Three familial cases presenting with an immobile spine. Rigid spine or Emery-Dreifuss syndrome?

A father and his two sons presented with slowly progressive muscular weakness, contractures of the spine, elbows and ankles, and cardiac conduction disturbances in the father. Clinical and histological findings are discussed in relation to the hitherto reported cases of autosomal dominant variant of the Emery-Dreifuss syndrome and the distinction from the rigid spine syndrome.

Enzyme activity patterns of myosin ATPase, alpha-glycerophosphate dehydrogenase and succinate dehydrogenase within different muscle fibre types.

Muscle fibre compositions of five different rabbit muscles were determined by combining two enzyme-histochemical reactions (NADH tetracolium oxidoreductase and myosin ATPase after alkaline preincubation). The differentiation into the fibre types, fast twitch glycolytic (FTG), fast twitch oxidative (FTO), and slow twitch oxidative (STO) was possible by a reliable staining classification. Aim of the study was the estimation of enzyme activity patterns within the three different fibre types. For this purpose, four serial cross-sections with several enzyme histochemical reactions were performed: alkaline combination method for fibre type determination, the reactions of myosin ATPase, alpha-glycerophosphate dehydrogenase (GPDH), and succinate dehydrogenase (SDH). The measurement procedure for the estimation of enzyme activities was based on the proportionality between the intensity of the enzyme histochemical staining reaction and the degree of enzyme activity. The activities of GPDH (indicator for glycolytic metabolism) and SDH (oxidative metabolism) were inverse. The calcium-activated myosin ATPase showed only little activity in slow twitch fibres after alkaline preincubation. In contrast to slow twitch fibres, ATPase activity in fast twitch fibres was relatively high. The results showed that the classification of muscle fibre types due to their myosin ATPase activities and their main metabolisms (oxidative and glycolytic respectively) is justified.

Pitfalls in the histochemical demonstration of alpha-glucan phosphorylase activity in glycogen-depleted skeletal muscle fibres.

In the present communication, an investigation is described into the reliability of histochemical methods for the demonstration of alpha-glucan phosphorylase activity in glycogen-depleted skeletal muscle fibres. Human skeletal muscles with glycogen-depleted fibres from patients with diseases of the neuromuscular system and from subjects who had suffered from malignant hyperthermia were used for the study. The location of phosphorylase activity and glycogen was demonstrated with histochemical techniques. Biochemical techniques were used to assay the activity of phosphorylase and the content of glycogen. Biochemical determinations of phosphorylase activity did frequently not reveal significant differences between glycogen-depleted and non-depleted skeletal muscle fibres. In contrast, all histochemical methods investigated, showed little or no phosphorylase activity in the glycogen depleted fibres, indicating that none of the existing histochemical methods revealed reliable staining results in these fibres. Owing to the invalid staining results of the histochemical methods for glycogen-depleted muscle fibres, it is necessary that for metabolic studies a biochemical assay for phosphorylase activity is also to be performed.

[Age characteristics of the normal human skeletal musculature--mathematical description of postnatal skeletal muscle growth]. / Alterskennzahlen der normalen menschlichen Skelettmuskulatur--Mathematische Beschreibung des postnatalen Skelettmuskelwachstums.

The number of muscle fibres per mm2 is age dependent, and therefore briefly denoted as age specific number (Alterskennzahl AK). We determined the AKs for the age groups up to 25 years, separated after the sexes and for M. vastus lateralis et deltoideus. According to the trend of the original data the approximations have been carried out applying 4 functions of organismic growth in modified form, i.e. the Pütter (1920), Bertalanffy (1934), Richards (1959), Janoschek extended by Sager (1984) and Richards extended after Sager (1980). Curve fitting is reached by regression analysis and nonlinear regressions using the sums of the linear deviations as a criterion for the goodness of fit. Results including initial as well as final values are summarized in tables with the parameters of the calculation methods added. The AKs allow judging the degree of maturity in the skeletal musculature during childhood. Transposing of the equations for AK = W yields t as a function of the normally adjunctive age specific number. The difference against real age reveals to which degree the musculature is eventually underdeveloped. Concerning the interpretation the fact should be kept in mind that biological processes are involved. The relation of the fibre types too implies a characteristic age dependency. This statement and the fibre diameters gained from the same material allow a mutual control and an exact fixation in each case.

[Neurogenic tissue syndrome. Review and specific results]. / Das neurogene Gewebssyndrom. Ubersicht und eigene Ergebnisse.

A review is given of the skeletal muscle and specific methods required for its examination, before major findings from the neurogenic tissue syndrome are discussed in some detail. These findings, not specific of the diseases involved, may be grouped as follows along three lines: alterations resulting from (repetitive) denervation; re-innervation; secondary myopathic alterations (also called concomitant myopathy). Evaluation and rating of all findings and data relative to percentual incidence are followed by postulation of a guideline for diagnosis.

[Nosologic evaluation of oculopharyngeal myopathic syndromes]. / Nosologischer Stellenwert okulopharyngealer myopathischer Syndrome.

Three patients with oculopharyngeal involvement of neuromuscular origin are presented: one patient suffering from an oculopharyngeal neuromuscular disease (developing an oculopharyngeal muscular dystrophy?) and two patients representing a neuromuscular mitochondriopathy. There is no evidence that the oculopharyngeal myopathy and neuromuscular disease, respectively, are the same, despite the simularity of the syndrome. The different clinico-pathological types of oculopharyngeal syndromes are discussed. Following-up the development of further manifestations of the oculopharyngeal syndrome can helf classifying them.

[Facioscapulohumeral neuromuscular syndromes--problems of differential and early diagnosis and genetic counseling]. / Fazioskapulohumerale neuromuskuläre Syndrome--Probleme der Differential und Frühdiagnose und genetischen Beratung.

Among 20 kinships affected by facioscapulohumeral and scapulohumeroperoneal neuromuscular syndromes 6 probands with autosomal dominant transmission and 5 obviously sporadic cases revealed myopathic changes on biopsy and were classified to have facioscapulohumer (operone)al muscle dystrophies. 5 autosomal dominant cases and one sporadic case with neurogenic muscle changes and 3 other non-dystrophic phenocopies emphasize the necessity of muscle biopsy for nosological assignment. Definite correlations between mode of inheritance, clinical and morphological findings could not be found. Pathological ultrasound and EMG findings in parents and children of seemingly sporadic cases suggest to assume autosomal dominant inheritance with incomplete penterance in such cases.

[Secondary muscular carnitine deficiency following immunosuppressive treatment]. / Sekundärer muskulärer Carnitinmangel nach immunsuppressiver Behandlung.

Carnitine deficiency syndromes can be classified into two groups: primary carnitine deficiency and secondary carnitine deficiency syndromes. A lipid storage myopathy with carnitine deficiency following an immunosuppressive therapy is described in a young man suffering from a possible polymyositis. After treatment with L-carnitine both biochemical and morphological features recovered. A secondary carnitine deficiency syndrome due to an immunosuppressive therapy is supposed.

Myopathy with mitochondrial abnormalities and rimmed vacuoles.

A man of 44 years suffering from an exercise-induced neuromuscular disease with mitochondrial abnormalities and rimmed vacuoles is reported. The mitochondrial abnormalities and rimmed vacuoles (autophagic vacuoles) are interpreted as sequential changes of the same pathogenetic process depending on the degree of energy deficiency.

[Pathological myophosphorylase reaction in malignant hyperthermia]. / Pathologische Myophosphorylasereaktion bei der malignen Hyperthermie.

In malignant hyperthermia, myophosphorylase reaction shows characteristic changes that take place within minutes: (1) a generally strongly weakened reaction; (2) numerous negatively reacting fibres; (3) frequently, fibre sections that show spotty and/or striatal weak or negative reactions and fibre sections with strong striatal reactions with relatively narrow sarcomere spacings (a "sign of hypercontraction"). Obviously, the morphological findings that show characteristic "striated fibres" are typical of the malignant hyperthermia syndrome! It is important to note that the muscular fibres showing such changes are, as a rule, inconspicuous when using other stains and reactions. These pathological myophosphorylase reactions were observed in five deceased patients (one independently of anaesthesia after an extended walk) and in 19 pigs (18 times after halothane testing and once in an experimental animal with clinical evidence of the presence of malignant hyperthermia). These reactions were not noted in pigs with negative halothane reactivity or prior to halothane testing. They were also not seen in a large number of very different healthy and diseased control and reference cases from our biopsy and autopsy material. Myophosphorylase reaction enables convincing demonstration of malignant hyperthermia, past or present. Hence, it is possible to elucidate puzzling deaths or verify apparently clear death occurring during or subsequent to anaesthesia or simply following stress ("human stress syndrome"). Many of these deaths doubtlessly escape the attention of clinicians using the usual morphological examination methods. However, the reaction cannot be used to identify potential victims.

[Metabolic triglyceride storage disorders. A report of 2 cases of systemic carnitine deficiency]. / Stoffwechselstörungen mit Triglyzeridspeicherungen Ein Bericht über 2 Fälle von systemischem Karnitinmangel.

Two cases of triglyceride storage in liver, kidney, heart, and skeletal muscle are described in infants who died at the age of 1 1/2 years and 4 d, respectively. In the first patient, a previously normal girl, the clinical symptoms began two months before death with encephalopathy (vomiting, unconsciousness), liver enlargement, hypoglycemia, increase in serum transaminases. These signs disappeared within the following days. Some weeks later she died during the second attack. The 4-d-old boy, the second child of healthy consanguineous parents, showed at the third day of life an impaired sucking, muscular hypotonia, respiratory arrest and bradycardia. An intensive therapy was inefficient. At autopsy gross examination showed only a moderately enlarged yellow liver and an edematous brain in the first case and pale organs in the second one but no cause of death. The microscopial examination of all tissues of both cases showed fat storage within the four organs mentioned above. The common histochemical methods for neutral lipids were positive, the Schultz-reaction for cholesterol and cholesterol esters was negative. The lipid loaden cells did not show birefringence in polarized light. A predominance and strong fat storage of the type I fibres was found in the skeletal muscle. The storage of triglyceride could be confirmed by histochromatography, a thin-layer chromatography of tissue sections. The triglyceride accumulation in liver, heart, kidney, and skeletal muscle is a characteristic feature of systemic carnitine deficiency. The clinical symptoms of the first patient are in agreement with reports of this disease also. A carnitine deficiency in a newborn was not yet described. Family studies revealed a low carnitine concentration in the mother's serum in both cases, while the serum of father and brother resp. sister showed normal carnitine levels.

[Sporadic occurrence of benign myopathy with early contractures (Emery, Dreifuss and Rotthauwe)]. / Sporadisches Auftreten der benignen Myopathie mit Frühkontrakturen (Emergy-Dreifuss und Rotthauwe).

A myopathy which sporadically appeared in a young male corresponds clinically, electromyographically, histologically and cardiologically to the rare picture of the X-chromosomally recessive benign myopathy with early contractures. The coordination to the clinical picture mentioned and the genetic advice, taking into consideration the X-chromosomally recessive heredity, are discussed and proved.