G.K. Van Wijngaarden

Familial "myotubular" myopathy.

THE EXISTENCE of central nuclei, so-called myotubes, or type I fiber hypotrophy in muscle diseases has been described by several authors. These diseases were given different names. Spiro et al.,l Kinoshita et a1.,2 and Coleman et al.3 described their cases as “myotubular myopathy,” because the main pathology consisted of fibers resembling fetal myotubes. Sher et aL4 and Bethlem et al.5 called their cases “centronuclear myopathy,” because they regarded the presence of the many centrally placed nuclei as the most characteristic feature. Engel et al.6 reported a case as “type I fiber hypotrophy and central nuclei,” thus describing the two principal histopathological features. Bethlem et al.7 listed <‘type I fiber atrophy, central nuclei, and myotube-like structures” as the most conspicuous findings in their patient. The clinical picture of these cases was variable. Both males and females were affected. The onset was at birth or in early infancy. All patients showed widespread muscle involvement combined with areflexia. Involvement of extraocular or facia1 muscles or both was a frequent but not constant finding. In the family to be described, at least 6 siblings suffered from a muscle disease that showed many similarities to the above-mentioned cases.

X‐linked myotubular myopathy with fatal neonatal asphyxia

A second family with X-linked myotubular myopathy is described. The clinical picture includes decreased fetal movements; hydramnios, in at least three cases, probably resulting from insufficient swallowing in utero; and asphyxia at birth. In three autopsy cases many myotubes were found in the muscle tissue. In five definite female carriers, muscle biopsy revealed changes, including myotubes in four. This family probably is not related to the earlier described family with X-linked myotubular myopathy, from which it differs in its 100 percent fatal outcome in the neonatal period, as compared with 25 percent in the earlier described family. A most important finding, in both families, is the possibility of recognizing clinically healthy female carriers by muscle biopsy.

Spinal muscular atrophy and hypertrophy of the calves

In 100 patients (59 males and 41 females) suffering from proximal spinal muscular atrophy, 23 presented with hypertrophy of the calves. These were all males. They all showed an elevation of serum CK-activity. The combination of spinal muscular atrophy, hypertrophy of the calves and elevated serum CK activity was not found in females.

Changes in motor innervation and histochemical pattern of muscle fibers in some congenital myopathies

Changes in motor innervation were compared with histologic and histochemical pattern of muscle fibers in three biopsies of central core disease, four biopsies of nemaline myopathy, one biopsy of myotubular myopathy, and three biopsies of mitochondrial myopathy. Evidence of collateral reinnervation was obtained only in one biopsy from central core disease. In other biopsies, no structural or ultrastructural abnormality of axis cylinders, myelin, or myoneural junction suggesting denervation were observed. The only relevant change found in centronuclear myopathy and to a lesser extent in nemaline myopathy was an unusual smallness and simplification of motor endings, suggesting delayed or impaired maturation. Muscle fibers strongly reactive for both adenosinetriphosphatase and nicotinamide-adenine dinucleotide diaphorase, observed in central core disease and mitochondrial myopathy, were not associated with increased terminal innervation ratio.

Familial focal loss of cross striations

SummaryTwo patients, a brother and sister, both suffering from congenital generalized muscle weakness with a progressive course are reported. Muscle biopsy revealed areas with loss of cross striations in the muscle fibers, electronmicroscopically presenting complete disorganization of the myofibrils with streaming of the Z discs and absence of mitochondria. Vesicular nuclei with prominent nucleoli were present in these areas. There was a type I fiber prodominance in both cases. The mean diameter of the type I muscle fibers in one of the cases was too small. Motor endplate alterations in this patient gave no evidence of denervation but were suggestive of a delayed development of motor nerves.ZusammenfassungEs werden zwei Patienten beschrieben, Bruder und Schwester, beide an einer kongenitalen, generalisierten, progressiven Muskelschwäche leidend. Die Muskelbiopsie zeigte Zonen mit Verlust der Querstreifung in den Muskelfasern, und bei elektronenmikroskopischer Untersuchung zeigte sich eine totale Unordnung der Myofibrillen mit Strömung der Z-Scheiben und Fehlen von Mitochondrien. In diesen Bezirken fanden sich blasige Kerne mit prominenten Nukleolen. In beiden Fällen zeigte sich ein starkes Überwiegen der Typ-I-Fasern. Der mittlere Durchmesser der Typ-I-Muskelfasern war in einem der Fälle zu gering. Veränderungen in der motorischen Endplatte in diesem Fall zeigten keine Denervierung, sondern deuteten auf eine verzögerte Entwicklung der motorischen Nerven.

Familial carnitine deficiency. A fatal case and subclinical state in a sister.

A 15-year-old girl with a large accumulation of lipid in the muscle fibers, was suffering from systemic carnitine deficiency. She died in acidosis. The blood carnitine level was normal. At necropsy, carnitine levels were low in skeletal muscles and heart, whilst a normal level was found in the liver. Carnitine palmitoyltransferase II and palmitoyl-CoA synthetase activities were increased, whereas carnitine acetyltransferase, glycerol-3-phosphate dehydrogenase (FAD) and succinate dehydrogenase were decreased. Investigation of blood and skeletal muscle of the family members revealed marked abnormalities in a 7-year old sister who had only minor neurological symptoms. Histochemical investigation revealed abnormal accumulations of lipid between the myofibrils. Carnitine was decreased in her skeletal muscle and blood. Muscular carnitine palmitoyltransferase II and palmitoyl-CoA synthetase were again increased in activity while glycerol-3-phosphate dehydrogenase (FAD) was decreased. The activities of succinate dehydrogenase, carnitine palmitoyltransferase I and glycerol-3-phosphate dehydrogenase (NAD+) were normal. The unexpected normal carnitine level in blood and liver of the deceased patient was attributed to muscle wasting, which was confirmed by the very high blood level of creatine phosphokinase. This fatal case indicates that the fasting condition must be avoided in persons with carnitine deficiency. In crises, glucose supply is necessary since gluconeogenesis may be blocked.

The incidence of lobulated fibres in the facioscapulohumeral type of muscular dystrophy and the limb-girdle syndrome

Abstract A description is given of the histopathological and electron-microscopic properties of a hitherto unreported structural change of the muscle fibre. In transverse sections these fibres have a lobulated aspect and are therefore termed “lobulated fibres”. Lobulated fibres were found in 13 of 300 consecutive muscle biopsies from patients suffering from neuromuscular diseases. Of these 13 cases there were 7 with the facioscapulohumeral type of muscular dystrophy, 2 with the limb-girdle type of muscular dystrophy, 2 with chronic spinal muscular atrophy and 2 with an autosomal dominant hereditary neuromuscular disease that could not be classified. It is stressed that of 7 patients with the facioscapulohumeral type of muscular dystrophy 4 showed signs indicative of a neurogenic pathogenesis. Although lobulated fibres constitute a nonspecific structural change of muscle fibres, their frequent occurrence in the facioscapulohumeral type of muscular dystrophy appears to be a significant finding.

A case of intradural arteriovenous aneurysm of the posterior fossa

The patient was a 65-year-old woman who had always been in good health except for recurrent “rheumatic” symptoms in the joints. At the age of 63, she had a mastectomy for a circumscribed carcinoma of the left breast. The postoperative course was uneventful and the patient remained asymptomatic. In April 1964, five months before we examined the patient, she was awakened one night by a loud thumping and squeaking sound in the left ear, synchronous with the pulse. She noticed that the sound diminished or disappeared when she rested the left occipital region of her skull on the pillow. The patient herself detected the cause of this phenomenon when she felt a pulsating blood vessel behind the left ear. The sound disappeared when she compressed this vessel with a finger and returned when she discontinued the pressure. The sound persisted during the next five months without a change in character or intensity. There were no other symptoms. Exanimtion. Auscultation of the skull disclosed a loud bruit synchronous with the heart beat, with maximum intensity over the left mastoid and left occipital region. The bruit immediately disappeared on compression of the left common carotid artery and also on conipression of the left occipital artery, which pulsated more distinctly than the right occipital artery. Neurological examination revealed no abnormality. The blood pressure was 150/100, and the pulse rate was 80 per minute. There were no abnonnalities on general examination. Routine blood counts, urinalysis, and liver function tests were normal. Serological tests for syphilis were negative. The electrocardiogram was normal. An electroencephalogram was characterized by instability of the alpha rhythm and discrete local disturbances in the left parieto-

Observations on central core disease

Abstract A description is given of 2 patients who had cores in their muscle fibres. Patient 1 was a 5-year-old girl suffering from a non-progressive myopathy mainly involving the pelvic girdle. Histochemical investigation of the muscle tissue did not permit a differentiation into type I and type II fibres. Cores were present in 10% of the muscle fibres. Patient 2 was a 12-year-old boy suffering from a severely progressive myopathy. The first manifestation of the disease was facial diplegia. Cores were found in 10% of the type I fibres. The father and mother of both patients showed myopathic features on electromyographic examination.

Epsilon-Aminocaproic Acid Myopathy

A case of acute necrotic myopathy due to epsilon-aminocaproic acid (EACA) is described and compared with similar cases in the literature. This myopathy has only been noted after prolonged administrati