Does the motor cortex influence denervation in ALS? EMG studies of muscles with both contralateral and bilateral corticospinal innervation Mamede de Carvalho a,⇑ , Susana Pinto b , Michael Swash a,c a Department of Neurosciences, St. Maria Hospital, Lisbon, Portugal b Institute of Molecular Medicine, Faculty of Medicine, Lisbon, Portugal c Department of Neurology, Royal London Hospital, Queen Mary School of Medicine, University of London, London, UK article info Article history: Available online xxxx Keywords: Amyotrophic lateral sclerosis Trapezius muscle Sternomastoid muscle EMG Fasciculation potentials Transcranial magnetic stimulation abstract Objectives: To evaluate the pattern of degeneration of lower motor neuron progression in ALS in relation to the contralateral and ipsilateral corticospinal innervation of the tested muscles. Methods: EMG evaluation of the sternomastoid and trapezius muscles on one or both sides, and transcra- nial magnetic stimulation to record motor evoked responses from these muscles after ipsilateral and con- tralateral cortical stimulation. The sternomastoid muscle receives corticospinal input from both hemispheres, but the trapezius only a contralateral corticospinal innervation; however the power motor innervation of both these muscles is derived from the same spinal nucleus, and the same motor nerve. Seventy-five patients with ALS were studied at the time of diagnosis, and 54 control subjects, consisting of normal subjects and disease control subjects. MUP analysis and spontaneous activity were assessed. Results: We confirmed that the sternomastoid receives both contralateral and ipsilateral corticospinal innervation, and the trapezius usually only contralateral innervation. The MUP analysis revealed sym- metric changes in sternomastoid and trapezius muscles, and both muscles were equally affected. Conclusions: Our findings are in accord with the concept that LMN degeneration in ALS is related to local factors in the spinal cord. Significance: Our findings suggest that local factors in the spinal grey matter are important in causing LMN degeneration in ALS, but they do not rule out a corticomotoneuronal contribution. Ó 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. 1. Introduction There is uncertainty regarding the primary process of degener- ation of the motor system in amyotrophic lateral sclerosis (ALS). In particular, there is controversy as to whether the disease begins independently in upper motor neurons (UMN) and lower motor neurons (LMN) (Ravits and LaSpada, 2009) or whether it is initiated primarily in the motor cortex, involving the LMNs as a later phe- nomenon – a process termed the ‘‘dying forward hypothesis” (Eisen et al., 1992; Eisen, 2009; Vucic and Kiernan, 2006). Vucic et al. (2008) noted that in familial ALS cortical hyperexcitability seemed to precede the clinical onset of the disease, but this study did not include needle EMG examination. The long-held view that ALS becomes clinically evident as a result of dying-back change at the motor end plate associated with axonal degeneration associ- ated with axonal transport abnormalities and microtubular dys- function with proximal accumulation of neurofilaments (Breuer et al., 1987; Leigh et al., 1989; Cleveland and Rothstein, 2001) is supported by histological studies in transgenic SOD1 G93A mice (Kennel et al., 1996; Narai et al., 2009) and in human ALS (Fischer et al., 2004). ALS presents only after loss of sufficient functioning motor units to cause weakness (Wohlfart, 1957; Aggarwal and Nicholson, 2002). However, none of these studies have evaluated patients with sporadic ALS at disease onset, a limitation inevitably imposed by patient presentation some months after the onset of the first symptom. In neuropathological studies Pamphlett et al. (1995) found that UMN and LMN degeneration could occur inde- pendently, an observation confirmed by Ravits and LaSpada (2009). However, a possible relationship between UMN and LMN degeneration in ALS cannot be discarded since Ince et al. (2003) noted UMN degeneration in about half of their patients who had presented with progressive muscular atrophy, a disorder that is 1388-2457/$36.00 Ó 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2010.07.019 Abbreviations: ALS, amyotrophic lateral sclerosis; ALS-FRS, amyotrophic lateral sclerosis-functional rating score; AMAN, acute motor axonal neuropathy; EMG, electromyography; Fibs-sw, fibrillations/positive sharp waves; FPs, fasciculation potentials; LMN, lower motor neuron; MEP, motor evoked potential; MUP, motor unit potential; TMS, transcranial magnetic stimulation; UMN, upper motor neuron. ⇑ Corresponding author. Address: Department of Neurology, St. Maria Hospital, Lisbon 1649-028, Portugal. Tel.: +351 21 7805219; fax: +351 21 7520801. E-mail address: mamedemg@mail.telepac.pt (M. de Carvalho). Clinical Neurophysiology xxx (2010) xxx–xxx Contents lists available at ScienceDirect Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph Please cite this article in press as: de Carvalho M et al. Does the motor cortex influence denervation in ALS? EMG studies of muscles with both contralateral and bilateral corticospinal innervation. Clin Neurophysiol (2010), doi:10.1016/j.clinph.2010.07.019