Lower Limb Muscle MRI Research Articles

Development of an initial training and evaluation programme for manual lower limb muscle MRI segmentation

BackgroundMagnetic resonance imaging (MRI) quantification of intramuscular fat accumulation is a responsive biomarker in neuromuscular diseases. Despite emergence of automated methods, manual muscle segmentation remains an essential foundation. We aimed to develop a training programme for new observers to demonstrate competence in lower limb muscle segmentation and establish reliability benchmarks for future human observers and machine learning segmentation packages.MethodsThe learning phase of the training programme comprised a training manual, direct instruction, and eight lower limb MRI scans with reference standard large and small regions of interest (ROIs). The assessment phase used test–retest scans from two patients and two healthy controls. Interscan and interobserver reliability metrics were calculated to identify underperforming outliers and to determine competency benchmarks.ResultsThree experienced observers undertook the assessment phase, whilst eight new observers completed the full training programme. Two of the new observers were identified as underperforming outliers, relating to variation in size or consistency of segmentations; six had interscan and interobserver reliability equivalent to those of experienced observers. The calculated benchmark for the Sørensen-Dice similarity coefficient between observers was greater than 0.87 and 0.92 for individual thigh and calf muscles, respectively. Interscan and interobserver reliability were significantly higher for large than small ROIs (all p < 0.001).ConclusionsWe developed, implemented, and analysed the first formal training programme for manual lower limb muscle segmentation. Large ROI showed superior reliability to small ROI for fat fraction assessment.Relevance statementObservers competent in lower limb muscle segmentation are critical to application of quantitative muscle MRI biomarkers in neuromuscular diseases. This study has established competency benchmarks for future human observers or automated segmentation methods.Key points• Observers competent in muscle segmentation are critical for quantitative muscle MRI biomarkers.• A training programme for muscle segmentation was undertaken by eight new observers.• We established competency benchmarks for future human observers or automated segmentation methods.Graphical

Lower limb muscle MRI fat fraction is a responsive outcome measure in CMT X1, 1B and 2A.

With potential therapies for many forms of Charcot-Marie-Tooth disease (CMT), responsive outcome measures are urgently needed for clinical trials. Quantitative lower limb MRI demonstrated progressive calf intramuscular fat accumulation in the commonest form, CMT1A with large responsiveness. In this study, we evaluated the responsiveness and validity in the three other common forms, due to variants in GJB1 (CMTX1), MPZ (CMT1B) and MFN2 (CMT2A). 22 CMTX1, 21 CMT1B and 21 CMT2A patients and matched controls were assessed at a 1-year interval. Intramuscular fat fraction (FF) was evaluated using three-point Dixon MRI at thigh and calf level along with clinical measures including CMT examination score, clinical strength assessment, CMT-HI and plasma neurofilament light chain. All patient groups had elevated muscle fat fraction at thigh and calf levels, with highest thigh FF and atrophy in CMT2A. There was moderate correlation between calf muscle FF and clinical measures (CMTESv2 rho = 0.405; p = 0.001, ankle MRC strength rho = -0.481; p < 0.001). Significant annualised progression in calf muscle FF was seen in all patient groups (CMTX1 2.0 ± 2.0%, p < 0.001, CMT1B 1.6 ± 2.1% p = 0.004 and CMT2A 1.6 ± 2.1% p = 0.002). Greatest increase was seen in patients with 10-70% FF at baseline (calf 2.7 ± 2.3%, p < 0.0001 and thigh 1.7 ± 2.1%, p = 0.01). Our results confirm that calf muscle FF is highly responsive over 12 months in three additional common forms of CMT which together with CMT1A account for 90% of genetically confirmed cases. Calf muscle MRI FF should be a valuable outcome measure in upcoming CMT clinical trials.

Muscle MRI characteristic pattern for late-onset TK2 deficiency diagnosis

Background and objectiveTK2 deficiency (TK2d) is a rare mitochondrial disorder that manifests predominantly as a progressive myopathy with a broad spectrum of severity and age of onset. The rate of progression is variable, and the prognosis is poor due to early and severe respiratory involvement. Early and accurate diagnosis is particularly important since a specific treatment is under development. This study aims to evaluate the diagnostic value of lower limb muscle MRI in adult patients with TK2d.MethodsWe studied a cohort of 45 genetically confirmed patients with mitochondrial myopathy (16 with mutations in TK2, 9 with mutations in other nuclear genes involved in mitochondrial DNA [mtDNA] synthesis or maintenance, 10 with single mtDNA deletions, and 10 with point mtDNA mutations) to analyze the imaging pattern of fat replacement in lower limb muscles. We compared the identified pattern in patients with TK2d with the MRI pattern of other non-mitochondrial genetic myopathies that share similar clinical characteristics.ResultsWe found a consistent lower limb muscle MRI pattern in patients with TK2d characterized by involvement of the gluteus maximus, gastrocnemius medialis, and sartorius muscles. The identified pattern in TK2 patients differs from the known radiological involvement of other resembling muscle dystrophies that share clinical features.ConclusionsBy analyzing the largest cohort of muscle MRI from patients with mitochondrial myopathies studied to date, we identified a characteristic and specific radiological pattern of muscle involvement in patients with TK2d that could be useful to speed up its diagnosis.

Benign monomelic amyotrophy of lower limb in a cohort of chinese patients.

BackgroundBenign monomelic amyotrophy of lower limb (BMALL) is a neurogenic syndrome representing an unclear field. Further studies might be helpful to elucidate uncertainties regarding causation, outcome, and the risk of progression to amyotrophic lateral sclerosis (ALS).MethodsAccording to the inclusion and exclusion criteria, 37 patients with BMALL were retrospectively collected in three neuromuscular centers from January 2012 to October 2018. The detailed medical data were summarized. Multiple laboratory tests were examined. Routine electrophysiological examinations, muscle MRI of lower limbs, and muscle biopsy were conducted.ResultsThe cohort included 24 male and 13 female cases with median age of onset 47 years. Muscle MRI revealed that the distribution of involved muscles matched with the extent of fat infiltration, so the pattern muscle atrophy can be divided into the following four types: six patients with thigh atrophy (type I), 14 patients with leg atrophy (type II); 10 patients with disproportionate atrophy in both thigh and leg (type III); and seven patients with well‐proportionate atrophy in both thigh and leg (type IV). Electrophysiological findings showed neurogenic pattern, spontaneous activity, and abnormal H reflex, which suggested a disorder of spinal anterior horn cell in the patients with types I‐III. However, no electrophysiological abnormalities were found in the patients with type IV. Muscle pathology varied from almost normal pattern to advanced neurogenic pattern in nine biopsied patients. Follow‐up showed that two patients with type II developed to ALS four years later, and all patients with type IV were in stable condition without any complaints.ConclusionMuscle MRI was useful to exactly localize the distribution of involved muscles in BMALL patients. The distribution of atrophic muscles can be roughly divided into four types based on the MRI features. The classification of distributing types might be as an indicator for the prognosis of BMALL.

P.101Defining the phenotype of Andersen-Tawil syndrome: the largest reported series

Anderson Tawil syndrome (ATS) is a rare channelopathy traditionally characterised by periodic paralysis, cardiac arrhythmias and dysmorphic features. Mutations in the KCJN2 gene have been associated with ATS. Accurate and early diagnosis is important in facilitating treatment of episodic paralysis and preventing cardiac death. We aim to fully characterise the phenotype in a carefully stratified cohort including cognitive deficits and cardiac risk. 62 patients were identified with KCJN2 mutations. Comprehensive clinical information was collected for these patients. Cardiac symptoms were prominent - two thirds had daily or very frequent palpitations. 12.9% reported syncope. Serious cardiac complications requiring implantable cardiac defibrillator (ICD) occurred in 8.06% patients. 39% reported pain which has previously not been appreciated as part of ATS. Interestingly, 4 patients had fasciculations. 25% of patients had no decrement on Long exercise tests (LET) and 6.25% had less than 40% decrement despite having episodic weakness. Lower limb muscle MRI was abnormal in 6 patients. Excess sleepiness was reported, for which the aetiology requires further elucidation. While dysmorphic features exist, these can be subtle. Short stature is not ubiquitous. Heterogeneity within families was commonly seen. Evidently, the phenotypic spectrum of ATS is broader than currently appreciated. This is important to recognise in order to optimise accurate diagnosis as well as to develop screening and treatment regimens.

P.235Clinico-pathological characterisation of CACNA1S related congenital myopathy in children

Mutations in the CACNA1S gene were recently identified as a new cause of congenital myopathy (CM). To date only a few cases have been described, with limited phenotypic data. We report the clinical, pathological and radiological phenotype in five children with genetically confirmed CACNA1S-CM. →Patients were referred to our national highly specialised service for CM at The Dubowitz Neuromuscular Centre, UK. We conducted retrospective case note analysis. Two patients had recessive inheritance and three autosomal dominant. →Four of five patients (age range 7-18 years) had severe neonatal presentation with foetal akinesia, weakness, hypotonia, contractures, feeding difficulties and respiratory compromise. The 5th patient presented with motor delay in infancy. All five patients had proximal predominant, bulbar and facial weakness but showed spontaneous improvement over time. Ophthalmoplegia was noted in three. Two patients remain non-ambulant. Two developed scoliosis. Two are on nocturnal non-invasive ventilation initiated at age of 5 months and 7 years. All apart from one required nasogastric/gastrostomy feeding up until 2-5 years of age, but all were able to feed orally from age 5 years. One patient had clear history of periodic weakness well responding to Acetazolamide. Two children reported fatigue and limited endurance but no abnormalities of neuromuscular transmission were detected. All muscle biopsies showed fibre size variation and marked slow fibre predominance. Additional findings included mild central nucleation, few central cores and focally accentuated pseudo-dystrophic changes. Three out of the five patients had abnormal lower limb muscle MRI but with no specific muscle pattern. →CACNA1S related myopathy is a recently described form of congenital myopathy and should be considered in cases of undiagnosed dominant and recessive congenital myopathies with phenotypical features presented above.

Skeletal muscle MRI of lower limbs in patients with facioscapulohumeral dystrophy

Objective: To investigate MRI features of lower limbs in patients with facioscapulohumeral dystrophy(FSHD). Methods: The clinical manifestations, myopathological findings and MRI images of 5 FSHD patients were studied retrospectively from June 2016 to December 2017 at Department of Neurology, Henan Provincial People's Hospital, 3 of which had a family history. Analysis of T(1)WI images enabled us to describe muscle fatty infiltration and STIR images to describe muscle edema. Each muscle was scored according to its fatty degeneration (fat replacement score range from 0-4). Results: The 5 patients were all asymmetrically involved. At the thigh level, the hamstrings were more affected than anterior muscles in 4 patients, and anterior muscles were more affected than hamstrings in only 1 patient. The most affected thigh muscles were usually the adductor magnus, semimembranosus, semitendinosus, femoral biceps long head and vastus medialis muscles (average fat replacement score of each muscle was more than 3). The calves were less affected than thighs.The average fat replacement score of the calf muscles was 1.0 for soleus, 0.9 for medial gastrocnemius, 0.8 for tibialis anterior, and 0.4 for lateral gastrocnemius. There was no fatty infiltration in peroneus and tibialis posterior. 4 out of 5 patients had edema in the lower limb muscles. Conclusion: Asymmetric involvement is a definitely helpful clue suggesting FSHD, and edema is a common phenomenon. At the thigh level, no unique imaging pattern can be highlighted in all the FSHD patients, overall, the hamstring, adductor magnus and vastus medialis are usually the most severely affected muscles. The calf muscles are less affected than the thigh muscles or spared. Soleus, medial gastrocnemius, and tibialis anterior are preferentially involved at the calf level.

Recessive PYROXD1 mutations cause adult-onset limb-girdle-type muscular dystrophy

ObjectiveTo describe adult-onset limb-girdle-type muscular dystrophy caused by biallelic variants in the PYROXD1 gene, which has been recently linked to early-onset congenital myofibrillar myopathy.MethodsWhole exome sequencing was performed for adult-onset neuromuscular disease patients with no molecular diagnosis. Patients with PYROXD1 variants underwent clinical characterization, lower limb muscle MRI, muscle biopsy and spirometry. A yeast complementation assay was used to determine the biochemical consequences of the genetic variants.ResultsWe identified four patients with biallelic PYROXD1 variants. Three patients, who had symptom onset in their 20s or 30s, were homozygous for the previously described p.Asn155Ser. The fourth patient, with symptom onset at age 49, was compound heterozygous for p.Asn155Ser variant and previously unknown p.Tyr354Cys. All patients presented with a LGMD-type phenotype of symmetric muscle weakness and wasting. Symptoms started in proximal muscles of the lower limbs, and progressed slowly to involve also upper limbs in a proximal-predominant fashion. All patients remained ambulant past the age of 60. They had restrictive lung disease but no cardiac impairment. Muscle MRI showed strong involvement of anterolateral thigh muscles. Muscle biopsy displayed chronic myopathic changes. Yeast complementation assay demonstrated the p.Tyr354Cys mutation to impair PYROXD1 oxidoreductase ability.ConclusionPYROXD1 variants can cause an adult-onset slowly progressive LGMD-type phenotype.

LIMB-GIRDLE MUSCULAR DYSTROPHY I: P.11Clinical outcome study in dysferlinopathy: random forest approach to assess the relationship between baseline muscle MRI and longitudinal functional outcome measures

The Jain clinical outcome study (COS) is an international study of 203 adults with dysferlinopathy in 8 countries. Patients undergo six visits over three years, during which physiotherapy and medical assessments as well as muscle MRI were performed. Our aim is to analyse baseline muscle pathology by MRI in a large cohort of dysferlinopathy patients and to examine the relationship between baseline muscle MRI findings and the results of longitudinal functional outcome measures over one year. We aim to identify which muscles may predict a rapid decline over one year. Lower limb muscle MRI has been performed in 182 patients with a confirmed diagnosis of dysferlinopathy in 14 different centres, using 1.5T or 3T scanners from different manufacturers (Philips, General Electrics, Siemens). 74 patients also underwent upper limb muscle MRI at baseline. Muscles were scored on axial T1-weighted sequences with the semi quantitative Mercuri visual scale modified by fisher. Physiotherapy assessments included muscle strength (manual muscle testing; hand held dynamometry) and functional ability evaluations (adapted north star, brooke test, timed tests) and patient reported outcome measure (ACTIVLIM). We will present the outcome of the analysis between semi-quantitative MRI at baseline and disease progression over one year as measured by the north star assessment for dysferlinopathy, the 10 metre walk and the ACTIVLIM using the Random Forest approach (package ``random forest SRC'' in R). Random-forest studies will be used to identify whether combinations of muscle involvement at baseline can predict a change of more than 10% in muscle function tests at a one year visit. Muscle MRI is useful for the diagnosis of patients with muscle disorders, but also to identify patients at risk of having a quick progression of their symptoms.

Characteristics of muscle MRI of lower limbs in patients with GNE myopathy

Objective To summarize the characteristic of muscle MRI of lower limbs in patients with GNE myopathy and to explore the correlation between the fatty degenerative score of muscle MRI and clinical phenotype. Methods This was a prospective study. Seventeen patients with genetically confirmed GNE myopathy, having lower limb muscle MRI test and completed clinical and laboratory data.The degree of fatty degeneration in 18 muscles of lower limbs in each patient was grading. According to the GM-W score, these patients were divided into two groups. GM-W score ≤ 3 were divided into mild group (n=8) and GM-W score≥ 4 were divided into severe group(n=9). Kruskal-Wallis test was used to compare the fatty degenerative score in different muscles of the thigh and the calf level;Mann-Whitney U test was used to compare score of the same muscle between mild and severe group;Spearman rank correlation test was used to analysis the relationship between fatty degenerative score and the course of disease (year), GM-W score, creatinine kinase (IU/L), respectively. Results At the thigh level, the most severely involved muscle of GNE myopathy was semi-tendinosusand adductor, followed by semi-membranous, biceps femoris and gracilis. There was no statistically significant difference in the fatty degenerative score of the above-mentioned muscles (P=0.058). At the calf level, the most severely involved muscle was medial of soleus which score was 4.0(3.0, 4.0), followed by tibialis anterior,extensor digitorum longus and lateral of soleus. There was no significant difference of the above (P=0.259).The fatty degenerative score showed difference between the mild and severe group at sartorius and adductor (P<0.05).At the calf level, the fatty degenerative score in peroneus longus, medial of soleus, lateral of soleus, medial of gastrocnemius and lateral of gastrocnemius showed difference between groups(P<0.05).The total score of fatty degenerative of Lower limb muscles was positively correlated with GM-W score(r=0.730, P<0.05). There were positive correlations between the score of fatty degenerative of the sartorius, peroneal longus, lateral of soleus, medial of gastrocnemius, lateral of gastrocnemius and the GM-W scores(r=0.630, 0.845, 0.569, 0.591, 0.640, 0.659, P<0.05). The total score of fatty degenerative of Lower limb muscles was not correlated with the level of creatine kinase(P=0.582), course of disease(P=0.601) and age of onset(P=0.850). Conclusions GNE myopathy in the thigh level within the adductor muscle and posterior muscle involvement, calf level to the tibial anterior muscle early involvement. The total score of fatty degenerative of lower limb muscles is positively correlated with GM-W score, but not correlated with the level of creatine kinase, course of disease and age of onset. Key words: Magnetic resonance imaging; Comparative study; GNE myopathy

Muscle MR pattern of partial Laminin α2 deficient patients and its role in diagnostic algorithms

Objective: Laminin α2 (merosin) deficient muscular dystrophy (MDC1A) is one of the most frequent types of congenital muscular dystrophy (CMD) and it is due to LAMA2 gene mutations. The suspicion of classical phenotype with complete merosin deficiency is easy, based in a homogeneous and typical severe phenotype including floppy baby, hyperCKemia, not acquisition of walking ability and very striking abnormal white matter changes in brain MRI. Merosin deficiency is complete in muscle. Differential diagnosis may be difficult in partial deficiency patients who present later and with milder symptoms, often overlapping dystroglycanopathies and limb girdle muscular dystrophies. Methods and results: The authors present the cohort of pelvic girdle and lower limb muscle MRI findings from 7 patients with partial Laminin α2 deficiency, most of them ambulatory. The most affected muscles were gluteus medium and minimum, adductor magnus, soleus and gastrocnemios muscles. Relatively spared muscles were gracilis and tibialis posterior muscles. The pattern was similar for all patients except one. There was one interesting feature: the rim of peripheral involvement between vastus lateralis and intermedius muscles, and between gastrocnemius and soleus muscles (COL6 –like sign). Conclusion: The results of our cohort showed that muscle MRI of Laminin α2 deficient patients has a homogeneous and recognizable pattern, although sharing similar features in the lower limbs to another CMD with extracellular matrix abnormalities (collagen 6 –related myopathies such as Ullrich CMD or Bethlem myopathy). Further studies in whole-body MRI will be useful to search for selective or more specific involvement of merosin deficient patients. The results support the recommendation to use muscle MRI in diagnostic algorithm of early onset myopathies. This work was supported by COST ACTION project BM 1304.

Decreased Aerobic Capacity inANO5-Muscular Dystrophy.

Anoctaminopathies are muscle diseases caused by recessive mutations in the ANO5 gene. The effects of anoctaminopathy on oxidative capacity have not previously been studied in a controlled setting. To characterize oxidative capacity in a clinically and genetically well-defined series of patients with anoctaminopathy. We sequenced the ANO5 gene in 111 Finnish patients with suspected LGMD2. Patients with positive findings underwent close clinical examination, including electromyography, muscle MRI, and, in selected cases, muscle biopsy. Oxidative capacity was analyzed using spiroergometry and compared to age-matched healthy controls. We characterized 12 newly identified and 2 previously identified patients with ANO5 mutations from 11 families. Our material was genetically homogeneous with most patients homozygous for the Finnish founder variant c.2272C>T (p.Arg758Cys). In one family, we found a novel p.Met470Arg variant compound heterozygous with p.Arg758Cys. Lower limb muscle MRI revealed progressive fatty degeneration of specific posterior compartment muscles. Patients' spiroergometric profiles showed that anoctaminopathy significantly impaired oxidative capacity with increasing ventilation. Our findings support earlier reports that anoctaminopathy progresses slowly and demonstrate that the disease impairs the capacity for aerobic exercise.

Pilot phenotype and natural history study of hereditary neuropathies caused by mutations in the HSPB1 gene

Mutations in HSPB1 are one of the commonest causes of distal Hereditary Motor Neuropathy (dHMN). Transgenic mouse models of the disease have identified HDAC6 inhibitors as promising treatments for the condition paving the way for human trials. A detailed phenotype and natural history study of HSPB1 neuropathy is therefore required in order to inform the duration and outcome measures of any future trials. Clinical and neurophysiological data and lower limb muscle MRI were collected both prospectively and retrospectively from patients with mutations in HSPB1. The natural history was assessed by recording the weighted Charcot–Marie–Tooth Examination Score (CMTES) at annual intervals in a subset of patients. 20 patients from 14 families were recruited into the study. The average age of onset was in the 4th decade. Patients presented with a length dependent neuropathy but with early ankle plantar flexion weakness. Neurophysiology confirmed a motor neuropathy but also showed sensory nerve involvement in most patients. Cross sectional muscle MRI revealed soleus and medial gastrocnemius fat infiltration as an early signature of mutant HSPB1 disease. In this study neither semi quantitative muscle MRI, the CMTES nor neurophysiology were able to detect disease progression in HSPB1 neuropathy over 1 or 2 years. Further studies are therefore required to identify a suitable biomarker before clinical trials in HSPB1 neuropathy can be undertaken.

Calf hypertrophy and gastrocnemius MRI short tau inversion recovery (STIR) hyperintensity in a patient with asymptomatic hyperCKemia caused by caveolin-3 gene mutation

We present a 16-year-old man with asymptomatic hyperCKemia fluctuating between 900 and 2400 IU/L. His parents and his younger sister (13-year-old) were asymptomatic. Clinical examination showed no abnormalities apart of bilateral calf hypertrophy (calf circumference of 41 cm in both legs) (Fig. 1) [1]. Electromyography showed no abnormalities at rest, and small amplitude, brief, polyphasic action potentials, and early recruitment after muscle contraction in the proximal limb muscles. Lower limb muscle MRI (performed in the absence of unusual physical activity, exercise, or trauma preceding the MRI) confirmed calf hypertrophy and showed STIR hyperintensities in the bilateral medial gastrocnemius muscles (predominant on the right side) in the absence of abnormalities on T1-weighted imaging (Fig. 1), while the thighs did not show any abnormalities. Muscle biopsy of the right-sided medial gastrocnemius muscle showed myopathic changes (pathological fibre size variation, atrophic fibres, necrosis-regeneration, increased endomysial connective tissue, nuclear centralisation, core-like lesions) and immunohistochemical analyses showed normal expression of dystrophin, sarcoglycanes, dystroglycanes, merosin and nearly complete absence of caveolin-3 expression

Skeletal muscle MRI of lower limbs in patients with Dysferlinopathy

Objective To investigate muscle MRI characteristics of lower limbs in Chinese patients with dysferlinopathy. Methods Detailed clinical information of 42 patients with dysferlinopathy confirmed by Western blot or DYSF genetic test were studied retrospectively, including age, course, serum creatinine kinase (CK) and modified Gardner-Medwin and Walto score, and T1WI, STIR image. Each muscle was scored according to its fatty degeneration evaluated on T1WI (fat replacement score). The patients were divided into 3 groups: Miyoshi myopathy (MM), limb girdle muscle dystrophy 2B (LGMD 2B) and preclinical stage (asymptomatic hyperCKemia or exercise intolerance). The data including the scores of each muscle between MM and LGMD 2B were compared by ANOVA analysis and Chi square test. The relationship of fatty replacement score with course and GM-W score was analyzed by Spearman rank correlation analysis. Results Thirty nine patients underwent thigh MR scanning and 36 patients underwent leg MR scanning. At the thigh level, there is no specificity that the fatty replacement was found in both the anterior and posterior parts while the rectus femoris, sartorius and gracilis were rarely involved. At the leg level, the most severely involved muscle was the soleus, followed by gastrocnemius. It formed a sandwich-like pattern that the anterior part (anterior and posterior tibial muscle and peroneus longus muscle) and the posterior part(medial and lateral gastrocnemius) were less involved than the middle part (soleus). Of 42 patients, 14 cases were MM, and 24 were LGMD 2B. The fat replacement score of each muscle between two groups showed no significant differences (F=0.066 to 3.907,P all>0.05) except for the adductor muscle (F=5.239, P=0.028), semimembranosus (F=6.703, P=0.014) and semitendinosus (F=7.689, P=0.009). Of 4 pre-symptomatic cases, 3 showed edema of posterior part of leg on STIR, especially soleus. In all patients, the fat replacement score correlated positively with course (rs=0.732, P=0.000) and GM-W score (rs=0.485, P=0.001). Conclusions The MRI of Chinese patient with dysferlinopathy was characterized by the milder involvement of rectus femoris, sartorius and gracilis muscle in the thigh and a sandwich-like pattern in the leg, which is helpful for differential diagnosis of inflammatory Myopathy versus other types of muscular dystrophy. Key words: Muscular Diseases; Magnetic resonance imaging; Dysferlinopathy

Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy.

To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene. Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy predominantly affecting the lower limbs were identified at participating neuromuscular centers and referred for targeted sequencing of DYNC1H1. We report a cohort of 30 cases of SMA-LED from 16 families, carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel mutations. These patients are characterized by congenital or childhood-onset lower limb wasting and weakness frequently associated with cognitive impairment. The clinical severity is variable, ranging from generalized arthrogryposis and inability to ambulate to exclusive and mild lower limb weakness. In many individuals with cognitive impairment (9/30 had cognitive impairment) who underwent brain MRI, there was an underlying structural malformation resulting in polymicrogyric appearance. The lower limb muscle MRI shows a distinctive pattern suggestive of denervation characterized by sparing and relative hypertrophy of the adductor longus and semitendinosus muscles at the thigh level, and diffuse involvement with relative sparing of the anterior-medial muscles at the calf level. Proximal muscle histopathology did not always show classic neurogenic features. Our report expands the clinical spectrum of DYNC1H1-related SMA-LED to include generalized arthrogryposis. In addition, we report that the neurogenic peripheral pathology and the CNS neuronal migration defects are often associated, reinforcing the importance of DYNC1H1 in both central and peripheral neuronal functions.

P39 Quantitative lower limb muscle MRI in CMT1A demonstrates length-dependent fatty infiltration

P39 Quantitative lower limb muscle MRI in CMT1A demonstrates length-dependent fatty infiltration

Evolution of Charcot–Marie–Tooth disease type 1A duplication: a 2-year clinico-electrophysiological and lower-limb muscle MRI longitudinal study

The objective of this study was to analyze Charcot-Marie-Tooth disease type 1A (CMT1A) evolution. We conducted a 2-year longitudinal study in 14 CMT1A patients and 14 age- and sex-matched controls. In the patients, we performed neurological examination with hand-held dynamometry, electrophysiology, and lower-limb muscle MRI, both at baseline and 2 years later, while controls were examined at baseline only. Patients' ages ranged from 12 to 51 years. Outstanding manifestations on initial evaluation included pes cavus, areflexia, lower-limb weakness, and foot hypopallesthesia. In evaluating muscle power, good correlation was observed between manual testing and dynamometry. Compared to controls, Lunge, 10-Meter-Walking, and 9-Hole-Peg tests were impaired. Their CMT neuropathy score and functional disability scale showed that patients exhibited mild phenotype and at most slight walking difficulty. Electrophysiology revealed marked nerve conduction slowing and variable compound muscle action potential amplitude reduction. On lower-limb muscle MRI, there was distally accentuated fatty infiltration accompanied by edema in calf muscles. All these clinico-electrophysiological and imaging findings remained almost unaltered during monitoring. Using multivariate analysis, no significant predictors of progression associated to the disease were obtained. We conclude that in the 2-year period of study, CMT1A patients showed mild progression with good concordance between clinico-electrophysiological and imaging findings.

Muscle MRI in Becker muscular dystrophy

The aim of this study was to evaluate pelvis and lower limb muscle MRI scans of 46 patients affected by Becker muscular dystrophy (BMD), subdivided according to disease severity, ranging from clinically asymptomatic patients to patients who had lost ambulation. We found a distinct pattern on muscle imaging characterized by prominent involvement of the gluteus maximus and medius, adductor magnus, biceps femoris long head, semimembranosus and vasti. This pattern was consistent in all the 25 symptomatic patients. Milder changes in the same muscles were found in 13 of the 21 asymptomatic cases. The other 8 asymptomatic patients had a normal scan. The severity of muscle involvement was significantly correlated with age. Our results suggest that a distinct pattern of muscle involvement can be detected in BMD. The early identification of muscle changes in a proportion of asymptomatic patients may be useful as an additional tool in the diagnostic workup.

P2.38 Lower limb muscle MRI in a large cohort of FSHD patients

P2.38 Lower limb muscle MRI in a large cohort of FSHD patients