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We report a case of pseudo-prolongation of activated partial thromboplastin time (APTT), which was suspected to be caused by an animal-derived phospholipid. A 78-year-old woman was referred to our hospital because of an unexplained APTT prolongation. She had compensated alcoholic liver cirrhosis, with modestly decreased platelet count and normal prothrombin time, and no bleeding tendency. The APTT was 66 seconds in a test using phospholipid extracted from rabbit brain but was 34.9 seconds with synthetic phospholipids. The artifactual pseudo-prolongation of the APTT was seemingly attributable to the susceptibility of the test reagents to low factor XII levels. Thus, tests with different APTT reagents would be useful to physicians in the diagnosis of similar cases.
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Trastornos de la Coagulación Sanguínea , Animales , Pruebas de Coagulación Sanguínea , Femenino , Humanos , Indicadores y Reactivos , Tiempo de Tromboplastina Parcial , Tiempo de Protrombina , ConejosRESUMEN
STUDY DESIGN: Exploratory clinical study. OBJECTIVES: To localize the sites of conduction block in the spinal sensory and motor pathways for minimizing the level of surgical intervention despite MRI evidence of compression at several levels in degenerative cervical myelopathy (DCM). SETTING: Kochi Medical School Hospital, Japan. METHODS: We analyzed 83 DCM patients (69 ± 12 years) who underwent serial intervertebral recording of both ascending (A-SCEPs) and descending spinal cord-evoked potentials (D-SCEPs) after epidural and transcranial stimulation, respectively, during surgery before decompression procedures. The site of conduction block was identified by an abrupt reduction of the negative peak accompanied by an enlargement of the initial-positive peak. T1-weighted MRI allowed quantitative assessments of cord compression in relation to the level of conduction block. RESULTS: The A-SCEP and D-SCEP studies revealed conduction blocks at the same single level in 78 patients (94%) and at two separate levels in five patients (6%) for MRI abnormalities extending to 3.1 ± 1.1 levels. The site of conduction block had intense cord compression on MRI with either the smallest (81%) or the second smallest (19%) anteroposterior diameter and cross-sectional area of the cord. Based on the SCEP findings, 44 patients were treated by a single-level (35) or a two-level (9) anterior operation for MRI abnormalities of 2.7 ± 1.1 levels. CONCLUSIONS: Combined A-SCEP and D-SCEP studies served as useful additions to MRI in localizing the primary sites responsible for myelopathy, which helped exclude clinically silent compressions to minimize surgical intervention in 34 patients with anterior operation.
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Vértebras Cervicales/diagnóstico por imagen , Imagen por Resonancia Magnética , Conducción Nerviosa/fisiología , Traumatismos de la Médula Espinal/diagnóstico por imagen , Traumatismos de la Médula Espinal/cirugía , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Encéfalo/fisiopatología , Estimulación Eléctrica , Potenciales Evocados/fisiología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Japón , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Traumatismos de la Médula Espinal/fisiopatologíaRESUMEN
PURPOSE: To determine if cantilever transforaminal lumbar interbody fusion (C-TLIF) using the crescent-shaped titanium interbody spacer (IBS) favors acquisition of segmental and lumbar lordosis even for degenerative spondylolisthesis (DS) on a long-term basis. METHODS: We analyzed 23 consecutive patients who underwent C-TLIF with pedicle screw instrumentations fixed with compression for a single-level DS. Measurements on the lateral radiographs taken preoperatively, 2 weeks postoperatively and at final follow-up included disc angle (DA), segmental angle (SA), lumbar lordosis (LL), disc height (%DH) and slip rate (%slip). RESULTS: There was a good functional recovery with 100 % fusion rate at the mean follow-up of 62 months. Segmental lordosis (DA and SA) and %DH initially increased, but subsequently decreased with the subsidence of the interbody spacer, resulting in a significant increase (p = 0.046) only in SA from 13.2° ± 5.5° preoperatively to 14.7° ± 6.4° at the final follow-up. Changes of LL and %slip were more consistent without correction loss finally showing an increase of LL by 3.6° (p = 0.005) and a slip reduction by 6.7 % (p < 0.001). CONCLUSIONS: Despite the inherent limitation of placing the IBS against the anterior endplate of the upper vertebra in the presence of DS, the C-TLIF helped significantly restore segmental as well as lumbar lordosis on a long-term basis, which would be of benefit in preventing hypolordosis-induced back pain and the adjacent level disc disease.
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Lordosis/cirugía , Vértebras Lumbares/cirugía , Postura/fisiología , Fusión Vertebral/métodos , Espondilolistesis/cirugía , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Lordosis/diagnóstico por imagen , Vértebras Lumbares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Prótesis e Implantes , Radiografía , Fusión Vertebral/efectos adversos , Fusión Vertebral/instrumentación , Espondilolistesis/diagnóstico por imagen , Titanio , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate the diagnostic utility of the T reflexes elicited from the upper limb muscles during standardized volitional contraction monitored by a real-time integrating electromyographic analyzer. DESIGN: Prospective descriptive study. SETTING: Department of orthopedic surgery at a university hospital. PARTICIPANTS: Healthy subjects (n=80) evenly distributed across decades of age from 21 to 79 years, and 12 consecutive patients with a single cervical root lesion based on clinical and magnetic resonance imaging studies and diagnostic block. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Using a special hammer, which externally triggers the sweep on skin contact, we evoked T reflexes in the biceps (C5), brachioradialis (C6), triceps (C7), and the first dorsal interosseous muscles (C8). RESULTS: Simultaneous regression analyses yielded clinically useful upper limits of normative values for latencies, side-to-side differences, and amplitude ratios adjusted to age and arm span. Comparison of the T reflexes between the 2 sides localized the solitary root lesions with a high sensitivity (92%), specificity (81%), and accuracy (83%). T-reflex studies proved helpful to localize the lesion even in patients who solely complained of upper limb pain. CONCLUSIONS: The T reflexes with a standardized facilitation of the upper limb muscles provide a clinically useful, noninvasive measure to localize the C5 to C8 radiculopathies. This study contributes in reassessing the currently underused T reflex as an electrodiagnostic technique.
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Contracción Muscular/fisiología , Músculo Esquelético/fisiología , Radiculopatía/diagnóstico , Radiculopatía/fisiopatología , Reflejo/fisiología , Extremidad Superior/fisiología , Adulto , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Análisis de Regresión , Sensibilidad y EspecificidadRESUMEN
OBJECT: The purpose of this study is to analyze the data in terms of the number of channels employed to examine the usefulness of multi-channels in intraoperative spinal cord monitoring. METHODS: The prerequisites for inclusion in the baseline data were as follows: (1) cases in which only CMAP monitoring was conducted; (2) cases in which monitoring was conducted under the same stimulation condition and the recording condition. Cases where inhalation anesthesia was used or muscle relaxants were used as maintenance anesthesia was excluded from the baseline data. Of the 6,887 cases, 884 cases met the criteria. The items examined for each of the different numbers of channels were the sensitivity and specificity, the false positive rate, the false negative rate, and the coverage rate of postoperative motor deficit muscles. RESULT: To examine these two items in terms of the number of channels, the 4-channel group had lower sensitivity and specificity scores compared with the 8- and 16-channel groups (4 channels 73/93 %, 8 channels 100/97 %, 16 channels 100/95 %). Only four channels were derived for these cases and the coverage of postoperative motor deficit muscles was 38 % with only 30 out of the 80 postoperative motor deficit muscles in total being monitored. In the 8-channel group, it was 60 % with 12 of the 20 postoperative motor deficit muscles being monitored. The 16-channel group had 100 % coverage rate of postoperative motor deficit muscles. CONCLUSION: We suggest that multi-channel monitoring of at least eight channels is desirable for intraoperative spinal cord monitoring.
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Monitoreo Intraoperatorio/métodos , Monitoreo Fisiológico/métodos , Procedimientos Ortopédicos , Médula Espinal/fisiología , Columna Vertebral/cirugía , Recolección de Datos , Humanos , Japón , Monitoreo Intraoperatorio/instrumentación , Monitoreo Fisiológico/instrumentación , Estudios Retrospectivos , Sensibilidad y Especificidad , Sociedades Médicas , Encuestas y CuestionariosRESUMEN
INTRODUCTION: The plate fixation for anterior cervical discectomy and fusion (ACDF) has become increasingly widespread for facilitating early mobilization and improving fusion rate. However, apart from multilevel operations, there is still some controversy over its use for single-level ACDF. This retrospective study has compared the reoperation rates after single-level ACDFs performed at our institution between the procedures with and without plate fixation. METHODS: This retrospective study included a total of 131 patients with???1-year of follow-up after a single-level ACDF, consisting of 100 patients without plating (conventional ACDF) and 31 patients with plate fixation (plated ACDF). RESULTS: Eleven patients (8.4% of all patients):four conventional ACDFs (4% of the conventional ACDFs) and seven plated ACDFs (22.6% of the plated ACDFs), had reoperation surgeries. The incidence of reoperation was significantly higher in the plated ACDFs than in the conventional ACDFs (P=0.0037). The log-rank test revealed a significant difference (P=0.00003) in 5-year reoperation-free survival rates between the conventional (96.9%) and the plated groups (68.3%). CONCLUSION: Anterior cervical plating may have a negative impact on the adjacent segment integrity, resulting in an increased reoperation rate after a single-level ACDF at relatively shorter postoperative time points. J. Med. Invest. 70 : 334-342, August, 2023.
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Vértebras Cervicales , Fusión Vertebral , Humanos , Reoperación/métodos , Estudios Retrospectivos , Vértebras Cervicales/cirugía , Fusión Vertebral/métodos , Discectomía/métodos , Resultado del TratamientoRESUMEN
Ossification of the posterior longitudinal ligament of the spine (OPLL) is an intractable disease leading to severe neurological deficits. Its etiology and pathogenesis are primarily unknown. The relationship between OPLL and comorbidities, especially type 2 diabetes (T2D) and high body mass index (BMI), has been the focus of attention; however, no trait has been proven to have a causal relationship. We conducted a meta-analysis of genome-wide association studies (GWASs) using 22,016 Japanese individuals and identified 14 significant loci, 8 of which were previously unreported. We then conducted a gene-based association analysis and a transcriptome-wide Mendelian randomization approach and identified three candidate genes for each. Partitioning heritability enrichment analyses observed significant enrichment of the polygenic signals in the active enhancers of the connective/bone cell group, especially H3K27ac in chondrogenic differentiation cells, as well as the immune/hematopoietic cell group. Single-cell RNA sequencing of Achilles tendon cells from a mouse Achilles tendon ossification model confirmed the expression of genes in GWAS and post-GWAS analyses in mesenchymal and immune cells. Genetic correlations with 96 complex traits showed positive correlations with T2D and BMI and a negative correlation with cerebral aneurysm. Mendelian randomization analysis demonstrated a significant causal effect of increased BMI and high bone mineral density on OPLL. We evaluated the clinical images in detail and classified OPLL into cervical, thoracic, and the other types. GWAS subanalyses identified subtype-specific signals. A polygenic risk score for BMI demonstrated that the effect of BMI was particularly strong in thoracic OPLL. Our study provides genetic insight into the etiology and pathogenesis of OPLL and is expected to serve as a basis for future treatment development.
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Diabetes Mellitus Tipo 2 , Osificación del Ligamento Longitudinal Posterior , Animales , Ratones , Osteogénesis , Estudio de Asociación del Genoma Completo , Diabetes Mellitus Tipo 2/patología , Columna Vertebral/patología , Osificación del Ligamento Longitudinal Posterior/genética , Osificación del Ligamento Longitudinal Posterior/patologíaRESUMEN
The present study documents a phenomenon, which has received little attention despite its potential clinical importance. An 87-year-old woman presented with barely reported extravertebral gas and fluid collections probably originating from the contents of the adjacent cleft within the T10 collapsed osteoporotic vertebra. Her chief complaint was intractable pain radiating over the left thorax suggestive of intercostal neuralgia. The pain intensified when sitting up from a lateral decubitus position, correlating with a posture-related radiologic change of the intravertebral cleft, which appeared with a decubitus position and disappeared with a sitting position. Because these extravertebral collections were located where the 10th thoracic nerve root just exits the intervertebral foramina, her chest pain of a posture-dependent nature most likely resulted from nerve root compression by extravertebral gas and fluid forced out of the vertebral cleft. Posterior spinal fusion with pedicle screw instrumentation resulted in a complete resolution of the chest pain with disappearance of the extravertebral gas and fluid accumulations. An awareness of the possibility that the intravertebral cleft could communicate with the extravertebral space close to the nerve root will help avoid neurologic complications caused by bone cement leakage during vertebroplasty.
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This study reports on a 67-year-old woman with partial Brown-Séquard syndrome due to a recurrent cervical neurenteric cyst at C3 to C4. The myelopathic symptoms reappeared 22 years after a previous shunting operation performed posteriorly with a silicone tube connecting the intradural cervical cyst cavity to the subarachnoid space. We have now succeeded in removing the cyst nearly completely with the anterior approach. The surgical procedure consisted of right vertebral artery exposure at C3 and C4 and a subtotal corpectomy of C3 followed by microdissection of the cyst, duraplasty, and iliac strut graft fusion. Spinal cord monitoring with motor-evoked potential studies helped us safely dissect the cyst wall tightly adhering to the spinal cord. Duraplasty with Gore-Tex patch-grafting in conjunction with postoperative lumbar subarachnoid drainage worked well in preventing a spinal fluid fistula. At two years after surgery, the patient showed a nearly complete return of function without any recurrence of the cyst.
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STUDY DESIGN: Retrospective case-control study. OBJECTIVE: The purpose of this study was to examine the factors of postoperative paralysis in patients who have undergone thoracic ossification of posterior longitudinal ligament (OPLL) surgery. SUMMARY OF BACKGROUND DATA: A higher percentage of thoracic OPLL patients experience postoperative aggravation of paralysis than cervical OPLL patients, including patients that presented great difficulties in treatment. However, there were a few reports to prevent paralysis thoracic OPLL. METHODS: The 156 patients who had received thoracic OPLL surgery were selected as the subjects of this study. The items for review were the duration of disease; the preoperative muscle strength (Muscle Manual Testing); OPLL levels (T1/2-4/5: high, T5/6-8/9: middle, and T9/10-11/12: low); the spinal canal occupancy ratio; the ratio of yellow ligament ossification as a complication; the ratio of transcranial-motor evoked potential (Tc-MEP) derivation; the preoperative/postoperative kyphotic angles in the thoracic vertebrae; the correction angle of kyphosis; the duration of surgery; and the amount of bleeding. The subjects were divided into two groups based on the absence or presence of postoperative paralysis to determine the factors of postoperative paralysis. RESULTS: Twenty-three patients (14.7%) exhibited postoperative paralysis. Multivariate analysis identified factors associated with postoperative paralysis: the duration of disease (odds ratio, ORâ=â3.3); the correction angle of kyphosis (ORâ=â2.4); and the ratio of Tc-MEP derivation (ORâ=â2.2). CONCLUSION: The risk factors of postoperative paralysis are a short duration of disease and a small correction angle of kyphosis. In addition, ratios of Tc-MEP derivation below 50% may anticipate paralysis. LEVEL OF EVIDENCE: 4.
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Study Design Surgeon survey. Objective To analyze multimodal intraoperative monitoring (MIOM) for different combinations of methods based on the collected data and determine the best combination. Methods A questionnaire was sent to 72 training institutions to analyze and compile data about monitoring that had been conducted during the preceding 5 years to obtain data on the following: (1) types of monitoring; (2) names and number of diseases; (3) conditions of anesthesia; (4) condition of stimulation, the monitored muscle and its number; (5) complications; and (6) preoperative and postoperative manual muscle testing, presence of dysesthesia, and the duration of postoperative motor deficit. Sensitivity and specificity, false-positive rates, and false-negative rates were examined for each type of monitoring, along with the relationship between each type of monitoring and the period of postoperative motor deficit. Results Comparison of the various combinations showed transcranial electrical stimulation motor evoked potential (TcMEP) + cord evoked potential after stimulation to the brain (Br-SCEP) combination had the highest sensitivity (90%). The TcMEP + somatosensory evoked potential (SSEP) and TcMEP + spinal cord evoked potential after stimulation to the spinal cord (Sp-SCEP) combinations each had a sensitivity of 80%, exhibiting little difference between their sensitivity and that obtained when TcMEP alone was used. Meanwhile, the sensitivity was as low as 50% with Br-SCEP + Sp-SCEP (i.e., the cases where TcMEP was not included). Conclusions The best multimodality combination for intraoperative spinal cord monitoring is TcMEP + Br-SCEP, which had the highest sensitivity (90%), the lowest false-positive rate (6.1%), and the lowest false-negative rate (0.2%).
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This study reports on a 70-year-old man with recurrent cervical myelopathy 20 years after anterior decompression and fusion of C4-7 using a free vascularised strut graft. The recurrent myelopathy was secondary to a kyphotic deformity of a fractured graft and residual ossification of the posterior longitudinal ligament with stenosis at C3/4. Intraoperative spinal cord-evoked potentials indicated that spinal cord traction secondary to progressive kyphosis of the cervical spine after the graft fracture was the cause. The patient underwent laminoplasty at C3 and laminectomy at C4 to decompress the stenosis at C3/4 as well as posterior cervical spinal fusion at C3-7 with pedicle screws and a lateral mass screw and a bone graft to prevent further progression of the kyphosis. At postoperative 18 months, the patient's Japanese Orthopaedic Association score had improved to 14 from 8, and he could walk without support.
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Trasplante Óseo/efectos adversos , Vértebras Cervicales/cirugía , Descompresión Quirúrgica/métodos , Laminectomía/métodos , Enfermedades de la Médula Espinal/cirugía , Fracturas de la Columna Vertebral/complicaciones , Anciano , Vértebras Cervicales/lesiones , Progresión de la Enfermedad , Humanos , Masculino , Complicaciones Posoperatorias , Recurrencia , Enfermedades de la Médula Espinal/etiología , Fracturas de la Columna Vertebral/cirugía , Insuficiencia del TratamientoRESUMEN
OBJECTIVES: To determine whether repetitive tibial nerve stimulation (RTNS) affects neurogenic claudication and F-wave conduction in lumbar spinal stenosis. DESIGN: An intervention study: before/after trial. SUBJECTS: Data for 12 central lumbar spinal stenosis patients were compared with 13 age- and sex-matched healthy volunteers. METHODS: A conditioning RTNS at the ankle, 0.3-ms duration square-wave pulses with an intensity 20% higher than the motor threshold, was applied at a rate of 5/s for 5 min. We assessed the effects of RTNS on the claudication distance at which the lumbar spinal stenosis patients can no longer continue walking due to increasing leg symptoms, and on tibial F-wave measurements. RESULTS: A comparison between mean pre-RTNS and post-RTNS revealed a significant difference in claudication distance (66 m (standard deviation (SD) 19) vs 133 m (SD 37); p = 0.003), mean F-wave minimal latency (48.3 ms (SD 1.7) vs 44.8 ms (SD 1.0); p = 0.007) and mean F-wave conduction velocity (53.3 m/s (SD 2.0) vs 55.5 m/s (SD 1.9); p = 0.009) in the lumbar spinal stenosis group, but not in the control group. CONCLUSION: RTNS has beneficial effects on neurogenic claudication and F-wave conduction in central lumbar spinal stenosis patients. This phenomenon may have practical value in providing a new therapeutic modality for lumbar spinal stenosis.
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Claudicación Intermitente/fisiopatología , Claudicación Intermitente/rehabilitación , Estenosis Espinal/fisiopatología , Nervio Tibial/fisiología , Estimulación Eléctrica Transcutánea del Nervio/métodos , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Estudios Controlados Antes y Después , Femenino , Humanos , Vértebras Lumbares , Masculino , Neuronas Motoras/fisiología , Conducción Nerviosa , Resultado del Tratamiento , Caminata/fisiologíaRESUMEN
OBJECTIVES: To characterize waveform changes of descending spinal cord evoked potentials (D-SCEPs) seen in cervical spondylotic myelopathy (CSM). METHODS: Intraoperative D-SCEP recording from serial intervertebral discs after transcranial electrical stimulation in 19 CSM patients with cord compression at a single level. RESULTS: Compared to the baseline (100%) obtained one level rostrally, the D-SCEP recorded at the compression site showed a significantly (p<0.001) decreased amplitude (48%) and area (48%) of negative peak and increased amplitude (171%) and area (279%) of initial-positive peak. The degree in reduction of negative peak remained the same irrespective of the cord level involved, whereas enhancement of the positive peak tended to diminish with a more caudal compression. CONCLUSIONS: In intraoperative electrophysiological studies of CSM with D-SCEP, an abrupt reduction of the negative peak accompanied by an enhancement of the initial-positive peak helps identify the site of conduction block. We speculate that progressive loss of the descending motor volleys at the synapses in the cervical enlargement may account for limited or absent enhancement of positive peak seen caudally. SIGNIFICANCE: The current finding helps us understand the pros and cons of various electrophysiologic techniques for intraoperative localization of maximal cord involvement in CSM.
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Potenciales Evocados , Compresión de la Médula Espinal/fisiopatología , Médula Espinal/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Vértebras Cervicales , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Compresión de la Médula Espinal/cirugíaRESUMEN
OBJECT: Although multimodal intraoperative spinal cord monitoring provides greater accuracy, transcranial electrical stimulation motor evoked potential (TcMEP) monitoring became the gold standard for intraoperative spinal cord monitoring. However, there is no definite alarm point for TcMEPs because a multicenter study is lacking. Thus, based on their experience with 48 true-positive cases (that is, a decrease in potentials followed by a new neurological motor deficit postoperatively) encountered between 2007 and 2009, the authors set a 70% decrease in amplitude as the alarm point for TcMEPs. METHODS: A total of 959 cases of spinal deformity, spinal cord tumor, and ossification of the posterior longitudinal ligament (OPLL) treated between 2010 and 2012 are included in this prospective multicenter study (18 institutions). These institutions are part of the Japanese Society for Spine Surgery and Related Research monitoring working group and the study group on spinal ligament ossification. The authors prospectively analyzed TcMEP variability and pre- and postoperative motor deficits. A 70% decrease in amplitude was designated as the alarm point. RESULTS: There were only 2 false-negative cases, which occurred during surgery for intramedullary spinal cord tumors. This new alarm criterion provided high sensitivity (95%) and specificity (91%) for intraoperative spinal cord monitoring and favorable accuracy, except in cases of intramedullary spinal cord tumor. CONCLUSIONS: This study is the first prospective multicenter study to investigate the alarm point of TcMEPs. The authors recommend the designation of an alarm point of a 70% decrease in amplitude for routine spinal cord monitoring, particularly during surgery for spinal deformity, OPLL, and extramedullary spinal cord tumor.
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Estimulación Eléctrica/métodos , Potenciales Evocados Motores/fisiología , Monitoreo Intraoperatorio/métodos , Médula Espinal/cirugía , Humanos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sensibilidad y Especificidad , Médula Espinal/fisiología , Neoplasias de la Médula Espinal/cirugía , Curvaturas de la Columna Vertebral/cirugíaRESUMEN
Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common spinal disorder among the elderly that causes myelopathy and radiculopathy. To identify genetic factors for OPLL, we performed a genome-wide association study (GWAS) in â¼8,000 individuals followed by a replication study using an additional â¼7,000 individuals. We identified six susceptibility loci for OPLL: 20p12.3 (rs2423294: P = 1.10 × 10(-13)), 8q23.1 (rs374810: P = 1.88 × 10(-13)), 12p11.22 (rs1979679: P = 4.34 × 10(-12)), 12p12.2 (rs11045000: P = 2.95 × 10(-11)), 8q23.3 (rs13279799: P = 1.28 × 10(-10)) and 6p21.1 (rs927485: P = 9.40 × 10(-9)). Analyses of gene expression in and around the loci suggested that several genes are involved in OPLL etiology through membranous and/or endochondral ossification processes. Our results bring new insight to the etiology of OPLL.