关键词： Lower limb robotic exoskeleton   multiple sclerosis   neuro-rehabilitation   oxygen consumption   REX   stroke  

摘要： While neuro-recovery is maximized through active engagement, it has been suggested that the use of robotic exoskeletons in neuro-rehabilitation provides passive therapy. Using oxygen consumption (VO2) as an indicator of energy expenditure, we investigated the metabolic requirements of completing exercises in a free-standing robotic exoskeleton, with 20 healthy and 12 neurologically impaired participants (six with stroke, and six with multiple sclerosis (MS)). Neurological participants were evaluated pre- and post- 12 weeks of twice weekly robotic therapy. Healthy participants were evaluated in, and out of, the exoskeleton. Both groups increased their VO2 level from baseline during exoskeleton-assisted exercise (Healthy: mean change in VO2 = 2.10 +/- 1.61 ml/kg/min, p =< 0.001;Neurological: 1.38 +/- 1.22, p = 0.002), with a lower predicted mean in the neurological sample (-1.08, 95%CI -2.02, -0.14, p = 0.02). Healthy participants exercised harder out of the exoskeleton than in it (difference in VO2 = 3.50, 95%CI 2.62, 4.38, p =< 0.001). There was no difference in neurological participants' predicted mean VO2 pre- and post- 12 weeks of robotic therapy 0.45, 95%CI -0.20, 1.11, p = 0.15), although subgroup analysis revealed a greater change after 12 weeks of robotic therapy in those with stroke (MS: -0.06, 95%CI -0.78, 0.66, p = 0.85;stroke: 1.00, 95%CI 0.3, 1.69, p = 0.01;difference = 1.06, p = 0.04). Exercise in a free-standing robotic exoskeleton is not passive in healthy or neurologically impaired people, and those with stroke may derive more benefit than those with MS.

关键词： Brain tumour surgery   Postoperative neurological deficit   Complications   Time course  

摘要： Background The postoperative course after surgery for primary brain tumours can be difficult to predict. We examined the time course of postoperative neurological deficits and analysed possible predisposing factors. Method Hundred adults with a radiological suspicion of low- or high-grade glioma were prospectively included and the postoperative course analysed. Possible predictors of postoperative neurological deterioration were evaluated. Results New postoperative neurologic deficits occurred in 37% of the patients, and in 4%, there were worsening of a preoperative deficit. In 78%, the deficits occurred directly after surgery. The probable cause of deterioration was EEG-verified seizures in 7, ischemic lesion in 5 and both in 1, resection of eloquent tissue in 6, resection close to eloquent tissue including SMA in 11 and postoperative haematoma in 1 patient. Seizures were the main cause of delayed neurological deterioration. Two-thirds of patients with postoperative deterioration showed complete regression of the deficits, and in 6% of all patients, there was a slight disturbance of the function after 3 months. Remaining deficits were found in 6% and only in patients with preoperative neurological deficits and high-grade tumours with mainly eloquent locations. Eloquent tumour location was a predictor of postoperative neurological deterioration and preoperative neurological deficits of remaining deficits. Conclusions Postoperative neurological deficits occurred in 41% and remained in 6% of patients. Remaining deficits were found in patients with preoperative neurological deficits and high-grade tumours with mainly eloquent locations. Eloquent tumour location was a predictor of neurological deterioration and preoperative neurological deficits of remaining deficits.

摘要： Mesenchymal stem cells are a promising tool in regenerative medicine, and their functions can be enhanced through genetic modification. Recent advances in genetic engineering provide several methods that enable gene delivery to mesenchymal stem cells. However, it remains to be decided whether genetic modification of mesenchymal stem cells by vectors carrying reporter or therapeutic genes leads to adverse effects on morphology, phenotypic profiles, and viability of transplanted cells. In this regard, we focus on the description of genetic modification methods of mesenchymal stem cells, their effectiveness, and the impact on phenotype/cell behavior/proliferation and the differentiation ability of these cells in vitro and in vivo. Furthermore, we compare the main effects of genetically modified mesenchymal stem cells with native mesenchymal stem cells when applied in the therapy of neurological diseases.

关键词： Rodent models   Inhibitors   Peptides and proteins   Central nervous system   Selectivity  

摘要： The mechanistic target of rapamycin (mTOR) pathway is hyperactivated in cancer and neurological disorders. Rapalogs and mTOR kinase inhibitors (TORKi) have recently been applied to alleviate epileptic seizures in tuberous sclerosis complex (TSC). Herein, we describe a pharmacophore exploration to identify a highly potent, selective, brain penetrant TORKi. An extensive investigation of the morpholine ring engaging the mTOR solvent exposed region led to the discovery of PQR626 (8). 8 displayed excellent brain penetration and was well-tolerated in mice. In mice with a conditionally inactivated Tsc1 gene in glia, 8 significantly reduced the loss of Tsc1-induced mortality at 50 mg/kg p.o. twice a day. 8 overcomes the metabolic liabilities of PQR620 (52), the first-in-class brain penetrant TORKi showing efficacy in a TSC mouse model. The improved stability in human hepatocytes, excellent brain penetration, and efficacy in Tsc1(GFAP )CKO mice qualify 8 as a potential therapeutic candidate for the treatment of neurological disorders.

摘要： CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, immunoglobulin M [IgM] paraprotein, cold agglutinins, and disialosyl antibodies) is a rare syndrome characterized by chronic neuropathy with sensory ataxia, ocular, and/or bulbar motor weakness in the presence of a monoclonal IgM reacting against gangliosides containing disialosyl epitopes. Data regarding associated hematologic malignancies and effective therapies in CANOMAD are scarce. We conducted a French multicenter retrospective study that included 45 patients with serum IgM antibodies reacting against disialosyl epitopes in the context of evocating neurologic symptoms. The main clinical features were sensitive symptoms (ataxia, paresthesia, hypoesthesia;n = 45, 100%), motor weakness (n = 18, 40%), ophthalmoplegia (n = 20, 45%), and bulbar symptoms (n = 6, 13%). Forty-five percent of the cohort had moderate to severe disability (modified Rankin score, 3-5). Cold agglutinins were identified in 15 (34%) patients. Electrophysiologic studies showed a demyelinating or axonal pattern in, respectively, 60% and 27% of cases. All patients had serum monoclonal pattern respectively, patients IgM gammopathy (median, 2.6 g/L;range, 0.1-40 g/L). Overt hematologic malignancies were diagnosed in 16 patients (36%), with the most frequent being Waldenstrom macroglobulinemia (n = 9, 20%). Forty-one patients (91%) required treatment of CANOMAD. Intravenous immunoglobulins (IVIg) and rituximab-based regimens were the most effective therapies with, respectively, 53% and 52% of partial or better clinical responses. Corticosteroids and immunosuppressive drugs were largely ineffective. Although more studies are warranted to better define the optimal therapeutic sequence, IVIg should be proposed as the standard of care for first-line treatment and rituximab-based regimens for second-line treatment. These compiled data argue for CANOMAD to be included in neurologic monoclonal gammopathy of clinical significance.

关键词： Paraneoplastic neurological syndrome   Onconeural antibodies   Autoimmunity  

摘要： Introduction: Paraneoplastic neurological syndromes (PNS) are immune-mediated diseases that occur in patients with tumors and can be associated with onconeural antibodies. Our aim was to describe our cohort of patients with PNS. Methods: Retrospective analysis of a cohort of patients followed in a Portuguese tertiary center, with autoantibodies against intracellular antigens from our PNS panel, between 2012 and 2017. Results: Among the 882 patients with suspected PNS (1029 samples), 37 (4.2%) had positive and 27 (3.1%) weak positive antibodies. A total of 17 (29.3%) PNS were diagnosed, 5 were classic syndromes. Autoantibodies found were anti-Yo, anti-Hu, anti-titin, anti-Ma2, anti-SOX1, anti-Ri and anti-CV2/CRMP5. They were associated with thymoma, breast, colon, parotid gland and lung (small-cell, neuroendocrine or carcinoid) cancer. Among the 17 PNS patients, no tumor was found in 4 (mean follow-up of 46 months);no patients improved with tumor treatment, while 8 improved with immunotherapy;ten patients (59%) died during follow-up. Twenty (60.6%) patients with positive antibodies and 21 (84.0%) with weak positive were not diagnosed with a PNS. sions: PNS had highly heterogenous clinical presentations. Response to tumor treatment was overall poor, with an unfavorable prognosis. In our cohort, only 29.3% of the patients with positive antibodies were diagnosed with a PNS.

关键词： Mouse nerve growth factor   Intracerebral hemorrhage   Modified Rankin scale score   Randomized clinical trial  

摘要： Background: ew drugs were confirmed to be effective in the treatments of neurological dysfunction caused by acute intracerebral hemorrhage (ICH). The present prospective clinical trial aims to evaluate the effect of mouse nerve growth factor (mNGF) on neurological function in patients with acute ICH. Methods: 60 patients with acute spontaneous ICH were randomized to receive mNGF (mNGF group) and citicoline (control group) for 4 weeks within 24-72 h after onset, respectively. The primary outcome was difference in the neurological functional outcome at 3 months by the modified Rankin Scale score (mRS). The secondary outcomes were the changes in hematoma volume at 4 weeks and 3 months. Results: There were 55 patients receiving treatment (29 patients in the mNGF group, 26 patients in the control group). Among the patients, 46 patients finished the trial at 3 months;the odds of a shift towards death or dependence (mRS > 3) at 3 months in the mNGF group were lower than that in the control group with adjustment for age, sex, NIHSS at admission, and hematoma volume at admission (adjusted OR, 0.185;95%CI, 0.059-0.582;P = 0.0039). The hematoma was gradually reduced in all 46 patients and absorbed after nonsurgical treatment at 3 months. There was no significant difference in hematoma volume between the two groups. No serious adverse event was found. Conclusions: The administration of mNGF and citicoline was well-tolerated in patients with acute ICH. mNGF was associated with improved neurological function and less disability in patients with ICH. Therefore, the quality of life of patients with ICH may be improved by mNGF.

关键词： Ebola virus   peripheral nervous system   sympathetic nervous system   parasympathetic nervous system   somatic ganglion   autonomic ganglion   dorsal root ganglion   enteric plexus  

摘要： Neurological signs and symptoms are the most common complications of Ebola virus disease. However, the mechanisms underlying the neurologic manifestations in Ebola patients are not known. In this study, peripheral ganglia were collected from 12 rhesus macaques that succumbed to Ebola virus (EBOV) disease from 5 to 8 days post exposure. Ganglionitis, characterized by neuronal degeneration, necrosis, and mononuclear leukocyte infiltrates, was observed in the dorsal root, autonomic, and enteric ganglia. By immunohistochemistry, RNAscope in situ hybridization, transmission electron microscopy, and confocal microscopy, we confirmed that CD68(+) macrophages are the target cells for EBOV in affected ganglia. Further, we demonstrated that EBOV can induce satellite cell and neuronal apoptosis and microglial activation in infected ganglia. Our results demonstrate that EBOV can infect peripheral ganglia and results in ganglionopathy in rhesus macaques, which may contribute to the neurological signs and symptoms observed in acute and convalescent Ebola virus disease in human patients.

关键词： Brain reward Cascade (BRC)   Opioid use disorder (OUD)   Neurotransmission   Endorphinergic mechanisms   Genetic testing of addiction liability   Dopamine release and homeostasis   Reward deficiency syndrome (RDS)   Endorphinergic deficiency syndrome   Dopamine deficiency syndrome   Precision addiction management'  

摘要： The extant literature confirms that an array of polymorphic genes related to- neurotransmitters and second messengers govern the net release of dopamine in the Nucleus Accumbens (NAc) in the mesolimbic region of the brain. They are linked predominantly to motivation, anti-stress, incentive salience (wanting), and wellbeing. Notably, in 2000 the Nobel Prize was awarded to Carlsson, Greengard, and Kandel for their work on the molecular and cellular function of dopaminergic activity at neurons. This historical psychopharmacological work involved neurotransmission of serotonin, endorphins, glutamate, and dopamine, and the seminal work of Blum, Gold, Volkow, Nestler, and others related to neurotransmitter function and related behaviors. Currently, Americans are facing their second and worst opioid epidemic, prescribed opioids, and easy access drive this epidemic of overdoses, and opioid use disorders (OUDs). Presently the clinical consensus is to treat OUD, as if it were an opioid deficiency syndrome, with long-term to life-long opioid substitution therapy. Opioid agonist administration is seen as necessary to replace missing opioids, treat OUD, and prevent overdoses, like insulin is used to treat diabetes. Treatment of OUD and addiction, in general, is similar to the endocrinopathy conceptualization in that it views opioid agonist MATs as an essential core to therapy. Is this approach logical? Other than as harm reduction, is using opioids to treat OUD therapeutic or harmful in the long term? This historical Trieste provides a molecular framework to understand the current underpinnings of endorphinergic/dopaminergic mechanisms related to opioid deficiency syndrome and generalized reward processing depletion. WC 249.

关键词： SARS-CoV-2   COVID-19   Cerebrospinal fluid   Neurological symptoms  

摘要： Highlights•Largest cohort of patients with COVID-19 and neurological symptoms who underwent LP. •In all 30 cases, RT-PCR for SARS-CoV-2 from CSF was negative. •CSF analysis findings, including WBC, were normal in most patients with COVID-19. •Neurological symptoms in COVID-19 seem to be caused mainly by indirect mechanism.