Abstract
Article abstract Electromyography (EMG) could be useful in defining regional motor neuron vulnerability in ALS. We performed EMG in 36 sporadic ALS patients (9 with bulbar-onset and 27 with limb-onset symptoms). Active denervation was more frequent in limb than in corresponding paraspinal muscles, in the thoracic paraspinal, and in the bulbo-cervical muscles in patients with bulbar-onset symptoms. These results are consistent with a regional motor neuron vulnerability along with a nerve length-dependent liability.
The cause of ALS is unknown and different pathogenetic mechanisms have been postulated.1 Besides its diagnostic value,2 electromyography (EMG) could be useful in defining regional motor neuron (MN) vulnerability, because selective muscle involvement was often observed in ALS, possibly providing a clue to pathogenetic mechanisms of the disease.3 The purpose of this study was to evaluate the possible role of needle EMG examination of the cranial, paraspinal, and limb muscles in the detection of regional MN impairment in ALS.
Methods.
Patients.
We evaluated 36 consecutive patients with clinically defined sporadic ALS according to El Escorial diagnostic criteria. Nine patients (five men and four women), age 37 to 70 years (mean age, 54.9), showed bulbar-onset symptoms. Twenty-seven patients (20 men and 7 women), age 35 to 70 years (mean age, 55.7), showed limb-onset symptoms. All patients underwent electrodiagnostic study, neuroimaging analysis of the CNS (brain and spinal cord MRI), biochemical and hematologic screening (including anti-GM1 antibodies, immune electrophoresis, and paraneoplastic markers), and CSF examination. ALS-mimicking diseases were excluded.
Electrophysiologic studies.
Sensory (median, ulnar, and sural) and motor (median, ulnar, peroneal, and tibial) nerves were studied using standard methods. EMG was performed with a concentric needle electrode in muscles of the cranial (masseter, orbicularis oris, and tongue), paraspinal (cervical, thoracic, and lumbar), and limb (proximal and distal segments of four limbs) regions. Care was taken to ensure complete relaxation of patients during evaluation of spontaneous activity, particularly in the paraspinal muscles. For statistical purposes, we pooled the data obtained from the patients with bulbar- and limb-onset symptoms, comparing upper and lower limb with cervical and lumbar paraspinal muscles, on the assumption that the pathogenetic mechanism is the same for MNs with long and short axons.
Results.
Patients.
Clinical features of the patients are reported in table 1. The male:female ratio was 2.3:1. There was a greater incidence of bulbar symptoms in women (36.4%) than in men (20%) at the time of examination. Mean disease duration was longer in women than in men (18.1 versus 13.1 months), excluding two women who survived about 8 years from onset to our examination.
Characteristics of the ALS patients at examination
Electrophysiologic studies.
Results of sensory nerve conduction studies were normal. Motor nerve conduction studies were normal unless compound muscle action potential amplitudes were reduced, in which case conduction velocity was never below 70% of the mean for that nerve, and motor conduction blocks were not evident.4 The results of EMG studies are reported in table 2.
Regional abnormal electromyographic findings in 36 ALS patients (expressed as percent*)
Discussion.
The early clinical involvement of distal limb muscles in ALS patients has been emphasized, but the nerve length-dependent vulnerability has been questioned on the basis of a similar impairment of the thoracic paraspinal and limb muscles at EMG.3 In our patients, fibrillation was more evident in upper limb than in cervical paraspinal (100% versus 70%) and in the lower limb more than in lumbar paraspinal (97.2% versus 69.6%) muscles. Pooling our data from patients with bulbar- and limb-onset symptoms, active denervation was present in 99.08 ± 0.92% of limb muscles and 48.13 ± 10.81% of paraspinal muscles (p < 0.03, n = 8, Mann-Whitney U test), confirming the length-dependent vulnerability of MN axons.
Paraspinal active muscle denervation was more frequent in the thoracic (94.1%) than in cervical (70%) and lumbar segments (69.6%). To explain this pattern, we resorted to the concept of MN reserve, defined as the difference between the normal number of spinal MNs and threshold number at which clinical features of ALS are expressed. Because MN number is not homogeneous throughout the length of the spinal cord—being higher in cervical and lumbar enlargements and lower in the thoracic segments5,6—the physiologically smaller MN number in the thoracic segment represents the most logical explanation for the higher degree of active denervation in this region. Furthermore, because the blood supply to the midthoracic cord is relatively tenuous compared with the cervical and lumbar enlargements,7 one could also speculate on the possible role of a chronic hypoperfusion on the thoracic MN vulnerability observed in ALS. The concept of neuronal reserve was previously suggested to explain the age-dependent duration of the disease, because a greater neuronal reserve could be expected in younger patients.1 The presence of a MN reserve is more directly evident in our study, given the homogeneous age distribution in the ALS population. In fact, there is no neuropathologic evidence of MN loss up to age 60 years. Beyond that age the MN population diminishes.8 The concept of a neuron reserve has also been suggested in another neurodegenerative disease, AD, possibly related to brain size.9
When comparing ALS patients with bulbar- versus limb-onset symptoms, the active denervation in the cervical paraspinal muscles was significantly higher in the bulbar group (77.8% bulbar versus 25.9% limb onset), approaching the findings recorded in the tongue (77.8% bulbar versus 18.5% limb onset); no difference was detected between thoracic (88.9% bulbar versus 88.9% limb onset) and lumbar paraspinal muscles (44.4% versus 44.4%). Different manifestations of ALS (patients with bulbar- versus limb-onset symptoms) could represent different disorders, and multiple environmental agents have been suggested as a possible initial triggers of the disease.1 The similar EMG involvement of cervical and bulbar muscles in ALS patients with bulbar-onset symptoms in our series is suggestive of a common response of these two regions to the pathogenic insult. The similar involvement of lumbar paraspinal muscles between patients with bulbar- and limb-onset symptoms is more difficult to explain, but could be related to the more rapid progression of the bulbar form of ALS.
In the craniobulbar region, there was a grading of active denervation: fibrillation in the tongue (33.3%) was more abundant than in facial muscles (13.3%). No fibrillation was recorded in the masseter muscles. This grading was further evident in patients with bulbar- versus limb-onset symptoms (77.8% versus 18.5% in the tongue and 22.2% versus 7.4% in the facial muscles). These findings are consistent with an earlier involvement of the hypoglossal MNs as compared with other lower MN nuclei.10
Chronic denervation-reinnervation was also a common finding in cranial muscles of ALS patients (47.2% in the tongue, 33.3% in the facial, and 38.9% in the masseter muscles). However, the most common cranial abnormality was a reduced recruitment (tongue = 80.6%, facial = 70.0%, masseter 72.2%), suggesting that the frequent clinical involvement of these muscles is more often attributable to upper MN lesions.3
These findings represent a key feature to be addressed by future efforts to understand the intricate mechanisms of the disease.
Acknowledgments
Supported in part by the “Associazione Amici Centro Dino Ferrari” for Neuromuscular and Neurodegerative Diseases and by a grant from IRCCS Ospedale Maggiore, Milan.
Acknowledgment
The authors thank John P. Hemingway for critically reading the manuscript during its preparation.
- Received June 30, 1998.
- Accepted October 24, 1998.
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