Patients with Hodgkin's disease can develop paraneoplastic cerebellar ataxia because of the generation of autoantibodies against mGluR1 (mGluR1-Abs). Yet, the pathophysiological mechanisms underlying their motor coordination deficits remain to be elucidated. Here, we show that application of IgG purified from the patients' serum to cerebellar slices of mice acutely reduces the basal activity of Purkinje cells, whereas application to the flocculus of mice in vivo evokes acute disturbances in the performance of their compensatory eye movements. In addition, the mGluR1-Abs block induction of long-term depression in cultured mouse Purkinje cells, whereas the cerebellar motor learning behavior of the patients is affected in that they show impaired adaptation of their saccadic eye movements. Finally, postmortem analysis of the cerebellum of a paraneoplastic cerebellar ataxia patient showed that the number of Purkinje cells was significantly reduced by approximately two thirds compared with three controls. We conclude that autoantibodies against mGluR1 can cause cerebellar motor coordination deficits caused by a combination of rapid effects on both acute and plastic responses of Purkinje cells and chronic degenerative effects.
Annals of Neurology
325 - 336
Coesmans M, Sillevis Smitt P, Linden D, et al. Mechanisms underlying cerebellar motor deficits due to mGluR1-autoantibodies. Annals of Neurology. 2003;53(3):325-336. doi:10.1002/ana.10451
Coesmans, M., Sillevis Smitt, P., Linden, D., Shigemoto, R., Hirano, T., Yamakawa, Y., … De Zeeuw, C. (2003). Mechanisms underlying cerebellar motor deficits due to mGluR1-autoantibodies. Annals of Neurology, 53(3), 325–336. https://doi.org/10.1002/ana.10451
Coesmans, Michiel, Peter Sillevis Smitt, David Linden, Ryuichi Shigemoto, Tomoo Hirano, Yoshinori Yamakawa, Adriaan Van Alphen, et al. “Mechanisms Underlying Cerebellar Motor Deficits Due to MGluR1-Autoantibodies.” Annals of Neurology 53, no. 3 (2003): 325–36. https://doi.org/10.1002/ana.10451.
M. Coesmans et al., “Mechanisms underlying cerebellar motor deficits due to mGluR1-autoantibodies,” Annals of Neurology, vol. 53, no. 3, pp. 325–336, 2003.
Coesmans M, Sillevis Smitt P, Linden D, Shigemoto R, Hirano T, Yamakawa Y, Van Alphen A, Luo C, Van Der Geest J, Kros J, Gaillard C, Frens M, De Zeeuw C. 2003. Mechanisms underlying cerebellar motor deficits due to mGluR1-autoantibodies. Annals of Neurology. 53(3), 325–336.
Coesmans, Michiel, et al. “Mechanisms Underlying Cerebellar Motor Deficits Due to MGluR1-Autoantibodies.” Annals of Neurology, vol. 53, no. 3, Wiley-Blackwell, 2003, pp. 325–36, doi:10.1002/ana.10451.