Antititin antibody in early- and late-onset myasthenia gravis.

OBJECTIVES: Myasthenia gravis (MG) is an autoimmune disease caused by antibodies against neuromuscular junction proteins, 85% of patients have antibodies against acetylcholine receptor (AChR-MG). Antititin antibodies are present in a subset of patients with MG. We aimed to determine the value of antititin antibodies as severity markers and thymoma predictors in early- and late-onset MG. MATERIALS & METHODS: Two-hundred and ninety-five consecutive MG patients (188 F and 107 M) aged 12-89 years (mean 50y) were included. 164 patients had early-onset (EOMG, ≤50 years of age), 131 had late-onset MG (LOMG). Twenty-six patients had thymoma. symptoms, severity graded with MGFA scale, thymus histology, medications, and treatment results were analyzed. RESULTS: Antititin antibodies were present in 81 (27%) of all patients: 54% of thymoma MG, 0.6% of non-thymomatous EOMG, and 55% of LOMG, with proportion of titin-positive patients increasing linearly from 40% in the 6th to 88% in the 9th decade of life. Titin-positive patients had more bulbar symptoms (P = 0.003). Severity of MG, need for immunosuppression, myasthenic crisis risk or treatment results were not related to its presence. Antititin antibodies had 56% sensitivity, 99% specificity, 90% positive predictive value (PPV), and 95% negative predictive value (NPV) for thymoma diagnosis in EOMG, and 50% sensitivity, 75% specificity, 71% PPV and 55% NPV in LOMG. CONCLUSIONS: Antititin antibodies have high PPV and NPV for thymoma in EOMG. In MG without thymoma, antititin antibodies can be considered as markers of LOMG, but not of a severe course in our MG cohort.

Muscle pathology in 31 patients with calpain 3 gene mutations..

BACKGROUND AND PURPOSE: At present, more than 20 different forms of limb-girdle muscular dystrophies (LGMDs) are known (at least 7 autosomal dominant and 14 autosomal recessive). Although these different forms show some typical phenotypic characteristics, the existing clinical overlap makes their differential diagnosis difficult. Limb-girdle muscular dystrophy type 2 (LGMD2A) is the most prevalent LGMD in many European as well as Brazilian communities and is caused by mutations in the gene CAPN3. Laboratory testing, such as calpain immunohistochemistry and Western-blot analysis, is not totally reliable, since up to 20% of molecularly confirmed LGMD2A show normal content of calpain 3 and a third of LGMD2A biopsies have normal calpain 3 proteo-lytic activity in the muscle. Thus, genetic testing is considered as the only reliable diagnostic criterion in LGMD2A. MATERIAL AND METHODS: In an attempt to find a correlation between genotype and muscle pathology in limb-girdle muscular dystrophy 2A we performed histopathological investigation of a group of 31 patients subdivided according to the type of pathologic CAPN3 gene mutation. RESULTS: In all biopsies typical features of muscular dystrophy such as fiber necrosis and regeneration, variation in fiber size and fibrosis were noted. Lobulated fibers were often encountered in the muscle biopsies of LGMD2A patients. Such fibers were more frequent in patients with 550delA mutation. CONCLUSIONS: These findings may be helpful in establishing diagnostic strategies in LGMD.

IBM-type inclusions in a patient with slow-channel syndrome caused by a mutation in the AChR epsilon subunit.

We report a patient with a slow-channel congenital myasthenic syndrome who carries a novel slow-channel mutation in the epsilon subunit of the acetylcholine receptor and has tubulofilamentous inclusion bodies, in skeletal muscle of the type observed in hereditary and sporadic inclusion body myositis. Ultrastructural analysis of a muscle specimen obtained at the age of 9 years showed an endplate myopathy typical of the slow-channel syndrome. Twenty years later, a second muscle specimen again showed the endplate myopathy as well numerous nuclear and cytoplasmic tubulofilamentous inclusion bodies. Molecular genetic studies revealed a novel valine to phenylalanine mutation (epsilonV259F) in the M2 domain of the acetylcholine receptor. Coexistence of the slow-channel syndrome with a feature of IBM has not been observed before.

Lipid storage myopathy in Kearns-Sayre syndrome.

A 7-year-old girl had external ophthalmoplegia, limb weakness, short stature, hearing loss, pigmentary degeneration of the retina, and increased CSF protein content. Muscle biopsy revealed vacuolar myopathy with accumulation of lipids. Electronmicroscopy showed abnormalities of shape, size, and internal structure of muscle mitochondria. Muscle activity of palmitoyl-CoA synthetase was decreased, and the content of lipids was increased. Serum and muscle carnitine levels were normal, as were muscle carnitine palmitoyltransferase and carnitine acetyltransferase.

Follow-up study of myasthenic children after thymectomy.

The results of thymectomy of 28 myasthenic children observed from 1 to 9 years after operation are discussed. Improvement was obtained in 19 cases (67.8%), with full remission in 12 cases (42.8%). Six children died. No correlation was found between the results of thymectomy and the duration of the disease, sex or histological findings in the thymus. No increase of incidence or severity of infections were observed in thymectomized children. Caution is recommended regarding vaccination of myasthenic children.

Electromyographic findings in the so-called non-progressive myopathies.

Electrophysiological findings in 40 cases of non-progressive myopathies are reported, and compared with a group of 20 cases of Duchenne progressive muscular dystrophy and a control group. In all cases the electrophysiological changes were of the mild s. c. myogenic type. The involvement of proximal and distal muscles was equal without prevalence in proximal muscles as is typical for Duchenne's dystrophy. EMG reexaminations showed a slight progression of the diseases. A peculiar feature of myotubular myopathy was spontaneous activity (fibrillation) in 70% of muscles. A myogenic character of the process of congenital deficiency of muscle innervation with preserved number of motor units is suggested.

Is central core disease with structural core a fetal defect?

Morphological and biochemical studies were performed in three cases of congenital non-progressive myopathy in two generations of the same family. In the muscle biopsy nearly all the fibres were uniform in enzyme activity and belonged to type 2 C. Typical structural central cores were observed in 90% of the muscle fibres. Some ultrastructural characteristics of the core area, as well as disturbances of the myofibrillar proteins pattern, seen in the examined cases suggest that core formation may be a result of protein synthesis disturbances in an early stage of myogenesis.

A new familial congenital myopathy in children with desmin and dystrophin reacting plaques.

In 5 children with a progressive congenital myopathy representing 3 different families, unusual histological, immunohistochemical and ultrastructural changes in skeletal muscle have been found. Histologically, this myopathy was characterized by the presence of fine hyaline plaques devoid of oxidative as well as ATPase enzyme activities. At the ultrastructural level plaques were composed of helical filaments and amorphous dense material. Helical filament storage corresponded to strong desmin as well as ubiquitin immunoreactivity. In addition they were also dystrophin positive. The exclusive appearance of desmin, ubiquitin and dystrophin positive plaques in muscle specimens from 5 children emphasize the uniqueness of these plaques as well as this special form of a congenital myopathy.

Disintegration of the motor unit in post-polio syndrome. Part I. Electrophysiological findings in patients after poliomyelitis.

CN EMG and SF EMG were performed in 12 patients many years after acute poliomyelitis, without symptoms of post-polio syndrome. In 19 muscles with clinical symptoms and in 11 clinically normal muscles chronic neurogenic changes of a similar degree were observed. Fibre density was increased in both groups of muscles. In muscles with clinical symptoms complexes of single fibres with increased jitter and blocking were more frequent than in muscles without clinical manifestations. It seems that the reinnervation after acute polio is a continuing process and thus complete stabilization and integration of the motor unit cannot be achieved.

Disintegration of the motor unit in post-polio syndrome. Part II. Electrophysiological findings in patients with post-polio syndrome.

The aim of the study is to investigate the motor unit abnormalities in late postpolio muscular atrophy (PPMA) as compared to those found in patients who had polio 20-30 years prior to examination without any new clinical signs. The quantitative concentric needle EMG and a single fiber EMG techniques were employed. Spontaneous activity, the parameters of individual motor units potentials (MUP), number of complex potentials and their stability, jitter and blocking as well as fiber density (FD) have been evaluated. In PPMA patients (5 subjects) we found in newly weakened muscles: spontaneous activity, high percentage of complex potentials, increased jitter, increased FD. The EMG findings in muscles previously affected but without any signs of progression have been similar. In the patients with stable nonprogressing postpolio muscle atrophy (12) all MUP-s parameters indicated changes similar to PPMA but less marked in initially affected muscle with complete or incomplete recovery as well as sometimes in initially clinically unaffected muscles. These findings suggest that the signs of ongoing reinnervation processes persist many years after polio and that PPMA occurring later in life represents disintegration of the previously reinnervated motor units. It is still unclear whether this disintegration depends on decompensation by different factors of fully reinnervated motor units or whether most of the motor units after polio never regained a stable reinnervation.

Diagnostic value of satellite potentials in clinical EMG.

Complex motor unit potentials (CMUPs) with satellites were recorded and analysed in 231 electromyograms of patients with spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophy (DMD) and a healthy control group. In the control adult group only few CMUPs with satellites were found; no CMUP were found in children. In SMA and DMD patients the CMUPs were present with similar frequency but their morphology, i.e. shape, duration, amplitude of the main and satellite spike components and number of satellites was different. In ALS patients a significant difference between severely involved interosseous muscle and proximal muscles was found. The pathomechanism of CMUPs with satellites is different in myopathic and neurogenic processes, in both however they reflect remodelling of the motor unit. In myopathy they reflect muscle fiber diameter variability and distribution of preserved muscle fibers within the motor unit under study. In neurogenic lesion the CMUPs with satellites are the result of increasing desynchronisation during progressive de- and reinnervation.

[Conduction velocity in peripheral nerves in healthy and sick children]. / Szybkosc przewodzenia w nerwach obwodowych u zdrowych i chorych dzieci

Conduction velocity was determined in motor fibres of peripheral nerves in healthy children aged from 4 months to 15 years and in children with spinal muscular atrophy, untreated phenylketonuria, myopathies and infantile cerebral palsy. Conduction velocity equalling that in adults is reached in the ulnar and peroneal nerves at the age of about 3 years, in the median nerve somewhat later (at the age of 4-5 years). In cases of untreated phenylketonuria, myopathies and infantile cerebral palsy conduction velocity was about normal. In spinal muscular atrophy decreased conduction velocity in the youngest children may indicate delayed myelination of peripheral nerves.

[Electromyographic findings in children with dermatomyositis]. / Obraz elektromiograficzny w zapaleniu skórno-miesniowym u dzieci.

The author analysed electromyographic records in 14 children wit dermatomyositis. The findings included primary muscular changes of great intensity and presence of activity at rest in 50% of cases. The intensity of primary muscular changes resembled that observed in Duchenne's dystrophy and the distribution of changes was similar to that in non-progressive myopathies. Electromyographic changes occur in all cases of dermatomyositis and confirm the clinical diagnosis.

[Changes in the neural conduction in spinal muscular atrophy of the Kennedy type]. / Zmiany w przewodzeniu czuciowym w rdzeniowym zaniku miesni typu Kennedy'ego.

Sensory conduction velocity of median and sural nerves was examined in 6 patients with spinal muscular atrophy (SMA) of Kennedy type. In all patients, except the youngest one, slight slowing of sensory conduction velocity and marked decrease of potential amplitude was observed. These changes might suggest that the Kennedy type of SMA differs from another types of SMA and, may be, does not fit into "pure" motoneuron disease.

[Epileptic seizures in children with myasthenia gravis]. / Napady padaczkowe u dzieci z miastenia.

In the studies material of 119 children with myasthenia epileptic seizures occurred in 8 cases (7%). They always preceded the appearance of myasthenic symptoms. The seizures were primarily generalized. The EEG tracings varied greatly in morphology and intensity. The authors discuss the relationship between myasthenia and epilepsy and the effects of the used drugs on both these diseases.

[Genotype-phenotype correlation in hereditary motor-sensory neuropathy type IA associated with duplication in chromosome 17p11.2-12]. / Korelacja genotypowo-fenotypowa w dziedzicznej neuropatii ruchowo-czuciowej typu I A zwiazanej z duplikacja w chromosomie 17p11.2-12.

Results of clinical, electrophysiological and morphological examination, were presented in 19 patients from 8 families with hereditary motor-sensory neuropathy type I (HMSN type I) with 17p11.2-12 duplication (i.e. CMT IA). The course of the disease was rather mild, slowly progressive. Generalized demyelinating lesion of peripheral nerves was found on EMG examination, with median nerve conduction velocity between 10-20 m/s and very prolonged F wave latency. Sural nerve biopsy was characteristic of chronic demyelinating process. Phenotypic characteristics of our HMSN type I patients shows clinical, electrophysiological and morphological homogeneity, however there are some data from literature indicating possibility of intrafamilial and interfamilial variability.

[Hereditary motor and sensory neuropathy. I. Principles of classification and clinical picture]. / Ruchowo-czuciowa neuropatia dziedziczna. I. Podstawy klasyfikacji, obraz kliniczny.

The clinical picture was analysed in two types of hereditary motor-sensory neuropathy isolated on the ground of electrophysiological criteria. Type I comprised 34 patients with the conduction velocity in median nerve below 38 m/sec. Type II 19 patients with the conduction velocity above 38 m/sec. The age of onset was similar in both types and cases with onset below the age of 5 years prevailed. The assessment of the clinical picture using a acoring system failed to show any significant differences between type I and type II. Cases of type I shows, however, a considerable variability of the clinical picture and the course of disease process. Cases of type II were more homogeneous.

[Sensorimotor hereditary neuropathy. IV. Clinical, electrophysiologic and histologic correlations. Summary of studies]. / Ruchowo-czuciowa neuropatia dziedziczna. IV. Korelacje kliniczno-elektrofizjologiczno-histologiczne. podsumowanie badan.

On the basis of a material comprising 53 cases of sensorimotor hereditary neuropathy from 40 families the authors discuss the results of studies on the clinico-electrophysiological-histological correlations. The electrophysiological and histological studies demonstrated the validity of separation of this disease into two types according to the criteria given by Harding and Thomas. No significant differences were found in the clinical manifestations between type I and type II of the disease. In type I the clinical and histological findings were more varied than in type II. No basis was found for isolation of an intermediate type of peroneal muscular atrophy.

[Motor-sensory hereditary neuropathy. III. Histological changes]. / Ruchowo-czuciowa neuropatia dziedziczna. III. Zmiany histologiczne.

The authors describe the results of histological examinations of the sural nerve in 40 cases of sensorimotor hereditary neuropathy. A comparison of the morphological findings with the values of conduction velocity showed that all cases with "primary demyelination" belonged to the I type of this neuropathy (with conduction velocity under 38 m/sec) while those with axonal changes (and conduction velocity over 38 m/sec) belonged to type II. In 2 cases the degree of demyelination and axonal changes was similar, but the electrophysiological criteria failed to correspond to those of the "intermediate" type. These observations confirmed the validity of the classification of Harding and Thomas, but give no basis for isolation of an "intermediate" group as suggested in the classification of Bradley et al. A progression of demyelination changes was observed with increasing intensity of the pathological process, and frequent coexistence of axonal changes in type I, and possibility of greater damage to the thin myelinated fibres in relation to thick fibres in type II.

[Idiopathic juvenile osteoporosis with the symptoms suggesting nervous system damage]. / Mlodziencza osteoporoza idiopatyczna z objawami sugerujacymi uszkodzenie ukladu nerwowego.

10 children with final diagnosis of idiopathic juvenile osteoporosis were admitted to the Department of Neurology because of suspected lesion of nervous system. The main clinical features were gait disturbances and pain. Radiological examination was decisive for diagnosis. The authors discuss the course of disease and effect of the treatment.