Association between Patellofemoral and medial Tibiofemoral compartment osteoarthritis progression: exploring the effect of body weight using longitudinal data from osteoarthritis initiative (OAI).

OBJECTIVES: To investigate the associations of medial and lateral patellofemoral osteoarthritis (PF-OA) at baseline with symptomatic and radiographic OA outcomes in the medial tibiofemoral compartment (MTFC) over 4 years, according to baseline overweight status. METHODS: Data and MRI images of 600 subjects in the FNIH-OA biomarkers consortium were used. Symptomatic worsening and radiographic progression of MTFC-OA were defined using Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scores and MTFC joint space narrowing (JSN) from baseline to 4-year follow-up. Baseline MRIs were read to establish PF-OA diagnosis. The association between baseline regional PF-OA pattern and odds for MTFC-OA progression was evaluated using regression models (adjusted for relevant confounding covariates including body mass index (BMI), age, sex, PF alignment measurements, KL grade, and knee alignment). To evaluate the effect modifying role for overweight status, stratification analysis was performed (BMI ≥ 25 vs. < 25 kg/m2). RESULTS: At baseline, 340 (56.7%), 255 (42.5%), and 199 (33.2%) subjects had OA in the medial, lateral, and both PF compartments. Baseline medial PF-OA was associated with WOMAC pain score and MTFC JSN progression at 4 years (Adjusted OR:1.56[95%CI:1.09-2.23] and 1.59[1.11-2.28], respectively) but not lateral PF-OA. In stratification analysis, overweight status was found to be an effect modifier for medial PF-OA and WOMAC pain (OR in overweight vs. non-overweight subjects:1.65[1.13-2.42] vs. 0.50[0.12-1.82]) as well as MTFC-JSN progression (1.63[1.12-2.4] vs. 0.75[0.19-2.81]). CONCLUSIONS: In addition to the known confounding effect of BMI for PF-OA and MTFC-OA, the overweight status may also play an effect modifier role in the association between baseline medial PF-OA and MTFC-OA progression, which is amenable to secondary prevention.

Lateral patellar tilt and its longitudinal association with patellofemoral osteoarthritis-related structural damage: Analysis of the osteoarthritis initiative data.

BACKGROUND: Increase in lateral patellar tilt-(LPT) can cause increased pressure on the lateral facet of the knee and can lead to patellar or femoral cartilage damage and further osseous changes. This study aims to test the hypothesis whether there is an association between increased LPT and MRI-based patellofemoral osteoarthritis-(OA) features at baseline and their worsening over a 2-year follow-up in participants of the Osteoarthritis Initiative-(OAI). METHODS: Recorded clinical and imaging data of 600 participants in the FNIH-OA biomarkers consortium was extracted from its database. The LPT-(as the angle betweenthe longest patella diameter and posterior aspect of condyles) was measured using theaxial knee MRI. Associations of LPT (every 5° increase) with MRI OA Knee Scoring-(MOAKS) for OA-related features, including cartilage and bone marrow lesions (BMLs) in addition to knee cartilage volume at baseline and their worsening after 2-year follow-up were assessed using regression models adjusted for several possible confounders. RESULTS: The mean LPT angle in this sample was 8.84° ± 5.19. In baseline, higher LPT was associated with lower cartilage volumes and higher cartilage lesions and BMLs MOAKS scores in the lateral trochlear and patellar subregions. Over the follow-ups, subjects with higher LPT measures in the baseline showed higher odds of experiencing BML score worsening in the lateral trochlear subregion-(OR:1.25[1.01-1.56]) over the 2-year follow-ups. CONCLUSIONS: Increase in LPT measures may be associated with OA-related features in the trochlear subregion. Therefore, aside from its use as an indicator of patellofemoral instability syndrome, LPT may be associated with longitudinal progression of patellofemoral OA.

Patellofemoral morphology measurements and their associations with tibiofemoral osteoarthritis-related structural damage: exploratory analysis on the osteoarthritis initiative.

OBJECTIVES: Given the coexistence and possible interactions between patellofemoral and tibiofemoral compartments, roles of patellofemoral morphology measurements in tibiofemoral osteoarthritis (OA) have not been investigated extensively. We aimed to determine whether patellofemoral morphology is associated with the presence and longitudinal worsening of tibiofemoral OA in participants of the Osteoarthritis Initiative (OAI). METHODS: Baseline knee MRIs of 600 participants were read by two independent blinded observers in consensus to determine patellofemoral morphology measurements including tibial tuberosity to trochlear groove (TT-TG) distance, trochlear groove depth (TGD), lateral patellar tilt (LPT), and Insall-Salvati ratio (ISR). Radiographic and MRI OA knee scoring (MOAKS) measurements were extracted from baseline and 2-year follow-up readings. Associations between baseline patellofemoral morphology metrics with radiographic medial tibiofemoral compartment (MTFC) joint space loss (> 0.7 mm, between baseline and 2nd-4th-year readings), and MRI-derived cartilage damage, bone marrow lesions (BMLs), and osteophytes (baseline to 2 years), were investigated using regression models adjusted for age, sex, body mass index, and knee alignment. P values were corrected using the Benjamini-Hochberg procedure. RESULTS: Patellofemoral morphology measurements were not associated with longitudinal joint space loss in the MTFC or MOAKS determinants. Only TT-TG distance was associated with the baseline number of subregions with cartilage defects (OR (95% CI), 1.09 (1.04-1.14), corrected p value ≤ 0.01), BMLs (OR (95% CI), 1.1 (1.04-1.17), corrected p value = 0.01), and osteophytes (OR (95% CI), 1.09 (1.05-1.14), corrected p value ≤ 0.01) in the lateral tibiofemoral compartment (LTFC), and worsening of LTFC cartilage defects over 2 years (OR (95% CI), 1.09 (1.03-1.16), corrected p value = 0.02). CONCLUSIONS: Higher TT-TG distance was associated with concurrent MRI-derived OA-related structural damages and 2-year follow-up worsening only in LTFC. No associations were detected between patellofemoral morphology measurements and MTFC OA progression. KEY POINTS: • Of all patellofemoral morphology measurements, the only lateralization of the tibial tubercle may be considered as a risk factor for lateral (not medial) tibiofemoral osteoarthritis worsening. • Patellofemoral morphology measurements of patella alta, trochlear dysplasia, patellar tilt, and lateralization of the tibial tubercle are not associated with radiographic and MRI-based medial tibiofemoral osteoarthritis worsening over 2 years. • Using longitudinal MRI data, each millimeter increase of TT-TG distance is associated with a 9% (95% confidence interval, 3-16%) increase in odds of longitudinal cartilage defects in the lateral tibiofemoral (but not medial) compartment over 2 years.

Tibial tuberosity to trochlear groove distance and its association with patellofemoral osteoarthritis-related structural damage worsening: data from the osteoarthritis initiative.

OBJECTIVES: To determine whether the tibial tuberosity-to-trochlear groove (TT-TG) distance is associated with concurrent patellofemoral joint osteoarthritis (OA)-related structural damage and its worsening on 24-month follow-up magnetic resonance imaging (MRI) in participants in the Osteoarthritis Initiative (OAI). METHODS: Six hundred subjects (one index knee per participant) were assessed. To evaluate patellofemoral OA-related structural damage, baseline and 24-month semiquantitative MRI Osteoarthritis Knee Score (MOAKS) variables for cartilage defects, bone marrow lesions (BMLs), osteophytes, effusion, and synovitis were extracted from available readings. The TT-TG distance was measured in all subjects using baseline MRIs by two musculoskeletal radiologists. The associations between baseline TT-TG distance and concurrent baseline MOAKS variables and their worsening in follow-up MRI were investigated using regression analysis adjusted for variables associated with tibiofemoral and patellofemoral OA. RESULTS: At baseline, increased TT-TG distance was associated with concurrent lateral patellar and trochlear cartilage damages, BML, osteophytes, and knee joint effusion [cross-sectional evaluations; overall odds ratio 95% confidence interval (OR 95% CI): 1.098 (1.045-1.154), p < 0.001]. In the longitudinal analysis, increased TT-TG distance was significantly related to lateral patellar and trochlear cartilage, BML, and joint effusion worsening (overall OR 95% CI: 1.111 (1.056-1.170), p < 0.001). CONCLUSIONS: TT-TG distance was associated with simultaneous lateral patellofemoral OA-related structural damage and its worsening over 24 months. Abnormally lateralized tibial tuberosity may be considered as a risk factor for future patellofemoral OA worsening. KEY POINTS: • Excessive TT-TG distance on MRI is an indicator/predictor of lateral-patellofemoral-OA. • TT-TG is associated with simultaneous lateral-patellofemoral-OA (6-17% chance-increase for each millimeter increase). • TT-TG is associated with longitudinal (24-months) lateral-patellofemoral-OA (5-15% chance-increase for each millimeter).

Superolateral Hoffa's fat pad (SHFP) oedema and patellar cartilage volume loss: quantitative analysis using longitudinal data from the Foundation for the National Institute of Health (FNIH) Osteoarthritis Biomarkers Consortium.

OBJECTIVES: To determine the association of superolateral Hoffa's fat pad (SHFP) oedema and patellofemoral joint structural damage in participants of Foundation for the National Institute of Health Osteoarthritis Biomarkers Consortium study. METHODS: Baseline and 24-month MRIs of 600 subjects were assessed. The presence of SHFP oedema (using 0-3 grading scale) and patellar morphology metrics were determined using baseline MRI. Quantitative patellar cartilage volume and semi-quantitative MRI osteoarthritis knee score (MOAKS) variables were extracted. The associations between SHFP oedema and patellar cartilage damage, bone marrow lesion (BML), osteophyte and morphology were evaluated in cross-sectional model. In longitudinal analysis, the associations between oedema and cartilage volume loss (defined using reliable change index) and MOAKS worsening were evaluated. RESULTS: In cross-sectional evaluations, the presence of SHFP oedema was associated with simultaneous lateral patellar cartilage/BML defects and inferior-medial patellar osteophyte size. A significant positive correlation between the degree of patella alta and SHFP oedema was detected (r = 0.259, p < 0.001). The presence of oedema was associated with 24-month cartilage volume loss (odds ratio (OR) 2.11, 95% confidence interval 1.46-3.06) and medial patellar BML size (OR 1.92 (1.15-3.21)) and number (OR 2.50 (1.29-4.88)) worsening. The optimal cut-off value for the grade of baseline SHFP oedema regarding both presence and worsening of patellar structural damage was ≥ 1 (presence of any SHFP hyperintensity). CONCLUSIONS: The presence of SHFP oedema could be considered as a predictor of future patellar cartilage loss and BML worsening, and an indicator of simultaneous cartilage, BML and osteophyte defects. KEY POINTS: • SHFP oedema was associated with simultaneous lateral patellar OA-related structural damage. • SHFP oedema was associated with longitudinal patellar cartilage loss over 24 months. • SHFP oedema could be considered as indicator and predictor of patellar OA.

The Neuroimaging Spectrum of Septum Posticum Derangement and Associated Thoracic Myelopathy.

BACKGROUND: Arachnoid cysts and meningeal membranes are among the differential diagnostic considerations of extra-medullary causes of thoracic myelopathy. In this case series of 7 patients, we present compressive meningeal membranes mimicking dorsal arachnoid cyst. The propensity of the meningeal membranes for the dorsal aspect of upper thoracic spine may reflect derangements of the septum posticum. OBJECTIVE: To provide the spectrum of imaging appearances and clinical presentations of pathology of the septum posticum to improve imaging utilization and to better guide treatment planning. METHODS: Seven patients aged 40 to 75 with MRI findings of ventral displacement and dorsal cord compression in the upper thoracic spine were further evaluated with CT-myelograms. The primary indication was to exclude dorsal arachnoid cyst. Two patients with progressive symptoms and lower extremity weakness were operated for decompression. RESULTS: CT-myelogram excluded space occupying lesions and cord herniation in all cases. Intradural dorsal meningeal webs and membranes were inconsistently visualized. In the 2 operated cases, thick coalescing membranes and hyperdynamic turbulent CSF flow were severely compressing the thoracic cord. CONCLUSION: Derangements of septum posticum may present a spectrum of findings that should be considered in the differential of thoracic myelopathy. Flattening of the posterior cord margin is a reliable imaging clue for a dorsal extra-medullary compressive lesion. Cord compression results from combination of adhesive membranes and turbulent CSF flow. The clinical course may be difficult to predict. Periodic imaging follow up can be helpful to confirm stability of findings in expectantly managed cases.

Application of basic physics principles to clinical neuroradiology: differentiating artifacts from true pathology on MRI.

OBJECTIVE: This article outlines artifactual findings commonly encountered in neuroradiologic MRI studies and offers clues to differentiate them from true pathology on the basis of their physical properties. Basic MR physics concepts are used to shed light on the causes of these artifacts. CONCLUSION: MRI is one of the most commonly used techniques in neuroradiology. Unfortunately, MRI is prone to image distortion and artifacts that can be difficult to identify. Using the provided case illustrations, practical clues, and relevant physical applications, radiologists may devise algorithms to troubleshoot these artifacts.

Application of basic principles of physics to head and neck MR angiography: troubleshooting for artifacts.

Neurovascular imaging studies are routinely used for the assessment of headaches and changes in mental status, stroke workup, and evaluation of the arteriovenous structures of the head and neck. These imaging studies are being performed with greater frequency as the aging population continues to increase. Magnetic resonance (MR) angiographic imaging techniques are helpful in this setting. However, mastering these techniques requires an in-depth understanding of the basic principles of physics, complex flow patterns, and the correlation of MR angiographic findings with conventional MR imaging findings. More than one imaging technique may be used to solve difficult cases, with each technique contributing unique information. Unfortunately, incorporating findings obtained with multiple imaging modalities may add to the diagnostic challenge. To ensure diagnostic accuracy, it is essential that the radiologist carefully evaluate the details provided by these modalities in light of basic physics principles, the fundamentals of various imaging techniques, and common neurovascular imaging pitfalls.

T2 hyperintensity of medial lemniscus: higher threshold application to ROI measurements is more accurate in predicting small vessel disease.

BACKGROUND: Medial lemniscus T2 hyperintensity (MLH) has been recently demonstrated as potential imaging marker for small vessel disease (SVD). Our purpose in this study is to improve accuracy of regions of interest (ROI) analysis for this imaging finding. METHODS AND METHODS: Two neuroradiologists retrospectively reviewed 103 consecutive outpatient brain MRI. Medial lemniscus signal in dorsal pons was evaluated; visually on FLAIR and with ROI on T2. Original MRI interpretations were divided into three categories; SVD, multiple sclerosis (MS), and nonspecific WM changes (non). RESULTS: Thirty-seven patients had SVD, 14 patients had MS, 52 had Non. Visual MLH was seen exclusively with SVD and was generally bilateral. Patients with visual MLH belonged to advanced SVD by imaging and clinical parameters. Compared to visual data, ROI analyses of MLH has been known to be compounded by false positives and negatives at low threshold (20% of adjacent to normal brainstem signal). With application of higher ROI threshold (25%), false positives were eliminated but false negatives increased. ROI analyses of MLH by experienced neuroradiologist were more reliable. CONCLUSION: MLH seen on high threshold ROI analysis is a reliable radiologic marker in predicting SVD. ROI analysis of MLH should be performed by an experienced neuroradiologist.

Brain-derived neurotrophic factor does not influence age at neurologic onset of Huntington's disease.

In Huntington's disease (HD), genetic factors in addition to the HD CAG repeat mutation play a significant role in determining age at neurologic onset. Brain-derived neurotrophic factor (BDNF), a survival factor for striatal neurons, has been implicated as a target of regulation by huntingtin and is an attractive candidate as a genetic modifier. We tested this hypothesis by genotyping a SNP known to alter BDNF function (rs6265, also termed Val66Met) and a SNP associated with Alzheimer disease (BDNF C270T), along with two BDNF intronic SNPs (rs7103411, rs11030104), in 228 cases with extreme young onset and 329 cases with extreme old onset of HD. No differences were seen between groups for allele frequencies or genotype frequencies for any SNP. Furthermore, no association to onset age was seen in GEE models controlling for HD repeat size or in haplotype analyses of these SNPs. These results indicate that BDNF does not influence significantly the mechanisms in HD pathogenesis that lead to neurologic onset.

Genetic analysis of the GRIK2 modifier effect in Huntington's disease.

BACKGROUND: In Huntington's disease (HD), age at neurological onset is inversely correlated with the length of the CAG trinucleotide repeat mutation, but can be modified by genetic factors beyond the HD gene. Association of a relatively infrequent 16 TAA allele of a trinucleotide repeat polymorphism in the GRIK2 3'UTR with earlier than expected age at neurological onset has been suggested to reflect linkage disequilibrium with a functional polymorphism in GRIK2 or an adjacent gene. RESULTS: We have tested this hypothesis by sequencing all GRIK2 exons, the exon-flanking sequences and 3'UTR in several individuals who were crucial to demonstrating the modifier effect, as they showed much earlier age at neurological onset than would be expected from the length of their HD CAG mutation. Though ten known SNPs were detected, no sequence variants were found in coding or adjacent sequence that could explain the modifier effect by linkage disequilibrium with the 16 TAA allele. Haplotype analysis using microsatellites, known SNPs and new variants discovered in the 3'UTR argues against a common ancestral origin for the 16 TAA repeat alleles in these individuals. CONCLUSION: These data suggest that the modifier effect is actually due to the TAA repeat itself, possibly via a functional consequence on the GRIK2 mRNA.

Genome-wide significance for a modifier of age at neurological onset in Huntington's disease at 6q23-24: the HD MAPS study.

BACKGROUND: Age at onset of Huntington's disease (HD) is correlated with the size of the abnormal CAG repeat expansion in the HD gene; however, several studies have indicated that other genetic factors also contribute to the variability in HD age at onset. To identify modifier genes, we recently reported a whole-genome scan in a sample of 629 affected sibling pairs from 295 pedigrees, in which six genomic regions provided suggestive evidence for quantitative trait loci (QTL), modifying age at onset in HD. METHODS: In order to test the replication of this finding, eighteen microsatellite markers, three from each of the six genomic regions, were genotyped in 102 newly recruited sibling pairs from 69 pedigrees, and data were analyzed, using a multipoint linkage variance component method, in the follow-up sample and the combined sample of 352 pedigrees with 753 sibling pairs. RESULTS: Suggestive evidence for linkage at 6q23-24 in the follow-up sample (LOD = 1.87, p = 0.002) increased to genome-wide significance for linkage in the combined sample (LOD = 4.05, p = 0.00001), while suggestive evidence for linkage was observed at 18q22, in both the follow-up sample (LOD = 0.79, p = 0.03) and the combined sample (LOD = 1.78, p = 0.002). Epistatic analysis indicated that there is no interaction between 6q23-24 and other loci. CONCLUSION: In this replication study, linkage for modifier of age at onset in HD was confirmed at 6q23-24. Evidence for linkage was also found at 18q22. The demonstration of statistically significant linkage to a potential modifier locus opens the path to location cloning of a gene capable of altering HD pathogenesis, which could provide a validated target for therapeutic development in the human patient.