare the incidence and clinical features of individuals presenting in emergency rooms (ER) with facial palsy during the Italian COVID‐19 outbreak and in the same period of 2019.

We retrospectively reviewed the medical records for all accesses to the six ER in the province of Reggio Emilia, Italy, during the first phase of the COVID‐19 pandemic (27 February‐3 May 2020) to identify all cases of diagnosed facial palsy. Clinical information was retrieved for each patient and compared with that of facial palsy cases presenting in 2019.

Between 27 February and 3 May 2020, 38 patients presented to provincial ERs for facial palsy; in 2019, there were 22 cases, for an incidence rate ratio of 1.73 (95% CI 1.02–2.92) for the 2020 cohort. Of the 2020 cohort, eight patients (21%) presented with active or recent symptoms consistent with COVID‐19 infection, compared with 2 (9%) in 2019 (p = .299); one was tested and resulted positive for SARS‐CoV‐2. Moreover, patients were younger (−11 years, p = .037) than those of the previous year and manifested a longer lag (+1.1 days, p = .001) between symptoms onset and ER presentation.

We observed a higher occurrence of facial palsy during the COVID‐19 outbreak compared to the same period of the previous year; 21% of patients presenting with facial palsy had active or recent symptoms consistent with SARS‐CoV‐2 infection, suggesting an excess risk of facial palsy during or after COVID‐19. These patients searched for medical attention later, probably because of the fear of contracting COVID‐19 during assistance.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation tool suited to alter cortical excitability and activity via the application of weak direct electrical currents. An increasing number of studies in the addiction literature suggests thattDCSmodulates subjective self‐reported craving through stimulation of dorsolateral prefrontal cortex (DLPFC). The major goal of this study was to explore effects of bilateralDLPFCstimulation on resting state networks (RSNs) in association with drug craving modulation. We targeted three large‐scaleRSNs; the default mode network (DMN), the executive control network (ECN), and the salience network (SN).

Fifteen males were recruited after signing written informed consent. We conducted a double‐blinded sham‐controlled crossover study. Twenty‐minute “real” and “sham”tDCS(2 mA) were applied over theDLPFCon two separate days in random order. Each subject received both stimulation conditions with a 1‐week washout period. The anode and cathode electrodes were located over the right and leftDLPFC, respectively. Resting statefMRIwas acquired before and after real and sham stimulation. Subjective craving was assessed before and after eachfMRIscan. TheRSNs were identified using seed‐based analysis and were compared using a generalized linear model.

Subjective craving decreased significantly after realtDCScompared to sham stimulation (p = .03). Moreover, the analysis shows significant modulation ofDMN,ECN, andSNafter realtDCScompared to sham stimulation. Additionally, alteration of subjective craving score was correlated with modified activation of the three networks.

Given the observed alteration of the targeted functional brain networks in methamphetamine users, new potentials are highlighted fortDCSas a network intervention strategy and rsfMRIas a suitable monitoring method for these interventions.

The neutrophil‐to‐lymphocyte ratio (NLR) has been shown to be a marker associated with inflammation and is independently associated with the adverse clinical outcomes of symptomatic intracranial hemorrhage, cancer, and cardiovascular disease. Hemorrhagic transformation (HT) is a serious complication of ischemic cerebral infarction and can be intensified by therapeutic interventions for acute ischemic stroke (AIS). The purpose of our research was to explore the predictive effect of NLR for HT in patients with AIS and to determine the best predictive value.

PubMed, Web of Science, EMBASE, MEDLINE, Cochrane, and Google Scholar were searched. The primary endpoint was HT, and subgroup analysis was performed. Review Manager software version 5.3 was used to statistically analyze the outcomes.

A total of seven studies including 3,726 patients met the inclusion criteria. The pooled odds ratio (OR) value of the high NLR that predicted HT in AIS patients was 1.53 (95% CI, 1.21–1.92; p = .0003). In addition, 1.10 (95% CI, 1.05–1.15; p < .0001) was the pooled OR of the high NLR associated with increased 3‐month mortality in patients with AIS. In the subgroup analysis with an NLR cutoff value of 7.5–11, the correlation between NLR above the cutoff value and the rate of HT in patients with AIS was statistically significant (OR, 7.93; 95% CI, 2.25–27.95; p = .001).

A high NLR can predict HT and 3‐month mortality in patients with AIS. Regardless of the country of origin and the sampling time, an NLR with a cutoff value of 7.5–11 was independently associated with HT in AIS patients.

The nature and frequency of nonmotor symptoms in primary adult‐onset cervical dystonia (CD) and blepharospasm (BSP) patients in Chinese populations remain unknown.

Hamilton's Depression Scale (HAMD), Hamilton's Anxiety Scale (HAMA), Addenbrooke's Cognitive Examination Revised (ACE‐R), Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale were used to evaluate NMS in 120 patients with primary focal adult‐onset dystonia (60 with BSP and 60 with CD) and 60 age‐, sex‐, and education level‐ matched healthy controls (HCs). Motor symptoms of BSP and CD patients were evaluated by Jankovic rating scale and Toronto Western Spasmodic Torticollis Rating Scale‐severity scale separately.

Twenty patients had depression, and 29 patients had anxiety. The mean HAMD and HAMA scores were significantly higher in patient groups. Thirty‐six patients had cognitive decline based on the cut‐off score of 75. The total score and scores of each domain of ACE‐R were significantly lower in patient groups than that in HCs. Quality of sleep was impaired in patient groups, and patients with CD had worse quality of sleep than patients with BSP. Thirty‐three BSP patients and 43 CD patients suffered from sleep disorder separately. The frequency of excessive daytime sleepiness did not differ between patients and HCs. No significant correlation was found between NMS and motor severity in the two forms of dystonia.

Current study suggests that NMS are prevalent in Chinese CD and BSP patients, and the motor severity of dystonia did not contribute to the severity of nonmotor symptoms. Assessment of nonmotor symptoms should be considered in clinical management of focal dystonia

The Danish Multiple Sclerosis Registry is the oldest operative and nationwide MS registry. We present The Danish Multiple Sclerosis Registry with its history, data collection, scientific contribution, and national and international research collaboration.

Detailed description of data collection, completeness, quality optimizing procedures, funding, and legal, ethical and data protection issues are provided.

The total number of registered cases with clinical isolated syndrome and multiple sclerosis since 1956 was by start of May 2020 30,023 of whom 16,515 cases were alive and residing in Denmark, giving a prevalence rate of about 284 per 100,000 population. The mean annual number of new cases receiving an MS diagnosis was 649 per year in the period 2010 to 2019. In total, 7,945 patients (48.1%) are receiving disease modifying therapy at the start of May 2020.

Multiple Sclerosis registers are becoming increasingly important, not only for epidemiological research but also by quantifying the burden of the disease for the patients and society and helping health care providers and regulators in their decisions. The Danish Multiple Sclerosis Registry has served as data source for a number of scientific publications including epidemiological studies on changes in incidence and mortality, cohort studies investigating risk factors for developing MS, comorbidities and socioeconomic outcomes in the MS population, and observational studies on effectiveness of disease modifying treatments outside the narrow realms of randomized clinical trials.