|Sciatica: Studies of symptoms, genetic factors, and treatment with periradicular infiltration|
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This is the first report of the phenotype of patients with the Trp2 allele, a gene mutation that is strongly associated with intervertebral disc disease (Annunen et al. 1999). Patients with the Trp2 allele were significantly more flexible than patients without the allele, which may be related to altered interactions between collagen IX and other matrix molecules. Their clinical symptoms, however, did not differ from those without the allele. Analysis of the radiological (MRI) phenotype revealed that radial tears in nonherniated discs seem to be more common in patients with the allele. Patients with and without the Trp2 allele did not differ with respect to end-plate or intervertebral disc degeneration, HIZ-lesions or dorsal transverse tears.
Tears of the anulus are suggested to play an important role in the degeneration of the intervertebral joint complex (Osti et al. 1990). Anular tears can be classified into concentric, transverse and radial tears, of which MRI can demonstrate the transverse and radial tears (Yu et al. 1988b). HIZ-lesions, on the other hand, represent a combination of radial and circumferential tears (Aprill & Bogduk 1992). Radial ruptures are interesting as they precede disc degeneration (Yu et al. 1988a, Osti et al. 1992), and are associated with subjective pain in discography (Moneta et al. 1994). Radial tears are also known to cause sciatic pain (Ohnmeiss et al. 1997). In the current study, patients with the Trp2 allele were mostly in sedentary jobs and relatively young, yet three of them, and none of the other patients, had a radial tear in a nonherniated disc in MRI. Moreover, two of them had nerve root oedema at the same level, which ensures the presence of a radial tear. Consistent with this finding, 3 family members with the Trp2 allele, and none of those without it, had a radial tear. The occurrence of radial ruptures at the most mobile lumbar disc, i.e. the L4-5 level, may relate to mechanical factors. In accordance, intervertebral disc degeneration is also most prominent at the L4-5 and L3-4 levels (Miller et al. 1988). Transverse tears and HIZ-lesions were comparable in patients with or without the Trp2 allele. Indeed, histological analysis of post-mortem lumbar spines has indicated that transverse tears are due to trauma rather than biochemical degradation (Osti et al. 1992).
The patients with the Trp2 allele did not differ from their controls with respect to intervertebral disc degeneration, but the patients (and their controls) had mostly sedentary work. A hard physical job, and, particulararly frequent lifting and postural stress, increase the risk of sciatica (Heliövaara 1989, Riihimäki et al. 1989), whereas a sedentary job may decrease the risk of both sciatica (Riihimäki et al. 1994) and intervertebral disc degeneration (Battie et al. 1995). Interestingly, family members with the Trp2 allele had significantly more disc degeneration at the L5-S1 level than those without the amino acid substitution. They were, however, slightly older and there might also exist some difference in occupational load, i.e. these two populations are not fully comparable.
The possible association of radial tears and the Trp2 allele should be verified by discography with a larger patient population. Recently, a German population of patients operated for an intervertebral disc herniation was screened for the presence of the Trp2 allele (Wrocklage et al. 2000). Three patients of 250 (1.2%) had this sequence variation. The patients with the Trp2 allele were older than the others, but their radiologic phenotype was not characterized. The role of collagen IX in intervertebral disc disease is supported by the findings in transgenic mice expressing mutant α1(IX) chain: there was accelerated intervertebral disc degeneration with partial disruption of end-plates and fissures in the anulus (Kimura et al. 1996).
|MRI findings versus symptoms and signs of sciatica (I)||Up||Phenotype of patients with the Trp3 allele (III)|