Worsening Of Neurological Deficits Research Articles

Would the one-stage combined approach lead to better long-term neurological outcomes than the posterior approach alone in multilevel degenerative cervical myelopathy patients with T2-Weighted increased signal intensity? An 8-year follow-up results and propensity score matching analysis

BackgroundT2-weighted increased signal intensity (ISI) is commonly recognized as a sign of more severe spinal cord lesions, usually accompanied by worse neurological deficits and possibly worse postoperative neurological recovery. The combined approach could achieve better decompression and better neurological recovery for multilevel degenerative cervical myelopathy (MDCM). The choice of surgical approach for MDCM with intramedullary T2-weighted ISI remains disputed. This study aimed to compare the neurological outcomes of posterior and one-stage combined posteroanterior approaches for MDCM with T2-weighted ISI.MethodsA total of 83 consecutive MDCM patients with confirmed ISI with at least three intervertebral segments operated between 2012 and 2014 were retrospectively enrolled. Preoperative demographic, radiological and clinical condition variables were collected, and neurological conditions were evaluated by the Japanese Orthopedic Assessment score (JOA) and Neck Disability Index (NDI). Propensity score matching analysis was conducted to produce pairs of patients with comparable preoperative conditions from the posterior-alone and combined groups. Both short-term and mid-term surgical outcomes were evaluated, including the JOA recovery rate (JOARR), NDI improvements, complications, and reoperations.ResultsA total of 83 patients were enrolled, of which 38 and 45 patients underwent posterior surgery alone and one-stage posteroanterior surgery, respectively. After propensity score matching, 38 pairs of comparable patients from the posterior and combined groups were matched. The matched groups presented similar preoperative clinical and radiological features and the mean follow-up duration were 111.6 ± 8.9 months. The preoperative JOA scores of the posterior and combined groups were 11.5 ± 2.2 and 11.1 ± 2.3, respectively (p = 0.613). The combined group presented with prolonged surgery duration(108.8 ± 28.0 and 186.1 ± 47.3 min, p = 0.028) and greater blood loss(276.3 ± 139.1 and 382.1 ± 283.1 ml, p<0.001). At short-term follow-up, the combined group presented a higher JOARR than the posterior group (posterior group: 50.7%±46.6%, combined group: 70.4%±20.3%, p = 0.024), while no significant difference in JOARR was observed between the groups at long-term follow-up (posterior group: 49.2%±48.5%, combined group: 59.6%±47.6%, p = 0.136). No significant difference was found in the overall complication and reoperation rates.ConclusionsFor MDCM patients with ISI, both posterior and one-stage posteroanterior approaches could achieve considerable neurological alleviations in short-term and long-term follow-up. With greater surgical trauma, the combined group presented better short-term JOARR but did not show higher efficacy in long-term neurological function preservation in patients with comparable preoperative conditions.

Melatonin at repeated doses alleviates hyperglycemia-exacerbated cerebral ischemia-reperfusion injury at 72 h via anti-inflammation and anti-apoptosis

ObjectiveWe aimed to investigate how hyperglycemia would exacerbate cerebral ischemia-reperfusion injury (CIRI) in a rat model of type 1 diabetes mellitus (T1DM) and explore the beneficial effects of multiple doses of melatonin in T1DM induced CIRI. MethodThe T1DM rat model was induced with streptozocin, and melatonin (10 mg/kg) was injected at 0.5 h before ischemia as well as at 24 and 48 h after reperfusion. ResultsWhen compared to normoglycemic (NG) rats, T1DM rats had hyperglycemia with weight loss before CIRI. Despite comparable degrees of ischemia and initial reperfusion, T1DM rats tended to have greater weight loss and had worse neurological deficits and larger infarct volume than NG rats up to 72 h after CIRI. Persistent activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway but not of apoptosis or calpains was a crucial factor in T1DM-mediated exacerbation of CIRI at 72 h. Despite lacking effects on baseline hyperglycemia, ischemia and initial reperfusion, melatonin at multiple doses lessened post-CIRI weight loss, neurological deficits and infarct volume in T1DM rats at 72 h. when compared to vehicle-treated T1DM rats with CIRI. Beneficial effects of melatonin treatment included decreased activation of NF-κB pathway, apoptosis and calpains, leading to reduced expression of inducible nitric oxide synthase and enhanced neuronal density. ConclusionMelatonin at multiple doses can alleviate T1DM-mediated exacerbation of CIRI at 72 h through anti-inflammation and anti-apoptosis.

Age-Associated with Worsening of Neurological Deficits in Ischemic Stroke Patients in Abdoel Wahab Sjahranie Regional Hospital, Samarinda

Highlights: The worsening of neurological deficits in ischemic stroke patients is associated with the patient’s age, with those over 45 years old having a higher risk. The worsening of neurological deficits in ischemic stroke patients does not correlate with hemoglobin level, hematocrit value, gender, smoking history, blood pressure, or hyperglycemic state. Abstract Introduction: Treatment of impairment is an important step to prevent advanced neurological deficits in ischemic stroke medicine. Ischemic stroke patients with likely worsening neurological deficits should receive appropriate interventions. Therefore, this study aimed to examine predictors that can identify worsening neurological deficits. Methods: This study used a cross-sectional design on 74 hospitalized ischemic stroke patients at Abdoel Wahab Sjahranie Regional Hospital, Samarinda. The worsening of neurological deficits was based on the progression of the National Institutes of Health Stroke Scale (NIHSS) scores at hospital admission and discharge. Age (p = 0.024), hemoglobin level, hematocrit value, gender, smoking history, blood pressure, and hyperglycemic state (p = 0.05) were based on patient data at the beginning of hospital admission. The Chi-Square and Fisher’s exact tests were used in bivariate analysis. Results: The results showed that age had a significant association with the worsening of neurological deficits in ischemic stroke patients (p = 0.024). Hemoglobin level, hematocrit value, gender, smoking history, blood pressure, and hyperglycemic state showed no relationship with worsening neurological deficits in ischemic stroke patients (p &gt; 0.05). Conclusion: Age can serve as a predictor of worsening neurological deficits in ischemic stroke patients, with those aged over 45 years old having a higher risk. Meanwhile, the other factors were not associated with a worsening neurological deficit in ischemic stroke patients.

An isolated pontine infarct extending to the basal pontine surface has a higher abnormal ankle-brachial index

Patients with ischemic stroke and branch atheromatous disease (BAD) have worse neurological deficits and prognoses than those with small vessel occlusion (SVO). However, both disorders are forms of deep brain infarctions. This study aimed to investigate an MRI-based etiological classification for isolated pontine infarctions and assess differences in vascular risk factors and peripheral arterial disease among etiological subtypes. Consecutive data of patients admitted for acute ischemic stroke or transient ischemic attack between August 2016 and July 2019 were reviewed. Acute isolated pontine infarcts were classified into 3 groups: BAD, SVO, and large-artery atherosclerosis (LAA), according to basilar or vertebral artery steno-occlusion and the extent of the infarct lesion on the basal pontine surface as displayed on magnetic resonance imaging and angiography. Vascular risk factors, ankle-brachial index (ABI), and brachial-ankle pulse wave velocity were analyzed in the 3 groups. Among 64 enrolled patients, BAD was the most common cause of isolated pontine infarct. The BAD group had a higher frequency of abnormal ABI and hypertension than the SVO group. The BAD group had abnormal ABI and hyperlipidemia more frequently than the LAA group. No significant difference was found in diabetes or brachial-ankle pulse wave velocity incidence between the BAD and SVO groups. ABI and vascular risk factors in the BAD group were more similar to those in the LAA group than to those in the SVD group. This finding suggests that pontine lesions extending to the basal pontine surface have an atherosclerotic mechanism in BAD, requiring potent antiplatelet therapy for the secondary prevention of ischemic stroke.

Low-flow extra-intracranial bypass in acute carotid and vertebrobasilar ischemic stroke (literature review)

Introduction. The effectiveness of the method of revascularization of the brain using extra‑intracranial bypass in chronic insufficiency of blood supply to the brain has been studied in several randomized multicenter studies. The analysis of available publications devoted to this technique for 10 years with acute strokes in the carotid basin and for 20 years with ischemic strokes in the vertebrobasilar basin was carried out.Aim. To improve the results of treatment of ischemic strokes with the help of emergency extra‑intracranial low‑flow bypasses in the acute and acute period. In 12 publications over the past 10 years, selected from the PubMed search engine, 194 cases of the use of emergency extra‑intracranial microbypasses in the acute and acute period of ischemic stroke in the carotid basin were identified, 127 cases of emergency extra‑intracranial bypass were found in 6 articles during the last 20 years in the acute phase of vertebra‑basilar area stroke. Middle patient age in carotid group was 61.9 years, and 65 years in vertebral patient’s group. The male / female ratio was 3 / 1. The main indications for the bypass creation were: worsening of neurologic deficit from 4 and more according to the Stroke Severity Scale of the US National Institutes of Health, mini mal or not significant computed tomography (CT) or diffusion‑weighted magnetic resonance imaging (DW‑MRI) ischemia brain changes (not lower than 8 points on the scale of assessment of initial changes in the computed tomographic (CT) examination for stroke Alberta Stroke Program Early CT Score, ASPECTS), signs of significant brachiocephalic arteries atherosclerotic stenosis. In 83 carotid group cases perfusion‑diffusion mismatch was distinguished before bypass creation. In 111 carotid cases and in priority of vertebra‑basilar cases clinic‑diffusion mismatch was the only indication for emergency extra‑intracranial bypass creation. During the first 24 hours 65 % of carotid group bypass were performed, in other 35 % of cases bypasses were performed during 1 week after the stroke onset. There were 78 % of good results (&lt;2 on the Rankin outcome scale, mRS) and 22 % of poor (mRS &gt;2) in carotid stroke group. Mortality was 3 %. In vertebral group, coma was not contraindication for emergence extra‑intracranial bypass creation. In most cases, 70 % of bypass were performed between superficial temporal artery and superior cerebellar artery. Mortality in vertebral stroke group was 5 %, mostly because of somatic pathology worsening. Good results were achieved in76 % of cases.Conclusion. In some cases of atherosclerotic carotid and vertebrobasilar ischemic stroke, results of recovery can be approved greatly with use of emergency low‑flow extra‑intracranial bypass, if intravenous thrombolysis and endovascular tromboextraction were failed.

Melatonin mitigates type 1 diabetes-aggravated cerebral ischemia-reperfusion injury through anti-inflammatory and anti-apoptotic effects.

Cerebral ischemia and diabetes mellitus (DM) are common diseases that often coexist and interact with each other. DM doubles the risk of ischemic stroke, and cerebral ischemia causes stress-induced hyperglycemia. Most experimental stroke studies used healthy animals. Melatonin is neuroprotective against cerebral ischemia-reperfusion injury (CIRI) in non-DM, normoglycemic animals through anti-oxidant effect, anti-inflammation, and anti-apoptosis. Previous studies have also reported a negative correlation between hyperglycemia and urinary melatonin metabolite. The present study investigated the effects of type 1 DM (T1DM) on CIRI in rats and the role of melatonin against CIRI in T1DM animals. Our results revealed that T1DM aggravated CIRI, leading to greater weight loss, increased infarct volume, and worse neurological deficit. T1DM aggravated the post-CIRI activation of nuclear factor kappa B (NF-κB) pathway and increase in pro-apoptotic markers. A single intraperitoneal injection of melatonin at 10mg/kg given 30min before ischemia onset attenuated CIRI in T1DM rats, resulting in less weight loss, decreased infarct volume, and milder neurological deficit when compared with the vehicle group. Melatonin treatment achieved anti-inflammatory and anti-apoptotic effects with reduced NF-κB pathway activation, reduced mitochondrial cytochrome C release, decreased calpain-mediated spectrin breakdown product (SBDP), and decreased caspase-3-mediated SBDP. The treatment also led to fewer iNOS+ cells, milder CD-68+ macrophage/microglia infiltration, decreased TUNEL+ apoptotic cells, and better neuronal survival. T1DM aggravates CIRI. Melatonin treatment is neuroprotective against CIRI in T1DM rats via anti-inflammatory and anti-apoptotic effects.

Air Crash Investigation: Pattern of Spinal Injuries, Management During the COVID-19 Pandemic, and Outcomes.

Spinal injuries following an air crash can be fatal, and recognizing the patients who need immediate attention and early management could save those patients from ending up with lifelong disabilities and other consequences. However, taking appropriate actions in a pandemic situation presents additional challenges. We present our report of air crash victims with spinal injuries, along with their patterns, morphology, management, and outcomes during the COVID-19 pandemic. An analysis was performed on the spinal injuries of victims of the Boeing 737 crash landing at the Karipur Airport (Calicut International Airport, Kerala, India) who were treated at a tertiary care referral hospital in August 2020. Details of the initial triage, patterns of injury, morphologies, mechanisms, management principles, and outcomes at 9 months postinjury were recorded and analyzed. Of the 47 patients received at our center, 44 survivors were triaged and 13 patients (29.5%) were identified to have spinal injuries of varying severities. The majority of the injuries were chance fractures at the lumbar level, followed by burst and compression fractures. A total of 6 patients underwent surgery, following all COVID-19 guidelines based on priority. All survivors had positive outcomes with our management. No complications such as secondary infections, worsening of neurological deficits, or implant failures were recorded. A high incidence of spinal injuries is seen in air crash victims. Early prioritized surgical management in selected patients provides excellent outcomes. Disaster management during a pandemic situation is a difficult task, where proper planning and execution is necessary to provide optimal results.

Dysregulated Hypothalamic-Pituitary-Adrenal Axis Is Associated With Increased Inflammation and Worse Outcomes After Ischemic Stroke in Diabetic Mice.

Diabetic patients have larger infarcts, worse neurological deficits, and higher mortality rate after an ischemic stroke. Evidence shows that in diabetes, the hypothalamic–pituitary–adrenal (HPA) axis was dysregulated and levels of cortisol increased. Based on the role of the HPA axis in immunity, we hypothesized that diabetes-dysregulated stress response exacerbates stroke outcomes via regulation of inflammation. To test this hypothesis, we assessed the regulation of the HPA axis in diabetic mice before and after stroke and determined its relevance in the regulation of post-stroke injury and inflammation. Diabetes was induced in C57BL/6 mice by feeding a high-fat diet and intraperitoneal injection of streptozotocin (STZ), and then the mice were subjected to 30 min of middle cerebral artery occlusion (MCAO). Infarct volume and neurological scores were measured in the ischemic mice. The inflammatory cytokine and chemokine levels were also determined in the ischemic brain. To assess the effect of diabetes on the stroke-modulated HPA axis, we measured the expression of components in the HPA axis including corticotropin-releasing hormone (CRH) in the hypothalamus, proopiomelanocortin (POMC) in the pituitary, and plasma adrenocorticotropic hormone (ACTH) and corticosterone. Diabetic mice had larger infarcts and worse neurological scores after stroke. The exacerbated stroke outcomes in diabetic mice were accompanied by the upregulated expression of inflammatory factors (including IL-1β, TNF-α, IL-6, CCR2, and MCP-1) in the ischemic brain. We also confirmed increased levels of hypothalamic CRH, pituitary POMC, and plasma corticosterone in diabetic mice before and after stroke, suggesting the hyper-activated HPA axis in diabetic conditions. Finally, we confirmed that post-stroke treatment of metyrapone (an inhibitor of glucocorticoid synthesis) reduced IL-6 expression and the infarct size in the ischemic brain of diabetic mice. These results elucidate the mechanisms in which the HPA axis in diabetes exacerbates ischemic stroke. Maintaining an optimal level of the stress response by regulating the HPA axis may be an effective approach to improving stroke outcomes in patients with diabetes.

OSASUD: A dataset of stroke unit recordings for the detection of Obstructive Sleep Apnea Syndrome

Polysomnography (PSG) is a fundamental diagnostical method for the detection of Obstructive Sleep Apnea Syndrome (OSAS). Historically, trained physicians have been manually identifying OSAS episodes in individuals based on PSG recordings. Such a task is highly important for stroke patients, since in such cases OSAS is linked to higher mortality and worse neurological deficits. Unfortunately, the number of strokes per day vastly outnumbers the availability of polysomnographs and dedicated healthcare professionals. The data in this work pertains to 30 patients that were admitted to the stroke unit of the Udine University Hospital, Italy. Unlike previous studies, exclusion criteria are minimal. As a result, data are strongly affected by noise, and individuals may suffer from several comorbidities. Each patient instance is composed of overnight vital signs data deriving from multi-channel ECG, photoplethysmography and polysomnography, and related domain expert’s OSAS annotations. The dataset aims to support the development of automated methods for the detection of OSAS events based on just routinely monitored vital signs, and capable of working in a real-world scenario.

Children with cavernous malformations of the central nervous system.

Cavernous malformations (CM) of the central nervous system (CNS) are a rare pathology in the pediatric population that may present with an acute onset of severe neurological symptoms. The aim of our study was to evaluate the clinical presentation, family history, genetic background, radiological features, treatment and outcome of children with CM. This observational cohort study included all children with CM of the CNS diagnosed in the period 2000-2020at University Children's Hospital in Ljubljana, Slovenia. Whole exome sequencing was utilized. We identified a cohort of 20 children with CM (mean age 9.3 years, range: 10 days-18.4 years). In our cohort, 16 patients were symptomatic and 4 were asymptomatic; 7 patients had a solitary lesion, and 13 had multiple lesions. Children with multiple lesions become symptomatic at an earlier age compared with children with solitary lesions. We identified five families with familiar cavernous malformation (FCM) syndrome affecting two or more generations; FCM represented 65% of all pediatric cases identified in our study. We confirmed a mutation in FCM associated genes in all but one patient with multiple lesions, with the KRIT1 mutation being the most common. Multiple CM lesions and symptomatic brainstem lesions are associated with worse neurological deficits in pediatric patients. Not all cases of multiple lesions can be linked to mutations in KRIT1, CCM2, or PDCD10, which may indicate that there are other as yet unidentified genes associated with FCM.

Utility of spinal angiography and arterial embolization in patients undergoing CT guided alcohol injection of aggressive vertebral hemangiomas.

The purpose of this study is to evaluate the role of spinal angiography and arterial embolization in avoiding spinal cord ischemia in patients undergoing CT-guided alcohol injection of aggressive vertebral hemangiomas. In this retrospective study, patients with vertebral hemangioma who underwent CT-guided direct alcohol injection between January 2007 and October 2018 were identified. Of 28 such patients, 26 had neurological deficits, and 2 had only back pain or radiculopathy. Direct alcohol injection without prior arterial embolization was done in 17 patients. Direct alcohol injection with prior arterial embolization was done in 11 patients. Clinical outcome was assessed immediately after the intervention and at follow-up. Three patients, who underwent alcohol injection without trans-arterial embolization, had worsening of neurological deficits in the post procedure period due to spinal cord ischemia. No complications related to spinal cord ischemia were noted in the embolization group. There was no significant difference in the outcomes between the two groups if the three patients with complications are excluded (p = 0.34). While CT-guided direct alcohol injection is effective in the management of symptomatic and aggressive vertebral hemangiomas, spinal angiography and trans-arterial embolization of the blood supply to the vertebral body hemangioma, prior to the direct transpedicular alcohol embolization of the lesion, improves the safety of the procedure.

Silencing of lncRNA XIST impairs angiogenesis and exacerbates cerebral vascular injury after ischemic stroke

The aim of this study was to investigate the function and regulatory mechanism of long non-coding RNA (lncRNA) X-inactive-specific transcript (XIST) in cerebral ischemic stroke (CIS). The impact of lncRNA XIST on CIS was evaluated in acute CIS patients, middle cerebral artery occlusion (MCAO) mice, and oxygen-glucose deprivation and restoration brain endothelial cells. Our results demonstrated that the expression of lncRNA XIST decreased during the early stages of CIS but then increased in the later stages in CIS patients and ischemic models in vivo and in vitro. In addition, the serum levels of lncRNA XIST negatively correlated with severity of neurological impairment of CIS patients. Further studies exhibited that lncRNA XIST regulated the expression of proangiogenic factor-integrin α5 (Itgα5) and anti-inflammation factor-Kruppel-like transcription factor 4 (KLF4) by targeting microRNA-92a (miR-92a). Silencing of lncRNA XIST impaired angiogenesis and exacerbated cerebral vascular injury following CIS, leading to larger infarcts and worse neurological deficits in transient MCAO mice. Mechanistic analysis revealed that lncRNA XIST modulated angiogenesis and alleviated cerebral vascular injury following CIS through mediating the miR-92a/Itgα5 or KLF4 axis, respectively. These data indicate that lncRNA XIST confers protection against CIS, providing a valuable target for future prevention and treatment of CIS.

AIOSA: An approach to the automatic identification of obstructive sleep apnea events based on deep learning

Obstructive Sleep Apnea Syndrome (OSAS) is the most common sleep-related breathing disorder. It is caused by an increased upper airway resistance during sleep, which determines episodes of partial or complete interruption of airflow. The detection and treatment of OSAS is particularly important in patients who suffered a stroke, because the presence of severe OSAS is associated with higher mortality, worse neurological deficits, worse functional outcome after rehabilitation, and a higher likelihood of uncontrolled hypertension. The gold standard test for diagnosing OSAS is polysomnography (PSG). Unfortunately, performing a PSG in an electrically hostile environment, like a stroke unit, on neurologically impaired patients is a difficult task; moreover, the number of strokes per day vastly outnumbers the availability of polysomnographs and dedicated healthcare professionals. Hence, a simple and automated recognition system to identify OSAS cases among acute stroke patients, relying on routinely recorded vital signs, is highly desirable. The vast majority of the work done so far focuses on data recorded in ideal conditions and highly selected patients, and thus it is hardly exploitable in real-life circumstances, where it would be of actual use. In this paper, we propose a novel convolutional deep learning architecture able to effectively reduce the temporal resolution of raw waveform data, like physiological signals, extracting key features that can be used for further processing. We exploit models based on such an architecture to detect OSAS events in stroke unit recordings obtained from the monitoring of unselected patients. Unlike existing approaches, annotations are performed at one-second granularity, allowing physicians to better interpret the model outcome. Results are considered to be satisfactory by the domain experts. Moreover, through tests run on a widely-used public OSAS dataset, we show that the proposed approach outperforms current state-of-the-art solutions.

A prospective study on role of magnetic resonance imaging in management of acute spinal trauma and assessing the extent of neurological deficit

Background: For Imaging neurological parts, like the spinal cord, magnetic resonance imaging (MRI) has been the gold standard. The use of magnetic resonance imaging (MRI) in the acute management of patients with spinal cord injuries has risen dramatically. Objectives: This study was conducted to evaluate the diagnostic role of magnetic resonance imaging in management of acute spinal trauma and to assess the extent of neurological deficit. Material and Methods: Thirty patients of spinal trauma. The patients undergoing MR imaging, magnetic resonance images were analysed and skeletal injuries, signal changes in vertebrae, ligaments, soft tissues were noted. Associated spinal cord injury findings were also noted, which helped in assessing the initial neurological deficit and compared with (ASIA) impairment scale. Results: Out of 30 patients of spinal trauma. 53.3 % injuries were in cervical region and 46.6% in thoracolumbar region. Most of the traumatic spinal injuries in cervical spine were unstable. (68.75%) and thoracolumbar spine were stable injuries (42.85%). Unstable spinal injuries (56.66%) in cervical and thoracolumbar were operated and stabilised. Cord oedema (36.6%) and next cord compression (33.3%) were common presentations of cord injuries; cord transection and compression have worse neurological deficit and presented with ASIA score A/B at the time of admission. Conclusion: CT provides superior depiction of bony anatomy but important limitation of this technique is inability to provide screening for ligamentous injury and spinal cord lesions. MRI is superior in this regard. Because of its high contrast resolution, absence of bony artifacts, multiplanar ability, and variety of pulse sequences, MRI allows for a more precise diagnosis of spinal trauma.

A prospective study of functional outcome in Thoracolumbar potts spine with posterior only approach

Introduction: surgical approach for thoracolumbar pott spine has been controversial. Traditionally, earlier anterior decompression and fixation had been long considered as the gold standard for treatment of tb of spine. Recently, the posterior approach has gained popularity based on the principle of adequate debridement, decompression and stable fixation with much lower complication rates, the present study aims to evaluate the results (functional, neurological, and radiological) of the posterior only approach in patients operated for thoracic and lumbar tuberculosis. Methods: all patients (n=40) who were included in the study had thoracolumbar tuberculosis of spine with or without neurological deficit and with or without deformity, were managed by only posterior decompression and fixation. Preoperative and postoperative visual analog scale, frankel neurological grading, radiologic fusion by bridwell criteria were compared and functional assessment was done by oswestry disability questionnaire. Results: Statistical significant improvement seen in Oswestry disability functional questionnaire and VAS scores (p < 0.05), the clinical outcomes were satisfactory at the end of final follow-up.no worsening of neurological deficit. Solid fusion was achieved in 85% patients after surgery. Two patient developed superficial wound infection which healed by Conservative methods and extended antibiotic therapy. Conclusion: Posterior decompression and fixation is safe and effective approach for management of patients with thoracolumbar pott spine, provides rapid relief of pain, neurological recovery by adequate decompression and prevents progression of deformity with posterior stabilization with fewer complications.

Abstract P813: Enhanced Stress Response is Associated With Increased Inflammation and Worse Outcomes Following Ischemic Stroke in Diabetic Condition

Introduction: Although stroke severity is increased in patients with diabetes (e.g., higher mortality, larger infarcts, and worse neurological deficits), the underlying mechanism(s) of the worse outcomes is not clear. Evidence shows that hypothalamic-pituitary-adrenal (HPA) axis is dysregulated and cortisol levels are increased in diabetes. Based on the role of HPA axis in immunity, we hypothesized that diabetes-enhanced stress response contributes to stroke injury via regulating inflammation. Methods: Diabetes was induced in C57BL/6 mice by feeding a diabetogenic diet and injecting streptozotocin. Mice were subjected to 30 min middle cerebral artery occlusion. Infarct volume and neurological scores were measured at 24h-post stroke. We measured expression of factors related to stress response, plasma corticosterone, c-Fos and corticotropin-releasing factor (CRH) in hypothalamus, and proopiomelanocortin (POMC) and corticotropin-releasing hormone receptor 1 (CRHR1) in pituitary. Inflammatory cytokine levels were also determined in the ischemic brain. Results: Diabetic mice showed hyperglycemia and delayed glucose clearance in blood. At 1d-post stroke, diabetic mice showed larger infarct and worse neurological score. Plasma corticosterone levels were significantly increased in diabetic mice. We also found increased c-Fos in hypothalamus, and CRHR1 and POMC in pituitary. These were accompanied by increased IL-1β, TNF-α, and IL-6 mRNA in the ischemic brain. Conclusion: Our results indicate that stress response is enhanced in diabetic conditions, and associated with increased inflammation in ischemic brain and worse stroke outcomes. It suggests that regulation of stress response may improve stroke outcomes in diabetic conditions.

ITRAQ-Based Quantitative Proteomics Indicated Nrf2/OPTN-Mediated Mitophagy Inhibits NLRP3 Inflammasome Activation after Intracerebral Hemorrhage.

Intracerebral hemorrhage- (ICH-) induced secondary brain injury (SBI) is a very complex pathophysiological process. However, the molecular mechanisms and drug targets of SBI are highly intricate and still elusive, yet a clear understanding is crucial for the treatment of SBI. In the current study, we aimed to confirm that nuclear factor-E2-related factor 2 (Nrf2)/Optineurin- (OPTN-) mediated mitophagy alleviated SBI by inhibiting nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation based on the isobaric tag for relative and absolute quantization (iTRAQ) quantification proteomics. Human ICH brain specimens were collected for iTRAQ-based proteomics analysis. Male Nrf2 wild-type (WT) and knockout (KO) mice were employed to establish ICH murine models. The survival rate, hematoma volume, neurofunctional outcomes, blood-brain barrier (BBB) permeability, brain edema, spatial neuronal death, NLRP3 inflammasome, inflammatory response, mitochondrial function, and mitophagy level were evaluated after ICH. The iTRAQ quantification analysis showed that the differentially expressed proteins (DEPs), Nrf2 and NLRP3, were closely associated with the initiation and development of SBI after ICH. The Nrf2 KO mice had a significantly lower survival rate, bigger hematoma volume, worse neurological deficits, and increased BBB disruption, brain edema, and neuronal death when compared with the Nrf2 WT mice after ICH. Furthermore, Nrf2 KO enhanced NLRP3 inflammasome activation and neuroinflammation as evidenced by the NF-κB activation and various proinflammatory cytokine releases following ICH. Moreover, Nrf2 could interact with and modulate the mitophagy receptor OPTN, further mediating mitophagy to remove dysfunctional mitochondria after ICH. Furthermore, OPTN small interfering RNA (siRNA) increased the NLRP3 inflammasome activation by downregulating mitophagy level and enhancing mitochondrial damage in the Nrf2 WT mice after ICH. Together, our data indicated that Nrf2/OPTN inhibited NLRP3 inflammasome activation, possibly via modulating mitophagy, therefore alleviating SBI after ICH.

Predictive Value of Heterogeneously Enhanced Magnetic Resonance Imaging Findings With Computed Tomography Evidence of Calcification for Severe Motor Deficits in Spinal Meningioma.

ObjectiveSpinal meningioma is mostly benign, but they can exhibit neurological deficit. The relationship between neurological impairment and its radiographic findings, including intratumor magnetic resonance imaging (MRI) gadolinium enhancement and calcification in computed tomography (CT) scan, has not been studied. The purpose of this study was to investigate the association of preoperative image findings with neurological status in spinal meningioma. MethodsPatients histologically diagnosed with spinal meningioma (n = 24), with an average age of 65.4 years, were included. The patients were classified into 2 groups, the homogeneous and heterogeneous groups, based on the contrast-enhanced T1-weighted MRI findings. Further, baseline demographics (age, sex, presence of preoperative paralysis [manual muscle testing 3 or worse neurological deficit in upper and/or lower limbs], tumor level, tumor length, and tumor occupation ratio), histological findings (Ki-67 index and histological subtypes), and CT findings (presence of intratumor calcification and Hounsfield unit [HU] value) were examined. ResultsPreoperative paralysis was observed in 33.3% (8 of 24) of the patients. These patients exhibited frequent heterogeneous contrast-enhanced MRI findings than those without preoperative paralysis (57.1% vs. 14.3%, p = 0.040). Further, preoperative paralysis did not associate with tumor level, tumor length, tumor-occupied ratio, Ki-67 index, and histological subtypes. The heterogeneous group showed 100% intratumor calcification and higher maximum HU than the homogeneous group (1,109.8 vs. 379.2, p = 0.001). ConclusionThe heterogeneous contrast-induced MRI findings in the spinal meningioma were significantly associated with preoperative neurological impairment. Moreover, the intratumor contrast-deficient region in the heterogeneously enhanced tumors reflected marked calcification. The tumor hardness due to calcification may be related to preoperative neurological deficit.

Surgical Outcome &amp; Cost Analysis of Single Stage Anterior Decompression and Cage Fixation in Patients with Thoracic and Lumbar Tuberculous Spondylitis: A Single Centre Experience Over Six – Years with Comprehensive Literature Review

Objective: For Tuberculous spondylitis (TS) the optimal mode of management for extensive tuberculous spondylitis is still a subject of debate. We determined the outcome for single stage anterior decompression and cage fixation for dorso-lumbar TS.&#x0D; Material and Methods: This prospective study was conducted between 2012 and 2018. Worsening or new onset neurological deficit, increasing deformity, large paraspinal abscess and those not responding to anti-tuberculous drug therapy were included. Patients with severe comorbidities (&gt; ASA class III) and recurrent cases were excluded. Demographics, clinical features, radiological characteristics, intraoperative details, postoperative complications and follow-up condition were recorded.&#x0D; Results: One patient with mean age of 45.6 ± 14.9 years with 17 (54.8%) males and 14 (45.2%) females. Mean symptoms duration was 71.9 ± 29.4 days. 41.9% had spasticity &amp; 25.8% had sphincter dysfunction on presentation. Half (48%) of patients had a Frankel grade 3 or less bilaterally. Mean length of the procedure was 137.4 ± 19.9 minutes. 19.4% (n = 6) had postoperative pulmonary complications, 16.1% (n = 5) wound infection, 9.7% (n = 3) had worsening of neurologic deficit and one (3.2%) remained static. Graft extrusion and cage subsidence were noted in one (3.2%) patient each. Favorable outcome was observed in 83.9% (n = 26) while 16.1% (n = 5) had unfavorable outcome. Mean out-of-pocket cost was 164677.4 ± 11469.9 rupees (USD: 1187 approx).&#x0D; Conclusion: Timely spinal decompression with stabilization at the onset of the Pott’s disease in patients who fulfil the criteria as surgical candidates carries a promising outcome.

Apolipoprotein E promotes white matter remodeling via the Dab1‐dependent pathway after traumatic brain injury

IntroductionAxonal injury results in long‐term neurological deficits in traumatic brain injury (TBI) patients. Apolipoprotein E (ApoE) has been reported to activate intracellular adaptor protein Disabled‐1 (Dab1) phosphorylation via its interaction with ApoE receptors. The Dab1 pathway acts as a regulator of axonal outgrowth and growth cone formation in the brain.AimsWe hypothesized that ApoE may alleviate axonal injury and regulate axonal regeneration via the Dab1 pathway after TBI.ResultsIn this study, we established a model of controlled cortical impact (CCI) to mimic TBI in vivo. Using diffusion tensor imaging to detect white matter integrity, we demonstrated that APOE‐deficient mice exhibited lower fractional anisotropy (FA) values than APOE+/+ mice at 28 days after injury. The expression levels of axonal regeneration and synapse plasticity biomarkers, including growth‐associated protein 43 (GAP43), postsynaptic density protein 95 (PSD‐95), and synaptophysin, were also lower in APOE‐deficient mice. In contrast, APOE deficiency exerted no effects on the levels of myelin basic protein (MBP) expression, oligodendrocyte number, or oligodendrocyte precursor cell number. Neurological severity score (NSS) and behavioral measurements in the rotarod, Morris water maze, and Y maze tests revealed that APOE deficiency caused worse neurological deficits in CCI mice. Furthermore, Dab1 activation downregulation by the ApoE receptor inhibitor receptor‐associated protein (RAP) or Dab1 shRNA lentivirus attenuated the beneficial effects of ApoE on FA values, GAP43, PSD‐95, and synaptophysin expression, and neurological function tests. Additionally, the effects of ApoE on axonal regeneration were further validated in vitro. In a mechanical scratch injury model of primary cultured neurons, recombinant ApoE protein treatment enhanced axonal outgrowth and growth cone formation in injured neurons; however, these effects were attenuated by Dab1 shRNA, consistent with the in vivo results.ConclusionCollectively, these data suggest that ApoE promotes axonal regeneration partially through the Dab1 pathway, thereby contributing to functional recovery following TBI.