G. Marconi

A multicentre follow-up study of 1152 patients with myasthenia gravis in Italy

SummaryA multicentre retrospective study was carried out on the characteristics and course of myasthenia gravis (MG) in Italy. Data from 1152 patients, fairly representative of the myasthenic population seeking medical advice, were analysed for diagnostic criteria, clinical aspects and therapeutic approaches. Mean follow-up was 4.9 years. The disease was correctly diagnosed within 2 years of the onset in 80% of cases. Onset of symptoms peaked in the second and third decade in females and fell between 20 and 59 years in males. At first observation 87% of the patients had generalized MG. Maximal worsening was observed within 3 years in 77% of patients. At the last follow-up, 35% of cases were symptom-free (pharmacological remission 24%, remission without treatment 11%). The more severe the disease at the first observation and at the maximal worsening of symptoms, the lower was the proportion of remissions. Steroids were given in 54% and immunosuppressants in 18%. Thymectomy was performed in 72%, mostly in women, younger than age 40, and with generalized MG. Thymectomy seemed to improve the course of the disease, mostly in patients operated on shortly after diagnosis and those with generalized mild-to-moderate disease and with a normally involuted thymus. MG was lethal in 4% of patients, principally men, older than 40, in grade 3 or worse at first observation, with a short history of disease, and with thymona.

Dysferlinopathy (LGMD2B): a 23-year follow-up study of 10 patients homozygous for the same frameshifting dysferlin mutations

The limb-girdle muscular dystrophies are a group of inherited neuromuscular disorders which are clinically and genetically heterogeneous. We have been able to carry out a follow-up study on 10 patients from a large Palestinian family with a confirmed mutation in the dysferlin gene. These patients have been followed for more than 23 years since the onset of the disease. They all had normal developmental milestones. The onset of the disease was usually in the second decade, more rarely in the third and fourth decades. The first symptoms were difficulty with running and climbing stairs. Patients showed a distinct type of gait due to the unique pattern of muscle involvement which was characterised by early involvement of the posterior muscle compartment of the thighs and legs (hamstrings, adductors, gastrocnemius and soleus). The shoulder and upper limb musculature became involved later, especially supra and infraspinatus and biceps. In the early stages of disease these patients may clinically show only proximal lower limb-girdle muscle weakness; however, the use of muscle imaging techniques were very important, always detecting in these patients also distal lower limb muscle involvement, so that the pattern of muscle involvement found in dysferlin deficiency may not strictly conform to the definition of limb-girdle muscular dystrophy. The pattern of muscular dystrophy is essentially uniform and has clearly distinct features (involving mainly the initial pattern of muscle involvement and the mode of gait) which differ significantly from the well reported clinical features associated with sarcoglycanopathy, calpainopathy and Miyoshi myopathy.

The phenotype of chromosome 2P-linked limb-girdle muscular dystrophy

This study reports on a detailed clinical, electrophysiological, muscle computed tomography (CT) and laboratory investigation carried out on five families with definite linkage to chromosome 2p. Some clinical and laboratory features were common to most of the patients, such as the very high serum creatine kinase (CK) levels (mean 43.70 times the normal). The onset was most frequently in the late teens or early twenties with weakness and wasting of the pelvic girdle muscles. All patients had normal motor milestones and had not complained of any symptoms of muscle disease in early childhood. The clinical course was variable both between and within some families, but was most often slowly progressive. Some variability in the pattern of muscle involvement between the different families has also been observed.

Axial myopathy – an unrecognised entity

Abstract. Axial myopathy (AM) is a rare neuromuscular disorder characterised by selective involvement of the spinal muscles with a bent spine and/or drooping head as leading clinical features. We here report the results of clinical, histopathological, MRI, molecular genetics and electrophysiological investigations carried out on six patients affected by pure axial myopathy. Symptoms appeared within an age range of 35 to 56 years. The first symptoms were difficulty in keeping the trunk and head in an upright position. Both bent spine and dropped head were reduced in a supine position. The disease was slowly progressive. Muscle strength examination and muscle imaging revealed involvement of the spinal and neck extensor muscles only. Serum CK was normal to slightly increased. EMG and muscle biopsy specimens obtained from spinal muscles showed an advanced chronic myopathic pattern. We conclude that axial myopathy may be much more common than previously thought, because gradual progression of cervical kyphosis may often be explained as a feature of normal ageing or as an associated sign of several neurological disorders and vertebral degeneration diseases.

A large inbred Palestinian family with two forms of muscular dystrophy

This paper reports the results of a clinical, genetic and histopathological study of 19 patients belonging to a large inbred Palestinian family living in Um-El-Fahem, a town located in Israel, which is solely inhabited by Arabs. Their custom of marrying only among relatives has kept the genetic homogeneity of the families intact. There were ten cases of congenital muscular dystrophy (CMD) and nine cases of adult limb-girdle muscular dystrophy (LGMD) belonging to two generations of the same family. Both forms showed autosomal recessive inheritance. The patients with congenital muscular dystrophy had generalized muscular weakness and hypotonia at birth without arthrogryposis or CNS involvement and then had a relatively benign evolution with stabilization of the clinical picture at different ages and variable degree of severity. Muscle biopsy showed a dystrophic pattern. The other nine patients presented with the picture of adult limb-girdle muscular dystrophy but with an unusual tendency to the stabilization of symptoms.

Limb‐girdle muscular dystrophy: a follow‐up study of 79 patients

The limb‐girdle muscular dystrophies (LGMD) are autosomally inherited neuromuscular diseases. Recently six different loci for LGMD have been reported: 5q (LGMD1A), 15q (LGMD2A), 2p (LGMD2B), 13q (LGMD2C), 17q (LGMD2D) and 4p‐14‐q21.2 (LGMD2E) respectively. We have studied 79 patients affected by LGMD during the period 1976 to 1995. All patients were examined clinically, and various investigations, including genetics were performed. According to their data we divided them as follow: 1) Cases with autosomal recessive inheritance (34.19%) of these two families are linked to chromosome 2p and the others were subdivided according to the age at onset into childhood LGMD and juvenile‐adult LGMD; 2) Cases with dominant inheritance (13.92%); 3) Sporadic cases (51.89%). Onset of symptoms occurs from the first to the third decade. The clinical course varies considerably, as does the degree of disability. Our study allowed to identify two different groups of patients who relatively homogeneous with respect to their clinical and laboratory characteristics.

Familial amyloid polyneuropathy with genetic anticipation associated to a gly47glu transthyretin variant in an Italian kindred

The most frequent localization of amyloid in transthyretin (TTR) mutations is in the peripheral nerve, causing familial amyloid polyneuropathy (FAP). It is generally accompanied by involvement of other organs such as the myocardium and kidney. To date, over 70 TTR point mutations have been reported in literature, with different phenotypes depending on the location of the mutation in the TTR gene. This paper deals with a point mutation in exon 2 position 47 of the TTR gene, encoding the substitution ofgly-cine with glutamate. The mutation was found in an Italian family with 5 patients over 3 generations. The phenotype was characterised by peripheral neuropathy and autonomic dysfunction, associated in some patients with cardiomyopathy and renal involvement. The symptoms were very severe and the patients did not survive long, thus suggesting the aggressive nature of the pathological process. Moreover, in the succeeding generations of this family, there was genetic anticipation in the age of onset of the disease.

Sarcoplasmic reticulum Ca2+-ATPase and acylphosphatase activities in muscle biopsies from patients with Duchenne muscular dystrophy

Sarcoplasmic reticulum Ca2+-ATPase, acylphosphatase and other soluble enzymes (creatine kinase, lactate dehydrogenase, aldolase and pyruvate kinase) were assayed in muscle biopsies from patients affected by Duchenne muscular dystrophy (DMD) and from normal controls. Specific activities of all the soluble enzymes were decreased in dystrophic muscle, acylphosphatase exhibiting the most marked and significant decrease comparable to that of creatine kinase, in spite of a moderate increase in serum levels. Also, Ca2+-ATPase, particularly the calcium-dependent activity, was decreased in dystrophic muscle. A positive correlation, higher than with the other soluble enzymes, was obtained between acylphosphatase specific activity and the percentage of Ca2+-activation of Ca2+-ATPase. These findings: suggest an impairment of microsomal calcium uptake which could be, at least in part, responsible for sarcoplasmic calcium accumulation observed in DMD; do not disagree with an hypothesized role of acylphosphatase in intracellular calcium homeostasis, consistent with the enzymes demonstrated hydrolytic activity on the phosphorylated intermediate of Ca2+-ATPase.

Muscle CT in peripheral neuropathies.

We studied retrospectively the muscle CT scans of 60 acquired and 40 congenital motor peripheral neuropathies in order to define the diagnostic usefulness of muscle CT in these disorders. Fifty‐five percent of the acquired and 72% of the congenital forms showed muscle CT pathological changes correlated to the clinical severity. The typical finding was pure muscle atrophy but several patients also revealed areas of hypodensity. In most of the acquired forms, muscle changes affected both the thighs and legs with a prevalent involvement of the posterior muscles. The congenital forms showed early involvement of the anterior leg muscles. Our study suggests that a CT scan might be useful in evaluating the severity of muscular atrophy, its evolution in time and the prognosis of motor function, in confirming the diagnosis of acquired or congenital neuropathies, and in some cases in defining the phenotypes of congenital forms.

Pure quadriceps myopathy in two sisters.

The authors carried out a clinical, laboratory and muscle computed tomographgy CT follow‐up study of 18–21 years on two sisters affected by quadriceps myopathy (QM). The onset in the fourth decade was a weakness in the thighs. During the follow‐up study, the patients showed only vasti muscles involvement, normal creatine kinase (CK) levels, myopathic muscle biopsy and electromyography (EMG) and normal membrane protein expression on immunocytochemical analysis. Therefore, all muscle pathologies known to have quadriceps involvement as a leading feature have been ruled out. We conclude that our patients have pure QM with probable autosomal recessive inheritance.