Plasma Cystatin C correlates with plasma NfL levels and predicts disease progression in Parkinson's disease

INTRODUCTION: Previous studies reported increased plasma levels of Cystatin C (Cys-C) in Parkinson's disease (PD) and claimed for a possible association with disease severity and progression. The aim of this study was to evaluate plasma Cys-C in PD and healthy controls (HC) and test its association with markers of peripheral inflammation, neurodegeneration and clinical progression in a longitudinal study. METHODS: Plasma Cys-C, high-sensitive C-reactive protein (hsCRP), interleukin 6 (IL-6) and Neurofilament Light Chain (NfL) were assessed at the baseline in 71 consecutive non-demented PD and 69 HC. PD patients underwent an extensive motor and cognitive assessment at baseline and after 2 years of follow-up. The association of Cys-C with disease severity was evaluated in a multilinear model adjusted for the effect of age, sex, disease duration and peripheral inflammation. RESULTS: Cys-C levels appeared to be higher in PD compared to controls and correlated with the plasma neuronal marker NfL (r = 0.204, p = 0.046). In longitudinal analyses, PD patients with higher Cys-C levels exhibited faster motor progression at two years of follow-up independently from the peripheral inflammatory profile. CONCLUSIONS: Cys-C was associated with higher NfL levels and a remarkably faster motor progression in PD independently from peripheral inflammation. Further studies are needed in order to understand the mechanisms underpinning the association of Cys-C with higher neuronal damage markers in neurodegenerative diseases

Serum NFL as a predictor of disease progression in dementia with Lewy bodies

AbstractBackgroundCSF and plasma neurofilament light chain (NfL) levels have been consistently proposed as reliable markers of neurodegeneration able to discriminate between Parkinson's disease (PD) and atypical parkinsonisms. Increased Serum NfL might predict worse motor and cognitive progression in PD patients at single subject level.Methodplasma NfL was assessed in a longitudinal study including 93 patients with Parkinson's disease and 27 patients with DLB who underwent an extensive motor and cognitive assessment and after 2 years of follow‐up. The study evaluated the correlation between NfL plasma levels and motor, non‐motor symptoms, cognitive and behavioral abnormalities in the two cohorts, as well as benignant/malignant phenotypes and motor/cognitive progression in PD after 2 years of follow‐up.ResultSerum NfL correlated with age and age at onset in the cohort. In DLB, NfL correlated with disease duration, hyposmia and neuropsychiatric symptoms, but not with motor function assessed by UPDRS‐III. We found no significant associations between NfL and disease progression in DLB patients. In PD, higher NfL levels correlated with hyposmia (p=0.01), total UPDRS‐II and UPDRS‐III scores (0.001), gait speed (0.04) and several disability milestones, including mild cognitive impairment (0.001), symptomatic dysautonomia (0.001), loss of independency in activities of daily living (p=0.01) and instrumental daily living (p=0.001). At two years of follow‐up, NfL was the best marker in multivariate regression analyses for both motor and cognitive progression beyond malignant/benignant phenotypes.ConclusionElevated serum NfL levels are associated with fast progression in PD patients and could thus represent target of interventions in specific subpopulation of patients

Imaging features and ultraearly hematoma growth in intracerebral hemorrhage associated with COVID-19

Purpose: Intracerebral hemorrhage (ICH) is an uncommon but deadly event in patients with COVID-19 and its imaging features remain poorly characterized. We aimed to describe the clinical and imaging features of COVID-19-associated ICH. Methods: Multicenter, retrospective, case-control analysis comparing ICH in COVID-19 patients (COV19\u2009+) versus controls without COVID-19 (COV19\u2009-). Clinical presentation, laboratory markers, and severity of COVID-19 disease were recorded. Non-contrast computed tomography (NCCT) markers (intrahematoma hypodensity, heterogeneous density, blend sign, irregular shape fluid level), ICH location, and hematoma volume (ABC/2 method) were analyzed. The outcome of interest was ultraearly hematoma growth (uHG) (defined as NCCT baseline ICH volume/onset-to-imaging time), whose predictors were explored with multivariable linear regression. Results: A total of 33 COV19\u2009+\u2009patients and 321 COV19\u2009-\u2009controls with ICH were included. Demographic characteristics and vascular risk factors were similar in the two groups. Multifocal ICH and NCCT markers were significantly more common in the COV19\u2009+\u2009population. uHG was significantly higher among COV19\u2009+\u2009patients (median 6.2 mL/h vs 3.1 mL/h, p\u2009=\u20090.027), and this finding remained significant after adjustment for confounding factors (systolic blood pressure, antiplatelet and anticoagulant therapy), in linear regression (B(SE)\u2009=\u20090.31 (0.11), p\u2009=\u20090.005). This association remained consistent also after the exclusion of patients under anticoagulant treatment (B(SE)\u2009=\u20090.29 (0.13), p\u2009=\u20090.026). Conclusions: ICH in COV19\u2009+\u2009patients has distinct NCCT imaging features and a higher speed of bleeding. This association is not mediated by antithrombotic therapy and deserves further research to characterize the underlying biological mechanisms

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Premorbid vulnerability and disease severity impact on Long-COVID cognitive impairment

Background Cognitive deficits have been increasingly reported as possible long-term manifestations after SARS-CoV-2 infection. Aims In this study we aimed at evaluating the factors associated with cognitive deficits 6 months after hospitalization for Coronavirus Disease 2019 (COVID-19). Methods One hundred and six patients, discharged from a pneumology COVID-19 unit between March 1 and May 30 2020, accepted to be evaluated at 6 months according to an extensive neurological protocol, including the Montreal Cognitive Assessment (MoCA). Results Abnormal MoCA scores at 6 months follow-up were associated with higher pre-hospitalization National Health System (NHS) score (Duca et al. in Emerg Med Pract 22:1-2, 2020) (OR 1.27; 95% CI 1.05-1.6; p = 0.029) and more severe pulmonary disease expressed by the Brescia-COVID Respiratory Severity Scale (Duca et al. in Emerg Med Pract 22:1-2, 2020) (BCRSS > 1OR 4.73; 95% CI 1.53-14.63; p = 0.003) during the acute phase of the disease. Discussion This longitudinal study showed that the severity of COVID-19, indicated by BCRSS, and a complex score given by age and premorbid medical conditions, expressed by NHS, play a major role in modulating the long-term cognitive consequences of COVID-19 disease. Conclusions These findings indicate that the association of age and premorbid factors might identify people at risk for long-term neurological consequences of COVID-19 disease, thus deserving longer and proper follow-up

Evidence of white matter changes on diffusion tensor imaging in frontotemporal dementia

BACKGROUND: Two major clinical variants of frontotemporal dementia (FTD) have been described: frontal variant (fvFTD) and temporal variant (tvFTD). OBJECTIVE: To analyze white matter (WM) and gray matter (GM) tissue organization in patients with fvFTD and tvFTD by means of diffusion tensor imaging and voxel-based morphometry, and the correlations with neuropsychological and behavioral variables. DESIGN AND SETTING: Frontotemporal dementia clinic-based cohort and structural magnetic resonance imaging acquisition for voxel-based morphometry and diffusion tensor imaging measurements. Abnormalities were detected by a comparison with healthy control subjects. These variables were also correlated with clinical scores. Patients Thirty-six patients (28 with fvFTD and 8 with tvFTD) in early disease stage and 23 healthy controls who underwent standardized clinical and neuropsychological evaluation and magnetic resonance imaging. INTERVENTIONS: Diffusion tensor imaging and voxel-based morphometry. MAIN OUTCOME MEASURES: Neuroimaging analyses resulted in localized GM atrophy and reductions of white matter densities; the latter correlated with behavioral scores. RESULTS: Voxel-based morphometry analysis showed separate patterns of GM atrophy in the 2 groups. Diffusion tensor imaging showed different WM reduction patterns in patients with fvFTD and tvFTD. The fvFTD group showed a selective WM reduction in the superior longitudinal fasciculus, interconnecting the frontal and occipital and the temporal and parietal regions. Conversely, patients with tvFTD were characterized by WM reductions in the inferior longitudinal fasciculus, which affected the connections between anterior temporal and frontal regions. The WM reductions in fvFTD paralleled both behavioral disturbances measured by Frontal Behavioral Inventory and neuropsychological deficits affecting frontal functions. CONCLUSIONS: The fvFTD and tvFTD variants are associated not only with selective local GM reductions but also with significant WM damage in early disease phase. The different WM patterns contribute to the different clinical syndromes in FTD and could be responsible for the further progression of atrophy in the later disease stages

Where SUNCT Contacts TN: A Case Report

BACKGROUND.-: Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) and trigeminal neuralgia (TN) are unilateral painful conditions that can share the same triggering factors, autonomic features and the main location, as well as the cyclically recurrent crises. Both these syndromes are associated with a high percentage of findings of vascular malformation touching the trigeminal nerve, suggesting a pathophysiological relationship. CASE.-: In this paper, we report a new case with the main purpose to shine a light on the pathophysiology of these conditions. CONCLUSION.-: Many authors described a SUNCT case deriving from TN or vice versa, suggesting that these conditions are strongly related. Every case of transformed TN or SUNCT should therefore be reported to gather and compare further information