Pharmacological enhancement of disc diffusion and differentiation of healthy, ageing and degenerated discs

Abstract

Degenerative disc disease (DDD) 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 DDD and the status of the endplate (EP) 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 receptors but the possibility of enhancing diffusion pharmacologically by dilation of these vessels has not been probed. Although it is well accepted that EP damage will affect diffusion and thereby nutrition, there is no described method to quantify the extent of EP 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 DDD 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 (TEPS) was derived by adding the EP score of the two endplates for each concerned disc. The base line value (SI(base)) and the signal intensity at particular time periods were used to derive the enhancement percentage for each time period (Enhancement (%) = SI(tp) - SI(base)/SI(base) x 100). The enhancement percentage for each time period, the time for peak enhancement (T-max) and the time intensity curve (TIC) 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 representing a total abnormality in diffusion. Degeneration was classified according to Pfirrmann's grading and this was correlated to the TEPS and the alterations in diffusion patterns. The relationship of TEPS on the increase in DDD was evaluated by a logistic curve and the cut point for severe DDD was found by ROC curve. The influence of the variables of age, level, Modic changes, instability, annulus fibrosis defect (DEBIT), TEPS and diffusion patterns on DDD was analyzed by multiple and stepwise regression analysis. Oral nimodipine study: 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 vert...

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