|Sciatica: Studies of symptoms, genetic factors, and treatment with periradicular infiltration|
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The results of this study suggest that the Trp3 allele is strongly associated with TLS in sciatic patients. On the basis of the matched pair analysis, the Trp3 allele also enhances the likelihood of intervertebral disc degeneration at the L4-5 level, but other MRI and clinical characteristics were similar in patients with or without the allele. These and our previous findings emphasise the importance of collagen IX for end-plate and intervertebral disc integrity (Annunen et al. 1999, Paassilta et al. 2001).
Scheuermann’s disease already presents typically as rigid kyphosis of the thoracic or thoracolumbar spine in adolescence (Lowe 1999). The association of the Trp3 allele with TLS is a clinically important finding, because TLS predisposes to low back pain (Lings & Mikkelsen 1982, Greene et al 1985, Lowe 1999). Its incidence reportedly ranges from 4 % to 8 % among patients with low back pain, although it is probably underestimated through being missed or attributed to poor posture (Lowe 1999). A Danish study among patients with low back pain found considerably higher prevalences of both high (=thoracic; 28%) and low (=thoracolumbar; 26%) Scheuermann’s disease (Lings & Mikkelsen 1982).
TLS may also associate with lower lumbar discogenic disease. In one study 9 % of 1419 patients with TLS also had lower lumbar disc disease, and since 81 % were under 40 years and 9 % younger than 21 years, the authors proposed the term “juvenile discogenic disease” (Heithoff et al. 1994). The association of the two diseases and the early onset also led them to suggest that an intrinsic defect of the disc and/or end-plate, principally in proteoglycan or collagen, could be responsible for the structural weakness (Heithoff et al. 1994). The co-occurrence of Scheuermann-type changes with discogenic disease is also supported by findings from a Finnish long-term follow-up study. Children and adolescents with intervertebral disc degeneration and Scheuermann’s disease had an increased risk of recurrent low back pain at this age, and also a long-term risk of recurrent pain up to early adulthood (Paajanen et al. 1989b, Tertti et al. 1991, Salminen et al. 1999).
The aetiology of TLS is obscure. Our observation that it appears significantly more often in sciatic patients with the Trp3 allele (44 %) than without it (19 %) emphasises the importance of genetic factors. Further support comes from reports suggesting that TLS is inherited autosomally dominantly with incomplete penetrance and variable expression (Lowe 1999). In addition, histologic findings suggest that abnormal collagen matrix may be an aetiologic factor in the disease (Aufdermaur 1981). The importance of intact collagen IX for the development of TLS is also highlighted by the present finding that both individuals who were homozygous for the allele had the disease. Moreover, the finding that collagen IX defect is associated with TLS accords with the the presence of the protein in both the intervertebral disc and endplate. Thus, a defect in collagen IX, especially combined with other risk factors like physical job and male sex, may predispose to recurrent low back pain problems. The role of other risk factors is supported by findings that TLS is associated with repetitive trauma, and tends to occur primarily in adolescent boys engaged in heavy physical activity (Lowe 1999).
Patients with the Trp3 allele had significantly more disc degeneration on T2-weighted scans at the L4-5 level than those without the allele. Intervertebral disc degeneration has multifactorial aetiology (Battie et al. 1995). Among identical twins disc degeneration may be explained primarily by genetic influences and unidentified factors, which may include complex, unpredictable interactions (Battie et al. 1995). Involvement of genetic factors in intervertebral disc degeneration is strengthened by recent reports of an association between the disease and both vitamin D receptor gene polymorphism (Videman et al. 1998) and aggrecan gene polymorphism (Kawaguchi et al. 1999).
|Phenotype of patients with the Trp2 allele (II)||Up||Intention-to-treat analysis of periradicular infiltration (IV)|