Journal of neurology, neurosurgery, and psychiatry
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The pathogenic missense mutations of the gelsolin (GSN) gene lead to familial amyloidosis of the Finnish type (FAF); however, our previous study identified GSN frameshift mutations existed in patients with Alzheimer's disease (AD). The GSN genotype-phenotype heterogeneity and the role of GSN frameshift mutations in patients with AD are unclear. ⋯ GSN frameshift mutations may be associated with AD. An increase in plasma GSN is probably a compensatory reaction in AD, which is a potential biomarker for early AD.
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J. Neurol. Neurosurg. Psychiatr. · Jun 2023
Decrease of natalizumab drug levels after switching from intravenous to subcutaneous administration in patients with multiple sclerosis.
Natalizumab is effective in the treatment of multiple sclerosis (MS). In 2021, the European Medicines Agency approved the subcutaneous (SC) variant of natalizumab which can be used instead of intravenous administration. However, the course of drug levels varies between administration routes, and the Food and Drug Administration rejected the request for approval of natalizumab SC for reasons that were not disclosed. Our objective was to evaluate the course of natalizumab trough drug levels in patients who switched from natalizumab intravenous to SC on various treatment intervals. ⋯ Natalizumab trough drug levels can decrease after switching from natalizumab intravenous to SC administration. We advise to monitor trough drug levels in patients with low natalizumab drug levels during intravenous treatment, patients with higher body mass index or patients on extended treatment intervals who switch to SC administration of natalizumab.
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J. Neurol. Neurosurg. Psychiatr. · Jun 2023
Ocrelizumab concentration and antidrug antibodies are associated with B-cell count in multiple sclerosis.
The majority of patients with multiple sclerosis on ocrelizumab have B-cell depletion after standard interval dosing of 26 weeks. With B-cell-guided dosing patients receive their next dose when B-cell repopulation occurs. Prediction of B-cell repopulation using ocrelizumab concentrations could aid in personalising treatment regimes. The objectives of this study were to evaluate the association between ocrelizumab drug concentration, antidrug antibodies (ADAs) and CD19 B-cell count, and to define a cut-off ocrelizumab concentration for start of B-cell repopulation (defined by ≥10 CD19+ B cells/µL). ⋯ Serum ocrelizumab concentration was strongly associated with B-cell count. Measurement of ocrelizumab drug concentrations and ADAs could play an important role to further personalise treatment and predict the start of B-cell repopulation.
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J. Neurol. Neurosurg. Psychiatr. · Jun 2023
Elevated plasma p-tau181 levels unrelated to Alzheimer's disease pathology in amyotrophic lateral sclerosis.
Phosphorylated-tau181 (p-tau181), a specific marker of Alzheimer's disease (AD) pathology, was found elevated in plasma but not in cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS). We expanded these findings in a larger patient cohort, exploring clinical/electrophysiological associations, prognostic value and longitudinal trajectories of the biomarker. ⋯ Plasma p-tau181 is elevated in patients with ALS, independently from CSF levels, and is firmly associated with LMN dysfunction. The finding indicates that p-tau181 of putative peripheral origin might represent a confounding factor in using plasma p-tau181 for AD pathology screening, which deserves further investigation.
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J. Neurol. Neurosurg. Psychiatr. · Jun 2023
Clinical TrialCognitive performance is associated with glomerular filtration rate in patients with chronic kidney disease: results from the CKD-REIN cohort.
Chronic kidney disease (CKD) is associated with cognitive impairment in general population. We assessed the association between kidney and cognitive functions in patients with CKD and the influence of cardiovascular (CV) risk factors, and depression on this association. ⋯ In patients with CKD, lower eGFR was associated with worse cognitive performance and incident cognitive events, independently of demographics, CV risk factors and depression.