Estimating motor unit numbers from a CMAP scan: Repeatability study on three muscles at 15 centres.

OBJECTIVE: To assess the repeatability and suitability for multicentre studies of MScanFit motor unit number estimation (MUNE), which involves modelling compound muscle action potential (CMAP) scans. METHODS: Fifteen groups in 9 countries recorded CMAP scans twice, 1-2 weeks apart in healthy subjects from abductor pollicis brevis (APB), abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. The original MScanFit program (MScanFit-1) was compared with a revised version (MScanFit-2), designed to accommodate different muscles and recording conditions by setting the minimal motor unit size as a function of maximum CMAP. RESULTS: Complete sets of 6 recordings were obtained from 148 subjects. CMAP amplitudes differed significantly between centres for all muscles, and the same was true for MScanFit-1 MUNE. With MScanFit-2, MUNE differed less between centres but remained significantly different for APB. Coefficients of variation between repeats were 18.0% for ADM, 16.8% for APB, and 12.1% for TA. CONCLUSIONS: It is recommended for multicentre studies to use MScanFit-2 for analysis. TA provided the least variable MUNE values between subjects and the most repeatable within subjects. SIGNIFICANCE: MScanFit was primarily devised to model the discontinuities in CMAP scans in patients and is less suitable for healthy subjects with smooth scans.

Neurophysiological localisation of ulnar neuropathy at the elbow: Validation of diagnostic criteria developed by a taskforce of the Danish Society of clinical neurophysiology.

OBJECTIVE: This study validates consensus criteria for localisation of ulnar neuropathy at elbow (UNE) developed by a taskforce of the Danish Society of Clinical Neurophysiology and compares them to the existing criteria from the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM). The Danish criteria are based on combinations of conduction slowing in the segments of the elbow and forearm expressed in Z-scores, and difference between the segments in m/s. Examining fibres to several muscles and sensory fibres can increase the certainty of the localisation. METHODS: Diagnostic accuracy for UNE was evaluated on 181 neurophysiological studies of the ulnar nerve from 171 peer-reviewed patients from a mixed patient-group. The diagnostic reference standard was the consensus diagnosis based on all available clinical, laboratory, and electrodiagnostic information reached by a group of experienced Danish neurophysiologists. RESULTS: The Danish criteria had high specificity (98.4%) and positive predictive value (PPV) (95.2%) and fair sensitivity (76.9%). Compared to the AANEM criteria, the Danish criteria had higher specificity (p<0.001) and lower sensitivity (p=0.02). CONCLUSIONS: The Danish consensus criteria for UNE are very specific and have high PPV. SIGNIFICANCE: The Danish criteria for UNE are reliable and well suited for use in different centres as they are based on Z-scores.

Fabry disease in children: agalsidase-beta enzyme replacement therapy.

Fabry disease is a rare, multiorgan disease. The most serious complications involve the kidney, brain and heart. This study aims to assess the effect of enzyme replacement therapy (ERT) using agalsidase-beta in children with Fabry disease. We carried out a nationwide, descriptive and observational retrospective cohort study of 10 children (9-16 years at baseline), who underwent regular systematic investigations for 1-8 years after initiation of ERT with agalsidase-beta (Fabryzyme®, Genzyme). Ophthalmological, echocardiographic abnormalities and hypohidrosis were found at baseline and during the follow-up period. Serious kidney, heart or brain involvement had not developed at the last follow-up examination. For the majority of the patients improvements were found concerning headache, acroparaesthesias and gastrointestinal pain during the follow-up period. The level of energy and physical activity also increased. Treatment with agalsidase-beta was associated with a reduction of neuropathic and abdominal pain and headache. Although all aspects of the Fabry pain phenotype cannot be treated with ERT, the observed effects were clinically significant in the lives of the majority of Fabry children and together with the absence of serious Fabry manifestations at last follow-up, we argue that early initiation of ERT may be considered.

Responsiveness of the Multiple Sclerosis Impairment Scale in comparison with the Expanded Disability Status Scale.

The Multiple Sclerosis Impairment Scale (MSIS) is a measure of accumulated deficits assessed by means of a standard neurological examination. We compared the responsiveness of the MSIS with that of the Expanded Disability Status Scale (EDSS). We reviewed 4300 records collected systematically from 1995 to 2003 and identified 534 patients who had clinically definite multiple sclerosis and had had at least two clinical assessments with a time interval of 2-5 years. The rate of deterioration was significantly higher on the MSIS than on the EDSS. The annualized change in EDSS exhibited a maximum at baseline EDSS 4 and a subsequent rapid decline at higher baseline EDSS, while the annualized change in MSIS was fairly stable over a wide middle range of baseline MSIS. The variance of the annualized change in EDSS fluctuated markedly between the baseline EDSS categories, being highest at baseline EDSS 2, while the variance of the annualized change in MSIS was stable. The study indicates that the responsiveness of the MSIS is better than that of the EDSS in terms of both magnitude and stability over the range of measurement

[Thrombolytic treatment of acute cerebral infarction]. / Trombolysebehandling af akut cerebralt infarkt.

INTRODUCTION: Thrombolytic therapy of acute ischaemic stroke within three hours of the onset of symptoms is approved by health authorities in the USA and Canada, but not in Europe. METHODS: We report seven patients treated with recombinant tissue plasminogen activator (rtPA) within three hours of the onset of stroke according to an open protocol following internationally accepted guidelines. RESULTS: Three patients with initial severe neurological deficits made an almost complete recovery within the first 24 hours after treatment. Two patients had a partial remission, and two patients had no benefit. There were no bleeding complications. DISCUSSION: The present results are in accordance with the Cochrane Library's analysis of published data regarding thrombolytic therapy.

Self-reported food intolerance in chronic inflammatory bowel disease.

BACKGROUND: Although suggested, it has never been convincingly documented that food sensitivity is of pathogenetic importance in chronic inflammatory bowel disease. However, many patients may relate their gastrointestinal symptoms to specific food items ingested and may restrict their diet accordingly. METHODS: A questionnaire was sent to all patients with chronic inflammatory bowel disease who attended the outpatient clinic, Medical Dept., Roskilde County Hospital in Køge, Denmark, in the year 1993. The patients were asked whether they had problems with any particular food item and, if so, to describe the symptoms experienced from it. A control group of 70 healthy persons were included. RESULTS: Among 189 patients, 132 (70%) responded. One hundred and thirty had completed the questionnaire, 52 males and 78 females aged 13-89 years (median, 43 years). Fifty-three (41%) had Crohn's disease (CD), 69 (53%) ulcerative colitis (UC), and 8 (6%) unclassified colitis. Forty-one patients (31 CD, 10 UC) were-operated on; 51 (19 CD, 32 UC) had disease activity. Sixty-five per cent of the patients and 14% of the controls reported being intolerant to one or more food items (P < 0.0001). The intolerance covered a wide range of food products. The commonest symptoms among patients were diarrhoea, abdominal pain, and meteorism and among controls, regurgitation. Food intolerance was equally common in CD (66%) and UC (64%) and was not related to previous operation, disease activity or disease location. CONCLUSION: Most patients with chronic inflammatory bowel intolerance disease feel intolerant to different food items and may restrict their diet accordingly. The frequency and pattern of food intolerance did not differ between patients with CD and UC. The food intolerance was probably unspecific rather than of pathogenetic importance.

[Fulminant cytomegalovirus colitis without prior immune deficiency or colonic disease]. / Fuliminant cytomegalovirus-colitis uden tilgrundliggende immundefekt eller colonsygdom.

Fulminant primary Cytomegalovirus (CMV) colitis can occur in immunocompetent individuals and mimics inflammatory bowel disease. Cytomegalovirus inclusions are found in rectal or colonic biopsy specimens. Thus, careful histological evaluation of mucosa biopsies is essential for the diagnosis of this entity.

On the mechanism of the post-activation depression of the H-reflex in human subjects.

It was demonstrated that the soleus H-reflex was depressed for more than 10 s following a preceding passive dorsiflexion of the ankle joint. This depression was caused by activation of large-diameter afferents with receptors located in the leg muscles, as an ischaemic block of large-diameter fibres just below the knee joint abolished the depression, whereas a similar block just proximal to the ankle joint was ineffective. The depression of the H-reflex was not caused by changes in motoneuronal excitability, as motor-evoked potentials by magnetic brain stimulation were not depressed by the same passive dorsiflexion. Therefore it was concluded that the long-lasting depression is due to mechanisms acting at presynaptic level. The transmission of the monosynaptic Ia excitation from the femoral nerve to soleus motoneurones was not depressed by the ankle dorsiflexion. The depression thus seems to be confined to those afferents that were activated by the conditioning dorsiflexion. In parallel experiments on decerebrate cats, more invasive methods have complemented the indirect techniques used in the experiments on human subjects. A similar long-lasting depression of triceps surae monosynaptic reflexes was evoked by a preceding conditioning stimulation of the triceps surae Ia afferents. This depression was accompanied by a reduction of the monosynaptic Ia excitatory postsynaptic potential recorded intracellularly in triceps surae motoneurones, but not by changes in the input resistance or membrane potential in the motoneurones. Stimulation of separate branches within the triceps surae nerve demonstrated that the depression is confined to those afferents that were activated by the conditioning stimulus. This long-lasting depression was not accompanied by a dorsal root potential. It is concluded that the long-lasting depression is probably caused by a presynaptic effect, but different from the "classical" GABAergic presynaptic inhibition which is widely distributed among afferent fibres and accompanied by dorsal root potentials. It is more probably related to the phenomenon of a reduced transmitter release from previously activated fibres, i.e. a homosynaptic post-activation depression. The consequences of this post-activation depression for the interpretation of results on spinal mechanisms during voluntary movements in man are discussed.

A reliable method to estimate the association constant for a monoclonal antibody and a protein antigen by enzyme linked immunosorbent assay, ELISA.

The association constant Ka for mouse monoclonal antibody raised against human angiotensinogen was calculated using a mathematical model, SAM I. K1 represents the equilibrium constant for the binding of antibody to the solid phase with antigen previously absorbed. K2 represents the interaction between antibody and antigen in solution (Ag + Ab = AgAb). K3 represents binding to the antigen absorbed on the solid phase by an antigen-antibody complex. K4 represents the second binding of the antigen to the antigen-antibody complex (AgAb + AgAb = (Ag)2Ab). The model unveils cooperativity for the first (K1 and K2) and second (K3 and K4) binding of antigen to antibody. The model gives the association constant in a high affinity interaction between antigen and antibody.

Latency of effects evoked by electrical and magnetic brain stimulation in lower limb motoneurones in man.

1. The latency of effects in the tibialis anterior (TA) and soleus (Sol) muscles evoked by electrical and magnetic stimulation of the motor cortex was evaluated in human subjects by H reflex testing. Post-stimulus time histograms (PSTHs) were established for the discharge of single voluntarily activated motor units and motor-evoked potentials (MEPs) in the surface electromyogram. 2. At rest both electrical and magnetic stimulation evoked an inhibition of the Sol H reflex at the lowest intensities of stimulation. In some subjects a facilitation with an earlier onset was seen when increasing the stimulation strength. When the anode for the electrical stimulation was placed at the vertex directly above the leg motor area, the inhibition or facilitation often had the same latency as when evoked by magnetic stimulation. However, when the anode was placed 2-3 cm lateral to the vertex, effects evoked by the electrical stimulus often occurred 1-2 ms earlier. 3. Short-latency peaks in the PSTH of the discharges of single TA motor units also tended to occur earlier when evoked by electrical stimulation with the anode lateral to the vertex than when evoked by magnetic stimulation or electrical stimulation with the anode at the vertex. 4. In one subject, near-maximal electrical stimulation evoked MEPs with a latency corresponding to that seen following stimulation of the brainstem by electrodes placed bilaterally over the mastoid processes approximately 16 cm more distal. Maximal magnetic stimulation, in contrast, never resulted in responses with a latency shorter than that seen with the weakest electrical stimuli at the vertex. 5. The initial facilitation of the Sol H reflex evoked by magnetic stimulation and by electrical anodal stimulation at the vertex increased when the subject performed a voluntary plantarflexion. In contrast, the earlier facilitation evoked by electrical anodal stimulation 2-3 cm lateral to the vertex had the same size both at rest and during contraction. 6. We suggest that magnetic stimulation and electrical anodal stimulation at the vertex may preferentially activate descending cortical cells at, or close to, the cell soma. The initial responses evoked by these two stimuli may therefore be influenced by the excitability of the cortical cells. On the other hand, electrical stimulation with the anode 2-3 cm lateral to the vertex seems to often activate the axons at a deeper level. The initial responses evoked by this type of stimulation may therefore not be influenced by the excitability of the cortical cells.

Disynaptic reciprocal inhibition of ankle extensors in spastic patients.

The soleus Hoffmann-reflex (H-reflex) was conditioned by a preceding stimulation of the common peroneal nerve in 74 healthy control subjects and 39 patients with spasticity in the lower extremities due to multiple sclerosis. At a conditioning-test interval of 1-3 ms a decrease of the size of the soleus H-reflex was seen in the healthy subjects. The decrease was most likely caused by disynaptic reciprocal Ia inhibition (Crone et al., 1987). In the spastic patients a similar short-latency inhibition was rarely seen. On the contrary, in several patients a facilitation was seen at a conditioning-test interval of 3-4 ms. A short-latency inhibition as pronounced as in healthy subjects was seen in four patients. These four patients did not differ from the other patients regarding the degree of spasticity or any other clinical parameter. However, they all used an external peroneal nerve stimulator daily as a walking aid. It is suggested that the lack of short-latency reciprocal inhibition reflects a deficient control of the interneurons which mediate this inhibitory spinal mechanism between antagonistic muscles in man. This might contribute to the pathophysiology of spasticity and it might be related to the frequent occurrence of co-contraction of functionally antagonistic muscles during gait in spastic patients. The existence of a pronounced reciprocal inhibition in patients receiving frequent stimulation of the peroneal nerve may suggest that regular activation of peripheral nerves is of importance for the maintenance of the activity in spinal pathways.

Task-related changes in the effect of magnetic brain stimulation on spinal neurones in man.

1. The effect of magnetic stimulation of the human motor cortex on the excitability of soleus, tibialis anterior and flexor carpi radialis motoneurones was investigated by H reflex testing in ten healthy subjects. 2. At rest, an early facilitation of the flexor capri radialis and tibialis anterior H reflexes was always seen, whereas a similar early facilitation of the soleus H reflex was seen in only two out of seven subjects. For all three motoneuronal pools the facilitation was curtailed 1-5 ms later by an inhibition which lasted for another 3-4 ms. In five subjects an inhibition without any evidence of an earlier facilitation was seen for the soleus H reflex. 3. The intensity of the magnetic stimulation was subsequently decreased so that it had no effect on the H reflex at rest. When the subject then performed a voluntary agonist contraction a facilitatory effect with an early onset and a duration of 20-25 ms was observed for all three muscles. When the subject performed a voluntary antagonist contraction an inhibition was seen for the soleus H reflex with an onset 1-3 ms later than the facilitation. This is interpreted as resulting from the excitation by the magnetic stimulus of corticospinal neurones voluntarily activated in relation to the given motor task. 4. The initial part of the facilitation was significantly smaller during co-contraction of both agonists and antagonists than during isolated agonist contraction. 5. Whereas the early part of the facilitation always occurred during plantarflexion when the H reflex was conditioned by magnetic stimulation, this was never the case when it was conditioned by electrical stimulation of the cortex with the stimulus regimes used in these experiments. 6. It is suggested that the early part of the facilitation observed during agonist contraction is caused by activation of cortico-motoneuronal cells projecting to the agonist motoneuronal pool and that the inhibition observed during antagonist contraction is caused by activation of corticospinal cells projecting both to the antagonist motoneuronal pool and Ia inhibitory interneurones to the agonist motoneuronal pool. The smaller size of the earliest part of the facilitation observed during co-contraction in relation to agonist contraction suggests a different cortical control of the two tasks.

H-reflexes are less depressed following muscle stretch in spastic spinal cord injured patients than in healthy subjects.

The size of the soleus H-reflex was measured after a slow (17 deg/s) passive stretch of ankle plantarflexors and compared to its control size without muscle stretch in ten neurologically healthy subjects and in six spastic spinal-cord-injured patients. Two seconds after the end of the stretch, the size of the H-reflex was reduced to about 30% of its pre-stretch size in the healthy subjects. The depression remained for 10-15 s. In the spastic, spinal-cord-injured patients, stretch caused significantly less reduction in the size of the H-reflex. The H-reflex also regained its pre-stretch size much faster than in healthy subjects. We suggest that the smaller depression of the H-reflex observed in spastic patients may be involved in the pathophysiology of spasticity.

Histologic examination of the rat central nervous system after intrathecal administration of human beta-endorphin.

The objective of this study was to evaluate histologically the toxicity of human beta-endorphin on the rat central nervous system after intrathecal administration. Animals received a single injection of 5 micrograms (n = 9) or 50 micrograms (n = 10) on each of four consecutive days, while others received 50 micrograms (n = 8) as a single dose. The control groups received either physiologic saline (n = 10) during each of four consecutive days or had sham operations (n = 4). Tests for nociception (tail-flick latency), motor function, and reflexes (righting reflex, eye-blink reflex, and inclined plane) were performed 5, 15, 30, 60, and 120 min after injection. Both dosages produced a dose-dependent impact on these parameters. In the 50-micrograms group, there were no significant differences in analgesia between the first and the fourth doses injected. The 50-micrograms dose produced catalepsy in some animals. All changes returned to baseline within 24 h. One animal in the 50-micrograms group developed hind limb paralysis after a single injection. Histologic sections from brain, brain stem, and spinal cord were prepared. No changes in histology were found except for that in the paretic animal, which had anoxic changes in the hippocampus and other cortical areas. Human beta-endorphin produced no neurotoxicity. The effect on nociception, reflexes, and motor function confirmed the results of previous studies.

Monoclonal antibodies against human angiotensinogen, their characterization and use in an angiotensinogen enzyme linked immunosorbent assay.

Monoclonal antibodies were produced against human angiotensinogen. An enzyme linked immunosorbent assay (ELISA) was developed using a high affinity monoclonal antibody as catching antibody and a polyclonal rabbit anti human angiotensinogen antibody as detecting antibody in a "sandwich" ELISA. Linear range of the ELISA was 15-450 pmol/l of human angiotensinogen. Intra- and inter- assay variation coefficients were in the range of 2% to 8%. A correlation coefficient, r = 0.97, (n = 20), with values obtained by radioimmunoassay. This correlation coefficient, obtained by using both normal and pregnant sera, confirmed that the ELISA fulfill the requirements for clinical useful assay. Characterization of the antibodies were performed with respect to affinity constant and epitopes.