Risk Factors for Hypoglycemia with the Use of Enteral Glyburide in Neurocritical Care Patients.

OBJECTIVE: Intravenous glyburide has demonstrated safety when used for attenuation of cerebral edema, although safety data are lacking for enteral glyburide when used for this indication. We aimed to determine the prevalence of and risk factors for hypoglycemia in neurocritical care patients receiving enteral glyburide. METHODS: We performed a retrospective case-control chart review (hypoglycemia vs. no hypoglycemia) of adult patients who received enteral glyburide for prevention or treatment of cerebral or spinal cord edema. Hypoglycemia was defined as a blood glucose <55.8 mg/dL. Descriptive statistics were used, with multivariate analysis to measure the association of risk factors and outcomes. Logistic regression was applied to outcomes with an exposure. Potential confounders were evaluated using the t-test or the Wilcoxon rank-sum test for continuous variables, and the χ2 test or the Fisher exact test for categorical variables. RESULTS: Seventy-one patients (60.6% men, median age 60 years) were included. The majority received 2.5 mg of enteral glyburide twice daily. Diagnoses included tumors (35.2%), intracerebral hemorrhage (28.2%), postspinal surgery (12.7%), and ischemic stroke (12.7%). Hypoglycemia occurred in 17 (23.9%) patients. Multivariate analysis identified admission serum creatinine (odds ratio, 27.2; [1.661, 445.3]; P < 0.05) as a risk factor for hypoglycemia, whereas body mass index >30 (odds ratio, 0.085; [0.008, 0.921]; P < 0.05) was protective. CONCLUSIONS: Hypoglycemic episodes are common following enteral glyburide in neurocritical care patients. Both patients with and without diabetes mellitus are at risk of hypoglycemia. Elevated admission serum creatinine may increase the risk of hypoglycemia when utilizing glyburide for prevention or treatment of cerebral or spinal cord edema.

[Radiotherapy and spinal toxicity: News and perspectives]. / Radiothérapie et toxicité médullaire : actualités et perspectives.

Radiation-induced myelopathy is a devastating late effect of radiotherapy. Fortunately, this late effect is exceptional. The clinical presentation of radiation myelopathy is aspecific, typically occurring between 6 to 24 months after radiotherapy, and radiation-induced myelopathy remains a diagnosis of exclusion. Magnetic resonance imaging is the most commonly used imaging tool. Radiation oncologists must be extremely cautious to the spinal cord dose, particularly in stereotactic radiotherapy and reirradiation. Conventionally, a maximum dose of 50Gy is tolerated in normofractionated radiotherapy (1.8 to 2Gy per fraction). Repeat radiotherapies lead to consider cumulative doses above this recommendation to offer individualized reirradiation. Several factors increase the risk of radiation-induced myelopathy, such as concomitant or neurotoxic chemotherapy. The development of predictive algorithms to prevent the risk of radiation-induced myelopathy is promising. However, radiotherapy prescription should be cautious, regarding to ALARA principle (as low as reasonably achievable). As the advent of immunotherapy has improved patient survival data and the concept of oligometastatic cancer is increasing in daily practice, stereotactic treatments and reirradiations will be increasingly frequent indications. Predict the risk of radiation-induced myelopathy is therefore a major issue in the following years, and remains a daily challenge for radiation oncologists.

Neurophysiological monitoring of spinal cord function during spinal deformity surgery: 2020 SRS neuromonitoring information statement.

The Scoliosis Research Society has developed an updated information statement on intraoperative neurophysiological monitoring of spinal cord function during spinal deformity surgery. The statement reviews the risks of spinal cord compromise associated with spinal deformity surgery; the statement then discusses the various modalities that are available to monitor the spinal cord, including somatosensory-evoked potentials, motor-evoked potentials, and electromyographic (EMG) options. Anesthesia considerations, the importance of a thoughtful team approach to successful monitoring, and the utility of checklists are also discussed. Finally, the statement expresses the opinion that utilization of intraoperative neurophysiological spinal cord monitoring in spinal deformity surgery is the standard of care when the spinal cord is at risk.

Direct Peritoneal Resuscitation with Pyruvate Protects the Spinal Cord and Induces Autophagy via Regulating PHD2 in a Rat Model of Spinal Cord Ischemia-Reperfusion Injury.

Direct peritoneal resuscitation with pyruvate (Pyr-PDS) has emerged as an interesting candidate to alleviate injury in diverse organs, while the potential mechanism has yet to be fully elucidated. To explore the effect of autophagy in the spinal cord ischemia-reperfusion (SCIR) injury and the underlying mechanism, we established a model of SCIR in vivo and in vitro. In vivo, male SD rats underwent aortic occlusion for 60 min and then followed by intraperitoneally infused with 20 mL of pyruvate or normal saline for 30 min, and the spinal cords were removed for analysis after 48 h of reperfusion. The functional and morphological results showed that Pyr-PDS alleviated SCIR injury; meanwhile, the expression of autophagy-related genes and transmission electron microscopy displayed autophagy was activated by SCIR injury, and Pyr-PDS treatment could further upregulate the degree of autophagy which plays a protective part in the SCIR injury, while there is no significant difference after treatment with saline. In addition, SCIR injury inhibited expression of PHD2, which results to activate its downstream HIF-1α/BNIP3 pathway to promote autophagy. In the Pyr-PDS, the results revealed PHD2 was further inhibited compared to the SCIR group, which could further activate the HIF-1α/BNIP3 signaling pathway. Additionally, oxygen-glucose deprivation and reoxygenation were applied to SH-SY5Y cells to mimic anoxic conditions in vitro, and the expression of autophagy-related genes, PHD2, and its downstream HIF-1α/BNIP3 pathway showed the same trend as the results in vivo. Besides, IOX2, a specific inhibitor of PHD2 was also treated to SH-SY5Y cells during reoxygenation, in which the result is as same as the pyruvate group. Then, we observed the expression of autophagy-related genes and the HIF-1α signal pathway in the process of reoxygenation; the results showed that as the reoxygenation goes, the expression of the HIF-1α signal pathway and degree of autophagy came to decrease gradually, while treated with pyruvate could maintain autophagy high and stable through keeping PHD2 at a lower level during reoxygenation, and the latter was observed downregulated during reoxygenation process from 0 to 24 hours in a time-effect way. The above results indicated that direct peritoneal resuscitation with pyruvate showed effective protection to ischemia-reperfusion of the spinal cord through activating autophagy via acting on PHD2 and its downstream HIF-1α/BNIP3 pathway.

The protective effort of GPCR kinase 2-interacting protein-1 in neurons via promoting Beclin1-Parkin induced mitophagy at the early stage of spinal cord ischemia-reperfusion injury.

In spinal cord ischemia-reperfusion (I/R) injury, large amounts of reactive oxygen species can cause mitochondrial damage. Therefore, mitophagy acts as the main mechanism for removing damaged mitochondria and protects nerve cells. This study aimed to illustrate the important role of GPCR kinase 2-interacting protein-1 (GIT1) in mitophagy in vivo and in vitro. The level of mitophagy in the neurons of Git1 knockout mice was significantly reduced after ischemia-reperfusion. However, the overexpression of adeno-associated virus with Git1 promoted mitophagy and inhibited the apoptosis of neurons. GIT1 regulated the phosphorylation of Beclin-1 in Thr119, which could promote the translocation of Parkin to the mitochondrial outer membrane. This process was independent of PTEN-induced kinase 1 (PINK1), but it could not rescue the role in the absence of PINK1. Overall, GIT1 enhanced mitophagy and protected neurons against ischemia-reperfusion injury and, hence, might serve as a new research site for the protection of ischemia-reperfusion injury.

Microglial pannexin-1 channel activation is a spinal determinant of joint pain.

Chronic joint pain such as mechanical allodynia is the most debilitating symptom of arthritis, yet effective therapies are lacking. We identify the pannexin-1 (Panx1) channel as a therapeutic target for alleviating mechanical allodynia, a cardinal sign of arthritis. In rats, joint pain caused by intra-articular injection of monosodium iodoacetate (MIA) was associated with spinal adenosine 5'-triphosphate (ATP) release and a microglia-specific up-regulation of P2X7 receptors (P2X7Rs). Blockade of P2X7R or ablation of spinal microglia prevented and reversed mechanical allodynia. P2X7Rs drive Panx1 channel activation, and in rats with mechanical allodynia, Panx1 function was increased in spinal microglia. Specifically, microglial Panx1-mediated release of the proinflammatory cytokine interleukin-1ß (IL-1ß) induced mechanical allodynia in the MIA-injected hindlimb. Intrathecal administration of the Panx1-blocking peptide 10panx suppressed the aberrant discharge of spinal laminae I-II neurons evoked by innocuous mechanical hindpaw stimulation in arthritic rats. Furthermore, mice with a microglia-specific genetic deletion of Panx1 were protected from developing mechanical allodynia. Treatment with probenecid, a clinically used broad-spectrum Panx1 blocker, resulted in a striking attenuation of MIA-induced mechanical allodynia and normalized responses in the dynamic weight-bearing test, without affecting acute nociception. Probenecid reversal of mechanical allodynia was also observed in rats 13 weeks after anterior cruciate ligament transection, a model of posttraumatic osteoarthritis. Thus, Panx1-targeted therapy is a new mechanistic approach for alleviating joint pain.

Reducing risk of spinal haematoma from spinal and epidural pain procedures.

BACKGROUND AND AIMS: Central neuraxial blocks (CNB: epidural, spinal and their combinations) and other spinal pain procedures can cause serious harm to the spinal cord in patients on antihaemostatic drugs or who have other risk-factors for bleeding in the spinal canal. The purpose of this narrative review is to provide a practise advisory on how to reduce risk of spinal cord injury from spinal haematoma (SH) during CNBs and other spinal pain procedures. Scandinavian guidelines from 2010 are part of the background for this practise advisory. METHODS: We searched recent guidelines, PubMed (MEDLINE), SCOPUS and EMBASE for new and relevant randomised controlled trials (RCT), case-reports and original articles concerning benefits of neuraxial blocks, risks of SH due to anti-haemostatic drugs, patient-related risk factors, especially renal impairment with delayed excretion of antihaemostatic drugs, and specific risk factors related to the neuraxial pain procedures. RESULTS AND RECOMMENDATIONS: Epidural and spinal analgesic techniques, as well as their combination provide superior analgesia and reduce the risk of postoperative and obstetric morbidity and mortality. Spinal pain procedure can be highly effective for cancer patients, less so for chronic non-cancer patients. We did not identify any RCT with SH as outcome. We evaluated risks and recommend precautions for SH when patients are treated with antiplatelet, anticoagulant, or fibrinolytic drugs, when patients' comorbidities may increase risks, and when procedure-specific risk factors are present. Inserting and withdrawing epidural catheters appear to have similar risks for initiating a SH. Invasive neuraxial pain procedures, e.g. spinal cord stimulation, have higher risks of bleeding than traditional neuraxial blocks. We recommend robust monitoring routines and treatment protocol to ensure early diagnosis and effective treatment of SH should this rare but potentially serious complication occur. CONCLUSIONS: When neuraxial analgesia is considered for a patient on anti-haemostatic medication, with patient-related, or procedure-related risk factors, the balance of benefits against risks of bleeding is decisive; when CNB are offered exclusively to patients who will have a reduction of postoperative morbidity and mortality, then a higher risk of bleeding may be accepted. Robust routines should ensure appropriate discontinuation of anti-haemostatic drugs and early detection and treatment of SH. IMPLICATIONS: There is an on-going development of drugs for prevention of thromboembolic events following surgery and childbirth. The present practise advisory provides up-to-date knowledge and experts' experiences so that patients who will greatly benefit from neuraxial pain procedures and have increased risk of bleeding can safely benefit from these procedures. There are always individual factors for the clinician to evaluate and consider. Increasingly it is necessary for the anaesthesia and analgesia provider to collaborate with specialists in haemostasis. Surgeons and obstetricians must be equally well prepared to collaborate for the best outcome for their patients suffering from acute or chronic pain. Optimal pain management is a prerequisite for enhanced recovery after surgery, but there is a multitude of additional concerns, such as early mobilisation, early oral feeding and ileus prevention that surgeons and anaesthesia providers need to optimise for the best outcome and least risk of complications.

Institutional Protocol for Prevention of TEVAR-related Spinal Cord Ischemia - The First 9 Cases.

INTRODUCTION: Spinal cord ischemia (SCI) is a feared complication after endovascular correction of thoracic aortic diseases (TEVAR). The guidelines of the European Society for Vascular Surgery recommend prophylactic lumbar drainage (LD) of cerebrospinal fluid in high-risk patients undergoing TEVAR. Our institutional protocol considers as high-risk patients as: coverage of the origin of the Adamkiewicz artery (T9-T12), aortic coverage >15 cm, involvement of collaterals (treated or untreated abdominal aortic aneurysm, left subclavian artery revascularization or bilateral occlusion of the internal iliac arteries) and symptomatic SCI. The objective of the study was to demonstrate the efficacy and safety of LD in preventing or treating SCI after TEVAR. METHODS: Patients submitted to LD in the perioperative period of TEVAR under the institutional protocol, between May 2015 and April 2017, were prospectively included. PRIMARY OUTCOME: prevention and/or reversal of neurological symptoms (efficacy). Secondary Outcome: complications related to the technique (safety). RESULTS: We included 8 patients with thoracoabdominal aneurysms and 1 patient with type B aortic dissection, aged 63- 75 years. Eight interventions were elective and one was urgent. The LD catheter was placed before surgery in 8 cases and in the postoperative period in 1 case due to symptomatology of SCI that reverted after liquor drainage. Of those placed pre-operatively, 2 had symptoms of SCI in the postoperative period, which alleviated with increased drainage and hemodynamic and hemoglobin optimization. The patient undergoing urgent TEVAR for ruptured thoracoabdominal aneurysm evolved with multiorgan dysfunction and death 24 hours after surgery. There were no other complications. CONCLUSION: In this initial experience, the institutional protocol with LD placement proved to be safe and effective in preventing and treating SCI after TEVAR.

Cervical myelopathy due to atraumatic odontoid fracture in patients with rheumatoid arthritis: A case series.

To highlight the risk of cervical myelopathy due to occult, atraumatic odontoid fracture in patients with rheumatoid arthritis, we retrospectively reviewed radiographic findings and clinical observations for 7 patients with this disorder. This fracture tends to occur in patients with long-lasting rheumatoid arthritis and to be misdiagnosed as simple atlantoaxial dislocation. Since this fracture causes multidirectional instability between C1 and C2 and is expected to have poor healing potential due to bone erosion and inadequate blood supply, posterior spinal arthrodesis surgery is indicated upon identification of the fracture to prevent myelopathy.

Management Strategy of Osteoblastomas Localized in the Occipitocervical Junction.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Reducing the global burden of HTLV-1 infection: An agenda for research and action.

Even though an estimated 10-20 million people worldwide are infected with the oncogenic retrovirus, human T-lymphotropic virus type 1 (HTLV-1), its epidemiology is poorly understood, and little effort has been made to reduce its prevalence. In response to this situation, the Global Virus Network launched a taskforce in 2014 to develop new methods of prevention and treatment of HTLV-1 infection and promote basic research. HTLV-1 is the etiological agent of two life-threatening diseases, adult T-cell leukemia and HTLV-associated myelopathy/tropical spastic paraparesis, for which no effective therapy is currently available. Although the modes of transmission of HTLV-1 resemble those of the more familiar HIV-1, routine diagnostic methods are generally unavailable to support the prevention of new infections. In the present article, the Taskforce proposes a series of actions to expand epidemiological studies; increase research on mechanisms of HTLV-1 persistence, replication and pathogenesis; discover effective treatments; and develop prophylactic and therapeutic vaccines.

[Intensity-modulated radiotherapy of head and neck cancers. Dose constraint for spinal cord and brachial plexus]. / Radiothérapie conformationnelle avec modulation d'intensité des cancers des voies aérodigestives supérieures. Dose de tolérance des tissus sains : moelle épinière et plexus brachial.

Given the ballistic opportunities it offers, intensity-modulated radiotherapy has emerged as the gold standard treatment for head and neck cancers. Protection of organs at risk is one of the objectives of optimization during the planning process. The compliance of dose constraints to the nervous system must be prioritized over all others. To avoid complications, it is recommended to respect a maximum dose of 50Gy to the spinal cord, and 60Gy to the brachial plexus using conventional fractionation of 2Gy per fraction. These constraints can be adapted depending on the clinical situation; they will probably be refocused by the follow-up of the IMRT studies.

[Cervical myelopathy after low grade distortion of the cervical spine. Possible association with pre-existing spondylosis of the cervical spine]. / Zervikale Myelopathie nach leichter HWS-Distorsion Grad 1. Möglicher Zusammenhang mit vorbestehender Spondylose der HWS.

A patient with spondylosis deformans of the cervical spine with no neurological deficits developed rapidly progressive tetraparesis 1 day after a whiplash injury due to a car accident (rear end collision), although initially there were no clinical symptoms. Surgical decompression and spondylodesis led to relief of the neurological deficits. This case demonstrates that even a low grade whiplash injury (grade 1) can cause severe neurological symptoms later and that a degenerative disease of the spine is a predisposing factor.

Cilostazol, a selective Type III phosphodiesterase inhibitor: prevention of cervical myelopathy in a rat chronic compression model.

OBJECT: Regional blood flow is decreased in experimental models of chronic spinal cord compression, and the alteration presumably contributes to the development of myelopathy. Cilostazol (Otsuka Pharmaceuticals Co.), a selective Type III phosphodiesterase inhibitor, has been shown to be neuroprotective in cerebral hypoperfusion animal models and clinically effective in preventing the recurrence of cerebral infarction. To investigate the neuroprotective effect of cilostazol on cervical spondylotic myelopathy, the preventive effect against progressive motor dysfunction and the loss of anterior horn motor neurons were assessed using a chronic cord compression model in rats. METHODS: To produce chronic cervical cord compression in male Wistar rats, thin polyurethane sheets (3 × 5 × 0.7 mm) that gradually expand over 48-72 hours by absorbing water were implanted under the C5-6 laminae. In sham operations, the sheets were momentarily placed and then immediately removed. This model has been shown to reproduce characteristic features of clinical cervical myelopathy, with progressive motor disturbances after a latency period and insidious neuronal loss preceding the onset of symptoms. In the treatment group, cilostazol (30 mg/kg/day) was orally administered to the rats once a day, starting the day after surgery and continuing through the entire observation period of 25 weeks. In the control group, vehicle solution was administered under the same protocol. Changes in motor function were monitored by measuring bilateral forepaw grip strength and the duration of forced running on a treadmill. Twenty-five weeks after surgery, cervical spinal cords were examined histopathologically. RESULTS: Cilostazol preserved both forepaw grip strength and forced running capability. The drug also preserved anterior horn motor neurons in the C5-6 spinal cord segment, which diminished in number in the untreated chronic compression group. The drug decreased the number of TUNEL-positive apoptotic cells. CONCLUSIONS: These results indicate that cilostazol is neuroprotective in the chronically compressed cervical cord and is potentially useful in the treatment of cervical spondylotic myelopathy.

Avaliação fenotípica e funcional dos linfócitos T citotóxicos de indivíduos infectados pelo HTLV-1 com diagnóstico de HAM/TSP / Phenotypic and functional assessment of cytotoxic T lymphocytes from individuals infected with HTLV-1 diagnosed with HAM / TSP

O Brasil representa uma das áreas endêmicas para o vírus linfotrópico de células T humanas do tipo 1 (HTLV-1) e a cidade de Salvador, Bahia, possui a maior prevalência nacional da infecção por este retrovírus (1,8%), com cerca de 50.000 pessoas infectadas. O HTLV-1 foi o primeiro retrovírus humano descrito e está classicamente associado à leucemia/linfoma de células T do adulto (ATLL) e à mielopatia associada ao HTLV-1/paraparesia espástica tropical (HAM/TSP). A HAM/TSP é uma doença inflamatória do sistema nervoso central, cujos mecanismos imunopatogênicos não estão completamente elucidados. O papel dos linfócitos T citotóxicos na patogênese desta doença ainda não está bem definido. Neste estudo, foram avaliados o fenótipo e a função de linfócitos T citotóxicos de pacientes infectados pelo HTLV-1 com HAM/TSP...

Brazil represents one of the largest endemic areas for human T-lymphotropic virus cells type 1 (HTLV-1) infection and associated diseases. Salvador, Bahia, is considered as the Brazilian city with the highest national HTLV-1prevalence (around 1.8% in the general population). HTLV -1 was the first human retrovirus described and is classically associated with adult Tcell leukemia/lymphoma (ATLL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is a chronic and progressive inflammatory disease of the central nervous system and your immunopathogenic mechanisms are not completely understood. The role of cytotoxic T-lymphocytes (CTLs) in the pathogenesis of this disease is still undefined. In this study we evaluated the phenotype and function of cytotoxic Tlymphocytes from HTLV-1-infected patients with HAM/TSP...

Novel biodegradable lamina for lamina repair and reconstruction.

BACKGROUND CONTEXT: Posterior laminectomy is an effective spinal surgical procedure. The adhesion of postoperative scar tissue to surgically exposed dura and, occasionally, to nerve roots can cause failed back surgery syndrome. The establishment of a barrier between scar tissue and dura that is made of hard material may prevent scar adhesions. PURPOSE: To evaluate the efficacy of a novel biodegradable multi-amino acid copolymer/nanohydroxyapatite composite artificial lamina. METHODS: A cervical laminectomy animal model in goats was used, and the animals were randomly divided into three groups. In the test group, cervical 4 was removed by laminectomy and the artificial lamina was inserted (n=12). In the control group, the incision was closed directly without implantation (n=9). The goats in the normal group did not undergo any procedure or treatment. Copolymer efficiency was tested by using X-ray, computed tomography scanning, magnetic resonance imaging, scanning electronic microscope, and histologic and biomechanical measurements 4, 12, and 24 weeks postoperation. RESULTS: No shifting of the artificial lamina or dural adhesion pressure was observed. New cervical natural bone formed in the defect and the bony spinal canal was rebuilt. In the control group, fibrous scar tissue filled the defect and exerted pressure on the dura. No paralysis was observed, and gait was normal in all test and control goats. CONCLUSIONS: Artificial lamina can prevent the epidural adhesions surrounding the defect and promote effectively bone tissue repair and new bone formation.

[Low back pain in the elderly]. / Rückenschmerzen im Alter.

Elderly people often complain of back pain which lead to functional limitation and reduced independence. Degenerative changes together with their consequences are in the fore, on top of it illnesses which go hand-in-hand and lead to a certain deconditioning have to be considered. Lumbar spinal stenosis leads to progressingly reduced walking distances and is often surgically treated. Degenerative scoliosis is a progressive course of disease and should first of all be treated conservatively although surgical options are also possible. In old age vertebral osteomyelitis is more frequent and should be conspired when assessing a case. Here typical causes of back problems are shown in case studies.

Metabolic, nutritional, and toxic myelopathies.

This review article identifies and describes the clinical manifestations of various metabolic, nutritional, and toxic conditions that result in symptoms of myelopathy and, in some cases, myeloneuropathy. It includes discussions of the clinical pictures that occur secondary to these causes. Familiarity with the clinical symptoms may lead to accurate diagnosis through laboratory and imaging studies and to treatment with successful identification of the underlying causes.