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1.  Complications of transpedicular screw fixation in the cervical spine 
European Spine Journal  2005;15(3):327-334.
Today, posterior stabilization of the cervical spine is most frequently performed by lateral mass screws or spinous process wiring. These techniques do not always provide sufficient stability, and anterior fusion procedures are added secondarily. Recently, transpedicular screw fixation of the cervical spine has been introduced to provide a one-stage stable posterior fixation. The aim of the present prospective study is to examine if cervical pedicle screw fixation can be done by low risk and to identify potential risk factors associated with this technique. All patients stabilized by cervical transpedicular screw fixation between 1999 and 2002 were included. Cervical disorders included multisegmental degenerative instability with cervical myelopathy in 16 patients, segmental instability caused by rheumatoid arthritis in three, trauma in five and instability caused by infection in two patients. In most cases additional decompression of the spinal cord and bone graft placement were performed. Pre-operative and post-operative CT-scans (2-mm cuts) and plain X-rays served to determine changes in alignment and the position of the screws. Clinical outcome was assessed in all cases. Ninety-four cervical pedicle screws were implanted in 26 patients, most frequently at the C3 (26 screws) and C4 levels (19 screws). Radiologically 66 screws (70%) were placed correctly (maximal breach 1 mm) whereas 20 screws (21%) were misplaced with reduction of mechanical strength, slight narrowing of the vertebral artery canal (<25%) or the lateral recess without compression of neural structures. However, these misplacements were asymptomatic in all cases. Another eight screws (9%) had a critical breach. Four of them showed a narrowing of the vertebral artery canal of more then 25%, in all cases without vascular problems. Three screws passed through the intervertebral foramen, causing temporary paresis in one case and a new sensory loss in another. In the latter patient revision surgery was performed. The screw was loosened and had to be corrected. The only statistically significant risk factor was the level of surgery: all critical breaches were seen from C3 to C5. Percutaneous application of the screws reduced the risk for misplacement, although this finding was not statistically significant. There was also a remarkable learning curve. Instrumentation with cervical transpedicular screws results in very stable fixation. However, with the use of new techniques like percutaneous screw application or computerized image guidance there remains a risk for damaging nerve roots or the vertebral artery. This technique should be reserved for highly selected patients with clear indications and to highly experienced spine surgeons.
doi:10.1007/s00586-004-0861-7
PMCID: PMC3489301  PMID: 15912352
Cervical spine; Pedicle screw fixation; Complication; Posterior fusion
2.  Obese elderly women exhibit low postural stability: a novel three-dimensional evaluation system 
Clinics  2012;67(5):475-481.
OBJECTIVE:
The aim of this study was to evaluate the multisegmental static postural balance of active eutrophic and obese elderly women using a three-dimensional system under different sensory conditions.
METHODS:
A cross-sectional study was conducted on 31 elderly women (16 eutrophic and 15 obese) aged 65 to 75 years. The following anthropometric measurements were obtained: weight, height, waist and hip circumference, and handgrip strength. The physical activity level was evaluated using the International Physical Activity Questionnaire. Body composition was measured using the deuterium oxide dilution technique. The Polhemus® Patriot (three-dimensional) equipment was used to measure the parameters of postural balance along the anteroposterior and laterolateral axes. The data acquisition involved one trial of 60 s to test the limit of stability and four trials of 90 s each under the following conditions: (1) eyes open, stable surface; (2) eyes closed, stable surface; (3) eyes open, unstable surface; and (4) eyes closed, unstable surface.
RESULTS:
For the limit of stability, significant differences were observed in the maximum anteroposterior and laterolateral displacement (p<0.01) and in the parameter maximum anteroposterior displacement in the eyes closed stable surface condition (p<0.01) and maximum anteroposterior and laterolateral displacement in the eyes open unstable surface (p<0.01 and p = 0.03) and eyes closed unstable surface (p<0.01 and p<0.01) conditions.
CONCLUSIONS:
Obese elderly women exhibited a lower stability limit (lower sway area) compared with eutrophic women, leaving them more vulnerable to falls.
doi:10.6061/clinics/2012(05)12
PMCID: PMC3351265  PMID: 22666792
Elderly; Obesity; Postural Balance; Sensory Deprivation; Three-Dimensional System
3.  Multisegmental spondylitis due to Tropheryma whipplei: Case report 
We report a patient who presented with inflammatory back pain due to multisegmental spondylitis. Following a vertebral biopsy which failed to detect an infectious organism, the patient was treated with etanercept, a tumor necrosis factor (TNF)-α inhibitor, for suspected undifferentiated spondyloarthritis. The back pain worsened and the spondylitic lesions increased. Only in a vertebral rebiopsy with polymerase chain reaction (PCR) amplification of Tropheryma whipplei, the causative agent of Whipple's disease was identified. Tropheryma whipplei should be considered as a cause of spondylitis even with multisegmental involvement and in the absence of gastrointestinal symptoms. In this clinical setting, routine PCR for Tropheryma whipplei from vertebral biopsies is recommended.
doi:10.1186/1750-1172-4-13
PMCID: PMC2697142  PMID: 19493331
4.  Nerve potentials and afferent conduction velocities in the differential diagnosis of amyotrophy of the hand 
Nerve action potentials recorded over the elbow after stimulation of the wrist were studied in patients with hand amyotrophy of different origin. In amyotrophic lateral sclerosis the amplitude of nerve action potentials does not change significantly even with extreme muscle wasting and loss of motor units.
Studies of multisegmental afferent conduction velocities may demonstrate a strictly localized lesion with normal values above the compression.
Images
PMCID: PMC494193  PMID: 4346024
5.  Somatosensory evoked potentials after multisegmental lower limb stimulation in focal lesions of the lumbosacral spinal cord 
OBJECTIVES—Recording techniques permit the separate analysis of the response from cauda equina roots and the spinal potential that is probably generated by the activation of dorsal horn cells. To improve the functional assessment of focal lesions of the lumbosacral cord, lower limb somatosensory evoked potentials (SEPs) were measured by multisegmental stimulation.
METHODS—Common peroneal and tibial nerves SEPs were recorded in 14 patients in whom MRI demonstrated compressive cord damage ranging from T9 to L1 levels. SEPs were recorded in each patient at the lumbar level (cauda equina response), lower thoracic level (spinal response), and from the scalp (cortical response).
RESULTS—Abnormalities in spinal response occurred in 50% and 70% of tibial and common peroneal nerve SEPs respectively; these findings were well explained by the radiological compression level, involving in most of the patients lumbar rather than sacral myelomeres. The SEPs were often more effective than the clinical examination in showing the actual extension of damage.
CONCLUSIONS—The recording of spinal SEPs after multisegmental lower limb stimulation proved useful in assessing cord dysfunction and determining the cord levels mainly involved by the compression.


doi:10.1136/jnnp.69.1.91
PMCID: PMC1737022  PMID: 10864611
6.  Up-regulation of p55 TNF alpha-receptor in dorsal root ganglia neurons following lumbar facet joint injury in rats 
European Spine Journal  2007;16(8):1273-1278.
The rat L5/6 facet joint is multisegmentally innervated from the L1 to L6 dorsal root ganglia (DRG). Tumor necrosis factor (TNF) is a known mediator of inflammation. It has been reported that satellite cells are activated, produce TNF and surround DRG neurons innervating L5/6 facet joints after facet injury. In the current study, changes in TNF receptor (p55) expression in DRG neurons innervating the L5/6 facet joint following facet joint injury were investigated in rats using a retrograde neurotransport method followed by immunohistochemistry. Twenty rats were used for this study. Two crystals of Fluorogold (FG; neurotracer) were applied into the L5/6 facet joint. Seven days after surgery, the dorsal portion of the capsule was cut in the injured group (injured group n = 10). No injury was performed in the non-injured group (n = 10). Fourteen days after the first application of FG, bilateral DRGs from T13 to L6 levels were resected and sectioned. They were subsequently processed for p55 immunohistochemistry. The number of FG labeled neurons and number of FG labeled p55-immunoreactive (IR) neurons were counted. FG labeled DRG neurons innervating the L5/6 facet joint were distributed from ipsilateral L1 to L6 levels. Of FG labeled neurons, the ratio of DRG neurons immunoreactive for p55 in the injured group (50%) was significantly higher than that in the non-injured group (13%). The ratio of p55-IR neurons of FG labeled DRG neurons was significantly higher in total L1 and L2 DRGs than that in total L3, 4, 5 and 6 DRGs in the injured group (L1 and 2 DRG, 67%; L3, 4, 5 and 6 DRG, 37%, percentages of the total number of p55-IR neurons at L1 and L2 level or L3–6 level/the total number of FG-labeled neurons at L1 and L2 level or L3–6 level). These data suggest that up-regulation of p55 in DRG neurons may be involved in the sensory transmission from facet joint injury. Regulation of p55 in DRG neurons innervating the facet joint was different between upper DRG innervated via the paravertebral sympathetic trunks and lower DRG innervated via other direct routes.
doi:10.1007/s00586-007-0365-3
PMCID: PMC2200776  PMID: 17468886
Sensory innervation; Lumbar facet joint; p55 tumor necrosis factor receptor; Dorsal root ganglion
7.  Pulmonary embolism due to compression of the inferior vena cava by a hepatic hemangioma. 
Texas Heart Institute Journal  1993;20(1):66-68.
We describe a 35-year-old man who had a pulmonary embolism with thrombosis of the inferior vena cava, apparently resulting from compression by a hepatic hemangioma. The diagnosis of pulmonary embolism was confirmed by pulmonary angiography; however, the hemangioma was detected only incidentally, as a hyperechoic mass, during an echocardiogram for intracardiac thrombosis. Abdominal sonography, computed tomography, celiac angiography, technetium 99m-labeled red blood cell scintigraphy, and ultrasound-guided liver biopsy all assisted in the diagnosis of hepatic hemangioma and its compression of the inferior vena cava. Because of the multisegmental and perihilar involvement of the tumor, surgery was not performed. For dissolution of the clots, the patient was given thrombolytic therapy followed by heparin administration. He was then placed on long-term warfarin therapy and is well after 5 years; the size of the hemangioma is unchanged. Cases of pulmonary embolism due to diseases of the upper abdominal organs are rare and probably underestimated. This case stresses the need for a systematic investigation of the abdomen when a pulmonary embolism is present without evidence of deep vein thrombosis.
Images
PMCID: PMC325057  PMID: 8508068
8.  Grading of degenerative disk disease and functional impairment: imaging versus patho-anatomical findings 
European Spine Journal  2008;17(12):1705-1713.
Degenerative instability affecting the functional spinal unit is discussed as a cause of symptoms. The value of imaging signs for assessing the resulting functional impairment is still unclear. To determine the relationship between slight degrees of degeneration and function, we performed a biomechanical study with 18 multisegmental (L2-S2) human lumbar cadaveric specimens. The multidirectional spinal deformation was measured during the continuous application of pure moments of flexion/extension, bilateral bending and rotation in a spine tester. The three flexibility parameters neutral zone, range of motion and neutral zone ratio were evaluated. Different grading systems were used: (1) antero-posterior and lateral radiographs (degenerative disk disease) (2) oblique radiographs (facet joint degeneration) (3) macroscopic and (4) microscopic evaluation. The most reliable correlation was between the grading of microscopic findings and the flexibility parameters; the imaging evaluation was not as informative.
doi:10.1007/s00586-008-0787-6
PMCID: PMC2587674  PMID: 18839226
Spinal biomechanics; Degenerative disk disease; Flexibility parameters; Radiographic findings; Pathological findings
9.  Analytic IMRT dose calculations utilizing Monte Carlo to predict MLC fluence modulation 
Medical physics  2006;33(4):828-839.
A hybrid dose-computation method is designed which accurately accounts for multileaf collimator (MLC)-induced intensity modulation in intensity modulated radiation therapy (IMRT) dose calculations. The method employs Monte Carlo (MC) modeling to determine the fluence modulation caused by the delivery of dynamic or multisegmental (step-and-shoot) MLC fields, and a conventional dose-computation algorithm to estimate the delivered dose to a phantom or a patient. Thus, it determines the IMRT fluence prediction accuracy achievable by analytic methods in the limit that the analytic method includes all details of the MLC leaf transport and scatter. The hybrid method is validated and benchmarked by comparison with in-phantom film dose measurements, as well as dose calculations from two in-house, and two commercial treatment planning system analytic fluence estimation methods. All computation methods utilize the same dose algorithm to calculate dose to a phantom, varying only in the estimation of the MLC modulation of the incident photon energy fluence. Gamma analysis, with respect to measured two-dimensional (2D) dose planes, is used to benchmark each algorithm’s performance. The analyzed fields include static and dynamic test patterns, as well as fields from ten DMLC IMRT treatment plans (79 fields) and five SMLC treatment plans (29 fields). The test fields (fully closed MLC, picket fence, sliding windows of different size, and leaf-tip profiles) cover the extremes of MLC usage during IMRT, while the patient fields represent realistic clinical conditions. Of the methods tested, the hybrid method most accurately reproduces measurements. For the hybrid method, 79 of 79 DMLC field calculations have γ ≤1 (3% /3 mm) for more than 95% of the points (per field) while for SMLC fields, 27 of 29 pass the same criteria. The analytic energy fluence estimation methods show inferior pass rates, with 76 of 79 DMLC and 24 of 29 SMLC fields having more than 95% of the test points with γ ≤1 (3% /3 mm). Paired one-way ANOVA tests of the gamma analysis results found that the hybrid method better predicts measurements in terms of both the fraction of points with γ ≤1 and the average gamma for both 2% /2 mm and 3% /3 mm criteria. These results quantify the enhancement in accuracy in IMRT dose calculations when MC is used to model the MLC field modulation.
PMCID: PMC2621101  PMID: 16696458
IMRT; MLC; dose computation; Monte Carlo simulation; fluence
10.  Glutamate Receptor Blockade in the Rostral Ventromedial Medulla Reduces the Force of Multisegmental Motor Responses to Supramaximal Noxious Stimuli 
Neuroscience letters  2007;426(3):175-180.
The rostral ventromedial medulla (RVM) has been established as part of a descending pain-modulatory pathway. While the RVM has been shown to modulate homosegmental nociceptive reflexes such as tail flick or hindpaw withdrawal, it is not known what role the RVM plays in modulating the magnitude of multisegmental, organized motor responses elicited by noxious stimuli. Using local blockade of glutamate receptors with the non-specific glutamate receptor antagonist kynurenate (known to selectively block nociceptive facilitatory ON-cells), we tested the hypothesis that the RVM facilitates the magnitude of multi-limb movements elicited by intense noxious stimuli. In male Sprague-Dawley rats, we determined the minimum alveolar concentration (MAC) of isoflurane necessary to block multilimb motor responses to noxious tail clamp. MAC was determined so that all animals were anesthetized at an equipotent isoflurane concentration (0.7 MAC). Supramaximal mechanical stimulation of the hindpaw or electrical stimulation of the tail elicited synchronous, repetitive movements in all four limbs that ceased upon, or shortly after (<5sec) termination of the stimulus. Kynurenate microinjection (2 nmol) into the RVM significantly attenuated, by 40- 60%, the peak and integrated limb forces elicited by noxious mechanical stimulation of the hindpaw (p< 0.001; two-way ANOVA; n= 8) or electrical stimulation of the tail (peak force: p<0.011, two-way ANOVA; n= 8), with significant recovery 40-60 min following injection. The results suggest that glutamatergic excitation of RVM neurons, presumably ON-cells, facilitates organized, multi-limb escape responses to intense noxious stimuli.
doi:10.1016/j.neulet.2007.08.060
PMCID: PMC2675539  PMID: 17904740
nociception, pain; descending modulation; glutamate; motor reflex; rostral ventromedial medulla
11.  Anterior cervical pedicle screw and plate fixation using fluoroscope-assisted pedicle axis view imaging: a preliminary report of a new cervical reconstruction technique 
European Spine Journal  2009;18(6):911-916.
Anterior procedures in the cervical spine are feasible in cases having anterior aetiologies such as anterior neural compression and/or severe kyphosis. Halo vests or anterior plates are used concurrently for cases with long segmental fixation. Halo vests are bothersome and anterior plate fixation is not adequately durable. We developed a new anterior pedicle screw (APS) and plate fixation procedure that can be used with fluoroscope-assisted pedicle axis view imaging. Six patients (3 men and 3 women; mean age, 54 years) with anterior multisegmental aetiology were included in this study. Their original diagnoses comprised cervical myelopathy and/or radiculopathy (n = 4), posterior longitudinal ligament ossification (n = 1) and post-traumatic kyphosis (n = 1). All patients underwent anterior decompression and strut grafting with APS and plate fixation. Mean operative time was 192 min and average blood loss was 73 ml. Patients were permitted to ambulate the next day with a cervical collar. Local sagittal alignment was characterised by 3.5° of kyphosis preoperatively, which improved to 6.8° of lordosis postoperatively and 5.2° of lordosis at final follow-up. Postoperative improvement and early bony union were observed in all cases. There was no serious complication except for two cases of dysphagia. Postoperative imaging demonstrated screw exposure in one screw, but no pedicle perforation. APS and plate fixation is useful in selected cases of multisegmental anterior reconstruction of cervical spine. However, the adequate familiarity and experience with both cervical pedicle screw fixation and the imaging technique used for visualising the pedicle during surgery are crucial for this procedure.
doi:10.1007/s00586-009-0949-1
PMCID: PMC2899659  PMID: 19343377
Anterior pedicle screw; Cervical spine; Pedicle axis view; Fluoroscope
12.  Fifty Years of CPGs: Two Neuroethological Papers that Shaped the Course of Neuroscience 
Half a century ago, two independent papers that described unexpected results of experiments on locomotion in insects and crayfish appeared almost simultaneously. Together these papers demonstrated that an animal's central nervous system (CNS) was organized to produce behaviorally important motor output without the need for constant sensory feedback. These results contradicted the established line of thought that was based on interpretations of reflexes and ablation experiments, and established that in these animals the CNS contained neural circuits that could produce complex, periodic, multisegmental patterns of activity. These papers stimulated a flowering of research on central pattern-generating mechanisms that displaced reflex-based thinking everywhere except in medical physiology texts. Here we review these papers and their influence on thinking in the 1960s, 1970s, and today. We follow the development of ideas about central organization and control of expression of motor patterns, the roles of sensory input to central pattern-generating circuits, and integration of continuous sensory signals into a periodic motor system. We also review recent work on limb coordination that provides detailed cellular explanations of observations and speculations contained in those original papers.
doi:10.3389/fnbeh.2010.00045
PMCID: PMC2917247  PMID: 20700502
motor pattern; central pattern-generation; flight; swimmeret; command neuron
13.  Segment-by-segment stabilization for degenerative disc disease: a hybrid technique 
European Spine Journal  2010;19(6):1010-1020.
Patients with multisegmental degenerative disc disease (DDD) resistant to conservative therapy are typically treated with either fusion or non-fusion surgical techniques. The two techniques can be applied at adjacent levels using Dynesys® (Zimmer GmbH, Winterthur, Switzerland) implants in a segment-by-segment treatment of multiple level DDD. The objective of this study was to evaluate the clinical and radiological outcome of patients treated using this segment-by-segment application of Dynesys in some levels as a non-fusion device and in other segments in combination with a PLIF as a fusion device. A consecutive case series is reported. The sample included 16 females and 15 males with a mean age of 53.6 years (range 26.3–76.4 years). Mean follow-up time was 39 months (range 24–90 months). Preoperative Oswestry disability index (ODI), back- and leg-pain scores (VAS) were compared to postoperative status. Fusion success and system failure were assessed by an independent reviewer who analyzed AP and lateral X-rays. Back pain improved from 7.3 ± 1.7 to 3.4 ± 2.7 (p < 0.000002), leg pain from 6.0 ± 2.9 to 2.3 ± 2.9 (p < 0.00006), and ODI from 51.6 ± 13.2% to 28.7 ± 18.0% (p < 0.00001). Screw loosening occurred in one of a total of 222 implanted screws (0.45%). The results indicate that segment-by-segment treatment with Dynesys® in combination with interbody fusion is technically feasible, safe, and effective for the surgical treatment of multilevel DDD.
doi:10.1007/s00586-010-1282-4
PMCID: PMC2899972  PMID: 20130934
Hybrid stabilization; Segment-by-segment treatment; Dynesys; PLIF; Multilevel DDD treatment
14.  Takotsubo Cardiomyopathy Associated with Titration of Duloxetine 
Texas Heart Institute Journal  2011;38(5):573-576.
Takotsubo cardiomyopathy is characterized by transient multisegmental left ventricular dysfunction, dynamic electrocardiographic changes that mimic acute myocardial infarction, and the absence of obstructive coronary disease. Takotsubo cardiomyopathy has been solidly associated with antecedent emotional and physical stressors that trigger catecholamine surges, which lead to coronary vasospasm or direct myocardial injury. Some medications can also cause catecholamine surges, although this phenomenon is not as well described. Duloxetine is a combined serotonin and norepinephrine reuptake inhibitor (SNRI). The basic goal of SNRIs is to increase catecholamine levels in neuronal tissue. However, the increased catecholamine levels may also affect the cardiovascular system.
Herein, we report the case of a 59-year-old woman whose takotsubo cardiomyopathy was temporally associated with the titration of duloxetine. The duloxetine therapy was subsequently discontinued, and the patient's left ventricular function recovered completely 1 month after the index event. The purpose of this report is to alert clinicians to a possible association between SNRI medications and takotsubo cardiomyopathy.
PMCID: PMC3231522  PMID: 22163139
Adrenergic uptake inhibitors/adverse effects; cardiomyopathies/chemically induced; catecholamines/blood; chest pain/etiology; drug therapy/adverse effects; duloxetine; norepinephrine/blood; serotonin uptake inhibitors/adverse effects; takotsubo cardiomyopathy/chemically induced/physiopathology; ventricular dysfunction, left/chemically induced
15.  Vertebral growth modulation by hemicircumferential electrocoagulation: an experimental study in pigs 
European Spine Journal  2011;20(Suppl 3):367-375.
Introduction
This experimental study in pigs was aimed at evaluating spinal growth disorders after partial arrest of the vertebral epiphyseal plates (EP) and neurocentral cartilages (NCC). Unilateral and multisegmental single or combined lesions of the physeal structures were performed by electrocogulation throughout a video-assisted thoracoscopical approach.
Materials and methods
Thirty 4-week-old domestic pigs (mean weight 16 kg) were included in the experiments. The superior and inferior epiphyseal plates of T5 to T9 vertebra were damaged in ten animals by hemicircumferential electrocoagulation (group I). In other ten pigs (group II), right NCC at the same T5–T9 levels were damaged. Ten other animals underwent combined lesions of the ipsilateral hemiepiphyseal plates and NCC at the T5–T9 levels. A total of 26 animals could be evaluated after 12 weeks of follow-up using conventional X-rays, CT scans and histology.
Results
The pigs with hemicircumferential EP damage developed very slight concave non-structured scoliotic deformities without vertebral rotation.(mean 12° Cobb; range10–16°). Some of the damaged vertebra showed a marked wedgening with unilateral development alteration of the vertebral body, including the adjacent discs The animals with damage of the NCC developed mild scoliotic curves (mean 19° Cobb; range 16–24°) with convexity opposite to the damaged side and loss of physiological kyphosis. The injured segments showed an asymmetric growth with hypoplasia of the pedicle and costovertebral joints at the damaged side. The pigs undergoing combined EP and NCC lesions developed minimal non-structured curves, ranging from 10 to 12° Cobb. In these animals there was a lack of growth of a vertebral hemibody and disc hypoplasia at the damaged segments. Both damage of the NCC and the EP affect the height of the vertebral body. No spinal stenosis was found in any case. In most cases, the adjacent superior and inferior vertebral EP to damaged segments had a compensatory growth that maintained the straight spinal shape.
Conclusions
In summary, unilateral direct lesion of the EP by hemicircumferential thoracoscopic electrocoagulation modifies vertebral growth, but is not able to induce true scoliostic curves in pigs. Only animals with damaged NCC developed mild scoliotic curves of lordotic type. This work rediscovers and emphasizes the decisive role of the neurocentral cartilage in the ethiopatogeny of idiopathic scoliosis.
doi:10.1007/s00586-011-1909-0
PMCID: PMC3175833  PMID: 21779856
Experimental scoliosis; Epiphyseal vertebral plate; Neurocentral cartilage; Spinal growth
16.  Titanium mesh cages (TMC) in spine surgery 
European Spine Journal  2004;14(3):211-221.
The introduction of the titanium mesh cage (TMC) in spinal surgery has opened up a variety of applications that are realizable as a result of the versatility of the implant. Differing applications of TMCs in the whole spine are described in a series of 150 patients. Replacement and reinforcement of the anterior column represent the classic use of cylindrical TMCs. The TMC as a multisegmental concave support in kyphotic deformities and as a posterior interlaminar spacer or lamina replacement after wide laminectomy are additional applications. Implant subsidence, pseudarthrosis and implant loosening are the complications typically encountered with use of TMCs. The versatility of the implant permits its use in unusual surgical situations.
doi:10.1007/s00586-004-0748-7
PMCID: PMC3476740  PMID: 15340827
Titanium mesh cages; Spinal surgery; Anterior column support; Kyphotic deformity; Lamina replacement
17.  Characteristics of sensory DRG neurons innervating the lumbar facet joints in rats 
European Spine Journal  2005;14(6):559-564.
The rat L5/6 facet joint, from which low-back pain can originate, is multisegmentally innervated from the L1 to L5 dorsal root ganglions (DRGs). Sensory fibers from the L1 and L2 DRGs are reported to non-segmentally innervate the paravertebral sympathetic trunks, whilst those from the L3 to L5 DRGs segmentally innervate the L5/6 facet joint. In the current study, characteristics of sensory DRG neurons innervating the L5/6 facet joint were investigated in rats, using a retrograde neurotransport method, lectin affinity- and immuno-histochemistry. We used four markers: (1) calcitonin gene-related peptide (CGRP) as a marker of small peptide containing neurons, (2) the glycoprotein binding the isolectin from Griffonia simplicifolia (IB4) or (3 the purinergic P2X3 receptor for small, non-peptide containing neurons, and (4) neurofilament 200 (NF200) for small and large myelinated fibers. IB4-binding and CGRP and P2X3 receptor containing neurons are typically involved in pain sensation, whereas NF200 is associated with pain and proprioception. Neurons innervating the L5/6 facet joints, retrogradely-labeled with fluoro-gold (FG), were distributed throughout DRGs from L1 to L5. Of FG-labeled neurons, the ratios of NF200 immunoreactive (IR) neurons and CGRP-IR neurons were 37% and 35% respectively. The ratio of IB4-binding and P2X3 receptor-IR neurons was 10%, significantly less than the ratio of CGRP-IR neurons to FG-labeled neurons. The ratios of IB4-binding and P2X3 receptor-IR neurons were significantly higher, and that of CGRP-IR neurons was significantly less in L1 and L2 DRGs than those in L3, L4 or L5 DRGs. Under physiological conditions in rats, DRG neurons transmit several types of sensations, such as proprioception or nociception of the facet joint. Most neurons transmitting pain are CGRP-IR peptide-containing neurons. They may have a more significant role in pain sensation in the facets via peptidergic DRG neurons.
doi:10.1007/s00586-004-0834-x
PMCID: PMC3489236  PMID: 15690212
Sensory innervation; Lumbar facet joint; Calcitonin gene-related peptide; Isolectin B4; Dorsal root ganglion; Low back pain
18.  Lumbar spinal angiolipoma: case report and review of the literature 
European Spine Journal  2005;15(6):1025-1028.
Spinal angiolipomas are extremely rare benign tumors composed of mature lipomatous and angiomatous elements. Most are symptomatic due to progressive spinal cord or root compression. This article describes the case of a 60-year-old woman who presented with a 6-month history of low back pain radiating to her right leg. The pain was multisegmental. The condition had worsened with time. Lumbar magnetic resonance imaging revealed a dorsal epidural mass at L5 and erosion of the lamina of the L5 vertebra. Laminectomy was performed, and an extradural tumor was totally excised. Neuropathologic examination identified it as a lumbar spinal angiolipoma. There was no evidence of recurrence in follow-up 12 months later. This rare clinical entity must be considered in the differential diagnosis for any spinal epidural lesion.
doi:10.1007/s00586-005-1028-x
PMCID: PMC3489428  PMID: 16172903
Angiolipoma; Spinal tumor
19.  Up-regulation of TNFα in DRG satellite cells following lumbar facet joint injury in rats 
European Spine Journal  2006;15(6):953-958.
The rat L5/6 facet joint, from which low back pain can originate, is multisegmentally innervated from the L1 to L5 dorsal root ganglia (DRG). Sensory fibers from the L1 and L2 DRG are reported to non-segmentally innervate the paravertebral sympathetic trunks, while those from the L3 to L5 DRGs segmentally innervate the L5/6 facet joint. Tumor necrosis factor alpha (TNFα) is a mediator of peripheral and central nervous system inflammatory response and plays a crucial role in injury and its pathophysiology. In the current study, change in TNFα in sensory DRG neurons innervating the L5/6 facet joint following facet joint injury was investigated in rats using a retrograde neurotransport method and immunohistochemistry. Neurons innervating the L5/6 facet joints, retrogradely labeled with fluoro-gold (FG), were distributed throughout DRGs from L1 to L5. Most DRG FG-labeled neurons innervating L5/6 facet joints were immunoreactive (IR) for TNFα before and after injury. In the DRG, glial fibrillary acidic protein (GFAP)-IR satellite cells emerged and surrounded neurons innervating L5/6 facet joints after injury. These satellite cells were also immunoreactive for TNFα. The numbers of activated satellite cells and TNFα-IR satellite cells were significantly higher in L1 and L2 DRG than in L3, L4, and L5 DRG. These data suggest that up-regulation of glial TNFα may be involved in the pathogenesis of facet joint pain.
doi:10.1007/s00586-005-1031-2
PMCID: PMC3489457  PMID: 16758109
Sensory innervation; Lumbar facet joint; Tumor necrosis factor; Satellite cells; Dorsal root ganglion; Low back pain
20.  Surgical management of recurrent thoracolumbar spinal sarcoma with 4-level total en bloc spondylectomy: description of technique and report of two cases 
European Spine Journal  2011;21(1):1-9.
Introduction
The descriptions of total spondylectomy and further development of the technique for the treatment of vertebral sarcomas offered for the first time the opportunity to achieve oncologically sufficient resection margins, thereby improving local tumor control and overall survival. Today, single level en bloc spondylectomies are routinely performed and discussed in the literature while only few data are available for multi-level resections. However, due to the topographic vicinity of the spinal cord and large vessels, the multisegmental resections are technically demanding, represent major surgery and only few case reports are available. Surgical options are even more limited in cases of revision surgery and local recurrences when en bloc spondylectomy was considered to be not feasible due to high risk of vital complications in expanding resection margins. Deranged anatomy, implants in situ and extensive intra-/paraspinal scar tissue formation resulting from previously performed approaches and/or radiation are considered the principal complicating factors that usually hold back spine surgeons to perform revision for resection leaving the patient to palliative treatment.
Methods
We present two patient cases with previously performed piecemeal vertebrectomy in the thoracic spine due to a solitary high-grade spinal sarcoma. After extensive re-staging, both patients underwent a multi (4)-level en bloc spondylectomy in our department (one patient with combined en bloc lung resection). Except a local wound disturbance, there was no severe intra- or postoperative complication.
Results
After multilevel en bloc spondylectomy both patients showed a good functional outcome without neurological deficits, except those resulting from oncologically scheduled resection of thoracic nerve roots. After a median follow-up of 13 months, there was no local recurrence or distant metastasis. The reconstruction using a posterior screw rod system that is interconnected to an anterior vertebral body replacement with a carbon composite cage showed no implant failure or loosening. In summary, the approach of a multilevel en bloc surgery for revision and oncologically sufficient resection in cases of spinal sarcoma recurrences seems possible. However, interdisciplinary decision making in a tumor board, realistic evaluation of surgical resectability to attain tumor free margins, advanced experiences in spinal reconstructions and involvement of vascular, visceral and thoracic surgical expertise are essential preconditions for acceptable oncological and functional outcome.
doi:10.1007/s00586-011-1859-6
PMCID: PMC3252440  PMID: 21818598
En bloc spondylectomy; Spinal sarcoma; Solitary metastases; Local recurrence
21.  Call-Fleming Syndrome (Reversible Cerebral Artery Vasoconstriction) and Aneurysm Associated with Multiple Recreational Drug Use 
Drug abuse represents a significant health issue. Evidence suggests that recreational drug use has a direct effect on the cerebral vasculature and is of greater concern in those with undiagnosed aneurysms or vascular malformations. The authors report a case of thunderclap headache with a negative head CT and equivocal lumbar puncture after a drug-fueled weekend. The patient underwent diagnostic cerebral angiogram which demonstrated multisegmental, distal areas of focal narrowing of the middle, anterior, posterior, and posterior inferior cerebral artery and an incidental aneurysm. It is often difficult to determine the exact origin of symptoms; thus we were left with a bit of a chicken or the egg debate, trying to decipher which part came first. Either the aneurysm ruptured with associated concomitant vasospasm or it is a case of Call-Fleming syndrome (reversible cerebral artery vasoconstriction) with an incidental aneurysm. The authors proposed their management and rationale of this complex case.
doi:10.1155/2013/729162
PMCID: PMC3582080  PMID: 23476840
22.  Principles of management of osteometabolic disorders affecting the aging spine 
European Spine Journal  2003;12(Suppl 2):S113-S131.
Osteoporosis is the most common contributing factor of spinal fractures, which characteristically are not generally known to produce spinal cord compression symptoms. Recently, an increasing number of medical reports have implicated osteoporotic fractures as a cause of serious neurological deficit and painful disabling spinal deformities. This has been corroborated by the present authors as well. These complications are only amenable to surgical management, requiring instrumentation. Instrumenting an osteoporotic spine, although a challenging task, can be accomplished if certain guidelines for surgical techniques are respected. Neurological deficits respond equally well to an anterior or posterior decompression, provided this is coupled with multisegmental fixation of the construct. With the steady increase in the elderly population, it is anticipated that the spine surgeon will face serious complications of osteoporotic spines more frequently. With regard to surgery, however, excellent correction of deformities can be achieved, by combining anterior and posterior approaches. Paget's disease of bone (PD) is a non-hormonal osteometabolic disorder and the spine is the second most commonly affected site. About one-third of patients with spinal involvement exhibit symptoms of clinical stenosis. In only 12–24% of patients with PD of the spine is back pain attributed solely to PD, while in the majority of patients, back pain is either arthritic in nature or a combination of a pagetic process and coexisting arthritis. In this context, one must be certain before attributing low back pain to PD exclusively, and antipagetic medical treatment alone may be ineffective. Neural element dysfunction may be attributed to compressive myelopathy by pagetic bone overgrowth, pagetic intraspinal soft tissue overgrowth, ossification of epidural fat, platybasia, spontaneous bleeding, sarcomatous degeneration and vertebral fracture or subluxation. Neural dysfunction can also result from spinal ischemia when blood is diverted by the so-called "arterial steal syndrome". Because the effectiveness of pharmacologic treatment for pagetic spinal stenosis has been clearly demonstrated, surgical decompression should only be instituted after failure of antipagetic medical treatment. Surgery is indicated as a primary treatment when neural compression is secondary to pathologic fractures, dislocations, spontaneous epidural hematoma, syringomyelia, platybasia, or sarcomatous transformation. Five classes of drugs are available for the treatment of PD. Bisphosphonates are the most popular antipagetic drug and several forms have been investigated.
doi:10.1007/s00586-003-0600-5
PMCID: PMC3591829  PMID: 14505119
Osteoporosis; Fractures; Neurological deficit; Deformity; Paget's disease; Back pain; Spinal stenosis; Myelopathy; Treatment
23.  A Model for Protein Sequence Evolution Based on Selective Pressure for Protein Stability: Application to Hemoglobins 
Negative selection against protein instability is a central influence on evolution of proteins. Protein stability is maintained over evolution despite changes in underlying sequences. An empirical all-site stability-based model of evolution was developed to focus on the selection of residues arising from their contributions to protein stability. In this model, site rates could vary. A structure-based method was used to predict stationary frequencies of hemoglobin residues based on their propensity to promote protein stability at a site. Sites with destabilizing residues were shown to change more rapidly in hemoglobins than sites with stabilizing residues. For diverse proteins the results were consistent with stability-based selection. Maximum likelihood studies with hemoglobins supported the stability-based model over simple Poisson-based methods. These observations are consistent with suggestions that purifying selection to maintain protein structural stability plays a dominant role in protein evolution.
PMCID: PMC2747123  PMID: 19812731
protein stability; negative selection; protein structure; evolutionary model
24.  The Role of the Sensorimotor System in the Athletic Shoulder 
Journal of Athletic Training  2000;35(3):351-363.
Objective:
To discuss the role of the sensorimotor system as it relates to functional stability, joint injury, and muscle fatigue of the athletic shoulder and to provide clinicians with the necessary tools for restoring functional stability to the athletic shoulder after injury.
Data Sources:
We searched MEDLINE, SPORT Discus, and CINAHL from 1965 through 1999 using the key words “proprioception,” “neuromuscular control,” “shoulder rehabilitation,” and “shoulder stability.”
Data Synthesis:
Shoulder functional stability results from an interaction between static and dynamic stabilizers at the shoulder. This interaction is mediated by the sensorimotor system. After joint injury or fatigue, proprioceptive deficits have been demonstrated, and neuromuscular control has been altered. To restore stability after injury, deficits in both mechanical stability and proprioception and neuromuscular control must be addressed. A functional rehabilitation program addressing awareness of proprioception, restoration of dynamic stability, facilitation of preparatory and reactive muscle activation, and implementation of functional activities is vital for returning an athlete to competition.
Conclusions/Recommendations:
After capsuloligamentous injury to the shoulder joint, decreased proprioceptive input to the central nervous system results in decreased neuromuscular control. The compounding effects of mechanical instability and neuromuscular deficits create an unstable shoulder joint. Clinicians should not only address the mechanical instability that results from joint injury but also implement both traditional and functional rehabilitation to return an athlete to competition.
Images
PMCID: PMC1323397  PMID: 16558648
proprioception; neuromuscular control; functional stability
25.  Influence of Fatigue in Neuromuscular Control of Spinal Stability 
Human factors  2004;46(1):81-91.
Lifting-induced fatigue may influence neuromuscular control of spinal stability. Stability is primarily controlled by muscle recruitment, active muscle stiffness, and reflex response. Fatigue has been observed to affect each of these neuromuscular parameters and may therefore affect spinal stability. A biomechanical model of spinal stability was implemented to evaluate the effects of fatigue on spinal stability. The model included a 6-degree-of-freedom representation of the spine controlled by 12 deformable muscles from which muscle recruitment was determined to simultaneously achieve equilibrium and stability. Fatigue-induced reduction in active muscle stiffness necessitated increased antagonistic cocontraction to maintain stability resulting in increased spinal compression with fatigue. Fatigueinduced reduction in force-generating capacity limited the feasible set of muscle recruitment patterns, thereby restricting the estimated stability of the spine. Electromyographic and trunk kinematics from 21 healthy participants were recorded during sudden-load trials in fatigued and unfatigued states. Empirical data supported the model predictions, demonstrating increased antagonistic cocontraction during fatigued exertions. Results suggest that biomechanical factors including spinal load and stability should be considered when performing ergonomic assessments of fatiguing lifting tasks. Potential applications of this research include a biomechanical tool for the design of administrative ergonomic controls in manual materials handling industries.
PMCID: PMC1633714  PMID: 15151156

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