Reactions Weekly | 2021
Cyclophosphamide/immune-globulin
Abstract
Lack of efficacy: case report A 15-year-old girl exhibited a lack of efficacy during treatment with cyclophosphamide and immune-globulin for anti-N-methyl-Daspartate receptor (NMDAR) encephalitis [not all routes stated; not all dosages stated]. The girl was admitted with headache, high fever and consciousness disturbance. At the time of admission, she was found to be positive for influenza-A virus infection. Based on examinations following admission, influenza encephalopathy was suspected. Therefore, she sequentially received first-line therapy with glucocorticoid pulse therapy, high-dose IV immunoglobulins (IVIG), and plasma exchange (PE). Additionally, due to the development of status epilepticus, she was mechanically ventilated with a tracheostomy. She did not respond to the first-line treatment leading to anti-NMDAR antibodies in CSF remained positive. Subsequently, she was diagnosed with left ovarian teratoma. Hence, she underwent a left oophorectomy. Additionally, she started receiving second-line treatment with cyclophosphamide pulse therapy. However, she remained unconscious, but her status epilepticus subsided. Thereafter, she was transferred to the hospital. Subsequent Brain MRI showed atrophy of the hippocampus and dilation of the lateral and third ventricles, and slight cerebellar atrophy. A single-photon emission computed tomography (SPECT) using N-isopropyl-p-[123I] iodoamphetamine showed a blood flow decrease in the bilateral frontal lobes with slight hypoperfusion in the right anteromedial portion of the cerebellum. She was weaned off the ventilator 11 months after onset. However, her involuntary movements extended to the whole body and became ballistic. The anti-NMDAR antibodies in CSF remained positive in subsequent follow-up. Hence, she started receiving methotrexate therapy. Her symptoms gradually improved following methotrexate therapy. After significant improvement, she was discharged from the hospital. On SPECT, hypoperfusion in the frontal lobe disappeared, while hypoperfusion of the cerebellum was more marked and extended bilaterally with right posterior side predominance. The anti-NMDAR antibodies in CSF remained positive in subsequent follow-up. However, her methotrexate was discontinued. SPECT showed hypoperfusion of the cerebellum. Although mild impairments including working memory and verbal fluency persisted, she eventually returned to high school 3 years after onset. Profound cerebellar hypoperfusion was suspected for her working memory impairment and speaking problems.