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PURPOSE: We surveyed the treatment of acute spinal cord injuries in the UK and compared current practices with 10 years ago. METHODS: A questionnaire survey was conducted amongst neurosurgeons, neuroanaesthetists, and neurointensivists that manage patients with acute spinal cord injuries. The survey gave two scenarios (complete and incomplete cervical spinal cord injuries). We obtained opinions on the speed of transfer, timing and aim of surgery, choice of anaesthetic, intraoperative monitoring, targets for physiological parameters, and drug treatments. RESULTS: We received responses from 78.6% of UK units that manage acute spinal cord injuries (33 neurosurgeons, 56 neuroanaesthetists/neurointensivists). Most neurosurgeons operate within 12 h for incomplete (82%) and complete (64%) injuries. There is a significant shift from 10 years ago, when only 61% (incomplete) and 30% (complete) of neurosurgeons operated within 12 h. The preferred anaesthetic technique in 2022 is total intravenous anaesthesia (TIVA), used by 69% of neuroanaesthetists. Significantly more intraoperative monitoring is now used at least sometimes, including bispectral index (91%), non-invasive cardiac output (62%), and neurophysiology (73-77%). Methylprednisolone is no longer used by surgeons. Achieving at least 80 mmHg mean arterial blood pressure is recommended by 70% neurosurgeons, 62% neuroanaesthetists, and 75% neurointensivists. CONCLUSIONS: Between 2012 and 2022, there was a paradigm shift in managing acute spinal cord injuries in the UK with earlier surgery and more intraoperative monitoring. Variability in practice persists due to lack of high-quality evidence and consensus guidelines.
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Anestésicos , Traumatismos de la Médula Espinal , Humanos , Traumatismos de la Médula Espinal/epidemiología , Traumatismos de la Médula Espinal/cirugía , Metilprednisolona/uso terapéutico , Cuidados Críticos , Anestésicos/uso terapéutico , Reino Unido/epidemiologíaRESUMEN
OBJECTIVE: This study aims to determine the relationship between spinal cord perfusion pressure (SCPP) and breathing function in patients with acute cervical traumatic spinal cord injuries. METHODS: We included 8 participants without cervical TSCI plus 13 patients with cervical traumatic spinal cord injuries, American Spinal Injury Association Impairment Scale grades A-C. In the TSCI patients, we monitored intraspinal pressure from the injury site for up to a week and computed the SCPP as mean arterial pressure minus intraspinal pressure. Breathing function was quantified by diaphragmatic electromyography using an EDI (electrical activity of the diaphragm) nasogastric tube as well as by ultrasound of the diaphragm and the intercostal muscles performed when sitting at 20°-30°. RESULTS: We analysed 106 ultrasound examinations (total 1370 images/videos) and 198 EDI recordings in the patients with cervical traumatic spinal cord injuries. During quiet breathing, low SCPP (< 60 mmHg) was associated with reduced EDI-peak (measure of inspiratory effort) and EDI-min (measure of the tonic activity of the diaphragm), which increased and then plateaued at SCPP 60-100 mmHg. During quiet and deep breathing, the diaphragmatic thickening fraction (force of diaphragmatic contraction) plotted versus SCPP had an inverted-U relationship, with a peak at SCPP 80-90 mmHg. Diaphragmatic excursion (up and down movement of the diaphragm) during quiet breathing did not correlate with SCPP, but diaphragmatic excursion during deep breathing plotted versus SCPP had an inverse-U relationship with a peak at SCPP 80-90 mmHg. The thickening fraction of the intercostal muscles plotted versus SCPP also had inverted-U relationship, with normal intercostal function at SCPP 80-100 mmHg, but failure of the upper and middle intercostals to contract during inspiration (i.e. abdominal breathing) at SCPP < 80 or > 100 mmHg. CONCLUSIONS: After acute, cervical traumatic spinal cord injuries, breathing function depends on the SCPP. SCPP 80-90 mmHg correlates with optimum diaphragmatic and intercostal muscle function. Our findings raise the possibility that intervention to maintain SCPP in this range may accelerate ventilator liberation which may reduce stay in the neuro-intensive care unit.
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Traumatismos de la Médula Espinal , Humanos , Perfusión , Respiración , Diafragma/diagnóstico por imagenRESUMEN
BACKGROUND: There is uncertainty regarding delayed removal versus retention of minimally invasive screws following percutaneous fixation for thoracolumbar fractures. We conducted a systematic review and case-control study to test the hypothesis that delayed metalwork removal following percutaneous fixation for thoracolumbar fractures improves outcome. METHODS: A systematic review was performed in accordance with the PRISMA guidelines. Our case-control study retrospectively evaluated 55 consecutive patients with thoracolumbar fractures who underwent percutaneous fixation in a single unit: 19 with metalwork retained (controls) and 36 with metalwork removed. Outcomes were the Oswestry Disability Index (ODI), a supplemental questionnaire, and complications. RESULTS: The systematic review evaluated nine articles. Back pain was reduced in most patients after metalwork removal. One study found no difference in the ODI after versus before metalwork removal, whereas three studies reported significant improvement. Six studies noted no significant alterations in radiological markers of stability after metalwork removal. Mean complication rate was 1.7% (0-6.7). Complications were superficial wound infection, screw breakage at the time of removal, pull-out screw, and a broken rod. In the case-control study, both groups were well matched. For metalwork removal, mean operative time was 69.5 min (range 30-120) and length of stay was 1.3 days (0-4). After metalwork removal, 24 (68.6%) patients felt better, 10 (28.6%) the same and one felt worse. Two patients had superficial hematomas, one had a superficial wound infection, and none required re-operation. Metalwork removal was a significant predictor of return to work or baseline household duties (odds ratio 5.0 [1.4-18.9]). The ODI was not different between groups. CONCLUSIONS: The findings of both the systematic review and our case-control study suggest that removal of metalwork following percutaneous fixation of thoracolumbar fractures is safe and is associated with improved outcome in most patients.
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Fracturas Óseas , Tornillos Pediculares , Fracturas de la Columna Vertebral , Humanos , Estudios de Casos y Controles , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/cirugía , Estudios Retrospectivos , Fijación Interna de Fracturas/efectos adversos , Tornillos Pediculares/efectos adversos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Vértebras Torácicas/diagnóstico por imagen , Vértebras Torácicas/cirugía , Vértebras Torácicas/lesiones , Resultado del TratamientoRESUMEN
OBJECTIVES: To determine the feasibility of monitoring tissue oxygen tension from the injury site (pscto2) in patients with acute, severe traumatic spinal cord injuries. DESIGN: We inserted at the injury site a pressure probe, a microdialysis catheter, and an oxygen electrode to monitor for up to a week intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), tissue glucose, lactate/pyruvate ratio (LPR), and pscto2. We analyzed 2,213 hours of such data. Follow-up was 6-28 months postinjury. SETTING: Single-center neurosurgical and neurocritical care units. SUBJECTS: Twenty-six patients with traumatic spinal cord injuries, American spinal injury association Impairment Scale A-C. Probes were inserted within 72 hours of injury. INTERVENTIONS: Insertion of subarachnoid oxygen electrode (Licox; Integra LifeSciences, Sophia-Antipolis, France), pressure probe, and microdialysis catheter. MEASUREMENTS AND MAIN RESULTS: pscto2 was significantly influenced by ISP (pscto2 26.7 ± 0.3 mm Hg at ISP > 10 mmHg vs pscto2 22.7 ± 0.8 mm Hg at ISP ≤ 10 mm Hg), SCPP (pscto2 26.8 ± 0.3 mm Hg at SCPP < 90 mm Hg vs pscto2 32.1 ± 0.7 mm Hg at SCPP ≥ 90 mm Hg), tissue glucose (pscto2 26.8 ± 0.4 mm Hg at glucose < 6 mM vs 32.9 ± 0.5 mm Hg at glucose ≥ 6 mM), tissue LPR (pscto2 25.3 ± 0.4 mm Hg at LPR > 30 vs pscto2 31.3 ± 0.3 mm Hg at LPR ≤ 30), and fever (pscto2 28.8 ± 0.5 mm Hg at cord temperature 37-38°C vs pscto2 28.7 ± 0.8 mm Hg at cord temperature ≥ 39°C). Tissue hypoxia also occurred independent of these factors. Increasing the Fio2 by 0.48 increases pscto2 by 71.8% above baseline within 8.4 minutes. In patients with motor-incomplete injuries, fluctuations in pscto2 correlated with fluctuations in limb motor score. The injured cord spent 11% (39%) hours at pscto2 less than 5 mm Hg (< 20 mm Hg) in patients with motor-complete outcomes, compared with 1% (30%) hours at pscto2 less than 5 mm Hg (< 20 mm Hg) in patients with motor-incomplete outcomes. Complications were cerebrospinal fluid leak (5/26) and wound infection (1/26). CONCLUSIONS: This study lays the foundation for measuring and altering spinal cord oxygen at the injury site. Future studies are required to investigate whether this is an effective new therapy.
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Presión del Líquido Cefalorraquídeo , Traumatismos de la Médula Espinal , Glucosa , Humanos , Oxígeno , Médula EspinalRESUMEN
BACKGROUND: We describe a novel progressive neurological syndrome complicating traumatic spinal cord injury (TSCI). Based on clinical and radiological features, we propose the term 'Chronic Relapsing Ascending Myelopathy' (CRAM). We distinguish between the previously described sub-acute progressive ascending myelopathy (SPAM) and post-traumatic syringomyelia (PTS), which may lie on a spectrum with CRAM. CASE REPORT: A 60-year-old man sustained a T4 ASIA-A complete TSCI. Four months post-injury, he developed a rapidly progressive ascending sensory level to C4. Clinical and radiological evaluation revealed ascending myelopathy with progressive T2 hyper-intense cord signal change. He underwent cord detethering and expansion duroplasty. Following an initial dramatic resolution of symptoms, the patient sustained two relapses, each 1-month post-discharge characterised by recurrence of disabling ascending sensory changes, each correlating with the radiological recurrence of cord signal change. Symptoms and radiological signal change permanently resolved with more extensive detethering and expansion duroplasty. There is radiological and clinical resolution at 1-year follow-up. CONCLUSION: Acute neurological deterioration post-TSCI may be due to SPAM or may occur after years due to PTS. We propose CRAM as a previously unrecognised phenomenon. The radiological characteristics overlap with SPAM. However, CRAM presents later and, clinically, behaves like PTS, but without cord cystic change. Cord detethering with expansion duroplasty are an effective treatment.
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Traumatismos de la Médula Espinal , Siringomielia , Masculino , Humanos , Persona de Mediana Edad , Cuidados Posteriores , Alta del Paciente , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/cirugía , Siringomielia/diagnóstico por imagen , Siringomielia/etiología , Siringomielia/cirugía , Laminectomía/efectos adversos , Enfermedad Crónica , Médula Espinal/diagnóstico por imagen , Médula Espinal/cirugía , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: Acute, severe traumatic spinal cord injury often causes fecal incontinence. Currently, there are no treatments to improve anal function after traumatic spinal cord injury. Our study aims to determine whether, after traumatic spinal cord injury, anal function can be improved by interventions in the neuro-intensive care unit to alter the spinal cord perfusion pressure at the injury site. METHODS: We recruited a cohort of patients with acute, severe traumatic spinal cord injuries (American Spinal Injury Association Impairment Scale grades A-C). They underwent surgical fixation within 72 h of the injury and insertion of an intrathecal pressure probe at the injury site to monitor intraspinal pressure and compute spinal cord perfusion pressure as mean arterial pressure minus intraspinal pressure. Injury-site monitoring was performed at the neuro-intensive care unit for up to a week after injury. During monitoring, anorectal manometry was also conducted over a range of spinal cord perfusion pressures. RESULTS: Data were collected from 14 patients with consecutive traumatic spinal cord injury aged 22-67 years. The mean resting anal pressure was 44 cmH2O, which is considerably lower than the average for healthy patients, previously reported at 99 cmH2O. Mean resting anal pressure versus spinal cord perfusion pressure had an inverted U-shaped relation (È2 = 0.82), with the highest resting anal pressures being at a spinal cord perfusion pressure of approximately 100 mmHg. The recto-anal inhibitory reflex (transient relaxation of the internal anal sphincter during rectal distension), which is important for maintaining fecal continence, was present in 90% of attempts at high (90 mmHg) spinal cord perfusion pressure versus 70% of attempts at low (60 mmHg) spinal cord perfusion pressure (P < 0.05). During cough, the rise in anal pressure from baseline was 51 cmH2O at high (86 mmHg) spinal cord perfusion pressure versus 37 cmH2O at low (62 mmHg) spinal cord perfusion pressure (P < 0.0001). During anal squeeze, higher spinal cord perfusion pressure was associated with longer endurance time and spinal cord perfusion pressure of 70-90 mmHg was associated with stronger squeeze. There were no complications associated with anorectal manometry. CONCLUSIONS: Our data indicate that spinal cord injury causes severe disruption of anal sphincter function. Several key components of anal continence (resting anal pressure, recto-anal inhibitory reflex, and anal pressure during cough and squeeze) markedly improve at higher spinal cord perfusion pressure. Maintaining too high of spinal cord perfusion pressure may worsen anal continence.
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Incontinencia Fecal , Traumatismos de la Médula Espinal , Adulto , Anciano , Canal Anal , Incontinencia Fecal/complicaciones , Humanos , Persona de Mediana Edad , Perfusión/efectos adversos , Adulto JovenRESUMEN
BACKGROUND/OBJECTIVE: We have recently developed monitoring from the injury site in patients with acute, severe traumatic spinal cord injuries to facilitate their management in the intensive care unit. This is analogous to monitoring from the brain in patients with traumatic brain injuries. This study aims to determine whether, after traumatic spinal cord injury, fluctuations in the monitored physiological, and metabolic parameters at the injury site are causally linked to changes in limb power. METHODS: This is an observational study of a cohort of adult patients with motor-incomplete spinal cord injuries, i.e., grade C American spinal injuries association Impairment Scale. A pressure probe and a microdialysis catheter were placed intradurally at the injury site. For up to a week after surgery, we monitored limb power, intraspinal pressure, spinal cord perfusion pressure, and tissue lactate-to-pyruvate ratio. We established correlations between these variables and performed Granger causality analysis. RESULTS: Nineteen patients, aged 22-70 years, were recruited. Motor score versus intraspinal pressure had exponential decay relation (intraspinal pressure rise to 20 mmHg was associated with drop of 11 motor points, but little drop in motor points as intraspinal pressure rose further, R2 = 0.98). Motor score versus spinal cord perfusion pressure (up to 110 mmHg) had linear relation (1.4 motor point rise/10 mmHg rise in spinal cord perfusion pressure, R2 = 0.96). Motor score versus lactate-to-pyruvate ratio (greater than 20) also had linear relation (0.8 motor score drop/10-point rise in lactate-to-pyruvate ratio, R2 = 0.92). Increased intraspinal pressure Granger-caused increase in lactate-to-pyruvate ratio, decrease in spinal cord perfusion, and decrease in motor score. Increased spinal cord perfusion Granger-caused decrease in lactate-to-pyruvate ratio and increase in motor score. Increased lactate-to-pyruvate ratio Granger-caused increase in intraspinal pressure, decrease in spinal cord perfusion, and decrease in motor score. Causality analysis also revealed multiple vicious cycles that amplify insults to the cord thus exacerbating cord damage. CONCLUSION: Monitoring intraspinal pressure, spinal cord perfusion pressure, lactate-to-pyruvate ratio, and intervening to normalize these parameters are likely to improve limb power.
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Traumatismos de la Médula Espinal , Adulto , Humanos , Lactatos , Perfusión , Piruvatos , Médula EspinalRESUMEN
We describe the unique case of a 51-year-old lady who developed a contralateral lumbosacral plexopathy two days after a lumbar microdiscectomy. This is the first report to date of this complication occurring following this procedure. We review the literature regarding lumbosacral plexopathy and discuss the evidence base behind investigating and managing this condition and the potential pathophysiological mechanisms which underlie its development. We draw comparisons with the more widely recognised post-operative brachial neuritis, characterised by delayed onset brachial plexopathy developing after cervical decompression, and propose an immune-mediated inflammatory mechanism linking the two conditions.
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Columna Vertebral , Neuropatías del Plexo Braquial/diagnóstico , Neuropatías del Plexo Braquial/etiología , Femenino , Humanos , Persona de Mediana Edad , Columna Vertebral/cirugíaRESUMEN
BACKGROUND/OBJECTIVES: We recently developed techniques to monitor intraspinal pressure (ISP) and spinal cord perfusion pressure (SCPP) from the injury site to compute the optimum SCPP (SCPPopt) in patients with acute traumatic spinal cord injury (TSCI). We hypothesized that ISP and SCPPopt can be predicted using clinical factors instead of ISP monitoring. METHODS: Sixty-four TSCI patients, grades A-C (American spinal injuries association Impairment Scale, AIS), were analyzed. For 24 h after surgery, we monitored ISP and SCPP and computed SCPPopt (SCPP that optimizes pressure reactivity). We studied how well 28 factors correlate with mean ISP or SCPPopt including 7 patient-related, 3 injury-related, 6 management-related, and 12 preoperative MRI-related factors. RESULTS: All patients underwent surgery to restore normal spinal alignment within 72 h of injury. Fifty-one percentage had U-shaped sPRx versus SCPP curves, thus allowing SCPPopt to be computed. Thirteen percentage, all AIS grade A or B, had no U-shaped sPRx versus SCPP curves. Thirty-six percentage (22/64) had U-shaped sPRx versus SCPP curves, but the SCPP did not reach the minimum of the curve, and thus, an exact SCPPopt could not be calculated. In total 5/28 factors were associated with lower ISP: older age, excess alcohol consumption, nonconus medullaris injury, expansion duroplasty, and less intraoperative bleeding. In a multivariate logistic regression model, these 5 factors predicted ISP as normal or high with 73% accuracy. Only 2/28 factors correlated with lower SCPPopt: higher mean ISP and conus medullaris injury. In an ordinal multivariate logistic regression model, these 2 factors predicted SCPPopt as low, medium-low, medium-high, or high with only 42% accuracy. No MRI factors correlated with ISP or SCPPopt. CONCLUSIONS: Elevated ISP can be predicted by clinical factors. Modifiable factors that may lower ISP are: reducing surgical bleeding and performing expansion duroplasty. No factors accurately predict SCPPopt; thus, invasive monitoring remains the only way to estimate SCPPopt.
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Circulación Sanguínea/fisiología , Presión del Líquido Cefalorraquídeo/fisiología , Monitorización Neurofisiológica/métodos , Traumatismos de la Médula Espinal/diagnóstico , Traumatismos de la Médula Espinal/fisiopatología , Médula Espinal/irrigación sanguínea , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Traumatismos de la Médula Espinal/cirugía , Adulto JovenRESUMEN
OBJECTIVES: To characterize the effect of fever after acute, traumatic spinal cord injury on injury site metabolism and patient outcome. DESIGN: Longitudinal cohort study. In 44 patients (London cohort), we determined the effect of fever on intrathecal injury site metabolism by analyzing 1,767 hours of intraspinal pressure and 759 hours of microdialysis data. We also determined the effect of fever burden, computed for the first 2 weeks in hospital, on neurologic outcome. A distinct cohort of 33 patients (Berlin cohort) was used to independently validate the effect of fever burden on outcome. SETTING: ICUs in London and Berlin. PATIENTS: Seventy-seven patients with acute, traumatic spinal cord injuries. INTERVENTIONS: In the London patients, a pressure probe and a microdialysis catheter were placed intradurally on the surface of the injured cord for up to a week. MEASUREMENTS AND MAIN RESULTS: Fever (> 37.5°C) occurs frequently (37% of the time) after spinal cord injury. High-grade fever (≥ 38°C) was associated with significantly more deranged metabolite levels than normothermia (36.5-37.5°C), that is, lower tissue glucose (median 2.0 vs 3.3 mM), higher lactate (7.8 vs 5.4 mM), higher glutamate (7.8 vs 6.4 µM), and higher lactate-to-pyruvate ratio (38.9 vs 29.3). High-grade fever was particularly detrimental on injury site metabolism when the peripheral leukocyte count was high. In the London and Berlin cohorts, high fever burden correlated with less neurologic improvement. CONCLUSIONS: Early after spinal cord injury, fever is associated with more deranged injury site metabolism than normothermia and worse prognosis.
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Fiebre/complicaciones , Recuperación de la Función , Traumatismos de la Médula Espinal/metabolismo , Adulto , Temperatura Corporal , Fiebre/metabolismo , Glucosa/metabolismo , Humanos , Unidades de Cuidados Intensivos , Estudios Longitudinales , Masculino , Microdiálisis , Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/complicacionesRESUMEN
The aquaporins (AQPs) are plasma membrane water-transporting proteins. AQP4 is the principal member of this protein family in the CNS, where it is expressed in astrocytes and is involved in water movement, cell migration and neuroexcitation. AQP1 is expressed in the choroid plexus, where it facilitates cerebrospinal fluid secretion, and in dorsal root ganglion neurons, where it tunes pain perception. The AQPs are potential drug targets for several neurological conditions. Astrocytoma cells strongly express AQP4, which may facilitate their infiltration into the brain, and the neuroinflammatory disease neuromyelitis optica is caused by AQP4-specific autoantibodies that produce complement-mediated astrocytic damage.
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Acuaporinas/fisiología , Astrocitos/metabolismo , Sistema Nervioso/citología , Agua/metabolismo , Animales , Acuaporinas/clasificación , Transporte Biológico/fisiología , Humanos , Sistema Nervioso/metabolismoRESUMEN
OBJECTIVE: There is lack of monitoring from the injury site to guide management of patients with acute traumatic spinal cord injury. Here, we describe a bedside microdialysis monitoring technique for optimizing spinal cord perfusion and drug delivery at the injury site. METHODS: Fourteen patients were recruited within 72 hours of severe spinal cord injury. We inserted intradurally at the injury site a pressure probe, to monitor continuously spinal cord perfusion pressure, and a microdialysis catheter, to monitor hourly glycerol, glutamate, glucose, lactate, and pyruvate. The pressure probe and microdialysis catheter were placed on the surface of the injured cord. RESULTS: Microdialysis monitoring did not cause serious complications. Spinal cord perfusion pressure 90 to 100mm Hg and tissue glucose >4.5mM minimized metabolic derangement at the injury site. Increasing spinal cord perfusion pressure by â¼10mm Hg increased the entry of intravenously administered dexamethasone at the injury site 3-fold. INTERPRETATION: This study determined the optimum spinal cord perfusion pressure and optimum tissue glucose concentration at the injury site. We also identified spinal cord perfusion pressure as a key determinant of drug entry into the injured spinal cord. Our findings challenge current guidelines, which recommend maintaining mean arterial pressure at 85 to 90mm Hg for a week after spinal cord injury. We propose that future drug trials for spinal cord injury include pressure and microdialysis monitoring to optimize spinal cord perfusion and maximize drug delivery at the injury site. Ann Neurol 2016;80:522-531.
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Antiinflamatorios/farmacocinética , Presión Sanguínea/fisiología , Dexametasona/farmacocinética , Glucosa/metabolismo , Microdiálisis/métodos , Monitoreo Fisiológico/métodos , Guías de Práctica Clínica como Asunto , Traumatismos de la Médula Espinal , Adulto , Anciano , Antiinflamatorios/administración & dosificación , Dexametasona/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/fisiopatología , Adulto JovenRESUMEN
Aquaporins are protein channels that facilitate the flow of water across plasma cell membranes in response to osmotic gradients. This review summarizes the evidence that aquaporins play key roles in tumor biology including tumor-associated edema, tumor cell migration, tumor proliferation and tumor angiogenesis. Aquaporin inhibitors may thus be a novel class of anti-tumor agents. However, attempts to produce small molecule aquaporin inhibitors have been largely unsuccessful. Recently, monoclonal human IgG antibodies against extracellular aquaporin-4 domains have become available and could be engineered to kill aquaporin-4 over-expressing cells in the malignant brain tumor glioblastoma. We conclude this review by discussing future directions in aquaporin tumor research. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.
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Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Acuaporinas/genética , Neoplasias Encefálicas/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica , Glioblastoma/tratamiento farmacológico , Anticuerpos Monoclonales/química , Antineoplásicos/química , Acuaporinas/antagonistas & inhibidores , Acuaporinas/metabolismo , Transporte Biológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patología , Humanos , Inmunoglobulina G/química , Inmunoglobulina G/uso terapéutico , Inmunotoxinas/química , Neovascularización Patológica/prevención & control , Ósmosis , Transducción de Señal , Agua/metabolismoRESUMEN
The management of patients having traumatic spinal cord injury would benefit from understanding and monitoring of spinal cord metabolic states. We hypothesized that the metabolism of the injured spinal cord could be visualized using Kohonen self-organizing maps. Sixteen patients with acute, severe spinal cord injuries were studied. Starting within 72 h of the injury, and for up to a week, we monitored the injury site hourly for tissue glucose, lactate, pyruvate, glutamate, and glycerol using microdialysis as well as intraspinal pressure and spinal cord perfusion pressure. A Kohonen map, which is an unsupervised, self-organizing topology-preserving neural network, was used to analyze 3366 h of monitoring data. We first visualized the different spinal cord metabolic states. Our data show that the injured cord assumes one or more of four metabolic states. On the basis of their metabolite profiles, we termed these states near-normal, ischemic, hypermetabolic, and distal. We then visualized how patients' intraspinal pressure and spinal cord perfusion pressure affect spinal cord metabolism. This revealed that for more than 60% of the time, spinal cord metabolism is patient-specific; periods of high intraspinal pressure or low perfusion pressure are not associated with specific spinal cord metabolic patterns. Finally, we determined relationships between spinal cord metabolism and neurological status. Patients with complete deficits have shorter periods of near-normal spinal cord metabolic states (7 ± 4% vs. 58 ± 12%, p < 0.01, mean ± standard error) and more variable injury site metabolic responses (metabolism spread in 70 ± 11 vs. 40 ± 6 hexagons, p < 0.05), compared with patients who have incomplete neurological deficits. We conclude that Kohonen maps allow us to visualize the metabolic responses of the injured spinal cord and may thus aid us in treating patients with acute spinal cord injuries.
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Metaboloma/fisiología , Microdiálisis/métodos , Traumatismos de la Médula Espinal/diagnóstico , Traumatismos de la Médula Espinal/metabolismo , Adulto , Anciano , Vértebras Cervicales , Femenino , Estudios de Seguimiento , Humanos , Unidades de Cuidados Intensivos , Vértebras Lumbares , Masculino , Persona de Mediana Edad , Vértebras Torácicas , Adulto JovenRESUMEN
This paper challenges the current management of acute traumatic spinal cord injury based on our experience with monitoring from the injury site in the neurointensive care unit. We argue that the concept of bony decompression is inadequate. The concept of optimum spinal cord perfusion pressure, which differs between patients, is introduced. Such variability suggests individualized patient treatment. Failing to optimize spinal cord perfusion limits the entry of systemically administered drugs into the injured cord. We conclude that monitoring from the injury site helps optimize management and should be subjected to a trial to determine whether it improves outcome.
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Presión Arterial/fisiología , Perfusión/métodos , Traumatismos de la Médula Espinal/terapia , Animales , Presión Sanguínea/fisiología , Duramadre/fisiopatología , Humanos , Unidades de Cuidados Intensivos/organización & administración , Unidades de Cuidados Intensivos/normas , Imagen por Resonancia Magnética , Metilprednisolona/farmacología , Metilprednisolona/uso terapéutico , Ratones , Monitoreo Fisiológico/métodos , Atención Dirigida al Paciente/métodos , Traumatismos de la Médula Espinal/cirugía , Esteroides/farmacología , Esteroides/uso terapéutico , Porcinos , Heridas y Lesiones/terapiaRESUMEN
Intracranial pressure (ICP) is routinely measured in patients with severe traumatic brain injury (TBI). We describe a novel technique that allowed us to monitor intraspinal pressure (ISP) at the injury site in 14 patients who had severe acute traumatic spinal cord injury (TSCI), analogous to monitoring ICP after brain injury. A Codman probe was inserted subdurally to measure the pressure of the injured spinal cord compressed against the surrounding dura. Our key finding is that it is feasible and safe to monitor ISP for up to a week in patients after TSCI, starting within 72 h of the injury. With practice, probe insertion and calibration take less than 10 min. The ISP signal characteristics after TSCI were similar to the ICP signal characteristics recorded after TBI. Importantly, there were no associated complications. Future studies are required to determine whether reducing ISP improves neurological outcome after severe TSCI.
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Monitoreo Fisiológico , Presión , Traumatismos de la Médula Espinal/fisiopatología , Médula Espinal/irrigación sanguínea , Espacio Subdural , Adolescente , Adulto , Anciano , Presión Arterial , Vértebras Cervicales/cirugía , Estudios de Factibilidad , Femenino , Humanos , Presión Intracraneal , Laminectomía , Masculino , Persona de Mediana Edad , Tornillos Pediculares , Traumatismos de la Médula Espinal/complicaciones , Fracturas de la Columna Vertebral/complicaciones , Fracturas de la Columna Vertebral/cirugía , Fusión Vertebral , Vértebras Torácicas/cirugía , Adulto JovenRESUMEN
Following a traumatic brain injury (TBI), intracranial pressure (ICP) increases, often resulting in secondary brain insults. After a spinal cord injury, here the cord may be swollen, leading to a local increase in intraspinal pressure (ISP). We hypothesised that waveform analysis methodology similar to that used for ICP after TBI may be applicable for the monitoring of patients with spinal cord injury.An initial cohort of 10 patients with spinal cord injury, as presented by the first author at a meeting in Cambridge in May 2012, were included in this observational study. The whole group (18 patients) was recently presented in the context of clinically oriented findings (Werndle et al., Crit Care Med, 42(3):646-655, 2014, PMID: 24231762). Mean pressure, pulse and respiratory waveform were analysed along slow vasogenic waves.Slow, respiratory and pulse components of ISP were characterised in the time and frequency domains. Mean ISP was 22.5 ± 5.1, mean pulse amplitude 1.57 ± 0.97, mean respiratory amplitude 0.65 ± 0.45 and mean magnitude of slow waves (a 20-s to 3-min period) was 3.97 ± 3.1 (all in millimetres of mercury). With increasing mean ISP, the pulse amplitude increased in all cases. This suggests that the ISP signal is of a similar character to ICP recorded after TBI. Therefore, the methods of ICP analysis can be helpful in ISP analysis.
Asunto(s)
Presión , Traumatismos de la Médula Espinal/fisiopatología , Espacio Subdural , Estudios de Cohortes , Humanos , Presión Intracraneal , Monitoreo Fisiológico , Análisis de la Onda del Pulso , Respiración , Canal MedularRESUMEN
MR scans from 65 patients with traumatic spinal cord injury were analysed; on admission 95% had evidence of cord compression - in 26% due to the dura, and in the remaining 74% due to extradural factors. Compression due to dural factors resolved with a half-life of 8.7 days. These findings suggest that bony decompression alone may not relieve spinal cord compression in the quarter of patients in whom dural factors are significant.
Asunto(s)
Duramadre/patología , Compresión de la Médula Espinal/patología , Traumatismos de la Médula Espinal/patología , Adolescente , Adulto , Anciano , Descompresión Quirúrgica , Duramadre/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Dolor de Cuello/diagnóstico por imagen , Dolor de Cuello/etiología , Enfermedades del Sistema Nervioso/etiología , Compresión de la Médula Espinal/diagnóstico por imagen , Compresión de la Médula Espinal/etiología , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/diagnóstico por imagen , Adulto JovenRESUMEN
BACKGROUND: It is unclear why AQP4-IgG primarily causes central nervous system lesions by activating complement, but generally spares peripheral AQP4-expressing organs. OBJECTIVES: To determine whether peripheral AQP4-expressing cells are protected from complement-mediated damage by expressing complement regulators. METHODS: Human tissue and cultured human cells were immunostained for aquaporin-4 (AQP4), CD46, CD55 and CD59. We also determined the vulnerability to AQP4-IgG and complement-mediated damage of astrocytes cultured alone or co-cultured with endothelial cells. RESULTS: In normal brain, astrocyte end-feet express AQP4, but are devoid of CD46, CD55 and CD59. Immunoreactivity for CD46, CD55 and CD59 is not increased in or around neuromyelitis optica lesions. In kidney AQP4 is co-expressed with CD46 and CD55, in stomach AQP4 is co-expressed with CD46 and in skeletal muscle AQP4 is co-expressed with CD46. Astrocytes cultured alone co-express AQP4 and CD59 but, in astrocyte-endothelial co-cultures, AQP4 is found in cell processes devoid of CD59. Astrocytes co-cultured with endothelial cells are more vulnerable to AQP4-IgG and complement-mediated lysis than astrocytes cultured alone. CONCLUSIONS: Complement regulators protect peripheral organs, but not the central nervous system, from AQP4-IgG and complement-mediated damage. Our findings may explain why neuromyelitis optica primarily damages the central nervous system, but spares peripheral organs.
Asunto(s)
Acuaporina 4/inmunología , Astrocitos/metabolismo , Encéfalo/metabolismo , Proteínas del Sistema Complemento/inmunología , Neuromielitis Óptica/inmunología , Acuaporina 4/metabolismo , Astrocitos/inmunología , Encéfalo/inmunología , Antígenos CD55/inmunología , Antígenos CD55/metabolismo , Antígenos CD59/inmunología , Antígenos CD59/metabolismo , Células Cultivadas , Técnicas de Cocultivo , Vía Clásica del Complemento/inmunología , Proteínas del Sistema Complemento/metabolismo , Células Endoteliales/inmunología , Células Endoteliales/metabolismo , Mucosa Gástrica/metabolismo , Humanos , Inmunoglobulina G/inmunología , Riñón/metabolismo , Proteína Cofactora de Membrana/inmunología , Proteína Cofactora de Membrana/metabolismo , Músculo Esquelético/metabolismo , Neuromielitis Óptica/metabolismoRESUMEN
Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the CNS and affects women of childbearing age. Most patients with NMO have circulating Abs, termed NMO-IgG, against the astrocytic water channel protein aquaporin-4. In the CNS, NMO-IgG causes complement-mediated astrocyte damage, inflammatory cell infiltration, and myelin loss. In this study, we show that aquaporin-4 is expressed in the syncytiotrophoblast of human and mouse placenta. Placental aquaporin-4 expression is high during mid-gestation and progressively decreases with advancing pregnancy. Intraperitoneally injected NMO-IgG binds mouse placental aquaporin-4, activates coinjected human complement, and causes inflammatory cell infiltration into the placenta and placental necrosis. There was no damage to maternal organs that express aquaporin-4, including the brain, spinal cord, kidneys, and skeletal muscle. In control experiments, no placentitis was found in mice injected with NMO-IgG without complement, non-NMO-IgG with human complement, or in aquaporin-4 null mice injected with NMO-IgG and human complement. The infiltrating cells were primarily neutrophils with a few scattered eosinophils and macrophages. NMO-IgG and human complement-induced placentitis caused fetal death, but some fetuses were born normal when lower amounts of NMO-IgG and human complement were injected. Sivelestat, a neutrophil elastase inhibitor, and aquaporumab, a nonpathogenic IgG that competes with NMO-IgG for aquaporin-4 binding, significantly reduced NMO-IgG and human complement induced placentitis and fetal death. Our data suggest that NMO-IgG can cause miscarriage, thus challenging the concept that NMO affects only the CNS. These findings have implications for the management of NMO during pregnancy.