Muscle Pseudohypertrophy Research Articles

Hoffman′s syndrome

Hoffman's syndrome is characterized by hypothyroidism with muscle stiffness and pseudo hypertrophy We herewith present a case report of 28 years male with cramps of both lower limbs associated swelling of both calf muscles. Investigations revealed hypothyroidism with elevated TSH and TPO antibodies with focal hypertrophy and hyperplasia of calf muscles on biopsy with normal nerve conduction studies.

Chronic AMPK activation induces beneficial phenotypic adaptations in mdx mouse skeletal muscle

A therapeutic approach for Duchenne muscular dystrophy (DMD) is to upregulate utrophin levels in skeletal muscle in an effort to compensate for the lack of dystrophin. We have previously hypothesized that promotion of the slow, oxidative myogenic program, which triggers utrophin upregulation, can attenuate the dystrophic pathology in mdx animals, the murine model of DMD. Indeed, treatment of mdx mice with the PPARδ activator GW501516 shifted muscle phenotype and ameliorated the disease pathology (Miura et al. Hum Mol Genet. 18:4640–49, 2009). Treatment of healthy mice with the AMPK activator AICAR enhances oxidative capacity and triggers a fast-to-slow fiber-type transition. Our purpose was to evaluate the effects of chronic AICAR administration on muscle gene expression and the dystrophic pathology in mdx mice. AICAR mitigated muscle pseudo-hypertrophy and attenuated central nucleation. Furthermore, we observed an elevation in mitochondrial enzyme activity, an increase in MHC IIa-positive fibers, and slower twitch contraction kinetics in the EDL muscle. Utrophin and PGC-1α proteins were augmented in response to AICAR, concomitant with a reduction in RIP140. Exercise increased utrophin A, PGC-1α, and PPARδ mRNAs. This effect was attenuated with AICAR. Our data suggest that AICAR-evoked muscle plasticity results in beneficial phenotypic adaptations in mdx mice. Supported by MDA (USA), CIHR and NSERC.

Kocher-Debré-Sémélaigne syndrome diagnosed by autopsy associated with disseminated intravascular coagulation

Kocher-Debré-Sémélaigne syndrome is a rare disease with little literature, which develops with myopathy in infancy associated with neuromuscular alterations, polymyositis with symmetrical proximal muscle weakness, pseudohypertrophy, muscular rigidity and spasms, exercise intolerance, myxoedema, short stature, and cretinism. Male patient aged 18 years old, 1.52 m in height, admitted in the General Hospital of Triângulo Mineiro Federal University on November 11, 2003, complaining of intense diffuse abdominal pain like severe cramps, without triggering factors, associated with asthenia and hyporexia. This seems to be one of the few reports of KDS syndrome diagnoses by autopsy, where alterations in the thyroid gland connected with hypotrophy and probable congenital hypothyroidism were described and resulted in complications such as disseminated intravascular coagulation and hemophagocytic syndrome with fast progression to death of an 18-year-old patient.

HoffMann′s syndrome: A rare neurological presentation of hypothyroidism

The neurological manifestations of hypothyroidism are very unusual to see as initial symptoms and they usually occur late in the course of disease. Muscle hypertrophy is an extremely rare finding in hypothyroid patients. Hypothyroidism presenting as muscle stiffness and muscle pseudo hypertrophy in adults is known as Hoffmann's syndrome. Laboratory investigation in hypothyroid myopathy generally shows increased levels of muscle enzyme. The electrophysiological study may reveal features suggestive of myopathy, neuropathy or mixed pattern. The symptoms and also the serum levels of enzymes return to normal with hormone replacement therapy. We report a case of hypothyroidism with calf muscle hypertrophy and proximal myopathy as the initial symptoms.

A young lady with swelling and stiffness of calf muscles

Hypothyroidism causes a variety of changes in the body. Though uncommon, hypothyroidism can present as myopathy. Hoffman's syndrome is a specific, rare form of hypothyroid myopathy, which causes proximal weakness and pseudohypertrophy of muscles.

Congenital Hypopituitarism due to POU1F1 Gene Mutation

POU1F1 (Pit-1; Gene ID 5449) is an anterior pituitary transcriptional factor, and POU1F1 mutation is known to cause anterior pituitary hypoplasia, growth hormone and prolactin deficiency and various degree of hypothyroidism. We report here a patient who presented with growth failure and central hypothyroidism since early infancy. However, treatment with thyroxine gave no effect and he subsequently developed calf muscle pseudohypertrophy (Kocher-Debre-Semelaigne syndrome), elevation of creatinine kinase, dilated cardiomyopathy and pericardial effusion. Final diagnosis was made by combined pituitary function test and sequencing analysis that revealed POU1F1 gene C.698T > C (p.F233S) mutation. The rarity of the disease can result in delayed diagnosis and treatment.

811 Progressive Muscular Dystrophy: Clinical and Genetical Study

Background and aims: Progressive muscular dystrophies represent a group of genetic diseases with insidious onset in childhood; they are characterized by muscle fatigue associated with pseudohypertrophy of the muscles, high level of creatinkinase; electrophysiological, histological and molecular biology studies distinguish the primary disorder of the muscles. Methods: Prospective study that included 16 patients (1-5 years old) in a period of 2 years (2006- 2008). Patients were evaluated clinically, functionally, paraclinical (muscle enzyme), neurophysiology. In all patients muscle biopsy was performed and in 8 cases genetic tests. Results: In this trial 12 children (75%) had pseudohypertrophy of calf muscles, 8 children (50%) had signs of muscular disease (the weakness of proximal muscles, a positive Gowers's sign), 5 children (31.25%) had increased levels of transaminases, creatinkinase and lactic dehydrogenases. Genetic studies were performed in 8 of the patients, 6 presenting deletions and point mutations 2. Conclusions: Progressive muscular dystrophy is a relative frequent disorder in children, which can be recognized early; if the high levels of transaminases are find, without other sings of hepatic disease, is necessary to determine the creatinkinase level. Genetic studies are required to specify the type of mutation in the initiation of therapies to slow evolution.

Sporadic centronuclear myopathy with muscle pseudohypertrophy, neutropenia, and necklace fibers due to a DNM2 mutation

Dynamin 2 gene ( DNM2) mutations result in an autosomal dominant centronuclear myopathy (CNM) and a Charcot-Marie-Tooth (CMT) neuropathy. DNM2-CMT but not DNM2-CNM patients were noted to have neutropenia. We here report a man with paravertebral muscles hypertrophy and mild neutropenia. His muscle biopsy was typical for CNM with additional “necklace” fibers. Sequencing of DNM2 revealed a known heterozygous c.1269C > T (p.Arg369Trp) mutation. Necklace fibers were considered as a pathological hallmark of late onset X-linked CNM due to mutations in MTM1 but have not been observed in DNM2-CNM. The findings broaden the features of DNM2-myopathy.

Molecular characterization of co‐occurring Duchenne muscular dystrophy and X‐linked oculo‐facio‐cardio‐dental syndrome in a girl

Duchenne muscular dystrophy is an X-linked condition at the severe end of the spectrum of dystrophinopathies. Females with dystrophin mutations are at risk for cardiomyopathy, but are usually asymptomatic during childhood. However, some girls can exhibit features of Duchenne muscular dystrophy because of skewed X-inactivation, aneuploidy, or chromosomal rearrangement. Oculo-facio-cardio-dental syndrome is a rare X-linked disorder, lethal in males, that comprises microphthalmia, congenital cataracts, congenital heart defect, canine radiculomegaly, and digital anomalies. We report on a 7-year-old girl who was referred for muscular hypotonia, with clinical features of Duchenne muscular dystrophy, including elevated serum creatine phosphokinase, pseudohypertrophy of calf muscles, and muscle weakness, which became evident at 3 years of age. In addition, she had multiple congenital anomalies including atrial septal defect, cataracts, dental and digital anomalies, a constellation that suggested the diagnosis of oculo-facio-cardio-dental syndrome, a condition caused by mutations in BCOR. Immunohistochemistry and Western blot analysis of muscle, and mutation analysis of DMD showed a maternally inherited deletion of exons 30-43, confirming the diagnosis of Duchenne muscular dystrophy. Studies of lymphocytes showed essentially complete skewing of X-inactivation. Mutation analysis of BCOR revealed a de novo frameshift mutation (c.1005delC). Thus, we report for the first time on an individual with the co-occurrence of Duchenne muscular dystrophy and oculo-facio-cardio-dental syndrome.

Generalized muscle pseudo-hypertrophy and stiffness associated with the myotilin Ser55Phe mutation: A novel myotilinopathy phenotype?

Myotilinopathies are a group of muscle disorders caused by mutations in the MYOT gene. It was first described in two families suffering from limb girdle muscle dystrophy type 1 (LGMD 1A), and later identified in a subset of dominant or sporadic patients suffering from myofibrillar myopathy, as well as in a family with spheroid body myopathy. Disease phenotypes associated with MYOT mutations are clinically heterogeneous and include pure LGMD forms as well as late-onset distal myopathies. We report here on a 53-year-old male suffering from a unique clinical profile characterized by generalized symmetrical increase in muscle bulk leading to a Herculean appearance. Muscle weakness and stiffness in the lower extremities were the patient's main complaints. Muscle MRI showed extensive fatty infiltration in the thigh and leg muscles and a muscle biopsy showed a myofibrillar myopathy with prominent protein aggregates. Gene sequencing revealed a Ser55Phe missense mutation in the myotilin gene. The mutation was identified in his older brother, who presented a mild hypertrophic appearance and had a myopathic pattern in EMG, despite not presenting any of the complaints of the proband and having normal muscle strength. This finding, and his deceased father and paternal aunt's similar gait disorders, suggest that this is in fact a new autosomal dominant kindred. The present observations further expand the spectrum of clinical manifestations associated with mutations in the myotilin gene.

A ‘muscle’ man without exercise: muscle pseudohypertrophy in myeloma-associated generalized amyloidosis

A ‘muscle’ man without exercise: muscle pseudohypertrophy in myeloma-associated generalized amyloidosis

Pseudohypertrophy of the Calf Muscles in a Patient with Diabetic Neuropathy: A Case Report

Partial or complete loss of innervation of skeletal muscle leads to muscle weakness and atrophic changes, resulting in decreased muscle volume with fatty replacement. Rarely, enlargement of the affected muscle may occur, related to two processes: true hypertrophy and pseudohypertrophy. We report CT and MR findings of the pseudohypertrophy of calf muscles, especially the soleus and gastrocnemius muscles, in a patient with diabetic neuropathy that showed increased muscle volume with diffuse fatty replacement and the presence of scanty muscle fibers.

Kocher-debre-semelaigne syndrome with pericardial effusion

We report a 10-year-old female child with hypothyroidism and limb muscle pseudohypertrophy (i.e. Kocher-Debre-Semelaigne syndrome) with pericardial effusion. The child presented with generalized swelling, breathlessness and difficulty in walking and in getting up from sitting position (of chronic duration). She had bradycardia, dull facies, marked hypertrophy of both calf muscles and nonpitting edema of legs. Pericardial effusion was detected clinically and confirmed on investigations. Muscle pseudohypertrophy was a striking feature and hypothyroidism was confirmed on thyroid studies. The response to thyroxine replacement was excellent, with resolution of the pericardial effusion and clinical improvement. The unusual presence of pericardial effusion in Kocher-Debre-Semelaigne syndrome is discussed in the report.

Unusual clinical presentation of primary hypothyroidism in a very young infant caused by autoimmune thyroiditis: case report and update of the literature

Acquired primary hypothyroidism in infancy can be related to autoimmune thyroiditis and can present with unusual symptoms, such as muscle pseudohypertrophy and pituitary tumor. This condition can cause permanent deficits in psychomotor development and growth despite adequate replacement with L: -thyroxine.

Gross muscle pseudohypertrophy in myeloma-associated light chain amyloidosis

A 73-year-old woman developed muscle enlargement, stiffness, and signs of congestive heart failure over 2 years (figure, A). Examination revealed proximal weakness and reduction of subcu-taneous fat. Macroglossia was absent. Endocrinology was normal.Muscle biopsy showed amyloid deposition (figure, B), and a plas-macytoma with λ …

Consequence of parvalbumin deficiency in the mdx mouse: histological, biochemical and mechanical phenotype of a new double mutant

We tested the hypothesis whether the mild dystrophy in mdx mice could result from the contribution of the cytosolic calcium buffer parvalbumin in maintaining a normal cytosolic [Ca 2+] i, in spite of an increased passive Ca 2+ influx. By crossing mdx mice with parvalbumin-deficient mice, double mutant mice, lacking both dystrophin and parvalbumin, were obtained. Though resting cytosolic [Ca 2+] i and total calcium content were similar to that of mdx muscles, this new animal model presented a slightly more severe phenotype than the mdx mouse. Muscle pseudo-hypertrophy, the density of myotubes and of centronucleated fibres as well as the loss of IIB fibres were all increased in parvalbumin-deficient mdx mice. Many of these deficits were overcome in late adulthood, albeit fibrosis was clearly more pronounced than in mdx muscles. At 90 days, parvalbumin-deficient mdx mice showed higher levels of creatine phosphokinase and lower muscle strength, in vivo, than mdx mice. Isometric tension of isolated muscle was reduced, but the susceptibility to eccentric contraction was not increased. The slight aggravation of muscle dystrophy observed in mdx mice deprived of parvalbumin cannot explain the severity of the affection observed in xmd dogs and Duchenne dystrophy patients where parvalbumin is constitutively not expressed.

Hereditary neuromuscular diseases

This article presents the actual classification of neuromuscular diseases based on present expansion of our knowledge and understanding due to genetic developments. It summarizes the genetic and clinical presentations of each disorder together with CT findings, which we studied in a large group of patients with neuromuscular diseases. The muscular dystrophies as the largest and most common group of hereditary muscle diseases will be highlighted by giving detailed information about the role of CT and MRI in the differential diagnosis. The radiological features of neuromuscular diseases are atrophy, hypertrophy, pseudohypertrophy and fatty infiltration of muscles on a selective basis. Although the patterns and distribution of involvement are characteristic in some of the diseases, the definition of the type of disease based on CT scan only is not always possible.

Muscular dystrophy.

Muscular dystrophy.

Myopathy in primary systemic amyloidosis.

To define the natural history of primary systemic amyloidosis when muscle involvement is prominent at presentation. A retrospective review was carried out of all patients seen at the tertiary referral practice of the Mayo Clinic between 1 January 1960 and 31 December 1994. All patients with primary systemic amyloidosis and proof of amyloid deposits by muscle biopsy were included for analysis. No patients were lost to follow up. Twelve patients were identified with amyloidosis in muscle. Muscle involvement was the most prominent symptom in patients who had widespread visceral involvement, which included the heart, peripheral nerve, and tongue. Of the 12, three had skeletal muscle pseudohypertrophy. All patients had a demonstrable dysproteinaemia by the finding of free light chain in the serum or urine, a discrete monoclonal peak on serum or urine protein electrophoresis, or a monoclonal population of plasma cells in the bone marrow. Measurement of creatine kinase was not a useful test. Of eight patients treated with chemotherapy based on alkylating agents, three responded. The median survival for the entire group was 12 months. The finding of a monoclonal protein in a patient with muscle weakness is an important clue to the diagnosis of primary systemic amyloidosis. Most patients have visceral involvement outside the musculoskeletal system. A subset of patients seems to respond to systemic chemotherapy. The overall survival, however, remains poor, with most patients dying of cardiac failure. Immunoelectrophoresis of serum and urine should be a routine diagnostic test during the evaluation of myopathy of unknown cause.

PS-49-8 Muscle pseudohypertrophy in a patient with distal myopathy and rimmed vacuoles

PS-49-8 Muscle pseudohypertrophy in a patient with distal myopathy and rimmed vacuoles