Low frequency of N-methyl-D-aspartate receptor autoimmunity in tick-borne encephalitis

by Jakob Morén, Barbro Persson, Anna Sörman, Åke Lundkvist, Hanin Shihab, Marie Studahl, Malin Veje, Göran Günther, Gabriel Westman

Background

Tick-borne encephalitis is a viral infection of the central nervous system that may cause severe illness and long-term sequelae, to which underlying mechanisms are not completely understood. Autoantibodies against the N-methyl-D-aspartate receptor (anti-NMDAR) may be triggered by immunologic events, occur sporadically, and can cause autoimmune encephalitis. Following herpes simplex encephalitis and Japanese encephalitis, anti-NMDAR autoantibodies may develop and have been associated with relapse or impaired cognitive recovery. Tick-borne encephalitis has been shown to trigger anti-NMDAR encephalitis in sporadic cases, but the frequency of autoimmunization is unknown.

Objectives

The objective of this study was to assess the frequency of intrathecal anti-NMDAR antibody development following tick-borne encephalitis and to explore whether such antibodies could be relevant to cognitive complaints.

Methods

Adult patients with tick-borne encephalitis were included retrospectively from one cohort and prospectively from another. A stored post-acute cerebrospinal fluid sample was required for anti-NMDAR analysis. Two commercial kits (Euroimmun AG, Lübeck, Germany) were used to detect anti-NMDAR IgG antibodies in cerebrospinal fluid.

Results

A total of 71 cerebrospinal fluid samples from 53 patients were analyzed for anti-NMDAR antibodies. Samples were obtained at a median of 91 days (range 21–471) after onset of central nervous system symptoms. Anti-NMDAR antibodies were detected in two samples from a single tick-borne encephalitis patient, corresponding to 1.9% of patients (95% CI: 0.05–10.1%).

Conclusions

The development of intrathecal anti-NMDAR autoantibodies following tick-borne encephalitis is a rare event, and further studies are needed to clarify their potential relevance to cognitive outcomes in a minority of cases. Testing for anti-NMDAR antibodies in cerebrospinal fluid may be considered in patients who experience clinical deterioration following an initial recovery.

Sickness absence and disability pension trajectories among individuals on sickness absence due to stress-related disorders. Two prospective population-based cohorts with 13-month follow-up

by Katalin Gémes, Emma Pettersson, Sara Sjölund Andoff, Kristin Farrants, Emilie Friberg, Kristina Alexanderson

Background

Stress-related disorders are common diagnoses for sickness absence (SA) and disability pension (DP) in many Western countries. Knowledge on future SA/DP trajectories among those starting such a SA spell is limited. The aims were to identify future SA/DP days trajectories among individuals starting an SA spell due to stress-related disorder and investigate socio-demographic and morbidity characteristics associated with specific trajectories.

Methods

Using microdata from nationwide registers, we established two cohorts of all living in Sweden who started a new SA spell >14 days due to stress-related disorder in 2011 (N = 32,417) or in 2018 (N = 65,511), respectively. Group-based trajectory models were used to identify trajectories of monthly average SA/DP days during the following 13 months, separate for each cohort. We used multinomial logistic regression to investigate the associations between sociodemographic and morbidity-related predictors and trajectory membership.

Results

We identified six SA/DP trajectories in the two cohorts: steep drop (30.6% and 35.9% of all included in 2018 and 2011); constant fluctuating (8.7%, 11.2%); fast decrease (25.5%, 24.4%); medium decrease (18.1%, 13.1%); slow decrease (10.8%, 7.3%), and constant high (6.2%, 8.0%). The distributions of sociodemographic factors, multi-morbidity, and history of SA/DP differed between the trajectory groups. For example, compared to the steep drop trajectory, individuals in the other trajectories were more likely to be a woman, older, having had prior SA/DP or specialized outpatient healthcare visits.

Conclusions

In these two explorative, population-wide cohorts, we identified six different trajectories of SA/DP days among all with a new SA spell with stress-related disorders. The trajectory groups differed regarding both sociodemographic and health-related covariates.

Executive functioning is associated to everyday interference of pain in patients with chronic pain

by Nils Berginström, Sofia Wåhlin, Linn Österlund, Anna Holmqvist, Monika Löfgren, Britt-Marie Stålnacke, Marika C. Möller

Dysfunction in executive functions is common among patients with chronic pain. However, the relationships between executive functioning and pain management have not been extensively studied. In this study, 189 outpatients (160 women, 29 men; mean age 33.15) with chronic pain underwent an extensive neuropsychological assessment, including several tests of executive functions. In addition, all participants completed self-assessment questionnaires regarding pain and interference of pain in everyday life. After adjusting for effects of age, education, and depression, several aspects of executive functioning were significantly associated with self-assessed everyday interference of pain (rs = 0.13–0.22, all ps 0.05). This indicates that lower performance on tests of executive functioning was significantly associated with a higher degree of pain interference and a lower degree of life control. Pain characteristics such as pain intensity, pain duration, and pain spreading were not associated with executive functioning. These results suggest that preserved executive functions are related to better coping with pain, but not directly to the pain itself, in patients with chronic pain. Depression was also associated with self-management of pain, indicating that patients with lower executive functioning in combination with depression may need special attention during rehabilitation.