Thomas Wehrum1, Lena-Alexandra Beume2, Oliver Stich2, Irina Mader2, Mathias Mäurer2, Adam Czaplinski2, Cornelius Weiller2, Sebastian Rauer2. 1. From the Departments of Neurology and Neuroscience (T.W., L.-A.B., O.S., C.W., S.R.) and Neuroradiology (I.M.), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg; Department of Neurology (M.M.), Stiftung Juliusspital Würzburg, Germany; and Neurozentrum Bellevue (A.C.), Zürich, Switzerland. thomas.wehrum@uniklinik-freiburg.de. 2. From the Departments of Neurology and Neuroscience (T.W., L.-A.B., O.S., C.W., S.R.) and Neuroradiology (I.M.), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg; Department of Neurology (M.M.), Stiftung Juliusspital Würzburg, Germany; and Neurozentrum Bellevue (A.C.), Zürich, Switzerland.
Abstract
OBJECTIVE: To report 3 patients with multiple sclerosis showing severe activation of disease during immunotherapy with alemtuzumab. METHODS: Retrospective case series. RESULTS: Patient 1, a 21-year-old woman, developed severe cognitive impairment, sight deterioration, severe gait ataxia, urinary retention, and extensive progression of cerebral lesion load, including new lesions that exhibited gadolinium ring enhancement and dominance of CD19/20-positive B lymphocytes, 6 months after induction of alemtuzumab. Patient 2, a 28-year-old man, developed left-sided hemihypesthesia and ∼60 new cerebral and spinal lesions including lesions with gadolinium ring enhancement 6 months after induction of alemtuzumab. Patient 3, a 37-year-old woman, developed ataxia and numbness of the left thigh, 16 new gadolinium-positive supratentorial lesions, and partly ring-enhancing and dominance of CD19/20-positive B lymphocytes 6 months after induction of alemtuzumab. CONCLUSION: This is a case series reporting severe activation of disease during immunotherapy with alemtuzumab. All patients showed onset of symptoms 6 months after induction of alemtuzumab, strikingly similar MRI lesion morphology, and unexpected high total B cell count, which may suggest a B-cell-mediated activation of disease. Whether this is due to different rates of B- and T cell repopulation has to be the subject of further research. Moreover, further effects on the interactions between the adaptive and innate immunity as well as between B and T cell lineages might explain the observed disease activation.
OBJECTIVE: To report 3 patients with multiple sclerosis showing severe activation of disease during immunotherapy with alemtuzumab. METHODS: Retrospective case series. RESULTS:Patient 1, a 21-year-old woman, developed severe cognitive impairment, sight deterioration, severe gait ataxia, urinary retention, and extensive progression of cerebral lesion load, including new lesions that exhibited gadolinium ring enhancement and dominance of CD19/20-positive B lymphocytes, 6 months after induction of alemtuzumab. Patient 2, a 28-year-old man, developed left-sided hemihypesthesia and ∼60 new cerebral and spinal lesions including lesions with gadolinium ring enhancement 6 months after induction of alemtuzumab. Patient 3, a 37-year-old woman, developed ataxia and numbness of the left thigh, 16 new gadolinium-positive supratentorial lesions, and partly ring-enhancing and dominance of CD19/20-positive B lymphocytes 6 months after induction of alemtuzumab. CONCLUSION: This is a case series reporting severe activation of disease during immunotherapy with alemtuzumab. All patients showed onset of symptoms 6 months after induction of alemtuzumab, strikingly similar MRI lesion morphology, and unexpected high total B cell count, which may suggest a B-cell-mediated activation of disease. Whether this is due to different rates of B- and T cell repopulation has to be the subject of further research. Moreover, further effects on the interactions between the adaptive and innate immunity as well as between B and T cell lineages might explain the observed disease activation.
Authors: Jessica Frau; Francesco Saccà; Alessio Signori; Damiano Baroncini; Giuseppe Fenu; Pietro Annovazzi; Marco Capobianco; Elisabetta Signoriello; Alice Laroni; Sara La Gioia; Arianna Sartori; Giorgia Teresa Maniscalco; Simona Bonavita; Marinella Clerico; Cinzia Valeria Russo; Antonio Gallo; Caterina Lapucci; Antonio Carotenuto; Maria Pia Sormani; Eleonora Cocco Journal: J Neurol Date: 2019-06-17 Impact factor: 4.849