J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.48.9.882 on 1 September 1985. Downloaded from Journal of Neurology, Neurosurgery, and Psychiatry 1985;48:882-886 Tubular aggregates: their association with myalgia ENAYAT NIAKAN,* YADOLLAH HARATI,* MORIS J DANONt From the Department ofNeurology, Baylor College of Medicine, Houston * and Department ofNeurologyt University of Illinois Medical Center, Chicago, USA SUMMARY Three thousand consecutive muscle biopsies were reviewed for the presence of tubular aggregates and their association with clinical symptomatology. Tubular aggregates were detected in 19 patients (0.6%). Twelve of these nineteen patients had severe myalgia, and the most abundant tubular aggregates were found in biopsies of patients with myalgia. Seven patients had only myalgia as their clinical symptomatology with normal physical examination. An additional five patients with tubular aggregates and myalgia had concomitant amyotrophic lateral sclerosis (2) or neuropathy (3). The high incidence of myalgia associated with tubular aggregates in our patients and the fact that tubular aggregates originate from sarcoplasmic reticulum suggest a role played by this structure in the pathogenesis of myalgia. guest. Protected by copyright. Tubular aggregates are visible by light microscopy quadriceps or biceps muscles. For histochemical studies, within Type II muscle fibres as a mass in the subsar- tissue had been frozen with liquid nitrogen, sectioned colemmal region with strong NADH-tetrazolium at 10,1L in a cryostat, and stained with the following reductase (NADH-TR) and negative succinic methods: Modified Gomori Trichrome (TRI), NADH-TR, adenosine triphosphatase (ATPase) at pH 9-4, succinic dehydrogenase reactions. Ultrastructurally they are dehydrogenase and phosphorylase. For electon micros- closely packed, parallel, double-walled tubules copy, tissue had been fixed in 1 % glutaraldehyde buffered which appear to be a proliferation of sarcoplasmic at pH 7-4 for 11/2 h and then fixed in 1% osmium tetroxide reticulum.' The diagnostic importance of tubular for another hour. Some material was then embedded in aggregates is uncertain because they are present in Epon and sections 1 ,u thick were cut for all blocks, stained muscles of patients with a wide variety of disor- with toluidine blue and examined under the light micros- ders.' -21 Recently tubular aggregates have been copy. Thin sections for electron microscopy were then described in muscle biopsy specimens of patients stained with uranyl acetate and with lead citrate. with myalgia who are otherwise normal.2'26 The fact that tubular aggregates originates from sarco- Results plasmic reticulum, which has an important role in regulation of muscle contracture and relaxation, Among 3000 patients 19 (0.6%) had histochemi- suggests a relationship between tubular aggregates, cally typical tubular aggregates; 17 patients were sarcoplasmic reticulum and myalgia. To clarify this male and two female. With the TRI stain, the tubu- we reviewed muscle biopsy specimens lar aggregates appeared as bright red staining sub- relationship, seen for the presence of tubular aggregates and their sarcolemmal material. Tubular aggregates were http://jnnp.bmj.com/ association with clinical symptomatology. only in the Type II fibres, were darkly stained by the NADH-TR, and unstained by ATPase and succi- Methods nate dehydrogenase (fig 1). Further studies includ- ing electron microscope and epoxy resin histology We analysed all 3000 muscle biopsy specimens at our were done in some cases which showed closely institution in the preceeding seven years. All were from the packed, parallel, double-walled tubules (fig 2). Five biopsies showed less than 1% fibres affected Presented in part at the Thirty-Sixth Annual Meeting of the and six between on September 30, 2021 by Boston, April, 1984 with tubular aggregates, 1-10%, American Academy of Neurology, eight had more than 10% fibres with tubular aggre- Address for reprint requests: Dr Harati, Department of Neurology, gates. This was determined after obtaining a 10OX Baylor College of Medicine, 6501 Fannin, Houston, Texas 77030, photograph of each biopsy specimen and counting USA. the number of tubular aggregates per 200 muscle Received 5 June 1984 and in revised form 27 August 1984 fibres. Accepted 1 September 1984 Clinically, 12 of 19 patients had severe myalgia, 882 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.48.9.882 on 1 September 1985. Downloaded from Tubular aggregates: their association with myalgia 883 .. s i:: .....Q -~~~~~~~'C .2'~~~~~~~~~~~~3 zd--~~~- V.- -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~.. ~ 6a,W A . .r S~~~~~~~~~~~~~~~~~~t.~Mlg A-.,T v-~ ~ ~ ~ ~ ~ guest. 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