Assessment of the Matrix Degenerative Effects of MMP-3, ADAMTS-4 and HTRA1 injected into a bovine Intervertebral Disc Organ Culture Model

Study Design. In vitro study to develop an intervertebral disc degeneration (IDD) organ culture model, using coccygeal bovine intervertebral discs (IVDs) and injection of proteolytic enzymes MMP-3, ADAMTS-4 and HTRA1.Objective. This study aimed to develop an in-vitro model of enzyme-mediated IDD to mimic the clinical outcome in humans for investigation of therapeutic treatment options.Summary of Background Data. Bovine IVDs are comparable to human IVDs in terms of cell composition and biomechanical behavior. Researchers injected papain and trypsin into them to create an IDD model with a degenerated nucleus pulposus (NP) area. They achieved macroscopic cavities as well as a loss of glycosaminoglycans (GAGs). However, none of these enzymes are clinically relevant.Methods. Bovine IVDs were harvested maintaining the endplates. Active forms of MMP-3, ADAMTS-4 and HTRA1 were injected at a dose of 10μg/ml each. Phosphate buffered saline (PBS) was injected as a control. Discs were cultured for 8 days and loaded diurnally (day 1 to day 4 with 0.4 MPa for 16 h) and left under free swelling condition from day 4 to day 8 to avoid expected artifacts due to dehydration of the NP. Outcome parameters included disc height, metabolic cell activity, DNA content, glycosaminoglycan (GAG) content, total collagen content, relative gene expression and histological investigation.Results. The mean metabolic cell activity was significantly lower in the NP area of discs injected with ADAMTS-4 compared to the day 0 control discs. Disc height was decreased following injection with HTRA1, and was significantly correlated with changes in GAG/DNA of the NP tissue. Total collagen content tended to be lower in groups injected with ADAMTS4 and MMP-3.Conclusion. MMP-3, ADAMTS-4 and HTRA1 neither provoked visible matrix degradation nor major shifts in gene expression. However, cell activity was significantly reduced and HTRA1 induced loss of disc height which positively correlated with changes in GAG/DNA content. The use of higher doses of these enzymes or a combination thereof may therefore be necessary to induce disc degeneration

Cell therapy for intervertebral disc repair: advancing cell therapy from bench to clinics

Intervertebral disc (IVD) degeneration is a major cause of pain and disability; yet therapeutic options are limited and treatment often remains unsatisfactory. In recent years, research activities have intensified in tissue engineering and regenerative medicine, and pre-clinical studies have demonstrated encouraging results. Nonetheless, the translation of new biological therapies into clinical practice faces substantial barriers. During the symposium "Where Science meets Clinics", sponsored by the AO Foundation and held in Davos, Switzerland, from September 5-7, 2013, hurdles for translation were outlined, and ways to overcome them were discussed. With respect to cell therapy for IVD repair, it is obvious that regenerative treatment is indicated at early stages of disc degeneration, before structural changes have occurred. It is envisaged that in the near future, screening techniques and non-invasive imaging methods will be available to detect early degenerative changes. The promises of cell therapy include a sustained effect on matrix synthesis, inflammation control, and prevention of angio- and neuro-genesis. Discogenic pain, originating from "black discs" or annular injury, prevention of adjacent segment disease, and prevention of post-discectomy syndrome were identified as prospective indications for cell therapy. Before such therapy can safely and effectively be introduced into clinics, the identification of the patient population and proper standardisation of diagnostic parameters and outcome measurements are indispensable. Furthermore, open questions regarding the optimal cell type and delivery method need to be resolved in order to overcome the safety concerns implied with certain procedures. Finally, appropriate large animal models and well-designed clinical studies will be required, particularly addressing safety aspects.

Patient-rated Outcomes of Lumbar Fusion in Patients with Degenerative Disease of the Lumbar Spine: Does Age Matter?

Introduction: Current demographic changes are characterized by population aging, such that the surgical treatment of degenerative spine conditions in the elderly is gaining increasing relevance. However, there is a general reluctance to consider spinal fusion procedures in this patient age group due to the increased likelihood of complications. The aim of this study was to assess the patient-rated outcome and complication rates associated with lumbar fusion procedures in three different age groups. Methods: This was a retrospective analysis of prospectively collected data from consecutive patients who underwent first-time, one to three level posterior instrumented fusion between 2004 and 2011, due to degenerative disease of the lumbar spine. Data were obtained from our Spine Surgery Outcomes Database (linked to the International Spine Tango Register). Before surgery, patients completed the multidimensional Core Outcome Measures Index (COMI), and at 3 and 12 months after surgery they completed the COMI and rated the Global Treatment Outcome (GTO) and their satisfaction with care. Patients were divided into three groups according to their age: younger (≥50y <65y; n = 317), older (≥65y <80y; n = 350), and geriatric (≥ 80y; n = 40). Results: 707 consecutive patients were included. The preoperative comorbidity status differed significantly (p < 0.0001) between the age groups, with the highest scores in the geriatric group. General medical complications during surgery were lower in the younger age group (7%) than in the older (13.4%; p = 0.006) and geriatric groups (17.5%; p = 0.007). Duration of hospital stay was longer (p = 0.006) in the older group (10.8 ± 3.7 days) than the younger (10.0 ± 3.6 days) group. There were no significant group differences (p>0.05) for any of the COMI domains covering pain, function, symptom specific well-being, general quality of life, and social and work disability at either 3 months’ or 12 months’ follow-up. Similarly, there were no differences (p>0.05) between the age groups for GTO and patient-rated satisfaction at either follow-up. Conclusions: Preoperative comorbidity and general medical complications during lumbar fusion for degenerative disorders of the lumbar spine are both greater in geriatric patients than in younger patients. However, patient-rated outcome is as good in the elderly as it is in younger age groups. These data suggest that geriatric age per se is not a contraindication to instrumented fusion for lumbar degenerative disease.

Evaluation of HA-fibrin-based hydrogel for restoration of degenerated intervertebral disc

Introduction: Intervertebral disc degeneration is associated with loss of nucleus pulposus (NP) tissue and reduced disc height[1]. A number of therapies, including synthetic and natural biomaterials, have been developed to restore full disc function and to minimize the pain and disability caused by this disease. Fibrin-based biomaterials are used as a replacement for NP or as a cell carrier for tissue engineering approaches[2]. While the behavior of such gels is well-characterized from a material point of view, little is known about their contribution to intervertebral disc (IVD) restoration under dynamic loads. The aim of the present study is the evaluation of a hyaluronic acid fibrin-based hydrogel (ProCore) used to repair an in vitro model of disc degeneration under dynamic loading. Methods: In vitro model of disc degeneration was induced in intact coccygeal bovine IVD by papain digestion of the NP as previously described[3]. In order to characterize fibrin hydrogels, four experimental groups were considered: 1) intact IVD (control), 2) IVD injected with PBS, 3) injection of hydrogels in degenerative IVD and 4) injection of hydrogels in combination with human bone marrow-derived mesenchymal stem cells (MSC) in degenerative IVD. All of the groups were subjected to dynamic loading protocols consisting of 0.2MPa static compression superimposed with ±2° torsion at 0.2Hz for 8h per day and maintained for 7 days. Additionally, one group consisted of degenerative IVD injected with hydrogel and subjected to static compression. Disc heights were monitored after the duration of the loading and compared to the initial disc height. The macrostructure of the formed tissue and the cellular distribution was evaluated by histological means. Results: After one week of loading, the degenerative IVD filled with hydrogel in combination with MSC (dynamic load), hydrogels (dynamic load) and hydrogels (static load) showed a reduction in height by 30%, 15% and 20%, respectively, as compared to their initial disc height. Histological sections showed that the HA-fibrin gel fully occupied the nucleotomized region of the disc and that fibrin was effective in filling the discontinuities of the cavity region. Furthermore, the cells were homogenously distributed along the fibrin hydrogels after 7 days of loading. Discussion: In this study, we showed that fibrin hydrogels showed a good integration within the papain-induced model of disc degeneration and can withstand the applied loads. Fibrin hydrogels can contribute to disc restoration by possibly maintaining adequate stiffness of the tissue and thus preventing disorganization of the surrounding IVD. References: 1. Jarman, J.P., Arpinar, V.E., Baruah, D., Klein, A.P., Maiman, D.J., and Tugan Muftuler, L. (2014). Intervertebral disc height loss demonstrates the threshold of major pathological changes during degeneration. Eur Spine J . 2. Colombini, A., Ceriani, C., Banfi, G., Brayda-Bruno, M., and Moretti, M. (2014). Fibrin in intervertebral disc tissue engineering. Tissue Eng Part B Rev . 3. Chan, S.C., Bürki, A., Bonél, H.M., Benneker, L.M., and Gantenbein-Ritter, B. (2013). Papain-induced in vitro disc degeneration model for the study of injectable nucleus pulposus therapy. Spine J 13, 273-283. Acknowledgement We thank the Swiss National Science Foundation SNF #310030_153411 for funding.

RASSF7 expression and its regulatory roles on apoptosis in human intervertebral disc degeneration

Apoptosis plays an important role in intervertebral disc degeneration (IDD). Overwhelming evidence indicates that RASSF7 is essential for cell growth and apoptosis. Recently, it has been noted that the JNK signaling can be negatively regulated by suppressing phosphorylated-MKK7 activation during pro-apoptosis. We aimed to investigate the RASSF7 expression level in human degenerative nucleus pulposus (NP) cells and non-degenerative NP cells and the link between RASSF7-JNK with NP cells apoptosis. We harvested NP tissues from 20 IDD patients as disease group and 8 cadaveric donors as normal controls. We detected RASSF7 expression by Real-time-PCR and western blotting. Consequently, we found that the expression of RASSF7 was higher in non-degenerative group than in degenerative group (P<0.05). Overexpression of RASSF7 in degenerative NP cells led to decreased apoptosis rate than that in scramble group (P<0.05). Collectively, our findings suggest that RASSF7 plays an important role in human IDD and RASSF7 might be potentially developed as a curative agent.

Patient-Rated Outcomes of Lumbar Fusion in Patients with Degenerative Disease of the Lumbar Spine: Does Age Matter?

STUDY DESIGN Single centre retrospective study of prospectively collected data, nested within the Eurospine Spine Tango data acquisition system. OBJECTIVE The aim of this study was to assess the patient-rated outcome and complication rates associated with lumbar fusion procedures in three different age groups. SUMMARY OF BACKGROUND DATA There is a general reluctance to consider spinal fusion procedures in elderly patients due to the increased likelihood of complications. METHODS Before and at 3, 12, and 24 months after surgery, patients completed the multidimensional Core Outcome Measures Index (COMI). At the 3-, 12-, and 24-month follow-ups they also rated the Global Treatment Outcome (GTO) and their satisfaction with care. Patients were divided into three age groups: younger (≥50y < 65y; n = 317), older (≥65y < 80y; n = 350), and geriatric (≥ 80y; n = 40). RESULTS 707 consecutive patients were included. The preoperative comorbidity status differed significantly (p < 0.0001) between the age groups, with the highest scores in the geriatric group. Medical complications during surgery were lower in the younger age group (7%) than in the older (13.4%; p = 0.006) and geriatric groups (17.5%; p = 0.007); surgical complications tended to be higher in the elderly group (younger, 6.3%; older, 6.0%; geriatric, 15.0%; p = 0.09). There were no significant group differences (p > 0.05) for the scores on any of the COMI domains, GTO, or patient-rated satisfaction at either 3-, 12-, and 24-months follow-up. CONCLUSIONS Despite greater comorbidity and complication rates in geriatric patients, the patient-rated outcome was as good in the elderly as it was in younger age groups up to two years after surgery. These data indicate that geriatric age needs careful consideration of associated risks but is not per se a contraindication for fusion for lumbar degenerative disease. LEVEL OF EVIDENCE 4.

Influence of previous surgery on patient-rated outcome after surgery for degenerative disorders of the lumbar spine.

PURPOSE Few studies have used multivariate models to quantify the effect of multiple previous spine surgeries on patient-oriented outcome after spine surgery. This study sought to quantify the effect of prior spine surgery on 12-month postoperative outcomes in patients undergoing surgery for different degenerative disorders of the lumbar spine. METHODS The study included 4940 patients with lumbar degenerative disease documented in the Spine Tango Registry of EUROSPINE, the Spine Society of Europe, from 2004 to 2015. Preoperatively and 12 months postoperatively, patients completed the multidimensional Core Outcome Measures Index (COMI; 0-10 scale). Patients' medical history and surgical details were recorded using the Spine Tango Surgery 2006 and 2011 forms. Multiple linear regression models were used to investigate the relationship between the number of previous surgeries and the 12-month postoperative COMI score, controlling for the baseline COMI score and other potential confounders. RESULTS In the adjusted model including all cases, the 12-month COMI score showed a 0.37-point worse value [95 % confidence intervals (95 % CI) 0.29-0.45; p < 0.001] for each additional prior spine surgery. In the subgroup of patients with lumbar disc herniation, the corresponding effect was 0.52 points (95 % CI 0.27-0.77; p < 0.001) and in lumbar degenerative spondylolisthesis, 0.40 points (95 % CI 0.17-0.64; p = 0.001). CONCLUSIONS We were able to demonstrate a clear "dose-response" effect for previous surgery: the greater the number of prior spine surgeries, the systematically worse the outcome at 12 months' follow-up. The results of this study can be used when considering or consenting a patient for further surgery, to better inform the patient of the likely outcome and to set realistic expectations.

Nutritional status of selenium in Alzheimer`s disease patients

Studies have shown that various antioxidants are decreased in different age-related degenerative diseases and thus, oxidative stress would have a central role in the pathogenesis of many disorders that involve neuronal degeneration, including Alzheimer`s disease (AD). The present study aimed to assess the nutritional status of Se in AD patients and to compare with control subjects with normal cognitive function. The case control study was carried out on a group of elderly with AD (n 28) and compared with a control group (n 29), both aged between 60 and 89 years. Se intake was evaluated by using a 3-d dietary food record. Se was evaluated in plasma, erythrocytes and nails by using the method of hydride generation atomic absorption spectroscopy. Deficient Se intake was largely observed in the AD group. AD patients showed significantly lower Se levels in plasma, erythrocytes and nails (32.59 mu g/l, 43.74 mu g/l and 0.302 mu g/g) when compared with the control group (50.99 mu g/l, 79.16 mu g/l and 0.400 mu g/g). The results allowed us to suggest that AD has an important relation with Se deficiency.

Depression in Parkinson`s disease: Convergence from voxel-based morphometry and functional magnetic resonance imaging in the limbic thalamus

Depression is the most frequent psychiatric disorder in Parkinson`s disease (PD). Although evidence Suggests that depression in PD is related to the degenerative process that underlies the disease, further studies are necessary to better understand the neural basis of depression in this population of patients. In order to investigate neuronal alterations underlying the depression in PD, we studied thirty-six patients with idiopathic PD. Twenty of these patients had the diagnosis of major depression disorder and sixteen did not. The two groups were matched for PD motor severity according to Unified Parkinson Disease Rating Scale (UPDRS). First we conducted a functional magnetic resonance imaging (fMRI) using an event-related parametric emotional perception paradigm with test retest design. Our results showed decreased activation in the left mediodorsal (MD) thalamus and in medial prefrontall cortex in PD patients with depression compared to those without depression. Based upon these results and the increased neuron count in MD thalamus found in previous studies, we conducted a region of interest (ROI) guided voxel-based morphometry (VBM) study comparing the thalamic volume. Our results showed an increased volume in mediodorsal thalamic nuclei bilaterally. Converging morphological changes and functional emotional processing in mediodorsal thalamus highlight the importance of limbic thalamus in PD depression. In addition this data supports the link between neurodegenerative alterations and mood regulation. (C) 2009 Elsevier Inc. All rights reserved.

Effect of Disease Severity on the Performance of Cirrus Spectral-Domain OCT for Glaucoma Diagnosis

PURPOSE. To evaluate the effect of disease severity on the diagnostic accuracy of the Cirrus Optical Coherence Tomograph (Cirrus HD-OCT; Carl Zeiss Meditec, Inc., Dublin, CA) for glaucoma detection. METHODS. One hundred thirty-five glaucomatous eyes of 99 patients and 79 normal eyes of 47 control subjects were recruited from the longitudinal Diagnostic Innovations in Glaucoma Study (DIGS). The severity of the disease was graded based on the visual field index (VFI) from standard automated perimetry. Imaging of the retinal nerve fiber layer (RNFL) was obtained using the optic disc cube protocol available on the Cirrus HD-OCT. Pooled receiver operating characteristic (ROC) curves were initially obtained for each parameter of the Cirrus HD-OCT. The effect of disease severity on diagnostic performance was evaluated by fitting an ROC regression model, with VFI used as a covariate, and calculating the area under the ROC curve (AUCs) for different levels of disease severity. RESULTS. The largest pooled AUCs were for average thickness (0.892), inferior quadrant thickness (0.881), and superior quadrant thickness (0.874). Disease severity had a significant influence on the detection of glaucoma. For the average RNFL thickness parameter, AUCs were 0.962, 0.932, 0.886, and 0.822 for VFIs of 70%, 80%, 90%, and 100%, respectively. CONCLUSIONS. Disease severity had a significant effect on the diagnostic performance of the Cirrus HD-OCT and thus should be considered when interpreting results from this device and when considering the potential applications of this instrument for diagnosing glaucoma in the various clinical settings. (Invest Ophthalmol Vis Sci. 2010;51:4104-4109) DOI:10.1167/iovs.094716

Intra- and inter-observer reliability of MRI examination of intervertebral disc abnormalities in patients with cervical myelopathy

Purpose: Intervertebral cervical disc herniation (CDH) is a relatively common disorder that can coexist with degenerative changes to worsen cervicogenic myelopathy. Despite the frequent disc abnormalities found in asymptomatic populations, magnetic resonance imaging (MRI) is considered excellent at detecting cervical spine myelopathy (CSM) associated with disc abnormality. The objective of this study was to investigate the intra- and inter-observer reliability of MRI detection of CSM in subjects who also had co-existing intervertebral disc abnormalities. Materials and methods: Seven experienced radiologists reviewed twice the MRI of 10 patients with clinically and/or imaging determined myelopathy. MRI assessment was performed individually, with and without operational guidelines. A Fleiss Kappa statistic was used to evaluate the intra- and inter-observer agreement. Results: The study found high intra-observer percent agreement but relatively low Kappa values on selected variables. Inter-observer reliability was also low and neither observation was improved with operational guidelines. We believe that those low values may be associated with the base rate problem of Kappa. Conclusion: In conclusion, this study demonstrated high intra-observer percent agreement in MR examination for intervertebral disc abnormalities in patients with underlying cervical myelopathy, but differing levels of intra- and inter-observer Kappa agreement among seven radiologists. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

Validation of the Brazilian version of the quality of life scale for patients with Alzheimer`s disease and their caregivers (QOL-AD)

Quality of life (QOL) has been extensively studied in clinical trials and in research on chronic degenerative diseases and dementia. The aim of this study was to assess the reliability and construct validity of the Brazilian version of the QOL scale in Alzheimer`s disease (AD; QOL-AD). The QOL-AD was administered to 60 patients with mild or moderate AD and to their caregivers. The construct validation was accomplished through correlations amongst total scores of patients` and caregivers` reports on patients` quality of life (PQOL and C-PQOL, respectively), and data related to cognitive impairment, depressive symptoms, functional performance, behavioral disturbances and a generic instrument of quality of life (WHOQOL-brief), as well as correlation of total score of caregivers` reports on their own quality of life (CQOL) with the measurements cited above, QOL-AD patient reports, and depressive symptoms. The reliability was high for PQOL, C-PQOL, and CQOL versions (Cronbach`s alpha = 0.80, 0.83, and 0.86, respectively). We observed significant correlations in the construct validity of all three versions regarding the variables associated with the disease and also with WHOQOL-brief. The scale took, on average, six min for each version. The results indicate reliability and construct validity of the Brazilian version of the QOL-AD in the studied sample.

Complex language functions and subcortical mechanisms: evidence from Huntington's disease and patients with non-thalamic subcortical lesions

The neuropathological changes associated with Huntington's disease (HD) are most marked in the head of the caudate nucleus and, to a lesser extent, in the putamen and globus pallidus, suggesting that at least part of the language impairments found in patients with HD may result from non-thalamic subcortical (NTS) pathology. The present study aimed to test the hypothesis that a signature profile of impaired language functions is found in patients who have sustained damage to the non-thalamic subcortex, either focally induced or resulting from neurodegenerative pathology. The language abilities of a group of patients with Huntington's disease (n=13) were compared with those of an age- and education-matched group of patients with chronic NTS lesions following stroke (n=13) and a non-neurologically impaired control group (n=13). The three groups were compared on language tasks that assessed both primary and more complex language abilities. The primary language battery consisted of The Western Aphasia Battery and The Boston Naming Test, whilst the more complex cognitive-linguistic battery employed selected subtests from The Test of Language Competence-Expanded, The Test of Word Knowledge and The Word Test-Revised. On many of the tests of primary language function from the Western Aphasia Battery, both the HD and NTS participants performed in a similar manner to the control participants. The language performances of the HD participants were significantly more impaired (p<0.05 using modified Bonferroni adjustments) than the control group, however, on various lexico-semantic tasks (e. g. the Boston Naming Test and providing definitions), on both single-word and sentence-level generative tasks (e. g. category fluency and formulating sentences), and on tasks which required interpretation of ambiguous, figurative and inferential meaning. The difficulties that patients with HD experienced with tasks assessing complex language abilities were strikingly similar, both qualitatively and quantitatively, to the language profile produced by NTS participants. The results provide evidence to suggest that a signature language profile is associated with damage to the non-thalamic subcortex resulting from either focal neurological insult or a degenerative disease.

Dynamics of Gray Matter Loss in Alzheimer's Disease

We detected and mapped a dynamically spreading wave of gray matter loss in the brains of patients with Alzheimer's disease (AD). The loss pattern was visualized in four dimensions as it spread over time from temporal and limbic cortices into frontal and occipital brain regions, sparing sensorimotor cortices. The shifting deficits were asymmetric (left hemisphere >right hemisphere) and correlated with progressively declining cognitive status ( p 15% loss). The maps distinguished different phases of AD and differentiated AD from normal aging. Local gray matter loss rates (5.3 +/- 2.3% per year in AD v 0.9 +/- 0.9% per year in controls) were faster in the left hemisphere ( p < 0.029) than the right. Transient barriers to disease progression appeared at limbic/frontal boundaries. This degenerative sequence, observed in vivo as it developed, provides the first quantitative, dynamic visualization of cortical atrophic rates in normal elderly populations and in those with dementia.

Espetroscopia (1H) por ressonância magnética do disco intervertebral lombar no adulto e sua aplicação na rotina imagiológica

Objetivos – Demonstrar o potencial da espetroscopia (1H) por ressonância magnética na doença degenerativa discal lombar e defender a integração desta técnica na rotina clínico‑imagiológica para a precisa classificação da involução vs degenerescência dos discos L4‑L5 e L5‑S1 em doentes com lombalgia não relacionável com causa mecânica. Material e métodos – O estudo incluiu 102 discos intervertebrais lombares de 123 doentes. Foram estudados 61 discos de L4‑L5, 41 discos de L5‑S1 e 34 discos de D12‑L1. Utilizou‑se um sistema de ressonância magnética de 1,5 T e técnica monovoxel. Obtiveram‑se os rácios [Lac/Nacetyl] e [Nacetyl/(Lac+Lípidos)] e aplicou‑se a ressonância de lípidos para avaliar a bioquímica do disco com o fim de conhecer o estado de involução vs degenerescência que o suscetibilizam para a instabilidade e sobrecarga. Avaliou‑se o comportamento dos rácios e do teor lipídico dos discos L4‑L5‑S1 e as diferenças apresentadas em relação a D12‑L1. Foi também realizada a comparação entre os discos L4‑L5, L5‑S1 e D12‑L1 na ponderação T2 (T2W), segundo a classificação ajustada (1‑4) de Pfirrmann. Resultados – Verificou‑se que os rácios e o valor dos lípidos dos discos L4‑L5‑S1 apresentaram diferenças estatisticamente significativas quando relacionados com os discos D12‑L1. O rácio [Lac/Nacetyl] em L4‑L5‑S1 mostrou‑se aumentado em relação a D12‑L1 (p=0,033 para os discos com grau de involução [1+2] e p=0,004 para os discos com grau [3+4]). Estes resultados sugerem que a involução vs degenerescência dos discos nos graus mais elevados condiciona um decréscimo do pico do Lactato. O rácio [Nacetyl/(Lac+Lip)] discrimina os graus de involução [1+2] do [3+4] no nível L4‑L5, apresentando os valores dos rácios (média 0,65 e 0,5 respetivamente com p=0,04). O rácio médio de [Nacetyl/(Lac+Lip)] dos discos L4‑L5 foi 1,8 vezes mais elevado do que em D12‑L1. O espetro lipídico em L4‑L5‑S1 nos graus mais elevados não mostrou ter uma prevalência constante quanto às frequências de ressonância. Conclusão – A espetroscopia (1H) dos discos intervertebrais poderá ter aplicação na discriminação dos graus de involução vs degenerescência e representar um contributo semiológico importante em suplemento à ponderação T2 convencional. As ressonâncias de lípidos dos discos L4‑L5 e L5‑S1, involuídos ou degenerados, devem ser avaliadas em relação a D12‑L1, utilizando este valor como referência, pois este último é o nível considerado estável e com baixa probabilidade de degenerescência.