关键词： Functional neurological disorder   Conversion disorder   Neuropsychiatry   Formulation   Psychodynamic therapy   Cognitive behavioural therapy  

摘要： Background Functional Neurological Disorder (FND) is a complex neuropsychiatric condition with a multifactorial aetiology. The heterogeneity of patients with FND is rarely considered in psychotherapy trials, which may contribute to variable outcomes. Shared Individual Formulation Therapy (SIFT) is a new, brief (four session) psychotherapy that aims to accommodate heterogeneity by providing a personalised, trans-theoretical formulation of the person's difficulties and accompanying management plan. Methods An open-label, prospective trial of outpatient SIFT for adults with FND was conducted, using health-related quality of life (SF-12) as the principal outcome measure, with secondary measures of mental health, dissociation, health care use and attitude to the FND diagnosis. Measures were collected at baseline, end of treatment and 6- and 12-month follow-ups. Results Twenty-nine participants with various FND symptoms enrolled. Twenty-four completed all four sessions and 25 completed follow-up measures at 12 months. SF-12 scores improved significantly at end of treatment and were sustained throughout follow-up with moderate effect sizes (0.39-0.47;all p < 0.001). Most secondary outcomes also improved significantly at all time points. The intervention was highly acceptable and tolerable to patients and perceived as beneficial. Conclusion This trial provides preliminary evidence for initial and sustained benefit from SIFT for adults with FND. Further study is needed to validate these findings.

关键词： brain-derived neurotrophic factor (BDNF)   cognition   intellectual disability   intelligence quotient (IQ)   learning and memory   S100B  

摘要： Background Brain-derived neurotrophic factor (BDNF) and S100B are reported to play an important role in neurodevelopment and may contribute to developmental pathogenesis in neuropsychiatric diseases. In this study, we aimed to examine the possible roles of BDNF and S100B in the pathogenesis of nonsyndromic intellectual disability (NS-ID) and their relationship with cognitive performance. Methods Thirty-three patients with intellectual disability (ID) and 30 typically developing children were compared. BDNF and S100B serum levels were measured with ELISA. The Wechsler Intelligence Scale for Children-Revised Short form (WISC-R) and Leiter intelligence test were administered to determine the intelligence levels of subjects. Leiter intelligence test was applied to 10 participants (30.31%) in the ID group because they had speech and communication problems. All other participants underwent WISC-R. Results Brain-derived neurotrophic factor levels were found to be significantly low in the patient group (mean +/- SD, 67.43 +/- 29.74 pg/mL) compared with the control group (94.67 +/- 32.55 pg/mL) (P = 0.002). When S100B is assessed, there was no significant difference found between the patient group (335.05 +/- 279.89 pg/mL) and control group (295.30 +/- 146.55 pg/mL) (P = 0.901). There was a significant positive correlation between BDNF and performance IQ (r = 0.424 and P = 0.001) in all participants. In addition, positive correlations were found between BDNF levels and initiating speech time (r = -0.369 and P = 0.003). Conclusions Brain-derived neurotrophic factor deficiency is proposed to have a possible role in the pathology of NS-ID. High BDNF levels may be associated with better cognitive performance.

关键词： Brain injuries   Critical care   Cytokines   Immunosuppression   Infection  

摘要： Background Neurological injury can alter the systemic immune system, modifying the functional capacity of immune cells and causing a dysfunctional balance of cytokines, although mechanisms remain incompletely understood. The objective of this study was to assess the temporal relationship between changes in the activation status of circulating invariant natural killer T (iNKT) cells and the balance of plasma cytokines among critically ill patients with neurological injury. Methods We conducted an exploratory prospective observational study of adult (18 years or older) intensive care unit (ICU) patients with acute neurological injury (n = 20) compared with ICU patients without neurological injury (n = 22) and healthy controls (n = 10). Blood samples were collected on days 1, 2, 4, 7, 14, and 28 following ICU admission to analyze the activation status of circulating iNKT cells by flow cytometry and the plasma concentration of inflammation-relevant immune mediators, including T helper 1 (T(H)1) and T helper 2 (T(H)2) cytokines, by multiplex bead-based assay. Results Invariant natural killer T cells were activated in both ICU patient groups compared with healthy controls. Neurological patients had decreased levels of multiple immune mediators, including T(H)1 cytokines (interferon-gamma, tumor necrosis factor-alpha, and interleukin-12p70), indicative of immunosuppression. This led to a greater than twofold increase in the ratio of T(H)2/T(H)1 cytokines early after injury (days 1 - 2) compared with healthy controls, a shift that was also observed for ICU controls. Systemic T(H)2/T(H)1 cytokine ratios were positively associated with iNKT cell activation in the neurological patients and negatively associated in ICU controls. These relationships were strongest for the CD4(+) iNKT cell subset compared with the CD4(-) iNKT cell subset. The relationships to individual cytokines similarly differed between patient groups. Forty percent of the neurological patients developed an in

关键词： Diseases of the nervous system   Funding   Gene therapy   Life Sciences   general   Biotechnology   Biomedicine   Agriculture   Biomedical Engineering/Biotechnology   Bioinformatics  

关键词： Rhabdomyolysis   HyhyperCKemia   Creatine kinase   Myopathy   Acute kidney injury  

摘要： The objective of this retrospective cohort study was to evaluate demographic, clinical and laboratory characteristics of patients with rhabdomyolysis as defined by a serum creatine kinase (sCK) activity > 950 U/L. A total of 248 patients were recruited from the Department of Neurology, Medical University of Vienna, between 01/2000 and 12/2017, with a median sCK activity of 2,160U/I (IQR 1,342-4,786). Seizures (31.9%), illicit drugs/alcohol (9.7%) and exercise (8.5%) were the most common trigger factors. Rhabdomyolysis incidence rates in specific neurological diseases as estimated by the ratio between rhabdomyolysis cases and the total number of cases with the corresponding disease were highest in myopathies (49.8/1,000 person-years, 95% CI 32.3-67.4), followed by epilepsy (16.4/1,000 person-years, 95% CI 12.8-20.0) and stroke (11.9/1,000 person-years, 95% CI 8.4-15.4). The half-life of sCK activity was 1.5 days in the total cohort. In myopathies, sCK activity was significantly higher as compared to other disease entities 7 days after the peak measurement (p = 0.0023). Acute kidney injury (AKI) developed in 18 patients (7.3%) with no AKI-related deaths during the study period. In conclusion, rhabdomyolysis occurred in a broad range of neurological entities but was associated with a favorable prognosis in most cases rarely resulting in AKI and death. (C) 2021 The Author(s). Published by Elsevier B.V.

关键词： Neurological disorders   Neuroscience   Biomedicine   general   Cancer Research   Metabolic Diseases   Infectious Diseases   Molecular Medicine   Neurosciences  

摘要： Emerging reports of rare neurological complications associated with COVID-19 infection and vaccinations are leading to regulatory, clinical and public health concerns. We undertook a self-controlled case series study to investigate hospital admissions from neurological complications in the 28 days after a first dose of ChAdOx1nCoV-19 (n = 20,417,752) or BNT162b2 (n = 12,134,782), and after a SARS-CoV-2-positive test (n = 2,005,280). There was an increased risk of Guillain-Barre syndrome (incidence rate ratio (IRR), 2.90;95% confidence interval (CI): 2.15-3.92 at 15-21 days after vaccination) and Bell's palsy (IRR, 1.29;95% CI: 1.08-1.56 at 15-21 days) with ChAdOx1nCoV-19. There was an increased risk of hemorrhagic stroke (IRR, 1.38;95% CI: 1.12-1.71 at 15-21 days) with BNT162b2. An independent Scottish cohort provided further support for the association between ChAdOx1nCoV and Guillain-Barre syndrome (IRR, 2.32;95% CI: 1.08-5.02 at 1-28 days). There was a substantially higher risk of all neurological outcomes in the 28 days after a positive SARS-CoV-2 test including Guillain-Barre syndrome (IRR, 5.25;95% CI: 3.00-9.18). Overall, we estimated 38 excess cases of Guillain-Barre syndrome per 10 million people receiving ChAdOx1nCoV-19 and 145 excess cases per 10 million people after a positive SARS-CoV-2 test. In summary, although we find an increased risk of neurological complications in those who received COVID-19 vaccines, the risk of these complications is greater following a positive SARS-CoV-2 test. A self-controlled case series analysis of nearly 32 million people in England shows an increased risk of rare neurological complications in those who received COVID-19 vaccines and following SARS-CoV-2 infection. The results highlight 38 excess cases of Guillain-Barre syndrome per 10 million ChAdOx1nCoV-19 vaccinations.

摘要： Aim To explore the breadth of pediatric neurological conditions for which neuromuscular electrical stimulation (NMES) has been studied. Method Databases (PubMed, Google Scholar, Scopus, and Embase) were searched from 2000 to 2020, using the search terms 'neuromuscular electrical stimulation' OR 'functional electrical stimulation' with at least one of the words 'pediatric OR child OR children OR adolescent', and without the words 'dysphagia OR implanted OR enuresis OR constipation'. Articles focused on adults or individuals with cerebral palsy (CP) were excluded. Results Thirty-five studies met the inclusion criteria, with a total of 353 pediatric participants (293 unique participants;mean age 7y 4mo, range 1wk-38y). NMES was applied in a range of pediatric conditions other than CP, including stroke, spinal cord injury, myelomeningocele, scoliosis, congenital clubfoot, obstetric brachial plexus injury, genetic neuromuscular diseases, and other neuromuscular conditions causing weakness. Interpretation All 35 studies concluded that NMES was well-tolerated and most studies suggested that NMES could augment traditional therapy methods to improve strength. Outcome measurements were heterogeneous. Further research on NMES with larger, randomized studies will help clarify its potential to improve physiology and mobility in pediatric patients with neuromuscular conditions.

关键词： Bone cysts   Aneurysmal   Spine   Neoplasms   Sodium tetradecyl sulfate   Sclerotherapy  

摘要： Objective To assess the clinical efficacy, technical feasibility, and safety profile of percutaneous sclerotherapy utilizing sodium tetradecyl-sulfate foam (STS) as a first-line treatment strategy for aggressive spinal aneurysmal bone cysts (sABCs) presenting with neurological compromise. Materials and methods Between July 2013 and September 2019, eight consecutive patients (5 males;3 females;mean age 22 +/- 17, range 7-52) underwent fluoroscopic/CT-guided intraosseous sclerotherapy for sABCs. Pain and/or neurological compromise was the primary indications. Procedural data, complications, imaging, and clinical results were analyzed. Results Technical success was achieved in all cases. Mean procedure time was 25 +/- 15 min (range 6-167);1 to 5 repeat treatment cycles (mean 3.7 +/- 1.2) utilizing a mean 2.6mls +/- 1.3 (range 1-6) of agitated 3% STS, with a DLP mean dose of 158 +/- 91 mGy*cm (range 62-331) per procedure. One reported a minor complication (pain), but no significant complications. Two patients had persistent neurological deficit due to cord compression despite successful sclerotherapy, requiring surgical resection (and were thereby excluded from the final outcome analysis). The remaining six patients demonstrated a significant reduction in tumor volume (p = 0.028), pain (p = 0.027), and SINS (spinal instability neoplastic score) (p = 0.027) at up to 5 years of follow-up (mean 20 +/- 16.7, range 7-51 months). Conclusion Percutaneous sclerotherapy with STS is a minimally invasive, technically feasible, safe, and effective first-line treatment for primary sABCs causing pain and neurological compromise, alleviating the need for extensive surgery. It is most effective with three or more treatment cycles, in patients with higher SINS, pain scores, or tumor volumes at the initial presentation.

关键词： Ionized calcium   Hypocalcemia   Spontaneous subarachnoid hemorrhage   Coagulation abnormalities  

摘要： Background Spontaneous subarachnoid hemorrhage (SSAH) is associated with significant morbidity and mortality. Pathophysiological processes following initial bleeding are complex and not fully understood. In this study, we aimed to determine whether a low level of ionized calcium (Ca++), an essential cofactor in the coagulation cascade and other cellular processes, is associated with adverse neurological outcome, development of early hydrocephalus, and symptomatic vasospasm among patients with SSAH. Methods This was a retrospective single-center cohort study of all patients admitted for SSAH between January 1, 2009, and April 31, 2020. The primary outcome was an unfavorable neurological status at discharge, defined as a modified Rankin Scale score greater than or equal to 3. Secondary outcomes were the development of early hydrocephalus and symptomatic vasospasm. Multivariable logistic regression was performed to determine whether Ca++ was an independent predictor of these outcomes. Results A total of 255 patients were included in the final analysis. Hypocalcemia, older age, admission Glasgow Coma Scale (GCS) score, and admission Hunt-Hess classification scale (H&H) grades IV and V were independently associated with unfavorable neurological outcome, with adjusted odds ratios (ORs) of 1.93 (95% confidence interval [CI] 1.1-3.4;p = 0.02) for each 0.1 mmol L-1 decrease in the Ca++ level, 1.04 (95% CI 1.01-1.08;p = 0.02) for each year increase, 0.82 (95% CI 0.68-0.99;p = 0.04), and 6.29 (95% CI 1.14-34.6;p = 0.03), respectively. Risk factors for the development of hydrocephalus were hypocalcemia and GCS score, with ORs of 1.85 (95% CI 1.26-2.71;p = 0.002) for each 0.1 mmol L-1 decrease in the Ca++ level and 0.83 (95% CI 0.73-0.94;p = 0.005), respectively. Ca++ was not associated with symptomatic vasospasm (OR 1.04 [95% CI 0.76-1.41];p = 0.81). Among patients with admission H&H grade I-III bleeding, hypocalcemia was independently associated with unfavorable neurological o

关键词： experimental models   gene therapy   in vivo tracking   mesenchymal stem cells   nervous system   neuroimmune   transplantation  

摘要： Neurological disorders are diseases of the central nervous system (CNS), characterized by a progressive degeneration of cells and deficiencies in neural functions. Mesenchymal stem cells (MSCs) are a promising therapy for diseases and disorders of the CNS. Increasing evidence suggests that their beneficial abilities can be attributed to their paracrine secretion of extracellular vesicles (EVs). Administration of EVs that contain a mixture of proteins, lipids, and nucleic acids, resembling the secretome of MSCs, has been shown to mimic most of the effects of the parental cells. Moreover, the small size and safety profile of EVs provide a number of advantages over cell transplantation. Intranasal (IN) administration of EVs has been established as an effective and reliable way to bypass the blood-brain barrier (BBB) and deliver drugs to the CNS. In addition to pharmacological drugs, EVs can be loaded with a diverse range of cargo designed to modulate gene expression and protein functions in recipient cells, and lead to immunomodulation, neurogenesis, neuroprotection, and degradation of protein aggregates. In this review, we will explore the proposed physiological pathways by which EVs migrate through the nasal route to the CNS where they can actively target a region of injury or inflammation and exert their therapeutic effects. We will summarize the functional outcomes observed in animal models of neurological diseases following IN treatment with MSC-derived EVs. We will also examine key mechanisms that have been suggested to mediate the beneficial effects of EV-based therapy.