Endovascular treatment of acute intracranial vertebrobasilar artery occlusion: a multicenter retrospective observational study.

PURPOSE: This study aimed to evaluate prognostic parameters associated with favorable clinical prognosis and assess the feasibility and safety of three different treatment strategies in patients with acute intracranial vertebrobasilar artery occlusion (VBAO). METHODS: A total of 159 patients with acute VBAO at 3 stroke centers between September 2015 and October 2018 were retrospectively analyzed. Eighty-nine patients underwent mechanical thrombectomy (MT) alone, 43 underwent MT with additional rescue angioplasty, and 27 underwent primary balloon angioplasty (without or with stenting). In patients treated with primary or rescue balloon angioplasty (without or with stenting), a low-dose intra-arterial tirofiban injection was used. The reperfusion status was assessed after the procedure, and the functional outcome was assessed at 90-day follow-up. The baseline characteristics and 90-day prognosis of three different treatment subgroups were comparatively analyzed. RESULTS: Overall, successful reperfusion and a favorable outcome were achieved in 96.86% (154/159) and 46.54% (74/159) patients, respectively. The onset to puncture time (461.96 min vs 603.59 min, P = 0.000), procedure time (64.12 min vs 70.47 min, P = 0.007), and onset to reperfusion time (526.08 min vs 674.47 min, P = 0.000) were significantly shorter in patients with favorable outcomes than in those with poor outcomes. Among different endovascular treatment subgroups, no significant differences were found in successful reperfusion and 90-day outcome. Low-dose tirofiban did not increase the risk of symptomatic intracranial hemorrhage and the 90-day mortality in patients with acute VBAO. CONCLUSION: Individualized endovascular treatment strategy for selected patients with acute VBAO could achieve satisfactory reperfusion rate and favorable prognosis.

A novel RAB39B gene mutation in X-linked juvenile parkinsonism with basal ganglia calcification.

OBJECTIVES: Mutations in RAB39B have been reported as a potential cause of X-linked Parkinson's disease (PD), a rare form of familial PD. We conducted a genetic analysis on RAB39B to evaluate whether RAB39B mutations are related to PD in the Chinese population. METHODS: In this study, 2 patients from an X-linked juvenile parkinsonism pedigree were clinically characterized and underwent whole-exome sequencing. A comprehensive screening for RAB39B mutations in 505 sporadic patients with PD and 510 healthy controls in a Chinese population was also performed. RESULTS: A novel mutation, c. 536dupA (p.E179fsX48), in RAB39B was identified in the juvenile parkinsonism pedigree. Brain MRI and CT scans in the 2 patients revealed calcification within the bilateral globus pallidus. No other potentially disease-causing RAB39B mutations were found in sporadic PD patients and controls. CONCLUSIONS: X-linked juvenile parkinsonism could be caused by a RAB39B mutation, and basal ganglia calcification may be a novel clinical feature of RAB39B-related parkinsonism. © 2016 International Parkinson and Movement Disorder Society.

Effects of tetrathiomolybdate and penicillamine on brain hydroxyl radical and free copper levels: a microdialysis study in vivo.

Wilson disease is an inherited disorder of excessive copper accumulation. The commonly used drug d-penicillamine (PA) or trientine both cause a high incidence (10-50%) of neurological worsening, which rarely occurs with tetrathiomolybdate (TM) treatment. To investigate the mechanisms of neurologic deterioration after the initiation of chelation therapy, brain hydroxyl radical and free copper were assessed in vivo in this study. On days 3, 7, 14, and 21 after PA or TM administration, striatal hydroxyl radical levels of both TX mice and controls were assessed by terephthalic acid (TA) combined with microdialysis and high-performance liquid chromatography (HPLC). Within the same microdialysis samples, free copper was measured by inductively coupled plasma mass spectrometry (ICP-MS). The results showed that both hydroxyl radical and free copper markedly increased in the striatum of TX mice during PA administration but were not elevated when administering TM. These results suggested that the further increased free copper in the brain and oxidative stress caused by some chelators might contribute to the neurological deterioration.

Vitamin D and ischemic stroke - Association, mechanisms, and therapeutics.

Confronting the rising tide of ischemic stroke and its associated mortality and morbidity with ageing, prevention and acute management of ischemic stroke is of paramount importance. Mounting observational studies have established a non-linear association of vitamin D status with cardiovascular diseases, including ischemic stroke. Paradoxically, current clinical trials fail to demonstrate the cardiovascular benefits of vitamin D supplementation. We aim to update recent clinical and experimental findings on the role of vitamin D in the disease course of ischemic stroke, from its onset, progression, recovery, to recurrence, and the established and alternative possible pathophysiological mechanisms. This review justifies the necessities to address stroke etiological subtypes and focus on vitamin D-deficient subjects for investigating the potential of vitamin D supplementation as a preventive and therapeutic approach for ischemic stroke. Well-powered clinical trials are warranted to determine the efficacy, safety, timing, target individuals, optimal dosages, and target 25OHD concentrations of vitamin D supplementation in the prevention and treatment of ischemic stroke.

An overview on CV2/CRMP5 antibody-associated paraneoplastic neurological syndromes.

Paraneoplastic neurological syndrome refers to certain malignant tumors that have affected the distant nervous system and caused corresponding dysfunction in the absence of tumor metastasis. Patients with this syndrome produce multiple antibodies, each targeting a different antigen and causing different symptoms and signs. The CV2/collapsin response mediator protein 5 (CRMP5) antibody is a major antibody of this type. It damages the nervous system, which often manifests as limbic encephalitis, chorea, ocular manifestation, cerebellar ataxia, myelopathy, and peripheral neuropathy. Detecting CV2/CRMP5 antibody is crucial for the clinical diagnosis of paraneoplastic neurological syndrome, and anti-tumor and immunological therapies can help to alleviate symptoms and improve prognosis. However, because of the low incidence of this disease, few reports and no reviews have been published about it so far. This article intends to review the research on CV2/CRMP5 antibody-associated paraneoplastic neurological syndrome and summarize its clinical features to help clinicians comprehensively understand the disease. Additionally, this review discusses the current challenges that this disease poses, and the application prospects of new detection and diagnostic techniques in the field of paraneoplastic neurological syndrome, including CV2/CRMP5-associated paraneoplastic neurological syndrome, in recent years.

Two distinct neuroanatomical subtypes of migraine without aura revealed by heterogeneity through discriminative analysis.

The neurobiological heterogeneity in migraine is poorly studied, resulting in conflicting neuroimaging findings. This study used a newly proposed method based on gray matter volumes (GMVs) to investigate objective neuroanatomical subtypes of migraine. Structural MRI and clinical measures of 31 migraine patients without aura and 33 matched healthy controls (HCs) were explored. Firstly, we investigated whether migraine patients exhibited higher interindividual variability than HCs in terms of GMVs. Then, heterogeneity through discriminative analysis (HYDRA) was applied to categorize migraine patients into distinct subtypes by regional volumetric measures of GMVs. Voxel-wise volume and clinical characteristics among different subtypes were also explored. Migraine patients without aura exhibited higher interindividual GMVs variability. Two distinct and reproducible neuroanatomical subtypes of migraine were revealed. These two subtypes exhibited opposite neuroanatomical aberrances compared to HCs. Subtype 1 showed widespread decreased GMVs, while Subtype 2 showed increased GMVs in limited regions. The total intracranial volume was significantly positively correlated with cognitive function in Subtype 2. Subtype 1 showed significantly longer illness duration and less cognitive scores compared to Subtype 2. The present study shows that migraine patients without aura have high structural heterogeneity and uncovers two distinct and robust neuroanatomical subtypes, which provide a possible explanation for conflicting neuroimaging findings.

FcRn inhibitors: a novel option for the treatment of myasthenia gravis.

Myasthenia gravis is an acquired, humoral immunity-mediated autoimmune disease characterized by the production of autoantibodies that impair synaptic transmission at the neuromuscular junction. The intervention-mediated clearance of immunoglobulin G (IgG) was shown to be effective in controlling the progression of the disease. The neonatal Fc receptor (FcRn) plays a key role in prolonging the serum half-life of IgG. Antagonizing FcRn to prevent its binding to IgG can accelerate the catabolism of the latter, resulting in decreased levels of IgG, including pathogenic autoantibodies, thereby achieving a therapeutic effect. In this review, we detail the substantial research progress, both basic and clinical, relating to the use of FcRn inhibitors in the treatment of myasthenia gravis.

Clinical and Genetic Analysis in Neurological Wilson's Disease Patients With Neurological Worsening Following Chelator Therapy.

Objectives: None of the previous studies have focused on the genetic effect on neurological worsening in neurological Wilson's disease (WD) patients following chelator therapy. We aimed to evaluate the clinical and genetic role in the occurrence of neurological worsening. Methods: We retrospectively reviewed the medical records of neurological WD patients who received initial chelator therapy and genetic test. Clinical, laboratory, and genetic data were collected. The genotype was classified into two types: 1) severe mutation genotype: patients who carried at least one of the following three types of mutations: frameshift mutation, splicing mutation, or nonsense mutation; 2) non-severe mutation genotype: patients who only carried missense mutations. Then, the clinical features and genotype of the patients with and without neurological worsening were investigated. Results: Forty-seven neurological WD patients were identified with a median age at onset of 16.17 years (range 7.75-47 years) and 35 (74.5%) males. The mean interval from onset to diagnosis was 0.6 years (range: 0.5 months-6.25 years). Neurological deterioration was observed in 29 patients (61.7%) and the other 18 patients (38.3%) were stable or improved during anti-copper treatment. The neurological worsening was completely irreversible in 6 cases (20.7%) and partially irreversible in 16 cases (55.2%). The common deteriorated symptoms were as follows: rigidity in 20 cases (69%), speech difficulties in 20 cases (69%)), walking difficulties in 13 cases (44.8%), dysphagia in 9 cases (31%), and salivation in 9 cases (31%). The patients with neurological worsening had significantly younger age (p = 0.028), shorter delayed diagnosis time (p = 0.011), higher rate of dystonia (p = 0.003), and severe mutation genotype (p = 0.036), compared to those without neurological worsening. Conclusion: We found that younger age of onset, the presence of dystonia, and genotype with severe mutations may be predictive of neurological worsening in the neurological WD patients that received chelator therapy. For those patients, chelator therapy should be given with caution and needs closer observation during follow-up.

Neutrophil Percentage-to-Albumin Ratio: A Good Parameter for the Evaluation of the Severity of Anti-NMDAR Encephalitis at Admission and Prediction of Short-Term Prognosis.

Objectives: The purpose of this study was to investigate the association of neutrophil percentage-to-albumin ratio (NPAR) with the severity at admission and discharge (short-term prognosis) in patients with anti-N-methyl-D-aspartic acid receptor (NMDAR) encephalitis. Methods: Multivariable logistic regression models such as NPAR were constructed based on univariable regression results. Receiver operating characteristic (ROC) curves, nomograms, and concordance index (c-index) were used to evaluate the efficacy of the models in assessing disease severity at admission and predicting short-term prognosis, validated by bootstrap, Hosmer-Lemeshow goodness-of-fit test, calibration curves, and decision curve analysis. Results: A total of 181 patients with anti-NMDAR encephalitis diagnosed at the First Affiliated Hospital of Zhengzhou University were included. The results showed that NPAR had good sensitivity and specificity in assessing disease severity at admission and predicting short-term prognosis. The multivariable logistic regression models based on NPAR and other influencing factors had good discrimination, consistency, accuracy, calibration ability, applicability, and validity in assessing the severity at admission and predicting short-term prognosis. Conclusion: NPAR has good clinical value in assessing disease severity at admission and predicting short-term prognosis of patients with anti-NMDAR encephalitis.

Structural and Functional Brain Changes in Patients With Classic Trigeminal Neuralgia: A Combination of Voxel-Based Morphometry and Resting-State Functional MRI Study.

Objectives: Brain structural and functional abnormalities have been separately reported in patients with classic trigeminal neuralgia (CTN). However, whether and how the functional deficits are related to the structural alterations remains unclear. This study aims to investigate the anatomical and functional deficits in patients with CTN and explore their association. Methods: A total of 34 patients with CTN and 29 healthy controls (HCs) with age- and gender-matched were recruited. All subjects underwent structural and resting-state functional magnetic resonance imaging (fMRI) scanning and neuropsychological assessments. Voxel-based morphometry (VBM) was applied to characterize the alterations of gray matter volume (GMV). The amplitude of low-frequency fluctuation (ALFF) method was used to evaluate regional intrinsic spontaneous neural activity. Further correlation analyses were performed between the structural and functional changes and neuropsychological assessments. Results: Compared to the HCs, significantly reduced GMV was revealed in the right hippocampus, right fusiform gyrus (FFG), and temporal-parietal regions (the left superior/middle temporal gyrus, left operculo-insular gyrus, left inferior parietal lobule, and right inferior temporal gyrus) in patients with CTN. Increased functional activity measured by zALFF was observed mainly in the limbic system (the bilateral hippocampus and bilateral parahippocampal gyrus), bilateral FFG, basal ganglia system (the bilateral putamen, bilateral caudate, and right pallidum), left thalamus, left cerebellum, midbrain, and pons. Moreover, the right hippocampus and FFG were the overlapped regions with both functional and anatomical deficits. Furthermore, GMV in the right hippocampus was negatively correlated with pain intensity, anxiety, and depression. GMV in the right FFG was negatively correlated with illness duration. The zALFF value in the right FFG was positively correlated with anxiety. Conclusion: Our results revealed concurrent structural and functional changes in patients with CTN, indicating that the CTN is a brain disorder with structural and functional abnormalities. Moreover, the overlapping structural and functional changes in the right hippocampus and FFG suggested that anatomical and functional changes might alter dependently in patients with CTN. These findings highlight the vital role of hippocampus and FFG in the pathophysiology of CTN.

Alterations of degree centrality and functional connectivity in classic trigeminal neuralgia.

Objectives: Recent neuroimaging studies have indicated a wide range of structural and regional functional alterations in patients with classic trigeminal neuralgia (CTN). However, few studies have focused on the intrinsic functional characteristics of network organization in the whole brain. Therefore, the present study aimed to characterize the potential intrinsic dysconnectivity pattern of the whole brain functional networks at the voxel level using the degree centrality (DC) analysis in CTN patients. Methods: Thirty-four patients with CTN and twenty-nine well-matched healthy controls (HCs) participated in this study. All subjects underwent resting-state functional magnetic resonance imaging (rs-MRI) examination and clinical and neuropsychologic assessments. DC is a graph theory-based measurement that represents the overall functional connectivity (FC) numbers between one voxel and other brain voxels. We first investigated brain regions exhibiting abnormal DC, and further identified their perturbation on FC with other brain regions using a seed-based FC analysis in patients with CTN. In addition, correlation analyses were performed to evaluate the relationship between the abnormal DC value and clinical variables in CTN patients. Results: Compared with the HCs, the patients with CTN exhibited significantly greater DC values in the right pallidum and right putamen, and lower DC values in the right lingual gyrus, right calcarine sulcus, left paracentral lobule, and left midcingulate cortex. A further seed-based FC analysis revealed that the right lingual gyrus showed decreased FC within the visual network and with other core brain networks, including the sensorimotor network, default mode network, and salience network, relative to HCs. Additionally, the left midcingulate cortex exhibited decreased FC within the middle cingulate cortex and the visual network in CTN patients. Moreover, the DC value in the left midcingulate cortex was negatively correlated with the illness duration. Conclusion: The present study shows that CTN patients exhibited specific functional connectivity network alterations in the basal ganglia, visual network, and salience network, which may reflect the aberrant neural network communication in pain processing and modulation. These findings may provide novel insight for understanding the mechanisms of pain chronicity in CTN patients.

Zinc monotherapy for young patients with oligosymptomatic Wilson disease: A single center, retrospective study.

BACKGROUND AND AIMS: Few studies have focused on the treatment failure of zinc monotherapy for oligosymptomatic Wilson disease (WD) patients. Therefore, we aimed to evaluate the long-term efficacy of zinc monotherapy in oligosymptomatic patients and to analyze the possible factors that may influence the outcome of this treatment. METHODS: We retrospectively reviewed the medical records of oligosymptomatic WD patients who received zinc monotherapy from the time of diagnosis. Then, the characteristics of patients who were treated with zinc monotherapy successfully and those who experienced treatment failure were investigated. RESULTS: Forty oligosymptomatic WD patients were identified that have received zinc monotherapy as initial treatment, with a median age of 3.83 years at the time of diagnosis. 36 (90%) patients had abnormal alanine transaminase/aspartate transaminase levels at baseline. None of the patients became symptomatic during zinc monotherapy. 28 (70%, Group 1) patients were treated with zinc monotherapy successfully for a median period of 2.4 years. In Group 1, serum aminotransferase levels significantly decreased 6 and 12 months after zinc therapy compared to the baseline levels (P <  0.05). 12 (30%, Group 2) patients experienced treatment failure with zinc monotherapy due to uncontrolled serum liver enzyme levels, and d-penicillamine was combined. The baseline 24-hour urine copper levels before treatment were significantly higher in Group 2 compared to that in Group 1 (182.5 vs 90.92 µg /day, P = 0.018). Comparing the age at onset; ceruloplasmin, serum copper, ALT, and AST levels; and proportions of abdominal ultrasonography abnormality at baseline between Group 1 and 2 revealed no statistically significant differences. CONCLUSIONS: We found that high initial 24 -h urinary copper levels may lead to treatment failure of zinc monotherapy in oligosymptomatic WD patients. It might be reasonable to follow up liver function tests more closely during zinc monotherapy and to begin combination treatment with chelators early in patients with high level of 24 -h urinary copper.

Role of contrast-enhanced magnetic resonance high-resolution variable flip angle turbo-spin-echo (T1 SPACE) technique in diagnosis of transverse sinus stenosis.

PURPOSE: Transverse sinus stenosis (TSS) is the most sensitive imaging characteristic of idiopathic intracranial hypertension (IIH). This study aimed to assess the diagnostic performance of contrast-enhanced magnetic resonance high-resolution variable flip angle turbo-spin-echo (T1 SPACE) technique in TSS patients and evaluate the diagnostic accuracy of enhanced T1 SPACE, and phase-contrast magnetic resonance venography (PC MRV) with digital subtraction angiography (DSA) as standard imaging. METHOD: This prospective study enrolled 62 patients with suspected IIH and PC MRV-confirmed transverse sinus stenosis. All patients underwent lumbar puncture, PC MRV, enhanced T1 SPACE sequences and DSA examination. The accuracy, sensitivity, and specificity of enhanced T1 SPACE in detecting venous sinus stenosis were calculated and compared with those of PC MRV. Intermodality agreement (Kendall's rank correlation coefficients and weighted kappa statistic) was assessed. RESULTS: Sixty-two patients were enrolled from November 2016 to October 2018. For the measured stenosis, better correlation was observed in enhanced T1 SPACE and DSA (AUC = 0.953) than PC MRV (AUC = 0.871). Intermodality agreement of enhanced T1 SPACE (rk = 0.895 and weighted ĸ = 0.868) was better than PC MRV (rk = 0.753 and weighted ĸ = 0.653) compared with DSA. Thirty-seven intrasinus filling defects were detected by contrast-enhanced T1 SPACE, while only twenty of them were detected on source imaging of PC MRV. CONCLUSIONS: The contrast-enhanced T1 SPACE sequence was more sensitive and specific compared with PC MRV in assessing stenosis and detecting lesions in TSS patients. Accurate determination of the presence and extent of TSS using this technique might be useful in patient selection and guiding the treatment.

Clinical efficacy of combined sodium dimercaptopropanesulfonate and zinc treatment in neurological Wilson's disease with D-penicillamine treatment failure.

OBJECTIVES: There are limited pharmacological treatments for patients with neurological Wilson's disease (WD) and a history of copper-chelating treatment failure. METHODS: We retrospectively evaluated the clinical records of 38 patients with WD who were treated with sodium dimercaptopropanesulfonate (DMPS) and zinc (group 1) or zinc alone (group 2). All patients had a history of neurological deterioration during their previous treatment with D-penicillamine (DPA). RESULTS: Twenty-one patients were treated with intravenous DMPS for 4 weeks, followed by zinc gluconate for 6 months, and the treatment protocol was repeated twice. Relative to the baseline, repeated DMPS therapy and zinc maintenance therapy decreased neurological scores continuously (p < 0.01). Sixteen patients (76.2%) demonstrated neurological improvements after 1 year of therapy and four patients (19.0%) exhibited neurological deterioration at the follow-up session. In addition, 17 patients were treated with zinc monotherapy for 12 months. Two patients (11.8%) demonstrated neurological improvements and five patients (29.4%) exhibited neurological deterioration. Compared with the patients in group 2, a greater improvement ratio (p < 0.01) and lower deterioration ratio (p < 0.01) were observed in the patients in group 1 after 1 year of therapy. CONCLUSIONS: Our findings indicate that the safety and efficacy of combined treatment of DMPS and zinc is superior to those of zinc monotherapy in patients with neurological WD with a history of DPA treatment failure.

Plasma Homocysteine, Vitamin B12 and Folate Levels in Multiple System Atrophy: A Case-Control Study.

BACKGROUND: Multiple system atrophy (MSA) is a neurodegenerative disease, and its pathological hallmark is the accumulation of α-synuclein proteins. Homocysteine (Hcy) is an intermediate amino acid generated during the metabolism of methionine. Hcy may contribute to the pathogenesis of neurodegenerative disorders. Vitamin B12 and folate are cofactors necessary for the methylation of homocysteine. METHODS: This study compared the levels of serum Hcy, vitamin B12 and folate in patients with MSA with those in healthy people to reveal the possible association between MSA and plasma levels of Hcy, vitamin B12 and folate. We enrolled 161 patients with MSA and 161 healthy people in this study. The association between MSA and the levels of Hcy, vitamin B12 and folate were analyzed using binary logistic regression. RESULTS: The mean level of Hcy in patients with MSA was significantly higher than that in healthy controls (16.23 ± 8.09 umol/l vs 14.04 ± 4.25 umol/l, p < 0.05). After adjusting for age, sex and medical history, the odds ratio for Hcy was 1.07 (95% CI = 1.01-1.13, p < 0.05) for patients with MSA. Vitamin B12 and folate levels were not significantly different between patients with MSA and controls. CONCLUSION: Our data suggest that higher levels of Hcy may be associated with an increased risk for MSA.

Transplantation of Induced Pluripotent Stem Cells Alleviates Cerebral Inflammation and Neural Damage in Hemorrhagic Stroke.

BACKGROUND: Little is known about the effects of induced pluripotent stem cell (iPSC) treatment on acute cerebral inflammation and injuries after intracerebral hemorrhage (ICH), though they have shown promising therapeutic potentials in ischemic stoke. METHODS: An ICH model was established by stereotactic injection of collagenase VII into the left striatum of male Sprague-Dawley (SD) rats. Six hours later, ICH rats were randomly divided into two groups and received intracerebrally 10 µl of PBS with or without 1 × 10(6) of iPSCs. Subsequently, neural function of all ICH rats was assessed at days 1, 3, 7, 14, 28 and 42 after ICH. Inflammatory cells, cytokines and neural apoptosis in the rats' perihematomal regions, and brain water content were determined on day 2 or 3 post ICH. iPSC differentiation was determined on day 28 post ICH. Nissl(+) cells and glial fibrillary acidic protein (GFAP)(+) cells in the perihematoma and the survival rates of rats in two groups were determined on post-ICH day 42. RESULTS: Compared with control animals, iPSCs treatment not only improved neurological function and survival rate, but also resulted in fewer intracephalic infiltrations of neutrophils and microglia, along with decreased interleukin (IL)-1ß, IL-6 and tumour necrosis factor-alpha (TNF-α), and increased IL-10 in the perihematomal tissues of ICH rats. Furthermore, brain oedema formation, apoptosis, injured neurons and glial scar formation were decreased in iPSCs-transplanted rats. CONCLUSIONS: Our findings indicate that iPSCs transplantation attenuate cerebral inflammatory reactions and neural injuries after ICH, and suggests that multiple mechanisms including inflammation modulation, neuroprotection and functional recovery might be involved simultaneously in the therapeutic benefit of iPSC treatment against hemorrhagic stroke.

Increased frequency of circulating regulatory T cells in patients with acute cerebral hemorrhage.

Cerebral hemorrhage (ICH) is a serious stroke subtype, currently lacking effective treatment. Recent research has shown that CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) play a key role in the immune response of ischemic stroke. However, Tregs in human hemorrhagic stroke are poorly investigated. In this study, a total of 90 ICH patients and 60 healthy controls were recruited. The frequency of circulating Tregs, plasma levels of TGF-ß and IL-10, and the severity of neural dysfunction in ICH patients were investigated at different time points post ICH. We found that the peripheral frequency of Tregs in ICH patients was significantly increased, accompanied by boosted activated T cells. Importantly, the elevation of circulating Tregs in patients with severe dysfunction was much higher than that in less-severe patients, suggesting that disease severity affects circulating Tregs to exert regulatory function. Furthermore, both TGF-ß and IL-10 that are related to the function of Tregs, were also increased in the peripheral blood of ICH patients. Our results demonstrate that Tregs-mediated immune imbalance might affect the development and severity of ICH, and suggest that Tregs may be used as tools and targets of cellular immunotherapy to effectively treat acute hemorrhagic stroke.

Nerve growth factor for the treatment of spinocerebellar ataxia type 3: an open-label study.

BACKGROUND: Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of SCA worldwide, and runs a slowly progressive and unremitting disease course. There is currently no curable treatment available. Growing evidence has suggested that nerve growth factor (NGF) may have therapeutic effects in neurodegenerative diseases, and possibly also in SCA3. The objective of this study was to test the efficacy of NGF in SCA3 patients. METHODS: We performed an open-label prospective study in genetically confirmed adult (>18 years old) SCA3 patients. NGF was administered by intramuscular injection (18 µg once daily) for 28 days consecutively. All the patients were evaluated at baseline and 2 and 4 weeks after treatment using the Chinese version of the scale for assessment and rating of ataxia (SARA). RESULTS: Twenty-one SCA3 patients (10 men and 11 women, mean age 39.14 ± 7.81 years, mean disease duration 4.14 ± 1.90 years, mean CAG repeats number 77.57 ± 2.27) were enrolled. After 28 days of NGF treatment, the mean total SARA score decreased significantly from a baseline of 8.48 ± 2.40 to 6.30 ± 1.87 (P < 0.001). Subsections SARA scores also showed significant improvements in stance (P = 0.003), speech (P = 0.023), finger chase (P = 0.015), fast alternating hand movements (P = 0.009), and heel-shin slide (P = 0.001). CONCLUSIONS: Our preliminary data suggest that NGF may be effective in treating patients with SCA3.