Donald L. Schotland

Muscle is electrically inexcitable in acute quadriplegic myopathy

We directly stimulated muscle in three patients with acute quadriplegic myopathy to determine whether paralyzed muscle in this syndrome is electrically excitable. Two of the patients had been treated with neuromuscular blocking agents and corticosteroids, and one patient had been treated with corticosteroids alone. We found that paralyzed muscle is electrically inexcitable in affected patients. Muscle regained electrical excitability over weeks to months. The recovery of muscle excitability paralleled the clinical recovery of patients, suggesting that paralysis in this syndrome is secondary to electrical inexcitability of muscle membrane.

Abnormal hemoglobin as a cause of neurologic disease.

A VARIETY OF NEUROLOGIC DISORDERS has been attributed to sickle-cell disease.’-20 However, it is not clear which of these are causally related to the sickling abnormality. Furthermore, during the past decade, several abnormal hemoglobins have been identified in association with disease states, the symptoms of which may vary.21 In an attempt to evaluate these problems, the experience of the’ Columbia-Presbyterian Medical Center since 1940 has been reviewed.

Cytochrome‐c‐oxidase deficiency in a floppy infant

We report an infant with cytochrome-c-oxidase deficiency whose clinical presentation is identical to that of two previously reported patients, including failure to thrive, respiratory decompensation, acidosis, DeToni-Fanconi-Debre syndrome, and mitochondrial myopathy leading to death.

Freeze fracture studies of muscle plasma membrane in human muscular dystrophy

SummaryFreeze fracture analysis of intramembranous particle density in skeletal muscle plasma membrane from 7 patients with Duchenne muscular dystrophy (DMD), 5 patients with facioscapulohumeral muscular dystrophy (FSH) and 5 patients with myotonic dystrophy (MyD) were carried out. Marked deplction of intramembranous particles including orthogonal arrays were significantly decreased in FSH. No abnormalities were noted in MyD.

Quantitative ultrastructural study of muscle satellite cells in Duchenne dystrophy

Quantitative ultrastructural studies of satellite cell populations, and nuclear chromatin analysis of satellite cell nuclei and true subsarcolemmal nuclei were carried out in normal and Duchenne muscular dystrophy (DMD) muscles. There was a remarkable increase in the number of satellite cells in muscles of patients with mild to moderate stages of DMD, as compared to preclinical or very early and probably advanced stages of DMD, and a significant increase in euchromatin content was found in the satellite cell nuclei in DMD. Since it is generally accepted that satellite cells participate actively in muscle fiber regeneration, this study suggests that muscle fiber regeneration is ineffective in DMD.

Ultrastructural studies of muscle in McArdle's disease.

An electron microscopic study of the flexor carpi radialis muscle from 2 patients with MeArdles disease is presented. Glycogen accumulation occurred primarily in the intermyofibrillar space of the I band and under the sarcolemma. Increased amounts of glycogen were also noted between the thin filaments within the I band and. occasionally, between filaments in the A band. The most significant alteration in the muscle fiber, in terms of muscle fiber function, was disorganization of the myofibrils at the level of the I band. This was due to compression of the myofibrils by excess glycogen in the inter-myofibrillar space and displacement or replacement of thin filaments within the myofibrils by glycogen deposits. It is suggested that these alterations in myofibril structure, due to glycogen deposition, may lie one of the causes of the permanent weakness that has been observed in the later stages of McArdles disease. The distribution of excels glycogen in McArdles disease may provide indirect evidence for tile localization of skeletal muscle phosphorylase. Electron microscopic study of phosphorylase deficient muscle in physiological contracture, removed 30 minutes after the onset of ischemic exercise, revealed mitochondrial alterations and dilatation of portions of the sarco-plasmic reticulum.

Electron cytochemistry of crystalline inclusions in human skeletal muscle mitochondria

Limb muscle biopsies from a patient with idiopathic progressive ophthalmoplegia and a patient with a slowly progressive neuromuscular disorder since infancy revealed by conventional electron microscopy the presence of crystalline inclusions in the mitochondria as the most prominent morphological finding. Electron cytochemical studies on fresh tissue blocks showed no cytochrome C oxidase or carnitine acetyl transferase activity within the crystalline inclusions. The study of respiration linked accumulation of electron dense strontium supported by either NAD or flavoprotein linked substrates on freshly isolated mitochondrial fractions showed no electron dense strontium within the crystalline inclusions. These electron cytochemical findings suggest that the crystalline inclusions are space occupying structures that do not have an active functional role within the mitochondrion.

The clinical diagnosis of McArdle's disease. Identification of another family with deficiency of muscle phosphorylase.

APPLICATION of biochemical techniques to the study of human disease has permitted the recognition of several new syndromes. Although biochemical in nature, these disorders can often be identified on clinical grounds and by relatively simple laboratory tests. McArdle’s disease, or inherited deficiency of muscle phosphorylase, is such a disorder, as illustrated by the following histories of two brothers and an analysis of cases reported previously.

Myasthenic myopathy and thymoma

When language is ambiguous, thought is imprecise and vice versa. The phrase “myasthenic myopathy” ought to mean something, but each of the words that the term comprises is ambiguous when used alone and even more so when used together. We have seen several cases that warrant this designation, but they differ from each other and there is n o terminology t o illuminate these differences. Before presenting these cases, it is therefore desirable t o indicate the numerous implications of these words as they have been used in the recent literature. Myasthenic ought to be an adjective or adverb, modifying a noun or verb t o indicate that there is a similarity to myasthenia gravis. I t has been used to signify excessive fatigue, but this is usually an emotional disorder, psychasthenia rather than myasthenia, o r similar fatigue in other muscle diseases. This usage is ap t t o be more confusing than helpful. Normal fatigue is not defined, and muscles weakened from any (cause probably tire more rapidly than normal. W e therefore defined myasthenia as a syndrome characterized by weakness lacking any of the conventional signs of neural injury, varying in severity, with predilection for cranial muscles as well as limb muscles, and improving after administration of cholinergc drugs.’ Fatigue does not enter into this definition, and it does not include electrophysiologc characteristics. Although there is a specific pattern of electro-

Freeze‐fracture studies of erythrocyte plasma membrane in human neuromuscular diseases

Freeze-fracture studies were conducted in erythrocyte plasma membrane from 8 patients with Duchenne muscular dystrophy (DMD), 8 age-matched controls, 3 adult controls, 10 patients with myotonic muscular dystrophy, and 26 other neuromuscular disease controls. There was marked depletion of intramembranous particles in Duchenne dystrophy, whereas intramembranous particle density counts in other neuromuscular diseases were within normal limits. Therefore, the internal molecular architecture of the erythrocyte membrane is abnormal in Duchenne dystrophy, supporting the concept that a membrane defect involving multiple tissues is present in this disorder.