Surgical Treatment for Severe Fixed Hyperkyphosis in an Adult Patient Suffering From Ankylosing Spondylitis and Hereditary Hypophosphatemia With Vertebral Osteopetrosis.

PURPOSE: Ankylosing spondylitis and hereditary hypophosphatemia with long-term high dose supplementation of phosphorous and calcitriol can both lead to severe structural abnormalities of the vertebrae. Impairment of spinal mobility and spinal deformity may ultimately necessitate surgical treatment. A severe fixed hyperkyphosis in a patient with ankylosing spondylitis is a surgically demanding condition, therefore, the indication for surgical treatment should be thoroughly considered and chosen individually. METHODS: This is an uncommon case with a combination of a severe fixed hyperkyphosis with a Cobb-angle of 105 degrees between Th2 and L4 in an adult male patient suffering from ankylosing spondylitis and X-linked hypophosphatemia with surprisingly massive osteopetrosis. In this paper, the coexisting conditions of late-stage ankylosing spondylitis and long-term treated hereditary hypophosphatemia are highlighted. The surgical treatment with different techniques, complications, and results are well explained. RESULTS: A normal gait and stand were achieved by a long posterior fusion with 3 pedicle subtraction osteotomies on L1, L3, and L5. The surgical correction was performed in 3 stages. Postoperative the patient was administered to a rehabilitation center for 3 months. The hyperkyphosis, the C7 plumbline, and the pelvic retroversion were corrected. CONCLUSIONS: Surgical treatment of a severe fixed hyperkyphosis due to ankylosing spondylitis is technically demanding but can be successfully achieved if all surgical challenges and comorbidities are adequately addressed including intraoperative surprising findings like osteopetrotic bone in a patient with hereditary hypophosphatemia as in our case.

Recovery kinetics following spinal deformity correction: a comparison of isolated cervical, thoracolumbar, and combined deformity morphometries.

BACKGROUND CONTEXT: The postoperative recovery patterns of cervical deformity patients, thoracolumbar deformity patients, and patients with combined cervical and thoracolumbar deformities, all relative to one another, is not well understood. Clear objective benchmarks are needed to quantitatively define a "good" versus a "bad" postoperative recovery across multiple follow-up visits, varying deformity types, and guide expectations. PURPOSE: To objectively define and compare the complete 2-year postoperative recovery process among operative cervical only, thoracolumbar only, and combined deformity patients using area-under-the-curve (AUC) methodology. STUDY DESIGN/SETTING: Retrospective review of 2 prospective, multicenter adult cervical and spinal deformity databases. PATIENT SAMPLE: One hundred seventy spinal deformity patients. OUTCOME MEASURES: Common health-related quality of life (HRQOL) assessments across both databases included the EuroQol 5-Dimension Questionnaire and Numeric Rating Scale (NRS) back pain assessment. In order to compare disability improvements, the Neck Disability Index (NDI) and the Oswestry Disability Index (ODI) were merged into one outcome variable, the ODI-NDI. Both assessments are gauged on the same scale, with minimal question deviation. Sagittal Radiographic Alignment was also assessed at pre- and all postoperative time points. METHODS: Operative deformity patients >18 years old with baseline (BL) to 2-year HRQOLs were included. Patients were stratified by cervical only (C), thoracolumbar only (T), and combined deformities (CT). HRQOL and radiographic outcomes were compared within and between deformity groups. AUC normalization generated normalized HRQOL scores at BL and all follow-up intervals (6 weeks, 3 months, 1 year, and 2 year). Normalized scores were plotted against follow-up time interval. AUC was calculated for each follow-up interval, and total area was divided by cumulative follow-up length, determining overall, time-adjusted HRQOL recovery (Integrated Health State, IHS). Multiple linear regression models determined significant predictors of HRQOL discrepancies among deformity groups. RESULTS: One hundred seventy patients were included (27 C, 27 T, and 116 CT). Age, BMI, sex, smoking status, osteoporosis, depression, and BL HRQOL scores were similar among groups (p >. 05). T and CT patients had higher comorbidity severities (CCI: C 0.696, T 1.815, CT 1.699, p = .020). Posterior surgical approaches were most common (62.9%) followed by combined (28.8%) and anterior (6.5%). Standard HRQOL analysis found no significant differences among groups until 1-year follow-up, where C patients exhibited comparatively greater NRS back pain (4.88 vs. 3.65 vs. 3.28, p = .028). NRS Back pain differences between groups subsided by 2-years (p>.05). Despite C patients exhibiting significantly faster ODI-NDI minimal clinically important difference (MCID) achievement (33.3% vs. 0% vs. 23.0%, p < .001), all deformity groups exhibited similar ODI-NDI MCID achievement by 2-years (51.9% vs. 59.3% vs. 62.9%, p = 0.563). After HRQOL normalization, similar results were observed relative to the standard analysis (1-year NRS Back: C 1.17 vs. T 0.50 vs. CT 0.51, p < .001; 2-year NRS Back: 1.20 vs. 0.51 vs. 0.69, p = .060). C patients exhibited a worse NRS back normalized IHS (C 1.18 vs. T 0.58 vs. CT 0.63, p = .004), indicating C patients were in a greater state of postoperative back pain for a longer amount of time. Linear regression models determined postoperative distal junctional kyphosis (adjusted beta: 0.207, p = .039) and osteoporosis (adjusted beta: 0.269, p = .007) as the strongest predictors of a poor NRS back IHS (model summary: R2 = 0.177, p = .039). CONCLUSIONS: Despite C patients exhibiting a quicker rate of MCID disability (ODI-NDI) improvement, they exhibited a poorer overall recovery of back pain with worse NRS back scores compared with BL status and other deformity groups. Postoperative distal junctional kyphosis and osteoporosis were identified as primary drivers of a poor postoperative NRS back IHS. Utilization of the IHS, a single number adjusting for all postoperative HRQOL visits, in conjunction with predictive modelling may pose as an improved method of gauging the effect of surgical details and complications on a patient's entire recovery process.

Suppression of mTORC1 activation in acid-α-glucosidase-deficient cells and mice is ameliorated by leucine supplementation.

Pompe disease is due to a deficiency in acid-α-glucosidase (GAA) and results in debilitating skeletal muscle wasting, characterized by the accumulation of glycogen and autophagic vesicles. Given the role of lysosomes as a platform for mTORC1 activation, we examined mTORC1 activity in models of Pompe disease. GAA-knockdown C2C12 myoblasts and GAA-deficient human skin fibroblasts of infantile Pompe patients were found to have decreased mTORC1 activation. Treatment with the cell-permeable leucine analog L-leucyl-L-leucine methyl ester restored mTORC1 activation. In vivo, Pompe mice also displayed reduced basal and leucine-stimulated mTORC1 activation in skeletal muscle, whereas treatment with a combination of insulin and leucine normalized mTORC1 activation. Chronic leucine feeding restored basal and leucine-stimulated mTORC1 activation, while partially protecting Pompe mice from developing kyphosis and the decline in muscle mass. Leucine-treated Pompe mice showed increased spontaneous activity and running capacity, with reduced muscle protein breakdown and glycogen accumulation. Together, these data demonstrate that GAA deficiency results in reduced mTORC1 activation that is partly responsible for the skeletal muscle wasting phenotype. Moreover, mTORC1 stimulation by dietary leucine supplementation prevented some of the detrimental skeletal muscle dysfunction that occurs in the Pompe disease mouse model.

Arginine metabolism by macrophages promotes cardiac and muscle fibrosis in mdx muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is the most common, lethal disease of childhood. One of 3500 new-born males suffers from this universally-lethal disease. Other than the use of corticosteroids, little is available to affect the relentless progress of the disease, leading many families to use dietary supplements in hopes of reducing the progression or severity of muscle wasting. Arginine is commonly used as a dietary supplement and its use has been reported to have beneficial effects following short-term administration to mdx mice, a genetic model of DMD. However, the long-term effects of arginine supplementation are unknown. This lack of knowledge about the long-term effects of increased arginine metabolism is important because elevated arginine metabolism can increase tissue fibrosis, and increased fibrosis of skeletal muscles and the heart is an important and potentially life-threatening feature of DMD. METHODOLOGY: We use both genetic and nutritional manipulations to test whether changes in arginase metabolism promote fibrosis and increase pathology in mdx mice. Our findings show that fibrotic lesions in mdx muscle are enriched with arginase-2-expressing macrophages and that muscle macrophages stimulated with cytokines that activate the M2 phenotype show elevated arginase activity and expression. We generated a line of arginase-2-null mutant mdx mice and found that the mutation reduced fibrosis in muscles of 18-month-old mdx mice, and reduced kyphosis that is attributable to muscle fibrosis. We also observed that dietary supplementation with arginine for 17-months increased mdx muscle fibrosis. In contrast, arginine-2 mutation did not reduce cardiac fibrosis or affect cardiac function assessed by echocardiography, although 17-months of dietary supplementation with arginine increased cardiac fibrosis. Long-term arginine treatments did not decrease matrix metalloproteinase-2 or -9 or increase the expression of utrophin, which have been reported as beneficial effects of short-term treatments. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that arginine metabolism by arginase promotes fibrosis of muscle in muscular dystrophy and contributes to kyphosis. Our findings also show that long-term, dietary supplementation with arginine exacerbates fibrosis of dystrophic heart and muscles. Thus, commonly-practiced dietary supplementation with arginine by DMD patients has potential risk for increasing pathology when performed for long periods, despite reports of benefits acquired with short-term supplementation.

Sagittal spinal alignment in paraplegics: a new paradigm for the rehabilitation under neuromuscular electrical stimulation.

STUDY DESIGN: Radiographic analysis of sagittal spinal alignment of paraplegics in a standing position under surface neuromuscular electrical stimulation (NMES). OBJECTIVES: Describing the radiographic parameters of the sagittal spinal alignment of paraplegics going through a rehabilitation program with NMES. SETTING: The University Hospital's Ambulatory (UNICAMP), Campinas, São Paulo, Brazil. METHODS: Panoramic X-ray images in profile were taken for 10 paraplegics. All patients participated in the rehabilitation program and were able to perform gait through NMES of the femoral quadriceps muscles. The radiographic parameters used for the analysis were the same as those described in the literature for healthy people. The results were didactically organized into three groups: anatomical shape of the spine, morphology and kinetics of the pelvis and spinopelvic alignment. RESULTS: The physiological curvature of the spine in paraplegics showed average values similar to those described in the literature for healthy patients. The inversion of the pelvic tilt and the increase in the sacral slope were defined by the anterior backward rotation of the pelvis. The existing theoretical mathematical formulas that define lumbar lordosis, pelvic incidence and pelvic tilt showed normal values, despite the anterior intense sagittal imbalance. CONCLUSIONS: The adaptive posture of the spine in paraplegics standing through the stimulation of the femoral quadriceps does not allow for a neutral sagittal alignment. This novel radiographic detailed description of the various segments of the spine can be of assistance toward the understanding of the global postural control for such subjects.

[Decreased bone mineral density as a risk factor in the development of spinal deformities in neurofibromatosis]. / Csökkent csontdenzitás, mint lehetséges tényezó a neurofibromatosist kíséró gerincdeformitások kialakulásában.

Neurofibromatosis-1 is a here-do-familiar disorder that is associated with a variety of skeletal anomalies, mostly with spinal deformities in 10-50% of the patients. Intraoperatively, a poor vertebral bone quality has been observed. Efforts have been made to identify factors preventing curve progression, to optimize operational planning and to explain the pathomechanism. As part of the preoperative evaluation, the authors used a dual X-ray absorptiometry to assess the bone mineral density of the lumbar spine in 12 non operated patients with neurofibromatosis-1, supplemented by laboratory blood/urine investigations. A significant decrease in bone mineral density of lumbar spine was measured. An inverse relation was suggested between the severity of scoliosis and the lumbar spine Z-scores. No pivotal alterations were identified in the laboratory measurements. The bony tissue abnormality observed intraoperatively in neurofibromatosis-1 patients may be described as a diminution of the axial bone mineral density. The evaluation of bone mineral density in the course of the preoperative planning is proposed in neurofibromatosis-1.

Case study: acceleration/deceleration injury with angular kyphosis.

OBJECTIVE: To discuss the case of a patient who received upper cervical chiropractic care after trauma-induced arcual kyphosis in the cervical spine. A practical application of conservative management for posttrauma cervical spine injury in the private office setting is described. CLINICAL FEATURES: A 17-year-old female patient suffered an unstable C3/C4 motor segment after a lateral-impact motor vehicle collision. Additional symptoms on presentation included vertigo, tinnitus, neck and shoulder pain, and confusion. INTERVENTION AND OUTCOME: Conservative management consisted exclusively of upper cervical-specific adjustments guided by radiographic analysis and paraspinal bilateral skin temperature differential analysis of the cervical spine. During 10 weeks of care and 22 office visits, all symptoms subsided and the instability of C3/C4 motor segment appeared to be completely resolved. CONCLUSION: This study provides support for the use of upper cervical chiropractic management in cervical spine trauma cases. The clinical work-up consisted of physical examination, radiographic analysis, computer-administered and scored cognitive function testing, and audiometric examination. After conservative care, these examinations were repeated and demonstrated that the objective findings concurred with the subjective improvements reported by the patient.

A normal sagittal spinal configuration: a desirable clinical outcome.

OBJECTIVE: Traditional forms of chiropractic treatment methods have attempted to restore alignment of vertebrae to proposed "normal" positions. Although this approach has existed throughout chiropractic's 100-yr history, little has been written in the scientific literature in support of this approach. The objective of this review is to study further the rationale behind this approach and evaluate some of the mechanical, anatomical and physiological evidence upon which this chiropractic approach is based. STUDY SELECTION: Articles and studies were selected that discuss analysis of stress and strains in spinal tissues from gravitational loading and experimental deformation in human and animal models. Studies that included radiographic measurements and classifications of spinal configuration in the sagittal plane were reviewed for their relevance to the chiropractic concept of a typical, usual or normal spinal configuration against which to compare patients. CONCLUSION: The usual, typical or normal configuration of the cervical spine in the sagittal dimension is a lordosis with a range of 16.5-66 degrees when measured as tangent lines along the cervical curve of the posterior vertebral body margins of C2 and C7. An analysis of stresses and strains supports this claim, as do studies from the scientific literature that attempt to measure and classify average cervical configuration from large population bases. The use of normative data as a gauge against which to measure patients' structural health and as an outcome of the degree of success or failure of chiropractic interventions seem to be logical consequences of these findings.

Effectiveness of upper versus lower cervical adjustments with respect to the amelioration of passive rotational versus lateral-flexion end-range asymmetries in otherwise asymptomatic subjects.

The effects of cervical spinal adjustments delivered bilaterally either to the upper cervical region (C2-C3) or to the lower cervical region (C6-C7), were compared in groups of asymptomatic subjects exhibiting goniometrically verified left-right rotational or left-right lateral-flexion passive end-range asymmetries of greater than 10 degrees. Goniometric evaluation both prior to, and again within 30 min following treatments revealed that lower cervical adjustments were far more effective for the amelioration of lateral-flexion asymmetries than were upper cervical ones, whereas upper cervical adjustments were found to be more effective for the amelioration of rotational asymmetries than those delivered to the lower cervical region. These results are consistent with the view that passive movement restriction exhibited along the rotational axis is attributable to factors related primarily to the upper cervical region, whereas restrictions of passive movement along the lateral axis are more attributable to factors related to the lower cervical region. Further support for the regional independence of these axis-specific relationships is provided by similar results obtained in groups of subjects who happened to exhibit both rotational as well as lateral-flexion asymmetries of greater than 10 degrees on the day of the experiment.