Publications by authors named "Manuela Tondelli"

26 Publications

  • Page 1 of 1

Anosognosia in Early- and Late-Onset Dementia and Its Association With Neuropsychiatric Symptoms.

Front Psychiatry 2021 13;12:658934. Epub 2021 May 13.

Department of Biomedical, Metabolic, and Neural Science, University of Modena and Reggio Emilia, Modena, Italy.

The symptom anosognosia or unawareness of disease in dementia has mainly been studied in patients with late-onset dementia (LOD, ≥65 years), whereas little is known on whether it is also present in patients with early-onset dementia (EOD, <65 years). We aimed at investigating differences in anosognosia between LOD and EOD, by also studying its association with different clinical variants of EOD and the presence of neuropsychiatric symptoms. A total of 148 patients, 91 EOD and 57 LOD, were recruited and underwent extended clinical assessment and caregiver interview that included questionnaires aimed at measuring anosognosia and neuropsychiatric symptoms. Differences in anosognosia between EOD and LOD and between subgroups with different clinical variants were investigated, as well as correlation between anosognosia and neuropsychiatric symptoms. A regression analysis was applied to explore the association between anosognosia and development of neuropsychiatric symptoms during disease progression. Median levels of anosognosia were not significantly different between EOD and LOD. Anosognosia increased overtime with disease progression and was higher in frontotemporal dementia patients or, more precisely, in frontotemporal dementia and Alzheimer's disease variants associated with involvement of the frontal lobes. Higher levels of early anosognosia were associated with higher frequency and severity of subsequent neuropsychiatric symptoms, in particular apathy, later in the course of the disease. Anosognosia is a frequent symptom of EOD, occurring in 94.5% of all-cause EOD, and it is associated with higher risk of developing neuropsychiatric symptoms during disease progression. Recognising anosognosia may be helpful for clinicians and families to reduce diagnostic delay and improve disease managment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2021.658934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155545PMC
May 2021

Platelet Function Monitoring Performed after Carotid Stenting during Endovascular Stroke Treatment Predicts Outcome.

J Stroke Cerebrovasc Dis 2021 Jul 5;30(7):105800. Epub 2021 May 5.

Stroke Unit, Neurology Unit, Department of Neuroscience, Ospedale Civile, Azienda Ospedaliera Universitaria di Modena, Via Giardini 1355, Modena, Emilia Romagna 41126, Italy. Electronic address:

Objectives: Many studies showed that platelet reactivity testing can predict ischemic events after carotid stenting or ischemic stroke. The aim of our study was to assess the role of early platelet function monitoring in predicting 90-days functional outcome, stent thrombosis and hemorrhagic transformation in patients with ischemic stroke treated with endovascular procedures requiring emergent extracranial stenting.

Materials And Methods: We performed a retrospective study on consecutive patients with acute anterior circulation stroke admitted to our hospital between January 2015 and March 2020, in whom platelet reactivity testing was performed within 10 days from stenting. Patients were divided according to validated cutoffs in acetylsalicylic acid and Clopidogrel responders and not responders. Group comparison and regression analyses were performed to identify differences between groups and outcome predictors.

Results: We included in the final analysis 54 patients. Acetylsalicylic acid resistance was an independent predictor of poor 90 days outcome (OR for modified Rankin scale (mRS) ≤ 2: 0.10 95% CI: 0.02 - 0.69) whereas Clopidogrel resistance was an independent predictor of good outcome (OR for mRS ≤ 2: 7.09 95%CI: 1.33 - 37.72). Acetylsalicylic acid resistance was also associated with increased 90-days mortality (OR: 18.42; 95% CI: 1.67 - 203.14).

Conclusion: We found a significant association between resistance to acetylsalicylic acid and poor 90-days functional outcome and between resistance to Clopidogrel and good 90-days functional outcome. If confirmed, our results might improve pharmacological management after acute carotid stenting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105800DOI Listing
July 2021

Olfactory function and viral recovery in COVID-19.

Brain Behav 2021 03 19;11(3):e02006. Epub 2021 Jan 19.

Neurology Unit, OCB Hospital, Azienda Ospedaliera-Universitaria, Modena, Italy.

Background: Olfactory and taste disorders were reported in up to 30%-80% of COVID-19 patients. The purpose of our study was to objectively assess smell impairment in COVID-19 patients and to correlate olfactory function with viral recovery.

Methods: Between 15 and 30 April 2020, hospitalized patients with confirmed SARS-CoV-2 infection underwent an objective assessment of olfactory function with the Smell Identification subtest of the Sniffin' Sticks Test (SI-SST). Association between viral recovery and SI-SST performance was evaluated.

Results: 51 patients were enrolled (49% males, mean age 66.2 ± 14.6 years). At the time of test administration, 45% were clinically recovered and 39% were virus-free. Objective hyposmia/anosmia was found in 45% of the patients. Subjective olfactory disorders showed no association with the clinical or viral recovery status of the patients. On the contrary, none of the patients with anosmia and the 5% of hyposmic patients at test had viral recovery. The relative risk for hyposmic patients to be still positive at swab test was 10.323 (95% CI 1.483-71.869, p < .0001). Logistic regression analysis showed an independent and significant correlation between viral clearance and SI-SST scores (OR = 2.242; 95% CI 1.322-3.802, p < .003). ROC curve analysis confirmed that a SI-SST > 10.5 predicts viral clearance with 79% sensitivity and 87% specificity (AUC = 0.883).

Conclusion: Hyposmia is part of COVID-19 symptoms; however, only objectively assessed olfactory function is associated with viral recovery. SI-SST is an easy and safe instrument, and further large multicentric studies should assess its value to predict infection and recovery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/brb3.2006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994699PMC
March 2021

Predictors of Long-Term Outcome of Subthalamic Stimulation in Parkinson Disease.

Ann Neurol 2021 03 9;89(3):587-597. Epub 2021 Jan 9.

Movement Disorders Unit, University Hospital Center, Grenoble Alpes University, Grenoble, France.

Objective: This study was undertaken to identify preoperative predictive factors of long-term motor outcome in a large cohort of consecutive Parkinson disease (PD) patients with bilateral subthalamic nucleus deep brain stimulation (STN-DBS).

Methods: All consecutive PD patients who underwent bilateral STN-DBS at the Grenoble University Hospital (France) from 1993 to 2015 were evaluated before surgery, at 1 year (short-term), and in the long term after surgery. All available demographic variables, neuroimaging data, and clinical characteristics were collected. Preoperative predictors of long-term motor outcome were investigated by performing survival and univariate/multivariate Cox regression analyses. Loss of motor benefit from stimulation in the long term was defined as a reduction of less than 25% in the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III scores compared to the baseline off-medication scores. As a secondary objective, potential predictors of short-term motor outcome after STN-DBS were assessed by performing univariate and multivariate linear regression analyses.

Results: In the long-term analyses (mean follow-up = 8.4 ± 6.26 years, median = 10 years, range = 1-17 years), 138 patients were included. Preoperative higher frontal score and off-medication MDS-UPDRS part III scores predicted a better long-term motor response to stimulation, whereas the presence of vascular changes on neuroimaging predicted a worse motor outcome. In 357 patients with available 1-year follow-up, preoperative levodopa response, tremor dominant phenotype, baseline frontal score, and off-medication MDS-UPDRS part III scores predicted the short-term motor outcome.

Interpretation: Frontal lobe dysfunction, disease severity in the off-medication condition, and the presence of vascular changes on neuroimaging represent the main preoperative clinical predictors of long-term motor STN-DBS effects. ANN NEUROL 2021;89:587-597.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.25994DOI Listing
March 2021

Dietary Habits and Risk of Early-Onset Dementia in an Italian Case-Control Study.

Nutrients 2020 Nov 29;12(12). Epub 2020 Nov 29.

Environmental, Genetic and Nutritional Epidemiology Research Center (CREAGEN), Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.

Risk of early-onset dementia (EOD) might be modified by environmental factors and lifestyles, including diet. The aim of this study is to evaluate the association between dietary habits and EOD risk. We recruited 54 newly-diagnosed EOD patients in Modena (Northern Italy) and 54 caregivers as controls. We investigated dietary habits through a food frequency questionnaire, assessing both food intake and adherence to dietary patterns, namely the Greek-Mediterranean, the Dietary Approaches to Stop Hypertension (DASH), and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets. We modeled the relation between dietary factors and risk using the restricted cubic spline regression analysis. Cereal intake showed a U-shaped relation with EOD, with risk increasing above 350 g/day. A high intake (>400 g/day) of dairy products was also associated with excess risk. Although overall fish and seafood consumption showed no association with EOD risk, we found a U-shaped relation with preserved/tinned fish, and an inverse relation with other fish. Similarly, vegetables (especially leafy) showed a strong inverse association above 100 g/day, as did citrus and dry fruits. Overall, sweet consumption was not associated with EOD risk, while dry cake and ice-cream showed a positive relation and chocolate products an inverse one. For beverages, we found no relation with EOD risk apart from a U-shaped relation for coffee consumption. Concerning dietary patterns, EOD risk linearly decreased with the increasing adherence to the MIND pattern. On the other hand, an inverse association for the Greek-Mediterranean and DASH diets emerged only at very high adherence levels. To the best of our knowledge, this is the first study that explores the association between dietary factors and EOD risk, and suggests that adherence to the MIND dietary pattern may decrease such risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu12123682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760835PMC
November 2020

Environmental Risk Factors for Early-Onset Alzheimer's Dementia and Frontotemporal Dementia: A Case-Control Study in Northern Italy.

Int J Environ Res Public Health 2020 10 29;17(21). Epub 2020 Oct 29.

Neurology Unit, Modena Policlinico-University Hospital, 41126 Modena, Italy.

: Early-onset dementia (EOD) is defined as dementia with symptom onset before 65 years. The role of environmental risk factors in the etiology of EOD is still undefined. We aimed at assessing the role of environmental risk factors in EOD etiology, taking into account its different clinical types. : Using a case-control study, we recruited all EOD cases referred to Modena hospitals from 2016 to 2019, while the referent population was drawn from cases' caregivers. We investigated residential history, occupational and environmental exposures to chemicals and lifestyle behaviors through a self-administered questionnaire. We computed the odds ratios of EOD risk (overall and restricting to the Alzheimer's dementia (AD) or frontotemporal dementia (FTD) diagnoses) and the corresponding 95% confidence intervals using an unconditional logistic regression model. : Fifty-eight EOD patients (19 FTD and 32 AD) and 54 controls agreed to participate. Most of the investigated exposures, such as occupational exposure to aluminum, pesticides, dyes, paints or thinners, were associated with an increased odds ratio (OR) for FTD but not for AD. Long-term use of selenium-containing dietary supplements was associated with increased OR for EOD and, particularly, for FTD. For both EOD forms, smoking and playing football showed an increased odds ratio, while cycling was associated with increased risk only in FTD. Overall sports practice appeared to be a protective factor for both types. : Our results suggest a role of environmental and behavioral risk factors such as some chemical exposures and professional sports in EOD etiology, in particular with reference to FTD. Overall sports practice may be associated with a reduced EOD risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph17217941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663191PMC
October 2020

Epidemiology of early onset dementia and its clinical presentations in the province of Modena, Italy.

Alzheimers Dement 2021 01 11;17(1):81-88. Epub 2020 Sep 11.

Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Università di Modena e Reggio Emilia, Modena, Italy.

Introduction: Patients with early onset dementia (EOD), defined as dementia with symptom onset at age <65, frequently present with atypical syndromes. However, the epidemiology of different EOD presentations, including variants of Alzheimer's disease (AD) and frontotemporal dementia (FTD), has never been investigated all together in a population-based study. Epidemiologic data of all-cause EOD are also scarce.

Methods: We investigated EOD epidemiology by identifying patients with EOD seen in the extended network of dementia services of the Modena province, Northern Italy (≈700,000 inhabitants) from 2006 to 2019.

Results: In the population age 30 to 64, incidence was 13.2 per 100,000/year, based on 160 new cases from January 2016 to June 2019, and prevalence 74.3 per 100,000 on June 30, 2019. The most frequent phenotypes were the amnestic variant of AD and behavioral variant of FTD.

Discussion: EOD affects a significant number of people. Amnestic AD is the most frequent clinical presentation in this understudied segment of the dementia population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alz.12177DOI Listing
January 2021

Valproate Use Is Associated With Posterior Cortical Thinning and Ventricular Enlargement in Epilepsy Patients.

Front Neurol 2020 2;11:622. Epub 2020 Jul 2.

Neurology Unit, OCSAE Hospital, AOU Modena, Modena, Italy.

Valproate is a drug widely used to treat epilepsy, bipolar disorder, and occasionally to prevent migraine headache. Despite its clinical efficacy, prenatal exposure to valproate is associated with neurodevelopmental impairments and its use in children and adults was associated with rare cases of reversible brain atrophy and ventricular enlargement. To determine whether valproate use is related with structural brain changes we examined through a cross-sectional study cortical and subcortical structures in a group of 152 people with epilepsy and a normal clinical brain MRI. Patients were grouped into those currently using valproate ( = 54), those taking drugs other than valproate ( = 47), and drug-naïve patients ( = 51) at the time of MRI, irrespectively of their epilepsy syndrome. Cortical thickness and subcortical volumes were analyzed using Freesurfer, version 5.0. Subjects exposed to valproate (either in mono- or polytherapy) showed reduced cortical thickness in the occipital lobe, more precisely in the cuneus bilaterally, in the left lingual gyrus, and in left and right pericalcarine gyri when compared to patients who used other antiepileptic drugs, to drug-naïve epilepsy patients, and to healthy controls. Considering the subgroup of patients using valproate monotherapy ( = 25), both comparisons with healthy controls and drug-naïve groups confirmed occipital lobe cortical thickness reduction. Moreover, patients using valproate showed increased left and right lateral ventricle volume compared to all other groups. Notably, subjects who were non-valproate users at the time of MRI, but who had valproate exposure in the past ( = 27) did not show these cortical or subcortical brain changes. Cortical changes in the posterior cortex, particularly in the visual cortex, and ventricular enlargement, are present in people with epilepsy using valproate, independently from clinical and demographical variables. These findings are relevant both for the efficacy and adverse events profile of valproate use in people with epilepsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2020.00622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351506PMC
July 2020

The ENIGMA-Epilepsy working group: Mapping disease from large data sets.

Hum Brain Mapp 2020 May 29. Epub 2020 May 29.

Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico.

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller-scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well-established by the ENIGMA Consortium, ENIGMA-Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event-based modeling analysis. We explore age of onset- and duration-related features, as well as phenomena-specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA-Epilepsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.25037DOI Listing
May 2020

Selenium and selenium species in the etiology of Alzheimer's dementia: The potential for bias of the case-control study design.

J Trace Elem Med Biol 2019 May 7;53:154-162. Epub 2019 Mar 7.

Center for Neurosciences and Neurotechnology, Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, 287 Via Campi, Modena 41125, Italy; Department of Neurosciences, Azienda Ospedaliero-Universitaria di Modena, 71 Via del Pozzo, Modena 41124, Italy.

Several human studies imply that the trace element selenium and its species may influence the onset of neurological disease, including Alzheimer's dementia (AD). Nevertheless, the literature is conflicting, with reported associations between exposure and risk in opposite direction, possibly due to biases in exposure assessment. After conducting a cohort study that detected an excess AD risk associated with higher levels of inorganic-hexavalent selenium in subjects with mild cognitive impairment (MCI), we investigated the relation between selenium and AD using a case-control study design. We determined cerebrospinal fluid levels of selenium species in 56 MCI participants already included in the cohort study, considered as referents, and in 33 patients with established AD. AD risk was inversely correlated with inorganic selenium species and with the organic form bound to selenoprotein P. Selenium bound to other organo-selenium species was positively correlated with AD risk, suggesting compensatory selenoprotein upregulation following increased oxidative stress. The finding of an increased AD risk associated with inorganic-hexavalent selenium from the cohort study was not replicated. This case-control study yielded entirely different results than those generated by a cohort study with a partially overlapping participant population, suggesting that case-control design does not allow to reliably assess the role of selenium exposure in AD etiology. This inability appears to be due to exposure misclassification, falsely indicating an etiologic role of selenium deficiency likely due to reverse causation, and involving most selenium species. The case-control design may instead lend insights into the pathologic process underlying disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtemb.2019.03.002DOI Listing
May 2019

Neural Correlates of Anosognosia in Alzheimer's Disease and Mild Cognitive Impairment: A Multi-Method Assessment.

Front Behav Neurosci 2018 17;12:100. Epub 2018 May 17.

Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Università di Modena e Reggio Emilia, Modena, Italy.

Patients with Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) may present anosognosia for their cognitive deficits. Three different methods have been usually used to measure anosognosia in patients with AD and MCI, but no studies have established if they share similar neuroanatomical correlates. The purpose of this study was to investigate if anosognosia scores obtained with the three most commonly used methods to assess anosognosia relate to focal atrophy in AD and MCI patients, in order to improve understanding of the neural basis of anosognosia in dementia. Anosognosia was evaluated in 27 patients (15 MCI and 12 AD) through clinical rating (Clinical Insight Rating Scale, CIRS), patient-informant discrepancy (Anosognosia Questionnaire Dementia, AQ-D), and performance discrepancy on different cognitive domains (self-appraisal discrepancies, SADs). Voxel-based morphometry correlational analyses were performed on magnetic resonance imaging (MRI) data with each anosognosia score. Increasing anosognosia on any anosognosia measurement (CIRS, AQ-D, SADs) was associated with increasing gray matter atrophy in the medial temporal lobe including the right hippocampus. Our results support a unitary mechanism of anosognosia in AD and MCI, in which medial temporal lobes play a key role, irrespectively of the assessment method used. This is in accordance with models suggesting that anosognosia in AD is primarily caused by a decline in mnemonic processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnbeh.2018.00100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966556PMC
May 2018

Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study.

Brain 2018 02;141(2):391-408

Comprehensive Epilepsy Center, Department of Neurology, New York University School of Medicine, New York, USA.

Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls. We ranked brain structures in order of greatest differences between patients and controls, by meta-analysing effect sizes across 16 subcortical and 68 cortical brain regions. We also tested effects of duration of disease, age at onset, and age-by-diagnosis interactions on structural measures. We observed widespread patterns of altered subcortical volume and reduced cortical grey matter thickness. Compared to controls, all epilepsy groups showed lower volume in the right thalamus (Cohen's d = -0.24 to -0.73; P < 1.49 × 10-4), and lower thickness in the precentral gyri bilaterally (d = -0.34 to -0.52; P < 4.31 × 10-6). Both MTLE subgroups showed profound volume reduction in the ipsilateral hippocampus (d = -1.73 to -1.91, P < 1.4 × 10-19), and lower thickness in extrahippocampal cortical regions, including the precentral and paracentral gyri, compared to controls (d = -0.36 to -0.52; P < 1.49 × 10-4). Thickness differences of the ipsilateral temporopolar, parahippocampal, entorhinal, and fusiform gyri, contralateral pars triangularis, and bilateral precuneus, superior frontal and caudal middle frontal gyri were observed in left, but not right, MTLE (d = -0.29 to -0.54; P < 1.49 × 10-4). Contrastingly, thickness differences of the ipsilateral pars opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = -0.27 to -0.51; P < 1.49 × 10-4). Lower subcortical volume and cortical thickness associated with a longer duration of epilepsy in the all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b < -0.0018; P < 1.49 × 10-4). In the largest neuroimaging study of epilepsy to date, we provide information on the common epilepsies that could not be realistically acquired in any other way. Our study provides a robust ranking of brain measures that can be further targeted for study in genetic and neuropathological studies. This worldwide initiative identifies patterns of shared grey matter reduction across epilepsy syndromes, and distinctive abnormalities between epilepsy syndromes, which inform our understanding of epilepsy as a network disorder, and indicate that certain epilepsy syndromes involve more widespread structural compromise than previously assumed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/brain/awx341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837616PMC
February 2018

A selenium species in cerebrospinal fluid predicts conversion to Alzheimer's dementia in persons with mild cognitive impairment.

Alzheimers Res Ther 2017 Dec 19;9(1):100. Epub 2017 Dec 19.

Helmholtz Zentrum München GmbH-German Research Center for Environmental Health GmbH, Research Unit Analytical BioGeoChemistry, 1 Ingolstaedter Landstrasse, Neuherberg, 85764, Germany.

Background: Little is known about factors influencing progression from mild cognitive impairment to Alzheimer's dementia. A potential role of environmental chemicals and specifically of selenium, a trace element of nutritional and toxicological relevance, has been suggested. Epidemiologic studies of selenium are lacking, however, with the exception of a recent randomized trial based on an organic selenium form.

Methods: We determined concentrations of selenium species in cerebrospinal fluid sampled at diagnosis in 56 participants with mild cognitive impairment of nonvascular origin. We then investigated the relation of these concentrations to subsequent conversion from mild cognitive impairment to Alzheimer's dementia.

Results: Twenty-one out of the 56 subjects developed Alzheimer's dementia during a median follow-up of 42 months; four subjects developed frontotemporal dementia and two patients Lewy body dementia. In a Cox proportional hazards model adjusting for age, sex, duration of sample storage, and education, an inorganic selenium form, selenate, showed a strong association with Alzheimer's dementia risk, with an adjusted hazard ratio of 3.1 (95% confidence interval 1.0-9.5) in subjects having a cerebrospinal fluid content above the median level, compared with those with lower concentration. The hazard ratio of Alzheimer's dementia showed little departure from unity for all other inorganic and organic selenium species. These associations were similar in analyses that measured exposure on a continuous scale, and also after excluding individuals who converted to Alzheimer's dementia at the beginning of the follow-up.

Conclusions: These results indicate that higher amounts of a potentially toxic inorganic selenium form in cerebrospinal fluid may predict conversion from mild cognitive impairment to Alzheimer's dementia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13195-017-0323-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735937PMC
December 2017

Cortical and Subcortical Brain Changes in Children and Adolescents With Narcolepsy Type 1.

Sleep 2018 Feb;41(2)

Department of Biomedical, Metabolic, and Neural Science, University of Modena and Reggio Emilia, Modena, Italy.

Study Objectives: Neuroimaging studies on structural alterations in patients with type 1 narcolepsy (NT1) have shown controversial and heterogeneous results. The purpose of this study was to investigate microstructural brain changes in patients with NT1 close to disease onset.

Methods: We examined cortical and subcortical grey matter volumes in 20 drug-naïve children and adolescents with NT1 compared with 19 healthy controls; whole-brain voxel-based morphometry, shape and volumetric analyses, and cortical thickness analysis were used.

Results: When compared with controls, NT1 patients revealed reduced grey matter volume in cerebellum and medial prefrontal cortex and increased volume in right hippocampus. Cortical thickness in frontal lobe was also reduced in patients compared with controls. Increased volume and shape expansion in right hippocampus in patients compared with controls were also confirmed by both vertex and volumetric analyses.

Conclusions: Our results indicate that subtle structural brain changes involving attentional and limbic circuits are detectable in children and adolescents with NT1. Cerebellum involvement might be related to the childhood NT1 clinical phenotype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/sleep/zsx192DOI Listing
February 2018

Factors affecting outcome in ocular myasthenia gravis.

Int J Neurosci 2018 Jan 17;128(1):15-24. Epub 2017 Jul 17.

a Department of Biomedical, Metabolic and Neural Sciences , University Hospital , Modena , Italy.

Aim Of The Study: 50%-60% of patients with ocular myasthenia gravis (OMG) progress to generalized myasthenia gravis (GMG) within two years. The aim of our study was to explore factors affecting prognosis of OMG and to test the predictive role of several independent clinical variables.

Materials And Methods: We reviewed a cohort of 168 Caucasian patients followed from September 2000 to January 2016. Several independent variables were considered as prognostic factors: gender, age of onset, results on electrophysiological tests, presence and level of antibodies against acetylcholine receptors (AChR Abs), treatments, thymic abnormalities. The primary outcome was the progression to GMG and/or the presence of bulbar symptoms. Secondary outcomes were either achievement of sustained minimal manifestation status or worsening in ocular quantitative MG subscore (O-QMGS) or worsening in total QMG score (T-QMGS), assessed by Myasthenia Gravis Foundation of America (MGFA) quantitative scores. Changes in mental and physical subscores of health-related quality of life (HRQoL) were assessed with SF-36 questionnaire. Variance analysis was used to interpret the differences between AChR Ab titers at different times of follow up among the generalized and non-generalized patients.

Results: Conversion to GMG occurred in 18.4% of patients; it was significantly associated with sex, later onset of disease and anti-AChR Ab positivity. Antibody titer above the mean value of 25.8 pmol/mL showed no significant effect on generalization. Sex and late onset of disease significantly affected T-QMGS worsening. None of the other independent variables significantly affected O-QMGS and HRQoL.

Conclusions: Sex, later onset and anti-AChR Ab positivity were significantly associated with clinical worsening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00207454.2017.1344237DOI Listing
January 2018

Mortality, morbidity and refractoriness prediction in status epilepticus: Comparison of STESS and EMSE scores.

Seizure 2017 Mar 7;46:31-37. Epub 2017 Feb 7.

Department of Biomedical, Metabolic, and Neural Science, Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, Modena, Italy; Unit of Neurology, OCSAE Hospital, AOU Modena, Italy. Electronic address:

Purpose: Status epilepticus (SE) is a neurological emergency, characterized by high short-term morbidity and mortality. We evaluated and compared two scores that have been developed to evaluate status epilepticus prognosis: STESS (Status Epilepticus Severity Score) and EMSE (Epidemiology based Mortality score in Status Epilepticus).

Methods: A prospective observational study was performed on consecutive patients with SE admitted between September 2013 and August 2015. Demographics, clinical variables, STESS-3 and -4, and EMSE-64 scores were calculated for each patient at baseline. SE drug response, 30-day mortality and morbidity were the outcomes measure.

Results: 162 episodes of SE were observed: 69% had a STESS ≥3; 34% had a STESS ≥4; 51% patients had an EMSE ≥64. The 30-days mortality was 31.5%: EMSE-64 showed greater negative predictive value (NPV) (97.5%), positive predictive value (PPV) (59.8%) and accuracy in the prediction of death than STESS-3 and STESS-4 (p<0.001). At 30 days, the clinical condition had deteriorated in 59% of the cases: EMSE-64 showed greater NPV (71.3%), PPV (87.8%) and accuracy than STESS-3 and STESS-4 (p<0.001) in the prediction of this outcome. In 23% of all cases, status epilepticus proved refractory to non-anaesthetic treatment. All three scales showed a high NPV (EMSE-64: 87.3%; STESS-4: 89.4%; STESS-3: 87.5%) but a low PPV (EMSE-64: 40.9%; STESS-4: 52.9%; STESS-3: 32%) for the prediction of refractoriness to first and second line drugs. This means that accuracy for the prediction of refractoriness was equally poor for all scales.

Conclusions: EMSE-64 appears superior to STESS-3 and STESS-4 in the prediction of 30-days mortality and morbidity. All scales showed poor accuracy in the prediction of response to first and second line antiepileptic drugs. At present, there are no reliable scores capable of predicting treatment responsiveness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.seizure.2017.01.004DOI Listing
March 2017

Cortical and subcortical brain alterations in Juvenile Absence Epilepsy.

Neuroimage Clin 2016 18;12:306-11. Epub 2016 Jul 18.

Department of Biomedical, Metabolic, and Neural Science, University of Modena and Reggio Emilia, Modena, Italy; NOCSAE Hospital, AUSL Modena, Italy.

Despite the common assumption that genetic generalized epilepsies are characterized by a macroscopically normal brain on magnetic resonance imaging, subtle structural brain alterations have been detected by advanced neuroimaging techniques in Childhood Absence Epilepsy syndrome. We applied quantitative structural MRI analysis to a group of adolescents and adults with Juvenile Absence Epilepsy (JAE) in order to investigate micro-structural brain changes using different brain measures. We examined grey matter volumes, cortical thickness, surface areas, and subcortical volumes in 24 patients with JAE compared to 24 healthy controls; whole-brain voxel-based morphometry (VBM) and Freesurfer analyses were used. When compared to healthy controls, patients revealed both grey matter volume and surface area reduction in bilateral frontal regions, anterior cingulate, and right mesial-temporal lobe. Correlation analysis with disease duration showed that longer disease was correlated with reduced surface area in right pre- and post-central gyrus. A possible effect of valproate treatment on brain structures was excluded. Our results indicate that subtle structural brain changes are detectable in JAE and are mainly located in anterior nodes of regions known to be crucial for awareness, attention and memory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nicl.2016.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4983643PMC
November 2017

Long-term disability and prognostic factors in polyneuropathy associated with anti-myelin-associated glycoprotein (MAG) antibodies.

Int J Neurosci 2017 May 7;127(5):439-447. Epub 2016 Jun 7.

a Department of Biomedical, Metabolic and Neural Science , University of Modena & Reggio Emilia , Modena , Italy.

Aim Of The Study: Neuropathy associated with IgM monoclonal gammopathy (MGUS) represents distinctive clinical syndrome, characterized by male predominance, late age of onset, slow progression, predominantly sensory symptoms, deep sensory loss, ataxia, minor motor impairment. More than 50% of patients with neuropathy-associated MGUS possess antibodies against myelin-associated glycoprotein (MAG). Purpose of our study was to assess effects on disease progression of demographic, clinical and neurophysiological variables in our large cohort of patients.

Materials And Methods: Forty-three Caucasians patients were followed every eight months for median duration time of 93 months. Extremity strength was assessed with Medical Research Council (MRC) Scale, disability with overall disability status scale (ODSS), modified Rankin Scale and sensory function with Inflammatory Neuropathy Cause and Treatment (INCAT) sensory scale (ISS). Statistical analyses were conducted with parametric or non-parametric measures as appropriate. Survival analysis was used to test predictive value of clinical, demographical and neurophysiological variables. Variance analysis was conducted to explain difference on MRC between patients and groups at different time from onset.

Results: Results showed that demyelinating pattern, older age and absence of treatment were significant risk factors for disability worsening. No other factors emerged as predictors including gender, ataxia and tremor at baseline, level of anti-MAG and IgM protein concentration in serum. Despite worsening of all outcome measures between first and last visit, quality of life (HRQol) judged by patients did not vary significantly.

Conclusions: Our study provides evidence that electrophysiologic pattern, age of onset and absence of treatment are strong predictor of prognosis in anti-MAG polyneuropathy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00207454.2016.1191013DOI Listing
May 2017

IgM MGUS anti myelin-associated glycoprotein neuropathy can rarely express as a predominantly distal motor neuropathy.

Muscle Nerve 2016 May 21;53(5):827-8. Epub 2016 Jan 21.

Department of Biomedical, Metabolic, and Neural Science, University of Modena & Reggio Emilia, Modena, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mus.25020DOI Listing
May 2016

Cerebrospinal fluid tau proteins in status epilepticus.

Epilepsy Behav 2015 Aug 6;49:150-4. Epub 2015 May 6.

Neurology Unit, NOCSAE Hospital, AUSL Modena, Italy.

Tau protein is a phosphorylated microtubule-associated protein, principally localized at neuronal level in the central nervous system (CNS). Tau levels in the cerebrospinal fluid (CSF) are considered to index both axonal and neuronal damage. To date, however, no study has specifically evaluated the CSF levels of tau proteins in patients with status epilepticus (SE). We evaluated these established biomarkers of neuronal damage in patients with SE who received a lumbar puncture during SE between 2007 and 2014. Status epilepticus cases due to acute structural brain damage, including CNS infection, were excluded. Clinical, biological, therapeutic, and follow-up data were collected. Group comparison between patients stratified according to SE response to antiepileptic drugs (AEDs), disability, and epilepsy outcomes were performed. Twenty-eight patients were considered for the analyses (mean age 56 years): 14 patients had abnormally high CSF t-tau level, six patients had abnormally high CSF p-tau level, and only three patients had abnormally low Aβ1-42 level. Cerebrospinal fluid t-tau value was higher in patients who developed a refractory SE compared to patients with seizures controlled by AED. Cerebrospinal fluid t-tau values were positively correlated with SE duration and were higher in patients treated with propofol anesthesia compared to patients that had not received this treatment. Patients with higher CSF t-tau had higher risk of developing disability (OR = 32.5, p = 0.004) and chronic epilepsy (OR = 12; p = 0.016) in comparison with patients with lower CSF t-tau level. Our results suggest that CSF t-tau level might be proposed as a biomarker of SE severity and prognosis. Prospective studies are needed to evaluate the effects of propofol on tau pathology in this setting. This article is part of a Special Issue entitled "Status Epilepticus".
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2015.04.030DOI Listing
August 2015

Recurrent cerebrospinal fluid basophilia in neurosarcoidosis.

Acta Neurol Belg 2015 Sep 21;115(3):497-9. Epub 2014 Dec 21.

Unit of Neurology, Nuovo Ospedale Civile Sant'Agostino Estense (NOCSAE) Hospital, University of Modena e Reggio Emilia, AUSL Modena, Via Giardini 1355, Modena, Italy,

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13760-014-0406-8DOI Listing
September 2015

Role of cerebrospinal fluid biomarkers to predict conversion to dementia in patients with mild cognitive impairment: a clinical cohort study.

Clin Chem Lab Med 2015 Feb;53(3):453-60

Background: Cerebrospinal fluid (CSF) levels assessment of Aβ1-42 and Tau proteins may be accurate diagnostic biomarkers for the differentiation of preclinical Alzheimer's disease (AD) from age-associated memory impairment, depression and other forms of dementia in patients with mild cognitive impairment (MCI). The aim of our study was to explore the utility of CSF biomarkers in combination with common cognitive markers as predictors for the risk of AD development, and other forms of dementia, and the time to conversion in community patients with MCI.

Methods: A group of 71 MCI patients underwent neurological assessment, extended neuropsychological evaluation, routine blood tests, ApoE determination, and lumbar puncture to dose t-tau, p-tau181, Aβ1-42. We investigated baseline CSF and neuropsychological biomarker patterns according to groups stratified with later diagnoses of AD conversion (MCI-AD), other dementia (MCI-NAD) conversion, or clinical stability (sMCI).

Results: Baseline Aβ1-42 CSF levels were significantly lower in MCI-AD patients compared to both sMCI and MCI-NAD. Additionally, p-tau181 was higher in the MCI-AD group compared to sMCI. The MCI-AD subgroup analysis confirmed the role of Aβ1-42 in its predictive role of time to conversion: rapid converters had lower Aβ1-42 levels compared to slow converters. Logistic regression and survival analysis further supported the key predictive role of baseline Aβ1-42 for incipient AD and dementia-free survival.

Conclusions: Our results confirm the key role of CSF biomarkers in predicting patient conversion from MCI to dementia. The study suggests that CSF biomarkers may also be reliable in a real world clinical setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/cclm-2014-0414DOI Listing
February 2015

The visual system in eyelid myoclonia with absences.

Ann Neurol 2014 Sep 11;76(3):412-27. Epub 2014 Aug 11.

Department of Biomedical, Metabolic, and Neural Science, University of Modena and Reggio Emilia, Nuovo Ospedale Civile S. Agostino Estense (NOCSAE) Hospital, AUSL Modena, NOCSE Hospital, Modena.

Objective: To investigate the functional and structural brain correlates of eyelid myoclonus and absence seizures triggered by eye closure (eye closure sensitivity [ECS]).

Methods: Fifteen patients with eyelid myoclonus with absences (EMA, Jeavons syndrome), 14 patients with idiopathic generalized epilepsies (IGE) without ECS, and 16 healthy controls (HC) underwent an electroencephalography (EEG)-correlated functional magnetic resonance imaging (fMRI) and voxel brain morphometry (VBM) protocol. The functional study consisted of 30-second epochs of eyes-open and eyes-closed conditions. The following EEG events were marked and the relative fMRI maps obtained: (1) eye closure times, (2) spontaneous blinking, and (3) spontaneous and eye closure-triggered spike and wave discharges (SWD; for EMA and IGE). Within-group and between-groups comparisons were performed for fMRI and VBM data as appropriate.

Results: In EMA compared to HC and IGE we found: (1) higher blood oxygenation level-dependent (BOLD) signal related to the eye closure over the visual cortex, the posterior thalamus, and the network implicated in the motor control of eye closure, saccades, and eye pursuit movements; and (2) increments in the gray matter concentration at the visual cortex and thalamic pulvinar, whereas decrements were observed at the bilateral frontal eye field area. No BOLD differences were detected when comparing SWD in EMA and IGE.

Interpretation: Results demonstrated altered anatomo-functional properties of the visual system in EMA. These abnormalities involve a circuit encompassing the occipital cortex and the cortical/subcortical systems physiologically involved in the motor control of eye closure and eye movements. Our work supports EMA as an epileptic condition with distinctive features and provides a contribution to its classification among epileptic syndromes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.24236DOI Listing
September 2014

Pearls & Oy-sters: rapidly progressive dementia: prions or immunomediated?

Neurology 2014 Apr;82(17):e149-52

From the Department of Neuroscience (F.C., J.M., M.T., F.V., S.V., E.G., F.B., P.N.), S. Agostino-Estense Hospital and University of Modena and Reggio Emilia, Modena; and IRCCS Institute of Neurological Sciences of Bologna and Department of Biomedical and Neuromotor Sciences (DIBINEM) (C.S., R.L., P.P.), University of Bologna, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000000354DOI Listing
April 2014

Structural MRI changes detectable up to ten years before clinical Alzheimer's disease.

Neurobiol Aging 2012 Apr 22;33(4):825.e25-36. Epub 2011 Jul 22.

Dipartimento di Neuroscienze, Università di Modena e Reggio Emilia, Modena, Italy.

Structural brain changes have been described in both mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, less is known about whether structural changes are detectable earlier, in the asymptomatic phase. Using voxel-based morphometry (VBM) and shape analyses of magnetic resonance imaging (MRI) data, we investigated structural brain differences between groups of healthy subjects, stratified by subsequent diagnoses of MCI or AD during a 10-year follow-up. Images taken at baseline, at least 4 years before any cognitive symptoms, showed that subjects with future cognitive impairment (preclinical AD and MCI) had reduced brain volume in medial temporal lobes, posterior cingulate/precuneus, and orbitofrontal cortex, compared with matched subjects who remained cognitively healthy for 10 years (HC). For only those subjects later diagnosed as AD, significantly greater atrophy at baseline was detected in the right medial temporal lobe, which was also confirmed by shape analysis of the right hippocampus in these subjects. Our results demonstrate that structural brain changes occur years before clinical cognitive decline in AD and are localized to regions affected by AD neuropathology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neurobiolaging.2011.05.018DOI Listing
April 2012