ABSTRACT
Objective: To investigate features of Guillain-Barré syndrome (GBS) following SARS-CoV-2 vaccines and evaluate for a causal link between the two. Methods: We captured cases of GBS after SARS-CoV-2 vaccination through a national, open-access, online surveillance system. For each case, the certainty of GBS was graded using the Brighton criteria, and the relationship to the vaccine was examined using modified WHO Causality Assessment criteria. We compared age distribution of cases with that of prepandemic GBS cases and clinical features with the International GBS Outcome Study (IGOS). Results: Between 1 January and 30 June 2021, we received 67 reports of GBS following the ChAdOx1 vaccine (65 first doses) and three reports following the BNT162b2 vaccine (all first doses). The causal association with the vaccine was classified as probable for 56 (80%, all ChAdOx1), possible for 12 (17%, 10 ChAdOx1) and unlikely for two (3%, 1 ChAdOx1). A greater proportion of cases occurred in the 50-59 age group in comparison with prepandemic GBS. Most common clinical variants were sensorimotor GBS (n=55; 79%) and facial diplegia with paraesthesias (n=10; 14%). 10% (n=7/69) of patients reported an antecedent infection, compared with 77% (n=502/652) of the IGOS cohort (p<0.00001). Facial weakness (63% (n=44/70) vs 36% (n=220/620); p<0.00001) and sensory dysfunction (93% (n=63/68) vs 69% (n=408/588); p=0.00005) were more common but disease severity and outcomes were similar to the IGOS study. Interpretation: Most reports of GBS followed the first dose of ChAdOx1 vaccine. While our study cannot confirm or refute causation, this observation, together with the absence of alternative aetiologies, different than expected age distribution and the presence of unusual clinical features support a causal link. Clinicians and surveillance bodies should remain vigilant to the possibility of this very rare adverse event and its atypical variants.
ABSTRACT
Background: Glucocorticoid resistance-reduced function of the glucocorticoid receptor (GR)-is seen in many depressed patients. It is argued that this resistance to glucocorticoids leads to failure of normal feedback regulation on the immune system. High levels of pro-inflammatory cytokines result. Purpose: We sought to identify evidence supporting or refuting a link between glucocorticoid resistance and immune dysregulation in depression and to summarize retrieved evidence in aggregate form. Methods: We systematically reviewed and meta-analyzed studies that examined cytokine levels in depressed patients compared with controls and that also reported a measure of glucocorticoid resistance. These measures included plasma cortisol, the dexamethasone suppression test (DST), GR expression levels, and the results of in vitro assays of GR function. We conducted four separate meta-analyses to test for moderating effects of glucocorticoid resistance on cytokine production in depression. Results: After sub-grouping 32 studies by the ratio of cortisol levels in patients compared with controls, we observed a trend for increasing glucocorticoid resistance (i.e., the most hypercortisolemic patients) to be associated with increased production of interleukin (IL)-6 [d = 0.94; 95% CI (0.29, 1.59)] and tumour necrosis factor (TNF)-α [d = 0.46; 95% CI (0.12, 0.79)]. We stratified nine studies that reported DST results by relative glucocorticoid resistance between patients and controls, identifying a trend for higher glucocorticoid resistance in patients, compared with controls, to be associated with higher cytokine production in patients (170 patients and 187 controls). This was particularly evident when studies were sub-grouped by source of cytokine-plasma (d = 1.04; 95% CI, 0.57-1.50) versus in vitro (d = 0.24; 95% CI, -0.20 to 0.67). Stratifying the four studies (147 patients and 118 controls) that used in vitro assays of GR function or GR expression to quantify glucocorticoid resistance revealed variable contributions to cytokine production in patients compared with controls (overall effect size: d = 1.35; 95% CI 0.53-2.18). Combining our analyses of studies that reported DST results with those that used in vitro assays of GR function or GR expression to quantify glucocorticoid resistance (302 patients and 277 controls), we noted that although depressed patients produced more cytokines than controls (d = 1.02; 95% CI, 0.55-1.49), there was no evident positive correlation between glucocorticoid resistance and inflammation. Conclusions: Our work provides some support for a model conceptualizing glucocorticoid resistance as a requisite for increased inflammation in depression. The limited number of studies identified highlights the need for purpose-designed investigations that directly examine the relationship between glucocorticoid resistance and cytokine production in depression.
ABSTRACT
PURPOSE OF REVIEW: Functional movement disorders are common and disabling causes of abnormal movement control. Here, we review the current state of the evidence on the use of neuroimaging in Functional movement disorders, particularly its role in helping to unravel the pathophysiology of this enigmatic condition. RECENT FINDINGS: In recent years, there has been a shift in thinking about functional movement disorder, away from a focus on high-level psychological precipitants as in Freudian conversion theories, or even an implicit belief they are 'put-on' for secondary gain. New research has emphasised novel neurobiological models incorporating emotional processing, self-representation and agency. Neuroimaging has provided new insights into functional movement disorders, supporting emerging neurobiological theories implicating dysfunctional emotional processing, self-image and sense of agency. Recent studies have also found subtle structural brain changes in patients with functional disorders, arguing against a strict functional/structural dichotomy.
