Neurological Motor Deficits Research Articles

Anti-Zn2+-Toxicity of 4-Hydroxybenzyl Alcohol in Astrocytes and Neurons Contribute to a Robust Neuroprotective Effects in the Postischemic Brain.

4-Hydroxybenzyl alcohol (4-HBA) is an important phenolic constituent of Gastrodia elata (GE) Blume, which is used as a traditional herbal medicine in East Asia. Many activities have been reported to underlie the beneficial effects of 4-HBA in brain, such as, anti-oxidative, anti-inflammatory, anti-excitotoxic, and anti-apoptotic effects in neurons and microglia. Here, the authors demonstrate the robust neuroprotective effects of 4-HBA in rat middle cerebral artery occlusion (MCAO) model of stroke, and showed anti-Zn2+ toxicity in neurons and astrocytes as a molecular mechanism contributing to these effects. Intraperitoneal administration of 4-HBA (20mg/kg) in Sprague-Dawley rats 1h after MCAO reduced infarct volumes to 27.1±9.2% of that of MCAO controls and significantly ameliorated motor impairments and neurological deficits. Significant suppressions of Zn2+-induced cell death, ROS generation, and PARP-1 induction by 4-HBA were observed in primary cortical cultures. 4-HBA also protected astrocytes from Zn2+-induced toxicity and suppressing ROS generation by employing slightly different molecular mechanisms, i.e., suppressing PARP-1 induction and NAD depletion under acute Zn2+-treatment and suppressing p67 NADPH oxidase subunit induction under chronic Zn2+-treatment. Results indicate that the protective effects of 4-HBA against Zn2+-toxicity in neurons and astrocytes contribute to its robust neuroprotective effects in the postischemic brain. Considering the pleiotropic effects of 4-HBA, which have been reported in previous reports and added in the present study, it has therapeutic potential for the amelioration of ischemic brain damage.

Investigation of left and right lateral fluid percussion injury in C57BL6/J mice: In vivo functional consequences

Although rodent models of traumatic brain injury (TBI) reliably produce cognitive and motor disturbances, behavioral characterization resulting from left and right hemisphere injuries remains unexplored. Here we examined the functional consequences of targeting the left versus right parietal cortex in lateral fluid percussion injury, on Morris water maze (MWM) spatial memory tasks (fixed platform and reversal) and neurological motor deficits (neurological severity score and rotarod). In the MWM fixed platform task, right lateral injury produced a small delay in acquisition rate compared to left. However, injury to either hemisphere resulted in probe trial deficits. In the MWM reversal task, left-right performance deficits were not evident, though left lateral injury produced mild acquisition and probe trial deficits compared to sham controls. Additionally, left and right injury produced similar neurological motor task deficits, impaired righting times, and lesion volumes. Injury to either hemisphere also produced robust ipsilateral, and modest contralateral, morphological changes in reactive microglia and astrocytes. In conclusion, left and right lateral TBI impaired MWM performance, with mild fixed platform acquisition rate differences, despite similar motor deficits, histological damage, and glial cell reactivity. Thus, while both left and right lateral TBI produce cognitive deficits, laterality in mouse MWM learning and memory merits consideration in the investigation of TBI-induced cognitive consequences.

P033 Transcranial direct current stimulation in a mouse model of traumatic brain injury

Introduction Traumatic brain injury (TBI) causes long-term neurological disability in 7% of survivors for which there is no clinically proven therapies. Transcranial direct current stimulation (tDCS) is a prospective treatment currently being clinically tested in TBI patients. However, due to a lack of animal studies, the mechanisms and optimal stimulation parameters for tDCS are unknown. Objectives Our objective is to evaluate mechanisms and the efficacy of tDCS in a mouse model of TBI. We hypothesized that tDCS, applied during recovery phase after TBI, improves long-term neurologic outcome involving a sustained increase in cerebral blood flow (CBF). Materials & methods TBI was induced by controlled cortical impact (CCI) with a Benchmark Controlled Cortical Stereotaxic Impactor using a 3-mm flat-tip impounder deployed at a velocity of 5 m/s and a depth of 2.0 mm from the cortical surface. Pre-trained mice were subjected to TBI and tested at 3 weeks after trauma by Rotarod for neurologic motor deficits. Anodal tDCS (0.1 mA/15 min) or sham stimulation were applied every day for 4 days, starting 2 weeks after TBI. Using in vivo 2-photon laser scanning microscopy over the parietal cortex we monitored changes in microvascular blood flow and tissue oxygenation (NADH) before and after tDCS treatment. Results Anodal tDCS improved motor function in mice after TBI compared to sham treated mice as shown by latency to fall from the rotating rod (75.4 ± 12 s. vs. 55.6 ± 16 s, n = 4, P Conclusions tDCS acutely increases brain microvascular flow and tissue oxygenation that could contribute to neurologic improvement after TBI. The vasodilation observed may be mediated by tDCS-stimulated nitric oxide release. Support NIH-NIGMS P20GM109089-01A1, Rio Grande Neurosciences.

Treatment and outcome of neuroblastoma with intraspinal extension: A systematic review.

We performed a systematic review to define the long-term health problems and optimal treatment strategy for patients with neuroblastoma with intraspinal extension. Of 685 identified studies, 28 were included in this review. The burden of long-term health problems is high; a median of 50% of patients suffered from neurological motor deficit, 34% from sphincter dysfunction, and 30% from spinal deformity. The currently available literature remains suboptimal as a guide for treatment of NBL with intraspinal extension. More well-designed, prospective studies are needed to determine the optimal treatment strategy.

Surgical treatment of eloquent brain area tumors using neurophysiological mapping of the speech and motor areas and conduction tracts

To evaluate the efficacy of intraoperative neurophysiological mapping in removing eloquent brain area tumors (EBATs). Sixty five EBAT patients underwent surgical treatment using intraoperative neurophysiological mapping at the Pirogov National Medical and Surgical Center in the period from 2014 to 2015. On primary neurological examination, 46 (71%) patients were detected with motor deficits of varying severity. Speech disorders were diagnosed in 17 (26%) patients. Sixteen patients with concomitant or isolated lesions of the speech centers underwent awake surgery using the asleep-awake-asleep protocol. Standard neurophysiological monitoring included transcranial stimulation as well as motor and, if necessary, speech mapping. The motor and speech areas were mapped with allowance for the preoperative planning data (obtained with a navigation station) synchronized with functional MRI. In this case, a broader representation of the motor and speech centers was revealed in 12 (19%) patients. During speech mapping, no speech disorders were detected in 7 patients; in 9 patients, stimulation of the cerebral cortex in the intended surgical area induced motor (3 patients), sensory (4), and amnesic (2) aphasia. In the total group, we identified 11 patients in whom the tumor was located near the internal capsule. Upon mapping of the conduction tracts in the internal capsule area, the stimulus strength during tumor resection was gradually decreased from 10 mA to 5 mA. Tumor resection was stopped when responses retained at a stimulus strength of 5 mA, which, when compared to the navigation data, corresponded to a distance of about 5 mm to the internal capsule. Completeness of tumor resection was evaluated (contrast-enhanced MRI) in all patients on the first postoperative day. According to the control MRI data, the tumor was resected totally in 60% of patients, subtotally in 24% of patients, and partially in 16% of patients. In the early postoperative period, the development or aggravation of a motor neurological deficit was detected in 18 patients: worsening of paresis was observed in 11 patients, and worsening of speech disorders occurred in 7 patients. After 4 months, motor and speech disorders regressed in 10 patients. Therefore, a persistent neurological deficit developed after surgery in 8 (12%) patients (motor deficit in 5 cases; speech deficit in 3 cases). Resection of eloquent brain area tumors using intraoperative neurophysiological monitoring enables complete resection of the tumor at a low risk of persistent neurological deficits, which ultimately improves the patient's life prognosis.

A Case Report of Complete Excision of Brachial Plexus Schwannoma: A Rare Entity

Brachial plexus schwannomas are rare benign nerve sheath tumors and only about 5% of schwannoma arise from the brachial plexus. They create a great challenge to surgeons due to their rare occurrence and complex anatomical location. We present a case of 37 yrs female presented with a right supraclavicular mass with severe radiating pain in right hand. Further investigation was done with MRI and FNAC which turns out to be huge right brachial plexus schwannoma. Gross total resection was done without any neurological motor defi cits. Nepal Journal of Neuroscience. Vol. 13, No. 2, 2016, Page: 92-93

Hsp70 inducer, 17-allylamino-demethoxygeldanamycin, provides neuroprotection via anti-inflammatory effects in a rat model of traumatic brain injury.

Traumatic brain injury (TBI) is the predominant cause of mortality in young adults and children living in China. TBI induces inflammatory responses; in addition, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 are important pro-inflammatory cytokines. Considering the observation that Hsp-70 overexpression can exert neuroprotection, identifying a drug that is able to induce the upregulation of Hsp70 has the potential to be a promising therapy for the treatment of neurological diseases. Thus, the present study assessed the clinical effectiveness of an anticancer drug and Hsp70 activator, 17-allylamino-demethoxygeldanamycin (17-AAG), to evaluate its potential as a treatment for patients with TBI. The aim of present study was to determine the neuroprotective effects of 17-AAG following trauma and to investigate the underlying mechanisms of action. To establish rat models, rats were subjected to a controlled cortical impact injury and randomly divided into vehicle or 17-AAG groups. In the 17-AAG group, rats were administered with an intraperitoneal injection of 17-AAG (80 mg/kg) immediately following the establishment of TBI. The motor function was measured using Neurologic Severity Score, and neuronal death was evaluated using immunofluorescence. The expression levels of GLT-1, Bcl-2 and Hsp-70 were detected by western blot analysis and the expression levels of inflammatory cytokines were quantified using ELISA. The present study determined that 17-AAG significantly reduced brain edema and motor neurological deficits (P<0.05), in addition to increasing neuronal survival. The aforementioned findings are associated with a downregulation of the expression levels of pro-inflammatory cytokines TNF-α, IL-1β and IL-6. Conversely, no significant changes of glutamate transporter-1 expression were observed. The present results suggest that 17-AAG treatment may provide a neuroprotective effect by reducing inflammation following TBI.

Management Strategy of Osteoblastomas Localized in the Occipitocervical Junction

The aim of this article was to analyze extracted patient data from the literature and highlight the best treatment options and survival outcomes for osteoblastomas in the occipitocervical region. A systematic literature search method was used to select articles containing information about the demographic features, tumor location, treatment characteristics, adjuvant therapies, and follow-up time. From 25 articles, 31 cases of osteoblastoma in the occipitocervical junction were selected for analysis. Average patient age was 17 years (range, 5-57 years); there were 21 male (67%) and 10 female (33%) patients. All patients had cervical pain as the presenting symptom. Other symptoms included torticollis (0.13%) and sensory or motor neurologic deficits (0.16%). The average follow-up time was 41 months, and the local recurrence rate was 0.125%. Recommendations of each article are categorized and discussed in detail. Osteoblastoma is a rare entity in the occipitocervical region, so treatment experiences are limited and mostly based on case reports. To determine the best treatment for these lesions, osteoblastomas should be staged using the Enneking staging system; different methods may be recommended for different stages, and the feasibility of fusion depends on the remaining amount of bony structures and joints. Additional adjuvant therapies may be recommended only in special cases.

An Eye-Blinking-Based Beamforming Control Protocol for Hearing Aid Users With Neurological Motor Disease or Limb Amputation.

For hearing-impaired individuals with neurological motor deficits or finger/arm amputation due to accident or disease, hearing aid adjustment using a conventional finger manipulation-based remote controller is unavailable, and a more dedicated, hands-free alternative is required. In this study, we propose an eye-blinking-based beamforming control scheme for hearing aid users. Three electroencephalogram signals measured around the ears were utilized to detect eye-blinking patterns based on a three-layer artificial neural network. The performance of the proposed control scheme was evaluated by both subjective experiments and objective index comparison tests in simulated situations. Experimental results from the subjective test demonstrated that without the pretraining phase, the accuracy and latency time were 68.57 ± 18.50% and 10.06 ± 0.94 s, respectively; in contrast, after the pretraining phase, both the accuracy and latency time were improved to 91.00 ± 4.69% and 8.60 ± 1.05 s, respectively. In index comparison tests, the proposed control scheme exhibited improvements in the signal-to-noise ratio (SNR) as well as the segmental SNR in all tested situations, as compared to a conventional forward-focusing beamforming algorithm. We believe that the proposed control scheme provides a novel, hands-free way in which to control the operation of hearing aids for hearing-impaired patients with additional motor deficits or amputation.

Spatial control of reflexes, posture and movement in normal conditions and after neurological lesions.

Control of reflexes is usually associated with central modulation of their sensitivity (gain) or phase-dependent inhibition and facilitation of their influences on motoneurons (reflex gating). Accumulated empirical findings show that the gain modulation and reflex gating are secondary, emergent properties of central control of spatial thresholds at which reflexes become functional. In this way, the system pre-determines, in a feedforward and task-specific way, where, in a spatial domain or a frame of reference, muscles are allowed to work without directly prescribing EMG activity and forces. This control strategy is illustrated by considering reflex adaptation to repeated muscle stretches in healthy subjects, a process associated with implicit learning and generalization. It has also been shown that spasticity, rigidity, weakness and other neurological motor deficits may have a common source – limitations in the range of spatial threshold control elicited by neural lesions.

Robust neuroprotective effects of 2-((2-oxopropanoyl)oxy)-4-(trifluoromethyl)benzoic acid (OPTBA), a HTB/pyruvate ester, in the postischemic rat brain.

Postischemic brain damage in stroke is proceded with complicated pathological events, and so multimodal drug treatments may offer better therapeutic means for improving clinical outcomes. Here, we report robust neuroprotective effects of a novel compound, 2-((2-oxopropanoyl)oxy)-4-(trifluoromethyl)benzoic acid (OPTBA), a 2-hydroxy-4-trifluoromethyl benzoic acid (HTB, a metabolite of triflusal)-pyruvate ester. Intravenous administration of OPTBA (5 mg/kg) 3 or 6 h after middle cerebral artery occlusion (MCAO) in Sprague-Dawley rats reduced infarct volumes to 38.5 ± 11.4% and 46.5 ± 15.3%, respectively, of that of MCAO controls, and ameliorated motor impairment and neurological deficits. Importantly, neuroprotective effects of OPTBA were far greater than those afforded by combined treatment of HTB and pyruvate. Furthermore, OPTBA suppressed microglial activation and proinflammatory cytokine inductions more effectively than HTB/pyruvate co-treatment in the postischemic brain and LPS-treated cortical slice cultures and also attenuated NMDA-induced neuronal death in hippocampal slice cultures. LC-MS analysis demonstrated that OPTBA was hydrolyzed to HTB and pyruvate with a t1/2 of 38.6 min in blood and 7.2 and 2.4 h in cortex and striatum, respectively, and HTB was maintained for more than 24 h both in blood and brain tissue. Together these results indicate OPTBA acts directly and via its hydrolysis products, thus acting as a multimodal neuroprotectant in the postischemic brain.

Spontaneous Resolution of Sequestrated Lumbar Disc Herniation: A Prospective Cohort Study

Objective Spontaneous regression of sequestrated lumbar disc well known entity. But, the current reports about this scenario are confined to case reports or small case series. To assess the chance of complete spontaneous resolution of sequestrated lumbar disc herniation and to report the outcome of regressed cases in a prospective study. Method From January 2010 to July 2015, 103 patients with acute lower limb mono-radiculopathy, but without neurological motor deficit secondary to a migrated lumbar disc herniation thought to be a sequestrated free disc fragment were prospectively studied for the possibility of their spontaneous regression with time. All the qualified patients initially fulfilled the study criteria. But seven patients were lost to follow up and 9 more cases preferred to do surgery within a few days to three weeks after clinical trial. Eighty seven patients remained for clinical evaluation and periodic magnetic resonance imaging for the possibility of spontaneous regression. These patients include 39 males and 48 females. The age of the patients ranged from 22 to67 years with the mean of 42.96, SD= 10.65. Results In 75 of these cases complete resolution of the offending disc occurred. This was associated with marked improvement or even disappearance of pain intensity in short and mid-term follow-up. Furthermore, where a case of same level contralateral disc herniation was seen, not a single case of same level same side recurrence could be encountered. The cost of treatment and work status of the patients were significantly better than surgically treated patients according to previously published reports. In mid-term follow, recovery rate (McNab Criteria %) of these 75 patients was either good or excellent. All these were satisfied and recommend this type of treatment for similar patients. The remaining 12 patients, ultimately underwent surgery. Surprisingly, all had subligamentous location Conclusion This study clarifies that conservative management might be considered as an appropriated cost-effective option in treatment of sequestrated lumbar disc herniation in the patients with minimal neurological impairment, with probably high chance of spontaneous regression of the offending disc. However, to compare conservative versus surgery, in this sub-type of disc herniation, further clinical trials are recommended.

How Safe is the XLIF Approach for a Skilled Surgeon, When He Starts to Perform It

Introduction The XLIF (extreme lateral interbody fusion) was introduced in 2001. It is useful as an alternative to ALIF approach especially in obese patients or in case of repeat surgeries to avoid vascular complications. This minimally invasive spine surgery allows to place big foot print implants, minimizing their subsidence and allows even to correct severe deformities. On the other side it is sophisticated, requires special instruments and neuromonitoring. One of the biggest disadvantages is a neurological deficit caused by the transpsoas access, despite of neuromonitoring. The incidence of mostly transient weakness and numbness reaches in the reports from 0,6 to 33%. The goal of this study was to estimate, if most of the reports were enthusiastic in terms of persistent deficits and if it is possible for a skilled surgeon to learn it in relatively short time. Material and Methods 40 patients (23 men and 23 women) in age of 25- 86 years (mean 63) underwent XLIF surgeries from march 2014 to august 2015 in our institution. All of them had neuromonitoring intraoperatively. Demographic data of the patients, indications, Op time, blood loss, outcome concerning neurological deficits and early complications were analyzed. The patients with deficit had at least 12 months follow up. We checked, if the surgery time becomes shorter, the more experience is present (4 skilled surgeons performed the procedures) and if deficits occur in the beginning of the learning curve. Results Most surgeries were monosegmental (37). Operated levels: L4/5: 26, L3/4: 9, L2/3: 5, L1/2: 3. Follow- up time was between 1 to 18 months (mean 7). Indications: instability: 15, degenerative: 13, discitis: 6, fractures: 4, deformity: 2. The Op time ranged from 37 to 134 minutes (mean76). In all patients the blood loss was not higher than 150 ml. 5 patients developed postoperatively motor neurological deficit. In 2 cases it was persistent (follow up time 13 and 12 months). The others were transient and resolved after 3 months. There were primarily 2 malpositions of implants (introduced into vertebral body of L 5 due to the angle of insertion), which leaded to 1 revision surgery. Persistent deficits occurred in 6. and 10. operated patients in the list, the transient in 18., 24. and 32. patient. 2 surgeries had to be abandoned due to the anatomical situation to avoid the iatrogenic nerve root damage. Conclusion The study shows, that even despite of correct neuromonitoring, neurological deficits can appear in XLIF approach. This complication seems to be dependent to the time of the retraction of the prevertebral structures. The longer the OP time (persistent weakness was associated with OP time longer than 120 minutes), the hazard of neurological arises (in transient ones Op times respectively: 58, 73 and 82 minutes). New technologies create often reluctance for many surgeons to accept it, as the learning curve may be long and complications rate high. After 4 surgeries the duration of the procedure was reduced at 35%. Compared with the data in the literature in own series, the neurological deficits were not higher and the learning curve relatively short. The accuracy of the approach (respecting the endplates space to avoid malpositioning) and the OP time has to be respected to avoid a nerve root damage. Reduction maneuvres and more manipulation may arise the ratio of complications. A skilled surgeon should be able to start performing the XLIF access without high rate of complications and become familiar with it after 4–5- surgeries.

Effects of Chinese medicine combined with rehabilitation care on motor function recovery and quality of life in stroke paralysis patients

Objective To explore the motor function recovery and quality of life effects of Chinese medicine combined with rehabilitation care for stroke paralysis patients. Methods A total of 140 stroke paralysis patients were equally randomly divided into treatment group and control group of 70 patients, both groups were given basic treatment with conventional rehabilitation care, on the basis of the treatment group were treated with acupuncture intervention, the intervention period were 3 months. Results The overall effective rate (97.1%) in the treatment group was significantly higher than that of the control group (80.0%) (P<0.05). The neurological deficits were significantly reduced, but motor function scores were increased significantly in the two groups after the intervention that compared with pre-intervention′s (P<0.05); at the same time, the neurological deficit motor function and motor function scores in the treatment group were also significantly better than that in the control group after intervention (P<0.05). The paralysis level after the intervention, both were significantly improved, and the level of paralysis in the treatment group were significantly better than that of the control group after the intervention (P<0.05). Conclusions Chinese medicine combined with rehabilitation care for stroke paralysis patients can improve motor function and neurological deficit recovery, and promote the improvement of the overall effects. Key words: Rehabilitation nursing; Acupuncture; Stroke; Paralysis; Motor function

Diffusion tensor imaging tractography and intraoperative neurophysiological monitoring in surgery of intracranial tumors located near the pyramidal tract

Practical application of methods for intravital examination of the brain pathways, such as preoperative diffusion tensor imaging (DTI) tractography and intraoperative neurophysiological monitoring, facilitates safer resection of intracranial tumors located near the pyramidal tracts (PTs). The study purpose was to investigate the relationships between intracerebral tumors of different histological nature and the pyramidal tract based on preoperative DTI tractography and various methods of intraoperative neurophysiological monitoring for intraoperative identification of the pyramidal tract, depending on different variants of the topographo-anatomic relationships between the pyramidal fascicle and the tumor. The study included 29 patients with supratentorial tumors of a different histological structure. Of these, 2 patients had grade I tumors, 8 patients had grade II tumors, 4 patients had grade III tumors, 11 patients grade IV tumors, and 4 patients had brain metastases. The patients underwent preoperative DTI tractography with PT reconstruction and evaluation of the topographo-anatomic relationships between the pyramidal tract and the tumor (tract: intact, infiltrated, displaced). Neurophysiological monitoring (direct electrical stimulation in 24 patients and transcranial motor evoked potentials in 26 patients) was used during surgery. The strength of stimulating current for direct stimulation was varied from 10 to 30 mA. Postoperatively, the motor function was evaluated by using a 5-score scale, and the data were compared to the preoperative data. According to preoperative DTI tractography in patients with grade I-II gliomas, the corticospinal tracts were infiltrated in 2 cases, displaced in 3 cases, and intact in 5 cases. In patients with grade III-IV gliomas and metastases, the tracts were infiltrated in 8 cases, displaced in 4 cases, and intact in 7 cases. Motor responses evoked by direct electrical stimulation were obtained in 5 out of 6 patients with the pyramidal tract displaced by the tumor and in 7 out of 8 patients with the tract infiltrated by the tumor. In the case of the intact tract, the PT to tumor distance and the stimulus strength play an important role: responses were obtained in 4 out of 10 patients. In the case of transcranial motor evoked potentials (TCMEPs), no dynamics of the potential amplitude was detected in 17 out of 26 patients during surgery; a reduced TCMEP amplitude was detected in 9 patients. 1. Patients with an infiltrated or displaced pyramidal tract had significantly more often hemiparesis before surgery and aggravation of hemiparesis after the surgery compared to patients with an intact tract. 2. In the case of direct electrical stimulation of the PT, motor responses (according to preoperative DTI tractography) were significantly more often observed for the pyramidal tract infiltrated and displaced by the tumor. 3. A reduction in the motor neurologic deficit in the postoperative period was significantly more often observed for application of a larger current strength during direct electrical stimulation. 4. Persistence of the TCMEP amplitude during surgery is a reliable predictor for no aggravation of the motor neurological deficit after surgery. Postoperative aggravation of hemiparesis was significantly more often observed when TC MEPs decreased during surgery.

Fibrocartilaginous Embolism of The Spinal Cord - A Case Report

Fibrocartilaginous embolism of the spinal cord is considered a rare ischemic vascular syndrome [1-4], though some authors believe it to be underdiagnosed. It results in abrupt onset and rapidly progressive sensory, motor and autonomic neurologic deficits. This paper reports a case of a teenage patient presenting with sudden onset rapidly progressive back pain associated with paraparesthesia, paraparesis and urinary retention after physical exertion. A magnetic resonance imaging (MRI) test led to a presumptive diagnosis of spinal cord fibrocartilaginous embolism.

Multi-institutional Nomogram Predicting Survival Free From Salvage Whole-Brain Radiation After Radiosurgery for Brain Metastases

(HP pZ0.043) and increased ECOG score (OR 4.76, 95%C.I. 2.4-9.4; p<0.001). 21.9% of the patients had neurologic deficits on initial presentation, 9.7% had cognitive decline, and 8.5% had seizures. When neurologic exam findings were included in a multivariable Cox model of all HP pZ0.001), cardiac comorbidities (OR 1.77, 95%C.I. 1.2-2.6; pZ0.005), neurologic comorbidities (OR 1.79, 95%C.I. 1.0-3.1; pZ0.042), and the presence of seizures (OR 1.8, 95%C.I. 1.05-3.15) predicted worse OS (Figure 1). Neurologic exam findings were not associated with OS. Interestingly, patients with neurologic motor deficits were more likely to have undergone surgical resection (p<0.001). Conclusion: Neurologic deficits are not associated with initial overall prognosis for patients with brain metastases undergoing radiosurgery. Despite the appeal for assuming that patient’s with a worse neurologic exam will fare more poorly, our findings confirm that when encountering new patients with brain metastases of unknown primary histology or systemic disease status, their prognosis should be informed by initial historical findings that delineate performance status, past medical history, and seizures. Author Disclosure: E. Oermann: None. M.A. Knoll: None. A.I. Yang: None. B.T. Collins: None. S.P. Collins: None. M. Ewend: None. D. Kondziolka: None.

Inhibition of Peripheral TNF-α and Downregulation of Microglial Activation by Alpha-Lipoic Acid and Etanercept Protect Rat Brain Against Ischemic Stroke.

Ischemic stroke, caused by obstruction of blood flow to the brain, would initiate microglia activation which contributes to neuronal damage. Therefore, inhibition of microglia-mediated neuroinflammation could be a therapeutic strategy for ischemic stroke. This study was aimed to elucidate the anti-inflammatory effects of alpha-lipoic acid and etanercept given either singly or in combination in rats subjected to middle cerebral artery occlusion. Both α-lipoic acid and etanercept markedly reduced cerebral infarct, blood-brain barrier disruption, and neurological motor deficits with the former drug being more effective with the dosage used. Furthermore, when used in combination, the reduction was more substantial. Remarkably, a greater diminution in the serum levels of tumor necrosis factor-alpha as well as the brain levels of microglial activation (e.g., microgliosis, amoeboid microglia, and microglial overexpression of tumor necrosis factor-α) was observed with the combined drug treatment as compared to the drugs given separately. We conclude that inhibition of peripheral tumor necrosis factor-alpha as well as downregulation of brain microglial activation by alpha-lipoic acid or etanercept protect rat brain against ischemic stroke. Moreover, when both drugs were used in combination, the stroke recovery was promoted more extensively.

A novel porcine model of ataxia telangiectasia reproduces neurological features and motor deficits of human disease.

Ataxia telangiectasia (AT) is a progressive multisystem disorder caused by mutations in the AT-mutated (ATM) gene. AT is a neurodegenerative disease primarily characterized by cerebellar degeneration in children leading to motor impairment. The disease progresses with other clinical manifestations including oculocutaneous telangiectasia, immune disorders, increased susceptibly to cancer and respiratory infections. Although genetic investigations and physiological models have established the linkage of ATM with AT onset, the mechanisms linking ATM to neurodegeneration remain undetermined, hindering therapeutic development. Several murine models of AT have been successfully generated showing some of the clinical manifestations of the disease, however they do not fully recapitulate the hallmark neurological phenotype, thus highlighting the need for a more suitable animal model. We engineered a novel porcine model of AT to better phenocopy the disease and bridge the gap between human and current animal models. The initial characterization of AT pigs revealed early cerebellar lesions including loss of Purkinje cells (PCs) and altered cytoarchitecture suggesting a developmental etiology for AT and could advocate for early therapies for AT patients. In addition, similar to patients, AT pigs show growth retardation and develop motor deficit phenotypes. By using the porcine system to model human AT, we established the first animal model showing PC loss and motor features of the human disease. The novel AT pig provides new opportunities to unmask functions and roles of ATM in AT disease and in physiological conditions.

Partially purified components of Uncaria sinensis attenuate blood brain barrier disruption after ischemic brain injury in mice.

BackgroundUncaria sinensis (US) has long been used in traditional Korean medicine to relieve various nervous-related symptoms and cardiovascular disease. We recently showed the neuroprotective and cerebrovascular protective effects of US on cerebral ischemia; however, its effects on the blood–brain barrier (BBB) are poorly understood. In this study, the effects of partially purified components of US (PPUS) on BBB disruption were investigated in mice subjected to ischemic brain injury.MethodsFocal cerebral ischemia was induced in C57BL/6J mice by photothrombotic cortical ischemia. PPUS was injected intraperitoneally 30 min before ischemic insults. Infarct volume, neurological score, wire-grip test, Evans blue leakage and brain water content were then examined 24 h after ischemic brain injury.ResultsInfarct volume was significantly reduced and neurological deficit and motor deficit were greatly improved in PPUS-pretreated mice relative to those treated with vehicle following photothrombotic cortical ischemia. Brain edema-induced change of Evans blue extravasation and water content in the ipsilateral hemisphere were alleviated by treatment with PPUS. In addition, PPUS significantly reduced ischemic brain injury-induced degradation of tight junction proteins and elevation of matrix metalloproteinase-9 (MMP-9).ConclusionsPPUS prevents cerebral ischemic damage by BBB protection, and these effects were associated with inhibition of tight junction degradation and MMP-9 induction.