A young male presented with a one week history of left leg weakness and sensory loss. On examination there was severe UMN weakness of the left leg and reduced sensation. An MRI head revealed a large right frontal lobe inflammatory lesion, with two further smaller lesions. He subsequently developed severe weakness in both legs, mild weakness in the left arm and urinary retention. He had brisk reflexes and a sensory level at T8. His MRI spine revealed diffuse long segment cord signal change between C6 and T4 in keeping with neuromyelitis optica so he was treated with high dose then weaning steroids. We consid- ered inflammatory, infective, and neoplastic differentials. His HIV screen was positive, he had a low CD4 count (242 cells/mm3) but also a low HIV viral load which is unusual for HIV 1; HIV 2 PCR was negative. HIV broadened the differential to vacuolar myelopathy, infections of the immunocompromised, and CNS lymphoma. Serum MOG and aquaporin 4 antibodies were negative. CSF testing for infections and hae- matological malignancies was negative and his viral load was low. He is improving with therapies, steroids and antiretrovirals. Currently the working diagnosis is seronegative neuromyelitis optica spectrum disorder.