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Background and purpose: The patterns of long-term risk of SARS-CoV-2 infection, hospitalization for COVID-19, and related death are uncertain in people with Parkinson disease (PD) or parkinsonism (PS). The aim of the study was to quantify these risks compared to a control population cohort, during the period March 2020–May 2021, in Bologna, Northern Italy. Methods: ParkLink Bologna cohort (759 PD, 192 PS) and controls (9226) anonymously matched (ratio=1:10) for sex, age, district, and comorbidity were included. Data were analysed in the whole period and in the two different pandemic waves (March–May 2020 and October 2020–May 2021). Results: Adjusted hazard ratio of SARS-CoV-2 infection was 1.3 (95% confidence interval [CI] = 1.04–1.7) in PD and 1.9 (95% CI=1.3–2.8) in PS compared to the controls. The trend was detected in both the pandemic waves. Adjusted hazard ratio of hospitalization for COVID-19 was 1.1 (95% CI=0.8–1.7) in PD and 1.8 (95% CI=0.97–3.1) in PS. A higher risk of hospital admission was detected in PS only in the first wave. The 30-day mortality risk after hospitalization was higher (p= 0.048) in PS (58%) than in PD (19%) and controls (26%). Conclusions: Compared with controls, after adjustment for key covariates, people with PD and PS showed a higher risk of SARS-CoV-2 infection throughout the first 15 months of the pandemic. COVID-19 hospitalization risk was increased only in people with PS and only during the first wave. This group of patients was burdened by a very high risk of death after infection and hospitalization.

Background The differential diagnosis between multiple system atrophy parkinsonism type (MSA-P) and Parkinson's disease with orthostatic hypotension (PD+OH) is difficult because the 2 diseases have a similar clinical picture. The aim of this study is to distinguish MSA-P from PD+OH by immunostaining for abnormal phosphorylated α-synuclein at serine 129 (p-syn) in cutaneous nerves. Method We recruited 50 patients with parkinsonism and chronic orthostatic hypotension: 25 patients fulfilled the diagnostic criteria for MSA-P and 25 patients for PD+OH. The patients underwent a skin biopsy from the cervical area, thigh, and leg to analyze somatic and autonomic skin innervation and p-syn in skin nerves. Results Intraneural p-syn positivity was found in 72% of patients with MSA-P, mainly in distal skin sites. More important, p-syn deposits in MSA-P differed from PD+OH because they were mainly found in somatic fibers of subepidermal plexi, whereas scant autonomic fiber involvement was found in only 3 patients. All patients with PD+OH displayed widely distributed p-syn deposits in the autonomic skin fibers of proximal and distal skin sites, whereas somatic fibers were affected only slightly in 4 patients with PD+OH. Skin innervation mirrored p-syn deposits because somatic innervation was mainly reduced in MSA-P. Sympathetic innervation was damaged in PD+OH but fairly preserved in MSA-P. Conclusions The p-syn in cutaneous nerves allows the differentiation of MSA-P from PD+OH; MSA-P mainly shows somatic fiber involvement with relatively preserved autonomic innervation; and by contrast, PD+OH displays prevalent abnormal p-syn deposits and denervation in autonomic postganglionic nerves. © 2020 International Parkinson and Movement Disorder Society.

Objective: Data on COVID-19 outcomes in persons with epilepsy (PWE) are scarce and inconclusive. We aimed to study the risk of hospitalization and death for COVID-19 in a large cohort of PWE from March 1, 2020 to October 31, 2021. Methods: The historical cohort design (EpiLink Bologna) compared adult PWE grouped into people with focal epilepsy (PFE), idiopathic generalized epilepsy (PIGE), and developmental and/or epileptic encephalopathy (PDEE), and a population cohort matched (ratio 1:10) for age, sex, residence, and comorbidity (assessed with the multisource comorbidity score), living in the local health trust of Bologna (approximately 800 000 residents). Clinical data were linked to health administrative data. Results: In both cohorts (EpiLink: n=1575 subjects, 1128 PFE, 267 PIGE, 148 PDEE, 32 other; controls: n=15 326 subjects), 52% were females, and the mean age was 50 years (SD=18). Hospital admissions for COVID-19 in the whole period were 49 (3.1%) in PWE and 225 (1.5%) in controls. The adjusted hazard ratio (aHR) in PWE was 1.9 (95% confidence interval [CI] = 1.4–2.7). The subgroups at higher risk were PFE (aHR=1.9, 95% CI=1.3–2.8) and PDEE (aHR=3.9, 95% CI=1.7–8.7), whereas PIGE had a risk comparable to the controls (aHR=1.1, 95% CI =.3–3.5). Stratified analyses of the two main epidemic waves (March–May 2020, October 2020–May 2021) disclosed a higher risk of COVID-19-related hospitalization during the first epidemic wave (March–May 2020; aHR=3.8, 95% CI=2.2–6.7). Polytherapy with antiseizure medications contributed to a higher risk of hospital admission. Thirty-day risk of death after hospitalization was 14% in both PWE and controls. Significance: During the first 20 months since the outbreak of COVID-19 in Bologna, PWE had a doubled risk of COVID-19 hospital admission compared to a matched control population. Conversely, epilepsy did not represent a risk factor for COVID-19-related death.

Narcolepsy type 1 (NT1) is due to selective loss of hypocretin (hcrt)-producing-neurons. Hcrt is a neuropeptide regulating the sleep/wake cycle, as well as feeding behavior. A subset of NT1 patients become overweight/obese, with a dysmetabolic phenotype. We hypothesized that mitochondrial DNA (mtDNA) sequence variation might contribute to the metabolic features in NT1 and we undertook an exploratory survey of mtDNA haplogroups in a cohort of well-characterized patients. We studied 246 NT1 Italian patients, fully defined for their metabolic features, including obesity, hypertension, low HDL, hypertriglyceridemia and hyperglycemia. For haplogroup assignment, the mtDNA control region was sequenced in combination with an assessment of diagnostic markers in the coding region. NT1 patients displayed the same mtDNA haplogroups (H, HV, J, K, T, U) frequency as those reported in the general Italian population. The majority of NT1 patients (64%) were overweight: amongst these, 35% were obese, 48% had low HDL cholesterol levels, and 31% had hypertriglyceridemia. We identified an association between haplogroups J, K and hypertriglyceridemia (P = 0.03, 61.5% and 61.5%, respectively vs. 31.3% of the whole sample) and after correction for age and sex, we observed a reduction of these associations (OR = 3.65, 95%CI = 0.76-17.5, p = 0.106 and 1.73, 0.52-5.69, p = 0.368, respectively). The low HDL level showed a trend for association with haplogroup J (P = 0.09, 83.3% vs. 47.4% of the whole sample) and after correction we observed an OR = 6.73, 95%CI = 0.65-69.9, p = 0.110. Our study provides the first indication that mtDNA haplogroups J and K can modulate metabolic features of NT1 patients, linking mtDNA variation to the dysmetabolic phenotype in NT1.

Background Increasing evidence supports the use of plasma biomarkers of neurodegeneration and neuroinflammation to screen and diagnose patients with dementia. However, confirmatory studies are required to demonstrate their usefulness in the clinical setting. Methods We evaluated plasma and cerebrospinal fluid (CSF) samples from consecutive patients with frontotemporal dementia (FTD) (n = 59), progressive supranuclear palsy (PSP) (n = 31), corticobasal syndrome (CBS) (n = 29), dementia with Lewy bodies (DLB) (n = 49), Alzheimer disease (AD) (n = 97), and suspected non-AD physiopathology (n = 51), as well as plasma samples from 60 healthy controls (HC). We measured neurofilament light chain (NfL), phospho-tau181 (p-tau181), and glial fibrillary acid protein (GFAP) using Simoa (all plasma biomarkers and CSF GFAP), CLEIA (CSF p-tau181), and ELISA (CSF NfL) assays. Additionally, we stratified patients according to the A/T/N classification scheme and the CSF α-synuclein real-time quaking-induced conversion assay (RT-QuIC) results. Results We found good correlations between CSF and plasma biomarkers for NfL (rho = 0.668, p < 0.001) and p-tau181 (rho = 0.619, p < 0.001). Plasma NfL was significantly higher in disease groups than in HC and showed a greater increase in FTD than in AD [44.9 (28.1–68.6) vs. 21.9 (17.0–27.9) pg/ml, p < 0.001]. Conversely, plasma p-tau181 and GFAP levels were significantly higher in AD than in FTD [3.2 (2.4–4.3) vs. 1.1 (0.7–1.6) pg/ml, p < 0.001; 404.7 (279.7–503.0) vs. 198.2 (143.9–316.8) pg/ml, p < 0.001]. GFAP also allowed discriminating disease groups from HC. In the distinction between FTD and AD, plasma p-tau181 showed better accuracy (AUC 0.964) than NfL (AUC 0.791) and GFAP (AUC 0.818). In DLB and CBS, CSF amyloid positive (A+) subjects had higher plasma p-tau181 and GFAP levels than A− individuals. CSF RT-QuIC showed positive α-synuclein seeding activity in 96% DLB and 15% AD patients with no differences in plasma biomarker levels in those stratified by RT-QuIC result. Conclusions In a single-center clinical cohort, we confirm the high diagnostic value of plasma p-tau181 for distinguishing FTD from AD and plasma NfL for discriminating degenerative dementias from HC. Plasma GFAP alone differentiates AD from FTD and neurodegenerative dementias from HC but with lower accuracy than p-tau181 and NfL. In CBS and DLB, plasma p-tau181 and GFAP levels are significantly influenced by beta-amyloid pathology.

ObjectiveTo compare the diagnostic accuracy of ice pack test (IPT) and single-fiber EMG (SF-EMG) in patients with suspected ocular myasthenia (OM) presenting with ptosis.MethodsWe studied consecutive patients referred for the clinical suspicion of OM. Patients underwent IPT and stimulated SF-EMG on the orbicularis oculi muscle. Receiver operating characteristic curve analysis was performed to determine the accuracy of IPT, SF-EMG, and their combination.ResultsWe included 155 patients, 102 with OM and 53 with other diagnosis (OD). The IPT had a sensitivity of 86% (95% confidence interval [CI] 79–93) and a specificity of 79% (95% CI 68–90). SF-EMG showed a sensitivity of 94% (95% CI 89–98) and a specificity of 79% (95% CI 68–90). Overall, IPT and SF-EMG showed discordant results in 30 cases, 16 OM and 14 OD. The combination of IPT and SF-EMG, using the positivity of at least one test for OM diagnosis, increased the sensitivity to 98% (95% CI 95–100), reducing the specificity to 66% (95% CI 53–78), whereas using the positivity of both tests, we obtained a sensitivity of 82% (95% CI 75–90) and a specificity of 92% (95% CI 85–99). The negativity of both tests had a 94% (95% CI 87–100) negative predictive value. Comparison of the areas under the curve showed no differences in the diagnostic accuracy of IPT, SF-EMG, and their combinations.ConclusionsIPT and SF-EMG have similar diagnostic accuracy in patients with OM presenting with ptosis. The negativity of both tests strongly suggests another diagnosis.Classification of evidenceThis study provides Class I evidence that both the IPT and SF-EMG accurately identify patients with OM.

Background Dysautonomic symptoms (DS) are frequent but often underrecognized in multiple sclerosis (MS) patients, despite the relevant impact on quality of life and physical performance. Objectives To assess frequency and characteristics of DS in our MS population compared with healthy controls (HC). To investigate the relationship between DS and disease characteristics (MS subtype, disease duration, Expanded Disability Status Scale (EDSS), clinical and/or radiological activity, disability progression). Patients and methods Cross-sectional study includes 324 MS patients (mean age 44.9 ± 10.7 years; 66% female) and 190 HC (mean age 40.60 ± 12.83 years; 63% female). DS were assessed using the Italian validated version of the Composite Autonomic Symptom Score-31 (COMPASS-31). Possible confounding factors were considered. Results More than 94% of enrolled MS patients reported alterations in ≥ 2 domains of the COMPASS-31 scale (score > 0) and significantly higher COMPASS-31 total and single domain median scores compared with HC, independently from possible confounding factors (orthostatic intolerance: p = 0.001; vasomotor: p = 0.017; secretomotor: p = 0.040; gastrointestinal: p = 0.047; bladder: p p p p p = 0.01; Rho = 0.25, p = 0.030; Rho = 0.28, p p p p = 0.025), gastrointestinal (p = 0.07), and bladder (p Conclusions Our findings confirm that MS-related DS are frequent and tend to increase paralleling disease duration and clinical worsening, reaching the highest clinical impact in progressive subtypes.

IntroductionNeurosurgical education should start during medical school to involve more students, favoring the recruitment of the most prepared and motivated ones and spreading this subject to the future medical generations. Despite multiple investigations, a dedicated educational plan does not exist. This study aims to assess the undergraduates' interests, needs, and perceptions of this subject.Materials and MethodsThe survey was structured to collect demographic data of the participants, and to explore their interest in neurosurgery, their consideration of its importance in medical school, their opinions about the role of this subject in medical education, their needs in this training, and, the usefulness of this subject for their future career.ResultsA total of 156 students participated in the survey. Interest in neurosurgery was shown by 76 (48.7%) participants, however, this subject was also perceived as intimidating by 86 (55.1%). Attending the first 2 years of medical school (p < 0.02), previous interest in neuroscience (p < 0.01), and in a surgical subject (p < 0.01) were the factors associated with a greater interest in this subject. Neurosurgery should be included in all students' education, according to 117 (75.0%) participants and practical operating room training should involve all students, according to 96 (61.5%). The most effective learning methods were considered internship (134, 85.9%), followed by participation in meetings or seminars (113, 72.4%). Online seminars were considered useful by 119 participants (76.3%). Neurosurgery was assessed as a potentially interesting career by 99 students (63.5%), who also considered that it can increase their preparation for other subjects (116, 74.4%).ConclusionsNeurosurgery was positively considered by medicals students, who, however, also perceived it as intimidating and hardly approachable. Demonstration that knowledge of neurosurgical concepts can improve their preparation also in general medical settings and, not only in the field of neuroscience, can be useful to promote their interest toward this subject. A combination of lectures and practical internships is considered an effective learning method, which can be fruitfully associated with new technologies.

BACKGROUND: In many clinical trials endovascular procedures are suggested as the treatment of choice for aneurysmal Subarachnoid Hemorrhage (aSAH) whenever possible. However, in clinical practice this management is often controversial. The aim of this study is to analyze factors involved in this decision. METHODS: Our study included 317 consecutive cases of aSAH between 2010 and 2016, assessing clinical and neuroradiological features to evaluate their role in this choice. RESULTS: In our series coiling was preferred in 119 (37.6%) patients, while 198 (62.4%) were treated surgically. On univariate analysis location of aneurysms (p < 0.001), GCS score on admission (p: 0.105), degree of midline shift (p:0.015), Fisher' score (p: 0.002) and presence of vessels in the aneurysmal neck (p: 0.071) proved the most relevant factors in the choice. Also multivariate analysis confirmed the location and Fisher' grade as influential factors. Conversely, other radiological parameters, such as morphology, aspect and dome-neck ratio, presence of pre-operative vasospasm or hydrocephalus were not associated with this decision. CONCLUSIONS: The decision process in aSAH requires a multidisciplinary team, to singularly evaluate each patient. We found that the location of aneurysms in Vertebro-Basilar circulation, PCoM and ICA, greater GCS score, absence of vessels in the aneurysmal neck, lower midline shift and Fisher' score are factors influencing in choosing coiling. Conversely, morphology, Aspect and Dome-Neck ratio proved not relevant to this decision, due to technological improvement and increasing skills in the endovascular treatment.

PROPAG-AGEING consortium., A prodromal phase of Parkinson’s disease (PD) may precede motor manifestations by decades. PD patients’ siblings are at higher risk for PD, but the prevalence and distribution of prodromal symptoms are unknown. The study objectives were (1) to assess motor and non-motor features estimating prodromal PD probability in PD siblings recruited within the European PROPAG-AGEING project; (2) to compare motor and non-motor symptoms to the well-established DeNoPa cohort. 340 PD siblings from three sites (Bologna, Seville, Kassel/Goettingen) underwent clinical and neurological evaluations of PD markers. The German part of the cohort was compared with German de novo PD patients (dnPDs) and healthy controls (CTRs) from DeNoPa. Fifteen (4.4%) siblings presented with subtle signs of motor impairment, with MDS-UPDRS-III scores not clinically different from CTRs. Symptoms of orthostatic hypotension were present in 47 siblings (13.8%), no different to CTRs (p = 0.072). No differences were found for olfaction and overall cognition; German-siblings performed worse than CTRs in visuospatial-executive and language tasks. 3/147 siblings had video-polysomnography-confirmed REM sleep behavior disorder (RBD), none was positive on the RBD Screening Questionnaire. 173/300 siblings had, This project has received funding from the European Union’s Horizon 2020 research and innovation program Propag‐Ageing under grant agreement no. 634821.

Pediatric type 1 narcolepsy (NT1) is often associated with overweight and obesity. Sodium oxybate (SO), approved for the treatment of narcolepsy with cataplexy from the age of 7 years old in the United States, has been associated with weight loss, although longitudinal pediatric studies are lacking. We report a retrospective cohort of 129 consecutive patients with a 4-year follow-up, to analyze the impact of different pharmacological treatments on body mass index (BMI) z-score. At baseline, the prevalence of obesity and overweight was 26.4% (34/129) and 29.5% (38/129), respectively. Patients were divided into three groups: children treated with SO alone (group 1), with SO-combined therapy (group 2), and without SO (group 3). At the end of the first year of follow-up, group 1 and group 2 showed a significant BMI z-score reduction compared to baseline: from 1.2 ± 1.1 to 0.4 ± 1.4 for group 1 (p < 0.001), and from 1.4 ± 1.1 to 1 ± 1.3 for group 2 (p = 0.002), independently from baseline clinical features. In the second year, only group 2 experienced a further and significant BMI z-score decrease (from 1.0 ± 1.2 to 0.6 ± 1.2, p = 0.037). No further significant BMI z-score changes were observed in SO-treated patients in the following years. Instead, children treated without SO developed a significant weight increase between the second and third year of therapy (BMI z-score from 0.3 ± 0.9 to 0.5 ± 0.9). In conclusion, SO treatment in pediatric NT1 is associated with a favorable weight reduction in the first year of treatment.

Introduction We aimed to create standardized protocol for language examination in patients who underwent video-EEG recording and assessed its efficacy in the characterization of ictal language impairment, its ability to differentiate this from impaired awareness, and interobserver reliability in clinical practice. Methods From our database of video-EEG recordings, we selected a representative sample of 63 focal seizures with presumed language impairment. A multidisciplinary team of epileptologists, EEG technicians, and speech therapists analyzed the selected videos to highlight the critical issues of ordinary ictal language evaluation. We subsequently followed a multi-step process to develop the protocol and assess its interobserver reliability. Results A protocol based on seven tests in hierarchical succession was created, summed up in the acronym CA-P-S C-A-R-E (Closed Answers, Pro-speak question, Simple orders, Common object denomination, Audio repetition, Reading, Evoke). Following its preliminary administration for 5 months, we assessed the inter-observer reliability of 16 healthcare professionals in distinguishing between language impairment and impaired awareness among a sample of 10 seizures, finding a substantial agreement (kappa 0.61). Conclusion The proposed protocol, made of simple and easy to memorize tests, is an effective tool that evaluates multiple domains beyond language. Its use could help to recognize ictal aphasia effectively and differentiate it from impaired awareness, minimizing inter-examiner variability.

Background The COVID-19 outbreak is severely affecting the overall mental health with unknown psychological consequences. Although a strong psychological impact is possible, scant evidence is available to date. Past studies have shown that resilience decreases the negative effects of stress. This study aimed to examine depression, anxiety, and stress among the Italian general population during the phase characterized by lockdown, and to investigate the role of resilience as a potential predictor. Methods A total sample of 6,314 Italian people participated in this study. Participants were recruited between March 29 and May 04 2020 through an online survey. The Depression Anxiety Stress Scales-21 (DASS-21) and the Resilience Scale (RS) were administered. Demographic data and lockdown related information were also collected. A correlational analysis was carried out to examine relationships between psychopathological domains and resilience. Three hierarchical regression analyses were conducted using the depression, anxiety, and stress as dependent variables and the resilience as independent variable controlling for age, gender, and education. COVID-19 specific variables were also included in the three regression analyses. A further exploratory analysis was carried out to examine which aspects of resilience predict depression, anxiety, and stress. Results The prevalence of moderate to extremely severe symptoms among participants was 32% for depression, 24.4% for anxiety, and 31.7% for stress. The sample mean scores on depression, anxiety, and stress were higher than the normal scores reported in the literature. Results of correlational analysis showed that resilience factors, such as meaningfulness, self-reliance, existential aloneness, and equanimity, are inversely associated with depression, anxiety, and stress. Results of regression analyses indicated that resilience was statically significant in predicting depression, anxiety, and stress. Geographic area of residence and infected acquaintances were also significant predictors. Regarding the resilience factors, results revealed that meaningfulness, perseverance, and equanimity were statistically significant in predicting all the DASS-21 scales. Conclusion About a third of respondents reported moderate to extremely severe depression, anxiety, and stress. The present study suggests that psychological resilience may independently contribute to low emotional distress and psychological ill-being. These findings can help explain the variability of individual responses during the COVID-19 outbreak.

ObjectiveTo compare the diagnostic accuracy and the prognostic value of blood and cerebrospinal fluid (CSF) tests across prion disease subtypes.MethodsWe used a single-molecule immunoassay to measure tau and neurofilament light chain (NfL) protein levels in the plasma and assessed CSF total(t)-tau, NfL and protein 14-3-3 levels in patients with prion disease (n=336), non-prion rapidly progressive dementias (n=106) and non-neurodegenerative controls (n=37). We then evaluated each plasma and CSF marker for diagnosis and their association with survival, taking into account the disease subtype, which is a strong independent prognostic factor in prion disease.ResultsPlasma tau and NfL concentrations were higher in patients with prion disease than in non-neurodegenerative controls and non-prion rapidly progressive dementias. Plasma tau showed higher diagnostic value than plasma NfL, but a lower accuracy than the CSF proteins t-tau and 14-3-3. In the whole prion cohort, both plasma (tau and NfL) and CSF (t-tau, 14-3-3 and NfL) markers were significantly associated with survival and showed similar prognostic values. However, the intrasubtype analysis revealed that only CSF t-tau in sporadic Creutzfeldt-Jakob disease (sCJD) MM(V)1, plasma tau and CSF t-tau in sCJD VV2, and plasma NfL in slowly progressive prion diseases were significantly associated with survival after accounting for covariates.ConclusionsPlasma markers have lower diagnostic accuracy than CSF biomarkers. Plasma tau and NfL and CSF t-tau are significantly associated with survival in prion disease in a subtype-specific manner and can be used to improve clinical trial stratification and clinical care.

Objective: Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy characterized by seizures occurring mostly during sleep, ranging from brief seizures with paroxysmal arousals (SPAs) to hyperkinetic seizures and ambulatory behaviors. SPAs are brief and stereotypic seizures representing the beginning of a major seizure. Distinguishing SPAs from disorders of arousal (DOAs) and their briefest episodes called simple arousal movements (SAMs) is difficult. We performed a characterization of SPAs and SAMs to identify video-polysomnographic (VPSG) features that can contribute to the diagnosis of SHE or DOA. Methods: Fifteen SHE, 30 DOA adult patients, and 15 healthy subjects underwent full-night VPSG. Two neurologist experts in sleep disorders and epilepsy classified all the sleep-related movements and episodes recorded. For each SPAs and SAMs, sleep stage at onset, duration, limb involvement, progression, and semiology have been identified. Results: A total of 121 SPAs were recorded, emerging mostly during stage 1-2 non–rapid eye movement (NREM) sleep (median duration: 5seconds). At the beginning, the SPAs motor pattern was hyperkinetic in 78 cases (64%), involving more than three non-contiguous or all body parts. The standard was a constant progression of movements during SPAs without any motor arrests. In DOA patients a total of 140 SAMs were recorded (median duration: 12seconds) mostly emerging during stage 3 NREM sleep. In SAMs, we did not observe any tonic/dystonic or hypermotor patterns or stereotypy; motor arrest was present over the course of about half of the episodes. In comparison with both DOA and healthy subjects, SHE patients showed a higher number of sleep-related movements per night and a reduction of sleep efficiency. Significance: SPAs and SAMs present different semiological and clinical features. Their recognition could be useful to drive the diagnosis when major episodes are not recorded during VPSG in patients with a clear clinical history of SHE or DOA.

Background In neurodegenerative dementias (NDs) such as prion disease, Alzheimer’s disease (AD), and frontotemporal lobar degeneration (FTLD), protein misfolding leads to the tissue deposition of protein aggregates which, in turn, trigger neuroinflammation and neurodegeneration. Cerebrospinal fluid (CSF) biomarkers have the potential to reflect different aspects of these phenomena across distinct clinicopathological subtypes and disease stages. Methods We investigated CSF glial markers, namely chitotriosidase 1 (CHIT1), chitinase-3-like protein 1 (YKL-40) and glial fibrillary acidic protein (GFAP) in prion disease subtypes (n = 101), AD (n = 40), clinicopathological subgroups of FTLD (n = 72), and controls (n = 40) using validated, commercially available ELISA assays. We explored glial biomarker levels’ associations with disease variables and neurodegenerative CSF biomarkers and evaluated their diagnostic accuracy. The genotype of the CHIT1 rs3831317 polymorphic site was also analyzed. Results Each ND group showed increased levels of CHIT1, YKL-40, and GFAP compared to controls with a difference between prion disease and AD or FTLD limited to YKL-40, which showed higher values in the former group. CHIT1 levels were reduced in both heterozygotes and homozygotes for the CHIT1 24-bp duplication (rs3831317) in FTLD and controls, but this effect was less significant in AD and prion disease. After stratification according to molecular subgroups, we demonstrated (i) an upregulation of all glial markers in Creutzfeldt-Jakob disease VV2 compared to other disease subtypes, (ii) a difference in CHIT1 levels between FTLD with TAU and TDP43 pathology, and (iii) a marked increase of YKL-40 in FTLD with amyotrophic lateral sclerosis (ALS) in comparison with FTLD without ALS. In prion disease, glial markers correlated with disease stage and were already elevated in one pre-symptomatic case of Gerstmann-Sträussler-Scheinker disease. Regarding the diagnostic value, YKL-40 was the only glial marker that showed a moderate accuracy in the distinction between controls and NDs. Conclusions NDs share a CSF profile characterized by increased levels of CSF CHIT1, YKL-40, and GFAP, which likely reflects a common neuroinflammatory response to protein misfolding and aggregation. CSF glial markers of neuroinflammation demonstrate limited diagnostic value but have some potential for monitoring the clinical and, possibly, preclinical phases of NDs.

Background and purpose Receiving clear, complete and up-to-date information and having a satisfying relationship with the health professional (HP) are of primary importance for MS patients. Healthcare organization plays a key role in promoting an effective relationship and communication between patients and HPs. The present study aims to explore which care organization and service characteristics provided by Italian MS centres best predict patients’ satisfaction with healthcare. Methods Eighty-one centres and 707 patients (502 women, mean age 40.5 years, SD 10.2; mean education 12.2 years, SD 3.6; time since diagnosis 5.9 years, SD 1.5) were included in the analysis. The care organization and service provided by each centre were evaluated in comparison with the National Institute for Health and Care Excellence (NICE) guidelines on management of MS. Patients’ satisfaction with care was measured using the patient self-assessed questionnaire ‘Comunicazione medico-paziente nella Sclerosi Multipla, revised’ section 2 (COSM-R section 2). Results The clinical characteristics of patients significantly affected their satisfaction. A multivariate regression model showed that higher patients’ satisfaction (COSM-R score) was inversely associated with hospital size (number of patients under care) (β = −0.21, 95% confidence interval −0.35; −0.07) and directly associated with psychological interventions (β = 2.44, 95% confidence interval 0.29; 4.59). Conclusions Multiple sclerosis patients from larger hospitals are less satisfied with the information received and the relationship with HPs. Building an individualized relationship between patients and HPs and tailoring the communication of information improve patients’ satisfaction. Such a goal is probably less likely to be accomplished in larger centres with many incoming patients. Moreover, when the centres also provide structured psychological interventions, the patients are more satisfied.

Current evidence indicating a role of the human prion protein (PrP) in amyloid-beta (Aβ) formation or a synergistic effect between Aβ and prion pathology remains controversial. Conflicting results also concern the frequency of the association between the two protein misfolding disorders and the issue of whether the apolipoprotein E gene (APOE) and the prion protein gene (PRNP), the major modifiers of Aβ- and PrP-related pathologies, also have a pathogenic role in other proteinopathies, including tau neurofibrillary degeneration. Here, we thoroughly characterized the Alzheimer’s disease/primary age-related tauopathy (AD/PART) spectrum in a series of 450 cases with definite sporadic or genetic Creutzfeldt-Jakob disease (CJD). Moreover, we analyzed: (i) the effect of variables known to affect CJD pathogenesis and the co-occurring Aβ- and tau-related pathologies; (II) the influence of APOE genotype on CJD pathology, and (III) the effect of AD/PART co-pathology on the clinical CJD phenotype. AD/PART characterized 74% of CJD brains, with 53.3% and 8.2% showing low or intermediate-high levels of AD pathology, and 12.4 and 11.8% definite or possible PART. There was no significant correlation between variables affecting CJD (i.e., disease subtype, prion strain, PRNP genotype) and those defining the AD/PART spectrum (i.e., ABC score, Thal phase, prevalence of CAA and Braak stage), and no difference in the distribution of APOE ε4 and ε2 genotypes among CJD subtypes. Moreover, AD/PART co-pathology did not significantly affect the clinical presentation of typical CJD, except for a tendency to increase the frequency of cognitive symptoms. Altogether, the present results seem to exclude an increased prevalence AD/PART co-pathology in sporadic and genetic CJD, and indicate that largely independent pathogenic mechanisms drive AD/PART and CJD pathology even when they coexist in the same brain. Electronic supplementary material The online version of this article (10.1186/s40478-019-0706-6) contains supplementary material, which is available to authorized users.

The angiogenic pathway plays a pivotal role in tumor growth, invasiveness and metastasis. The most important actors in the angiogenic pathway are VEGFA and its receptors VEGFR1, 2 and 3. These genes are polymorphic, and the presence of single nucleotide polymorphisms may result in angiogenic deregulation. Herein, we hypothesized that germline variants may affect sunitinib efficacy (TTP and OS) and/or toxicity. Therefore, we investigated 19 polymorphisms, in four genes, in 54 GIST patients, treated with second-line sunitinib and 147 healthy controls. Through a multiple candidate gene approach, we also investigated, for the first time, any possible significant associations with GIST susceptibility and clinical pathological features. The most important result shows two associations between polymorphisms in VEGFR3 rs6877011 (CC vs. CG, OR 9.7, 95% CI 3.31-28.4; P < 0.001) and rs7709359 (AA+AG vs. GG, OR 5.01, 95% CI 1.33-18.8; P = 0.017) and TTP. Interestingly, the association between VEGFR3 rs6877011 and TTP maintained the significance after applying the Bonferroni correction for multiple testing (P = 0.017). We also highlighted the association with sunitinib-related toxicity; in particular, VEGFA polymorphism rs3025039 (CT+TT vs. CC, OR 15.3, 95% CI 2.2-102.1; P = 0.005) is associated with severe toxicity, with the presence of the variant T allele associated with a grade a 3 AE. Because of the small sample size and large number of tests performed, we cannot ignore the possibility that some associations have been retrieved by chance. However, the influence of VEGF polymorphisms in angiogenesis is a hypothesis worthy of exploration in cellular models and confirmation in a sizeable cohort of patients.

Objective: Pituitary macroadenomas (PAs) are usually defined as benign intracranial tumors. However, they may present local aggressive course. High Ki67 labelling index (LI) values have been related to an aggressive tumor behavior. A recent clinicopathological classification of PA based on local invasiveness and proliferation indexes, divided them in groups with different prognosis. We evaluated the utility of conventional MRI (cMRI) and diffusion-weighted imaging (DWI), in predicting the Ki67- LI according the clinicopathological classification. Methods: 17 patients (12 M and 5 F) who underwent surgical removal of a PA were studied. cMRI features, quantification of T1W and T2W signal intensity, degree of contrast uptake (enhancement ratio, ER) and apparent diffusion coefficient (ADC) values were evaluated by using a 3 T scan. Statistics included Mann–Whitney test, Spearman’s test, and receiver operating characteristic analysis. A value of p ≤ 0.05 was considered significant for all the tests. Results: Negative correlations were observed between Ki-67 LI, ADCm (ρ = - 0.67, p value = 0.005) and ER values (ρ = −0.62; p = 0.008). ER values were significantly lower in the proliferative PA group (p = 0.028; p = 0.017). ADCm showed sensitivity and specificity of 90 and 85% respectively into predict Ki67-LI value. A value of ADCm ≤0, 711 x 10–6 mm2 emerged as a cut-off of a value of Ki67-LI ≥ 3%. Conclusion: Adding quantitative measures of ADC values to cMRI could be used routinely as a non-invasive marker of specific predictive biomarker of the proliferative activity of PA. Advances in knowledge: Routinely use of DWI on diagnostic work-up of pituitary adenomas may help in establish the likely biological aggressive lesions.

The early detection of colorectal cancer (CRC) can significantly improve the prognosis of affected patients. The loss of genomic stability and the resulting gene alteration play an important role in the molecular pathological steps that occur early in tumorigenesis of CRC. Thus, the identification of non-invasive biomarkers, whose function may provide useful insights into critical early events in the CRC process, is of great interest. In this regard, micronucleus (MN) frequency in peripheral blood lymphocytes (PBL) has become one of the most established biomarkers for studying DNA damage in the human population. This study investigated the MN frequency in the PBL of 82 subjects (30 females and 52 males; aged 50-70 years) who were participating in a screening programme for CRC prevention. All 82 patients were positive in fecal occult blood tests and they were subsequently classified, according to colonoscopy and histological findings, as patients with CRC, patients with colon polyps or subjects without intestinal lesion, referred to as study controls. This study also examined the relationship between the plasma clastogenic activity and the frequency of micronuclei of the study population. The MN frequency was significantly higher in CRC patients than in both colon polyp patients (16.82 ± 6.56 versus 12.23 ± 1.88; P = 0.002) and controls (16.82 ± 6.56 versus 8.00 ± 1.77; P < 0.001). An increased MN frequency was detected in the lymphocytes of the polyp group in comparison to the control group, although this was lower than that observed in CRC patients (12.23 ± 1.88 versus 8.00 ± 1.77; P < 0.001). In the overall study population, the increase of MN frequency, which was observed in the lymphocytes of the subjects involved, was significantly associated with the clastogenic activity detected in their plasma (r = 0.594, P < 0.001). Overall, the results suggest that the MN test can become a promising biomarker for the early detection of CRC.

BACKGROUND: The outcomes of patients admitted to a respiratory ICU (RICU) have been evaluated in the past, but no study has considered the influence of location prior to RICU admission. METHODS: We analyzed prospectively collected data from 326 consecutive patients admitted to a 7-bed RICU. The primary end points were survival and severity of morbidity-related complications, evaluated according to the patient's location prior to RICU admission. Three admission pathways were considered: step-down for patients transferred from the ICUs of our hospital; step-up for patients coming from our respiratory wards or other medical wards; and directly for patients coming from the emergency department. The secondary end point was the potential influence of several risk factors for morbidity and mortality. RESULTS: Of the 326 subjects, 92 (28%) died. Overall, subjects admitted in a step-up process had a significantly higher mortality ( P < .001) than subjects in the other groups. The mortality rate was 64% for subjects admitted from respiratory ward, 43% for those from medical wards, and 18% for subjects from both ICU and emergency department (respiratory ward vs medical ward P = .04, respiratory ward vs emergency department P < .001, respiratory ward vs ICU P < .001, medical ward vs emergency department P < .001, and medical ward vs ICU P < .001). Subjects admitted from a respiratory ward had a lower albumin level, and Simplified Acute Physiology Score II was significantly higher in subjects following a step-up admission. About 30% of the subjects admitted from a respiratory ward received noninvasive ventilation as a “ceiling treatment.” The highest odds ratios related to survival were subject location prior to RICU admission and female sex. Lack of use of noninvasive ventilation, younger age, female sex, higher albumin level, lower Simplified Acute Physiology Score II, higher Barthel score, and absence of chronic heart failure were also statistically associated with a lower risk of death. CONCLUSIONS: The pathway of admission to a RICU is a determinant of outcome. Patients following a step-up pattern are more likely to die. Other major determinants of survival are age, nutritional status and female sex.