Clinical outcome of neurological patients with COVID-19: the impact of healthcare organization improvement between waves.

OBJECTIVE: The aim of this study is to evaluate the differences in clinical presentations and the impact of healthcare organization on outcomes of neurological COVID-19 patients admitted during the first and second pandemic waves. METHODS: In this single-center cohort study, we included all patients with SARS-CoV-2 infection admitted to a Neuro-COVID Unit. Demographic, clinical, and laboratory data were compared between patients admitted during the first and second waves of the COVID-19 pandemic. RESULTS: Two hundred twenty-three patients were included, of whom 112 and 111 were hospitalized during the first and second pandemic waves, respectively. Patients admitted during the second wave were younger and exhibited pulmonary COVID-19 severity, resulting in less oxygen support (n = 41, 36.9% vs n = 79, 70.5%, p < 0.001) and lower mortality rates (14.4% vs 31.3%, p = 0.004). The different healthcare strategies and early steroid treatment emerged as significant predictors of mortality independently from age, pre-morbid conditions and COVID-19 severity in Cox regression analyses. CONCLUSIONS: Differences in healthcare strategies during the second phase of the COVID-19 pandemic probably explain the differences in clinical outcomes independently of disease severity, underlying the importance of standardized early management of neurological patients with SARS-CoV-2 infection.

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, interleukin 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 2 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.

Extrastriatal dopaminergic and serotonergic pathways in Parkinson's disease and in dementia with Lewy bodies: a 123I-FP-CIT SPECT study.

PURPOSE: The aim of the study was to evaluate extrastriatal dopaminergic and serotonergic pathways in patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB) using 123I-FP-CIT SPECT imaging. METHODS: The study groups comprised 56 PD patients without dementia, 41 DLB patients and 54 controls. Each patient underwent a standardized neurological examination and 123I-FP-CIT SPECT. Binding in nigrostriatal and extrastriatal regions of interest was calculated in each patient from spatially normalized images. The occipital-adjusted specific to nondisplaceable binding ratio (SBR) in the different regions was compared among the PD patients, DLB patients and controls adjusting for the effects of age, sex, disease duration and serotonergic/dopaminergic treatment. Covariance analysis was used to determine the correlates of local and long-distance regions with extrastriatal 123I-FP-CIT deficits. RESULTS: Both PD and DLB patients showed lower 123I-FP-CIT SPECT SBR in several regions beyond the nigrostriatal system, especially the insula, cingulate and thalamus. DLB patients showed significantly lower 123I-FP-CIT SBR in the thalamus than controls and PD patients. Thalamic and cingulate 123I-FP-CIT SBR deficits were correlated, respectively, with limbic serotonergic and widespread cortical monoaminergic projections only in DLB patients but exhibited only local correlations in PD patients and controls. CONCLUSION: PD and DLB patients both showed insular dopamine deficits, whereas impairment of thalamic serotonergic pathways was specifically associated with DLB. Longitudinal studies are necessary to determine the clinical value of the assessment of extrastriatal 123I-FP-CIT SPECT.

Neurological disorders throughout acute SARS-CoV2 infection: A comparative study between vaccinated and non-vaccinated patients.

BACKGROUND: The role of vaccination on Covid-19 severity in neurological patients is still unknown. We aim at describing clinical characteristics and outcomes of breakthrough and unvaccinated Covid-19 patients hospitalized for neurological disorders. METHODS: Two hundred thirty-two Covid-19 patients were admitted to a neuro-Covid Unit form March 1st 2021 to February 28th 2022. Out of the total sample, 74 (32%) were full vaccinated. The prevalence, clinical characteristics, disease severity, expressed by Brescia-COVID Respiratory Severity Scale (BCRSS) and National Early Warning Score 2 (NEWS2), and final outcomes of neurological syndromes were compared between vaccinated and unvaccinated cases. Cox regression analysis was implemented in order to investigate the combined effect of predictors of mortality. RESULTS: Breakthrough vaccinated cases were older (years 72.4 ± 16.3 vs 67.0 ± 18.9 years, p = 0.029), showed higher pre-admission comorbidity score and Clinical Frailty scale score (4.46 ± 1.6 vs 3.75 ± 2.0, p = 0.008) with no differences in terms of disease progression or mortality rate (16.2% vs 15.2%), compared to full-dose vaccinated patients. Cox-regression analysis showed age and NEWS2 score as the variables with a significant relation to mortality between the two groups, independently from pre-morbid conditions and inflammatory response. CONCLUSION: This study on breakthrough COVID-19 infection could help identify vulnerable neurological patients with higher risk of poor outcomes.

Dopaminergic connectivity reconfiguration in the dementia with Lewy bodies continuum.

INTRODUCTION: The impairment of nigrostriatal dopaminergic network is a core feature of dementia with Lewy bodies (DLB). The involvement and reconfiguration of extranigrostriatal dopaminergic circuitries in the DLB continuum is still theme of debate. We aim to investigate in vivo the dynamic changes of local and long-distance dopaminergic networks across DLB continuum. METHODS: Forty-nine patients (including 29 with dementia and 20 prodromal cases) and fifty-two controls entered the study. Each subject underwent a standardized clinical and neurological examination and performed Brain SPECT to measuring brain dopamine transporter (DAT) density. Spatially normalized images underwent the occipital-adjusted specific binding to obtain parametric data. The ANCOVA was applied to assess 123I-FP-CIT differences between pDLB, overt-DLB and CG, considering age, gender, and motor impairment as variables of no interest. Between-nodes correlation analysis measured molecular connectivity within the ventral and dorsal dopaminergic networks. RESULTS: Prodromal DLB and DLB patients showed comparable nigrostriatal deficits in basal ganglia regions compared with CG. Molecular connectivity analyses revealed extensive connectivity losses, more in ventral than in dorsal dopaminergic network in DLB dementia. Conversely, the prodromal group showed increased connectivity compared to CG, mostly putamen-thalamus-cortical and striatal-cortical connectivity. CONCLUSIONS: This study indicates a comparable basal ganglia deficit in nigrostriatal projections in DLB continuum and supports a different reorganization of extra-striatal dopaminergic connectivity in the prodromal phases of DLB. The shift from an increased to a decreased bilateral putamen-thalamus-cortex connectivity might be a hallmark of transition from prodromal to dementia DLB stages.

Suicide risk in frontotemporal lobe degeneration: to be considered, to be prevented.

Suicide is difficult to ascertain in elderly patients, and dementia might represent a risk factor, though predictors of suicide in dementia are still unknown. We report the case of a patient recently diagnosed as having a behavioral variant of frontotemporal lobar degeneration (FTLD), apathetic syndrome, who committed suicide by hanging. His personal and family history was negative for mental disorders; a depressive syndrome was diagnosed 1 year before FTLD diagnosis, and treated unsuccessfully. To the best of our knowledge, no data are available about self-harmful events in FTLD. This case report argues for the urgent need for developing specific tools for the assessment of suicidal ideation among at-risk population.

Plasma Neurofilament Light Chain Predicts Cognitive Progression in Prodromal and Clinical Dementia with Lewy Bodies.

Plasma neurofilament light chain (NfL) is a marker of neuronal damage in different neurological disorders and might predict disease progression in dementia with Lewy bodies (DLB). The study enrolled 45 controls and 44 DLB patients (including 17 prodromal cases) who underwent an extensive assessment at baseline and at 2 years follow-up. At baseline, plasma NfL levels were higher in both probable DLB and prodromal cases compared to controls. Plasma NfL emerged as the best predictor of cognitive decline compared to age, sex, and baseline severity variables. The study supports the role of plasma NfL as a useful prognostic biomarker from the early stages of DLB.

Plasma NfL, clinical subtypes and motor progression in Parkinson's disease.

INTRODUCTION: neurofilament light chain (NfL) levels have been proposed as reliable biomarkers of neurodegeneration in Parkinson's disease (PD) but the relationship between plasma NfL, clinical subtypes of PD and motor progression is still debated. METHODS: plasma NfL concentration was measured in 45 healthy controls and consecutive 92 PD patients who underwent an extensive motor and non-motor assessment at baseline and after 2 years of follow-up. PD malignant phenotype was defined as the combination of at least two out of cognitive impairment, orthostatic hypotension and REM sleep behavior disorder. PD patients were divided according to the age-adjusted cut-offs of plasma NfL levels into high and normal NfL (H-NfL and N-NfL, respectively). A multivariable linear regression model was used to assess the value of plasma NfL as predictor of 2-years progression in PD. RESULTS: NfL was higher in PD patients than in controls (p = 0.037). H-NfL (n = 16) group exhibited more severe motor and non-motor symptoms, higher prevalence of malignant phenotype and worse motor progression (MDS-UPDRS-III 11.3 vs 0.7 points, p = 0.003) compared to N-NfL group (n = 76). In linear regression analyses plasma NfL emerged as the best predictor of 2-year motor progression compared to age, sex, disease duration, baseline motor/non-motor variables. CONCLUSION: increased plasma NfL concentration is associated with malignant PD phenotype and faster motor progression. These findings support the role of NfL assessment as a useful measure for stratifying patients with different baseline slopes of decline in future clinical trials of putative disease-modifying treatments.

Clinical characteristics and outcomes of inpatients with neurologic disease and COVID-19 in Brescia, Lombardy, Italy.

OBJECTIVE: To report clinical and laboratory characteristics, treatment, and clinical outcomes of patients admitted for neurologic diseases with and without coronavirus disease 2019 (COVID-19). METHODS: In this retrospective, single-center cohort study, we included all adult inpatients with confirmed COVID-19 admitted to a neuro-COVID unit beginning February 21, 2020, who had been discharged or died by April 5, 2020. Demographic, clinical, treatment, and laboratory data were extracted from medical records and compared (false discovery rate corrected) to those of neurologic patients without COVID-19 admitted in the same period. RESULTS: One hundred seventy-three patients were included in this study, of whom 56 were positive and 117 were negative for COVID-19. Patients with COVID-19 were older (77.0 years, interquartile range [IQR] 67.0-83.8 years vs 70.1 years, IQR 52.9-78.6 years, p = 0.006), had a different distribution regarding admission diagnoses, including cerebrovascular disorders (n = 43, 76.8% vs n = 68, 58.1%), and had a higher quick Sequential Organ Failure Assessment (qSOFA) score on admission (0.9, IQR 0.7-1.1 vs 0.5, IQR 0.4-0.6, p = 0.006). In-hospital mortality rates (n = 21, 37.5% vs n = 5, 4.3%, p < 0.001) and incident delirium (n = 15, 26.8% vs n = 9, 7.7%, p = 0.003) were significantly higher in the COVID-19 group. Patients with COVID-19 and without COVID with stroke had similar baseline characteristics, but patients with COVID-19 had higher modified Rankin Scale scores at discharge (5.0, IQR 2.0-6.0 vs 2.0, IQR 1.0-3.0, p < 0.001), with a significantly lower number of patients with a good outcome (n = 11, 25.6% vs n = 48, 70.6%, p < 0.001). In patients with COVID-19, multivariable regressions showed increasing odds of in-hospital death associated with higher qSOFA scores (odds ratio [OR] 4.47, 95% confidence interval [CI] 1.21-16.5, p = 0.025), lower platelet count (OR 0.98, 95% CI 0.97-0.99, p = 0.005), and higher lactate dehydrogenase (OR 1.01, 95% CI 1.00-1.03, p = 0.009) on admission. CONCLUSIONS: Patients with COVID-19 admitted with neurologic disease, including stroke, have a significantly higher in-hospital mortality and incident delirium and higher disability than patients without COVID-19.

Vascular Risk Factors and Cognition in Parkinson's Disease.

Vascular risk factors have been associated with cognitive deficits and incident dementia in the general population, but their role on cognitive dysfunction in Parkinson's disease (PD) is still unclear. The present study addresses the single and cumulative effect of vascular risk factors on cognition in PD patients, taking clinical confounders into account. Standardized neuropsychological assessment was performed in 238 consecutive PD patients. We evaluated the association of single and cumulative vascular risk factors (smoking, diabetes, hypercholesterolemia, hypertension, and heart disease), with the diagnosis of PD normal cognition (PDNC, n = 94), mild cognitive impairment (PD-MCI, n = 111), and dementia (PDD, n = 33). The association between single neuropsychological tests and vascular risk factors was evaluated with covariance analyses adjusted for age at onset, educational levels, gender, disease duration, and motor performance. Age, educational levels, disease duration, and motor function were significantly different between PDNC, PD-MCI, and PDD. Heart disease was the only vascular factor significantly more prevalent in PDD compared with PDNC in adjusted analyses. Performance of tests assessing executive and attention functions were significantly worse in patients with hypertension, heart disease, and/or diabetes (p <  0.05). Heart disease is associated with dementia in PD, suggesting a potential window of intervention. Vascular risk factors act especially on attention and executive functions in PD. Vascular risk stratification may be useful in order to identify PD patients with a greater risk of developing dementia. These findings need to be verified in longitudinal studies.

Structural and functional imaging study in dementia with Lewy bodies and Parkinson's disease dementia.

INTRODUCTION: Dementia with Lewy Bodies (DLB) and Parkinson's disease with Dementia (PDD) are neurodegenerative disorders with complex clinical picture (parkinsonism, cognitive decline and neuropsychiatric disturbances). The conundrum of whether DLB and PDD represent the same or different entities is still under debate. Advanced neuroimaging techniques may represent a point of view to assess brain correlates in DLB and PDD. The study aimed at evaluating whether DLB and PDD may be labelled under the same disease entity or be considered distinctive pathologies. We compared DLB and PDD patients by assessing structural and functional brain imaging and including PD patients. METHODS: Patients with diagnosis of PD, PDD, DLB and a group of healthy controls for neuroimaging comparisons were recruited and changes in structural and resting-state functional MR (Regional Homogeneity, ReHo) were studied. RESULTS: No significant atrophy in VBM analysis was evident in PD. Conversely, PDD showed a significant bilateral frontal atrophy, whereas DLB was characterized by a predominant parietal, occipital atrophy; a similar involvement of subcortical regions in PDD and DLB was observed. ReHo demonstrated reduced local coherence of frontal regions in PD and in PDD, whereas DLB patients presented a reduced local connectivity in posterior regions. CONCLUSION: Different brain areas are specifically involved in PDD and DLB. In the former group, greater atrophy of frontal regions with concomitant functional connectivity impairment was evident; conversely, structural and functional damage in the posterior regions characterized DLB. Despite an overlapping clinical spectrum, DLB and PDD have different networks involved and different underlying pathogenic pathways.

Abnormalities in the pattern of platelet amyloid precursor protein forms in patients with mild cognitive impairment and Alzheimer disease.

CONTEXT: Patients affected by sporadic Alzheimer disease (AD) show a significant alteration of amyloid precursor protein (APP) forms in platelets when compared with patients with dementia but without AD and age-matched controls. OBJECTIVE: To evaluate the ratio of platelet APP forms (APPr) in early-stage AD and mild cognitive impairment (MCI) and its potential as a biomarker for the early identification of AD. SETTING: Community population-based sample of patients admitted to 4 AD centers for investigation of cognitive disturbances. DESIGN AND METHODS: Thirty-five patients with mild AD (mAD), 21 patients with very mild AD (vmAD), 30 subjects with MCI, and 25 age-matched controls were included. The APPr was evaluated by Western blot analysis in platelet homogenate. RESULTS: Compared with controls (mean +/- SD, 0.93 +/- 0.3), the mean APPr was decreased in patients with mAD (0.44 +/- 0.24; P<.001) and patients with vmAD (0.49 +/- 0.3; P<.001). Regarding the MCI group, a significant decrease in APPr was found compared with controls (0.62 +/- 0.33; P<.001). Fixing a cutoff score of 0.6, sensitivity was 88.6% (31/35) for patients with mAD and 85.7% (18/21) for patients with vmAD, whereas specificity was 88% (22/25) for controls. Among patients with MCI, 18 (60%) of 30 individuals displayed APPr values below the cutoff. CONCLUSIONS: Alteration of platelet APP forms is an early event in AD, and the measurement of APPr may be useful for the identification of preclinical AD in patients with MCI.

Is transient global amnesia a risk factor for amnestic mild cognitive impairment?

Transient Global Amnesia (TGA) is a common condition of unknown aetiology characterised by the abrupt onset of severe anterograde amnesia, which lasts less than 24 hours. Some authors have suggested that subclinical impairment of memory functions may persist for much longer, but neuropsychological assessment lasting years after TGA attack has not been performed so far. The aim of this study was to evaluate longterm cognitive functions in patients with a previous TGA episode. Fifty-five patients underwent a standardised neuropsychological assessment after at least one-year from the TGA attack, and were compared with 80 age-matched controls. TGA patients showed worse performances on tests evaluating verbal and nonverbal long-term memory and attention, with comparable global cognitive functions. By applying current criteria for amnestic Mild Cognitive Impairment (MCI-a) on TGA subjects, a group consisting of 18/55 (32.7%) MCI-a subjects was identified. There was no association between the presence of MCI-a and demographic variables, vascular risk factors, years since the TGA episode, or ApoE genotype. This study demonstrates that TGA appears to be a relatively benign syndrome although objective memory deficits fulfilling MCI-a criteria persist over time, as detected by multidimensional neuropsychological tasks performed at long-term follow-up.

Is mild vascular cognitive impairment reversible? Evidence from a study on the effect of carotid endarterectomy.

Mild vascular cognitive impairment (mVCI) is a broader term that is intended to detect cognitive loss before the development of dementia. The identification of preventable risk factors as well as therapeutic strategies of intervention is still unclear. It has been suggested that carotid endarterectomy (CEA) improves cognitive functions, beyond the well-known preventive effect upon future stroke events. In the present study, we evaluated the beneficial effect of CEA in restoring mVCI. Among a large sample of subjects, who underwent CEA for severe carotid stenosis, two groups were identified according to the absence (CON) or the presence of cognitive impairment (mVCI). A multidimensional neuropsychological and behavioural assessment was performed in the week prior, and at a 3-month follow-up after CEA. The incidence of mVCI in this sample was 38%. Seventy-eight patients completed the follow-up (48 CON, 30 mVCI). Both groups showed a clinical improvement after CEA, although the effect was significantly higher in the mVCI group in regard to verbal memory (short story, p < 0.05), and attention (digit span, p < 0.05) scores. At follow-up, 60% of mVCI subjects were classified as having normal cognitive functions. Index of disease severity and peripheral arterial disease were found to be the predictors of improvement. These findings support that mVCI represents a heterogeneous, in some cases reversible condition. CEA might be considered a therapeutic option to treat and prevent cognitive decline in mVCI patients.

Headache: Prevalence and relationship with office or ambulatory blood pressure in a general population sample (the Vobarno Study).

UNLABELLED: The association of headache and arterial hypertension is still controversial, although headache is usually considered a symptom of hypertension. The aim of this study is to evaluate the prevalence of headache in a general population sample and the relationship with arterial hypertension, as diagnosed by office measurements and ambulatory monitoring of blood pressure (BP). PATIENTS AND METHODS: In the randomized sample of the Vobarno population, 301 subjects (126 males, 175 females, age range 35-50 years) underwent a structured standardized headache questionnaire, office and 24-h ambulatory BP monitoring. RESULTS: Prevalence of lifetime headache and of migraine was greater in females than in males. Office and 24-h BP values did not differ between subjects without headache and subjects with headache. No differences in headache prevalence (58% vs 55%), migraine prevalence (32% vs 28%) and use of analgesic drugs in the presence of headache (82% vs 78%) were observed between hypertensive patients (93.5% newly diagnosed, 6.5% treated) and normotensive subjects. CONCLUSIONS: In a general population sample, hypertension (diagnosed by office and/or 24-h BP) is not associated with headache.