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.

Does EEG (visual and quantitative) reflect mental impairment in subcortical vascular dementia?

UNLABELLED: The aim of this study was to determine if the results of visual and quantitative EEG (QEEG) parameters reveal a correlation with mental impairment in subcortical vascular dementia (SVD), one of the most frequent causes of cognitive impairment in the elderly. In SVD, like in Alzheimer's disease disturbances were found in cholinergic transmission. The cholinergic deficit as manifested in changes of synaptic potentials is reflected in EEG signals. MATERIAL: 31 patients with probable SVD (according to NINCDS-AIREN and T. Erkinjuntii's criteria) and mean age 72.3 yrs;(M--43%, F--57%) and 14 healthy control subjects with mean age of 72.3 yrs (M-57%, F-43%). According to the Mini Mental Scale Examination (MMSE) the SVD group was divided into two subgroups with mild and moderate dementia, their EEGs being recorded with a Medelec and Neuroscan 4.2 system. Visual EEG findings were classified with the use of eight-degree scale of pathological changes by the presence of slow waves. Then QEEGs were made. The following parameters were calculated: alpha/slow wave power ratios, the mean wave frequency in all and in some selected derivations. RESULTS: A significant difference was found between QEEGs in SVD subgroups with mild and moderate dementia (p<0.05), but there was no significant difference between visual EEGs. A significant correlation between QEEG parameters such as alpha/slow wave ratio or mean wave frequency and mental impairment (according to MMSE results) was found (p<0.001), but there was no significant correlation between degree of EEG abnormalities in visual analysis and MMSE results. CONCLUSION: Only QEEGs are correlated with mental impairment in SVD. Visual EEG technique as a less precise tool does not reflect the mental impairment in SVD due to cholinergic deficit.

Atypical motor unit potentials in Emery-Dreifuss muscular dystrophy (EDMD).

OBJECTIVE: The aim of the study was to analyse electromyographic changes in Emery-Dreifuss muscular dystrophy (EDMD) that are atypical for myopathy. Our special interest was focused on high amplitude polyphasic motor unit potentials (MUPs), also termed irregular MUPs. METHODS: We studied 21 EDMD patients with the diagnosis based on clinical data, DNA analysis and immunohistochemical muscle studies. Rectus femoris muscle biopsies were investigated in all affected patients. Electrophysiological investigations involved quantitative concentric needle electromyography (CNEMG) of biceps brachii (BB) and rectus femoris (RF) muscles. Simulation studies were performed to approximate the number, diameter and distribution of muscle fibers, which contribute to irregular MUPs. RESULTS: The EMG data in EDMD were compatible with myopathy. Irregular MUPs showed longer duration, larger area, size index and higher amplitude then simple ones (P < 0.05). The approximation of features of muscle fibers contributing to irregular MUP also indicated smaller (<45 microm) and larger (>55 microm) diameters than normal (50 +/- 5 microm). Muscle biopsy specimens revealed the variable muscle fiber size due to atrophy, hypertrophy, and muscle fiber splitting. CONCLUSIONS: Irregular MUPs recorded in EDMD are due to hypertrophied and atrophied fibers as well as increased fiber density. They reflect reorganization of the motor unit in a slow progression myopathic process (muscle fiber hypertrophy and splitting). SIGNIFICANCE: Irregular MUPs in EDMD most probably reflect increased variability of the muscle fiber size.

Blink reflex in motor neuron disease.

The aim of the study was to analyse the diagnostic value of blink reflex (BR) in motor neuron disease (MND). We studied 25 patients with MND including amyotrophic lateral sclerosis (ALS) in 18 patients, primary muscular atrophy (PMA) in 4 patients, and primary lateral sclerosis (PLS) in 3 patients and 12 healthy volunteers. The blink reflex was obtained in typical way. In ALS group, statistically significant increase in latency and decreased amplitude of R2 responses were found compared to the control group (p < 0.05), whereas BR in patients with PLS and PMA was within normal limits. The presence of low amplitude of R2 responses in patients with ALS may suggest loss of lower brainstem neurons connecting trigeminal and facial system, and probably also decreased facilitator effect of central nervous system on reticular formation in the brainstem.

EMG dynamics in polymyositis and dermatomyositis in adults.

In order to analyze the EMG dynamics in acute and chronic polymyositis 44 patients were examined. Thirty-four were seen in the acute stage, 28 in the chronic stage and 18 serially. Investigations included quantitative electromyography using the Polish minicomputer "ANOPS 105" connected to a DISA electromyograph. Additionally fiber density was analyzed by single fiber electromyography in the chronic stage only. The acute stage findings confirmed the observations of earlier authors with the classical expression of excessive spontaneous activity, polyphasic potentials of short duration and low amplitude. In the chronic stage, motor unit potentials with increased duration and amplitude and with late components of the type seen in satellite potentials were noted. This was compared with the increased fiber density found at this stage. Additionally, in some muscles in the chronic stage, motor unit potentials were seen with increased duration, but also a reduction in the mean amplitude of motor unit potentials counted by the automatic analysis method. The decreased amplitude of the motor unit potentials in the chronic polymyositis may be the result of the smaller size of regenerating muscle fibers.

Macroemg in manifesting carriers of Duchenne muscular dystrophy.

The aim of present study was to analyse possible myopathic changes in the muscles of manifesting carriers of Duchenne Muscular Dystrophy (DMD) using concentric needle emg and macroemg methods. Our material consisted of 10 manifesting carriers aged 9-52 (mean 30 years) and 20 healthy age-matched females. Concentric needle emg (CNEMG) and macroemg was performed in biceps brachii (BB) muscle in both groups: carriers and controls. Myopathic changes were observed in BB muscle in 5 of 10 manifesting carriers using CNEMG and in all cases (10 carriers) using macroemg method. Macro electrode, which reflects total motor unit activity, i.e., the total number and size of component muscle fibres, supplies information about early myogenic lesion of the muscle. Therefore the macroemg seems to be a sensitive and useful electrophysiological diagnostic method in carriers of DMD.

Motor unit changes in inflammatory myopathy and progressive muscular dystrophy.

The aim of present study was to analyse the motor unit (MU) changes in progressive muscle dystrophy (PMD) and in inflammatory myopathy (IM) and to evaluate eventual neurogenic factors in MU reorganisation. The material consisted of 20 patients with (PMD), 20 patients with (IM) and 20 healthy age-matched volunteers. The shape of concentric needle motor unit potentials (cn MUPs), including their duration, amplitude, area, size index and number of phases, the interference pattern and the amplitude and area of macro MUPs were evaluated. The cn emg data satisfied the classical criteria for myopathy in all examined patients, at least in one of the tested muscles. A decreased amplitude and/or area of macro MUPs, compatible with myopathy, were observed in 32 of the 40 patients. In some cases of chronic IM and PDM the long duration polyphasic potentials were recorded. The size index (SI) value of long polyphasic MUPs was usually decreased or normal. This feature indicated that desynchronisation of "myopathic" MUPs results from a reduced number of muscle fibers and their degeneration and regeneration. The results indicated no difference in MU reorganization between PMD and IM and no evidence of neurogenic factors in MU changes.

[Analysis of EMG records obtained by using an "Anops" computer (their usefulness in the diagnosis of neuromuscular diseases]. / Analiza zapisów EMG uzyskanych przy zastosowaniu maszyny cyfrowej "Anops" (przydatnosc w diagnostyce chorób nerwowo-miesniowych).

The studied group included 179 individuals: a control group of 82 subjects, myopathy patients (55) and neurogenic atrophy cases (42). The records were obtained from 4 muscles (biceps, 1st interosseous muscles, quadriceps muscle, anterior tibialis muscle) using the method of automatic EMG analysis and quantitative conventional method. The obtained results demonstrated that in the control group Anops analysis showed no significant differences in the electromyographic parameters of a given muscle in three age groups (15-30, 31-45 and 46-60 years). The values of the mean duration of single potentials were calculated by the automatic method and in the control group they were shorter (by a mean value of 15%) than the mean duration of these potentials calculated by the conventional method. In cases of neuromuscular diseases the obtained measurements differentiated the normal records from the pathological ones, and myogenic from neurogenic lesions. The EMG parameters in the automatic analysis differentiating most evidently normal EMG from pathological EMG were: amplitude and mean duration of single potentials. These results seem to demonstrate the usefulness of automatic analysis of EMG records.

[Comparison of EMG tracings obtained by means of computer analysis and by routine quantitative method]. / Porównanie zapisów EMG uzyskanych przy zastosowaniu analizy komputerowej z rutynowa metoda ilosciowa (uwagi wstepne).

The purpose of the present work was to compare EMG tracings obtained by the automatic method using the computer ANOPS and by the method of quantitative electromyography. The measurements of the automatic method were found to be reliable and reproducible permitting to distinguish normal from pathological tracing, and in the pathological tracing to discriminate between the so called primary muscular and the neurogenic changes. The automatic method permits a much larger number of potentials to be evaluated, besides it is less time consuming and more objective since it rules out subjective selection of potentials which is a drawback in the conventional method.

[Cryoglobulinemia complicated by familial spastic spinal paralysis]. / Wspólistnienie krioglobulnemii z rdzeniowym kurczowym porazeniem rodzinnym.

A family with familial spastic spinal paralysis and cryoglobulinaemia is described. It seems that this coexistence was due rather to an accidental coincidence than to a genetic coupling of both genes determining these pathological states.

[Evaluation of the evoked potentials in various acquired polyneuropathies (Guillain-Barré syndrome and chronic recurrent polyneuropathy). Preliminary report]. / Ocena potencjalów wywolanych w niektórych, nabytych polineuropatiach (zespól Guillain-Barré i przewlekla, nawrotowa polineuropatia--PNP). Doniesienie wstepne.

In 15 patients with acquired polyneuropathy (Guillain-Barré syndrome and chronic recurrent polyneuropathy) the conduction velocity was measured in the peripheral nerves of the upper and lower extremities, the latency of the F wave was determined, and the somatosensory evoked potentials were assessed stimulating the median enerve and posterior tibial nerve. The abnormalities were assessed in the parameters of the obtained somatosensory evoked potentials comparing them with the changes of F wave and the velocity of conduction in peripheral nerves. The sensitivity and usefulness of these methods in acquired polyneuropathies are discussed.

[A case of myelopathy of probable vascular origin with favorable outcome]. / Przypadek mielopatii prawdopodobnie pochodzenia naczyniowego o pomyslnym przebiegu.

The reported case was observed in a 62-year-old female in whom a syndrome of vascular disturbances developed suddenly in the area vascularized by the artery of Adamkiewicz. In the analysis of the pathological mechanism of these changes compression injury, myelitis, pelvic phlebothrombosis were excluded. Thrombosis of the artery of Adamkiewicz due to atheromatosis of the spinal arteries, was diagnosed. The atheromatous process involves the anterior spinal artery in 4% of subjects aged from 60 to 70 years.

[Hereditary neuropathy with liability to pressure palsies caused by 17p11.2 chromosome deletion]. / Dziedziczna neuropatia z nadwrazliwoscia nerwów na ucisk spowodowana delecja w chromosomie 17p11.2.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder characterised by recurrent mononeuropathies. Electrophysiological studies reveal slowed conduction velocity in peripheral nerves. The main histopathological findings are focal thickenings of myelin-tomaculae. In most cases HNPP is associated with a deletion within PMP-22 (peripheral myelin protein; PMP) gene on chromosome 17p11.2. The gene penetration is almost complete but the expression may be variable. DNA analysis is of practical importance in diagnosing HNPP especially in sporadic cases and also in individuals without clinical and electrophysiological signs of neuropathy. We present the first Polish family with HNPP, in which the genetic defect has been confirmed by DNA analysis.

[Macro EMG in neuromuscular diseases]. / Zastosowanie metody makro-emg w diagnostyce chorób nerwowo-miesniowych.

The aim of this study is the introducing of macro-emg method as electrophysiological test used in diagnosis of neuromuscular diseases. The macro motor unit potentials (macro MUPs) obtained by recording macroelectrode (modified single-fibre electrode) represents temporal and spatial summation of individual single fiber action potentials belonging to whole motor unit territory--so the uptake area is larger for macroelectrode than for the concentric electrode, commonly used in emg routine work, when central main complex is generated only from less than 15 muscle fibers [10, 12, 13]. Additional information obtained by macro-emg method is spatial organisation of muscle fibers within the motor unit, so-called fiber density (F.D) In our study macro-emg examinations were performed in 20 healthy subjects, aged 21-55, without signs and symptoms of neuromuscular disorders. Macro MUPs were recorded using special programme for macro-emg and performed on electromyograph Counterpoint. 37 muscles (20 BB and 17 RF) were examined, and median values of amplitude, area of macro MUPs and F.D. in healthy subjects of different age were analyzed. Mean values of median for amplitude and area of macro MUPs in BB and RF muscles show respectively--148 microV, 382 microV x ms, and 319 microV, 763 microV x ms. Parameters of macro MUPs obtained in healthy subjects were compared to results obtained in 10 patients with myopathy and lower motor neuron lesion. Our results have confirmed the value of macro-emg method for investigating of the pathophysiological changes in motor units in neurogenic disorders, in myopathy the study should be continued.

[Diagnostic yield of electrophysiological and immunological studies in inflammatory myopathies]. / Zastosowanie badan elektrofizjologicznych i immunologicznych do diagnostyki miopatii w chorobach tkanki lacznej.

The aim of the study was to estimate the value of the immune markers in defining distinct subsets of inflammatory myopathies. The series of 76 patients was divided, on the basis of the clinical data, into 5 groups (polymyositis (PM), dermatomyositis (DM), scleromyositis (Scm), mixed connective tissue disease (MCTD), unclassified). In all cases detailed clinical, electrophysiological (concentric needle electromyography (CNEMG) and skin sympathetic response (SSR)) were performed as well as immunologic studies: the anti Mi-2, anti RNP, PM-Scl, Jo-1. The findings indicate that immune markers have a diagnostic value in differentiating the defined subsets of patients different in respect of course, prognosis and therapeutic indications. The authors stressed the value of the Jo-1 antibody in detecting the subset of polymyositis with coexisting interstitial lung disease. Electrophysiological data do not differentiate the groups of patients with different clinical syndrome and different immune markers. EMG results seem however to be useful in monitoring the course of the disease and response to the therapy.

The value of quantitative EEG in differential diagnosis of Alzheimer's disease and subcortical vascular dementia.

OBJECTIVE: To investigate whether quantitative EEG may be useful in differential diagnosis of AD and SVD and to determine the correlation between dementia and abnormalities in EEG. MATERIALS AND METHODS: The group under study was consisted of 62 patients with AD (mean age: 73.6 yrs; M 51%), 31 with SVD (mean age: 75.2 yrs, M 43%) and a control group of 14 healthy subjects (mean age: 69.5 yrs, M 43%). The patients were divided into subgroups of those with mild, moderate and marked dementia. EEG findings were classified using eight-degree scale according to the presence of slow waves, and then quantitative analysis was carried out by calculating the alpha/slow wave power ratios and the mean frequencies in all and some selected derivations. RESULTS: A significant difference between visual EEGs and QEEGs in AD and SVD was found. Only QEEG parameters differed in AD and SVD subgroups with the same degree of cognitive impairment: the mean wave frequencies of waves in temporal derivations in subgroups with mild and moderate dementia and alpha/delta waves power ratio in subgroups with moderate dementia. CONCLUSIONS: Visual EEGs and QEEGs could be used in addition to the differential diagnosis between AD and SVD, but only selected parameters of QEEG could be useful in differentiating between AD and SVD subgroups with the same degree of dementia.

The diagnostic yield of automatic EMG analysis in neuromuscular diseases.

The aim of the study was to evaluate the diagnostic yield of automatic EMG analysis employed in differentiating normal from diseased muscle and myogenic, neural and spinal lesions. The material comprised 520 patients with neuromuscular diseases. Only diagnostically confirmed cases were included into the study. The control group comprised 51 healthy subjects. In all patients and healthy subjects routine EMG examination was performed by means of both the conventional technique and automatic method. On the basis of the statistical analysis of the material the authors concluded that the method of automated EMG using the Polish minicomputer Anops makes possible distinction of the main types of pathological processes affecting the muscles with higher than previously objectivity and reliability. They stress, however, the important role of the examiner and his experience.