Muscle diffusion tensor imaging in facioscapulohumeral muscular dystrophy.

INTRODUCTION/AIMS: Muscle diffusion tensor imaging has not yet been explored in facioscapulohumeral muscular dystrophy (FSHD). We assessed diffusivity parameters in FSHD subjects compared with healthy controls (HCs), with regard to their ability to precede any fat replacement or edema. METHODS: Fat fraction (FF), water T2 (wT2), mean, radial, axial diffusivity (MD, RD, AD), and fractional anisotropy (FA) of thigh muscles were calculated in 10 FSHD subjects and 15 HCs. All parameters were compared between FSHD and controls, also exploring their gradient along the main axis of the muscle. Diffusivity parameters were tested in a subgroup analysis as predictors of disease involvement in muscle compartments with different degrees of FF and wT2 and were also correlated with clinical severity scores. RESULTS: We found that MD, RD, and AD were significantly lower in FSHD subjects than in controls, whereas we failed to find a difference for FA. In contrast, we found a significant positive correlation between FF and FA and a negative correlation between MD, RD, and AD and FF. No correlation was found with wT2. In our subgroup analysis we found that muscle compartments with no significant fat replacement or edema (FF < 10% and wT2 < 41 ms) showed a reduced AD and FA compared with controls. Less involved compartments showed different diffusivity parameters than more involved compartments. DISCUSSION: Our exploratory study was able to demonstrate diffusivity parameter abnormalities even in muscles with no significant fat replacement or edema. Larger cohorts are needed to confirm these preliminary findings.

Caveolinopathy: Clinical, histological, and muscle imaging features and follow-up in a multicenter retrospective cohort.

BACKGROUND AND PURPOSE: CAV3 gene mutations, mostly inherited as an autosomal dominant trait, cause various skeletal muscle diseases. Clinical presentations encompass proximal myopathy, distal myopathy, or isolated persistent high creatine kinase (CK) with a major overlapping phenotype. METHODS: Twenty-three patients with CAV3 symptomatic mutations, from 16 different families, were included in a retrospective cohort. Mean follow-up duration was 24.2 ± 15.0 years. Clinical and functional data were collected during the follow-up. The results of muscle imaging, electroneuromyography, muscle histopathology, immunohistochemistry, and caveolin-3 Western blot analysis were also compiled. RESULTS: Exercise intolerance was the most common phenotype (52%). Eighty percent of patients had calf hypertrophy, and only 65% of patients presented rippling. One patient presented initially with camptocormia. A walking aid was required in only two patients. Electroneuromyography was mostly normal. CK level was elevated in all patients. No patient had cardiac or respiratory impairment. Muscle imaging showed fatty involvement of semimembranosus, semitendinosus, rectus femoris, biceps brachialis, and spinal muscles. Almost all (87%) of the biopsies were abnormal but without any specific pattern. Whereas a quarter of patients had normal caveolin-3 immunohistochemistry results, Western blots disclosed a reduced amount of the protein. We report nine mutations, including four not previously described. No phenotype-genotype correlation was evidenced. CONCLUSIONS: Caveolinopathy has diverse clinical, muscle imaging, and histological presentations but often has limited functional impact. Mild forms of the disease, an atypical phenotype, and normal caveolin-3 immunostaining are pitfalls leading to misdiagnosis.

Ultrasound and MR muscle imaging in new onset idiopathic inflammatory myopathies at diagnosis and after treatment: a comparative pilot study.

OBJECTIVES: To prospectively compare ultrasound (US) and whole-body MRI for detection of muscle abnormalities compatible with idiopathic inflammatory myopathies (IIM). METHODS: Newly diagnosed IIM patients underwent US (14 muscles) and MRI (36 muscles) at diagnosis and after nine weeks monotherapy with intravenous immunoglobulin. Muscles were compatible with IIM when quantitative US echo-intensity (EI) z scores was ≥1.5, semi-quantitative US Heckmatt score was ≥2, qualitative US was abnormal, or when MRI showed oedema on T2-weighted images. At patient level, findings were classified as abnormal when quantitative US EI z scores was >1.5 (n = 3 muscles), >2.5 (n = 2 muscles) or >3.5 (n = 1 muscle), or if ≥3 muscles showed abnormalities as described above for the other diagnostic methods. RESULTS: At diagnosis, in 18 patients US of 252 muscles revealed abnormalities in 36 muscles (14%) with quantitative, in 153 (61%) with semi-quantitative and in 168 (67%) with qualitative analysis. MRI showed oedema in 476 out of 623 muscles (76%). Five patients (28%) reached abnormal classification with quantitative US, 16 (89%) with semi-quantitative and qualitative US, and all patients (100%) with MRI. Nine-week follow-up of 12 patients showed no change over time with quantitative US or MRI, and a decrease in abnormalities with semi-quantitative US (P <0.01), and qualitative US (P <0.01). CONCLUSION: At diagnosis, MRI was more sensitive than US to detect muscle abnormalities compatible with IIM. Semi-quantitative US and qualitative US detected abnormalities in the majority of the patients while evaluating fewer muscles than MRI and showed change over time after nine weeks of treatment.

5' UTR CGG repeat expansion in GIPC1 is associated with oculopharyngodistal myopathy.

Oculopharyngodistal myopathy is a late-onset degenerative muscle disorder characterized by ptosis and weakness of the facial, pharyngeal, and distal limb muscles. A recent report suggested a non-coding trinucleotide repeat expansion in LRP12 to be associated with the disease. Here we report a genetic study in a Chinese cohort of 41 patients with the clinical diagnosis of oculopharyngodistal myopathy (21 cases from seven families and 20 sporadic cases). In a large family with 12 affected individuals, combined haplotype and linkage analysis revealed a maximum two-point logarithm of the odds (LOD) score of 3.3 in chromosomal region chr19p13.11-p13.2 and narrowed the candidate region to an interval of 4.5 Mb. Using a comprehensive strategy combining whole-exome sequencing, long-read sequencing, repeat-primed polymerase chain reaction and GC-rich polymerase chain reaction, we identified an abnormal CGG repeat expansion in the 5' UTR of the GIPC1 gene that co-segregated with disease. Overall, the repeat expansion in GIPC1 was identified in 51.9% independent pedigrees (4/7 families and 10/20 sporadic cases), while the repeat expansion in LRP12 was only identified in one sporadic case (3.7%) in our cohort. The number of CGG repeats was <30 in controls but >60 in affected individuals. There was a slight correlation between repeat size and the age at onset. Both repeat expansion and retraction were observed during transmission but somatic instability was not evident. These results further support that non-coding CGG repeat expansion plays an essential role in the pathogenesis of oculopharyngodistal myopathy.

Screening Power of Short Tau Inversion Recovery Muscle Magnetic Resonance Imaging in Critical Illness Myoneuropathy and Guillain-Barre Syndrome in the Intensive Care Unit.

Introduction: Critical illness myoneuropathy (CIMN) or intensive care unit (ICU)-acquired weakness (AW) is a common cause of weakness in ICU patients. Guillain-Barre syndrome (GBS) is also a common cause of acute neurological weakness in the ICU. It is diagnosed by clinical features, nerve conduction studies (NCS), and muscle/nerve biopsies. Methods: The short tau inversion recovery (STIR) muscle magnetic resonance (MR) images of seven patients with suspected CIMN and seven GBS patients over a 5-year period from February 2015 till May 2020 were analyzed. Results: All seven patients with CIMN showed diffuse muscle edema, predominating in the lower limbs. Only one patient with GBS showed abnormal magnetic resonance imaging (MRI) changes (14%) and MRI was normal in 86%. The sensitivity of MRI to detect CIMN was 100%, whereas the specificity was 85.7%. Thus, the positive predictive value (PPV) of MRI in this situation was 87.5% and the negative predictive value (NPV) was 100%. Conclusion: Muscle STIR imaging may help to differentiate between CIMN and GBS. How to cite this article: Maramattom BV. Screening Power of Short Tau Inversion Recovery Muscle Magnetic Resonance Imaging in Critical Illness Myoneuropathy and Guillain-Barre Syndrome in the Intensive Care Unit. Indian J Crit Care Med 2022;26(2):204-209.

Expanding the clinical and genetic spectrum of pathogenic variants in STIM1.

INTRODUCTION/AIMS: Stromal interaction molecule 1 (STIM1) is a reticular Ca2+ sensor composed of a luminal and a cytosolic domain. Autosomal dominant mutations in STIM1 cause tubular aggregate myopathy and Stormorken syndrome or its variant York platelet syndrome. In this study we aimed to expand the features related to new variants in STIM1. METHODS: We performed a cross-sectional study of individuals harboring monoallelic STIM1 variants recruited at five tertiary centers involved in a study of inherited myopathies analyzed with a multigene-targeted panel. RESULTS: We identified seven individuals (age range, 26-57 years) harboring variants in STIM1, including five novel changes: three located in the EF-hand domain, one in the sterile α motif (SAM) domain, and one in the cytoplasmatic region of the protein. Functional evaluation of the pathogenic variants using a heterologous expression system and measuring store-operated calcium entry demonstrated their causative role and suggested a link of new variants with the clinical phenotype. Muscle contractures, found in three individuals, showed variability in body distribution and in the number of joints involved. Three patients showed cardiac and respiratory involvement. Short stature, hyposplenism, sensorineural hearing loss, hypothyroidism, and Gilbert syndrome were variably observed among the patients. Laboratory tests revealed hyperCKemia in six patients, thrombocytopenia in two patients, and hypocalcemia in one patient. Muscle biopsy showed the presence of tubular aggregates in three patients, type I fiber atrophy in one patient, and nonspecific myopathic changes in two patients. DISCUSSION: Our clinical, histological, and molecular data expand the genetic and clinical spectrum of STIM1-related diseases.

Whole-body muscle magnetic resonance imaging in patients with muscle symptoms: incidental findings and outcomes.

BACKGROUND AND PURPOSE: Whole-body muscle magnetic resonance imaging (MRI) has become widely used for diagnostic workup in patients with muscle diseases. The prevalence of incidental findings in diagnostic whole-body muscle MRI is unknown. Here, the prevalence and outcomes of incidentalomas in whole-body muscle MRI in a large cohort of patients with muscle symptoms were studied. METHODS: Two hundred and six patients who consulted at our neuromuscular clinic with muscle weakness and/or myalgia and/or increased serum creatine kinase and in whom a whole-body muscle MRI was performed between January 2016 and March 2020 were included. RESULTS: Whole-body muscle MRI revealed at least one incidentaloma in 132 patients (64.1%), with mean age at MRI examination 50.4 years (19-74 years). Most of the incidental findings were benign. However, diagnostic examinations were indicated in 16.3% of the incidentalomas, treatment was needed in 4.7% and, in retrospect, symptoms related to the incidental findings were identified in 14.3%. Three malignant (glioblastoma multiforme, renal cell carcinoma and hepato-splenomegaly related to a lymphoma) and one precancerous (low-grade appendiceal mucinous neoplasm) incidental findings were identified. In one patient an abdominal aortic aneurysm was detected and in another a large cerebral arteriovenous malformation. In 1.2% of the incidentalomas, i.e. periventricular white matter lesions (LAMA2 mutations) and fibrous dysplasia (ANO5 mutations), an indirect link with the muscle disease could be established. CONCLUSIONS: It is concluded that incidental findings in diagnostic whole-body muscle MRI in patients with muscle symptoms occur frequently. Most of them are benign, but in some timely detecting the incidentaloma leads to early treatment and can thus impact prognosis.

Disease duration and disability in dysfeRlinopathy can be described by muscle imaging using heatmaps and random forests.

INTRODUCTION: The manner in which imaging patterns change over the disease course and with increasing disability in dysferlinopathy is not fully understood. METHODS: Fibroadipose infiltration of 61 muscles was scored based on whole-body MRI of 33 patients with dysferlinopathy and represented in a heatmap. We trained random forests to predict disease duration, Motor Function Measure dimension 1 (MFM-D1), and modified Rankin scale (MRS) score based on muscle scoring and selected the most important muscle for predictions. RESULTS: The heatmap delineated positive and negative fingerprints in dysferlinopathy. Disease duration was related to infiltration of infraspinatus, teres major-minor, and supraspinatus muscles. MFM-D1 decreased with higher infiltration of teres major-minor, triceps, and sartorius. MRS related to infiltration of vastus medialis, gracilis, infraspinatus, and sartorius. DISCUSSION: Dysferlinopathy shows a recognizable muscle MRI pattern. Fibroadipose infiltration in specific muscles of the thigh and the upper limb appears to be an important marker for disease progression. Muscle Nerve 59:436-444, 2019.

A comparison of 3D ultrasound to MRI for the measurement and estimation of gastrocnemius muscle volume in adults and young people with and without cerebral palsy.

Muscle volume (MV) is an important parameter for understanding muscle morphology and adaptations to training, growth and pathology. In this study, we assessed the validity of freehand 3D ultrasound (3DUS) for measuring medial gastrocnemius MV in adults, typically developing (TD) children and children with cerebral palsy (CP). We also assessed the validity between our direct measures of MV and estimates derived from anatomical cross sectional area (ACSA) and muscle length (ML), using previously outlined methods. The medial gastrocnemius of all groups was scanned with 3DUS and MRI. Images from both methods were digitized to derive MV, ACSA and ML. Measured MV was compared between methods and compared to estimated MV derived from recently published algorithms. MV had a mean difference of -0.13% (standard error of estimate (SEE) = 2.23%, R2 = 0.99) between MRI and 3DUS and 19.82% (SEE = 4.73% and R2 = 0.99) and -3.11% (SEE = 6.55%, R2 = 0.99) mean differences between the measured and estimated MV from two methods of estimation. The 3DUS is a valid method for the measurement of MV in adults, TD children and those with CP. Estimation methods of MV may be useful in clinical practice, but require further replication on various populations and careful methodological consideration. Clin. Anat. 32:319-327, 2019. © 2018 Wiley Periodicals, Inc.

Muscle-ultrasound evaluation in healthy pediatric subjects: Age-related normative data.

INTRODUCTION: The muscle ultrasound examination (MUS) is a noninvasive and inexpensive technique for evaluating neuromyopathies. Standardized MUS normative data are incomplete in pediatric subjects. METHODS: We performed a MUS study with 120 healthy children (59 males; mean age, 10.44 years; age range, 2-16 years). We measured the width and the echogenicity bilaterally in the following muscles: biceps brachii and brachialis, brachioradialis, forearm-flexors, rectus femoris and vastus intermedius, tibialis anterior, extensor hallucis longus, lateral and medial gastrocnemius. RESULTS: The muscle thickness increased with age for all muscles. Confidence limits were set for each age group muscle width. Echogenicity increased with age only in some muscles. DISCUSSIONS: Our MUS study provides new data on physiological muscle structural changes in healthy children to address the limited available references in this age group. Muscle Nerve 58: 245-250, 2018.

MRI change metrics of facioscapulohumeral muscular dystrophy: Stir and T1.

INTRODUCTION: MRI evaluation in facioscapulohumeral muscular dystrophy (FSHD) demonstrates fatty replacement and inflammation/edema in muscle. Our previous work demonstrated short T1 inversion recovery (STIR)-hyperintense (STIR+) signal in muscle 2 years before fatty replacement. We evaluated leg muscle STIR changes and fatty replacement within 14 months. METHODS: FSHD subjects received 2 MRI scans of thigh and calf over a 6.9- to 13.8-month interval. Quality of life measures were collected. One Radiologist rated muscle changes on a semi-quantitative scale. RESULTS: Fifteen subjects completed longitudinal imaging. Four STIR + muscles and 3 STIR-normal (STIR-) muscles were rated as progressing to fatty tissue over the study period. DISCUSSION: STIR + muscles with confluent regions of fat at baseline increased more in fat, while STIR- muscles had increases in septal-fat over the study period. These changes may reflect two phases of FSHD, demonstrating MRI sensitivity is weighted toward gross pathological phases of the disease. Muscle Nerve 57: 905-912, 2018.

Clinical and imaging hallmarks of the MYH7-related myopathy with severe axial involvement.

INTRODUCTION: MYH7 gene mutations are related to a heterogeneous group of skeletal and cardiac myopathies. METHODS: We evaluated clinical and muscle MRI changes in patients with mutations in the rod domain of MYH7, including 1 with mosaicism and 3 with novel missense mutations. RESULTS: Patients presented in childhood with a distal and axial phenotype. Biopsy findings were variable. Half of the cases displaying some type of core pathology, including minicores and eccentric cores. Most patients demonstrated internal bands of infiltration ("inverted-collagen-VI sign") in multiple muscles, particularly the soleus, and prominent atrophy and fatty infiltration of the tongue and the paraspinal, gluteus minimus, sartorius, gracilis, tibialis anterior, and extensor digitorum longus muscles. DISCUSSION: Muscle imaging findings in patients with axial involvement provide significant clues permitting the distinction between MYH7-related myopathies and other axial myopathies such as those related to SEPN1 and LMNA genes. Muscle Nerve 58: 224-234, 2018.

Muscle involvement in systemic sclerosis: points to consider in clinical trials.

SSc is clinically and pathogenetically heterogeneous. Consensus standards for trial design and outcome measures are needed. International experts experienced in SSc clinical trial design and a researcher experienced in systematic literature review screened the PubMed and Cochrane Central Register of Controlled Trials in order to develop points to consider when planning a clinical trial for muscle involvement in SSc. The experts conclude that SSc-associated muscle involvement is heterogeneous and lacks a universally accepted gold-standard for measuring therapeutic response. Although outcome studies are currently limited by the inability to clearly distinguish active, reversible muscle inflammation from irreversible muscle damage and extramuscular organ involvement, strong consideration should be given to enrolling patients with a myopathy that features several elements of likely reversibility such as muscle weakness, biopsy-proven active inflammation, an MRI indicating muscle inflammation and a baseline serum creatinine kinase above three times the upper limit of normal to prevent floor effect. Randomized controlled trials are preferred, with a duration of at least 24 weeks. Outcome measures should include a combination of elements that are likely to be reversible, such as muscle weakness, biopsy-proven active inflammation, creatinine kinase/aldolase and a quality of life questionnaire. The individual measurements might require a short pre-study for further validation. A biological sample repository is recommended.

Application of intravoxel incoherent motion perfusion imaging to shoulder muscles after a lift-off test of varying duration.

Intravoxel incoherent motion (IVIM) MRI is a method to extract microvascular blood flow information out of diffusion-weighted images acquired at multiple b-values. We hypothesized that IVIM can identify the muscles selectively involved in a specific task, by measuring changes in activity-induced local muscular perfusion after exercise. We tested this hypothesis using a widely used clinical maneuver, the lift-off test, which is known to assess specifically the subscapularis muscle functional integrity. Twelve shoulders from six healthy male volunteers were imaged at 3 T, at rest, as well as after a lift-off test hold against resistance for 30 s, 1 and 2 min respectively, in three independent sessions. IVIM parameters, consisting of perfusion fraction (f), diffusion coefficient (D), pseudo-diffusion coefficient D* and blood flow-related fD*, were estimated within outlined muscles of the rotator cuff and the deltoid bundles. The mean values at rest and after the lift-off tests were compared in each muscle using a one-way ANOVA. A statistically significant increase in fD* was measured in the subscapularis, after a lift-off test of any duration, as well as in D. A fD* increase was the most marked (30 s, +103%; 1 min, +130%; 2 min, +156%) and was gradual with the duration of the test (in 10(-3) mm(2) /s: rest, 1.41 ± 0.50; 30 s, 2.86 ± 1.17; 1 min, 3.23 ± 1.22; 2 min, 3.60 ± 1.21). A significant increase in fD* and D was also visible in the posterior bundle of the deltoid. No significant change was consistently visible in the other investigated muscles of the rotator cuff and the other bundles of the deltoid. In conclusion, IVIM fD* allows the demonstration of a task-related microvascular perfusion increase after a specific task and suggests a direct relationship between microvascular perfusion and the duration of the effort. It is a promising method to investigate non-invasively skeletal muscle physiology and clinical perfusion-related muscular disorders.

Muscle-fat MRI: 1.5 Tesla and 3.0 Tesla versus histology.

INTRODUCTION: We evaluated muscle/fat fraction (MFF) accuracy and reliability measured with an MR imaging technique at 1.5 Tesla (T) and 3.0T scanner strengths, using biopsy as reference. METHODS: MRI was performed on muscle samples from pig and rabbit species (n = 8) at 1.5T and 3.0T. A chemical shift based 2-point Dixon method was used, collecting in-phase and out-of-phase data for fat/water of muscle samples. Values were compared with MFFs calculated from histology. RESULTS: No significant difference was found between 1.5T and 3.0T (P values = 0.41-0.96), or between histology and imaging (P = 0.83) for any muscle tested. CONCLUSIONS: RESULTS suggest that a 2-point Dixon fat/water separation MRI technique may provide reliable quantification of MFFs at varying field strengths across different animal species, and consistency was established with biopsy. The results set a foundation for larger scale investigation of quantifying muscle fat in neuromuscular disorders.

Hybrid ultrasound and single wavelength optoacoustic imaging reveals muscle degeneration in peripheral artery disease.

Peripheral arterial disease (PAD) leads to chronic vascular occlusion and results in end organ damage in critically perfused limbs. There are currently no clinical methods available to determine the muscular damage induced by chronic mal-perfusion. This monocentric prospective cross-sectional study investigated n = 193 adults, healthy to severe PAD, in order to quantify the degree of calf muscle degeneration caused by PAD using a non-invasive hybrid ultrasound and single wavelength optoacoustic imaging (US/SWL-OAI) approach. While US provides morphologic information, SWL-OAI visualizes the absorption of pulsed laser light and the resulting sound waves from molecules undergoing thermoelastic expansion. US/SWL-OAI was compared to multispectral data, clinical disease severity, angiographic findings, phantom experiments, and histological examinations from calf muscle biopsies. We were able to show that synergistic use of US/SWL-OAI is most likely to map clinical degeneration of the muscle and progressive PAD.

Distal myopathies.

The distal myopathies are a heterogeneous group of genetic disorders defined by a predominant distal weakness at onset or throughout the evolution of the disease and by pathological data supporting a myopathic process. The number of genes associated with distal myopathies continues to increase. Fourteen distinct distal myopathies are currently defined by their gene and causative mutations, compared to just five entities delineated on clinical grounds two decades ago. The known proteins affected in the distal myopathies are of many types and include a significant number of sarcomeric proteins. The useful indicators for clinicians to direct towards a correct molecular diagnosis are the mode of inheritance, the age at onset, the pattern of muscle involvement, the serum creatine kinase level and the muscle pathology findings. This review gives an overview of the clinical and genetic characteristics of the currently identified distal myopathies with emphasis on some recent findings.

Study 3: Anterior segment optical coherence tomography-guided surgical approach in slipped medial rectus muscle.

Purpose: To discuss the novel swept-source anterior segment optical coherence tomography (SS-ASOCT)-guided surgical approach in slipped medial rectus muscles. Methods: Prospectively (between February 2020 and July 2022), six patients with a clinical suspicion of slipped medial rectus muscle were recruited. After complete ophthalmic and orthoptic evaluation, the missing medial rectus muscle is screened using Anterior Segment Optical Coherence Tomography (ASOCT). In presence of a traceable muscle, its morphology, depth, and distance from a fixed anatomical landmarks were noted; in its absence, the status of other recti was noted. Intraoperatively, the features were confirmed and the intended intervention was performed. Results: The mean age of six patients was 25.66 ± 9.72 years, two with surgical trauma and four with penetrating trauma (66.66%). In five patients, the ASOCT traced the slipped medial rectus muscle successfully (83.33%); intraoperatively, the same was confirmed (within 1-2 millimeters) with favorable outcomes. ASOCT made a significant contribution in all subjects by reducing the number of interventions and muscle surgeries. Conclusions: In eyes with slipped medial rectus muscle, especially those which are within a finite distance from the angle can be traced using ASOCT. This approach impacts the outcomes in many ways.

Characteristics of the muscle involvement along the disease progression in a large cohort of oculopharyngodistal myopathy compared to oculopharyngeal muscular dystrophy.

BACKGROUND AND OBJECTIVES: Oculopharyngodistal myopathy (OPDM) is an autosomal dominant myopathy clinically characterized by distal muscle weakness. Even though the identification of four causative genes, LRP12, GIPC1, NOTCH2NLC and RILPL1, it is unclear whether the myopathy progressed similarly among OPDM subtypes. We aimed to establish diagnostic clues in muscle imaging of OPDM in comparison with clinicopathologically similar oculopharyngeal muscular dystrophy (OPMD). METHODS: Axial muscle CT and/or T1-weighted MRI data from 54 genetically confirmed patients with OPDM (OPDM_LRP12; n = 43, OPDM_GIPC1; n = 6, OPDM_NOTCH2NLC; n = 5) and 57 with OPMD were evaluated. We scored the degree of fat infiltration in each muscle by modified Mercuri score and performed hierarchical clustering analyses to classify the patients and infer the pattern of involvement on progression. RESULTS: All OPDM subtypes showed a similar pattern of distribution in the affected muscles; soleus and medial gastrocnemius involved in the early stage, followed by tibialis anterior and extensor digitorum longus. For differentiating OPDM and OPMD, severely affected gluteus medius/minimus and adductor magnus was indicative of OPMD. DISCUSSION: We identified a diagnostic muscle involvement pattern in OPDM reflecting its natural history. The results of this study will help in the appropriate intervention based on the diagnosis of OPDM, including its stage.

Five-year follow-up study on quantitative muscle magnetic resonance imaging in facioscapulohumeral muscular dystrophy: The link to clinical outcome.

BACKGROUND: It is unclear how changes in quantitative muscle magnetic resonance imaging (MRI) relate to changes in clinical outcome in facioscapulohumeral muscular dystrophy (FSHD), although this information is crucial for optimal use of MRI as imaging biomarker in trials. We therefore assessed muscle MRI and clinical outcome measures in a large longitudinal prospective cohort study. METHODS: All patients were assessed by MRI at baseline and at 5-year follow-up, employing 2pt-Dixon and turbo inversion recovery magnitude (TIRM) sequences, after which fat fraction and TIRM positivity of 19 leg muscles were determined bilaterally. The MRI compound score (CoS) was defined as the mean fat fraction of all muscles weighted for cross-sectional area. Clinical outcome measures included the Ricci-score, FSHD clinical score (FSHD-CS), MRC sumscore (MRC-SS), and motor-function-measure (MFM). RESULTS: We included 105 FSHD patients [mean age 54 ± 14 years, median Ricci-score 7 (range 0-10)]. The median change over 5 years' time in the MRI-CoS was 2.0% (range -4.6 to +12.1; P < 0.001). The median change over 5 years' time in clinical outcome measures was small in all measures, with z-scores ranging from 5.0 to 7.2 (P < 0.001). The change in MRI-CoS correlated with change in FSHD-CS and Ricci-score (ρ = 0.25, respectively; ρ = 0.23, P < 0.05). The largest median increase in MRI-CoS was seen in baseline subgroups with an MRI-CoS 20-40% (6.1%), with ≥2 TIRM positive muscles (3.5%) or with an FSHD-CS 5-10 (3.1%). CONCLUSIONS: This 5-year study showed significant changes in MRI and clinical outcome measures and a significant correlation between changes in MRI-CoS and changes in clinical outcome measures. In addition, we identified subgroups of patients that are most prone to radiological disease progression. This knowledge further establishes quantitative MRI parameters as prognostic biomarkers in FSHD and as efficacy biomarkers in upcoming clinical trials.