Psychiatric Disorders in Alzheimer Disease With the Presenilin-1 L226F Mutation.

The presenilin-1 (PSEN1) L226F mutation has been linked to very early onset of prominent behavioral and psychiatric disturbances followed by cognitive decline within a few years. We report a novel case of early-onset Alzheimer disease that was originally diagnosed as psychotic depression in a patient with this gene mutation. We also compare our patient's clinical data to those of other cases of this mutation that have been described in the literature. Because atypical behavioral and psychiatric disturbances in young (<40 years) individuals can herald Alzheimer disease, a tight collaboration between psychiatrists and neurologists is crucial for an early diagnosis.

Role of Chitinase 3-like 1 as a Biomarker in Multiple Sclerosis: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is an autoimmune disease confined in the CNS, and its course is frequently subtle and variable. Therefore, predictive biomarkers are needed. In this scenario, we conducted a systematic review and meta-analysis to evaluate the reliability of chitinase 3-like 1 as a biomarker of MS. METHODS: Research through the main scientific databases (PubMed, Scopus, Web of Science, and Cochrane Library) published from January 2010 to December 2020 was performed using the following keywords: "chitinase 3-like 1 and multiple sclerosis" and "YKL40 and multiple sclerosis." Articles were selected according to the 2020 updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines by 2 authors independently, and data were extracted; 20 of the 90 studies screened were included in the meta-analysis. The main efficacy measure was represented by the standardized mean difference of CSF and blood CHI3L1 levels; Review Manager version 5.4 and R software applications were used for analysis. RESULTS: Higher levels of CHI3L1 were found in CSF of 673 patients with MS compared with 336 healthy controls (size-weighted mean difference [SMD] 50.88; 95% CI = 44.98-56.79; p < 0.00001) and in 461 patients with MS than 283 patients with clinically isolated syndrome (CIS) (SMD 28.18; 95% CI = 23.59-32.76; p < 0.00001). Mean CSF CHI3L1 levels were significantly higher in 561 converting than 445 nonconverting CIS (SMD 30.6; 95% CI = 28.31-32.93; p < 0.00001). CSF CHI3L1 levels were significantly higher in patients with primary progressive MS (PPMS) than in patients with relapsing-remitting MS (RRMS) (SMD 43.15; 95% CI = 24.41-61.90; p < 0.00001) and in patients with secondary progressive MS (SMD 41.86 with 95% CI = 32.39-51.33; p < 0.00001). CSF CHI3L1 levels in 407 patients with MS during remission phase of disease were significantly higher than those in 395 patients with MS with acute relapse (SMD 10.48; 95% CI = 08.51-12.44; p < 0.00001). The performances of CHI3L1 in blood for differentiating patients with MS from healthy controls were not significant (SMD 0.48; 95% CI = -1.18 to 2.14; p: 0.57). DISCUSSION: CSF levels of CHI3L1 have a strong correlation with the MS pathologic course, in particular with the mechanism of progression of the disease; it helps to distinguish the PPMS from the RRMS. The potential role of CHI3L1 in serum needs to be further studied in the future.

A Novel Automated Chemiluminescence Method for Detecting Cerebrospinal Fluid Amyloid-Beta 1-42 and 1-40, Total Tau and Phosphorylated-Tau: Implications for Improving Diagnostic Performance in Alzheimer's Disease.

Recently, a fully automated instrument for the detection of the Cerebrospinal Fluid (CSF) biomarker for Alzheimer's disease (AD) (low concentration of Amyloid-beta 42 (Aß42), high concentration of total tau (T-tau) and Phosphorylated-tau (P-tau181)), has been implemented, namely CLEIA. We conducted a comparative analysis between ELISA and CLEIA methods in order to evaluate the analytical precision and the diagnostic performance of the novel CLEIA system on 111 CSF samples. Results confirmed a robust correlation between ELISA and CLEIA methods, with an improvement of the accuracy with the new CLEIA methodology in the detection of the single biomarkers and in their ratio values. For Aß42 regression analysis with Passing−Bablok showed a Pearson correlation coefficient r = 0.867 (0.8120; 0.907% 95% CI p < 0.0001), T-tau analysis: r = 0.968 (0.954; 0.978% 95% CI p < 0.0001) and P-tau181: r = 0.946 (0.922; 0.962 5% 95% CI p < 0.0001). The overall ROC AUC comparison between ROC in ELISA and ROC in CLEIA confirmed a more accurate ROC AUC with the new automatic method: T-tau AUC ELISA = 0.94 (95% CI 0.89; 0.99 p < 0.0001) vs. AUC CLEIA = 0.95 (95% CI 0.89; 1.00 p < 0.0001), and P-tau181 AUC ELISA = 0.91 (95% CI 0.85; 0.98 p < 0.0001) vs. AUC CLEIA = 0.98 (95% CI 0.95; 1.00 p < 0.0001). The performance of the new CLEIA method in automation is comparable and, for tau and P-tau181, even better, as compared with standard ELISA. Hopefully, in the future, automation could be useful in clinical diagnosis and also in the context of clinical studies.

Respiratory dysfunction in Parkinson's disease: a narrative review.

The presence of respiratory symptoms in Parkinson's disease (PD) has been known since the first description of the disease, even though the prevalence and incidence of these disturbances are not well defined. Several causes have been reported, comprising obstructive and restrictive pulmonary disease and changes in the central ventilatory control, and different pathogenetic mechanisms have been postulated accordingly. In our review, we encompass the current knowledge about respiratory abnormalities in PD, as well as the impact of anti-Parkinsonian drugs as either risk or protective factors. A description of putative pathogenetic mechanisms is also provided, and possible treatments are discussed, focusing on the importance of recognising and treating respiratory symptoms as a key manifestation of the disease itself. A brief description of respiratory dysfunctions in atypical Parkinsonism, especially α-synucleinopathies, is also provided.

Bilateral ischemia of the insular cortex after high altitude climbing: A case report.

High altitude exposure could be related to neurological events such as stroke-like episodes, even if the exact pathogenic mechanism is still debated. We describe the case of a caucasian woman who had a bilateral insular ischemic stroke after a rapid ascent above 4000 m in which a secondary embolic dissemination due to a right insular stroke, maybe related to high altitude hemoconcentration, could be hypothesized. In our opinion a prolonged cardiac rhythm monitoring have to be considered especially when no other embolic sources are found and for lesions involving the insular cortex.