Severe Cognitive Impairment Associated With Intrathecal Antibodies to the NR1 Subunit of theN-Methyl-D-Aspartate Receptor in a Patient With Multiple Sclerosis

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Some patients with multiple sclerosis (MS) can either present with or develop severe cognitive impairment during the course of their disease. However, the mechanisms underlying severe cognitive dysfunction in MS are not well understood.


We report on a woman who was diagnosed as having MS at age 33 years and who after giving birth at age 37 years developed cognitive impairment with severe memory dysfunction as the leading symptom. Treatment with different immunotherapies, including cyclophosphamide and natalizumab, did not improve her cognitive deficits, necessitating admission to a nursing home at age 39 years. During a thorough reevaluation at age 43 years, analysis of current and stored cerebrospinal fluid and serum samples demonstrated an intrathecal synthesis of IgG antibodies to the NR1 subunit of the N-methyl-D-aspartate receptor, that is, the characteristic laboratory finding of anti–N-methyl-D-aspartate receptor encephalitis. Although the patient initially stabilized under therapy with corticosteroids, plasma exchange, and mitoxantrone, severe cognitive impairment persisted and she eventually died from the sequelae of her disease.


This report suggests that the occasional occurrence of severe cognitive impairment in patients with MS may, in some cases, be related to a superimposed antibody-mediated autoimmune encephalitis.

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