Experimental serotonin myopathy.

One hundred and eight Wistar rats were injected with serotonin (20 mg per kilogram of body weight intraperitoneally) or imipramine hydrochloride (20 mg per kilogram intraperitoneally), or both, in a single cycle or in multiple (up to 18 weeks) weekly cycles. In contrast to previous reports, a characteristic myopathy was produced with serotonin alone, identical to that produced by serotonin and imipramine in combination. Imipramine alone produced no significant change. The myopathy produced was characterized by (1) preferential damage to myofibers with high oxidative capacity (types I and IIA), (2) prominent regenerative activity occurring as early as 48 hours, and (3) degeneratio of capillary endothelium (thickening, vacuolar degeneration, proliferation of marginal folds, dissolution of mitochondria). Small groups of degenerating fibers and increased connective tissue were not observed. There was no loss of myofibers or fat replacement. The changes suggested repeated acute insults followed the complete recovery. These observations suggest that although the pathogenesis of serotonin and serotonin-imipramine myopathy is primarily ischemic, it is not a satisfactory model of human Duchenne muscular dystrophy.

Immunocytochemical localization of immunoglobulins in the inflammatory lesions of polymyositis.

Biopsy material from the muscles of 40 patients with either polymyositis or dermatomyositis was examined with the immunoperoxidase method to compare the distribution of immunoglobulin (Ig)-containing cells in the inflammatory infiltrates and elsewhere in the muscle tissue. Large numbers of IgG-positive and occasional IgM-positive cells were found in the infiltrates in 23 of these biopsies in contrast to the rather sparse representation of plasma cells. It is suggested that the Ig-containing cells may either represent local B-cell differentiation and proliferation or that the cells are involved in antibody-dependent cell-mediated tissue damage.

Distal spinal muscular atrophy. A clinical and genetic study of 8 kindreds.

Twelve patients (8 kindreds) with distal SMA are described, and an analysis presented of their clinical and genetic features. Distal SMA accounted for 10% of all patients with SMA in a total population survey of this disease in North-East England. The parental consanguinity rate is high, occurring in 3 of the 8 kindreds reported; the sex ratio was 1.0; the segregation ratio of sibs did not differ from 0.25. Intrafamilial concordance for clinical features of the disease is high. This current data is consistent with a suggested aetiology of two separate autosomal recessive genes. Clinical features are discussed and a review of the literature presented. The disease is only slowly progressive, but one of the genetic types may present with infantile or early juvenile onset; there is no evidence that it shortens life. 50% of cases did not have a normal gait after 4 years of age; 50% could not run after 17 years of age; and 50% could not walk unaided after 28 years of age. Details of prognosis, and principles of genetic counselling in this disease are discussed.

Procainamide-induced myositis.

The risk of developing a syndrome resembling lupus erythematosus when taking procainamide has been well recognized for over 15 years, although the development of myopathy has been reported on one occasion only, in this instance without histopathological evidence of muscle inflammation. The patient reported in this paper developed a severe, rapidly progressive vasculitis, apparently limited to muscle, after taking procainamide for 42 months, his myopathy remitting rapidly after withdrawal of the drug and a short course of treatment with azathioprine. Although this man had no clinical evidence of SLE, he had impressive immunological evidence to support this diagnosis.

Moebius syndrome, peripheral neuropathy and hypogonadotrophic hypogonadism.

The association of congenital ophthalmoplegia and facial paresis (Moebius syndrome) with a variety of other developmental somatic defects has been widely recognised. Its co-existence with hypogonadism of hypothalamic/pituitary origin and subclinical peripheral neuropathy has been reported and in this paper we describe the second case of the Moebius syndrome in association with hypogonadotrophic hypogonadism and a progressive peripheral neuropathy of mixed axonal and demyelinating type.

Cardiac complications of polymyositis.

We report 3 cases of polymyositis, confirmed by enzyme assay and muscle biopsy, complicated by serious cardiac disease. They showed progressive fascicular block, despite immunosuppressive therapy sufficient to control the skeletal muscle disease, culminating in complete heart block with syncope, requiring the implantation of a pacemaker. In addition, all 3 showed echocardiographic evidence of dilated cardiomyopathy.

Mitochondrial myopathy.

Six clinically affected and 18 asymptomatic members of a six-generation family were investigated clinically, by estimation of serum CK levels, and in some cases by quantitative electromyographic techniques and muscle biopsy. It was concluded that the myopathy was probably inherited as an autosomal dominant trait with variable expression and incomplete penetrance although the possibility of mitochondrial inheritance could not be excluded in view of the almost exclusive transmission through the female line. Eight members of the family with myopathy also had diabetes mellitus, and 2 of these also had cerebellar ataxia. It is suggested that the myopathy, the cerebellar disorder and the diabetes may all be manifestations of the same underlying metabolic defect.

Carnitine-palmityl-transferase deficiency.

An increasing number of cases of myopathy due to disordered lipid metabolism have recently been recognised and these appear to fall into two contrasting clinical and biochemical categories. Some patients present with steadily prograssive proximal weakness which sometimes responds to steroid therapy and which is due to carnitine deficiency in skeletal muscle. In the second category, patients usually present with muscle cramps on exertion then followed by myoglobinuria without established proximal myopathy and their symptoms are associated with deficiency of carnitine palmityl transferase in skeletal muscle. In this paper we report a patient who has well-documented carnitine palmityl transferase deficiency, whose symptoms were triggered by violent exercise after fasting and in whom there was variable histochemical and ultrastructural evidence of lipid accumulation in muscle biopsy samples. Development of the patient's symptoms was suppressed by a high carbohydrate diet.

A comparison of the structure of small blood vessels in normal, denervated and dystrophic human muscle.

A light- and electron-microscopic study of the small arterial vessels and capillaries in muscle from 20 patients with Duchenne muscular dystrophy failed to adduce any direct morphological evidence that the necrobiotic muscle lesions in this disease are produced by muscle ischaemia. However the electron-microscopic studies showed that the basement membrane width in 3 out of 4 cases of Duchenne dystrophy so studied was significantly less than that or normal control material. In further case of Duchenne dystrophy, selected for study because some vessels in the biopsy muscle were surrounded by small round cell infilitrates, the basement membrane width was significantly greater than that in the normal control material. In the single case of spinal muscular atrophy studied, the basement membrane width was also significantly less than the control measurements. The possible relationship of these observations to the "ischaemic" theory of the pathogenesis of muscular dystrophy is discussed.

Symptomatic lumbar spinal arachnoiditis: fact or fallacy?

It is generally accepted that chronic adhesive lumbar arachnoiditis is a cause of symptoms, notably back pain and/or pain (of almost any type, not necessarily 'anatomical') in the lower limbs, although there is no clearly defined clinical pattern which is clearly associated with this syndrome. There is no doubt that arachnoiditis occurs as a pathological and radiological entity due to a number of causes. In the view of the present authors, the nexus between the pathology and radiology on the one hand, and the patients' symptoms on the other hand, has not been demonstrated with any degree of scientific rigor.

Clinical, biochemical and histological responses to treatment in polymyositis: a prospective study.

Routine methods of monitoring treatment responses in polymyositis patients, such as clinical strength assessments and measurements of ESR and serum creatine kinase, have been compared with functional strength measurements and assay of serum myoglobin levels, in a prospective study of nine cases followed for up to five years. Seven patients also underwent serial muscle biopsies during the first year of treatment in order to document the nature and chronology of histological changes during therapy. Inflammatory and necrobiotic changes indicating active myositis resolved within six months in all cases and no patient developed histological evidence of steroid myopathy. Scores on functional muscle strength assessments improved more slowly than static manual muscle strength test results, reflecting morphometric and architectural abnormalities in the biopsies which persisted throughout the period of observation. Serum creatine kinase levels returned to normal more rapidly than serum myoglobin. No statistical relationship was found between muscle strength measurements and biochemical or histological changes within the patients as a group, but variations in these indices in individual subjects reflected changes in clinical state.