“Necklace” fibers as a late clue to the interpretation of the forgotten “trilaminar” fibers

Abstract

In a recent article by Bevilacqua et al. [1] on ‘‘necklace fibers, a new histological marker of late-onset MTM1related centronuclear myopathy’’, impressive light micrographs of such fibers are presented which closely resemble those previously described as ‘‘trilaminar’’ fibers [2–4], as far as the different techniques applied at the earlier and present times allow identification. Both the clinical and the structural changes appear rather similar within a wide spectrum of individual variations. Ringel et al. [2] in 1978 reported on a sporadic myopathy with pronounced rigidity, lack of spontaneous movements, and increased CK values. Electromyography appeared to be normal. The muscle biopsy at the age of 7 weeks showed numerous fibers with three concentric zones leading to the designation as trilaminar fibers. The innermost zone showed accumulations of mitochondria, glycogen, and electron dense material with only few remnants of myofibrils. The intermediate zone consisted of myofibrils showing Z-band streaming. The outer zone resembled a sarcoplasmic mass. Histochemistry revealed extrajunctional acetylcholine receptor (AChR) between the intermediate and outer zone. Increased muscle tone was attributed to a disturbed neural influence, while increased CK activity was interpreted as being more characteristic for a primary muscle lesion. The female case of Schroder and Schonberger published in 1981 [3, 4] was clearly a familial one, deceasing at the age of 18 months from bronchopneumonia. The older brother was born with bilateral club feet dying at the age of 3 months due to aspiration pneumonia. A younger brother showed delayed motor milestones with tremor since birth. He died at the age of 9 months. One sister and the parents appeared to be unaffected. Therefore, autosomal recessive inheritance was assumed. Muscle biopsy showed at the light microscopic level in semithin sections many muscle fibers with an outer light zone, an intermediate darker ring, and a relatively light center (Fig. 1a–d). At the electron microscopic level (Fig. 2a, b), there were glycogen granules, mitochondria, components of the T-system and microtubules in the outer zone. The intermediate ring showed an increased density of myofibrillar structures, while the center was rather disorganized. The nuclei were located in the peripheral, not in the central zone similar to those in the recent biopsies. The trilaminar fibers were smaller than the normal ones but not severely atrophic. To me, there appears to be no essential difference between ‘‘necklace’’ and ‘‘trilaminar’’ fibers, although the published electron micrographs of necklace fibers show less impressive or representative changes than the light micrographs and the electron micrographs previously published of the trilaminar fibers. The anti-desmin and antiaB-crystalline labelling of the intermediate ring in necklace fibers corresponds quite closely to the electron dense intermediate zone of trilaminar fibers, which I would have liked to call ‘‘cockade’’ (in French ‘‘cocarde’’, in German: Kokarden-) fibers if there would not have been the national emblematic implication. ‘‘Trilaminar’’ or ‘‘necklace’’ fibers are obviously very rare because in 40 years (between 1965 and 2005) looking at more than 12,000 muscle biopsies there was not a single other one with similar changes, including myotonic dystrophy. Nevertheless, it is highly appreciated that the changes have now been attributed to a distinct molecular genetically defined myopathy, which is due to mutations in the phosphoinositide phosphatase myotubularin 1 protein (MTM1) gene [1]. J. M. Schroder (&) Department of Neuropathology, Aachen University Hospital, RWTH Aachen, Pauwelsstr. 30, 52074 Aachen, Germany e-mail: jmschroder@ukaachen.de