The Marburg variant of multiple sclerosis (Marburg MS) is the most aggressive form of MS, often leading to death soon after onset. Here we describe the case of a 26-year-old Marburg MS patient presenting with severe neurological deficits requiring intensive care. In spite of more than 100 gadolinium-enhancing MRI lesions, the patient recovered almost completely upon high-dose cyclophosphamide (HiCy) rescue treatment (four consecutive days with 50 mg/kg/day, cumulative absolute dose of 14 g). Following the acute treatment, her disease was stabilized by B cell depletion using ocrelizumab. Clinical amelioration was reflected by a decrease of MRI activity and a marked decline of serum neurofilament light chain levels. HiCy rescue treatment followed by ocrelizumab as a maintenance therapy prevented permanent disability and achieved an almost complete clinical and drastic radiological improvement in this Marburg MS patient.

BACKGROUND: In July 2018, a rare and serious adverse effect (AE), namely, communicating hydrocephalus unrelated to meningitis or bleeding, was reported in relation to five patients treated with nusinersen for spinal muscular atrophy (SMA). Some patients were managed using a ventriculo-peritoneal shunt (VPS) implant and continued to receive nusinersen treatment. However, there is limited information concerning the effectiveness and safety of nusinersen treatment for patients with a VPS.
METHODS: A female patient exhibited general hypotonia soon after birth and was diagnosed, using genetic analysis, with spinal muscular atrophy. She required permanent invasive ventilation from 2 months of age. She developed a progressive hydrocephalus and underwent placement of a VPS in infancy. Treatment with nusinersen was initiated when she was 7 years old. The neurofilament light-chain (NfL) concentration in the cerebrospinal fluid (CSF) decreased over time with nusinersen treatment. Twelve months have passed since the start of nusinersen treatment and no AEs have been observed.
CONCLUSIONS: Nusinersen treatment may be effective and safe, even after placement of a VPS. NfL levels in the CSF could be valuable markers of disease activity/treatment response even in advanced stages of SMA.