Seroprevalence of neuronal antibodies in diseases mimicking autoimmune encephalitis.

Detection of neuronal antibodies for autoimmune encephalitis and paraneoplastic neurological syndromes relies on commercially available cell-based assays and lineblots. However, lineblots may reveal the presence of neuronal antibodies in patients with various non-autoimmune etiologies. Herein we describe patients with non-autoimmune etiologies (cohort B) and detectable neuronal antibodies and compare them to definite cases of autoimmune encephalitis (cohort A) for differences in clinical data. All patients positive for at least one neuronal antibody were retrospectively evaluated for autoimmune encephalitis and/or paraneoplastic neurological syndrome between 2016 and 2022. 39 cases in cohort B and 23 in cohort A were identified. In cohort B, most common diagnoses were neurodegenerative disorders in 9/39 (23.1%), brain tumors in 6/39 (15.4%) while most common detected antibodies were anti-titin (N10), anti-recoverin (N11), anti-Yo (N8) and all were detected in serum only. Differential aspects between cohort A and B were CSF pleocytosis (14/23 (60.8%) vs 11/35 (31.4%), p = 0.042, respectively), MRI features suggestive of encephalitis (6/23 (26.1%) vs 0 (0%), p = 0.002, respectively) and epilepsy restricted to temporal lobes (14/23 (60.9%) vs 2/30 (6.7%), p = 0.0003, respectively). A large proportion of lineblot results were non-specific when only serum was tested and were frequently found in non-autoimmune neurological conditions.

Tumefactive demyelinating disorders as stroke mimics: Description of cases and systematic review of the literature.

BACKGROUND: tumefactive multiple sclerosis (TmMS) is a rare subtype of a demyelinating disease that develops over time. Cases of hyperacute presentations mimicking cerebrovascular disorders have been reported; however, detailed clinical and demographic data are lacking. METHODS: this study aimed to systematically review the literature on tumefactive demyelinating disorders presenting as strokes. After screening the PubMed, PubMed Central, and Web of Science databases, 39 articles describing 41 patients were identified, including 2 historical patients from our center. RESULTS: 23 (53.4%) patients were diagnosed with multiple sclerosis variants (vMS), 17 (39.5%) with inflammatory demyelinating variants (vInf), and 3 with tumors; however, only 43.5% of cases were verified histologically. In subgroup analysis, vMS differed from vInf in several aspects. Inflammatory cerebral spinal fluid parameters, including pleocytosis, proteinorachia was more commonly observed in vInf [11 (64.7%) vs. 1 (5.2%), P = 0.001 and 13/17 (76.4%) vs. 6/23 (31.5%), P = 0.02] than that in vMS. Neurological deterioration and fatal outcomes were more commonly observed in vInf [13/17 (76.4%) vs. 7/23 (30.4%), P = 0.003, and 11/17 (64.7%) vs. 0/23 (0%), P = 0.0001] than that in vMS. CONCLUSIONS: Clinicodemographic data might aid in recognizing different subtypes of TmMS and warrant consideration of unconventional therapies because outcomes may be poor in the vInf of TmMS.

Overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelial cells accelerates coronary artery disease in a mouse model of familial hypercholesterolemia.

OBJECTIVE: Overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelium leads to arterial calcification in mice. The purpose of this study was to examine the effect of elevated endothelial TNAP on coronary atherosclerosis. In addition, we aimed to examine endogenous TNAP activity in human myocardium. APPROACH AND RESULTS: A vascular pattern of TNAP activity was observed in human non-failing, ischemic, and idiopathic dilated hearts (5 per group); no differences were noted between groups in this study. Endothelial overexpression of TNAP was achieved in mice harboring a homozygous recessive mutation in the low density lipoprotein receptor (whc allele) utilizing a Tie2-cre recombinase (WHC-eTNAP mice). WHC-eTNAP developed significant coronary artery calcification at baseline compared WHC controls (4312 vs 0µm2 alizarin red area, p<0.001). Eight weeks after induction of atherosclerosis, lipid deposition in the coronary arteries of WHC-eTNAP was increased compared to WHC controls (121633 vs 9330µm2 oil red O area, p<0.05). Coronary lesions in WHC-eTNAP mice exhibited intimal thickening, calcifications, foam cells, and necrotic cores. This was accompanied by the reduction in body weight and left ventricular ejection fraction (19.5 vs. 23.6g, p<0.01; 35% vs. 47%, p<0.05). In a placebo-controlled experiment under atherogenic conditions, pharmacological inhibition of TNAP in WHC-eTNAP mice by a specific inhibitor SBI-425 (30mg*kg-1*d-1, for 5 weeks) reduced coronary calcium (78838 vs.144622µm2) and lipids (30754 vs. 77317µm2); improved body weight (22.4 vs.18.8g) and ejection fraction (59 vs. 47%). The effects of SBI-425 were significant in the direct comparisons with placebo but disappeared after TNAP-negative placebo-treated group was included in the models as healthy controls. CONCLUSIONS: Endogenous TNAP activity is present in human cardiac tissues. TNAP overexpression in vascular endothelium in mice leads to an unusual course of coronary atherosclerosis, in which calcification precedes lipid deposition. The prevalence and significance of this mechanism in human atherosclerosis requires further investigations.