Electrodiagnostic criteria for diagnosis of ALS

Abstract

A consensus meeting was held to determine the best use and interpretation of electrophysiological data in the diagnosis of ALS. The utility of needle EMG and nerve conduction studies was affirmed. It is recommended that electrophysiological evidence for chronic neurogenic change should be taken as equivalent to clinical information in the recognition of involvement of individual muscles in a limb. In addition, in the context of a suspected clinical diagnosis of ALS, fasciculation potentials should be taken as equivalent to fibrillation potentials and positive sharp waves in recognising denervation. The importance of searching for instability in fasciculation potentials and in motor unit potentials in ALS is stressed. These changes in the interpretation of electrophysiological data render obsolete the category Probable Laboratory-Supported ALS in the modified El Escorial diagnostic criteria for ALS. Methods for detection of upper motor neuron abnormality appear sensitive but require further study, particularly regarding their value when clinical signs of upper motor neuron lesion are uncertain.

Introduction

In the absence of an established biological marker ALS is primarily a clinical diagnosis (Li et al., 1991). In patients with generally increased reflexes, weak and wasted muscles in several body regions, a progressive history, often after a focal onset, the diagnosis is readily established after appropriate imaging and other tests designed to exclude other possible diagnoses (Brooks, 1994, Brooks et al., 2000). An experienced clinician may be virtually certain of the diagnosis in a patient with bilateral limb wasting, bilateral fasciculation in the tongue, or with wasting and hyperreflexia limited to a single limb, but none of these syndromes meet established criteria for a definite diagnosis of ALS (Beghi et al., 2002). Clinical neurophysiological examination is especially important in this context (de Carvalho et al., 2005), because it can extend the clinical findings by revealing lower motor neuron involvement in muscles in body regions otherwise regarded as unaffected. The electrophysiological features used in the diagnosis of ALS are based on the set of criteria proposed by Lambert (Lambert and Mulder, 1957, Lambert, 1969). An algorithm for utilizing electrophysiological data in diagnosis was incorporated in the revised El Escorial criteria for the diagnosis of ALS as Laboratory-Supported ALS (Brooks et al., 2000). However, as currently understood, EMG and clinical abnormalities cannot be combined in a single limb. Rather, the limb must be determined to be abnormal by one technique or the other.

Another factor that has limited the utility of clinical neurophysiology in the diagnosis of ALS is that current criteria require that muscles determined to be affected must show both ongoing denervation, defined by fibrillation potentials (fibs) or positive sharp waves (sw), and chronic partial reinnervation, implying reinnervation, defined by enlarged, frequently unstable motor units of increased duration, with a reduced interference pattern (Table 1). While the presence of active denervation and chronic denervation/reinnervation in the same muscle, although not specific for ALS, is diagnostically useful, many muscles do not show fibs-sw, so that the clinical neurophysiologist is left with insufficient findings to make the diagnosis of ALS (Behnia and Kelly, 1991, de Carvalho et al., 1999). In practice this is a significant problem; Traynor et al. (2000) found that, on current criteria, 22% of patients with ALS may die without reaching a level of diagnosis more certain than possible ALS.

It has become increasingly important to diagnose ALS early in the natural history of the disease, in order to arrange best management (Swash, 1998). It is intuitively likely that disease-modifying agents will be most successful when administered early, when a large population of motor neurons remains viable. Although specific disease modifying therapy is presently of limited efficacy, symptomatic treatments provide considerable benefit. In addition the pace of translational research in ALS promises an increasing number of experimental therapies, with opportunities to enter clinical trials.