No abstract

We have reviewed the cervical spine radiographs of 180 patients with athetoid cerebral palsy and compared them with those of 417 control subjects. Disc degeneration occurred earlier and progressed more rapidly in the patients, with advanced disc degeneration in 51%, eight times the frequency in normal subjects. At the C3/4 and C4/5 levels, there was listhetic instability in 17% and 27% of the patients, respectively, again six and eight times more frequently than in the control subjects. Angular instability was seen, particularly at the C3/4, C4/5 and C5/6 levels. We found a significantly higher incidence of narrowing of the cervical canal in the patients, notably at the C4 and C5 levels, where the average was 14.4 mm in the patients and 16.4 mm in normal subjects. The combination of disc degeneration and listhetic instability with a narrow canal predisposes these patients to relatively rapid progression to a devastating neurological deficit.

In the evaluation of patient satisfaction as an outcome in patients operated on for degenerative lumbar spinal stenosis, we should keep in mind that postoperative functioning is a weak correlate of satisfaction.

Pycnodysostosis is a rare autosomal recessive skeletal dysplasia characterized by short stature, osteosclerosis, acroosteolysis, bone fragility, and skull deformities. Recently, mutations in the gene encoding cathepsin K (CK), a lysosomal cysteine protease localized exclusively in osteoclasts, were found to be responsible for this disease. We analyzed genomic DNA from four unrelated Japanese patients with this disorder and identified three different mutations of their CK genes: a previously reported missense mutation (A277 V), a novel single base deletion mutation (531 del T) causing a frame shift from codon 142 that results in a premature termination codon, and a novel missense mutation (L9P) in the signal peptide region. To investigate whether the L9P mutation disrupts signal peptide function and decreases protein synthesis, mutant and wild-type CK complementary DNAs driven by the cytomegalovirus promoter were transfected into COS-7 cells, and their gene products were detected by immunohistochemistry and Western blotting. Expression of the mutant protein was markedly reduced, suggesting decreased mature CK production in this patient, which may have been due to dysfunction of the signal peptide. These results provide evidence that a structural change in the signal peptide of the CK protein was involved in the pathogenesis of pycnodysostosis.