Fatal CNS Hemorrhage in a Patient with Relapsing-Remitting MS Who Received Alemtuzumab

Background: Alemtuzumab is approved for treatment of relapsing forms of MS. In CARE-MS II (NCT00548405), alemtuzumab patients showed greater improvement on clinical/MRI outcomes vs SC IFNB-1a over 2 years, with durable efficacy and no new safety signals over 6 years in an extension (NCT00930553). 

Objectives: To report a case of fatal CNS hemorrhage in an RRMS patient who previously received alemtuzumab.

Methods: The patient received 2 courses of alemtuzumab 24 mg in CARE-MS II, and 3 additional courses of alemtuzumab 12 mg in the extension (total 5 courses at Months 0, 12, 25, 37, and 50 [300-mg total dose]).

Results: The patient (age 44 at study entry) previously received IFNB-1b and had history of episcleritis, osteoarthritis, and livedo reticularis. Clinical history and baseline MRI were consistent with severe MS. She responded well to alemtuzumab (no relapses over the next 2 years, and EDSS score decreased from 3.0 at baseline to 0–2.5). At Month 55, she developed eosinophilic pneumonitis, and was treated successfully with antibiotics, steroids, and later azathioprine and IFNB-1b. On 4 occasions over Months 67 to 74, she experienced neurologic worsening attributed to MS relapses, treated with pulsed IV steroids. At Month 77, she had febrile illness requiring multiple urgent outpatient visits over several days, confusion, severe headache, nausea, and vomiting; CT angiography showed normal large vessels and no intracerebral hemorrhage. Four days later, she developed nonsensical speech and right hemiplegia; elevated blood pressure was noted. MRI showed left basal ganglia hemorrhage extending into the ventricle. Digital subtraction cerebral angiography showed multifocal narrowing interpreted as vasospasm. Platelets, coagulation studies, and ESR were essentially normal. There were no serologic abnormalities. Neurologic status worsened, care was withdrawn, and the patient expired from herniation. An autopsy was not performed.

Conclusions: The patient suffered a large, deep cerebral hemorrhage with intraventricular extension. Etiology may be an unusual presentation of primary CNS granulomatous angiitis (not known to be associated with systemic or organ-specific autoimmunity); differential diagnosis includes non-traumatic spontaneous intracerebral hemorrhage or, less likely, aneurysmal or unsuspected arterial venous malformation-related hemorrhage. The only other case of intracerebral hemorrhage during alemtuzumab trials was due to immune thrombocytopenia.