Testing upper motor neuron function in amyotrophic lateral sclerosis: the most difficult task of neurophysiology

Clinical signs of upper motor neuron involvement are an essential observation to support the diagnosis of amyotrophic lateral sclerosis. However, clinical signs of upper motor neuron can be difficult to elicit in patients with motor neuron disease. One postulated reason for this problem is the presence of marked limb weakness and amyotrophy in motor neuron disease. This has been observed in patients with genetic mutations and clear-cut pathological evidence of upper and lower motor neuron degeneration. Less commonly , it has been recognized that the pattern of upper motor neuron lesion in amyotrophic lateral sclerosis is rather different from other conditions, in which there is damage to other descending motor fibres from extra-Rolandic motor cortical areas (Swash, 2012). In particular, the impact of the concomitant and spinal motor neuron loss and of spinal interneuron degeneration on the expression of the usual signs of upper motor neuron lesion are not well known (Swash, 2012). Probably, other clinical signs suggesting upper motor neuron dysfunction, such as mirror movements or the presence of apraxia, should be explored to support corticomo-tor involvement in motor neuron disease. Over the years, different techniques have been developed that help the neurologist to identify, measure and understand the upper motor neuron lesion in amyotrophic lateral sclerosis. Many transcranial magnetic stimulation methods have been used in this context to investigate integrity of the motor cortex and its descending pathways. A number of results reflecting delayed central conduction time and reduced motor-evoked potential amplitude indicate corticospinal tract damage (de Carvalho et al., 2003). Nonetheless, in amyotrophic lateral sclerosis, there is strong evidence for increased cortical excitability in early phases of the disease progression, suggesting either an initial phase in which the lower motor neuron demise is compensated or representing the initial pathogenic disturbance leading to lower motor neuron dys-function (Vucic and Kiernan, 2006). Nevertheless, the combination of positive (increased cortical excitability) and negative (delayed central conduction time and reduced motor response) findings make transcranial magnetic stimulation a difficult technique with which to document serial upper motor neuron degeneration. Many groups have devoted much time and effort seeking the most sensitive and simple neuroimaging technique for detection of the upper motor neuron lesion in motor neuron disease. Voxel-based morphometry has been inconsistent in measuring the motor area; surface-based morphometry reveals cortical thinning in the precentral gyrus, but with a poor correlation with clinical findings; fractional anisotropy as evaluated by diffusion tensor …