Muscle Involvement In Patients Research Articles

Prevertebral muscle involvement in nasopharyngeal carcinoma

The purpose of this study is to evaluate the prevalence and prognostic significance of prevertebral muscle involvement in patients with nasopharyngeal carcinoma (NPC). Between July 1990 and December 2001, 521 newly diagnosed patients with NPC treated at Koo Foundation Sun Yat-Sen Cancer Center (KF-SYSCC) were examined with magnetic resonance imaging (MRI) for evidence of prevertebral muscle involvement before treatment. Patients were staged according to the 1997 American Joint Committee on Cancer staging classification of NPC based on the physical exams and MRI findings. All patients received radiotherapy with or without chemotherapy. The association between clinical prevertebral muscle involvement and posttreatment outcomes (overall survival, locoregional recurrence, and distant metastasis) were evaluated using Cox regression model to adjust for other prognostic factors. Of 521 patients treated at KF-SYSCC, 181 (35%) patients were found to have prevertebral muscle involvement, one-third in those with Stage II/III tumors and two-thirds in those with Stage IV tumor. In multivariate analysis accounting for all previously known prognostic factors, prevertebral muscle invasion was associated with an increased risk for any recurrence (adjusted relative risk, 2.01; p<0.001), locoregional recurrence (adjusted relative risk, 2.69; p<0.001), and distant metastasis (adjusted relative risk, 2.25; p<0.001), and with a borderline significant increased risk for overall survival (adjusted relative risk, 1.44; p=0.10). Prevertebral muscle involvement is an independent prognostic factor for NPC recurrence.

Extreme variability of skeletal and cardiac muscle involvement in patients with mutations in exon 11 of the lamin A/C gene

Mutations of the LMNA gene, encoding the nuclear envelope proteins lamins A and C, give rise to Emery-Dreifuss muscular dystrophy and to limb-girdle muscular dystrophy 1B (EDMD and LGMD1B). With one exception, all the reported EDMD and LGMD1B mutations are confined to the first 10 exons of the gene. We report four separate cases, with mutations in the same codon of LMNA exon 11, characterized by remarkable variability of clinical findings, in addition to features not previously reported. One patient had congenital weakness and died in early childhood. In two other patients, severe cardiac problems arose early and, in one of these, cardiac signs preceded by many years the onset of skeletal muscle weakness. The fourth case had a mild and late-onset LGMD1B phenotype. Our cases further expand the clinical spectrum associated with mutations in the LMNA gene and provide new evidence of the role played by the C-terminal domain of lamin A.

Thyroid-Associated Orbitopathy with Superior Oblique Muscle Involvement: A Case Report

A 29-year-old male with a 5-year-history of hyperthyroidism complained of diplopia and proptosis. After subtotal thyroidectomy, he still had diplopia in a certain gaze. Computerized tomography showed inferior rectus muscle enlargement in the right eye and inferior rectus, medial rectus, and superior oblique muscle enlargement in the left eye. Ocular examination with the cover and uncover test revealed hyperphoria and exophoria in the left eye. The upward gaze of the right eye was more limited than that of the left eye. Since superior oblique muscle involvement in patients with thyroid orbitopathy is quite rare, we discuss its effect on ocular motility in patients with thyroid-associated orbitopathy.

Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 53

Inclusion body myopathy (IBM) is a myopathy causing asymmetric proximal and distal limb muscle involvement in patients over 50 years. Motor neuron disease (MND) is a neurodegenerative disorder involving upper and lower motor neuron in the spinal cord and brainstem, characterized by progressive muscle weakness resulting in paralysis. The pathogenesis of cell injury in both diseases is still unknown: several hypothesis have been proposed addressing viral, autoimmunity, genetic and oxidation stress factors. We report on 2 cases with clinical presentation of upper and/or lower motor neuron involvement and histopathological diagnosis of IBM. Case 1: a 68 years old man with an 18‐month history of progressive weakness, spasticity, dysarthria, dysphagia. Neurological examination showed generalized muscle weakness, wasting of the finger flexors and quadriceps, fasciculations, deep tendon hyperreflexia. Electromyography (EMG) showed neurogenic signs and fasciculations at limbs and tongue muscles. Nerve conduction studies showed reduced cMAP amplitude at the legs, Motor Evoked Potential (MEP) revealed marked pyramidal tract involvement. Blood examination showed increased E.S.R. with normal level of serum creatinine kinase, copper, ceruloplasmin, and iron. Antiganglioside antibodies titer was normal and blood lactate analysis showed normal values during exercise. Cerebrospinal fluid (CSF) examination showed increased protein level. Brain magnetic resonance imaging disclosed of involvement of the cortico‐spinal tract and deposits of paramagnetic material in the basal ganglia with normal dopaminergic receptorial SPECT binding. Muscle biopsy revealed a neurogenic myopathy with “rimmed vacuoles”. Case 2: a 64 years old woman with 20 month history of muscle weakness slowly progressing from upper to lower limbs. Neurological examination showed distal muscle weakness and wasting at the upper limbs, deep tendon hypo‐areflexia. EMG showed neurogenic signs and fasciculations at four limbs. MEP and nerve conduction studies were normal but H reflex and F late responses were absent. E.S.R. was increased, while antiganglioside antibodies titer, thyroid hormones dosage and CSF examination were normal. Muscle biopsy revealed a neurogenic myopathy with rare “rimmed vacuoles”. These case reports, although not nosologically defined, confirm the clinical variability of the IBM and rise questions on the possible mechanisms of neuronal damage in motor neuron syndromes.

Muscle MRI findings in a three-generation family affected by Bethlem myopathy

We report clinical and muscle magnetic resonance imaging (MRI) findings in three individuals (aged 6, 26 and 73 years) from a three-generation family with Bethlem myopathy, confirmed by molecular genetic analysis which showed an exon skipping mutation in the COL6A1 gene. The clinical severity ranged from mild proximal weakness and distal laxity in the younger patients, to inability to stand or walk and severe contractures in the 76-year-old grandmother. The pattern of muscle involvement showed variable severity in parallel with the severity of motor function impairment. Although there was a marked variability in the severity of the MRI findings, it was possible to recognize a specific pattern of muscle involvement in all three patients. This consisted of involvement of the peripheral region of the vastus lateralis and hamstrings muscles with relative sparing of their central part. This was best appreciated in the third decade of life, but could also be identified both in the younger patient with minimal MRI changes and in the oldest patient, despite her more severe and diffuse muscle involvement. This report suggests that muscle MRI could be used as an additional tool to establish the pattern and the degree of muscle involvement in patients with Bethlem myopathy. Further studies in a larger cohort are needed to evaluate the specificity of these findings.

Graves' ophthalmopathy: eye muscle involvement in patients with diplopia.

Diplopia identifies patients with eye muscle involvement in Graves' ophthalmopathy (GO). To identify clinical parameters that could eliminate the need for magnetic resonance imaging (MRI) to assess the activity of inflammation in the eye muscles of GO patients with diplopia. In 43 patients with GO with recently developed diplopia, orbital ultrasound and MRI were performed. Muscle diameters and MRI T2 relaxation times were measured, and the amount of orbital connective tissue was calculated from MRI scans and compared with ultrasound readings, diplopia grades, degree of protrusion, ocular pressure, tear production, antibody levels and hormonal parameters of thyroid function. No correlation was found between diameters of 233 extraocular muscles measured by MRI and by ultrasound. For each of the four muscles, there was a diameter above which ultrasound was always unreliable. MRI data were used in further analysis. Of the muscles examined, the inferior rectuses were the most frequently enlarged - at least one, in 93% of cases. Medial, lateral and superior rectuses were enlarged in 59%, 37% and 34% of the orbits respectively. The pattern of muscle involvement of the two orbits tended to be symmetric (r=0.49, P=0.003), particularly for the medial rectuses (r=0.90, P=0.000). Proptosis correlated with the sum of the muscle diameters for a given eye (right eye: r=0.54, P=0.003; left eye: r=0.57, P=0.001), but it failed to correlate with the amount of orbital connective tissue. In 53% of the patients, normal T2 relaxation times were found in all eight muscles. There was only a weak correlation between muscle thickness and T2 relaxation time (r=0.49, P=0.003), indicating that muscle enlargement alone is not a sign of disease activity. The severity of diplopia was independent of T2 relaxation time. The amount of orbital connective tissue showed a negative correlation with the greatest T2 relaxation time for a given eye (r= -0.52, P=0.004); this suggests that disease types exist that have predominant muscle involvement and predominant connective tissue expansion. No correlation between connective tissue expansion and proptosis, diplopia grade, muscle thickness or disease duration was found - that is, connective tissue expansion is not a major factor in diplopia. Both muscle and connective tissue findings were independent of thyroid function. Ultrasound and MRI eye muscle diameter readings do not correlate, because of the inherent inaccuracy of orbital ultrasound. Muscle enlargement alone does not mean oedematous swelling and active disease. Neither ultrasound, nor any combination of 11 clinical and laboratory parameters provided the degree of information on muscles and connective tissue that was obtainable by MRI. In unclear cases of recently developed diplopia, before orbital decompression surgery, in the case of treatment failure or if, for any other reason, imaging is needed in GO, MRI is the method of choice.

MR imaging in amyopathic dermatomyositis.

Amyopathic dermatomyositis is a distinct clinical entity with cutaneous involvement but no myopathy. We conducted a prospective study to investigate the role of MR imaging in these patients. Out of 40 Chinese patients presenting with dermatomyositis, based on clinical assessment and normal serum muscle enzymes 10 were diagnosed as having amyopathic dermatomyositis. These 10 patients underwent MR imaging for evaluation of any subclinical muscle involvement. Three patients demonstrated abnormal signal intensity in muscles on both T2- and fat suppression sequences. Thus, one-third of patients with dermatomyositis and clinically normal muscles may have detectable muscle inflammation on MR images, indicating that MR has a potential role for locating the relevant biopsy site and for longitudinal follow up. Six of the 10 patients had malignant disease diagnosed before or after diagnosis of the cutaneous manifestation. Nasopharyngeal carcinoma was the most common malignant disease in this group of patients. MR imaging is recommended for demonstrating subclinical muscle involvement in patients with the clinical diagnosis of amyopathic dermatomyositis. We also recommend screening for malignancy, particularly nasopharyngeal carcinoma, in Southern Chinese patients with dermatomyositis.

99mTc SESTAMIBI scintigraphic evaluation of skeletal muscle disease in patients with systemic sclerosis: diagnostic reliability and comparison with cardiac function and perfusion.

The diagnosis of skeletal muscle involvement in patients with systemic sclerosis (SSc) is usually based on clinical, laboratory, electromyographic, and bioptic evidence of muscle disorder, whereas SSc cardiac disease is well established by nuclear medicine techniques (radionuclide ventriculography and myocardial scintigraphy). Previous reports have retrospectively hypothesized a possible relationship between cardiac and muscle involvement in scleroderma patients. In order to improve overall diagnostic accuracy in the qualitative/quantitative assessment of skeletal muscle involvement in these patients and to compare these results with those obtained at the cardiac level, diethylenetriaminepentaacetic acid (DTPA)-99mTc radionuclide ventriculography and 99mTc SESTAMIBI myocardial and muscular scintigraphic examinations were performed in 10 SSc patients and in five healthy subjects. Muscular radioactivity, as assessed at thigh and calf levels by means of a segmental score, was significantly decreased in SSc patients in comparison with healthy subjects (global score value 15.6+/-2.2 vs 22.7+/-1.6, p<0.001), as well as right ventricular ejection fraction (RVEF, 34.3%+/-5.3 vs 53.6%+/-4.2, p<0.001) and myocardial segmental perfusion (global score value, 19.6+/-2 vs 25.9+/-1.1, p<0.01). The results show a high frequency of skeletal muscle involvement in patients with SSc. Moreover, scleroderma patients with muscle disorders, as evidenced by scintigraphy, show a comparable occurrence of cardiac involvement, even in the absence of clinical signs of cardiac dysfunction.

Mitochondrial encephalomyopathy: correlation of P-31 exercise MR spectroscopy with clinical findings.

To evaluate the sensitivity of standardized exercise phosphorus-31 magnetic resonance (MR) spectroscopy in screening for subclinical muscle involvement in mitochondrial encephalomyopathy and to estimate if changes seen at biopsy have functional consequences. Exercise MR spectroscopy was performed in 52 examinations of 18 healthy volunteers and 14 patients with defects of mitochondrial respiratory chain enzymes. Calculation and kinetic analysis of the phosphocreatine (PCr) index and pH time courses were standardized with a microcomputer program. PCr index scores and conventional test scores matched in 10 of 14 cases. No obvious correlation existed between pH parameters and clinical score. Muscle affection, according to pH parameter score, was rated moderate (n = 3), severe (n = 1), or maximum (n = 2) in six of 14 cases in which clinical test scores showed only mild affection. Exercise MR spectroscopic PCr index parameters provide diagnostic information on skeletal muscle involvement in patients with mitochondrial encephalopathy. The sensitivity of the PCr index parameter seems equal or superior to that of conventional diagnostic tests. The role of pH parameters, however, has yet to be defined.

Inflammatory myopathy in F1 hybrid mice with acute graft-versus-host reactions.

Polymyositis and myasthenia gravis-like syndromes have been seen in patients with GVH disease following bone marrow transplantation. We therefore investigated the histopathology of muscle in mice with acute graft-versus-host disease in order to determine whether these conditions are caused by injury from the GVH reaction itself or are due to radiation and drugs used to prepare the host for transplantation. GVH reactions were induced by intravenously infusing 50 x 50(6) lymph node and spleen cells from A/J-strain donors into (C57BL/6 x A/J)F1-hybrid recipients. These mice developed an active inflammatory myopathy beginning 15 days after engraftment. The inflammatory infiltrates were focal in distribution, initially around perimysial blood vessels, and later around muscle fibers. The infiltrating cell population was composed of lymphocytes, plasmacytoid cells, and macrophages. Muscle cell necrosis was observed and was temporally related to elevations in serum creatine kinase. Similar histologic changes were present in the myocardium. Our findings support the notion that muscle involvement in patients with GVH disease is caused by the disease itself. Myositis accompanying experimental GVH disease in mice may hold promise as a model of autoimmune inflammatory myopathy.