Minimum invasive posterior decompression for cervical spondylotic amyotrophy.

BACKGROUND: Cervical spondylotic amyotrophy (CSA), characterized by amyotrophy and muscular weakness of the upper limbs, is caused by damage to anterior spinal root or anterior horn of the spinal cord. Formerly, anterior decompression and fusion were performed for treatment of CSA, but it has recently been reported that posterior decompression is also effective. However, a consensus on the choice of procedure has not yet been reached. Selective laminoplasty as minimally invasive surgery is a posterior decompression procedure that alleviates axial neck pain. Because, for CSA patients, the responsible lesion level is localized, this procedure combined with foraminotomy enables simultaneous spinal cord and root decompression. Therefore, we report the results of this treatment for CSA. METHODS: Subjects were 28 patients (25 males, 3 females), average age 50.6 years and average follow-up 43.5 months. The muscles involved were deltoid for 14 patients, biceps for 11, and extensor digitorum communis and/or intrinsic muscles of the hand for 9. MMT scores were grade 2 for 23 cases and grade 3 for 5 cases. To evaluate the results of minimally invasive surgery, cervical ROM (C2-7) and postoperative neck pain (VAS) on the first postoperative day and 1 week after surgery were evaluated. RESULTS: Muscle strength improvement was rated as "excellent" for 18 patients, "good" for 9, and "fair" for 1, with none rated "poor". Four of 10 patients whose muscle strength did not fully improve had distal type CSA and/or had preoperative MMT scores of 2. Average %ROM was 91.2 % and almost complete cervical ROM was maintained. The average postoperative VAS score was 2.6 on the first postoperative day and 1.2 1 week after surgery. CONCLUSIONS: Selective laminoplasty with segmental decompression is advantageous for minimizing postoperative neck pain and for simultaneous decompression of the affected spinal cord segment and nerve root.

Correlation between T2 relaxation time and intervertebral disk degeneration.

OBJECTIVE: Magnetic resonance T2 mapping allows for the quantification of water and proteoglycan content within tissues and can be used to detect early cartilage abnormalities as well as to track the response to therapy. The goal of the present study was to use T2 mapping to quantify intervertebral disk water content according to the Pfirrmann classification. MATERIALS AND METHODS: This study involved 60 subjects who underwent lumbar magnetic resonance imaging (a total of 300 lumbar disks). The degree of disk degeneration was assessed in the midsagittal section on T2-weighted images according to the Pfirrmann classification (grades I to V). Receiver operating characteristic (ROC) analysis was performed among grades to determine the cut-off values. RESULTS: In the nucleus pulposus, T2 values tended to decrease with increasing grade, and there was a significant difference in T2 values between each grade from grades I to IV. However, there was no significant difference in T2 values in the anterior or posterior annulus fibrosus. T2 values according to disk degeneration level classification were as follows: grade I (>116.8 ms), grade II (92.7-116.7 ms), grade III (72.1-92.6 ms), grade IV (<72.0 ms). CONCLUSION: T2 values decreased with increasing Pfirrmann classification grade in the nucleus pulposus, likely reflecting a decrease in proteoglycan and water content. Thus, T2 value-based measurements of intervertebral disk water content may be useful for future clinical research on degenerative disk diseases.

Pyogenic spondylitis in the elderly: a report from Japan with the most aging society.

Pyogenic spondylitis can be life-threatening for elderly patients. To discuss the characteristics of the disease in the elderly, medical records of 103 consecutive cases of pyogenic spondylitis were reviewed. Of these, 45 cases were 65 years of age or older, and these 45 cases were enrolled into further study. In this study, the proportion of elderly patients among the total number with pyogenic spondylitis was 43.7%, and this figure has increased with the passing of time as follows: 37.5% (1988-1993), 44.4% (1994-1999), and 55.5% (2000-2005). The microorganisms were isolated in 16 cases: Staphylococcus aureus in 13 cases (including methicillin-resistant Staphylococcus aureus in nine) and others in three. Twenty-five patients had associated diseases: diabetes in 18 patients and malignant tumors in seven. Thirty patients were treated conservatively, and 15 patients underwent surgery. Twenty-six patients had paralysis. All 15 patients treated surgically, and eight of the 11 patients treated conservatively showed improvement in paralysis. Bone union was achieved in all cases except one. Our results indicate that a good outcome can be expected from conservative treatment in elderly patients as well as the young.

Clinical Presentation of Cervical Myelopathy at C1-2 Level.

STUDY DESIGN: Single-center retrospective study. PURPOSE: To clarify the clinical features of cervical myelopathy at the C1-2 level. OVERVIEW OF LITERATURE: Methods for distinguishing the affected level based on myelomere symptoms or dysfunction of the conducting pathway were established. However, no symptoms have been identified as being specific to the C1-2 level segment. METHODS: We evaluated 24 patients with cervical myelopathy due to spinal cord compression at the C1-2 level. Preoperative neurological assessment were investigated and compared with the rate and site of compression of the spinal cord using computed tomography-myelography. RESULTS: Impaired temperature and pain sensation were confirmed in 18 of the 24 patients with that localized to the upper arms (n=3), forearm (n=9), both (n=2), and whole body (n=4). Muscle weakness was observed in 18 patients, muscle weakness extended from the biceps brachii to the abductor digiti minimi in 10 patients, and in the whole body in 8 patients. Deep tendon reflexes were normal in 10 patients, whereas hyperactive deep tendon reflexes were noted in 14 patients. The rate of spinal cord compression was significantly higher in patients with perceptual dysfunction and muscle weakness compared with those with no dysfunction. However, no significant difference in the rate and site of compression was identified in those with dysfunction. CONCLUSIONS: Perceptual dysfunction and muscle weakness localized to the upper limbs was observed in 58% and 42% of patients, respectively. Neurological abnormalities, such as perceptual dysfunction and muscle weakness, were visualized in patients with marked compression.

Telomerized human multipotent mesenchymal cells can differentiate into hematopoietic and cobblestone area-supporting cells.

OBJECTIVE: To compare the hematopoietic support provided by telomerized human mesenchymal stem cells (MSCs) and telomerized MSC-derived stromal cells. METHODS: We transfected the human telomerase catalytic subunit (hTERT) gene into primary MSCs to establish hTERT-transduced MSCs (hTERT-MSCs). Stromal induction of hTERT-MSCs was performed by replacing the culture medium with Dexter-type culture medium. Hematopoietic support was examined by coculture with cord blood CD34(+) cells. RESULTS: The hTERT-MSCs were morphologically identical with the primary MSCs and expressed surface antigens including CD105, CD73, and CD166. hTERT-MSCs showed a similar doubling time as primary MSCs and continued to proliferate to over 80 population doublings (PD), although the primary MSCs underwent crisis in vitro at 16 PD. The osteogenic, chondrogenic, adipogenic, neurogenic, and stromal differentiation potential of hTERT-MSCs were maintained up to at least 40 PD. The degree of expansion of CD34(+) cells and total number of colony-forming units in culture (CFU-C) upon 12-day coculture with the hTERT-MSC-derived stromal cells were nearly the same as those upon 12-day coculture with hTERT-MSCs (CD34, 33.0-fold+/-2.8-fold vs 36.1-fold+/-1.7-fold of the initial cell number; CFUs, 344.4-fold+/-62.5-fold vs 239.3-fold+/-87.0-fold; CFU-mix, 368.4-fold+/-113.7-fold vs 341.3-fold+/-234.3-fold). However, on day 18 of coculture, the number of cobblestone areas (CA) observed beneath the stromal cells was 15 times higher than that beneath hTERT-MSCs (CA, 146.9+/-54.6 vs 9.4+/-8.1, p<0.01). CONCLUSION: Stromal induction of hTERT-MSCs exclusively enhanced the support of CA formation provided by hTERT-MSCs. Our human hTERT-MSCs will be useful for elucidating the mechanism of the formation of CAs.

Underutilization of antiosteoporotic drugs by orthopedic surgeons for prevention of a secondary osteoporotic fracture.

BACKGROUND: Despite the availability of effective treatment and well-publicized treatment guidelines for preventing osteoporotic fractures, there are significant gaps in implementing the recommendations, and it is unknown how many patients are treated for prevention of secondary osteoporotic fractures. In this study, we investigate what percentage of osteoporosis patients were treated with antiosteoporotic drugs after osteoporotic fractures of the hip, wrist, and proximal humerus, and we discuss here the need for improvement in the treatment of osteoporosis following fracture. METHODS: We studied 422 patients with osteoporotic fractures, 91 men and 331 women, with an average age of 77.1 years (range, 52-102 years). The 422 cases consisted of 299 hip fractures, 97 distal radius fractures, and 26 proximal humerus fractures. All patients underwent surgical intervention. The variables were examined to ascertain whether osteoporosis patients were medicated with antiosteoporotic drugs at postfracture. RESULTS: Fifty-five (13%) of the 422 patients received antiosteoporotic medication at postfracture. Pharmaceutical treatment was given in 44 cases (14.7%) of hip fractures, 8 cases (8.2%) of distal radius fractures, and 3 cases (11.5%) of proximal humerus fractures. Thirty-one (7.3% of total) of the 55 patients were taking the same medication pre- and postfracture. Seven (1.7%) of the 55 were administered a different drug compared to before the fracture, and 17 (4%) started to take an antiosteoporotic drug for the first time subsequent to the fracture. CONCLUSIONS: The present rate of treatment is insufficient given the high risk of secondary fractures and the availability of appropriate drugs that would reduce that risk.

Enhanced osteoinduction by mesenchymal stem cells transfected with a fiber-mutant adenoviral BMP2 gene.

BACKGROUND: Bone regeneration therapy using mesenchymal stem cells (MSCs) is beginning to come into clinical use. To overcome the difficulty of healing large bone defects, we previously reported the efficacy of using rat mesenchymal stem cells (rMSCs) carrying a modified adenoviral vector (Adv-F/RGD) with an RGD-containing peptide in the HI loop of the fiber knob domain of adenovirus type 5 (Ad5). METHODS: Firstly, we evaluated the transduction efficiency of Adv-F/RGD into bone-marrow-derived human MSCs (hMSCs) using a beta-galactosidase chemiluminescent assay. Next, we evaluated whether the vector AxCAhBMP2-F/RGD carrying the human bone morphogenetic protein 2 (BMP2) gene could enhance the osteogenic activity of hMSCs in vitro and in vivo (in an ectopic model). In the ectopic model, transduced hMSCs, hMSCs in the presence of recombinant human BMP2 (rhBMP2) or hMSCs alone were implanted into a subcutaneous site of nude mice. We also applied this vector system to an orthotopic model (large bone defect model) using rMSCs. RESULTS: The transduction efficiency of Adv-F/RGD into hMSCs was increased 10-fold over the vector containing the wild-type fiber (Adv-F/wt), as assessed by a beta-galactosidase chemiluminescent assay. AxCAhBMP2-F/RGD increased the osteogenic activity of hMSCs in vitro. In the ectopic model, AxCAhBMP2-F/RGD-transduced hMSCs were found to induce new bone at 1 week after transplantation, and a greater quantity of new bone was formed than in other groups. Similarly, AxCAhBMP2-F/RGD-transduced rMSCs induced a greater quantity of new bone than other groups (AxCAhBMP2-F/wt-transduced rMSCs, rMSCs in the presence of rhBMP2, rMSCs alone, or scaffolds alone) in the orthotopic model. CONCLUSIONS: These data suggest that Adv-F/RGD is useful for introducing foreign genes into MSCs and that it will be a powerful gene therapy tool for bone regeneration and other tissue-engineering applications.

Efficient BMP2 gene transfer and bone formation of mesenchymal stem cells by a fiber-mutant adenoviral vector.

Strategies using mesenchymal stem cell (MSC)-mediated gene therapy have been developed to improve bone healing. However, transduction efficiency into MSCs by each vector is not always high. To overcome this problem, we used a modified adenoviral vector (Adv-F/RGD) with an RGD-containing peptide in the HI loop of the fiber knob domain of adenovirus type 5 (Ad5). Transduction efficiency into bone marrow-derived MSCs with Adv-F/RGD increased 12-fold compared with a vector containing the wild-type fiber (Adv-F/wt) by beta-galactosidase chemiluminescent assay. As a next step, we constructed AxCAhBMP2-F/RGD and AxCAhBMP2-F/wt carrying human bone morphogenetic protein 2 (BMP2). At the same multiplicity of infection, MSCs infected with AxCAhBMP2-F/RGD produced higher amounts of BMP2 than cells infected with AxCAhBMP2-F/wt, and also differentiated towards the osteogenic lineage more efficiently in vitro. Furthermore, using ex vivo gene transduction, we evaluated the potential for ectopic bone formation by the transduced MSCs in vivo. Transduction with AxCAhBMP2-F/RGD exhibited greatly enhanced new bone formation. These data suggest that Adv-F/RGD is useful for introducing foreign genes into MSCs and that it will be a powerful gene therapy tool for bone regeneration and other tissue engineering.