Progressive myopathy in hyperkalemic periodic paralysis.

A progressive degenerative myopathy has been well described in hypokalemic periodic paralysis but is not as widely recognized in hyperkalemic periodic paralysis. We studied four families with the latter disease in which some members developed a progressive myopathy. Episodes of paralysis were prolonged, lasting for months in some cases, and in one case paralysis was sufficiently severe to require ventilatory support. The progressive myopathy tended to develop at a time when attacks of paralysis were decreasing in frequency. Muscle biopsy specimens showed variability in fiber size, internal nuclei, and fibers with vacuoles. Electron microscopy showed myofibrillary degeneration and tubular aggregates. An abnormal biopsy specimen was more common in older patients. Our experience suggests that a progressive myopathy is as common in hyperkalemic periodic paralysis as it is in the hypokalemic disorder.

Neonatal and adult myosin heavy chain isoforms in a nerve-muscle culture system.

When adult mouse muscle fibers are co-cultured with embryonic mouse spinal cord, the muscle regenerates to form myotubes that develop cross-striations and contractions. We have investigated the myosin heavy chain (MHC) isoforms present in these cultures using polyclonal antibodies to the neonatal, adult fast, and slow MHC isoforms of rat (all of which were shown to react specifically with the analogous mouse isoforms) in an immunocytochemical assay. The adult fast MHC was absent in newly formed myotubes but was found at later times, although it was absent when the myotubes myotubes were cultured without spinal cord tissue. When nerve-induced muscle contractions were blocked by the continuous presence of alpha-bungarotoxin, there was no decrease in the proportion of fibers that contained adult fast MHC. Neonatal and slow MHC were found at all times in culture, even in the absence of the spinal cord, and so their expression was not thought to be nerve-dependent. Thus, in this culture system, the expression of adult fast MHC required the presence of the spinal cord, but was probably not dependent upon nerve-induced contractile activity in the muscle fibers.

Mitochondrial myopathies. A clinico-pathological study of cases with and without extra-ocular muscle involvement.

The clinical and pathological features of 28 patients with mitochondrial myopathy were reviewed. The cases were divided into a group with involvement of the extra-ocular muscles alone or with limb muscle involvement, and a group with a facioscapulohumeral syndrome or generalised weakness without extra-ocular muscle involvement. Cardiac and central nervous system manifestations occurred particularly in the first group which included six patients with multisystemic features and two with the complete Kearns-Sayre syndrome. Diabetes mellitus occurred in the second group only. Quantitative histology on limb muscle biopsies showed a higher proportion of fibres with abnormal mitochondrial aggregates in the second group. No one type of mitochondrial inclusion or other ultrastructural change was specific for either group of cases. The findings illustrate the clinical heterogeneity of cases of mitochondrial myopathy and the lack of specificity of any of the myopathological changes for different subgroups of patients.

Quantitative studies of the abnormal axon-Schwann cell relationship in the peripheral motor and sensory nerves of the dystrophic mouse.

The nature and extent of abnormal axon-Schwann cell relationships in peripheral portions of dystrophic motor and sensory nerves were quantitatively evaluated between 1 and 9 months of age using teased fibres and electron micrographs. The results show that in the dystrophic (dy/dy) common peroneal (CPN) and tibial nerves (TN), and less in the dy/dy sural nerve (SN): (1) the number of Schwann cell nuclei associated with myelinated axons is increased with respect to normal; (2) the average internodal length is correspondingly reduced; (3) the average dystrophic internode elongates roughly in parallel with the average normal internode, and with the dystrophic limb; the longitudinal growth of the dystrophic limb is normal; (4) the variation of internodal length is greater than normal; it does not increase with age; (5) the incidence of the nodes of Ranvier which are wider than the normal 3 micrometers limit does not increase with age; and (6) the number of myelinated axons is reduced in the dy/dy CPN and TN but not in the dy/dy SN; it shows no change with age. These data indicate that: (1) in the dy/dy peripheral nerves (PNS) the abnormal axon-Schwann cell relationships and the reduced number of myelinated axons have been established prior to 1 month of age, thereafter progressive degenerative processes do not appear to take place, and (2) the dy/dy sensory nerves are less affected than the motor ones.

The nodes of Ranvier in the nerves of mice with muscular dystrophy.

Light microscopic, and scanning and transmission electron microscopic studies of the nodes of Ranvier of the distal peripheral nerves of mice with muscular dystrophy (dy/dy) are reported. Extensive widening of the nodes, retraction of Schwann cell cytoplasm and myelin, paranodal thinning of the myelin sheaths, and loss of nodal gap substance were observed. There was no loss of myelinated fibers. The changes at the nodes of Ranvier probably explain the slowed maximum conduction velocity observed in dystrophic peripheral nerves.

Neural abnormalities in the dystrophic mouse.

Neural abnormalities (area of amyelination) have been found in the cranial nerves and in the ventral cervical and lumbosacral roots and in the mixed spinal nerves of bar harbor dystrophic mice of both the severe (129 Re/J dy/dy) and benign (dy-2J DY-2J) forms. The significance of these findings is discussed.

Structural changes in the early stages of Duchenne muscular dystrophy.

The finding of a relative absence of degeneration and regeneration in a muscle biopsy taken at 2½ weeks of age from a boy who later showed the florid pathological changes of preclinical Duchenne muscular dystrophy prompted a review of muscle biopsies taken from boys in the preclinical and early clinical stages of this disease. Only one other biopsy obtained in the first year of life was available. In this, taken at 2 months, there were active changes present. These findings suggest that biopsies taken to detect preclinical cases should not be performed at less than 2 months of age, and raise the possibility of the existence of a stage in Duchenne muscular dystrophy before active degeneration when the muscle shows little or no change on light microscopy.