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BACKGROUND: Rituximab (RTX) resistance or early B-cells repopulation were observed in children but only few publications reported the use of Obinutuzumab and no recommendations were made concerning the dosage for children. METHODS: This study was a single-center retrospective cohort study of all the children followed-up in the Pediatric Neurology Department of Necker-Enfants malades Hospital in Paris, France, and treated with obinutuzumab, between November 1, 2019, and November 1, 2021. RESULTS: A total of eight children (three females, median age 4.5 years) were treated. Seven patients presented with autoimmune encephalitis and one with myeloradiculitis. The median delay of B-cell repopulation after a course of RTX was 87 days (range 41 to 160). A switch to obinutuzumab (anti-CD20) was performed for eight children. The median duration between the first RTX infusion and obinutuzumab administration was 6.6 months. The dosage regimen for obinutuzumab was one infusion of 1000 mg/1.73 m2, that is to say 580 mg/m2 (maximum 1000 mg/infusion), by extrapolation from the adult dosage. The median delay of B-cell repopulation after one course of obinutuzumab was 230 days (range 66 to 303 days) vs 87 days after one course of RTX (P < 0.01). None of the patients presented side effects with obinutuzumab treatment. All patients had a favorable evolution at the last-follow up. Median follow-up was 1.6 years. CONCLUSIONS: This study reports the use of obinutuzumab in neurological inflammatory diseases in a pediatric population. Obinutuzumab seems to have a better biological efficacy than RTX with a longer time of B-cell repopulation.
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BACKGROUND AND AIMS: Water-soluble vitamins play an essential coenzyme role in the nervous system. Acquired vitamin deficiencies are easily treatable, however, without treatment, they can lead to irreversible complications. This study aimed to provide clinical, laboratory parameters and neuroimaging data on vitamin deficiencies in an attempt to facilitate early diagnosis and prompt supplementation. METHODS: From July 1998 to July 2023, patients at Necker-Enfants-Malades Hospital presenting with acute neurological symptoms attributed to acquired vitamin deficiency were included. Clinical data were extracted from Dr Warehouse database. Neuroimaging, biochemical and electrophysiological data were reviewed. RESULTS: Patients with vitamin B1 deficiency exhibited abnormal eye movements (n = 4/4), fluctuations in consciousness (n = 3/4), and ataxia (n = 3/4). Brain MRI showed alterations of fourth ventricle region (n = 4/4), periaqueductal region (n = 4/4), tectum (n = 3/4), and median thalami (n = 3/4). Patients with vitamin B2 deficiency presented with early onset hypotonia (n = 3/4), hyperlactatemia (n = 4/4), and hyperammonemia (n = 4/4). Plasma acylcarnitines revealed a multiple acyl-coA dehydrogenase deficiency-like profile (n = 4/4). In vitamin B12 deficiency, young children presented with developmental delay (n = 7/7) and older children with proprioceptive ataxia (n = 3/3). Brain MRI revealed atrophy (n = 7/7) and spinal MRI hyperintensity in posterior cervical columns (n = 3/3). Metabolic findings showed elevated methylmalonic acid (n = 6/7) and hyperhomocysteinemia (n = 6/7). Patients with vitamin C deficiency exhibited gait disturbances and muscle weakness (n = 2/2). CONCLUSIONS: Acquired vitamin deficiencies may display reversible clinical symptoms mimicking inherited metabolic disorders. Some situations raise suspicion for diagnosis: concordant clinical presentation, suggestive neuroimaging findings, and/or biochemical evidence. Any acute neurological condition should be treated without waiting for definitive biochemical confirmation.
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The paradigm type I interferonopathy Aicardi-Goutières syndrome (AGS) is most typically characterized by severe neurological involvement. AGS is considered an immune-mediated disease, poorly responsive to conventional immunosuppression. Premised on a chronic enhancement of type I interferon signaling, JAK1/2 inhibition has been trialed in AGS, with clear improvements in cutaneous and systemic disease manifestations. Contrastingly, treatment efficacy at the level of the neurological system has been less conclusive. Here, we report our real-word approach study of JAK1/2 inhibition in 11 patients with AGS, providing extensive assessments of clinical and radiological status; interferon signaling, including in cerebrospinal fluid (CSF); and drug concentrations in blood and CSF. Over a median follow-up of 17 months, we observed a clear benefit of JAK1/2 inhibition on certain systemic features of AGS, and reproduced results reported using the AGS neurologic severity scale. In contrast, there was no change in other scales assessing neurological status; using the caregiver scale, only patient comfort, but no other domain of everyday-life care, was improved. Serious bacterial infections occurred in 4 out of the 11 patients. Overall, our data lead us to conclude that other approaches to treatment are urgently required for the neurologic features of AGS. We suggest that earlier diagnosis and adequate central nervous system penetration likely remain the major factors determining the efficacy of therapy in preventing irreversible brain damage, implying the importance of early and rapid genetic testing and the consideration of intrathecal drug delivery.
