Subcutaneous IGF-1 is not beneficial in 2-year ALS trial.

BACKGROUND: Previous human clinical trials of insulin-like growth factor type I (IGF-1) in amyotrophic lateral sclerosis (ALS) have been inconsistent. This phase III, randomized, double-blind, placebo-controlled study was undertaken to address whether IGF-1 benefited patients with ALS. METHODS: A total of 330 patients from 20 medical centers were randomized to receive 0.05 mg/kg body weight of human recombinant IGF-1 given subcutaneously twice daily or placebo for 2 years. The primary outcome measure was change in their manual muscle testing score. Secondary outcome measures included tracheostomy-free survival and rate of change in the revised ALS functional rating scale. Intention to treat analysis was used. RESULTS: There was no difference between treatment groups in the primary or secondary outcome measures after the 2-year treatment period. CONCLUSIONS: Insulin-like growth factor type I does not provide benefit for patients with amyotrophic lateral sclerosis.

Serial quantitative electrophysiologic studies in sporadic inclusion body myositis.

Sporadic inclusion body myositis (S-IBM) is a progressive, acquired myopathic process of unknown etiology. No known, successful or proven treatment exists. Quantitative EMG studies including concentric needle motor unit action potentials, interference pattern, macro-EMG and fiber density have allowed different measures to be made of the motor unit. These different measures allow inferences to be made in how the muscle fibers are distributed within both the normal and diseased motor unit. The present study is an effort to use multiple quantitative EMG measurements from the biceps brachii on a serial basis in order to study chronic changes in the motor unit with disease progression. Twenty-eight studies from 9 patients over a four-year period are shown. We conclude that while the concentric needle electrode is most helpful for diagnosing abnormality, the less selective macro-EMG and surface electrodes are better suited to monitor disease progression, especially in very weak muscles. These observations have practical applications for monitoring disease progression, or conversely, response to treatment.

"Facial" and standard concentric needle electrodes are not interchangeable.

Motor unit action potentials (MUAPs) were recorded using a standard concentric needle (SCN), a "facial" concentric needle (FCN) and a monopolar needle (MN) in the biceps brachii and first dorsal interosseous manus muscles of 7 normal subjects. For each muscle, the MUAP durations were similar for all electrodes. However, the FCN electrode more frequently registered high-amplitude MUAPs compared to the SCN electrode. Hence, the FCN and SCN needles should not be considered interchangeable in assessment of EMG signal amplitude. Although, the pattern of changes in amplitude and duration on FCN and MN recordings is similar, the electrodes have different uptake areas.

Influence of the surface EMG electrode on the compound muscle action potential.

The recording characteristics of surface EMG electrodes were investigated. Compound muscle action potential (CMAP) and surface recorded motor unit action potentials were recorded from different muscles, using different surface electrode shapes and sizes. The CMAP was smaller for larger surface electrodes. This was more pronounced in smaller muscles. The CMAP was minimally affected by the geometry of the recording surface. With larger surface electrodes, shunting contributes to the reduction in MUAP amplitude. This is offset by a larger uptake area which gives a much smaller reduction in the CMAP amplitude for the larger muscles.

Retrospective diagnosis of congenital cytomegalovirus infection and cortical maldevelopment.

Congenital cytomegalovirus (CMV) infection can cause malformations of cortical development (MCD). It is difficult to establish CMV as a cause of MCD several months postpartum. This can now be done by detection of CMV DNA in dried blood spots (DBS test) on Guthrie cards. The authors used DBS tests to assess 10 patients with MCD of unknown cause. Four of the 10 patients were positive for CMV.

Some observations on fibrillations and positive sharp waves.

Electromyographic recordings of fibrillation potentials (FPs) and positive sharp waves (PSWs) demonstrate transformation of FP to PSW and vice versa, atypical firing patterns, changes in waveform shape and amplitude, and time-locked potentials. The etiology of the waveform characteristics of FP and PSW is discussed based on abnormal propagation in a small section of muscle fiber that is "damaged" by the needle. The results of simple computer simulations are described.

Quantitative electrophysiologic studies in sporadic inclusion body myositis.

Sporadic inclusion body myositis (S-IBM) is a progressive, acquired disease of unknown etiology. Prior studies have suggested neurogenic involvement based on electrophysiologic data, although the biopsy is compatible with a myopathic process. Quantitative electrophysiologic studies were performed in the biceps brachii of 17 subjects with biopsy-proven S-IBM. Quantitative motor unit action potential (MUAP) analysis was compatible with myopathy in 16 subjects, with the remaining subject being within normal limits. Quantitative interference pattern was myopathic in all 13 subjects studied. Macro-EMG MUAP amplitude was reduced in 3 of 17 studies; the remainder were within normal range, and none was increased as would be expected in neurogenic disease. Fiber density was normal to borderline increased in all subjects. Possible reasons for encountering neurogenic-appearing MUAPs may include choice of muscle studies, because some patients have co-existing polyneuropathy and large-amplitude MUAPs from hypertrophied muscle fibers. The data from this study indicate that S-IBM is a myopathic process.

Incidence of dominant spinocerebellar and Friedreich triplet repeats among 361 ataxia families.

OBJECTIVE: To determine the incidence of spinocerebellar ataxia (SCA) types 1, 2, 3, 6, and 7 and Friedreich's ataxia (FA) among a large panel of ataxia families. BACKGROUND: The ataxias are a clinically and genetically heterogeneous group of neurodegenerative diseases that variably affect the cerebellum, brainstem, and spinocerebellar tracts. Trinucleotide repeat expansions have been shown to be the mutational mechanism for five dominantly inherited SCAs as well as FA. METHODS: We collected DNA samples and clinical data from patients representing 361 families with adult-onset ataxia of unknown etiology. Patients with a clinical diagnosis of FA were specifically excluded from our collection. RESULTS: Among the 178 dominant kindreds, we found SCA1 expansion at a frequency of 5.6%, SCA2 expansion at a frequency of 15.2%, SCA3 expansion at a frequency of 20.8%, SCA6 expansion at a frequency of 15.2%, and SCA7 expansion at a frequency of 4.5%. FA alleles were found in 11.4% of apparently recessive and 5.2% of apparently sporadic patients. Among these patients the repeat sizes for one or both FA alleles were relatively small, with sizes for the smaller allele ranging from 90 to 600 GAA repeats. The clinical presentation for these patients is atypical for FA, with one or more of the following characteristics: adult onset of disease, retained tendon reflexes, normal plantar response, and intact or partially intact sensory perceptions. CONCLUSIONS: Pathogenic trinucleotide repeat expansions were found among 61% of the dominant kindreds. Among patients with apparently recessive or negative family histories of ataxia, 6.8% and 4.4% tested positive for a CAG expansion at one of the dominant loci, and 11.4 and 5.2% of patients with apparently recessive or sporadic forms of ataxia had FA expansions. Because of the significant implications that a dominant versus recessive inheritance pattern has for future generations, it is important to screen patients who do not have a clearly dominant inheritance pattern for expansions at both the FA and the dominant ataxia loci.

Evaluation and management of polyneuropathy: a practical approach.

Disorders of peripheral nerves are commonly encountered by primary health care providers. This article reviews one of the most frequent patterns, that is, polyneuropathy (PN). PN is a common but complex entity. Understanding the pathophysiology of axons, the classification of PN, the biologic targets of toxins and the patterns of PN assist in the diagnosis of PN. The pathophysiology, symptoms, and signs are discussed along with basic steps to be taken in the evaluation, diagnosis, and management. Illustrative case studies are provided. Diagnosis may not be possible in all cases. When the etiology is unknown, ongoing monitoring of the polyneuropathy is emphasized, particularly in acquired processes where the polyneuropathy may be associated with systemic disease. In such instances, care of the client is directed toward symptomatic management.

On the selection of concentric needle electromyogram motor unit action potentials: is the rise time criterion too restrictive?

Concentric needle electromyogram motor unit action potentials (MUAPs) were recorded from the biceps brachii muscle of normal subjects and in patients with neuromuscular diseases. Although the MUAPs had a crisp sound and appeared sharp, their rise time (RT), measured from the maximum negative peak to the preceding maximum positive peak before it, was often > 500 microseconds. All MUAPs with a RT < or = 500 microseconds were recorded from within the motor unit (MU) territory. MUAP recordings from outside the MU territory had a long RT but also low amplitude (< 50 microV) and/or a characteristic initial negative deflection. In the remaining recordings from within the MU territory, MUAP duration remained relatively constant while MUAP amplitude and RT varied inversely with each other. These MUAPs may be useful in electrodiagnosis but discarded due to their longer RT. We feel that while the current RT criterion for MUAP selection ensures that the electrode tip is within the MU territory, it is also too restrictive.

Multi-motor unit action potential analysis (MMA)

We have developed an algorithm, called multi-motor unit action potential analysis (MMA), to aid quantification in routine needle EMG examination. In only 5-8 min, it was possible to extract, analyze, and validate 20 motor unit action potentials (MUAPs). In the biceps muscle of normal subjects, the MUAP measurements are compared with measurements using manual, triggered averaging, automatic decomposition, and other MMA algorithms described in the literature. The mean values of MUAP features by MMA fell between the extreme limits obtained from the amplitude-triggered method and the manual method described in the literature. In patients, the results are consistent with routine EMG and similar to those results described in the literature. Fast acquisition and analysis of MUAPs as well as interference pattern (IP) analysis make this technique useful to document EMG abnormalities in routine needle examination.

Recording characteristics of the surface EMG electrodes.

Routine motor nerve conduction studies are conducted using surface EMG electrodes. Most techniques of estimating the number of motor units (MUs) are based on surface EMG recordings. Therefore, it is important to assess the uptake area of these electrodes. We recorded surface EMG motor unit action potentials (SMUAPs) from the biceps muscle of normal subjects. The SMUAP amplitude fell from 42 microV for the superficially located MUs (i.e., within 10 mm of skin surface) to 11 microV for the deep MUs (i.e., more than 20 mm from the skin surface). We infer that the pickup radius of the surface electrode is less than 20 mm. The implications of the limited uptake area of the surface electrodes to the analysis of compound muscle action potentials, estimation of the number of MUs, and the surface EMG recordings are discussed.

Quantitative EMG in inflammatory myopathy.

Fifty-four quantitative electromyographic (EMG) studies were made in 37 patients with inflammatory myopathy (IM) at different points in their clinical course and treatment. All studies were performed in the biceps brachii which varied in clinical strength. Motor unit action potentials (MUAPs) in 45 studies and EMG interference pattern (IP) in 48 studies were recorded using a concentric needle electrode. Macroelectromyographic (Macro-EMG) MUAPs were recorded from 10 patients in 14 studies. MUAP analysis revealed a myopathic pattern (decreased duration and/or area: amplitude ratio) in 69% of studies. IP analysis was more sensitive than MUAP analysis, demonstrating a myopathic pattern in 83% of studies. Macro-EMG MUAP amplitudes were reduced in two studies, minimally increased in one study and normal in the remainder; in 6 (40%) studies, fiber density was slightly increased. Thus, reinnervation does not seem to play an important role in motor unit remodeling in IM.

Duchenne muscular dystrophy manifesting carriers.

Seven unrelated women were manifesting carriers of Duchenne muscular dystrophy. A manifesting carrier of Duchenne muscular dystrophy is defined as a female with a history of Duchenne muscular dystrophy in her pedigree who has symptomatic weakness. All were characterized by slowly progressive weakness that began in the second or third decade of life. Asymmetric weakness was present in only three of the seven patients. Serum creatine kinase values were elevated in all patients and none had an electrocardiogram indicating ventricular hypertrophy. The electromyogram and muscle biopsy specimens were reported as myopathic in all patients studied. In the absence of a male relative with Duchenne muscular dystrophy, clinical distinction from cases of autosomal recessive limb girdle muscular dystrophy may not be possible. The development of new techniques in molecular genetics should allow precise identification of manifesting carriers of Duchenne muscular dystrophy in the near future.

Evaluation of an automatic method of measuring features of motor unit action potentials.

This study was performed to evaluate an automatic method of motor unit action potential (MUAP) analysis developed in our laboratory. MUAPs were recorded from the biceps brachii muscle of 68 normal subjects and 122 patients with nerve or muscle disease. The values of mean MUAP durations from normal subjects obtained by automatic analysis were similar to those reported in the literature. However, the normal range of MUAP amplitude and the incidence of polyphasic MUAPs were much higher. Normal ranges of mean MUAP area, area/amplitude ratio, and the number of turns were also defined. Automatic analysis demonstrated an abnormality of at least one MUAP feature in 70% of patients. There was concordance between automated analysis and visual assessment of MUAPs in 76% of patients with neuropathy but in only 50% of patients with myopathy. The relationships between different MUAP features seen in neuropathy and myopathy are explained in physiologic terms.

Automatic analysis of the electromyographic interference pattern using the turns: amplitude ratio.

This study was performed to compare different techniques of analyzing the electromyographic interference pattern (IP). Recordings were made from the biceps muscle with a concentric needle electrode at different sites and at different constant levels of voluntary contraction. The number of turns per second (NT), the mean amplitude change between successive turns (MA) and NT:MA ratio were determined for epochs of 1 sec duration. Normal limits of individual epoch NT:MA ratios and the mean value of NT:MA ratio obtained from all epochs in each muscle were determined. The mean NT:MA ratio was less in normal males than in females. IP recordings were made in the biceps muscle of 69 patients with neuropathy and 54 patients with myopathy, though this muscle was not necessarily affected by the disease in all patients. The IP was abnormal by visual inspection in 82% of patients compared to 61% based on NT:MA ratio and 74% using a technique that automatically quantitates some features of the IP that are assessed subjectively by an electromyographer. All techniques demonstrated IP abnormalities in more than 80% of the muscles that were moderately to severely weak. Though measuring the NT:MA ratio without monitoring the force of contraction is not as sensitive as other IP analysis techniques, it may be useful in quantitating abnormalities when other techniques are not available.

Analysis of amplitude and area of concentric needle EMG motor unit action potentials.

Computer simulations indicate that measurements of the area of motor unit action potentials (MUAPs) recorded with a concentric needle electrode could be useful in differentiating between neuropathy and myopathy. However, MUAP area varies markedly when the position of the recording electrode is changed only slightly within the motor unit territory, mainly because of the changes in the MUAP amplitude produced by only slight electrode movements. The ratio of MUAP area to amplitude is much less affected by changes in electrode position and measures the 'thickness' of the MUAP wave form. We found that the MUAP area:amplitude ratio was reduced in myopathy even when the MUAP amplitude was normal or increased. In patients with neuropathy, the MUAP amplitude and area both tend to be increased while their ratio is normal or increased. The diagnostic yield obtained from MUAP area, amplitude and their ratio in combination was similar to that obtained using measurements of MUAP duration. Unlike the MUAP duration, the MUAP area, amplitude and area:amplitude ratio are robust features of the MUAP in that they are less sensitive to the signal-to-noise ratio and inter-operator differences in signal selection.

Jamaican neuropathy: an electrophysiological study.

Jamaican neuropathy (JN) is a common disorder in Jamaica and has characteristics similar to neurological diseases found in other tropical areas. JN is a clinical syndrome and occurs in two forms: spastic and ataxic. This is the first known electrophysiological study of this disease. In the spastic group of JN, peripheral electrophysiological findings were mostly normal, suggesting a central cause for their symptoms. The only patient with the ataxic form of JN had a chronic axonal peripheral neuropathy.

Jamaican neuropathy: an electrophysiological study

Jamaican neuropathy (JN) is a common disorder in Jamaica and has characteristics similar to neurological diseases found in other tropical areas. JN is a clinical syndrome and occurs in two forms: spastic and ataxic. This is the first known electrophysiological study of this disease. In the spastic group of JN, peripheral electrophysiological findings were mostly normal, suggesting a central cause for their symptoms. The only patient with the ataxic form of JN had a chronic axonal peripheral neuropathy. (AU)