Ryuichiro Sato

Cervical spondylotic myelopathy associated with kyphosis or sagittal sigmoid alignment: outcome after anterior or posterior decompression

OBJECT The effects of sagittal kyphotic deformities or mechanical stress on the development of cervical spondylotic myelopathy, or the reduction and fusion of kyphotic sagittal alignment have not been consistently documented. The aim in this study was to determine the effects of kyphotic sagittal alignment of the cervical spine in terms of neurological morbidity and outcome after 2 types of surgical intervention. METHODS The authors retrospectively reviewed the records of 476 patients who underwent cervical spine surgeries for spondylotic myelopathy between 1993 and 2006 at their university medical center. Among these were identified 43 patients-30 men and 13 women, with a mean age of 58.8 years-who had cervical kyphosis exceeding 10 degrees on preoperative sagittal lateral radiographs obtained in the neutral position, and their cases were analyzed in this study. Anterior decompression with interbody fusion was conducted in 28 patients, and en bloc open-door C3-7 laminoplasty in 15 patients. Both pre- and postoperative neurological, radiographic, and MR imaging findings were assessed in both surgical groups. RESULTS The mean preoperative kyphotic angle in all 43 patients was 15.9 +/- 5.9 degrees in the neutral position. Segmental instability was noted in 26 patients (61%) and reversed dynamic spinal canal stenosis at the level above the local kyphosis in 22 (51%). Preoperative T2-weighted MR images showed high-intensity signal within the cord at and around the level of maximal compression or segmental instability in 28 patients (65%). The mean kyphotic angle in both the neutral and flexion positions was significantly smaller at 4-6 weeks after surgery in the anterior spondylectomy group than in the laminoplasty group (p < 0.001). Furthermore, the angle in the neutral position was significantly smaller on follow-up in the anterior spondylectomy group than in the laminoplasty group (p = 0.034). The transverse area of the spinal cord was significantly larger in the anterior spondylectomy group than in the laminoplasty group on follow-up (p = 0.037). Preoperative neurological scores (assessed using the Japanese Orthopaedic Association scale) and improvement on follow-up > or = 2 years after treatment (average 3.3 years) were not significantly different between the 2 groups; however, there was a significant difference in Japanese Orthopaedic Association score at 4-6 weeks postoperatively (p = 0.047). CONCLUSIONS Kyphotic deformity and mechanical stress in the cervical spine may play an important role in neurological dysfunction. In a select group of patients with kyphotic deformity > or = 10 degrees , adequate correction of local sagittal alignment may help to maximize the chance of neurological improvement.

Thoracic ossification of the human ligamentum flavum: histopathological and immunohistochemical findings around the ossified lesion

OBJECT The object of this study was to histopathologically and immunohistochemically characterize ossification of the ligamentum flavum (OLF) in samples of the thoracic spine harvested en bloc during surgery and to enhance the understanding of the ossifying process, particularly calcification and ossification. METHODS Samples of OLF plaque were obtained en bloc from 43 patients who underwent posterior decompression. The histopathological findings were correlated with radiological subtypes using computed tomography. The expression of type I and type II collagens, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)beta, and bone morphogenetic protein (BMP)-2 was investigated. RESULTS Surgical decompression using the posterior floating and en bloc resection technique resulted in neurological improvement in 40 of 43 patients. Progression of the OLF lesion longitudinally and medially was associated with significant degeneration of elastic fibers, fiber bundle derangement, decrements in fiber diameter, and fragmentation. Calcification and ossification paralleled the degeneration of the elastic fibers, extended more medially, and fused in the central area. Expression of BMP-2, TGFbeta, and VEGF was significant in chondrocytes in the calcified cartilage and fibrocartilage layers, especially around the calcified front. CONCLUSIONS Histopathologically, the progress of calcification and ossification was closely associated with the degeneration of elastic fibers and with significant expression of BMP-2, TGFbeta, and VEGF in the ossification front.

Ossification of the posterior longitudinal ligament of the cervical spine: histopathological findings around the calcification and ossification front

OBJECT The authors studied the histological and immunohistochemical features of ossified posterior longitudinal ligament (PLL) of the cervical spine, especially in the calcification and ossification front. METHODS Samples of en bloc ossified PLL plaque obtained in 31 patients were stained with H & E and immunohistochemically prepared for collagens (types I and II), vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-beta, and bone morphogenetic protein (BMP)-2, and by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method for apoptosis. RESULTS Enchondral ossification was evident between the ligamentous enthesis and deep layer of the ligament, with irregularly disorganized arrangement of elastic fibers in association with advancement of the degenerative process. In the ossification front, many hypertrophic metaplastic chondrocytes were noted in the ossifying plaque immediately contiguous to the ligament fibers, together with a considerable degree of neovascularization. Both TGFbeta and BMP-2 were highly expressed in metaplastic hypertrophic chondrocytes in the ossification front, and BMP-2 was also expressed in fibroblastic cells near the ossified PLL plaque. Expression of type I collagen was significant in the matrix of the ossified PLL lesion, whereas that of type II was marked in metaplastic chondrocytes in the ossification front. Apoptotic hypertrophic chondrocytes were observed mainly in the fibrocartilaginous area near the calcification front. CONCLUSIONS The enchondral ossification process in the ossified PLL was closely associated with degenerative changes of elastic fibers and cartilaginous cartilage formation, together with the appearance of metaplastic hypertrophic cartilage cells and neovascularization. The authors also found that VEGF-positive metaplastic chondrocytes in the ossification front and different expression patterns of collagens probably play some role in the extension of the ossified PLL from the ossification front.

Calcium pyrophosphate crystal deposition in the ligamentum flavum of degenerated lumbar spine: histopathological and immunohistological findings

We investigated the histological and immunohistochemical features of degenerative changes in the ligamentum flavum of the lumbar spine with calcium crystal deposition. We investigated degenerative changes in 270 ligamentum flavum specimens harvested from 198 patients who underwent decompressive surgeries for lumbar spinal canal stenosis. En bloc sections of the ligamentum flavum were examined histologically. We also examined immunoreactivity for transforming growth factor (TGF)-β, vascular endothelial growth factor (VEGF), CD34, and CD68; immunoblot analysis for VEGF; and terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end-labeling (TUNEL) method. The ligamentum flavum showed fragmented and disorganized elastic fiber bundles with increased collagen fibrils in the matrix. Calcium deposition, which was identified as calcium pyrophosphate dihydrate crystals, was evident in 72 of 198 patients and in 99 of 270 samples, and was associated with appearance of hypertrophic chondrocytes and new blood vessel formation. Areas of calcium deposits were surrounded by abundant hypertrophic chondrocytes (with marked immunoreactivity to TGF-β and VEGF) and a significant number of TUNEL-positive chondrocytes. Calcium crystal deposition in the lumbar ligamentum flavum progresses with reduction in elastic fibers and accumulation of collagen fibrils in the matrix as well as expansion of chondrometaplastic areas.

Anterior and posterior decompressive surgery for progressive amyotrophy associated with cervical spondylosis: a retrospective study of 51 patients

OBJECT The aims of this study were to review the clinicoradiological findings in patients who underwent decompressive surgery for proximal and distal types of muscle atrophy caused by cervical spondylosis and to discuss the outcome and techniques of surgical intervention. METHODS Fifty-one patients (43 men and 8 women) with proximal (37, with arm drop) and distal muscle atrophy (14, with wrist drop) underwent cervical decompression (39 anterior decompressions and 12 open-door C3-7 laminoplasties with microsurgical foraminotomy) for muscle weakness in the upper extremities. The clinical course, type of spinal cord compression, abnormal signal intensity on high-resolution MR imaging, and postdecompression improvement in muscle power were reviewed at a mean follow-up of 2.6 years (range 0.8-9.4 years). RESULTS The most commonly affected vertebrae were C4-5 and C5-6, and C5-6 and C6-7 in patients with proximal or distal muscle atrophy, respectively; the respective numbers of affected vertebrae were 1.5 and 2.2. Transaxial MR imaging showed medial compression of the spinal cord in 20 patients (in 12 with proximal and 8 with distal muscle atrophy), paramedial compression in 22 (17 and 5 patients, respectively), and foraminal compression in 9 (8 and 1 patient, respectively). Increased signal intensity on MR imaging was observed in 85.0, 22.7, and 11.1% of cases of medial, paramedial, and foraminal compression, respectively. Increased signal intensity at the affected muscle segment level was observed in 52.9, 40.0, and 0% of cases, respectively. Sixty-two percent of patients with proximal muscle atrophy gained 1 or more grades of muscle power on manual muscle testing (MMT), whereas 64.3% with distal muscle atrophy failed to gain even 1 grade of improvement. The recovery of muscle power correlated with disease duration and the percent voltage of Erb point or wrist-stimulated muscle evoked potentials but not with preoperative MMT, longitudinal range of spinal cord compression, signal change on T2-weighted MR imaging, or surgical procedure. CONCLUSIONS Surgical outcome in patients with distal muscle atrophy was inferior to that in patients with proximal atrophy. The distal type was characterized by a long preoperative period, a greater number of cervical spine misalignments, a narrow spinal canal, and increased signal intensity on T2-weighted MR imaging. It is essential to perform a careful neurological evaluation, including sensory examination of the lower limbs, as well as neuroradiological and neurophysiological assessments to avoid confusion with motor neuron disease and to detect the coexistence of amyotrophic lateral sclerosis, especially when surgical treatment of cervical spondylosis is planned. The results of careful physical examination, MR imaging studies, and electromyography studies should be comprehensively evaluated to ascertain the pathophysiology of the muscle atrophy. It is very important to distinguish the pathophysiology caused by nerve root impingements from anterior horn dysfunction when making decisions about treatment strategy. Surgical treatment--with or without foraminotomy--for amyotrophy in cervical spondylosis requires urgent action with regard to human neuroanatomy and neural innervation of the paralyzed muscles.

Immunohistochemical findings of multiple ossified en plaque meningiomas in the thoracic spine

We describe a 76-year-old woman who presented with painful muscle weakness and numbness in both legs secondary to grossly ossified meningiomas at the T8 and T11-T12 vertebral levels. Midline durotomy followed by en bloc excision of the tumours, together with partial resection of the dura mater and the arachnoid, was performed. Histopathological examination showed both tumours consisted of three different histological patterns: psammomatous, fibrous, and metaplastic subtypes. Immunostaining for bone morphogenetic protein-2 and vascular endothelial growth factor was significantly positive in the areas surrounding mature bone tissues in the metaplastic and psammomatous subtypes.

Targeted retrograde gene delivery into the injured cervical spinal cord using recombinant adenovirus vector.

Direct routes of gene administration (intrathecal, intracerebroventricular or intraparenchymal infusion) have been used for effective and sustained gene delivery, but serious concerns exist about possible traumatic injury as well as neural damage that may lead to further tissue necrosis, apoptosis and cell death. We evaluated targeted retrograde gene delivery through the sternomastoid muscle (innervated by the spinal accessory nerves) into the injured cervical spinal cord using a recombinant adenovirus vector. LacZ gene expression in the cervical spinal cord was noted from 3 days to 4 weeks after the injection of vector into the sternomastoid muscles of the rats. Recombinant adenovirus vector was transferred via a retrograde mechanism into the injured cervical spinal cord with high transduction efficacy (80.6--98.9%) over certain adenoviral titer and dosage. Transduction was less efficient when the vector was injected 1 and 2 weeks after spinal cord injury (44.2--56.8%). Our results indicate retrograde delivery of recombinant adenovirus vector is possible immediately after spinal cord injury, and that this method is promising for gene delivery because it is effective, selective, less invasive to the injured spinal cord, has long-lasting gene expression, and is potentially feasible treatment choice for spinal cord injury.

Target muscles for retrograde gene delivery to specific spinal cord segments

Targeted retrograde gene delivery into the injured spinal cord is less invasive for the damaged tissue. One of the advantages of this approach is the possible selection of target organs according to the level of spinal cord injury. We evaluated nine candidate target organs for retrograde delivery of an adenovirus vector carrying beta-galactosidase (AdV-LacZ) gene to cervical, thoracic and lumbar spinal cord segments. One week after vector injection into each muscle, we assessed the LacZ gene expression in the spinal cord by X-gal staining. The most appropriate target organs with high transduction efficacy were the sternomastoid and clavotrapezius muscles for cervical spinal cord, tibialis anterior and the gastrocnemius muscles for the lumbar spinal cord. Retrograde gene delivery to the thoracic spinal cord was inefficient probably due to the small number of anterior horn neurons in the region. Gene expression was mainly identified over the anatomical area of innervation and not into other body organs. Our results suggested that retrograde delivery of adenovirus genome to the cervical and lumbar spinal cord segments seems feasible by injection of an adenoviral vector into the appropriate target organ. Adenovirus vector is an efficient retrograde tracer since it can deliver the carried gene to a wide area of the spinal cord and not to other body organs.

Cervical angina: a seemingly still neglected symptom of cervical spine disorder?

Study Design:Retrospective, case series.Design:A review of 10 surgical cases with symptoms of cervical angina.Objective:To stress the importance of symptoms of cervical angina in patients with cervical spine disorders.Setting:Fukui University Hospital, Japan.Results:A total of 10 patients complaining of symptoms of cervical angina were admitted with a tentative diagnosis of coronary artery disease. Pain relief was achieved by anterior surgical decompression in all patients.Conclusion:We stress that physicians should be aware of the symptoms of cervical angina and that surgical intervention often leads to complete relief of symptoms.

Cruciate paralysis and hemiplegia cruciata: report of three cases

Study design:Report of three cases of cruciate paralysis and hemiplegia cruciata.Objective:To stress the importance of upper cervical spine lesions causing neurological symptoms and signs.Setting:Neuro-orthopedic service, Fukui University Hospital, Japan.Results:Three patients (all females; one with congenital anomaly at the occiput-atlas level, one with assimilation of the atlas, and one with rheumatoid arthritis-related proliferative synovium) had clinical features of cruciate paralysis and hemiplegia cruciata. All three cases underwent decompressive surgeries.Conclusion:Neurological symptoms and signs of cruciate paralysis and hemiplegia cruciata should be carefully assessed, and surgical therapy should be based on the pathological condition.