While the number of new treatment options tested in patients with Duchenne muscular dystrophy (DMD) is increasing, there is still no defining of the most reliable assessments regarding therapeutic efficacy. We present clinical and radiological outcome measures used in ambulatory patients participating in our trial "Treatment with L-citrulline and metformin in Duchenne muscular dystrophy". The motor function measure is a validated test in patients with neuromuscular disorders that consists of 32 items and assesses all three dimensions of motor performance including standing and transfer (D1 subscore), axial and proximal motor function (D2 subscore), and distal motor function (D3 subscore). The test shows high intra- and inter-rater variability but only when strictly following guidelines of the materials, examination steps, and calculation of scores. The 6-minute walk test, timed 10-meter walk/run test, and supine-up time are commonly used timed functional tests that also sufficiently monitor changes in muscle function; however, they strongly depend on patient collaboration. Quantitative MRI is an objective and sensitive biomarker to detect subclinical changes, though the examination costs may be a reason for its limited use. In this study, a high correlation between all clinical assessments and quantitative MRI scans was found. The combinational use of these methods provides a better understanding about disease progression; however, longitudinal studies are needed to validate their reliability.
Abstract Objective To determine if patients with post‐polio syndrome (PPS) show spinal cord gray matter (SCGM) atrophy and to assess associations between SCGM atrophy, muscle strength and patient‐reported functional decline. Methods Twenty patients diagnosed with PPS (March of Dimes criteria) and 20 age‐ and sex‐matched healthy controls (HC) underwent 3T axial 2D‐rAMIRA magnetic resonance imaging at the intervertebral disc levels C2/C3–C6/C7, T9/T10 and the lumbar enlargement level ( T max ) (0.5 × 0.5 mm 2 in‐plane resolution). SCGM areas were segmented manually by two independent raters. Muscle strength, self‐reported fatigue, depression and pain measures were assessed. Results Post‐polio syndrome patients showed significantly and preferentially reduced SCGM areas at C2/C3 ( p = 0.048), C3/C4 ( p = 0.001), C4/C5 ( p < 0.001), C5/C6 ( p = 0.004) and T max ( p = 0.041) compared to HC. SCGM areas were significantly associated with muscle strength in corresponding myotomes even after adjustment for fatigue, pain and depression. SCGM area Tmax together with age and sex explained 68% of ankle dorsiflexion strength variance. No associations were found with age at or time since infection. Patients reporting PPS‐related decline in arm function showed significant cervical SCGM atrophy compared to stable patients adjusted for initial disease severity. Conclusions Patients with PPS show significant SCGM atrophy that correlates with muscle strength and is associated with PPS‐related functional decline. Our findings suggest a secondary neurodegenerative process underlying SCGM atrophy in PPS that is not explained by aging or residua of the initial infection alone. Confirmation by longitudinal studies is needed. The described imaging methodology is promising for developing novel imaging surrogates for SCGM diseases.
Little is known on longer term changes of spinal cord volume (SCV) in primary progressive multiple sclerosis (PPMS).Longitudinal evaluation of SCV loss in PPMS and its correlation to clinical outcomes, compared to relapse-onset multiple sclerosis (MS) subtypes.A total of 60 MS age-, sex- and disease duration-matched patients (12 PPMS, each 24 relapsing-remitting (RRMS) and secondary progressive MS (SPMS)) were analysed annually over 6 years of follow-up. The upper cervical SCV was measured on 3D T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) images using a semi-automatic software (CORDIAL), along with the total brain volume (TBV), brain T2 lesion volume (T2LV) and Expanded Disability Status Scale (EDSS).PPMS showed faster SCV loss over time than RRMS ( p < 0.01) and by trend ( p = 0.066) compared with SPMS. In contrast to relapse-onset MS, in PPMS SCV loss progressed independent of TBV and T2LV changes. Moreover, in PPMS, SCV was the only magnetic resonance imaging (MRI) measurement associated with EDSS increase over time ( p < 0.01), as opposed to RRMS and SPMS.SCV loss is a strong predictor of clinical outcomes in PPMS and has shown to be faster and independent of brain MRI metrics compared to relapse-onset MS.
Introduction Changes in resonance frequency caused by varying deoxyhemoglobin concentrations are the basis of blood oxygenation level dependent (BOLD) MR imaging (1). In functional brain studies mostly T2*-weighted sequences are used to detect BOLD signal levels. It has been shown that also balanced steady-state free precession (bSSFP) imaging sequences may be employed to measure deoxyhemoglobin concentration related frequency changes (2,3). Both methods base on the characteristic dependency of the bSSFP signal on the resonance frequency. Recent work demonstrates that diffusion in inhomogeneous magnetic fields affects the bSSFP signal amplitude depending on flip angle and repetition time (4). Due to this susceptibility sensitivity also the signal amplitude of an on-resonant balanced SSFP sequence depends on deoxyhemoglobin concentrations. The aim of this study was to verify the predicted dependency of measured balanced SSFP signal changes during a visual stimulation paradigm on flip angle and repetition time.
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