Nemaline myopathy: Histological, histochemical and ultrastructural studies

Abstract

Histological, histochemical and ultrastructural studies were performed on muscle biopsies from three siblings with congenital nemaline myopathy. Histological studies revealed type I fibre atrophy and type II fibre paucity. Ultrastructural studies of intramuscular nerves showed that the axonal diameters were very narrow compared with the width of myelin lamellae. Granular or membranous osmiophilic material occurred in the adaxonal Schwann cell cytoplasm and had a periodicity of 33--38 A. The neuromuscular junctions showed degenerative features such as glycogen granules or myelin figures in 27.1% of total terminal axons. The secondary synaptic clefts were markedly decreased in number and short in length. Myotendinous junction-like structures were found in 5.5% of the muscle fibres near the neuromuscular junctions, and often near sites of fibre-splitting. Rods in nemaline myopathy might be caused as a result of longitudinal splitting and disruption of fibres due to deficient regeneration of the muscle fibres associated with neurotrophic abnormalities.

Nemaline myopathy of cats

“…In staining characteristics and size, the rods were similar to those reported in human patients. 16,45 The observation that marked regional variation in morphological changes occurred in cats with what is undoubtedly a single nosologic entity supports the concept that human patients with quite varied morphological findings may have the same disease. Therefore, as suggested by other authors, the diagnosis of nemaline myopathy has to depend on the finding of large numbers of rods in affected m~s c l e s .~ On the other hand, the fact that some muscle sections in our study completely lacked rods illustrates that nemaline myopathy should be considered when other morphological changes and clinical signs are consistent with the diagnosis.…”

Familial Nemaline Myopathy

“…lity in terminal axons and neuromuscular junction in this disorder. On the contrary Fukuhara et al (1978) reported abnormalities in intramuscular nerves consisting in narrow axonal diameters in relation to the width of myelin sheath and in granular or membranous osmiophilic material in the Schwann cell cytoplasm. Neuromuscular junctions also displayed numerical reduction and shortening of secondary synaptic c1efts.…”

Muscle cofilin alters neuromuscular junction postsynaptic development to strengthen functional neurotransmission

“…Cfl2 mouse studies report no obvious NMJ defects; it is possible that a subtle change on the postsynaptic membrane would not be appreciated when only visualizing the motor neuron and acetylcholine receptors (Agrawal et al, 2012; Gurniak et al, 2014). Nevertheless, some reports from human NM patient biopsies imaged by TEM report alterations at the postsynapse, including collapsed or dilated primary and secondary synaptic clefts (Fukuhara et al, 1978; Heffernan et al, 1968; Karpati et al, 1971). We see a collapse of the synaptic cleft via TEM in the DmCFL KD model.…”

“…To further investigate the DmCFL KD model, we conducted RNA sequencing which identified changes in genes related to the neuromuscular junction (NMJ), the specialized synapse where the presynaptic motor neuron and postsynaptic muscle communicate. Early case reports examining NM muscle biopsies provide evidence of NMJ disruption, describing abnormal motor end plates and synaptic clefts (Fukuhara et al, 1978; Heffernan et al, 1968). Moreover, electromyography shows a myopathic pattern in NM patients, although it is unclear if there is additional superimposed NMJ transmission defect.…”