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These results suggest a progressive deterioration in breathing pattern and in respiratory muscle strength with progression of disease.

Amyotrophic lateral sclerosis (ALS) is considered a multifactorial, multisystem disease in which inflammation and the immune system play important roles in development and progression. The pleiotropic cytokine TNFα is one of the major players governing the inflammation in the central nervous system and peripheral districts such as the neuromuscular and immune system. Changes in TNFα levels are reported in blood, cerebrospinal fluid, and nerve tissues of ALS patients and animal models. However, whether they play a detrimental or protective role on the disease progression is still not clear. Our group and others have recently reported opposite involvements of TNFR1 and TNFR2 in motor neuron death. TNFR2 mediates TNFα toxic effects on these neurons presumably through the activation of MAP kinase-related pathways. On the other hand, TNFR2 regulates the function and proliferation of regulatory T cells (Treg) whose expression is inversely correlated with the disease progression rate in ALS patients. In addition, TNFα is considered a procachectic factor with a direct catabolic effect on skeletal muscles, causing wasting. We review and discuss the role of TNFα in ALS in the light of its multisystem nature.

SUMMARY Forty five patients with amyotrophic lateral sclerosis were investigated, by means of somatosensory evoked potentials, in order to detect the presence of subclinical sensory changes. Cervical SEPs from the median nerve and cortical SEPs from the median and tibial nerve were recorded, showing a delay of N1B and subsequent components; the latency of the first constant cortical potential was also increased in many patients. Only the SEPs from the tibial nerve showed a decrease of amplitude. These results suggest a pathological slowing of conduction along the central sensory pathways in amyotrophic lateral sclerosis.Amyotrophic lateral sclerosis is generally considered to be a system disease because of selective involvement of upper and lower motor neurons. Sensory disturbances characteristically are absent in typical amyotrophic lateral sclerosis, although cramps and paraesthesias may occur; nevertheless a certain number of detailed pathological studies have claimed to show the presence of changes in sensory nerve myelinated fibres,' 2 in spinocerebellar pathways,3 Clarke's nucleus,4 posterior columns5 ' and thalamus.8 These changes have been reported more frequently in familial than in sporadic amyotrophic lateral sclerosis.9 A patient with a chronic pain syndrome associated with amyotrophic lateral sclerosis has recently been described.'0 In a series of investigations about the possible involvement of subsystems other than motor neurons in sporadic amyotrophic lateral sclerosis, we have examined somatosensory evoked potentials (SEPs) in 45 patients in an attempt to detect the presence of subclinical alterations. The clinical picture of these patients were divided into: typical amyotrophic lateral sclerosis without bulbar signs, typical amyotrophic lateral sclerosis with bulbar signs, bulbar and pseudobulbar amyotrophic lateral sclerosis and amyotrophic lateral sclerosis with predominant lower motor neuron involvement (without pyramidal signs). The patients were further divided into three groups, according to the duration of the disease: I = up to 12 months, II = from 13 to 24 months, III = more than 24 months. The muscular impairment was classified as light, moderate or heavy, according to the clinical evaluation of the functional capacity. The tallness of the patients and the presence or the absence of cervical spondylosis on plain radiographs was also considered. These clinical features are shown in table 1.The control cases, matched for age, sex and tallness were sampled from normal subjects of the laboratory. The patients, relaxed in an arm-chair, in a silent room, were requested to close their eyes. The stimulating electrodes were placed on the skin overlying the median nerve at the wrist and the tibial posterior nerve at the ankle; both sides were sometimes examined. The stimulus had a duration of 0-1 ms, a frequency of 3 Hz and an intensity of 20% above that required to induce a modest muscular twitch. The recording silver-silver chloride electrodes were placed at C3 or at C4-Fpz (cortical SEPs aft...