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Combined pre- and postsynaptic action of IgG antibodies in Miller Fisher syndrome

B. Buchwald, MD*;, J. Bufler, MD*;, M. Carpo, MD, PhD;, F. Heidenreich, MD;, R. Pitz, PhD;, J. Dudel, MD;, E. Nobile–Orazio, MD, PhD; and K.V. Toyka, MD

From the Neurologische Klinik der Bayerischen Julius–Maximilians–Universität Würzburg, Germany; Neurologische Klinik der Technischen Universität München (Drs. Bufler and Pitz), Germany; "Giorgio Spagnol" Laboratory of Clinical Neuroimmunology (Drs. Carpo and Nobile–Orazio), Institute of Clinical Neurology, Centro Dino Ferrari, University of Milan, Italy; Neurologische Klinik der Medizinischen Hochschule Hannover (Dr. Heidenreich), Germany; and Physiologisches Institut der Technischen Universität München (Dr. Dudel), Germany.



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Figure 1. Reduction in quantal content by Miller Fisher syndrome (MFS) serum or purified immunoglobulin G (IgG). Ordinate: quantal content relative to the control normalized at 1 for each experiment; values are given as mean ± SD. Results of 11 different patients with MFS (Patients 1 to 11) and of the pooled IgG preparation from healthy donors (control) are shown.

 


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Figure 2. Amplitude distribution of quantal excitatory postsynaptic currents (qEPSC) before, during, and after application of the Miller Fisher syndrome (MFS) immunoglobulin G (IgG). Ordinates: numbers of observations per bin. Abscissae: amplitude of qEPSC at a constant depolarizing current (-0.4µA), bin width 200 pA. (A) Control solution; quantal content m = 0.7. (B) MFS-IgG of Patient 11; quantal content m = 0.2. (C) Wash-out (control solution); quantal content m = 0.5. All data were recorded from the same nerve terminal. The number of records evaluated for each distribution were 1,500 to 3,000, depending on quantal content. The solid line marks the gaussian distribution of single quanta.

 


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Figure 3. Concentration-dependent reduction in peak current amplitude by Miller Fisher syndrome (MFS) immunoglobulin G (IgG) from Patient 5. Amplitudes of single pulses of 1.0 mM acetylcholine to an outside-out patch were plotted versus time. Pulses were applied with a frequency of 0.25 Hz. The horizontal bars indicate duration of IgG application at the respective IgG concentration. Note that the reduction in peak current amplitude comes on faster and is more pronounced with high antibody concentrations.

 


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Figure 4. Time course of the depression of evoked quantal release by the Miller Fisher syndrome (MFS) immunoglobulin G (IgG) (Patient 1) obtained during the active stage of the disease and of the same patient after recovery from disease. Quantal content (logarithmic ordinate scale) versus time in minutes (abscissa). Each point of the curve was determined from the results of at least 256 stimuli; quantal content m was calculated using the Poisson formula. The arrows denote the instant of solution change in the electrode. Note that recovery serum did not block transmission.

 





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