Spinal involvement in mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio A syndrome): presentation, diagnosis and management.

Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio-Brailsford or Morquio A syndrome, is a lysosomal storage disorder caused by a deficiency of the enzyme N-acetyl-galactosamine-6-sulphate sulphatase (GALNS). MPS IVA is multisystemic but manifests primarily as a progressive skeletal dysplasia. Spinal involvement is a major cause of morbidity and mortality in MPS IVA. Early diagnosis and timely treatment of problems involving the spine are critical in preventing or arresting neurological deterioration and loss of function. This review details the spinal manifestations of MPS IVA and describes the tools used to diagnose and monitor spinal involvement. The relative utility of radiography, computed tomography (CT) and magnetic resonance imaging (MRI) for the evaluation of cervical spine instability, stenosis, and cord compression is discussed. Surgical interventions, anaesthetic considerations, and the use of neurophysiological monitoring during procedures performed under general anaesthesia are reviewed. Recommendations for regular radiological imaging and neurologic assessments are presented, and the need for a more standardized approach for evaluating and managing spinal involvement in MPS IVA is addressed

Recommendations for the management of MPS IVA: systematic evidence- and consensus-based guidance.

IntroductionMucopolysaccharidosis (MPS) IVA or Morquio A syndrome is an autosomal recessive lysosomal storage disorder (LSD) caused by deficiency of the N-acetylgalactosamine-6-sulfatase (GALNS) enzyme, which impairs lysosomal degradation of keratan sulphate and chondroitin-6-sulphate. The multiple clinical manifestations of MPS IVA present numerous challenges for management and necessitate the need for individualised treatment. Although treatment guidelines are available, the methodology used to develop this guidance has come under increased scrutiny. This programme was conducted to provide evidence-based, expert-agreed recommendations to optimise management of MPS IVA.MethodsTwenty six international healthcare professionals across multiple disciplines, with expertise in managing MPS IVA, and three patient advocates formed the Steering Committee (SC) and contributed to the development of this guidance. Representatives from six Patient Advocacy Groups (PAGs) were interviewed to gain insights on patient perspectives. A modified-Delphi methodology was used to demonstrate consensus among a wider group of healthcare professionals with experience managing patients with MPS IVA and the manuscript was evaluated against the validated Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument by three independent reviewers.ResultsA total of 87 guidance statements were developed covering five domains: (1) general management principles; (2) recommended routine monitoring and assessments; (3) disease-modifying interventions (enzyme replacement therapy [ERT] and haematopoietic stem cell transplantation [HSCT]); (4) interventions to support respiratory and sleep disorders; (5) anaesthetics and surgical interventions (including spinal, limb, ophthalmic, cardio-thoracic and ear-nose-throat [ENT] surgeries). Consensus was reached on all statements after two rounds of voting. The overall guideline AGREE II assessment score obtained for the development of the guidance was 5.3/7 (where 1 represents the lowest quality and 7 represents the highest quality of guidance).ConclusionThis manuscript provides evidence- and consensus-based recommendations for the management of patients with MPS IVA and is for use by healthcare professionals that manage the holistic care of patients with the intention to improve clinical- and patient-reported outcomes and enhance patient quality of life. It is recognised that the guidance provided represents a point in time and further research is required to address current knowledge and evidence gaps

Effects of local hypothermia-rewarming on physiology, metabolism and inflammation of acutely injured human spinal cord.

In five patients with acute, severe thoracic traumatic spinal cord injuries (TSCIs), American spinal injuries association Impairment Scale (AIS) grades A-C, we induced cord hypothermia (33 °C) then rewarming (37 °C). A pressure probe and a microdialysis catheter were placed intradurally at the injury site to monitor intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), tissue metabolism and inflammation. Cord hypothermia-rewarming, applied to awake patients, did not cause discomfort or neurological deterioration. Cooling did not affect cord physiology (ISP, SCPP), but markedly altered cord metabolism (increased glucose, lactate, lactate/pyruvate ratio (LPR), glutamate; decreased glycerol) and markedly reduced cord inflammation (reduced IL1β, IL8, MCP, MIP1α, MIP1β). Compared with pre-cooling baseline, rewarming was associated with significantly worse cord physiology (increased ICP, decreased SCPP), cord metabolism (increased lactate, LPR; decreased glucose, glycerol) and cord inflammation (increased IL1β, IL8, IL4, IL10, MCP, MIP1α). The study was terminated because three patients developed delayed wound infections. At 18-months, two patients improved and three stayed the same. We conclude that, after TSCI, hypothermia is potentially beneficial by reducing cord inflammation, though after rewarming these benefits are lost due to increases in cord swelling, ischemia and inflammation. We thus urge caution when using hypothermia-rewarming therapeutically in TSCI

Mutant Tau knock-in mice display frontotemporal dementia relevant behaviour and histopathology

Peer reviewedPostprin

Efficiency of spinal anesthesia versus general anesthesia for lumbar spinal surgery: a retrospective analysis of 544 patients.

BACKGROUND: Previous studies have shown varying results in selected outcomes when directly comparing spinal anesthesia to general in lumbar surgery. Some studies have shown reduced surgical time, postoperative pain, time in the postanesthesia care unit (PACU), incidence of urinary retention, postoperative nausea, and more favorable cost-effectiveness with spinal anesthesia. Despite these results, the current literature has also shown contradictory results in between-group comparisons. MATERIALS AND METHODS: A retrospective analysis was performed by querying the electronic medical record database for surgeries performed by a single surgeon between 2007 and 2011 using procedural codes 63030 for diskectomy and 63047 for laminectomy: 544 lumbar laminectomy and diskectomy surgeries were identified, with 183 undergoing general anesthesia and 361 undergoing spinal anesthesia (SA). Linear and multivariate regression analyses were performed to identify differences in blood loss, operative time, time from entering the operating room (OR) until incision, time from bandage placement to exiting the OR, total anesthesia time, PACU time, and total hospital stay. Secondary outcomes of interest included incidence of postoperative spinal hematoma and death, incidence of paraparesis, plegia, post-dural puncture headache, and paresthesia, among the SA patients. RESULTS: SA was associated with significantly lower operative time, blood loss, total anesthesia time, time from entering the OR until incision, time from bandage placement until exiting the OR, and total duration of hospital stay, but a longer stay in the PACU. The SA group experienced one spinal hematoma, which was evacuated without any long-term neurological deficits, and neither group experienced a death. The SA group had no episodes of paraparesis or plegia, post-dural puncture headaches, or episodes of persistent postoperative paresthesia or weakness. CONCLUSION: SA is effective for use in patients undergoing elective lumbar laminectomy and/or diskectomy spinal surgery, and was shown to be the more expedient anesthetic choice in the perioperative setting

Aerospace Medicine and Biology: A continuing bibliography with indexes

This bibliography lists 253 reports, articles, and other documents introduced into the NASA scientific and technical information system in October 1975

Protocol for electrophysiological monitoring of carotid endarterectomies.

Near zero stroke rates can be achieved in carotid endarterectomy (CEA) surgery with selective shunting and electrophysiological neuromonitoring. though false negative rates as high as 40% have been reported. We sought to determine if improved training for interpretation of the monitoring signals can advance the efficacy of selective shunting with electrophysiological monitoring across multiple centers, and determine if other factors could contribute to the differences in reports. Processed and raw beta band (12.5-30 Hz) electroencephalogram (EEG) and median and tibial nerve somatosensory evoked potentials (SSEP) were monitored in 668 CEA cases at six surgical centers. A decrease in amplitude of 50% or more in any EEG or SSEP channel was the criteria for shunting or initiating a neuroprotective protocol. A reduction of 50% or greater in the beta band of the EEG or amplitude of the SSEP was observed in 150 cases. No patient showed signs of a cerebral infarct after surgery. Selective shunting based on EEG and SSEP monitoring can reduce CEA intraoperative stroke rate to a near zero level if trained personnel adopted standardized protocols. We also found that the rapid administration of a protective stroke protocol by attending anesthesiologists was an important aspect of this success rate

Two-photon imaging and analysis of neural network dynamics

The glow of a starry night sky, the smell of a freshly brewed cup of coffee or the sound of ocean waves breaking on the beach are representations of the physical world that have been created by the dynamic interactions of thousands of neurons in our brains. How the brain mediates perceptions, creates thoughts, stores memories and initiates actions remains one of the most profound puzzles in biology, if not all of science. A key to a mechanistic understanding of how the nervous system works is the ability to analyze the dynamics of neuronal networks in the living organism in the context of sensory stimulation and behaviour. Dynamic brain properties have been fairly well characterized on the microscopic level of individual neurons and on the macroscopic level of whole brain areas largely with the help of various electrophysiological techniques. However, our understanding of the mesoscopic level comprising local populations of hundreds to thousands of neurons (so called 'microcircuits') remains comparably poor. In large parts, this has been due to the technical difficulties involved in recording from large networks of neurons with single-cell spatial resolution and near- millisecond temporal resolution in the brain of living animals. In recent years, two-photon microscopy has emerged as a technique which meets many of these requirements and thus has become the method of choice for the interrogation of local neural circuits. Here, we review the state-of-research in the field of two-photon imaging of neuronal populations, covering the topics of microscope technology, suitable fluorescent indicator dyes, staining techniques, and in particular analysis techniques for extracting relevant information from the fluorescence data. We expect that functional analysis of neural networks using two-photon imaging will help to decipher fundamental operational principles of neural microcircuits.Comment: 36 pages, 4 figures, accepted for publication in Reports on Progress in Physic

بررسی ميزان خونريزی در اعمال جراحی فيوژن خلفی مهره های کمری با پيش داروی کلونيدين خوراک

زمينه: خونريزی حين عمل هرچند از جمله مسائل مهم در اعمال جراحی ستون فقرات است،ولی درمورد روش­های کاهش وعوامل مؤثربر آن بر خلاف اعمال جراحی آرتروپلاستی هيپ وزانو؛در جراحی ستون فقرات مطالعات بسيار کمی ‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌انجام گرفته است.دراين مطالعه ما تأثيرکلونيدين را بصورت پيش داروی خوراکی بر خونريزی حين عمل در اعمال جراحی فيوژن خلفی مهره‌های کمری تحت بيهوشی با پروپوفول و رمي­فنتانيل مورد بررسی قرار داديم. مواد و روش­ها:دراين کارآزمايی بالينی تصادفی شدهَ دوسوکور ،۳۰ بيمارکانديدای فيوژن خلفی مهره‌های کمری بطور تصادفی در دو گروه قرار گرفتند. بيماران گروه مطالعه (گروه کلونيدين) ۹۰-۶۰ دقيقه قبل از بيهوشی قرص کلونيدين ۲۰۰ ميکروگرمی و بيماران گروه کنترل درهمان زمان پلاسبو دريافت کردند. روش القاء و نگهداری بيهوشی و فشارمتوسط شريانی هدف برای هيپوتانسيون کنترله با رمي­فنتانيل در دو گروه يکسان بود. دو گروه از جهات ميزان خونريزی،دوز رمي­فنتانيل تجويز شده درساعت،تعداد بيمارانی که برای رسيدن به فشارمتوسط شريانی هدف به نيتروگليسرين نياز بود (وقتی رمي­فنتانيل کافی نبود)،مدت عمل و رضايت جراح از يک فيلد عاری از خون با هم مورد مقايسه قرار گرفتند. يافته­ها:بين دو گروه از نظر خصوصيات دموگرافيک مانند سن (p = 115/0)،جنس(p = 349/0)، وضعيت فيزيکی ASA (p = 39/0)،وزن(p= 2/0) و مدت عمل(p = 899/0) تفاوت آماری معني­داری وجود نداشت. ميزانخونريزی حين عمل وميزان رمي­فنتانيل تجويز شده در ساعت در گروه کلونيدين بطور معني­داری (به ترتيب pکمتر از 002/0 و 001/0) کمتر از گروه کنترل بود. رضايت جراح بين دو گروه تفاوت معنی داری نداشت (p = 169/0). نتيجه­گيری: کلونيدين به صورت پيش داروی خوراکی مي­تواند موجب کاهش ميزان خونريزی در اعمال جراحی فيوژن خلفی مهره های کمری، در سطح يکسان فشار متوسط شريانی با گروه کنترل شود. مي­توان استفاده از آن­را به اين منظور در اعمال جراحی پيچيده­تر ستون فقرات نظير جراحی برای دفورميتی ستون فقرات که با خونريزی بيشتری همراه است مورد بررسی قرار داد