Admission Hemoglobin Is Prognostic for In-Hospital Mortality in Oldest-Old Patients with Acute Ischemic Stroke.

INTRODUCTION: Anemia is a common condition encountered in acute ischemic stroke, and only a few pieces of evidence has been produced suggesting its possible association with short-term mortality have been produced. The study sought to assess whether admission anemia status had any impact on short-term clinical outcome among oldest-old patients with acute ischemic stroke. MATERIALS AND METHODS: A retrospective review of Electronic Medical Recording System was performed in 2 tertiary hospitals. Data, from the oldest-old patients aged > = 80 years consecutively admitted with a diagnosis of acute ischemic stroke between January 1, 2015, and December 31, 2019, were analyzed. Admission hemoglobin was used as indicator for anemia and severity. Univariate and multivariate regression analyses were used to compare in-hospital mortality and length of in-hospital stay in different anemia statuses and normal hemoglobin patients. RESULTS: A total of 705 acute ischemic stroke patients were admitted, and 572 were included in the final analysis. Of included patients, 240 of them were anemic and 332 nonanemic patients. A statistical difference between the 2 groups was found in in-hospital mortality (p < 0.001). After adjustment for baseline characteristics, the odds ratio value of anemia for mortality were 3.91 (95% confidence intervals (CI) 1.60-9.61, p = 0.003) and 7.15 (95% CI: 1.46-34.90, p = 0.015) in moderate and severely anemic patients, respectively. Similarly, length of in-hospital stay was longer in anemic patients (21.64 ± 6.17 days) than in nonanemic patients (19.08 ± 5.48 days, p < 0.001). CONCLUSIONS: Increased severity of anemia may be an independent risk factor for increased in-hospital mortality and longer length of stay in oldest-old patients with acute ischemic stroke.

Inhibition of miR-103-3p Preserves Neurovascular Integrity Through Caveolin-1 in Experimental Subarachnoid Hemorrhage.

Caveolin-1 (Cav-1) is a constitutive structural protein of caveolae in the plasma membrane. It plays an important role in maintaining blood brain barrier (BBB) integrity. In this study, we identified that miR-103-3p, a hypoxia-responsive miRNA, could interact with Cav-1. In endothelial cells, miR-103-3p mimic diminished the expression of Cav-1 and tight junction proteins, which were rescued by the inhibition of miR-103-3p. We found a substantial increase of miR-103-3p and decease of Cav-1 in the rat subarachnoid hemorrhage (SAH) model. Pre-SAH intracerebroventricularly injection of miR-103-3p antagomir relieved Cav-1 loss, sequentially reduced BBB permeability and improved neurological function. Finally, we demonstrated that the salutary effects of miR-103-3p antagomir were abolished in Cav-1 knock-out mice, suggesting that Cav-1 was required for the miR-103-3p inhibition-induced neurovascular protection. Taken together, our findings suggest that the inhibition of miR-103-3p could exert neuroprotective effects through preservation of Cav-1 and BBB integrity, making miR-103-3p a novel therapeutic target for SAH.

An atypical pontine infarction presenting with segmental sensory disturbance and uncrossed sensory symptomatology: case report.

We reported a patient who presented with analgesia and thermanaesthesia from the face to T4 dermatome on the contralateral side to the lesion due to infarction of the dorsal tegmentum of the caudal pons, which was inconsistent with classical dorsolateral pontine infarction. We speculated that the lesion affected the trigeminothalamic tract deriving from the second-order neurons on the contralateral side and partial lateral spinothalamic tracts carrying pain and temperature sensation above T4 dermatome, while the spinal trigeminal tract and its nucleus on the ipsilateral side and other parts of lateral spinothalamic tracts were spared. This case showed the atypical presentations of dorsolateral pontine infarction and may provide clinicians with new diagnostic ideas.

Admission serum cholinesterase concentration for prediction of in-hospital mortality in very elderly patients with acute ischemic stroke: a retrospective study.

BACKGROUND: Cholinesterase as a sensitive biomarker for prognosis in a variety of conditions but it is rare in stroke studies. The very elderly (≥ 80 years of age) represent the most susceptible group of ischemic stroke. We aimed to determine whether admission serum cholinesterase concentration had any effect on clinical outcome in very elderly patients (individuals aged ≥ 80 years) with acute ischemic stroke. METHODS: A retrospective record review was conducted in two tertiary university hospitals. Elderly patients aged ≥ 80 years admitted with a diagnosis of acute ischemic stroke from January 1, 2014 to November 30, 2019, who had a cholinesterase concentration drawn, were included. The patients were grouped based on the inflection points of the locally weighted regression and smoothing scatterplot (LOESS) curve between cholinesterase levels and in-hospital mortality (study outcome) with lower concentration as reference group. RESULTS: A total of 612 patients were admitted with a diagnosis of acute ischemic stroke, and 569 met the inclusion criteria. A threshold effect was identified using regression smoothing scatterplot (LOESS), with one cutoff point of 4.0 KU/L. There was a significant difference in-hospital mortality was observed (P < 0.001). After adjusted demographic and clinical features, the OR of cholinesterase for mortality was 0.43 (95% CI 0.34-0.54, P < 0.001), suggesting that lower admission cholinesterase level was an independent risk factors for all-cause mortality among patients with AIS. CONCLUSIONS: We have demonstrated a significant association between admission cholinesterase concentration and in-hospital mortality in very elderly patients with AIS.

Effectiveness and safety of immunosuppressive therapy in neuromyelitis optica spectrum disorder during pregnancy.

OBJECTIVE: To evaluate the effectiveness and safety of immunosuppressive therapy in neuromyelitis optica spectrum disorder (NMOSD) during pregnancy. METHODS: Sixteen NMOSD patients who had at least one pregnancy after NMOSD onset were enrolled. The patients were divided into two groups according to whether they received immunosuppressive therapy during pregnancy. The annual relapse rate (ARR) before pregnancy (BP); during the first (DP1), second (DP2), and third trimesters (DP3); first trimester postpartum (PP1); and second trimester postpartum (PP2) were calculated. The Expanded Disability Status Scale (EDSS) was used to evaluate the degree of disability. Pregnancy outcomes were recorded and the children were followed up and their health condition was evaluated. RESULTS: In the group taking prednisone alone or in combination with azathioprine as immunosuppressive therapies, there was no difference among ARRs of each period (DP1, DP2, DP3, PP1, PP2) and BP. Compared with EDSS BP, EDSS increased slightly 6months postpartum with no statistical significance (p=0.102). In the group without immunosuppressive therapy, ARR increased during PP1 (p=0.014) and EDSS increased 6months postpartum as compared to BP (p=0.017). Moreover, the added EDSS value was higher in the group without immunosuppressive therapy than in the group with therapy (p=0.038). In 22 pregnancies from 16 patients, 16 pregnancies ended in live births and 6 pregnancies ended in abortions, including 2 spontaneous and 4 induced abortions. None of the children had congenital diseases or malformations. There were no records of abnormal growth among the children during 6months to 12years of follow-up. CONCLUSION: Untreated women showed a propensity for disease relapse in PP1 and increased degree of disability postpartum. Immunosuppressive therapy during pregnancy and postpartum period can reduce the risk of relapse and degree of disability. Immunosuppressive therapy with low-dose prednisone was relatively safe. However, the safety of azathioprine during pregnancy remains unclear and needs future reevaluation.

Axial MR diffusion tensor imaging and tractography in clinical diagnosed and pathology confirmed cervical spinal cord astrocytoma.

OBJECTIVE: To evaluate the diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) features of cervical spinal cord astrocytoma. METHODS: Eleven patients with cervical spinal cord astrocytomas and 10 healthy volunteers were recruited in this study. Conventional magnetic resonance imaging (MRI) and axial DTI were performed on a 3.0T MRI system. Apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) values for the lesions were measured. DTT was performed using the principal diffusion direction method. RESULTS: ADC values of the lesions and the normal-appearing tissue around the tumour (NATAT) on T2-weighted imaging (T2WI) increased. The ADC values of the lesions were higher. The FA values of the lesions and the NATAT decreased significantly, with the lesions having lower FA values. The RD value (1.36±0.49) of the tumours was significantly higher than those found in the healthy controls, but similar for the AD value (1.84±0.56). There were no differences in ADC or FA values between lesions and NATAT in McCormick Type I vs. Type II patients. Based on the DTT, 7 patients with solid mass tumours were classified as Type I. One patient with a solid mass, 2 patients with cystic degeneration inside the lesions, and 1 patient with a cyst around the mass were classified as Type II. CONCLUSIONS: FA values of the cervical spinal cord astrocytoma decreased, but the ADC values increased. DTI was sensitive for the evaluation of pathological changes that could not be visualized on T2WI. Our preliminary study indicates that DTT can be used to guide operation planning, and that axial images of DTT may be more valuable.

The potential of human umbilical cord-derived mesenchymal stem cells as a novel cellular therapy for multiple sclerosis.

Multiple sclerosis (MS) is a complex disease of neurological disability, affecting more than 300 out of every 1 million people in the world. The purpose of the study was to evaluate the therapeutic effects of human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation in MS patients. Twenty-three patients were enrolled in this study, and 13 of them were given hUC-MSC therapy at the same time as anti-inflammatory treatment, whereas the control patients received the anti-inflammatory treatment only. Treatment schedule included 1,000 mg/kg of methylprednisolone intravenously (IV) daily for 3 days and then 500 mg/kg for 2 days, followed by oral prednisone 1 mg/kg/day for 10 days. The dosage of prednisone was then reduced by 5 mg every 2 weeks until reaching a 5-mg/day maintenance dosage. Intravenous infusion of hUC-MSCs was applied three times in a 6-week period for each patient. The overall symptoms of the hUC-MSC-treated patients improved compared to patients in the control group. Both the EDSS scores and relapse occurrence were significantly lower than those of the control patients. Inflammatory cytokines were assessed, and the data demonstrated a shift from Th1 to Th2 immunity in hUC-MSC-treated patients. Our data demonstrated a high potential for hUC-MSC treatment of MS. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

A two-year follow-up study of cotransplantation with neural stem/progenitor cells and mesenchymal stromal cells in ischemic stroke patients.

Stem cell therapy is an emerging therapeutic modality in the treatment of stroke. We assessed the safety and feasibility of the cotransplantation of neural stem/progenitor cells (NSPCs) and mesenchymal stromal cells (MSCs) in patients with ischemic stroke. Eight patients were enrolled in this study. All patients had a hemisphere with infarct lesions located on one side of the territories of the cerebral middle or anterior arteries as revealed with cranial magnetic resonance imaging (MRI). The patients received one of the following two types of treatment: the first treatment involved four intravenous injections of MSCs at 0.5 × 10(6)/kg body weight; the second treatment involved one intravenous injection of MSCs at 0.5 × 10(6)/kg weight followed by three injections of MSCs at 5 × 10(6)/patient and NSPCs at 6 × 10(6)/patient through the cerebellomedullary cistern. The patients' clinical statuses were evaluated with the National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the Barthel index (BI). Six patients were given four cell transplantations. The most common side effect of stem cell transplantation in these six cases was low fever that usually lasted 2-4 days after each therapy. One patient exhibited minor dizziness. All side effects appeared within the first 2-24 h of cell transplantation, and they resolved without special treatment. There was no evidence of neurological deterioration or neurological infection. Most importantly, no tumorigenesis was found at a 2-year follow-up. The neurological functions, disability levels, and daily living abilities of the patients in this study were improved. While these observations support the use of the combination transplantation of NSPCs and MSCs as a safe and feasible method of improving neurological function, further studies that include larger samples, longer follow-ups, and control groups are still needed. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

Arachnoid involved in idiopathic hypertrophic pachymeningitis.

The cerebrospinal fluid (CSF) shows inflammatory changes in patients with idiopathic hypertrophic pachymeningitis (IHP), which is a rare disorder. However, systemic CSF research including immunoglobulins in patients with IHP are substantially lacking. In the study, clinical, laboratory, neuroradiologic and therapeutic data from 9 patients with IHP were retrospectively studied, and CSF changes were analyzed. Intracranial pressure was elevated in 4 patients. Protein levels in CSF were elevated in 5 patients (< 1g/L). IgA was elevated in 7 patients (> 0.5mg/dL), IgG was elevated in 8 patients (> 3.4 mg/dL) and IgM was elevated in 6 patients (>0.13 mg/dL) with IHP. CSF immunoglobulins, including IgA, IgG and IgM, were significantly elevated compared with levels in the control (P = 0.021, 0.018, 0.019). There were no linear correlations between IgG, IgM and protein in CSF, but there was a linear correlation between IgA and protein. In conclusion, CSF in IHP shows inflammatory changes, and protein levels are low to moderately elevated. CSF immunoglobulins, including IgA, IgG and IgM, also increased. The arachnoid is involved in IHP, a proportion of immunoglobulins may originate from the blood because of damage to the blood-CSF barrier at the arachnoid. Other intrathecal synthesis of immunoglobulins may be a secondary change due to alteration in the CSF's content to stabilize the internal environment or may be secreted by activated immune memory cells in the brain, which need further research.

Olanzapine-induced restless legs syndrome.

Only nine patients with olanzapine-induced restless legs syndrome (RLS) have been reported in the literature to our knowledge. We describe two patients with olanzapine-induced RLS treated at our hospital and review the nine reported patients. There were five women and six men aged between 28 and 62 years in the overall group. RLS symptoms emerged at olanzapine doses between 2.5 and 20mg. The symptoms improved in all patients when the dose was reduced and immediately disappeared when the medication was stopped. International Restless Legs Scale (IRLS) scores ranged from 10 to 35. Three patients had a family history of idiopathic RLS. Supplemental drugs were administered to control RLS symptoms in five patients. Ropinirole was effective in one patient, while two patients did not respond to the drug. Propoxyphene effectively relieved symptoms in one patient who did not respond to ropinirole or clonazepam. RLS symptoms did not recur following substitution of other antipsychotic drugs for olanzapine. In conclusion, olanzapine can induce RLS, particularly in patients with a family history of idiopathic RLS. More than half of the patients experienced severe to very severe symptoms. A dose-dependent relationship was observed between olanzapine and RLS symptoms. A gradual increase in dose may prevent olanzapine-induced RLS. The optimal treatment for olanzapine-induced RLS is discontinuation of olanzapine.

Idiopathic hypertrophic pachymeningitis: clinical, laboratory and neuroradiologic features in China.

Hypertrophic pachymeningitis is a rare chronic inflammatory disorder characterized by marked fibrous thickening of the cerebral and/or spinal dura mater. Clinical, laboratory, neuroradiologic and therapeutic data from 12 patients with idiopathic hypertrophic pachymeningitis (IHP) from our department were retrospectively studied. There were four men and eight women with a mean age of 49±15.3 years, and more than half of the patients (58%) were aged 40-60 years. Headache was the most common symptom, occurring in 92% of patients. Headache improved markedly and rapidly after glucocorticoid treatment. Optic nerve involvement was noted in seven patients (58%). C-reactive protein levels increased in 80% and the erythrocyte sedimentation rate increased in 71% of patients. Three patients were positive for autoantibodies, including antinuclear antibodies (ANA), perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA), anti-cardiolipin antibodies (ACA) and rheumatoid factor (RF). Cerebrospinal fluid showed inflammatory changes, and protein levels were low to moderately elevated. MRI revealed a thickened dura in all patients, and five patients (42%) were diagnosed with sinus stenosis/occlusion. IHP is a chronic inflammatory disorder of the dura with three groups of symptoms, namely headache, cranial nerve palsy and symptoms due to sinus stenosis/occlusion. However, IHP has different features in China in that it predominantly affects women and the age of onset is younger. Sinus stenosis/occlusion is relatively common in IHP patients in China.

Effects of transplanted GDNF gene modified marrow stromal cells on focal cerebral ischemia in rats.

OBJECTIVE: To evaluate the therapeutic effect of transplanted glial cell derived neurotrophic factor (GDNF) modified marrow stromal cells (MSCs) on an experimental ischemic brain injury based on the behavioral, morphological, and immunohistochemical observations. METHODS: The MSCs from four-week newborn rats were cultured in vitro. The cerebral ischemia and reperfusion model was established in adult Sprague-Dawley (SD) rats by using the suture method. Three days after model establishment, the animals were injected with prepared MSCs via their caudal veins. The animals were then divided into a sham-operation group, ischemia group, MSCs transplantation group, or GDNF+ MSCs transplantation group and were scored for their neurobehavioral manifestations at 3, 14, and 28 days after the transplantation was performed. At this time, the survival condition of intracerebral transplanted cells was measured by laser confocal microscopy while the effect of transplantation on the Generic Digital Beam Former (GDNF) expression in the ischemic brain tissue was evaluated. RESULTS: The MSCs cells transfected with GDNF gene were characterized by green fluorescence. Three days after the transplantation, the animals that underwent the cell transplantation showed significantly better behavioral data than the controls. Fourteen days after transplantation, the animals transplanted with GDNF gene modified MSCs were better than those transplanted with common MSCs. As compared with common MSCs transplantation, GDNF+MSCs transplantation was significantly more effective in reducing apoptotic cell volume and enhancing Bcl-2 expression, which was favorable for the ischemic brain injury. CONCLUSIONS: Transplanted GDNF modified MSCs can improve the nervous function and have a protective effect on the ischemic brain injury through reducing apoptotic cell volume and enhancing the expression of anti-apoptotic gene Bcl-2.

[Effects of altered peptide ligands (APLs) of proteolipid(136-150) on T-cell clone 4B.14a].

AIM: By investigating the effects of APLs of PLP(136-150) on T cell clone 4B.14a in-vitro and in-vivo, to determine the feasibility of APLs to prevent relapsing multiple sclerosis (MS) in human. METHODS: To mimic the clinic course of relapsing MS, SJL/J female mice were first irradiated at 450R and intravenously infused with 1x10(7) resting 4B.14a T cells per mouse. Then mice were immunized with 50 microg/mouse APL for inducing passive experiment allergic encephalomyelitis (EAE). The proliferation and cytokine production of 4B.14a T cells in response to APLs were also examined. RESULTS: Except 139A, 143A, 144A, 145A and 148A, other APLs triggered T cells to induce passive EAE; 4B.14a T cells well responded to the most APLs, weakly responded to 137A, 144A and 148A, but the response was suppressed by 139A. CONCLUSION: The effects of some APLs on 4B.14a T cells are different in-vitro and in-vivo. It may be feasible to select some APLs to prevent relapsing MS in human.