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Background and ObjectivesDeterminants of disease activity and prognosis are limited in anti-NMDA receptor (NMDAR) encephalitis. Neurofilament light chains (NfL) are markers of axonal damage and have been identified as valuable biomarkers for neurodegenerative and other neuroinflammatory disorders. We aimed to investigate serum NfL levels in patients with anti-NMDAR encephalitis as a biomarker for disease severity and outcome.MethodsIn this retrospective study, NfL values were measured in all available pretreatment serum and paired CSF samples of the nationwide anti-NMDAR encephalitis cohort. The values were analyzed in duplicate using single-molecule array and compared with measurements in healthy references. Follow-up sera were tested to analyze longitudinal responsiveness, if at least available from 2 time points after diagnosis. Serum NfL levels were compared with data on disease activity (seizures, MRI, and CSF findings), severity (modified Rankin Scale [mRS] score, admission days, and intensive care unit admission), and outcome (mRS score and relapses), using regression analysis.ResultsWe have included 71 patients (75% female; mean age 31.4 years, range 0–85 years) of whom pretreatment serum samples were analyzed. Paired CSF samples were available of 33 patients, follow-up serum samples of 20 patients. Serum NfL levels at diagnosis were higher in patients (mean 19.5 pg/mL, 95% CI 13.7–27.7) than in references (mean 6.4 pg/mL, 95% CI 5.8–7.2,p< 0.0001). We observed a good correlation between serum and CSF NfL values (R= 0.84,p< 0.0001). Serum NfL levels and age correlated in patients (PearsonR= 0.57,p< 0.0001) and references (R= 0.62,p< 0.0001). Increased NfL values were detected in patients post–herpes simplex virus 1 encephalitis (mean 248.8 vs 14.1 pg/mL,p< 0.0001) and in patients with brain MRI lesions (mean 27.3 vs 11.1 pg/mL,p= 0.019). NfL levels did relate to the long-term follow-up (mRS score at 12 months; βNfL= 0.55,p= 0.013), although largely explained by the effect of age on NfL levels and prognosis. In serial samples, NfL values did roughly follow clinical disease activity, albeit with delay.DiscussionIncreased serum NfL levels reflect neuroaxonal damage in anti-NMDAR encephalitis. No relationship was identified with disease severity, whereas the association with outcome was confounded by age. The implied role of sampling timing on NfL levels also limits the applicability of NfL as a prognostic marker.

Background Tuberous sclerosis complex (TSC) is a highly variable condition and its clinical features cannot reliably be predicted from the genotype. Counselling of parents of a child with TSC is challenging because of the variability of the condition and the changing outlook due to new treatment options. This study explored current counselling strategies in TSC in the Netherlands, with the aim of developing a recommendation for counselling. Method We performed a nationwide survey using digital questionnaires. Questionnaires were sent to parents of children diagnosed with TSC, and to medical doctors involved in counselling, both no more than ten years prior to the study. Questions focused on general information about the child with TSC, medical doctors involved in counselling, type of information provided, mode of providing information, and recommendations for improvement of counselling. Results Parents of 34 children diagnosed with TSC (7 prenatally) and 18 medical doctors from different departments responded to the questionnaires. Almost all parents were informed on the neurological and cardiac symptoms of TSC, other symptoms were mentioned less often. Satisfaction on counselling was higher when more information on the variability of TSC was provided, preferentially during a clinical visit, when emotional support was provided, and when parents were notified of the TSC patient society. Conclusions Information on the variability in expression and quality of life is highly demanded by (expecting) parents of a child with TSC. Furthermore, reference should be made to institutions such as the support organisation for patients and social services for questions and support.