Is fatigue in patients with multiple sclerosis related to autonomic dysfunction?

Time-dependent frequency decomposition of fluctuations in cardiovascular signals (heart rate [HR], blood pressure, and blood flow) provides noninvasive and quantitative evaluation of autonomic activity during transient and steady-state conditions. This method was applied during a change of position from supine to standing in patients with multiple sclerosis (MS) who experienced unexplained fatigue and in age-matched control subjects. No difference in response to standing, as reflected in the time domain parameters (mean HR, mean blood pressure, and mean blood flow), was observed between patients with MS and control subjects. Moreover, no difference was observed in very-low-frequency and low-frequency (related to sympathetic activity) content of HR, blood pressure, blood flow, or high-frequency content of HR (related to parasympathetic activity). The only spectral estimates that showed a significant difference between groups were the ratio of low-frequency to high-frequency content of HR and low-frequency content of HR normalized to total power. Both these parameters provide an estimate of the sympathovagal balance. A significant increase in these two estimates on standing was observed in control subjects only, indicating possible impairment of the sympathovagal balance response to standing in patients with MS who experienced fatigue. The authors observed a significant age dependence between close age subgroups, which occurred in the MS group only and was observed in some of the investigated spectral estimates that reflect vagal activity. Therefore, the authors assumed that age-related reduction in vagal activity occurred earlier in patients with MS who experienced fatigue. This reduction could also explain the lack of increase in the sympathovagal balance on standing. To validate this enhanced age dependence, further investigation should be performed in a larger group of subjects with a wider age range.

Autoantibodies to phospholipids and brain extract in patients with the Guillain-Barre syndrome: cross-reactive or pathogenic?

Guillain-Barre syndrome (GBS) is a transient neurological disorder characterized by an inflammatory demyelination of peripheral nerves. Although the pathogenesis of GBS has not been elucidated, there is increasing evidence pointing to an autoimmune etiology. We have studied the reactivity of GBS sera with various phospholipids which are known to be important constituents of myelin, and serve as autoantigens in other autoimmune conditions. Sixteen Guillain-Barre syndrome (GBS) sera were studied for the presence of autoantibodies to ssDNA, dsDNA, cardiolipin (CL), phosphatidyl-ethanolamine (PE), phosphatidyl-choline (PC), phosphatidyl-serine (PS), and brain extract. Six of the 16 GBS sera had autoantibodies to one or more of the antigens studied. Three of the sera contained autoantibodies to brain extract (p < 0.05), two of the sera had autoantibodies to dsDNA, ssDNA, CL and PE, and one serum had autoantibodies to PC, and PS. As expected a significant proportion of the lupus sera contained autoantibodies to ssDNA and dsDNA, while the frequency of autoantibodies to different phospholipids was significantly high in sera of patients with systemic lupus erythematosus (SLE) and cerebritis. Absorption of GBS sera with cardiolipin, phosphatidyl-choline, or brain extract inhibited the binding of the sera to cardiolipin. Our results demonstrate that some GBS patients produce autoantibodies to various phospholipid and nuclear antigens. However, these autoantibodies are probably produced as a result of the myelin damage rather than cause the demyelination.