István Gáti

Classification and Diagnostic Investigation in Inflammatory Myopathies: A Study of 99 Patients

Objective. Insights into the pathogenesis of inflammatory myopathies have led to new diagnostic methods. The aims of our study were (1) to evaluate the consequences of using the classification of Amato/European Neuromuscular Centre Workshop (ENMC) compared to that of Bohan and Peter; and (2) to evaluate any diagnostic benefit in using an extended pathological investigation. Methods. From a consecutive retrospective database, we evaluated 99 patients for classification. Patients with inclusion body myositis (IBM) were classified according to Griggs, et al. In addition to routine stainings and immunohistochemistry, a multilevel serial sectioning procedure was performed on paraffin-embedded material, to identify scarce pathological findings. Results. Classification according to Bohan and Peter could be performed for 83 of the 99 patients, whereas only 60 patients met the Amato/ENMC criteria, the latter resulting in the following diagnostic groups: IBM (n = 18), nonspecific myositis (n = 14), polymyositis (n = 12), dermatomyositis (n = 10), dermatomyositis sine dermatitis (n = 5), and immune-mediated necrotizing myopathy (n = 1). Most of the Amato/ENMC diagnostic groups harbored patients from several of the Bohan and Peter groups, which included a substantial group lacking proximal muscle weakness. The serial sectioning procedure was essential for classification of 9 patients (15%), and led to a more specific diagnosis for 13 patients (22%) according to Amato/ENMC. Conclusion. The classification of Amato/ENMC was more restrictive, forming groups based on clinical criteria and specified myopathological findings, which clearly differed from the groups of the Bohan and Peter classification. An extended pathological investigation increased the diagnostic yield of a muscle biopsy and highlights the quantity and specificity of certain pathological findings.

Bent Spine Syndrome: A Phenotype of Dysferlinopathy or a Symptomatic DYSF Gene Mutation Carrier

Bent spine syndrome : a phenotype of dysferlinopathy or a symptomatic DYSF gene mutation carrier

Familial Scapuloperoneal Myopathy and Mitochondrial DNA Defect

The authors present 13 members of 4 generations in a family with scapuloperoneal myopathy. The disease showed autosomal dominant inheritance. In all 6 patients examined, the disease began in the third decade (18–31 years). Initially the shoulder girdle was involved, and the process slowly spread to the distal part of the lower extremities in several years or decades. The facial and pelvic muscles were only moderately involved; ocular muscle involvement was absent. Myopathy was proved by electromyography and muscle biopsy. In 1 case, electrophysiological evidence of peripheral neuropathy was found, and in 3 other patients central nervous system involvement (dementia, epilepsy) and optic atrophy complicated the syndrome. In the youngest patient, a mutation could be found in the ‘hot-spot region’ of the muscle mitochondrial DNA by polymerase chain reaction.

Culturing of diagnostic muscle biopsies as spheroid-like structures: a pilot study of morphology and viability.

Abstract Objective: The aim of this study was to establish three-dimensional cultures originating from muscle biopsies and evaluate the viability and morphology. Method: Muscle biopsies from patients with suspected neuromuscular disorders were obtained and established as primary muscle tissue cultures. Tissue pieces, 1–2 mm of diameters, were placed in culture medium and subjected to sporadic stirring to prevent attachment and outgrowth as monolayer cells. Morphology and ability to attach to the surface were investigated by light microscopy. Viability was evaluated by 99mTc-tetrofosmin uptake. After 1 month, histology was evaluated by light microscopy and immunocytochemistry. The findings of a healthy muscle and a dystrophic muscle were compared. Results: Initially, the tissue pieces were unshaped but formed spheroid-like structures during the culture period. For dystrophic muscle, attachment capacity to the surface was initially potent and decreased during the culture period, whereas control muscle showed weak attachment from the start that increased during the culture period. The uptake of 99mTc-tetrofosmin increased in control muscle, while it decreased in dystrophic muscle, during the culture period. The histological investigation demonstrated larger destruction of myofiber, weaker satellite cell activation and reduced myofiber regeneration in the dystrophic muscle as compared to the control muscle. Conclusion: The cellular components of the muscle tissue can survive and proliferate as spheroid-like primary cultures. The cellular composition resembles the in vivo condition, which allows studies of degeneration of the original fibers, and activation and proliferation of the satellite cells. The culture system may provide better understanding of the degeneration and regeneration processes in different muscle disorders and allow investigations of pharmacological interventions.

G.P.200

In standard muscle biopsy investigation regenerating fibers are commonly seen in dystrophic muscle, but not in neurogenic myopathy. Using immunohistochemistry these disease groups do differ in the expression of embryonic and fetal myosin heavy chain, but the significance of this is unknown. To learn more about regenerating processes in these groups we investigated the expression of several markers of satellite cells in different stages of activation, and of embryonic and fetal myosin heavy chain in muscle biopsies from patients with dystrophy and neurogenic myopathy, as well as in controls. Frozen sections from 10 patients with limb-girdle muscle dystrophies, 10 patients with motor neuron disease, 10 young and 10 elderly age matched control patients were selected. Immunohistological staining using following antibodies was performed: PAX7, N-CAM, MyoD1, myogenin, neonatal myosin heavy chain, developmental myosin heavy chain and spectrin. The same area in adjacent sections was photographed, followed by counting of fibers and satellite cells. The quotient of myogenin and PAX7 was used as an index for satellite cell activation, and the expressions of the variants of myosin heavy chain were compared between the groups. All biopsies were from the anterior tibial muscle. We found a significantly higher index of activated satellite cells in neurogenic myopathy than in dystrophic myopathy or controls. The higher index of satellite cell activation was paralleled by a higher expression of MyoD1 (indicating satellite cell proliferation). Embryonic myosin was more frequent in dystrophic compared to neurogenic myopathy. The parameters were low and did not differ between the young and elderly control biopsies. The results indicate that there is satellite cell activation in neurogenic myopathy exceeding the activation in dystrophies, and that regenerating fibers in this disease group may by pass the stage of expressing embryonic myosin.

External ophthalmoplegia associated with Hashimoto's thyroiditis and recovered on corticosteroid treatment.

Five-year follow-up of a young male patient is presented. Total external ophthalmoplegia developed 1 week after an upper respiratory tract infection. After 3 years of the course, hyperthyreosis and clinical signs of thyroid-associated ophthalmopathy occurred. Hashimotos thyroiditis and ultrastructural signs of mitochondrial damage of striated muscle were found by histological investigations. The paresis of the external ocular muscles recovered after long-term corticosteroid treatment. On the basis of clinical symptoms and histological results, the authors supposed that an immunological reaction had caused mitochondrial damage in the striated muscles, which also resulted in thyroiditis. This case history points that autoimmune mechanism more frequently might participate in the pathogenesis of chronic external ophthalmoplegia, and the symptoms might precede organ-specific or perhaps systemic autoimmune disorders.

Book Reviews / Announcement

This is a further nice example of a successful collection. The chapters are well written and have been well organized by the two editors. It is therefore a pity that the book title is rather misleading. Indeed ‘Degenerative Dementias’ would be more appropriate, since non-neurodegenerative diseases have been either omitted (dementia associated with systemic diseases) or superficially treated (vascular dementia). A few ‘new’ diseases are not mentioned, such as CADASIL (except in one table). Behavioural, cognitive and psychiatric features of dementia syndromes have also been omitted, as well as the psychosocial aspects. For these reasons, the book will be more useful to scientists, researchers and students looking for nosological updates than for clinicians dealing with day-to-day problems of demented patients. J. Bogousslavsky, Lausanne H. Duvernoy