A Rare Case of Unilateral Progressive Vision Loss and Pachymeningitis.

We describe a 32-year-old man with presumed Vogt-Koyanagi Harada (VKH) syndrome, whose presenting symptoms were headache and progressive loss of vision in the right eye. Neuro-ophthalmic examination showed anterior and posterior uveitis, and retinal detachment in the right eye. Ocular coherence tomography (OCT) showed extensive submacular fluid in the right eye, while the fundus fluorescein angiogram (FFA) confirmed perifoveal retinal pigment epithelium (RPE) disruption and multifocal fluorescein leakage in the right eye. The brain MRI showed a small crescent of dependent fluid layering in the right posterior globe adjacent to the right optic nerve head, and pachymeningeal enhancement of the skull base dura along the clivus.This case demonstrates the utility of brain MRI and OCT findings in the early diagnosis of VKH syndrome, in the absence of prominent clinical signs of meningitis. Aggressive treatment is critical to preserve vision and prevent development of other systemic complications of the disease.

Cryptococcal meningitis in a multiple sclerosis patient taking natalizumab.

IMPORTANCE: Natalizumab was approved in 2004 by the US Food and Drug Administration (US-FDA) for treatment of multiple sclerosis (MS), however it was temporarily withdrawn after its use was associated with progressive multifocal leukoencephalopathy (PML). Other reported adverse events have included melanoma, primary central nervous system (CNS) lymphoma, and gastrointestinal cryptosporidiosis. An MS exacerbation may occur after discontinuation and immune reconstitution inflammatory syndrome (IRIS), particularly in the setting of PML, is also possible. We present the first case of cryptococcal meningitis in a patient taking natalizumab. Managements of both cryptococcal meningitis and MS after discontinuation of natalizumab are the focus of this report. OBSERVATIONS: This is a case report describing a 49-year old Caucasian man with relapsing-remitting MS (RR-MS) on natalizumab. On the twenty-fourth month of natalizumab treatment, he developed cryptococcal meningitis, prompting its discontinuation. Two months later, off natalizumab, while on antifungal treatment, he developed an MS exacerbation. Cerebrospinal fluid (CSF) JC virus polymerase chain reaction (PCR) and human immunodeficiency virus (HIV) serology were repeatedly negative. CONCLUSIONS AND RELEVANCE: Although specific recommendations for treating natalizumab-associated cryptococcal meningitis do not exist, our patient discontinued natalizumab and started conventional anti-fungal treatment. Two months later, he was treated with steroids due to worsening neurologic status from a presumed MS attack. Subsequently, he improved with successful treatment of the cryptococcal meningitis, with no new clinical or radiographic exacerbations.

Glatiramer acetate-reactive T cells produce brain-derived neurotrophic factor.

Experimental and MRI evidence suggest that glatiramer acetate's (Copaxone) therapeutic effect in multiple sclerosis (MS) could be mediated by anti-inflammatory GA-reactive Th2 cells that enter the brain, cross-react with myelin antigens, and produce bystander suppression. Furthermore, a neuroprotective effect, possibly mediated by neurotrophic factors such as BDNF, has been suggested based on experimental evidence in animal models, and the observation that inflammatory cells can elaborate BDNF. Therefore, we examined BDNF production in 73 GA, 13 MBP, and 22 TT-reactive short-term T-cell lines from 12 MS patients treated with GA. Ten of 73 GA-TCL (14%), 1 of the MBP-TCL (3%), and 2 of the TT-TCL (9%) produced BDNF levels two standard deviations above the mean levels produced by resting TCL. RT-PCR analysis confirmed BDNF expression in some GA- and MBP-reactive TCL. The mean BDNF level produced by GA-TCL was significantly higher than that for MBP-TCL, or TT-TCL when lines originating from the same patients were compared (P=0.033). All 10 high BDNF-producing GA-reactive TCL were Th2-biased as determined by the IL-5/IFN-gamma levels ratio. A positive correlation was observed between BDNF and IL-5 (Th2 indicator) (P=0.006) but not with IFN-gamma Th1 indicator) levels in GA-TCL derived from MS patients during but not pre-treatment. We conclude that while BDNF production by T cells is not antigen-specific, GA-reactive TCL are more likely to produce BDNF, and to be Th2-biased.