ABSTRACT
Background: Neuropsychiatric lupus (NPSLE) refers to the neurological and psychiatric manifestations that are commonly observed in patients with systemic lupus erythematosus (SLE). An important question regarding the pathogenesis of NPSLE is whether the symptoms are caused primarily by CNS-intrinsic mechanisms or develop as a consequence of systemic autoimmunity. Currently used spontaneous mouse models for SLE have already contributed significantly to unraveling how systemic immunity affects the CNS. However, they are less suited when interested in CNS primary mechanisms. In addition, none of these models are based on genes that are associated with SLE. In this study, we evaluate the influence of A20, a well-known susceptibility locus for SLE, on behavior and CNS-associated changes in inflammatory markers. Furthermore, given the importance of environmental triggers for disease onset and progression, the influence of an acute immunological challenge was evaluated. Methods: Female and male A20 heterozygous mice (A20+/-) and wildtype littermates were tested in an extensive behavioral battery. This was done at the age of 10±2weeks and 24 â± â2 weeks to evaluate the impact of aging. To investigate the contribution of an acute immunological challenge, LPS was injected intracerebroventricularly at the age of 10±2weeks followed by behavioral analysis. Underlying molecular mechanisms were evaluated in gene expression assays on hippocampus and cortex. White blood cell count and blood-brain barrier permeability were analyzed to determine whether peripheral inflammation is a relevant factor. Results: A20 heterozygosity predisposes to cognitive symptoms that were observed at the age of 10 â± â2 weeks and 24 â± â2 weeks. Young A20+/- males and females showed a subtle cognitive phenotype (10±2weeks) with distinct neuroinflammatory phenotypes. Aging was associated with clear neuroinflammation in female A20+/- mice only. The genetic predisposition in combination with an environmental stimulus exacerbates the behavioral impairments related to anxiety, cognitive dysfunction and sensorimotor gating. This was predominantly observed in females. Furthermore, signs of neuroinflammation were solely observed in female A20+/- mice. All above observations were made in the absence of peripheral inflammation and of changes in blood-brain barrier permeability, thus consistent with the CNS-primary hypothesis. Conclusions: We show that A20 heterozygosity is a predisposing factor for NPSLE. Further mechanistic insight and possible therapeutic interventions can be studied in this mouse model that recapitulates several key hallmarks of the disease.
ABSTRACT
Data regarding the magnetic resonance imaging (MRI) features in Wernicke-Korsakoff syndrome (WKS) are scarce. WKS usually combines a cerebellar syndrome, oculomotor disorder and confusion. The aim of this study was to determine more precisely the clinical presentation of WKS and the frequency and topography of MRI abnormalities. Furthermore, we try to assess the prognostic value of both clinical signs and MRI abnormalities. We retrospectively studied 25 patients with WKS in which an MRI was available. We assessed the initial clinical presentation and the outcome. We also analyzed the frequency and the location of MRI lesions. We then correlated clinical and MRI data with the clinical outcome. Eleven patients (44 p. 100) had the full WKS. Fourteen of the 25 patients (56 p. 100) had a poor evolution. The occurrence of full WKS was correlated with a poor outcome (p < 0.02). Signal abnormalities on T2-weighted images were found in the periacqueducal region, in the thalami or in the mamillar bodies in 16 cases (64 p. 100). There was a correlation between an hypersignal in at least one region and a poor clinical outcome (p < 0.02). Our study demonstrates the high frequency of brain MRI lesions in WKS and the correlation of both initial clinical signs and MRI abnormalities with a poor clinical outcome.
Subject(s)
Brain/pathology , Korsakoff Syndrome/pathology , Magnetic Resonance Imaging , Adult , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
We report a case of acute deafness secondary to bilateral hemorrhages involving the external capsule and extending to both temporal isthmi. The lesions probably disrupted both auditory radiations. Deafness disappeared within 2 weeks leading to a transient auditory agnosia for environmental and verbal sounds. Performance on audiological and neurolinguistic tests were consistent with the hypothesis of a deficit of non-specific auditory processes. Psychoacoustical deficits related to subcortical lesions are very rare and might differ from those due to cortical lesions by the lack of aphasia. The present case and both previous cases with subcortical lesions might suffer from auditory agnosia of apperceptive type. Its characteristics and the role of non-specific auditory processes are discussed using the data obtained from this third case.
