Original contributionQuantitative Muscle Ultrasonography in Amyotrophic Lateral Sclerosis
Introduction
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease involving cell death of motor neurons in the cerebral cortex, brainstem and spinal cord. The disease course is characterized by progressive weakness and muscle atrophy, leading to disability and eventual death. The first symptoms are usually focal but they quickly generalize, affecting skeletal, bulbar and respiratory muscles. The mean time of survival is three years (Ringel et al. 1993).
The diagnosis of ALS is based on the presence of a combination of both upper and lower motor neuron signs. In 1994, more formal diagnostic criteria were developed (Brooks 1994, Brooks et al 2000). These so-called El Escorial criteria rely on a combination of upper and lower motor neuron signs in the same body region (bulbar, cervical, thoracal and lumbosacral). A higher degree of diagnostic certainty can be reached when more body regions are affected. In addition, the disease should be progressive and other disorders should be excluded. The El Escorial criteria also have a category “probable laboratory supported ALS,” in which neurophysiological testing is used to detect involvement of muscles in a body region that is not affected clinically. Currently, the only technique to increase diagnostic certainty in such a way is electromyography (EMG).
Despite the diagnostic criteria, it often remains difficult to reach a correct diagnosis, partly because of the lack of an objective biological marker (Belsh 1999, Belsh and Schiffman 1996). This is reflected in the average delay between symptom onset and final diagnosis, which may be as high as 16 mo, approximately one-third of the expected survival (Househam and Swash 2000, Iwasaki et al 2002, Zoccolella et al 2006a). Furthermore, the number of misdiagnoses is still unacceptably high, with a false-negative rate of 27 to 43% (Belsh and Schiffman 1990, Belsh and Schiffman 1996) and a false-positive diagnosis in about 8% (Davenport et al 1996, Traynor et al 2000). Therefore, new techniques to detect subclinically affected regions are welcome.
Muscle ultrasonography is an easily accessible, inexpensive and painless method to detect changes in muscle thickness and echo intensity (Heckmatt et al. 1982). Quantification of muscle thickness and echo intensity provides a sensitive and specific objective method to discriminate between neuromuscular and non-neuromuscular diseases (Maurits et al 2003, Pillen et al 2003, Pillen et al 2006b, Pillen et al 2007). Furthermore, quantitative muscle ultrasonography can be used complementary to regular physical and diagnostic tests in the detection of subclinical muscle pathology (Pillen et al. 2006a). In contrast to other imaging modalities like computed tomography or magnetic resonance imaging (MRI), ultrasonography can register movements and is therefore suitable to detect muscle movements such as fasciculations. Indeed, ultrasound seems to be more sensitive in detecting fasciculations when compared with needle EMG (Reimers et al. 1996).
To determine its possible diagnostic utility in ALS, we assessed whether quantitative muscle ultrasonography can detect structural muscle changes in an early phase of the disease. We performed bilateral ultrasound measurements of five muscle groups in 48 patients with ALS in the diagnostic stage.
Section snippets
Patients
We included 75 patients suspected of having ALS who were referred to our neuromuscular clinic between August 2003 and December 2005. All patients underwent a regular diagnostic workup consisting of at least a standard EMG examination and laboratory testing. When necessary, we excluded other diseases with additional diagnostic tests such as MRI or muscle biopsy. To assess the value of muscle ultrasound in detecting early disease-related changes, all ultrasound measurements were performed during
Results
Of the 75 patients included, 48 patients received a final diagnosis of ALS and were analyzed further (Table 1). All patients fulfilled the El Escorial criteria for (laboratory-supported) probable or definite ALS. The mean age was 64.1 ± 12.1 y. The average time from onset of symptoms to final diagnosis was 14 ± 12 mo.
Discussion
We show that muscle ultrasonography can detect muscle changes in the early stages of ALS. Quantitative analysis revealed an increase in echo intensity and a decrease in the thickness of several muscles. The forearm flexors were most affected, with mean z-scores of more than 2. These results are striking given the fact that ALS is a patchy disease (Ringel et al 1993, Zoccolella et al 2006b); therefore, the average results per muscle group also included a number of normal muscles.
Echo intensity
Acknowledgments
We thank Wilma van Kruijsbergen-Raijmann and Mirjam Heykers, clinical neurophysiology technicians, for performing the ultrasound measurements.
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