Clinical, serological and genetic predictors of response to immunotherapy in anti-IgLON5 disease.

Anti-IgLON5 disease is a newly defined clinical entity characterized by a progressive course with high disability and mortality rate. While precise pathogenetic mechanisms remain unclear, features characteristic of both autoimmune and neurodegenerative diseases were reported. Data on immunotherapy are limited, and its efficacy remains controversial. In this study, we retrospectively investigated an anti-IgLON5 disease cohort with special focus on clinical, serological and genetic predictors of the immunotherapy response and long-term outcome. Patients were recruited from the GENERATE (German Network for Research on Autoimmune Encephalitis) registry. Along with clinical parameters, anti-IgLON5 immunoglobulin (Ig)G in serum and CSF, anti-IgLON5 IgG1-4, IgA and IgM in serum, neurofilament light chain and glial fibrillary acidic protein in serum as well as human leukocyte antigen-genotypes were determined. We identified 53 patients (symptom onset 63.8 ± 10.3 years, female:male 1:1.5). The most frequent initial clinical presentations were bulbar syndrome, hyperkinetic syndrome or isolated sleep disorder [at least one symptom present in 38% (20/53)]. At the time of diagnosis, the majority of patients had a generalized multi-systemic phenotype; nevertheless, 21% (11/53) still had an isolated brainstem syndrome and/or a characteristic sleep disorder only. About one third of patients [28% (15/53)] reported subacute disease onset and 51% (27/53) relapse-like exacerbations during the disease course. Inflammatory CSF changes were evident in 37% (19/51) and increased blood-CSF-barrier permeability in 46% (21/46). CSF cell count significantly decreased, while serum anti-IgLON5 IgG titre increased with disease duration. The presence of human leukocyte antigen-DRB1*10:01 [55% (24/44)] was associated with higher serum anti-IgLON5 IgG titres. Neurofilament light chain and glial fibrillary acidic protein in serum were substantially increased (71.1 ± 103.9 pg/ml and 126.7 ± 73.3 pg/ml, respectively). First-line immunotherapy of relapse-like acute-to-subacute exacerbation episodes resulted in improvement in 41% (11/27) of patients and early initiation within the first 6 weeks was a predictor for therapy response. Sixty-eight per cent (36/53) of patients were treated with long-term immunotherapy and 75% (27/36) of these experienced no further disease progression (observation period of 20.2 ± 15.4 months). Long-term immunotherapy initiation during the first year after onset and low pre-treatment neurofilament light chain were significant predictors for a better outcome. In conclusion, subacute disease onset and early inflammatory CSF changes support the primary role of autoimmune mechanisms at least at initial stages of anti-IgLON5 disease. Early immunotherapy, prior to advanced neurodegeneration, is associated with a better long-term clinical outcome. Low serum neurofilament light chain at treatment initiation may serve as a potential biomarker of the immunotherapy response.

Effects of state-wide implementation of the Los Angeles Motor Scale for triage of stroke patients in clinical practice.

BACKGROUND: The prehospital identification of stroke patients with large-vessel occlusion (LVO), that should be immediately transported to a thrombectomy capable centre is an unsolved problem. Our aim was to determine whether implementation of a state-wide standard operating procedure (SOP) using the Los Angeles Motor Scale (LAMS) is feasible and enables correct triage of stroke patients to hospitals offering (comprehensive stroke centres, CSCs) or not offering (primary stroke centres, PSCs) thrombectomy. METHODS: Prospective study involving all patients with suspected acute stroke treated in a 4-month period in a state-wide network of all stroke-treating hospitals (eight PSCs and two CSCs). Primary endpoint was accuracy of the triage SOP in correctly transferring patients to CSCs or PSCs. Additional endpoints included the number of secondary transfers, the accuracy of the LAMS for detection of LVO, apart from stroke management metrics. RESULTS: In 1123 patients, use of a triage SOP based on the LAMS allowed triage decisions according to LVO status with a sensitivity of 69.2% (95% confidence interval (95%-CI): 59.0-79.5%) and a specificity of 84.9% (95%-CI: 82.6-87.3%). This was more favourable than the conventional approach of transferring every patient to the nearest stroke-treating hospital, as determined by geocoding for each patient (sensitivity, 17.9% (95%-CI: 9.4-26.5%); specificity, 100% (95%-CI: 100-100%)). Secondary transfers were required for 14 of the 78 (17.9%) LVO patients. Regarding the score itself, LAMS detected LVO with a sensitivity of 67.5% (95%-CI: 57.1-78.0%) and a specificity of 83.5% (95%-CI: 81.0-86.0%). CONCLUSIONS: State-wide implementation of a triage SOP requesting use of the LAMS tool is feasible and improves triage decision-making in acute stroke regarding the most appropriate target hospital.