Constitutional risk factors for focal neuropathies in patients referred for electromyography.

BACKGROUND AND PURPOSE: It is well established that patient-related constitutional features predispose to focal peripheral neuropathies. Some of these risk factors were investigated in common focal neuropathies encountered in patients referred for electromyography. METHODS: Gender, age, height and body mass index (BMI) were analysed retrospectively as risk factors for 11 focal neuropathies. In all, 9686 patients (age range 18-96 years; 58% women) were included from three different centres, with identical methods and equipment. RESULTS: High BMI was related to carpal tunnel syndrome (CTS), ulnar neuropathy at the elbow (UNE), combined CTS and UNE, meralgia paraesthetica and lumbar radiculopathy. In women, CTS and Morton's metatarsalgia were more common, whilst long thoracic neuropathies, suprascapular neuropathies and UNE were more common in men. Older age increased the risk for CTS, UNE, Morton's metatarsalgia and radiculopathies. CONCLUSIONS: Age, gender and BMI are important risk factors for many common focal neuropathies.

Reference values for F wave parameters in healthy 3-20 year old subjects.

OBJECTIVE: To create a reference value database for F wave parameters from healthy subjects aged 3-20 yr. METHODS: We studied the following parameters: minimum F wave latency minus distal motor latency (FMINLAT), number of F waves/20 stimuli (FNUMBER) and F wave dispersion (FDISP). The median, ulnar, peroneal and tibial nerves were studied. All four nerves were not analyzed in all subjects, the number of subjects varied from 78 to 118 in each nerve. RESULTS: Age explained 71-87% of the variability of FLATMIN while height explained 80-95% of the variability. The FMINLAT increases by 0.12 ms/cm of height in the upper limb nerves and by 0.28 ms/cm in the lower limb nerves. Gender did not influence the FMINLAT. FDISP was not related with age, height or gender. FNUMBER was not related with age or height, it was somewhat larger in males than females but the difference was not significant in all nerves. CONCLUSIONS: The best model for FMINLAT was a linear regression model with height as an independent variable. FDISP and FNUMBER are not related to age, height or gender between the ages of 3 and 20 yr. SIGNIFICANCE: We have constructed clinically useful reference values for F wave parameters in healthy subjects aged 3-20 yr for the main motor nerves commonly studied.

Thalidomide therapy and polyneuropathy in myeloma patients.

Thalidomide is today an increasingly used therapy in advanced and refractory myeloma patients, especially in patients relapsing after high dose therapy. One important and well-known side effect of thalidomide is polyneuropathy (PNP). The purpose of this study was to investigate 1) how severe the thalidomide-induced PNP is in patients treated for myeloma 2) which neurophysiological tests and parameters are most sensitive in detecting the thalidomide-induced PNP and 3) how neuropathic symptoms correlate with neurophysiological changes. Twelve patients received thalidomide for treatment of relapsed multiple myeloma for at least 5 months. Prior to the thalidomide treatment, all patients had been treated with chemotherapy including vincristine, and seven patients had also received cisplatin. PNP symptoms, clinical findings and neurophysiological tests before and after the therapy were evaluated. Prior to thalidomide treatment, 7 patients had minimal and one patient slight PNP. After thalidomide treatment, 4 patients had minimal, 4 patients slight, and 3 patients moderate PNP. Thalidomide-induced PNP mainly affected sensory myelinated axons, but also alpha motor neuron axons were affected to some extent. Thermal thresholds were not altered, indicating that thin myelinated and unmyelinated axons are spared. The most sensitive parameter for detecting thalidomide-induced PNP was the sensory nerve compound action potential amplitude. The neuropathic symptoms deteriorated significantly during the therapy, but clinically, no patient developed a disabling PNP that would have required interrupting the therapy. The neuropathic side effects of thalidomide seem to be acceptable in myeloma patients.

Mediated exodus of L-dopa from human epidermal Langerhans cells.

L-3,4-dihydroxyphenylalanine (L-dopa) is not metabolized within human epidermal Langerhans cells (LC); yet they can take up substantial amounts of this amino acid which subsequently can be released into the extracellular space. We recently reported that human epidermal energy metabolism is predominantly anaerobic and that the influx mechanism is a unidirectional L-dopa/proton counter-transport system and now we describe conditions for the mediated transport of L-dopa out of the LC. It is demonstrated that certain amino acids and one dipeptide can effectively trigger the efflux of L-dopa taken up by the LC.Thus, alpha-methyl-dopa (alpha-m-dopa), D-dopa and the dipeptide, met-ala at the outside of the plasma membrane stimulated the efflux of L-dopa from L-dopa loaded LC. Similar effects were achieved by a variety of other amino acids in the extracellular fluid while some other amino acids were inactive. The time required for 50% D-methionine-induced exodus of L-dopa from L-dopa loaded LC was in the range of 5-7 min and a complete exodus of L-dopa was attained at about 20 min of incubation. This dislocation of L-dopa to the extracellular fluid is interpreted as an expression of trans-stimulation. In the case of alpha-m-dopa, D-dopa and met-ala, which admittedly were not able to penetrate the plasma membrane of LC, the concept of trans-stimulation was given a new purport, since none of them were able to participate in an exchange reaction. Finally, it could be concluded that L-dopa escaped by a route different from the one responsible for L-dopa uptake in LC.Thus, while the influx of L-dopa supports extrusion of protons deriving from anaerobic glycolysis in the LC, L-dopa efflux can provide the cells with useful amino acids in an energy-saving way, altogether a remarkable biological process. From this follows that L-dopa has a biological function of its own, besides being a precursor in the catecholamine and pigment syntheses.

Behavioural correlates of successful weight reduction over 3 y. Results from the Lean Habits Study.

OBJECTIVE: To examine behavioural characteristics of subjects with successful long-term weight reduction. DESIGN: Prospective cohort study with 3 y follow-up. SETTING: Multicentre study of participants of a commercial weight-reduction programme (BCM-Programme). SUBJECTS: Until February 2000, 6857 voluntary study participants were included. Analyses are based on 1247 subjects with complete 3 y data. INTERVENTIONS: Open-group dietary and behavioural counselling with initial meal substitutions. RESULTS: Subjects show a number of significant behavioural improvements, for example, choice of low-fat food, flexible control of eating behaviour and coping with stress. Subjects who maintain these changes by the end of the first year have a higher probability of successful weight reduction after 3 y. CONCLUSIONS: Successful weight maintenance is associated with more pronounced improvements of health behaviours after 1 y. The likelihood of success increases with the number of behavioural patterns which are involved in the process of change.

Peripheral nervous system in gyrate atrophy of the choroid and retina with hyperornithinemia.

OBJECTIVE: To evaluate peripheral nervous system involvement in gyrate atrophy of the choroid and retina with hyperornithinemia (GA). BACKGROUND: GA is an inborn error of amino acid metabolism caused by mutations in the enzyme ornithine aminotransferase. Patients with GA have hyperornithinemia, progressive centripetal loss of vision, minor CNS abnormalities, and type II muscle fiber atrophy with accumulation of tubular aggregates. The authors previously showed that muscle and brain creatine stores are depleted in the patients with GA. METHODS: The authors searched evidence of peripheral nervous involvement in 40 patients with GA (mean age 31.6 +/- 16.3 years; range 5 to 74 years) by using neurography, quantitative sensory threshold testing, and evoked potential testing. RESULTS: Neurography revealed abnormalities in 21 (53%) of the patients. The abnormalities associated with the severity of the ophthalmologic changes and the age of the patients. With quantitative sensory threshold testing, abnormal large-fiber function was found in seven (18%) and abnormal small-fiber function was found in four (10%) patients. Somatosensory evoked potential and brainstem auditory evoked potential responses were abolished in five patients. CONCLUSIONS: These findings of peripheral nervous system involvement in GA suggest that GA is a systemic disease affecting not only CNS but also the peripheral nervous system.

Hereditary Neuralgic Amyotrophy (HNA) is genetically heterogeneous.

Hereditary Neuralgic Amyotrophy (HNA) is an autosomal dominantly inherited recurrent focal neuropathy affecting mainly the brachial plexus. Linkage to markers on chromosome 17q25 was found in 1996 and subsequent reports confirmed linkage of HNA to this locus. Recently a family with a chronic undulating rather than remitting-relapsing clinical course of HNA was described by a Dutch group. This family did not have linkage to the 17q25 locus. Here we describe for the first time clinically and genetically two families with classic remitting-relapsing HNA that are not linked to the previously described HNA locus on chromosome 17q25. These results demonstrate that clinically homogeneous classical HNA is genetically heterogeneous.

Does dialysis therapy improve autonomic and peripheral nervous system abnormalities in chronic uraemia?

OBJECTIVES: Autonomic nervous system (ANS) dysfunction and peripheral neuropathy occur in patients with chronic renal insufficiency. Adequate renal replacement therapy should prevent development or correct these abnormalities. DESIGN AND SUBJECTS: We studied retrospectively ANS and peripheral neuropathy in 32 patients with chronic uraemia who received either haemodialysis (16) or peritoneal dialysis (16) therapy, and compared the observed dialysis efficiency with changes in neurological function. METHODS: Heart rate variability (HRV) time domain indices and peripheral sensory nerve conduction studies were followed for a mean of 2.9 years. The adequacy of haemodialysis (HD) efficiency was estimated by Kt/V, an index of fractional urea clearance. Adequacy of continuous ambulatory peritoneal dialysis (CAPD) was estimated on the basis of the patient's wellbeing and nutritional status as excellent, satisfactory or poor. Based on observed changes in HRV time domain measures, the observations were divided in three subgroups: improved, unchanged or deteriorated. RESULTS: The peripheral sensory nerve conduction studies were abnormal in 38% of the patients and did not change significantly during the study. Improvement in HRV time domain measures occurred in HD patients with mean Kt/V > 1.20 or in CAPD patients with satisfactory or excellent response to dialysis treatment. Values of Kt/V < 0.85 in HD patients were associated with progressive deterioration of autonomic neuropathy. Diabetic patients (n = 4) differed from others as their HRV was grossly abnormal and did not improve. CONCLUSIONS: The adequacy of haemodialysis is a predictor of improvement of cardiac autonomic nervous function in chronic uraemia. The same trend of improvement was seen also in CAPD patients.

Coping with unfair treatment at work--what is the relationship between coping and hypertension in middle-aged men and Women? An epidemiological study of working men and women in Stockholm (the WOLF study).

BACKGROUND: An important hypothesis in psychosomatic medicine is that exposure to psychosocial factors that arouse anger may accelerate the onset of hypertension, particularly if the subject is not allowed to show anger or to deal constructively with the factor that evoked it. For working men and women, being treated in an unfair way at work may be crucial. The present study was designed to answer the question whether the pattern of coping - primarily directed towards the aggressor (open) or directed inwards or towards others (covert) - is associated with hypertension among working men and women. STUDY GROUP: Five thousand seven hundred and twenty working men and women aged 15-64 participated in the study. The participation rate was 76%. METHODS: The coping pattern was studied by means of a Swedish version of a self-administered questionnaire that was originally introduced by Harburg et al. RESULTS: Significant results were confined to the age group 45-54. All analyses were adjusted for age and body mass index. Smoking habits and social class had no effect on the relationships. Low scores (lowest quartile) for open coping tended to be associated with an elevated prevalence ratio (PR) of hypertension both among men (PR 1.3, 95% confidence interval, CI, 0.9-1.7) and women (PR 1.4, 95% CI 1.0-2.0). High scores for covert coping (highest quartile) were associated with an elevated PR of hypertension among men (PR 1.6, 95% CI 1.2-2.2) but not in women. If the analysis was confined to cases without medication, the relationship between a high level of covert coping and high blood pressure was still significant for men. For women, however, no significant findings were made after this operation. Accordingly, the relationship between a low level of open coping and hypertension in women was confined to women with medication. Coping patterns were correlated with psychosocial work environment factors, in particular decision latitude. CONCLUSION: In men, covert coping was associated with prevalence of hypertension. In women, there tended to be a relationship between low scores for open coping and hypertension.

Postpolio muscular dysfunction: relationships between muscle energy metabolism, subjective symptoms, magnetic resonance imaging, electromyography, and muscle strength.

Eleven patients with previous polio were studied. The concentration of energy-related metabolites and energy charge was measured from the vastus lateralis muscle, as was isometric muscle strength of knee extension. Cross-sectional area of the quadriceps femoris muscle was calculated from magnetic resonance imaging. Reinnervation was studied using macroelectromyography. Muscle weakness, pain, and newly acquired muscle weakness in the legs was estimated by the patients. The findings in the legs in which the patients experienced new loss of muscle function were compared with the stable legs. There were no significant differences between these groups in any of the objectively measured variables. Only hip pain correlated with new loss of muscle function. Creatine phosphate was decreased in 5 patients. The symptoms and subjective muscle strength did not correlate with any of the objective measurements. There were no significant relationships between energy-related metabolites and postpolio symptoms.

F-wave latency, the most sensitive nerve conduction parameter in patients with diabetes mellitus.

In this study we examined the diagnostic sensitivity of minimal F-wave latency, F-wave persistence, motor nerve conduction velocity (MCV), and amplitude of the compound motor action potential (CMAP) of the median, ulnar, tibial, and peroneal nerves, and of sensory conduction velocity (SCV) and sensory nerve action potential (SNAP) amplitude of the sural nerve in 82 diabetic patients. For the median, ulnar, and tibial nerves the Z scores of the minimal F-wave latency were significantly larger than those of the MCV, and for all four motor nerves the Z scores of the minimal F-wave latency were significantly larger than those of the amplitude of the CMAP. The Z scores of the peroneal minimal F-wave latency exceeded those of peroneal MCV, sural SCV, and sural SNAP. F-wave persistence did not differ significantly from the reference values. In conclusion, minimal F-wave latency is the most sensitive measure for detection of nerve pathology and should be considered in electrophysiological studies of diabetic patients.

Proximal myotonic dystrophy--a family with autosomal dominant muscular dystrophy, cataracts, hearing loss and hypogonadism: heterogeneity of proximal myotonic syndromes?

We describe a family with an autosomal dominant, multisystem disorder, consisting of late-onset proximal muscular dystrophy, electrophysiological myotonia, cataracts, late-onset deafness and male hypogonadism. Four patients were available for clinical examinations. Examination of asymptomatic family members revealed another patient with bilateral cataracts but without definite muscle disorder. Five deceased members of the family had proximal muscle weakness, reportedly or confirmed in medical records. Molecular examination of genomic DNA showed no expansion of the unstable (CTG)n trinucleotide repeat on chromosome 19q13.3 associated with myotonic dystrophy (DM). Linkage to two loci implicated in other myotonic disorders, the muscle chloride channel (CLCN1) gene, and the muscle sodium channel (SCN4A) gene, was assessed and excluded. The clinical findings differ from those described in proximal myotonic myopathy (PROMM), in terms of the more severe muscle involvement with atrophy of affected muscles and the hearing loss. These findings suggest phenotypic and probably genetic heterogeneity among the proximal myotonic syndromes.

Motor unit size estimation: confrontation of surface EMG with macro EMG.

Surface EMG (SEMG) is little used for diagnostic purposes in clinical neurophysiology, mainly because it provides little direct information on individual motor units (MUs). One of the techniques to estimate the MU size is intra-muscular Macro EMG. The present study compares SEMG with Macro EMG. Fifty-eight channel SEMG was recorded simultaneously with Macro EMG. Individual MUPs were obtained by single fiber triggered averaging. All recordings were made from the biceps brachii of healthy subjects during voluntary contraction at low force. High positive correlations were found between all Macro and Surface motor unit potential (MUP) parameters: area, peak-to-peak amplitude, negative peak amplitude and positive peak amplitude. The MUPs recorded with SEMG were dependent on the distance between the MU and the skin surface. Normalizing the SEMG parameters for MU location did not improve the correlation coefficient between the parameters of both techniques. The two measurement techniques had almost the same relative range in MUP parameters in any individual subject compared to the others, especially after normalizing the surface MUP parameters for MU location. MUPs recorded with this type of SEMG provide useful information about the MU size.

The role of electromyography in neurology.

A review is given of the role of electromyography (EMG) for diagnosis, pathophysiological description and monitoring of patients with disorders of the peripheral nervous system. Various EMG methods are presented and their principal differences are discussed. The usefulness of these methods varies depending on the pathology to be studied. With modern quantitative methods for analysis, EMG has become more sensitive and accurate and is therefore an important part in the evaluation of the neurologic patient. EMG results are usually combined with findings from other neurophysiological investigations (neurography, evoked potentials), histochemistry, biochemistry and most importantly with the clinical signs to give as complete a picture of the condition as possible. The usefulness of EMG depends on a number of factors other than the quality of the investigation as such. These aspects are discussed briefly.

Significance of A-waves recorded in routine motor nerve conduction studies.

The occurrence of A-waves during routine F-wave studies was investigated in 556 consecutive patients referred to the Department of Clinical Neurophysiology at the University Hospital in Uppsala for various neuromuscular disorders. Altogether, 2367 nerves in the upper and lower extremities were studied. An A-wave, with a nearly constant latency and a uniform shape on consecutive stimulations, could be recorded in 184 nerves (7.8%) out of 124 patients (22.3%). More than 50% of patients with A-waves had various types of polyneuropathies. Of all patients with polyneuropathy, 65% had at least one nerve with A-waves. A-waves occurred somewhat less frequently in patients with radiculopathies. In other proximal local nerve lesions they were found less often and only exceptionally in patients with distal nerve lesions. A-waves were present in 6 out of 10 patients with motor neurone diseases. There was no correlation between the number of A-waves found in one nerve or the number of nerves in a given patient with A-waves and the aetiology or severity of the underlying disease. A-waves were found in 11 patients referred for various neurological symptoms in whom other neurophysiological findings were normal. This might be interpreted as an early sign of underlying disease because in 100 healthy controls no A-waves could be elicited, with the exception of 3 subjects who had A-waves in the abductor hallucis muscle when the tibial nerve was stimulated. We conclude that the appearance of A-waves should be considered a sign of either a local nerve lesion or a generalised neuropathy in all other nerves except for the tibial nerve.

Quantitative motor unit potential analysis.

A review of quantitative methods for electromyography is given. Background information about motor unit anatomy, physiology, and pathology is provided to explain some of the presented electrophysiological phenomena. Different aspects of quantitation, such as motor unit action potential parameters, automatic analysis methods, reference values, and findings in abnormal conditions, are discussed.

Evaluation of the diagnostic performance of the expert EMG assistant MUNIN.

The diagnostic performance of the medical expert system MUNIN for diagnosis of neuromuscular disorders was evaluated on a set of 30 test cases. The cases were provided by 7 experienced electromyographers who were subsequently invited to participate in the evaluation. To reasonably cover the range of disorders, the electromyographers were asked to provide cases from patients with different types of muscular dystrophy, with neuromuscular transmission disorders, with motor neurone disease, and with different types of polyneuropathies. In addition, patients with a range of local neuropathies were provided. Out of the 30 cases, 11 cases were evaluated by an "almost peer review" method and the remaining 19 cases were evaluated by a "silver standard" method. The number of cases evaluated by "almost peer review" was limited to 11 due to time constraints on the evaluation procedure. During the "almost peer review," each electromyographer was asked to diagnose patients, using a vocabulary that closely resembled MUNIN's vocabulary. Subsequently, we attempted to provide a consensus diagnosis for the patients based on discussion among the participating electromyographers. The electromyographers were also asked to assess how well MUNIN had performed in each case. The remaining 19 cases were evaluated by a "silver standard" procedure, where MUNIN's diagnosis was compared to the diagnosis of the expert who provided the case. The results indicated that MUNIN performed well, and the electromyographers considered "that MUNIN performed at the same level as an experienced neurophysiologist." In particular, it was noted that MUNIN handled cases with conflicting findings well, and that it was able to diagnose patients with multiple diseases.