Contribution of muscle MRI for diagnosis of myopathy.

Inherited myopathies are a group of disease, which, although distinct from a genetic and prognostic point of view, can lead to non-specific clinical pictures due to phenotypic overlap. Acquired immuno-mediated myopathies may also pose the problem of clinically accurate etiological orientation. The assessment of fatty infiltration and pathological increase in water volume of the muscle contingent on whole-body muscle MRI is becoming increasingly important in aiding the initial diagnosis of inherited and acquired myopathies. MRI helps orientating the clinical diagnostic hypotheses thanks to the patterns of muscle involved (more or less specific according to the entities), which led to the development of decision-making algorithms proposed in the literature. The aim of this article is to specify the proper MRI protocol for the evaluation of myopathies and the basis of the interpretation and to provide a summary of the most frequently inherited and acquired myopathies described in the literature.

Nusinersen treatment in adults with severe spinal muscular atrophy: A real-life retrospective observational cohort study.

BACKGROUND AND OBJECTIVES: Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease due to homozygous loss-of-function of the survival motor neuron gene SMN1 with absence of the functional SMN protein. Nusinersen, a costly intrathecally administered drug approved in 2017 in Europe, induces alternative splicing of the SMN2 gene, which then produces functional SMN protein, whose amount generally increases with the number of SMN2 gene copies. METHODS: We retrospectively collected data from consecutive wheelchair-bound adults with SMA managed at a single center in 2018-2020. The following were collected at each injection, on days 1, 14, 28, 63, 183, and 303: 32-item Motor Function Measurement (MFM) total score and D2 and D3 subscores; the Canadian Occupational Performance Measure (COPM) performance and satisfaction scores; and lung function tests. The patients were divided into two groups based on whether their MFM total score was

Bariatric surgery related proximal myopathy: A partially reversible complication.

Deficiency neuropathies and rhabdomyolysis have previously been reported after bariatric surgery (BS) but never myopathies. We report cases of five patients with morbid obesity who developed within 2 to 4 months of a BS, proximal myopathy following significant and rapid weight loss worsened by postoperative gastrointestinal complications. Muscle weakness concerned lower limbs in particular in quadriceps and less frequently in upper limbs and diaphragm, sometimes mimicked a Guillain-Barré syndrome. Muscle biopsy performed in 1 patient, revealed selective atrophy of type 2 fibers. Weakness slowly decreased with refeeding with vitamins supplementation. We enlarge here the clinical pattern of post-BS complications.

Basilar Artery Changes in Fabry Disease.

BACKGROUND AND PURPOSE: Dolichoectasia of the basilar artery is a characteristic finding of Fabry disease. However, its prevalence, severity, and course have been poorly studied. This study quantitatively evaluated, by MRA, a panel of basilar artery parameters in a large cohort of patients with Fabry disease. MATERIALS AND METHODS: Basilar artery mean diameter, curved length, "origin-to-end" linear distance (linear length), and tortuosity index ([curved length ÷ linear length] - 1) were retrospectively measured on 1.5T MRA studies of 110 patients with Fabry disease (mean age, 39.4 ± 18.6 years; 40 males) and 108 control patients (mean age, 42.0 ± 18.2 years; 40 males). RESULTS: Patients with Fabry disease had increased basilar artery mean diameter (P < .001) and basilar artery linear length (P = .02) compared with control patients. Basilar artery curved length and tortuosity index correlated with age in both groups (P < .001), whereas basilar artery linear length correlated with age only in patients with Fabry disease (P = .002). Patients with Fabry disease showed a basilar artery curved length mean increase of 4.2% (9.7% in male patients with Fabry disease versus male control patients), whereas the basilar artery mean diameter had a mean increase of 12.4% (14.3% in male patients with Fabry disease versus male control patients). Male patients with Fabry disease had increased basilar artery mean diameter, curved length, and tortuosity index compared with female patients with Fabry disease (P = .04, P = .02, and P < .001, respectively) and male control patients (P < .001, P = .01, and P = .006, respectively). Female patients with Fabry disease demonstrated an age-dependent increase of basilar artery mean diameter that became significant (P < .001) compared with female control patients above the age of 45 years. CONCLUSIONS: The basilar artery of patients with FD is subjected to major remodeling that differs according to age and sex, thus providing interesting clues about the pathophysiology of cerebral vessels in Fabry disease.

Myofibrillar myopathies: State of the art, present and future challenges.

Myofibrillar myopathies (MFM) have been described in the mid-1990s as a group of diseases sharing common histological features, including an abnormal accumulation of intrasarcoplasmic proteins, the presence of vacuoles and a disorganization of the intermyofibrillar network beginning at the Z-disk. The boundaries of this concept are still uncertain, and whereas six genes (DES, CRYAB, LDB3/ZASP, MYOT, FLNC and BAG3) are now classically considered as responsible for MFM, other entities such as FHL1 myopathy or Hereditary Myopathy with Early Respiratory Failure linked to mutations of titin can now as well be included in this group. The diagnosis of MFM is not always easy; as histological lesions can be focal, and muscle biopsy may be disappointing; this has led to a growing importance of muscle imaging, and the selectivity of muscle involvement has now been described in several disorders. Due to the rarity of these myopathies, if some clinical patterns (such as distal myopathy associated with cardiomyopathy due to desmin mutations) are now well known, surprises remain possible and should lead to systematic testing of the known genes in case of a typical histological presentation. In this paper, we aim at reviewing the data acquired on the six main genes listed above as well as presenting the experience from two French reference centres, Paris and Marseilles.

Bethlem myopathy: long-term follow-up identifies COL6 mutations predicting severe clinical evolution.

OBJECTIVE: Mutations in one of the 3 genes encoding collagen VI (COLVI) are responsible for a group of heterogeneous phenotypes of which Bethlem myopathy (BM) represents the milder end of the spectrum. Genotype-phenotype correlations and long-term follow-up description in BM remain scarce. METHODS: We retrospectively evaluated the long-term clinical evolution, and genotype-phenotype correlations in 35 genetically identified BM patients (23 index cases). RESULTS: Nineteen patients showed a typical clinical picture with contractures, proximal weakness and slow disease progression while 11 presented a more severe evolution. Five patients showed an atypical presentation, namely a limb girdle muscle weakness in 2 and a congenital myopathy pattern with either no contractures, or only limited to ankles, in 3 of them. Pathogenic COL6A1-3 mutations were mostly missense or in frame exon-skipping resulting in substitutions or deletions. Twenty one different mutations were identified including 12 novel ones. The mode of inheritance was, autosomal dominant in 83% of the index patients (including 17% (N=4) with a de novo mutation), recessive in 13%, and undetermined in one patient. Skipping of exon 14 of COL6A1 was found in 35% of index cases and was mostly associated with a severe clinical evolution. Missense mutations were detected in 39% of index cases and associated with milder forms of the disease. CONCLUSIONS: Long-term follow-up identified important phenotypic variability in this cohort of 35 BM patients. However, worsening of the functional disability appeared typically after the age of 40 in 47% of our patients, and was frequently associated with COL6A1 exon 14 skipping.

Diaphragmatic dysfunction in Collagen VI myopathies.

Collagen VI-related myopathies are hereditary disorders causing progressive restrictive respiratory insufficiency. Specific diaphragm involvement has been suggested by a drop in supine volumes. This pilot study aimed at characterizing the respiratory muscle phenotype in patients with COL6A1-3 genes mutations. Lung function, blood gases, muscle strength and respiratory mechanics were measured in 7 patients between 2002 and 2012. Patients were classified as Early-Severe (n = 3), Moderate-Progressive (n = 2) and Mild (n = 2) according to clinical disease presentation. Seven patients (aged 6-28) were evaluated. Forced vital capacity distinguished the Mild group (>60% predicted) from the two other groups (<50% predicted). This distinction was also possible using the motor function measure scale. Diaphragmatic dysfunction at rest was observed in all the Early-Severe and Moderate-Progressive patients. During a voluntary sniff maneuver diaphragmatic dysfunction was observed in all patients, as assessed by a negative gastric pressure. All patients had diaphragmatic fatigue assessed by a tension-time index over the threshold of 0.15. Diaphragmatic dysfunction during a maximal voluntary maneuver and diaphragmatic fatigue are constant features in Collagen VI myopathies. These observations can assist the diagnosis and should be taken in account for the clinical management, with the early detection of sleep-disordered breathing.

Current and future imaging of the peripheral nervous system.

Peripheral nervous system (PNS) imaging is usually carried out by ultrasound and MRI. Thanks to its wide availability and excellent spatial resolution, ultrasound is a mature investigation with clearly established indications, particularly in entrapment syndromes and tumors. MRI is generally a second-line examination, which provides decisive additional information thanks to its excellent contrast resolution and its multiplanar abilities. This review describes the current methods for imaging the PNS, concentrating on acquisition techniques, normal results and basic pathological semiology. Ongoing and future developments are described in order to underline the forthcoming changes in this very dynamic field of musculoskeletal radiology.

[Scoliosis and disability]. / Scoliose et handicap.

Upright standing radiographs of the entire spine, at times completed by supine radiographs, allow diagnosis and follow-up of scolioses to detect progression over time and enable timely intervention to avoid painful, esthetic, respiratory and cutaneous complications. Motor difficulties that may accompany severe scolioses may confine affected individuals to bed. Cross-sectional imaging with tridimensional reconstructions combined with myelographic MR imaging sequences allow complete evaluation of the disease and have alleviated the need for conventional myelography. Evaluation of the imaging data allows comprehensive patient management that may include therapy, image-guided spinal injections or surgery with the help of new titanium hardware enabling follow-up MRI.

[Imaging features of neurologic and orthopedic complications from severe trauma]. / Imagerie des complications neuro-orthopédiques des traumatismes graves.

Cranial and spinal trauma are a frequent cause of disability in the general population. Post-traumatic paraplegia or quadriplegia or hemiplegia from vascular injury (CVA) can lead to early complications (respiratory, cardiovascular, urinary, cutaneous, infectious...) that may have an impact on the immediate prognosis. Neurologic and orthopedic complications occur later and further impair the quality of life of patients. Orthopedic complications include: neurogenic paraosteoarthropathy (NPOA) or neurogenic osteoma or myositis ossificans (NMO). The nomenclature currently in use is NMO; Osseous complications: osteoporosis and secondary insufficiency fractures; Joint complications: degenerative arthropathy and stiffness; Overuse mechanical complications; Muscular complications; Infectious complications: arthritis and myositis complicating skin ulcers and bed sores. The purpose of this paper is to describe these neuro-orthopedic complications and review their imaging features.

[Spasticity: clinical and imaging features]. / La spasticité: de la clinique à l'imagerie.

Spasticity, a component of the pyramidal syndrome, characterized by increased tonic stretch reflexes and hyperactive deep tendon reflexes, occurs in patients with central nervous system lesions (stroke, brain or cord injury, multiple sclerosis, cerebral motor impairment). The implementation of standard procedures (patient positioning, increased examination time, turning off certain devices before MR imaging) allows the acquisition of high quality examinations in spastic patients. Worsening spasticity in a handicaped patients is due to an irritative process (deep seated infection, fracture, syrinx...) usually detectable with imaging. Ultrasound or CT guided injections of botulinum agents provides radiologists with the opportunity to further participate in the management of spastic patients.

[Imaging features of post-traumatic spine and cord lesions]. / Imagerie des séquelles médullaires et rachidiennes post-traumatiques.

The imaging evaluation of post-traumatic spine and cord injuries is part of the global management of chronically handicapped patients. Diagnosis and follow-up MR imaging of cord lesions allows differentiation of static lesions from progressive lesions that could require surgical intervention. Follow-up CT imaging is helpful in the evaluation of spine lesions to distinguish between late complications (deformity, malunion, pseudoarthrosis, complications related to surgical hardware) and lesions secondary to the handicap (neurogenic spinal arthropathy).

[Neuromuscular diseases: imaging of thoracic, digestive and urinary complications]. / Pathologies neuromusculaires: imagerie des complications thoraciques, digestives et urinaires.

Neuromuscular diseases have different characteristics. Respiratory and cardiovascular manifestations are frequent and severe. Respiratory difficulties secondary to muscle involvement and bronchial secretions worsen complications related to a frequent scoliosis. CT is a useful complement to standard radiographs in the setting of acute symptomatic deterioration and for presurgical evaluation of a scoliosis. Echocardiography is performed to determine the presence of cardiomyopathy. Gastrointestinal motility disorders are assessed with standard barium studies or CT in the acute setting. Urinary tract involvement also is possible in these patients given the increased survival and follow-up imaging may be helpful for palliative management. The imaging features of frequent manifestations will be discussed along with the imaging appearance of a few specific entities.

[Enzyme replacement therapy of lysosomal storage diseases]. / Thérapies enzymatiques substitutives des maladies lysosomales.

Extraction and purification of an acid ß-glucosidase from human placenta (alglucerase) for the treatment of Gaucher disease, replaced a few years later by a recombinant enzyme (imiglucérase, Cerezyme(®)), has paved the way to the development of enzyme replacement therapies (ERT) for the treatment of lysosomal storage diseases (LSD) among which Fabry disease for which the long-term efficacy of the two currently available preparations (agalsidase alfa, Replagal(®) and Fabrazyme(®)) is still being investigated. Mucopolysaccharidosis (MPS) type I (Hurler and Scheie diseases), II (Hunter syndrome) and VI (Maroteaux-Lamy disease) also benefit from ERT using laronidase (Aldurazyme(®)), idursulfase (Elaprase(®)) and galsulfase (Naglazyme(®)), respectively. ERT reduces the hepatosplenomegaly and improves the physical and respiratory capacities of MPS patients with a globally acceptable safety profile although the possibility of infusion-associated should always be kept in mind. Alglucosidase alpha (Myozyme(®)) improves the cardiomyopathy and life expectancy of infants suffering from Pompe disease and is under evaluation for the treatment of the juvenile and adult forms of the disease. CNS involvement remains a major challenge for many LSD and innovative research and approaches are needed to address the fact that recombinant enzymes do not cross the blood-brain barrier and therefore are not expected to lead to any improvement in CNS damages, except if alternative routes such as intrathecal administration would be developed. Molecular chaperones (e.g. migalastat for Fabry disease) and inhibitors of glucosylceramide synthesis (e.g. eliglustat tartrate for Gaucher disease) are currently under investigation in various clinical trials.