Tyler Lo, Lamisa Hassan, Shane Wilson, Rithvik Seri, Stephanie Hang
Long-term anti-CD20 therapy in primary progressive multiple sclerosis (PPMS) requires balancing expected neurologic benefit against infection risk as patients age and accumulate disability. A 61-year-old woman with PPMS and no recent clinical or radiographic evidence of inflammatory disease activity while receiving ocrelizumab every six months was hospitalized three times over approximately five months. The first hospitalization was complicated by viridans group streptococcal bacteremia associated with sialadenitis and a progressive pulmonary infiltrate with acute hypoxemic respiratory failure. She was readmitted with multifocal pneumonia, recurrent hypoxemia, metabolic encephalopathy, dysphagia with suspected aspiration, malnutrition, and further functional decline. She was later hospitalized a third time for a stage IV sacral pressure injury complicated by a methicillin-resistant Staphylococcus aureus (MRSA) abscess and sacral osteomyelitis. Serial neurologic evaluations showed no evidence of relapse, and magnetic resonance imaging revealed no active demyelination throughout. Although ocrelizumab may have increased susceptibility to infection, multiple coexisting risk factors, including aspiration risk, frailty, immobility, malnutrition, pressure injury, and recent healthcare exposure, complicated causal attribution. After the first two infectious admissions, the next scheduled infusion was withheld; following the osteomyelitis admission, neurology recommended discontinuation, and the patient remained off disease-modifying therapy without documented relapse at the last follow-up. This case underscores the need to reassess long-term therapy according to recent disease activity, cumulative treatment exposure, immunologic monitoring, infection history, functional status, comorbidities, care context, and patient goals. A single case cannot establish age-based or universal discontinuation thresholds; instead, it supports individualized shared decision-making regarding treatment continuation, interval extension, temporary interruption, or discontinuation.