Cutaneous presentation of cryptococcal infection with subclinical central nervous system involvement secondary to fingolimod therapy.

Fingolimod is a multiple sclerosis disease-modifying therapy which sequestrates lymphocytes in the lymph nodes, thereby reducing peripheral blood lymphocytes. Cryptococcal infection is an important adverse effect which should be recognised. We report a case of cutaneous and central nervous system infection who presented with isolated cutaneous symptoms in the absence of neurological or systemic manifestations.

Pregnancy outcome following exposure to ocrelizumab in multiple sclerosis.

Background: Ocrelizumab is a monoclonal antibody targeting CD20-expressing B cells used in the treatment of multiple sclerosis (MS). Currently, there is limited safety data in pregnancy. Objectives: To report the pregnancy outcome following exposure to ocrelizumab in MS. Methods: We retrospectively identified 14 pregnancies of 12 MS patients who had been exposed to ocrelizumab within 6 months prior to conception or during pregnancy from a specialty clinic in Western Australia. Results: 13 of 14 pregnancies resulted in live births. One pregnancy was electively terminated following detection of a chromosomal defect. One pregnancy was complicated with placental insufficiency and the infant developed hyaline membrane disease which was complicated by sepsis. There were no observed major congenital anomalies, preterm births, stillbirths or low birthweight. We did not observe any serious maternal infections. All patients were relapse-free despite a mean ocrelizumab-free interval of 65.1 weeks. Conclusions: We did not identify any major safety signals among the patients who received ocrelizumab prior to conception or during the first trimester of pregnancy. Our patients appeared to have a stable disease course despite a prolonged period of treatment interruption during pregnancy.

Central Nervous System Demyelination Related to Tumour Necrosis Factor Alpha Inhibitor.

BACKGROUND: An association between tumour necrosis factor alpha (TNF-α) inhibitors exposure and central nervous system (CNS) demyelinating disorders has been postulated but is poorly understood. OBJECTIVES: Describe the clinical spectrum and progress of a cohort of patients who developed demyelinating disorder following exposure to TNF-α inhibitor. METHODS: Retrospective chart review of patients who presented to a single neurologist in Western Australia between May 2003 and July 2020. RESULTS: 7 patients (6 females and 1 male) were identified. Mean age was 49.1 years. Mean follow-up time was 2.9 years. Mean interval between commencement of TNF-α inhibitor and onset of demyelinating event was 3 years. The spectrum of demyelinating events included transverse myelitis (N = 3), acute brainstem syndrome (N = 1) and optic neuritis (N = 1). 2 patients had an atypical presentation but had MRI findings which unequivocally showed demyelinating changes. 2 patients had a monophasic event while the other 5 patients were diagnosed to have multiple sclerosis. All symptomatic patients with multiple sclerosis were started on disease modifying therapy and remained relapse free during follow-up. CONCLUSION: Exposure to TNF-α inhibitor appears to increase the risk of demyelinating event. Whether TNFα inhibition directly results in CNS demyelination or trigger demyelination in susceptible individuals requires further research.