Lambert-Eaton myasthenic syndrome in childhood.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of the neuromuscular junction. LEMS can be associated with a variety of neoplasms. Patients present with proximal muscle weakness and fatigability, often combined with areflexia. Only 5% of reported cases are children. We report a case of 11-year old boy with non-neoplastic Lambert-Eaton myasthenic syndrome. Repetitive nerve stimulation test showed 83% increment after maximal voluntary contraction, presence of antibodies against voltage-gated calcium channels confirmed the diagnosis. The boy responded well to immunosuppressive treatment with prednisone and azathioprine and remains cancer-free for 4 years.

Charcot-Marie-Tooth disease type 4C4 caused by a novel Pro153Leu substitution in the GDAP1 gene.

Charcot-Marie-Tooth type 4C4 disease (CMT4C4) is an early onset, autosomal recessive neuropathy with hoarseness caused by mutations in the GDAP1 gene which maps to the 8q13 region. To date, only 24 mutations in the GDAP1 gene have been reported. Neuropathological findings of sural nerve biopsies have been published for a limited number of CMT4C4 patients. Herein, a novel Pro153Leu mutation in the GDAP1 gene identified in a consanguineous Polish family is described and longitudinal clinical and electrophysiological studies as well as morphological findings are presented.

Early onset Charcot-Marie-Tooth disease caused by a homozygous Leu239Phe mutation in the GDAP1 gene.

Mutations in the ganglioside -induced differentiation-associated protein 1 (GDAP1) gene are common a cause of the Charcot-Marie-Tooth (CMT4A) disease with autosomal recessive mode of inheritance. To date more than twenty mutations in the GDAP1 gene have been reported in patients suffering from the demyelinating, axonal or mixed form of Charcot-Marie-Tooth disease. Only in a few CMT4A affected patients sural nerve biopsy findings have been provided. We report a homozygous Leu239Phe mutation in the GDAP1 gene in a 39-year-old female with a severe form of mixed axonal and demyelinating Charcot-Marie-Tooth disease.

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.

Autosomal recessive axonal form of Charcot-Marie-Tooth Disease caused by compound heterozygous 3'-splice site and Ser130Cys mutation in the GDAP1 gene.

A recessive demyelinating subtype of Charcot-Marie-Tooth disease called CMT4 is a heterogeneous group of disorders. A relatively frequent form of recessive CMT (CMT4 A) has been mapped to the chromosome 8 q21 and shown to be caused by mutations in the ganglioside-induced differentiation protein 1 (GDAP1) gene. Twenty mutations in the GDAP1 gene have been reported in patients suffering from the axonal and demyelinating forms of CMT disease. In this study we report two novel mutations in the GDAP1 gene in a patient suffering from CMT2 disease and whose parents were asymptomatic carriers of a Ser130Cys and 3'-splice site (311-1G > A) mutation, respectively.

Mild early onset axonal Charcot-Marie-Tooth disease not linked to other axonal Charcot-Marie-Tooth loci.

Autosomal dominant axonal Charcot-Marie-Tooth disease type 2 (CMT2) is a heterogeneous group of disorders with seven chromosomal loci mapped in the uncomplicated forms of CMT2. The authors report clinical, electrophysiologic, and genetic analysis of a Polish CMT2 family. Nine known CMT2 gene loci and one MPZ gene locus have been excluded. The authors' findings suggest that this family represents a novel form of CMT2 disease.

A novel MPZ gene mutation in congenital neuropathy with hypomyelination.

Congenital hypomyelinating neuropathy (CHN; MIM# 605253) is a severe neuropathy with early infancy onset inherited as an autosomal dominant or recessive trait. Sural nerve biopsy shows a characteristic picture of nonmyelinated and poorly myelinated axons with basal lamina onion bulbs and lack of myelin breakdown products. Several mutations in the MTMR2, PMP22, EGR2, and MPZ genes have been found in patients with CHN. The authors describe the clinical and morphologic features of a patient with CHN and the identification of a novel Thr124Lys mutation in the MPZ gene.

Coexistence of X-linked recessive Emery-Dreifuss muscular dystrophy with inclusion body myositis-like morphology.

We reported three cases (two familial and one sporadic) of X-linked Emery-Dreifuss muscular dystrophy (EDMD), genetically documented. Two patients demonstrated a typical inclusion body myositis (IBM)-like morphology. The third patient had only minor changes. Patients had elbow and ankle contractures, progressive wasting of humeroperoneal muscles and cardiac failure (pacemaker implantation in all). There was a mutation within the Xq28 gene and complete absence of emerin in the nuclear membrane. Mononuclear cell infiltrations, rimmed vacuoles, amyloid deposits, as well as cytoplasmic and nuclear tubulofilamentous muscle inclusions were most unusual findings. Coexistence of IBM-like morphology and X-linked recessive EDMD might indicate that pathological features of IBM are nonspecific and may be present in other neuromuscular disorders.

Motor unit hyperexcitability in amyotrophic lateral sclerosis vs amino acids acting as neurotransmitters.

OBJECTIVES: Electrophysiological studies of amyotrophic lateral sclerosis (ALS) patients reveal not only lower motor neuron involvement, but also widespread signs of its hyperexcitability. They might be the consequence of changes in the level of amino acids acting as neurotransmitters. MATERIAL AND METHODS: Electrophysiological examination of 31 patients with sporadic ALS was performed. A hyperexcitability index (HI) was created to describe the amount of double discharges, fasciculation potentials or 'giant' F-waves. Glutamate, aspartate, glycine and GABA concentration in serum and cerebrospinal fluid (CSF) were estimated, using the high performance liquid chromatography technique. RESULTS: The electrophysiological studies revealed marked variability in HI in the patients group. HI did not correlate with duration of the disease and the degree of disability expressed with Norris score, as well as with the level of excitatory or inhibitory amino acids in the body fluids. CONCLUSION: Hyperexcitability of the motor unit observed in ALS is not directly related to changes in serum and CSF level of amino acids acting as neurotransmitters.

Clinical, electrophysiological and immunological remissions after thymectomy in myasthenia gravis.

OBJECTIVES: Approximately 50% of patients treated with thymectomy have a chance for symptom-free life. However, immunological and neurophysiological abnormalities may be detected in patients with clinical remission. Although improvement usually parallels decrease in acetylcholine receptor antibody (AChRAb) levels and jitter values, there is a question what factors influence immunological and electrophysiological remission in a population of myasthenia gravis (MG) patients. METHODS: We analyzed retrospectively clinical data of 32 MG patients operated for generalized MG, followed-up at our department for 17.2 (4-31) years. They were in clinical remission for 12.8 (2-25) years. All of them had single fiber electromyograhy (SFEMG) of extensor digitorum communis muscle (EDC) muscle and estimation of AChRAb level at the end of follow-up. Their age at onset of MG was 17 years (6-48) and at thymectomy 19 (6.4-58) years. Tensilon test was positive in 30, repetitive nerve stimulation in 29 cases. RESULTS: Clinical remission was reached on average 4.2 years after thymectomy. SFEMG jitter value normalized in 60% of cases. AChRAb were negative only in 34% of patients. Jitter values correlated with AChRAb levels (P=0.006, r=0.5) but were not related to clinical factors. Only time to thymectomy correlated with time from thymectomy to clinical remission (P=0.001, r=0.5). CONCLUSIONS: Clinical remission is not always accompanied by normalization of SFEMG and AChRAb. Although normalization of neuromuscular transmission in patients with remission of MG is individual, short duration of MG before thymectomy increases the chance of early remission.

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.

Identification of Gal(beta 1-3)GalNAc bearing glycoproteins in cerebrospinal fluid of amyotrophic lateral sclerosis (ALS) patients.

Glycoproteins in cerebrospinal fluid of 55 patients with amyotrophic lateral sclerosis (ALS), six disease controls (multifocal motor neuropathy, sensorimotor neuropathy, Guillain-Barré syndrome, spinal muscular atrophy type II, motor neuropathy with monoclonal gammopathy) and 20 healthy controls were separated by PAGE electrophoresis and then detected immunochemically with peanut agglutinin (PNA). In 36 amyotrophic lateral sclerosis patients the 262 kDa glycoprotein was significantly increased (over the normal mean +/- SD x 2), which was associated with a decrease in the 114 kDa fraction. In the remaining patients, both fractions were either equal in concentration or the 114 kDa glycoprotein predominated. In normal cerebrospinal fluid, the 114 kDa glycoprotein predominated over the other glycoproteins. The total amount of separated glycoproteins was increased in 15 amyotrophic lateral sclerosis patients. In 12 of them it was followed by an increase in the percentage of the 262 kDa glycoprotein. There was no correlation between the content of the peanut agglutinin-labelled glycoproteins and the patients' age, duration and severity of the disease. There was a correlation between the 262 kDa glycoprotein being increased in cerebrospinal fluid and the electrophysiological pattern of denervation seen in electromyographic study. The glycoproteins change, similar to that occurring in amyotrophic lateral sclerosis patients, was also observed in one case of multifocal motor neuropathy (MMN). We suggest that in amyotrophic lateral sclerosis and multifocal motor neuropathy, the peanut agglutinin-labelled glycoproteins are released in excess from the nervous tissues into the cerebrospinal fluid as a result of neuronal degeneration. The question to be answered is, whether the released glycoproteins are becoming targets for auto-antibodies.

[Electrophysiological abnormalities in acute and chronic inflammatory demyelinating polyneuropathies]. / Zmiany elektrofizjologiczne w ostrych i przewleklych zapalnych polineuropatiach demielinizacyjnych.

Electrophysiologic changes in G-B and CIDP polyneuropathy. Retrospective comparative study of the electrophysiologic changes in 7 cases of GBS and 12 cases of CIDP polyneuropathy were performed. In all cases nerve stimulation data fulfilled the diagnostic electrophysiologic criteria of demyelinated inflammatory polyneuropathy. Our material confirms that electrophysiological investigations are a very important diagnostic tool in inflammatory demyelinating polyneuropathy. However, different electrophysiologic features in individual cases and in the course of the disease cause that nerve stimulation data have no diagnostic value in differentiation between the GBS and CIDP cases.

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.

Double discharges of motor units in neuromuscular disorders.

Repetitive discharges (RDs) are observed in electromyograms recorded from healthy as well as diseased muscles. We have evaluated the prevalence of RDs in some neuromuscular diseases and analysed the time parameters of recordings displaying RDs as well as shapes of the potentials. In our clinical material, RDs have been observed exclusively in lower motor neuron lesions, never in healthy or in myopathic muscles. The prevalence index of RDs in amyotrophic lateral sclerosis (0.06) was found to be different from that in chronic spinal muscle atrophy (0.004). The types of double potential shape have been categorised. The relationships between the amplitude of the second component and the interspike duration and that between the interspike duration and the jitter were calculated. The amplitude of the second component diminished and jitter of the components increased with the shortening of the interval between components. The authors suggest that in lower motor neuron lesions, the RDs of the motorunit (MU) may be one of the first signs of the MU's dysfunction.

Shape irregularity of motor unit potentials in some neuromuscular disorders.

The aim of this study was to test whether analysis of the irregularity of the motor unit potential waveform may supplement conventional evaluation. We have found that the irregularity is not a characteristic feature of potentials either in neurogenic disorders or in myopathy. We have found, however, that within myo- and neuropathic disorders, the irregularities differ between slow (such as Becker muscle dystrophy and chronic spinal muscle atrophy) and fast progressing processes (such as amyotrophic lateral sclerosis and Duchenne muscle dystrophy). These differences depend on the different number of phases and turns contributing to wave formation. In slowly progressing processes, very irregular potentials are more often polyphasic, whereas in acute processes they may be polyturn or polyphasic. The results suggest that it is the irregularity of the potential that provides new information, not available so far, on the activity of the pathological process.

[Median nerve electrophysiological assessment in amyotrophic lateral sclerosis]. / Ocena elektrofizjologiczna nerwu obwodowego w stwardnieniu zanikowym bocznym.

Our material comparises 105 patients (62 men and 43 women) aged 26-73 years with amyotrophic lateral sclerosis (ALS). EMG examination confirmed the diagnosis of multilevel lesion of spinal motor neurons. Clinically, 94 of them had classical ALS, 3 had primary bulbar palsy (PBP), 6 had primary motor spinal atrophy (PSMA), and 2 had primary lateral sclerosis (PLS). Disease duration was 18.1 month, on the average, ranging from 2-60 months. In all patients motor and sensory nerve conduction was studied in median, peroneal and sural nerves. Conduction velocity, distal latency, F-wave latency of motor nerves, amplitude of M response and of sensory potentials were evaluated. Abnormalities were found most often in the motor fibres of median nerve: lowering of the M response amplitude in 44% of nerves studied, slowing of conduction velocity and elongation of distal latency in ca. 30%, elongation of F-wave latency in 27%. In the peroneal nerve the changes were less frequent: 38%, 21%, and 3%, respectively. They were also less marked. In the sensory fibres of median nerve slowing of conduction velocity was found in 25% of nerves, in sural nerve in 11%. Some slight decrease of amplitude of sensory potentials was seen in those nerves. The results obtained indicate a possibility of peripheral nerve lesion in the course of ALS which must be remembered in clinical diagnosing.

[Dysphonia as the first sign of myasthenia gravis]. / Dysfonia pierwszym objawem miastenii.

Ten cases of myasthenia are presented in which dysphonia was the initial sign. Isolated signs of dysphonia continued for several months or years, presenting diagnostic difficulties. Eventually neurologic examination followed by electrophysiological investigation (classical repetitive nerve stimulation and single fibre EMG) as well as edrophonium test allowed proper diagnosis of myasthenia, then confirmed by the clinical course. A possible diagnosis of myasthenia should be taken into consideration in cases with isolated dysphonic signs of uncertain origin.

[Is there true remission in myasthenia gravis? Long-term clinical and electrophysiological studies]. / Czy istnieja prawdziwe remisje w miastenii? Wieloletnia katamneza kliniczna i elektrofizjologiczna.

Twenty myasthenic patients were followed up who had in the years 1981-1982 full clinical remission (no drugs, no symptoms), lasting at that time at least several years. However, in 19 of them neuromuscular transmission defects were then found by single fibre electromyography (SFEMG). We then concluded that true remissions did not exist in myasthenia (J. Neurol., 1985, 231, 331). Recently, we were able to evaluate those patients. One patient, who had full long lasting remission after thymomectomy, died at the age of 69 of myocardial infarction in the course of a myasthenic relapse. Another patient had a relapse, 20 years after thymoma extirpation. Two patients had recurrent fluctuating relapses of myasthenia. One patient, who had undergone thymectomy in his childhood, developed immune thrombocytopenic syndrome. SFEMG done in 12 patients showed abnormalities in 5 cases only (mean jitter elongation, increased percentage of potential pairs with blocking and jitter elongation more than 55 microseconds). In 7 remaining patients the catamnesis covering more than 14 years revealed full clinical and electrophysiological remission. Thus, repeated analysis of the group of myasthenic patients with remission has lead us to revise our former opinion that there are no true remissions, clinical and electrophysiological, in myasthenia. They certainly occur but in some patients normalization of the electrophysiological pattern appears only several years after they have become clinically asymptomatic.