Cognitive impairment may be associated with aquaporin-4 antibody positive (AQP4+) NMOSD, particularly where there is prominent cerebral, corpus callosum, or thalamic involvement. It is unclear to what extent this phenomenon may be treatable after months to years. We describe two cases of AQP4+ NMOSD with
cognitive impairment persisting over more than 6 months, where cognition improved after
eculizumab was initiated. In the first case, a 51-year-old woman presented with a 2-month history of
cognitive decline and
ataxia, and diffuse involvement of the corpus callosum on MRI. AQP4 antibody testing returned positive.
Cognitive impairment persisted on
therapy with mycophenolate, then
rituximab. She was switched to
eculizumab from
rituximab 18 months after disease onset because of breakthrough
optic neuritis; memory and cognitive function improved on
eculizumab. In the second case, a 26-year-old woman initially presented with visual, auditory and
tactile hallucinations, and impairment in
activities of daily living, and was given a diagnosis of
schizophrenia. Nine months later she was hospitalized for increasing
confusion. MRI showed
leukoencephalopathy and diffuse involvement of the corpus callosum with multiple enhancing callosal lesions. AQP4 antibody testing was positive and CSF testing for other
antibodies of
autoimmune encephalitis was negative. She had some improvement in cognition with high dose
corticosteroids but remained significantly impaired. On follow-up, her repeat MRI showed a small new right inferomedial frontal enhancing lesion although she did not complain of any new cognitive issues, her MOCA score was 21/30, and she was started on
eculizumab. Two months after
eculizumab initiation she and her family reported cognitive improvement and MOCA score was 25/30. Common features of these two cases included extensive callosal involvement and an
element of ongoing
gadolinium enhancement on MRI. Our experience suggests the possibility that
cognitive impairment may be amenable to
immunotherapy in certain cases of NMOSD.