https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(98)01302-6.pdf

Natural history of scoliosis in spastic cerebral palsy

Osteogenesis Imperfecta (OI) is a human syndrome characterized by exquisitely fragile bones due to osteoporosis. The majority of autosomal dominant OI cases result from point or splice site mutations in the type I collagen genes, which are thought to lead to aberrant osteoid within developing bones. OI also occurs in humans with homozygous mutations in Prolyl-3-Hydroxylase-1 (LEPRE1). Although P3H1 is known to hydroxylate a single residue (pro-986) in type I collagen chains, it is unclear how this modification acts to facilitate collagen fibril formation. P3H1 exists in a complex with CRTAP and the peptidyl-prolyl isomerase cyclophilin B (CypB), encoded by the Ppib gene. Mutations in CRTAP cause OI in mice and humans, through an unknown mechanism, while the role of CypB in this complex has been a complete mystery. To study the role of mammalian CypB, we generated mice lacking this protein. Early in life, Ppib-/- mice developed kyphosis and severe osteoporosis. Collagen fibrils in Ppib-/- mice had abnormal morphology, further consistent with an OI phenotype. In vitro studies revealed that in CypB–deficient fibroblasts, procollagen did not localize properly to the golgi. We found that levels of P3H1 were substantially reduced in Ppib-/- cells, while CRTAP was unaffected by loss of CypB. Conversely, knockdown of either P3H1 or CRTAP did not affect cellular levels of CypB, but prevented its interaction with collagen in vitro. Furthermore, knockdown of CRTAP also caused depletion of cellular P3H1. Consistent with these changes, post translational prolyl-3-hydroxylation of type I collagen by P3H1 was essentially absent in CypB–deficient cells and tissues from CypB–knockout mice. These data provide significant new mechanistic insight into the pathophysiology of OI and reveal how the members of the P3H1/CRTAP/CypB complex interact to direct proper formation of collagen and bone.

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Severe osteogenesis imperfecta in cyclophilin B-deficient mice.

Object Selective dorsal rhizotomy (SDR) has been shown to provide considerable benefit to children with spastic cerebral palsy (CP). The authors sought to evaluate the risks of postoperative spinal deformities in patients following SDR. Methods All patients who underwent SDR at McGill University between 1991 and 2001 were identified. Hospital charts and radiographic spinal studies (both preoperative and the latest postoperative) were systematically reviewed. Univariate and multivariate regression analyses were conducted to test all independent variables of potential interest to determine risk factors more likely to be associated with spinal deformity. There were 98 patients whose mean age at surgery was 5.1 years; the mean radiographic follow-up duration was 5.8 years. Thirty-nine (44.8%) of 87 patients in whom postoperative weight-bearing radiographs were obtained had mild scoliosis, and 17 in whom standing radiographs were acquired had hyperlordosis. In all, 18 of 94 patients (19.1%) who had postoperati...

Spinal deformities following selective dorsal rhizotomy.

Study design Radiologic study for patients with athetoid cerebral palsy (CP), and a biomechanical study using the finite-element model (FEM). Objectives To understand the lumbar disorders of athetoid CP patients and the etiology based on the results from the FEM study. Summary of background data Cervical spondylotic myelopathy is a well-identified spinal disorder associated with cerebral palsy, especially in athetoid type. One can rationalize that the athetoid involuntary trunk movement may induce stress-related lumbar disorders. Until now, very few investigations have been conducted on lumbar disorders that could occur in patients with CP. Methods Sixty-one cases with athetoid cerebral palsy were clinically reviewed. Radiographs of the lumbar spine in 30 cases with low back pain were taken. From these radiographs, the incidence of lumbar spondylolysis and endplate lesion was analyzed. The biomechanical study was conducted using a three-dimensional FEM of the ligamentous lumbar spine. Axial compression of 400 N was applied to simulate preload on the spine during the standing position followed with 10.6 Nm moment to simulate extension and axial rotation. The combined motion of extension and axial rotation was also simulated. During supine position, pure extension and rotation were simulated, and no preload was applied. The von Mises stresses were computed at the pars interarticularis at the each level and compared for different motions. Results Among the 61 patients, 41 complained of symptoms such as low back and leg pain. Thirty of these 41 patients gave their consents to undergo radiographic evaluation. Twenty-eight of the 30 patients (93.3%) showed stress-related disorders such as the spondylolysis and/or vertebral endplate lesions. Spondylolysis was found in 18 of the 30 patients (60.0%). Spondylolysis was observed at the multiple levels in 4 patients involving two levels in 2 cases and three levels in the other 2 cases. Vertebral endplate lesions (deformity) were seen in 26 (86.7%) of the 30 patients. Overall, the lesions (deformity) were found in 109 of 330 endplates (33.0%) out of all lumbar endplates in the 30 patients. The FEM based results showed that stresses at pars interarticularis of L5 were the highest of all levels in all loading modes, with or without preload. However, compared with the extension or axial rotation alone modes, the combined motion of extension and rotation showed higher stresses at the pars interarticularis. Conclusions The athetoid involuntary movements in CP patients may cause stress-related lumbar disorders. Especially, combined extension and rotation due to the involuntary trunk motion may contribute to the high incidence of spondylolysis.

Lumbar Spinal Disorders in Patients With Athetoid Cerebral Palsy: A Clinical and Biomechanical Study

BACKGROUND:

To our knowledge, there have been no previous studies addressing the indications for and the results of treatment of patients with cerebral palsy and concomitant kyphosis or lordosis without scoliosis. The purpose of the present study was to identify the indications for and the results of treatment of patients with cerebral palsy who have a spinal curve deformity solely in the sagittal plane.

METHODS:

We conducted a retrospective review of the data on all patients with cerebral palsy who had a sagittal plane spinal deformity but no coronal plane deformity, had undergone posterior spinal fusion with unit rod instrumentation at our institution, and had been followed for at least two years. Medical records and radiographs were reviewed for symptoms, type and magnitude of deformity, age at surgery, duration of surgery, nutritional status, complications, and concomitant medical problems.

RESULTS:

Twenty-four patients-—ten boys and fourteen girls-—were identified. Eight patients had a hyperlordotic deformity, fourteen had a hyperkyphotic deformity, and two exhibited both. Surgical indications included severe seating problems that could not be rectified with wheelchair modifications (eighteen patients), severe back pain (four patients), superior mesenteric artery syndrome that was refractory to conservative treatment (two patients), and a hyperlordotic deformity with a loss of bowel and bladder control (one patient).

It was found that specific technical concerns had to be addressed when the unit rod instrumentation was used. The mean preoperative hyperkyphotic curve of 93.8° was corrected to a mean of 35.8° postoperatively and was a mean of 34.8° at the last visit. The mean preoperative hyperlordotic curve of 91.8° was corrected to a mean of 43.6° postoperatively and was a mean of 48.6° at the last visit. All patients with seating problems and back pain had improvement or resolution of the problem after the surgery. The superior mesenteric artery syndromes, losses of bowel and bladder function, and malnutrition all resolved completely after the surgery.

CONCLUSIONS:

Patients with cerebral palsy and a severe sagittal plane deformity (≥70°) can be treated successfully with posterior spinal fusion with use of unit rod instrumentation. Indications for treatment include loss of sitting ability or balance, back pain, loss of bowel or bladder function, and superior mesenteric artery syndrome that is unresponsive to medical management.

Correction of sagittal plane spinal deformities with unit rod instrumentation in children with cerebral palsy

The authors analyzed lateral deviation, anteroposterior deformity, and rotation of the spinal column of 11 patients with scoliosis associated with cerebral palsy (CP) and 11 patients with progressive muscular dystrophy (PMD). There was a correlation between the magnitude of Cobb angle and that of the vertebral rotation in scoliosis associated with both CP and PMD, but the ratio of spinal rotation to Cobb angle in the former was lower than that in the latter, The magnitudes of thoracic kyphosis and of lumbar lordosis were not correlated with Cobb angle in either group, but the sagittal plane deformity in the CP patients was less severe than that in the PMD patients, and the latter demonstrated kyphosis of the lumbar spine and lordosis of the thoracic spine.

Satoru Yamamoto

Papers

Three-dimensional spinal deformity in scoliosis associated with cerebral palsy and with progressive muscular dystrophy.