Tubular aggregates may be found in a variety of conditions and have been associated with a wide range of chemical and ischemic insults. We report clinical and histological features in a case of myopathy with tubular aggregates. The structure of these tubular aggregates was examined using antibodies to cytoskeletal proteins and heat shock proteins. Epitopes of the 72 kD heat shock protein were expressed in the areas of abnormality in this case and in a case of hypokalemic periodic paralysis with tubular aggregates. Heat shock proteins have a role in the modulation of the Jertiary structure of proteins and may be involved in the pathogenesis of tublrlar aggregates and other microtubular abnormalities in muscle. Key words: tubular aggregates heat shock proteins stress myopathy MUSCLE & NERVE 14~219-225 1991

EXPRESSION OF HEAT SHOCK PROTEIN EPITOPES IN TUBULAR AGGREGATES JOANNE E. MARTIN, MA, MB, BS, KANTI MATHER, MPhil, MICHAEL SWASH, MD, MRCPath, FRCP, and ALAN 8. GRAY, BSc

T h e syndrome of myopathy with tubular aggregates consists of muscle pain and stiffness on exertion that is relieved by rest, but often persists for several hours. These symptoms are much more marked in the legs than in the arms. All reported cases (Table 1) have been men. The disorder is of insidious onset, but seems benign because progression to severe muscular pain, weakness, or atrophy has not been recognized. Only 6 patients with this syndrome have been described in detai1,4,"24j33.44 but Rosenberg et aI.*% found 8 cases in a review of 1500 muscle biopsies, and Niakan et al.38 recognized 19 cases, 12 with severe myalgia and 7 with myalgia as the only symptom, in their review of 3000 muscle biopsies. I t is, therefore, possible that this syndrome, recognized in about 0.5% of muscle biopsies, is slightly more common than would be surmised from its rarity in the literature.

From the Deparlments of Histopathology and Neurology, The Royal London Hospital. Whitechapel, London, United Kingdom. Acknowledgment: JEM is an MRC training fellow and holds the British Medical Association Vera Down Award. Our work is generously supported by Mr J.C Lewis Address reprint requests to Dr. J.E Martin, Department of Histopathology. The Royal London Hospital, Whitechapel. London E l 155, United Kingdom Accepted February 8, 1990 CCC 0148- 639X/91/030219-07 $04.00 0 1991 John Wiley & Sons, Inc.

HSPs and Tubular Aggregates

Table 1. Associations of agents and syndromes with tubular aggregates. Cause Familial myopathy Myalgia syndrome Alcoholic myopathy Gyrate atrophy of the eye Congenital myasthenic syndrome Myotonic dystrophy and myotonia Periodic paralysis Inflammatory myopathy Diabetic amyotrophy Hyperaldosteronism Porphyria cutanea tarda Drug myopathy Muscle hypoxia, infarction Botulinum toxin injection Tetanus toxin injection Malignant hyperpyrexia Cold

Agent

Reference no.

7

19, 42 4, 5, 24, 33, 44 7, 36 47 32

7

Chemical 7

Calcium 7

46

Metabolic Immune Metabolic Metabolic Chemical Chemical Hypoxia Toxic Toxic Metabolic Metabolic

3 43 6 18

16 16, 17 26 12

13 41

40

Muscle pain induced by exertion is a feature of several metabolic myopathies.' However, tubular aggregates, which occur in many different disorders (Table l), are not themselves associated with any known single enzyme defect or abnormality of muscle metabolism. In this report we describe studies of heat shock protein expression in the tubular aggregates and in other tubular proliferations.

MUSCLE & NERVE

March 1991

219

CASEREPORT

A 42-year-old Bangladeshi man presented with pain and stiffness of leg muscles, especially of thighs and posterior calves, induced by moderate exertion, as by climbing stairs. These symptoms tended to subside only after several hours rest in a chair or in bed. There was no weakness, muscle atrophy, muscle tenderness o r fasciculation, but he had experienced muscle cramp after exercise. Examination revealed no neuromuscular abnormality, although he showed a marked reluctance to exert full strength during muscle testing. T h e tendon reflexes were all present and the plantar responses were flexor. General examination was normal. Investigation revealed no abnormality in hematology, li\ er function, electrolyte and renal function tests. Blood calcium, phosphorous, and alkaline phosphatase were normal. A glucose tolerance test and thyroid function tests were normal. C T x-ray scans of his lower limb muscles showed muscles of normal size and attenuation. Concentric needle EMG revealed patchy zones of short duration, low-amplitude action potentials consistent with myopathic change, and motor and sensory nerve conduction studies were normal. The serum creatine kinase was 86 UIL (normal

Expression of heat shock protein epitopes in tubular aggregates.

Tubular aggregates may be found in a variety of conditions and have been associated with a wide range of chemical and ischemic insults. We report clin...
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