Risk factors for development of myelopathy in patients with cervical spondylotic cord compression

Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common form of human myelopathy caused by a compression of the spinal cord by ectopic ossification of spinal ligaments. To elucidate the genetic basis for OPLL, we have been studying the ttw (tiptoe walking; previously designated twy) mouse, a naturally occurring mutant which exhibits ossification of the spinal ligaments very similar to human OPLL (refs 3,4). Using a positional candidate-gene approach, we determined the ttw phenotype is caused by a nonsense mutation (glycine 568 to stop) in the Npps gene which encodes nucleotide pyrophosphatase. This enzyme regulates soft-tissue calcification and bone mineralization by producing inorganic pyrophosphate, a major inhibitor of calcification. The accelerated bone formation characteristic of ttw mice is likely to result from dysfunction of NPPS caused by predicted truncation of the gene product, resulting in the loss of more than one-third of the native protein. Our results may lead to novel insights into the mechanism of ectopic ossification and the aetiology of human OPLL.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is a newly recognized entity. As the incidence of this disease was exceptionally high in Japan, the Japanese Ministry of Public Health and Welfare instituted a special commission for the investigation of this perplexing disease; since 1975 this committee has performed an intensive study of 2100 patients with OPLL in Japan. An epidemiologic study was conducted by this group in Japan and in eastern Asiatic countries. Symptoms and disabilities caused by the disease were described. Roentgenographic findings were classified as continuous, segmental, mixed, or localized. OPLL at the thoracic and lumbar levels combined with ossification of the yellow ligament was described, and the risk of spinal cord damage as well as the importance of tomography and computerized tomographic scanning were stressed. No conclusions were reached concerning etiology, but common findings included a generalized hyperostotic tendency, a tendency for abnormal glucose metabolism, and low enteral calcium absorption. A relatively high hereditary occurrence was noted. Conservative and surgical treatment methods were described, with particular reference to spinal canal-widening operations.

Spondylotic cervical cord compression detected by imaging methods is a prerequisite for the clinical diagnosis of spondylotic cervical myelopathy (SCM). Little is known about the spontaneous course and prognosis of clinically "silent" presymptomatic spondylotic cervical cord compression (P-SCCC). The aim of the present study was to update a previously published model predictive for the development of clinically symptomatic SCM, and to assess the early and late risks of this event in a larger cohort of P-SCCC subjects. A group of 199 patients (94 women, 105 men, median age 51 years) with magnetic resonance signs of spondylotic cervical cord compression, but without clear clinical signs of myelopathy, was followed prospectively for at least 2 years (range 2-12 years). Various demographic, clinical, imaging, and electrophysiological parameters were correlated with the time for the development of symptomatic SCM. Clinical evidence of the first signs and symptoms of SCM within the follow-up period was found in 45 patients (22.6%). The 25th percentile time to clinically manifested myelopathy was 48.4 months, and symptomatic SCM developed within 12 months in 16 patients (35.5%). The presence of symptomatic cervical radiculopathy and electrophysiological abnormalities of cervical cord dysfunction detected by somatosensory or motor-evoked potentials were associated with time-to-SCM development and early development ( 12 months) progression to symptomatic SCM. The multivariate predictive model based on these variables correctly predicted early progression into SCM in 81.4% of the cases. In conclusion, electrophysiological abnormalities of cervical cord dysfunction together with clinical signs of cervical radiculopathy and MRI hyperintensity are useful predictors of early progression into symptomatic SCM in patients with P-SCCC. Electrophysiological evaluation of cervical cord dysfunction in patients with cervical radiculopathy or back pain is valuable. Meticulous follow-up is justified in high-risk P-SCCC cases.