Diffusion and differentiation of healthy, ageing and degenerated discs
Pharmacological enhancement of disc diffusion and differentiation of healthy, ageing and degenerated discs : Results from in-vivo serial post-contrast MRI studies in 365 human lumbar discs
From: Eur Spine J. 2008 May;17(5):626-43
Degenerative disc disease is still a poorly understood phenomenon because of the lack of availability of precise definition of healthy, ageing and degenerated discs. Decreased nutrition is the final common pathway for degenerative disc disease and the status of the endplate plays a crucial role in controlling the extent of diffusion, which is the only source of nutrition. The vascular channels in the subchondral plate have muscarinic recptors but the possibility of enhancing diffusion pharmacologically by dilation of these vessels has not been probed. Although it is well accepted that endplate damage will affect diffusion and thereby nutrition, there is no described method to quantify the extent of endplate damage. Precise definitions with an objective method of differentiating healthy, ageing and degenerated discs on the basis of anatomical integrity of the disc and physiological basis of altered nutrition will be useful. This information is an urgent necessity for better understanding of degenerative disc disease and also strategizing prevention and treatment.
Seven hundred and thirty endplates of 365 lumbar discs from 73 individuals (26 healthy volunteers and 47 patients) with age ranging from 10-64 years were evaluated by pre-contrast and 10 min, 2, 4, 6 and 12 h post contrast MRI after IV injection of 0.3 mmol/kg of Gadodiamide. End plates were classified according to the extent of damage into six grades and an incremental score was given for each category. A total endplate score was derived by adding the endplate score of the two endplates for each concerned disc. The base line value and the signal intensity at particular time periods were used to derive the enhancement percentage for each time period. The enhancement percentage for each time period, the time for peak enhancement and the time intensity curve over 12 h were used to study and compare the diffusion characteristics. The differences in pattern of diffusion were obvious visually at 4 h which was categorized into five patterns-Pattern A representing normal diffusion to Pattern E rendplateresenting a total abnormality in diffusion. Degeneration was classified according to Pfirrmann’s grading and this was correlated to the total endplate score and the alterations in diffusion patterns. The relationship of total endplate score on the increase in degenerative disc disease was evaluated by a logistic curve and the cut point for severe degenerative disc disease was found by ROC curve. The influence of the variables of age, level, Modic changes, instability, annulus fibrosis defect, total endplate score and diffusion patterns on degenerative disc disease was analyzed by multiple and stepwise regression analysis.
Additional forty lumbar end-plates from four young healthy volunteers were studied to document the effect of oral nimodipine. Pre-drug diffusion levels were studied by pre and post contrast MRI (0.3 mmol/kg of gadodiamide) at 10 min, 2, 4, 6, 12 and 24 h. Oral nimodipine was administered (30 mg QID) for 5 days and post-contrast MRI studies were performed similarly. Enhancement was calculated at vertebral body; subchondral bone; Endplate Zone and at superior and inferior peripheral nucleus pulposus and central nucleus pulposus, using appropriate cursors by a blinded investigator. Paired sample t test and area under curve (AUC) measurements were done.The incidence of disc degeneration had a significant correlation with increasing total endplate score. Only one out of 83 (1.2%) disc had either Pfirrmann Grade IV or V when the score was 4 or below when compared to 34/190 (17.9%) for scores 5-7; 41 of 72 (56.9%) for scores 8-10 and 18 of 20 (90%) for scores 11 and 12. Pearson’s correlation between total endplate score and degenerative disc disease was statistically significant, irrespective of the level of disc or different age groups. Logistic curve fit analysis and ROC curve analysis showed that the incidence of degenerative disc disease increased abruptly when the total endplate score crossed six. With a progressive increase of end plate damage, five different patterns of diffusion were visualized. Pattern D and E rendplateresented totally altered diffusion pattern questioning the application of biological method of treatment in such situations. Four types of time intensity curves were noted which helped to differentiate between healthy, aged and degenerated discs. Multiple and stendplatewise regression analysis indicated that pattern of disc diffusion and total endplate score to be the most significant factors influencing degenerative disc disease, irrespective of age.
Nimodipine increased the average signal intensity for all regions-by 7.6% for vertebral body, 8% for subchondral bone and endplate zone and 11% for central nucleus pulposus at all time intervals. Although the increase was high at all time intervals, the maximum increase was at 2 h for vertebral body, subchondral bone and endplate zone; 4 h for peripheral nucleus pulposus and 12 h for central nucleus pulposus. It was also interesting that post-nimodipine, the peak signal intensity was attained early, was higher and maintained longer compared to pre-nimodipine values.Our study has helped to establish that endplate damage as a crucial event leading to structural failure thereby precipitating degenerative disc disease. An endplate damage score has been devised which had a good correlation to degenerative disc disease and discs with a score of six and above can be considered ‘at risk’ for severe degenerative disc disease. New data on disc diffusion patterns were obtained which may help to differentiate healthy, ageing and degenerated discs in in-vivo conditions. This is also the first study to document an increase in diffusion of human lumbar discs by oral nimodipine and poses interesting possibility of pharmacological enhancement of lumbar disc nutrition.
Nimodipine is used to treat symptoms resulting from a ruptured blood vessel in the brain (hemorrhage). It increases blood flow to injured brain tissue.
