Bert U. Kleine

Pulsed high-dose dexamethasone versus standard prednisolone treatment for chronic inflammatory demyelinating polyradiculoneuropathy (PREDICT study): a double-blind, randomised, controlled trial

BACKGROUND Pulsed high-dose dexamethasone induced long-lasting remission in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in a pilot study. The PREDICT study aimed to compare remission rates in patients with CIDP treated with high-dose dexamethasone with rates in patients treated with standard oral prednisolone. METHODS In eight neuromuscular centres in the Netherlands and one in the UK, patients aged 18 years or older who had newly diagnosed definite or probable CIDP were randomly assigned to a treatment regimen of either pulsed high-dose dexamethasone or standard oral prednisolone. Randomisation was done with a random number generator. The primary outcome measure was remission at 12 months, defined as improvement of at least three points on the Rivermead mobility index and improvement of at least one point on the inflammatory neuropathy cause and treatment disability scale. Analysis was by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN07779236. FINDINGS Between December, 2003, and December, 2008, 40 patients were treated: 24 received dexamethasone and 16 received prednisolone. At 12 months, 16 patients were in remission: ten in the dexamethasone group and six in the prednisolone group (odds ratio [OR] 1.2, 95% CI 0.3-4.4). Most adverse events were minor and did not differ substantially between treatment groups; however, sleeplessness and Cushings face occurred more often in the prednisolone group. INTERPRETATION Pulsed high-dose dexamethasone treatment did not induce remission more often than prednisolone treatment. A substantial proportion of patients were in remission at 12 months in both treatment groups. High-dose dexamethasone could be considered as induction therapy in CIDP, but comparison with intravenous immunoglobulin treatment is needed. FUNDING The Prinses Beatrix Fonds (MAR01-0213) and the Department of Neurology, Academic Medical Center.

Sensitivity and specificity of the 'Awaji' electrodiagnostic criteria for amyotrophic lateral sclerosis: retrospective comparison of the Awaji and revised El Escorial criteria for ALS.

Abstract The Awaji Commission recently proposed a modification of the electrodiagnostic criteria for ALS. We assessed whether the Awaji recommendations improve the sensitivity of the early diagnosis of ALS. In a retrospective study we reviewed clinical and neurophysiological data for 213 patients who visited our motor neuron disease outpatient clinic between October 2006 and December 2008. Using the El Escorial criteria, 51 patients were diagnosed with definite or probable ALS, 14 with probable laboratory-supported ALS, and 28 with possible ALS. An alternative diagnosis was present in 120 patients. Applying the Awaji recommendations, 66 patients were diagnosed with either definite or probable ALS, and 27 with possible ALS. Of the 14 patients diagnosed with probable laboratory-supported ALS, eight switched to probable ALS and six to possible ALS using the Awaji recommendations; none of the patients with an ALS mimic was diagnosed with ALS according to the Awaji recommendations. In conclusion, the new criteria for ALS do not result in a loss of specificity and can potentially improve the sensitivity by 16%. However, this diagnostic improvement appears eliminated if patients with probable laboratory-supported ALS – due to UMN signs in one region – should be categorized as possible ALS.

Muscle ultrasonography: a diagnostic tool for amyotrophic lateral sclerosis.

OBJECTIVE In a prospective study we tested whether muscle ultrasonography can differentiate between amyotrophic lateral sclerosis (ALS) and mimics. Furthermore, we assessed the ability of ultrasonography to identify subclinical lower motor neuron involvement. METHODS In 59 patients, suspected for adult onset motor neuron disease, ultrasound scans were made of 12 different muscle groups. Echo intensity was determined and each muscle was screened for fasciculations. Ultrasonography was considered diagnostic for ALS when echo intensity was 1.5 SD above normal in at least two muscles and fasciculations were present in at least four muscles. RESULTS Ultrasonography differentiated between ALS and mimics with 96% sensitivity and 84% specificity. In the 27 ALS patients, ultrasonography detected 15 regions with lower motor neuron involvement that were negative using either clinical examination or needle EMG. CONCLUSIONS Muscle ultrasound can differentiate between amyotrophic lateral sclerosis and mimics with high sensitivity and specificity, and is a sensitive tool to screen for regional lower motor neuron involvement. SIGNIFICANCE Muscle ultrasonography is a promising tool in the diagnostic work up of ALS.

The alpha-motoneuron pool as transmitter of rhythmicities in cortical motor drive

OBJECTIVE Investigate the effectiveness and frequency dependence of central drive transmission via the alpha-motoneuron pool to the muscle. METHODS We describe a model for the simulation of alpha-motoneuron firing and the EMG signal as response to central drive input. The transfer in the frequency domain is investigated. Coherence between stochastical central input and EMG is also evaluated. RESULTS The transmission of central rhythmicities to the EMG signal relates to the spectral content of the latter. Coherence between central input to the alpha-motoneuron pool and the EMG signal is significant whereby the coupling strength hardly depends on the frequency in a range from 1 to 100 Hz. Common central input to pairs of alpha-motoneurons strongly increases the coherence levels. The often-used rectification of the EMG signal introduces a clear frequency dependence. CONCLUSIONS Oscillatory phenomena are strongly transmitted via the alpha-motoneuron pool. The motoneuron firing frequencies do play a role in the transmission gain, but do not influence the coherence levels. Rectification of the EMG signal enhances the transmission gain, but lowers coherence and introduces a strong frequency dependency. We think that it should be avoided. SIGNIFICANCE Our findings show that rhythmicities are translated into alpha-motoneuron activity without strong non-linearities.

Fasciculation potentials in high-density surface EMG.

Summary: Fasciculation potentials (FPs) are observed in healthy individuals, but also in patients with neurogenic disorders. The exact site of origin and the clinical relevance in distinguishing, for example, amyotrophic lateral sclerosis (ALS) from other neurogenic diseases based on specific characteristics of the FPs is still a matter of debate and needs further exploration. This report describes the use of high-density surface EMG (HD-sEMG), with multiple electrodes in a compact grid to noninvasively record FPs. The technique provides both temporal and spatial information of fasciculations. Examples of the FPs of a patient diagnosed with definite ALS are presented. FPs are shown in different electrode montages and the unique spatial characteristics of different FPs are presented. During 30-second recordings, 137 FPs were detected that via a decomposition algorithm could be assigned to 11 different underlying sources. It is concluded that HD-sEMG, both because of its noninvasive character and the unique spatiotemporal information, is very suitable to examine fasciculations. It allows long stable recording times and provides quantitative information. This electrophysiologic tool is expected to expand the existing knowledge of FP properties.

Prevalence and distribution of fasciculations in healthy adults: Effect of age, caffeine consumption and exercise

Our objective was to determine the prevalence and distribution of fasciculations in healthy adults and to assess the effect of age, caffeine and exercise. Fasciculations were studied with ultrasonography in 58 healthy adults in various age categories. Questionnaires were used to determine effect of caffeine and regular exercise on the presence of fasciculations. Finally, we tested the effect of strenuous exercise on fasciculations in 10 healthy adults. Twenty-five subjects (43%) showed fasciculations on ultrasonography, mostly in the abductor hallucis longus muscle. Fasciculations were only sporadically encountered in muscle groups above the knee. Subjects with fasciculations were significantly older than those without. Caffeine and regular physical exercise did not influence the prevalence of fasciculations. However, strenuous physical exercise caused a temporary increase in fasciculations, but only in lower leg muscles. Fasciculations above the knee should raise suspicion and may warrant further investigation.

Fasciculations and their F-response revisited: High-density surface EMG in ALS and benign fasciculations

OBJECTIVE To compare the prevalence of fasciculation potentials (FPs) with F-responses between patients with amyotrophic lateral sclerosis (ALS) and patients with benign fasciculations. METHODS In seven patients with ALS and seven patients with benign fasciculations, high-density surface EMG was recorded for 15 min from the gastrocnemius muscle. Template matching was used to search for pairs of FPs with a repetition within 10-110 ms. RESULTS Interspike interval (ISI) histograms were constructed from 282 pairs of benign fasciculations and from 337 FP pairs in ALS. Peaks attributable to F-waves were found at latencies of 32 ms (benign) and 35 ms (ALS). Five patients with benign fasciculations and four patients with ALS had FPs with F-waves. CONCLUSIONS F-waves of FPs occur in both conditions - therefore they are not diagnostically helpful. SIGNIFICANCE F-waves confirm the distal origin of FPs for an individual axon. The occurrence of these FPs in a benign condition suggests that the generation of ectopic discharges in the distal axons is not specific to progressive neurodegeneration.

Measuring the cortical silent period can increase diagnostic confidence for amyotrophic lateral sclerosis

We evaluated a modified measurement of the cortical silent period (CSP) as a simple procedure to add further confidence in the diagnostic work‐up for ALS. Thirty‐seven consecutive patients with a suspicion of having ALS were included together with 25 healthy volunteers, and followed until a final diagnosis (ALS versus ‘ALS mimic’) was reached. Using a CSP cut‐off value of 200 ms for males and 150 ms for females, the following test characteristics were obtained for ALS versus ALS mimics together with controls: sensitivity for excluding ALS 0.83, specificity 0.56 (males) and sensitivity 0.81, specificity 0.82 (females). A CSP longer than the mentioned cut‐off values should alarm the clinician for the presence of a disorder other than ALS.

Ultrasonographic Detection of Fasciculations Markedly Increases Diagnostic Sensitivity of ALSAuthor Response

# {#article-title-2} Using muscle ultrasound, Misawa et al.1 found fasciculations in the tongue in 60% of 81 patients with amyotrophic lateral sclerosis (ALS), whereas with EMG they detected no fasciculation potentials. This intriguing finding has been reported by Sonoo et al.,2 who detected fasciculation potentials in the tongue in only 1 out of 104 patients with ALS. We had the same experience. The presumed explanation for the absence of tongue fasciculations is that complete relaxation of the tongue is rarely achieved, making it difficult to determine whether fasciculations are present. However, we suggest that “fasciculations in the tongue” are in fact fibrillations. First, what might appear as tongue …

Bridging function and structure of the neuromuscular system.

Neuromuscular diseases (NMDs) are usually diagnosed based on clinical evaluation, substantiated by means of electromyography and genetic, biochemical and/or muscle biopsy investigations. For a long time, clinical neurophysiological assessment of neuromuscular disorders has mainly been associated with functional tests of peripheral nerve and muscle. Of the above investigations, clinical EMG techniques deliver the most basic information on the functional status of the neuromuscular system. Although EMG reflects physiological characteristics, its diagnostic specificity is largely based on a direct interpretation into pathological anatomy. Increasing evidence is found for direct muscle imaging (CT, MRI, ultrasound) to be also helpful in supporting the diagnosis directly or guiding muscle biopsy (Clague et al., 1995). For the clinician it is not always clear how results from different techniques should be co-interpreted in the diagnostic work-up of neuromuscular symptoms. How do different abnormal findings arise, but also how are they related? Three aspects of clinical EMG in relation to imaging techniques come into view, taken into account the results of ‘electric impedance myography’ (EIM, Rutkove et al., 2006).