A remarkable effect of alemtuzumab in a patient suffering from narcolepsy with cataplexy

Abstract

We made a remarkable clinical observation in a patient suffering from narcolepsy with cataplexy that may add to the understanding of the pathophysiology of this disorder. Our patient, born in 1929, developed all classical symptoms of narcolepsy in 1946, and came to our attention in 1997. Cataplectic attacks were present on a daily basis, mostly partial, involving the face, neck and knees. Typical triggers were making witty remarks and laughter. He was overweight and used no medication because various treatments in the past had been ineffective or not tolerated. Nocturnal polysomnography showed fragmentation but no co-morbid disorders, and the multiple sleep latency test gave a mean sleep latency of 2.1 min and two SOREMs. He was HLA DQB1-0602*positive, and hypocretin-1 was undetectable in the cerebrospinal fluid. He refused to try any newly available treatment. We contacted him irregularly for participation in research protocols. In 2008, he developed a low grade T-cell lymphoma. A year later, he informed us that he had started treatment with alemtuzumab several months before, after which he had observed a complete absence of his cataplectic attacks, whereas prior to this treatment they had been present on a daily basis. The diagnosed lymphoma and initial therapy with methotrexate had not had any influence on the frequency, duration or pattern of his cataplectic attacks. He stated that as far as joking and witty remarks were concerned, his life had not changed. His wife who had observed his attacks for decades confirmed this. All other narcoleptic symptoms remained unchanged with alemtuzumab. His cataplexy did not return during the 1.5 years he was treated with alemtuzumab, until his death. Narcolepsy with cataplexy is considered to be an autoimmune disorder with T-cell involvement, although there is no final proof for this hypothesis. The main arguments are: the tight association with HLA (Mignot et al., 2001); the presence of HLA DQB1*0602 that is almost conditional; and a trans DRB1*1301-DQB1*0603 haplotype that is highly protective (Hor et al., 2010); the identification of Trib2 reactive autoantibodies; the association with polymorphisms in the T-cell receptor alpha locus in a genome-wide association study