Muscle fatigue and exercise intolerance are common and frequent symptoms complained by patients w... more Muscle fatigue and exercise intolerance are common and frequent symptoms complained by patients with neuromuscular disease. Muscle fatigue would occur when the intended physical activity can no longer be continued or is perceived as involving excessive effort and discomfort. Except for several rare myopathies with specific metabolic derangements leading to exercise-induced muscle fatigue, most studies fail to identify precise pathogenic mechanism of fatigue in this population of patients. On the other hand, apart from canonical examples of neuromuscular diseases, a number of conditions in which muscle apparatus can be involved is known to occur with high prevalence among certain people categories, such as elderly or people undergoing immobilization. In these cases exercise intolerance and muscle fatigue can be severely incapacitating in common daily activities. An objective and smart, unobtrusive techniques, able to objectively measure fatigue phenomenon, would be useful in monitoring muscle function in both NMD patients and patients with secondary skeletal muscle involvement. In this study, we report a novel, non-invasive assistive architecture for the elderly to assess muscle fatigue by biomedical sensors (surface electromyography) using wireless platform during exercise in an ergonomic platform.
The concept of cognitive reserve (CR) is being increasingly used to explain the observation that ... more The concept of cognitive reserve (CR) is being increasingly used to explain the observation that there is often a poor correspondence between the presence of pathology at autopsy and the level of cognitive decline in life. Since dementia affects an increasing proportion of the population, imposing a large economic burden on our society, in the absence of disease-modifying treatments it is crucial to detect lifestyle factors that may play a protective role in older individuals, delaying the onset of cognitive impairment. Subjective cognitive impairment (SCI), mild cognitive impairment (MCI) and Alzheimer’s disease (AD) are part of the same spectrum of disease progression. Since memory complaints represent a very common symptom reported by the older community population, early diagnosis of cognitive decline is not always easy, which makes it extremely important to find strategies that help detect individuals who deserve specific exams in a specialist setting. Therefore, we compared a ...
Train the Brain Consortium † Age-related cognitive impairment and dementia are an increasing soci... more Train the Brain Consortium † Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65-89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenationlevel-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects. The world is experiencing a substantial increase in the proportion of elderly adults in the population. With an aging society comes the increase in age related frailties, which may lead to cognitive impairments and to dementia, mostly in the form of Alzheimer's Disease (AD). Age is indeed the major risk factor for dementia: the age-specific incidence rates for AD demonstrate a doubling of incidence for about every six years of added life 1. The number of people with dementia worldwide was 35.6 million in 2010 and that is estimated to increase to 65.7 million by 2030 and 115.4 million by 2050 unless effective means of reducing the incidence of this disease are introduced 2. Several epidemiological studies have demonstrated that modifiable lifestyle factors, such as practicing physical exercise, being engaged in stimulating cognitive activities, maintaining an active social life into old age, and controlling nutrition, are correlated with maintaining good brain functioning, specifically in the elderly, and with reduced risk of developing dementia 3-8. Norton et al. 9 estimated that around one third of AD cases worldwide might be attributable to potentially modifiable risk factors which include several lifestyle habits. Interventions based on cognitive training 10 , diet 11 or physical activity 7,12,13 have indeed been found to produce positive effects on cognitive status in cognitively unimpaired adult or elderly subjects. Potential mechanisms underlying the effects of cognitive and physical activity on cognition, suggested also by studies in animal models, include increased hippocampal neurogenesis, increased Cerebral Blood Flow (CBF), and enhanced brain plasticity 14,15. An important point that has recently emerged both from the human and animal research, is that enhanced physical and cognitive activities seem to have additive effects on brain plasticity and age related cognitive decline 16. In this line, a very important study is the FINGER trial 17 , in which 1260 subjects, aged 60-77 years, with cognition in the mean level for age and elevated Dementia Risk Score, were randomized to a 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring, showing that cognitive performances improved more in the intervention than in the control group.
Mutations in the lamin A/C gene (LMNA) are known to be involved in several diseases such as Emery... more Mutations in the lamin A/C gene (LMNA) are known to be involved in several diseases such as Emery-Dreifuss muscular dystrophy, limb-girdle muscular dystrophy type 1B and dilated cardiomyopathies with conduction disease, with considerable phenotype heterogeneity. Here we report on a novel autosomal dominant mutation in LMNA in two direct relatives presenting with different clinical phenotypes, characterized by severe life-threatening limb-girdle muscle involvement and cardiac dysfunction treated with heart transplantation in the proband, and by ventricular tachyarrhythmias with preserved cardiac and skeletal muscle function in her young son. To our knowledge, this is the first report of a duplication in the LMNA gene. The two phenotypes described could reflect different clinical stages of the same disease. We hypothesize that early recognition and initiation of therapeutic manoeuvres in the younger patient may retard the rate of progression of the cardiomyopathy.
Astrocytes have long been considered as just providing trophic support for neurons in the central... more Astrocytes have long been considered as just providing trophic support for neurons in the central nervous system, but recently several studies have highlighted their importance in many functions such as neurotransmission, metabolite and electrolyte homeostasis, cell signaling, inflammation, and synapse modulation. Astrocytes are, in fact, part of a bidirectional crosstalk with neurons. Moreover, increasing evidence is stressing the emerging role of astrocyte dysfunction in the pathophysiology of neurological disorders, including neurodegenerative disease, stroke, epilepsy, migraine, and neuroinflammatory diseases.
Background and purpose: A quality of life (QoL) questionnaire for neuromuscular diseases was rece... more Background and purpose: A quality of life (QoL) questionnaire for neuromuscular diseases was recently constructed and validated in the United Kingdom in a sample of adult patients with a variety of muscle disorders. Preliminary results suggested it could be a more relevant and practical measure of QoL in muscle diseases than generic health measures of QoL. The purpose of our work was: (i) To validate INQoL in Italy on a larger sample of adult patients with muscle diseases (ii) to compare INQoL to SF-36. Methods: We have translated into Italian and applied language adaptations to the original UK INQoL version. We studied 1092 patients with different muscle disorders and performed (i) test-retest reliability (n = 80); (ii) psychometric (n = 345), knowngroup (n = 1092), external criterion (n = 70), and concurrent validity with SF-36 (n = 183). Results: We have translated and formally validated the Italian version of INQoL confirming and extending results obtained in the United Kingdom. In addition to good results in terms of reliability, known-group and criterion validity, a comparison with the SF-36 scales showed a stronger association between INQoL total index and SF-36 physical (r = )0.72) than mental (r = )0.38) summary health indexes. When considering comparable domains of INQoL and SF-36 with respect to an objective measure of muscle strength assessment (MMRC), regression analysis showed a stronger correlation using INQoL rather than SF-36 scores. Conclusions: INQoL is recommended to assess QoL in muscle diseases because of its ability to capture physical limitations that are specifically relevant to the muscle condition.
Mitochondrial diseases (MD) with respiratory chain defects are caused by genetic mutations that d... more Mitochondrial diseases (MD) with respiratory chain defects are caused by genetic mutations that determine an impairment of the electron transport chain functioning. Diagnosis often requires a complex approach with measurements of serum lactate, magnetic resonance spectroscopy (MRS), muscle histology and ultrastructure, enzymology, genetic analysis, and exercise testing. The ubiquitous distribution of the mitochondria in the human body explains the multiple organ involvement. Exercise intolerance is a common symptom of MD, due to increased dependence of skeletal muscle on anaerobic metabolism, with an excess lactate generation, phosphocreatine depletion, enhanced free radical production, reduced oxygen extraction and electron flux through the respiratory chain. MD treatment has included antioxidants (vitamin E, alpha lipoic acid), coenzyme Q10, riboflavin, creatine monohydrate, dichloroacetate and exercise training. Exercise is a particularly important tool in diagnosis as well as in...
Background: Cognitive reserve (CR) has been defined as a set of skills and repertoires, character... more Background: Cognitive reserve (CR) has been defined as a set of skills and repertoires, characterized by personal lifestyle and habits and is considered a protective factor against cognitive impairment (Scarmeas et al.,2003, Stern et al., 2009), particularly in the earlier stages. Indeed, a higher CR may be associated to a more efficient utilization of brain networks, as suggested by themore focused task-related neural responses found in functional magnetic resonance imaging (fMRI) studies in healthy individuals (Bernardi et al., 2011). Here we aim to determine the correlation between CR scores and patterns of brain response in both subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) subjects, while they perform a spatial attention task. Methods: Thirty-one MCI (14M, 74.0 yr 6 5.2) and 24 SCI (13M, 72.0 yr 6 5.8) patients underwent neuropsychological assessment and a fMRI experimental protocol (GE 1.5 T, GRE-EPI, TR 2.5s, TE 50ms, 33 Axial Slices, 3mm isotropic voxel, FA 90 , 180 volumes) during a visuo-spatial attention task (Bernardi et al., 2011). Cognitive Reserve Index (CRIq, Nucci et al., 2001) scores were correlated (Cox et al., 1996) to task-related brain responses, considering age as a confounding factor, after processing fMRI data at an individual and group level. Results: CRIq scores negatively correlated with neural responses (p<0.05 cluster corrected) in the task-related bilateral parietal areas (R 2 1⁄40.365) within the spatial dorsal stream, the superior, middle and inferior frontal cortex (R 2 1⁄40.373), and the posterior cingulate cortex (R 2 1⁄40.28). Conclusions: Our findings demonstrate that in the early stages of cognitive decline, neural response is inversely related to cognitive reserve both when the mental decline is clinically quantifiable (MCI) and when there is no supporting objective evidence from neuropsychological testing (SCI).
instructed prior to each "nap" to "stay awake as best as you can" as they underwent video/polysom... more instructed prior to each "nap" to "stay awake as best as you can" as they underwent video/polysomnographic monitoring while sitting upright in a bed with the lights turned off. The mean initial sleep latency (ISL) over the 4 "naps" for each subject was then calculated. Scores < 24 minutes are at the 15 th percentile based on normative data, and considered abnormal. Results: Nine DLB patients (8M, 1F) underwent the MWT with a median age of 72 (range 66-80) years and median CDR score of 1 (range 1-2). All subjects were using cholinesterase inhibitors, and none were using medications during the day which could cause significant sedation. The median value across all subjects for the mean ISL was 16.5 minutes (range 3.75 -23.88 minutes), with all scores falling below the cut-off. Conclusions: These data suggest that impairment in the ability to maintain wakefulness exists in at least some DLB subjects. Further assessment of the neurologic mechanisms subserving wakefulness, and the impact of pharmacotherapy on impaired wakefulness, in DLB subjects is warranted.
Objectives: Elevation of serum gamma-glutamyltransferase (GGT), in absence of a clinically signif... more Objectives: Elevation of serum gamma-glutamyltransferase (GGT), in absence of a clinically significant liver damage, is often found in Myotonic Dystrophy type-1 (DM1). In this study we investigated if a specific GGT fraction pattern is present in DM1. Designs and methods: We compared total and fractional GGT values (b-, m-, s-, f-GGT) among patients with DM1 or liver disease (LD) and healthy subjects (HS). Results: The increase of GGT in DM1 and LD, vs HS, was mainly due to s-GGT (median: 32.7; 66.7; and 7.9 U/L, respectively), and b-GGT (8.5; 18.9; and 2.1 U/L). The subset of DM1 patients matched with HS with corresponding serum GGT showed higher b-GGT (6.0 vs 4.2 U/L). Conclusions: DM1 patients with normal total GGT values showed an alteration of the production and release in the blood of GGT fractions. Since increased s-GGT is also found in LD, a sub-clinical liver damage likely occurs in DM1 subjects apparently free of liver disease.
The European journal of neuroscience, Jan 28, 2017
Mild Cognitive Impairment (MCI) is an intermediate condition between normal aging and dementia, a... more Mild Cognitive Impairment (MCI) is an intermediate condition between normal aging and dementia, associated with an increased risk of progression into the latter within months or years. Olfactory impairment, a well-known biomarker for neurodegeneration, might be present in the condition early, possibly representing a signal for future pathological onset. Our study aimed at evaluating olfactory function in MCI and healthy controls in relation to neurocognitive performance and endothelial function. A total of 85 individuals with MCI and 41 healthy controls, matched for age and gender, were recruited. Olfactory function was assessed by Sniffin' Sticks Extended Test (Burghart, Medizintechnik, GmbH, Wedel, Germany). A comprehensive neurocognitive assessment was performed. Endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery by ultrasound. MCI individuals showed an impaired olfactory function compared to controls. The overall olfactory score is able ...
Background: Myotonic dystrophy type 1 (Steinert's disease or DM1), the most common form of autoso... more Background: Myotonic dystrophy type 1 (Steinert's disease or DM1), the most common form of autosomal dominant muscular dystrophy in adults, is a multisystem disorder, affecting skeletal muscle as well as eyes, heart, gastrointestinal tract, endocrine system, and central nervous system, finally responsible of increasing disabilities and secondary social consequences. To date, DM1-related brain involvement represents a challenging field of research. It is well known that DM1 patients frequently present neuropsychological disturbances and psychiatric comorbidities among which reduced awareness of disease burden and its progression, also defined as anosognosia, is common in clinical practice, this leading to secondary misattribution of symptoms, delay in timely diagnostic procedures and low compliance to treatment. Methods: Here we present an observational cross sectional study in which disease-related cognitive dysfunctions and quality of life were assessed by a protocol finally designed to estimate the prevalence of disease awareness in a sample of 65 adult-onset DM1 patients. Results: Our analysis showed that in DM1 patients several cognitive functions, including executive and mnesic domains with visuo-spatial involvement, were affected. The assessment of anosognosia revealed that a high percentage (51.6 %) of DM1 subjects was disease unaware. The reduced illness awareness occurs across different physical and life domains, and it appears more prominent in Activities and Independence domains investigated by the Individualized Neuromuscular Quality Of Life (INQoL) questionnaire. Moreover, the unawareness resulted significantly related (at p <0.05 and p < 0.01) to the performance failure in cognitive tests, specifically in the domains of visuo-spatial memory, cognitive flexibility and conceptualization. Conclusions: The obtained data confirm, by a systematic analysis, what's the common clinical perceiving of disease unawareness in Steinert's disease, this related to the already known cognitive-behavioural impairment of frontal type in affected patients. We believe that a deep knowledge of this aspect will be useful for medical practice in the management of patients with DM1, also for guidance in occupational and social interventions, definition of outcome measures and in preparation of trial readiness.
Polysomnographic (PSG) studies in mild cognitive impairment (MCI) are not conclusive and are limi... more Polysomnographic (PSG) studies in mild cognitive impairment (MCI) are not conclusive and are limited only to conventional sleep parameters. The aim of our study was to evaluate sleep architecture and cyclic alternating pattern (CAP) parameters in subjects with MCI, and to assess their eventual correlation with cognition. Eleven subjects with MCI (mean age 68.5 ± 7.0 years), 11 patients with mild probable Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD; mean age 72.7 ± 5.9 years), referred to the Outpatient Cognitive Disorders Clinic, and 11 cognitively intact healthy elderly individuals (mean age 69.2 ± 12.6 years) underwent ambulatory PSG for the evaluation of nocturnal sleep architecture and CAP parameters. Rapid eye movement sleep, CAP rate, and CAP slow components (A1 index) were decreased in MCI subjects and to a greater extent in AD patients, compared to cognitively intact controls. AD showed also decreased slow wave sleep (SWS) relative to healthy elderly individuals. MCI nappers showed decreased nocturnal SWS and A1 subtypes compared to non-nappers. Several correlations between sleep variables and neuropsychological tests were found. MCI and AD subjects showed a decreased sleep instability correlated with their cognitive decline. Such a decrease may be considered as a potential biomarker of underlying neurodegeneration.
The hereditary peripheral neuropathies are a clinically and genetically heterogeneous group of di... more The hereditary peripheral neuropathies are a clinically and genetically heterogeneous group of diseases of the peripheral nervous system. Foot deformities, including the common pes cavus, but also hammer toes and twisting of the ankle, are frequently present in patients with hereditary peripheral neuropathy, and often represent one of the first signs of the disease. Pes cavus in hereditary peripheral neuropathies is caused by imbalance between the intrinsic muscles of the foot and the muscles of the leg. Accurate clinical evaluation in patients with pes cavus is necessary to exclude or confirm the presence of peripheral neuropathy. Hereditary peripheral neuropathies should be suspected in those cases with bilateral foot deformities, in the presence of family history for pes cavus and/or gait impairment, and in the presence of neurological symptoms or signs, such as distal muscle hypotrophy of limbs. Herein, we review the hereditary peripheral neuropathies in which pes cavus plays a ...
There are currently approximately 45 million people in Europe who report a long standing health p... more There are currently approximately 45 million people in Europe who report a long standing health problem or disability; according to the World Health Organization data the total number of persons chronically ill are 860 million at a worldwide level. Within a person centric health management framework, the modern healthcare systems must move away Assistive and health monitoring technologies can help to automatically identify and address major deficits. In this work we describe a wearable pervasive platform able to monitor the muscular fatigue during his/her daily life. Our system monitors the performance of a subject through the evaluation of sEMG signals using a wearable device aimed to immediately recognize the onset of muscular fatigue.
2010 8th IEEE International Conference on Pervasive Computing and Communications Workshops, PERCOM Workshops 2010, 2010
The profound, pervasive and enduring consequences of the ageing population present enormous chall... more The profound, pervasive and enduring consequences of the ageing population present enormous challenges as well as enormous opportunities for Information and Communication Technology. In this paper we report an architecture designed to monitor, support and manage the physical activities of the elderly. We realized an unobtrusive wireless body area network to ecologically track the lower body parts motion integrated with
Muscle fatigue and exercise intolerance are common and frequent symptoms complained by patients w... more Muscle fatigue and exercise intolerance are common and frequent symptoms complained by patients with neuromuscular disease. Muscle fatigue would occur when the intended physical activity can no longer be continued or is perceived as involving excessive effort and discomfort. Except for several rare myopathies with specific metabolic derangements leading to exercise-induced muscle fatigue, most studies fail to identify precise pathogenic mechanism of fatigue in this population of patients. On the other hand, apart from canonical examples of neuromuscular diseases, a number of conditions in which muscle apparatus can be involved is known to occur with high prevalence among certain people categories, such as elderly or people undergoing immobilization. In these cases exercise intolerance and muscle fatigue can be severely incapacitating in common daily activities. An objective and smart, unobtrusive techniques, able to objectively measure fatigue phenomenon, would be useful in monitoring muscle function in both NMD patients and patients with secondary skeletal muscle involvement. In this study, we report a novel, non-invasive assistive architecture for the elderly to assess muscle fatigue by biomedical sensors (surface electromyography) using wireless platform during exercise in an ergonomic platform.
The concept of cognitive reserve (CR) is being increasingly used to explain the observation that ... more The concept of cognitive reserve (CR) is being increasingly used to explain the observation that there is often a poor correspondence between the presence of pathology at autopsy and the level of cognitive decline in life. Since dementia affects an increasing proportion of the population, imposing a large economic burden on our society, in the absence of disease-modifying treatments it is crucial to detect lifestyle factors that may play a protective role in older individuals, delaying the onset of cognitive impairment. Subjective cognitive impairment (SCI), mild cognitive impairment (MCI) and Alzheimer’s disease (AD) are part of the same spectrum of disease progression. Since memory complaints represent a very common symptom reported by the older community population, early diagnosis of cognitive decline is not always easy, which makes it extremely important to find strategies that help detect individuals who deserve specific exams in a specialist setting. Therefore, we compared a ...
Train the Brain Consortium † Age-related cognitive impairment and dementia are an increasing soci... more Train the Brain Consortium † Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65-89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenationlevel-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects. The world is experiencing a substantial increase in the proportion of elderly adults in the population. With an aging society comes the increase in age related frailties, which may lead to cognitive impairments and to dementia, mostly in the form of Alzheimer's Disease (AD). Age is indeed the major risk factor for dementia: the age-specific incidence rates for AD demonstrate a doubling of incidence for about every six years of added life 1. The number of people with dementia worldwide was 35.6 million in 2010 and that is estimated to increase to 65.7 million by 2030 and 115.4 million by 2050 unless effective means of reducing the incidence of this disease are introduced 2. Several epidemiological studies have demonstrated that modifiable lifestyle factors, such as practicing physical exercise, being engaged in stimulating cognitive activities, maintaining an active social life into old age, and controlling nutrition, are correlated with maintaining good brain functioning, specifically in the elderly, and with reduced risk of developing dementia 3-8. Norton et al. 9 estimated that around one third of AD cases worldwide might be attributable to potentially modifiable risk factors which include several lifestyle habits. Interventions based on cognitive training 10 , diet 11 or physical activity 7,12,13 have indeed been found to produce positive effects on cognitive status in cognitively unimpaired adult or elderly subjects. Potential mechanisms underlying the effects of cognitive and physical activity on cognition, suggested also by studies in animal models, include increased hippocampal neurogenesis, increased Cerebral Blood Flow (CBF), and enhanced brain plasticity 14,15. An important point that has recently emerged both from the human and animal research, is that enhanced physical and cognitive activities seem to have additive effects on brain plasticity and age related cognitive decline 16. In this line, a very important study is the FINGER trial 17 , in which 1260 subjects, aged 60-77 years, with cognition in the mean level for age and elevated Dementia Risk Score, were randomized to a 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring, showing that cognitive performances improved more in the intervention than in the control group.
Mutations in the lamin A/C gene (LMNA) are known to be involved in several diseases such as Emery... more Mutations in the lamin A/C gene (LMNA) are known to be involved in several diseases such as Emery-Dreifuss muscular dystrophy, limb-girdle muscular dystrophy type 1B and dilated cardiomyopathies with conduction disease, with considerable phenotype heterogeneity. Here we report on a novel autosomal dominant mutation in LMNA in two direct relatives presenting with different clinical phenotypes, characterized by severe life-threatening limb-girdle muscle involvement and cardiac dysfunction treated with heart transplantation in the proband, and by ventricular tachyarrhythmias with preserved cardiac and skeletal muscle function in her young son. To our knowledge, this is the first report of a duplication in the LMNA gene. The two phenotypes described could reflect different clinical stages of the same disease. We hypothesize that early recognition and initiation of therapeutic manoeuvres in the younger patient may retard the rate of progression of the cardiomyopathy.
Astrocytes have long been considered as just providing trophic support for neurons in the central... more Astrocytes have long been considered as just providing trophic support for neurons in the central nervous system, but recently several studies have highlighted their importance in many functions such as neurotransmission, metabolite and electrolyte homeostasis, cell signaling, inflammation, and synapse modulation. Astrocytes are, in fact, part of a bidirectional crosstalk with neurons. Moreover, increasing evidence is stressing the emerging role of astrocyte dysfunction in the pathophysiology of neurological disorders, including neurodegenerative disease, stroke, epilepsy, migraine, and neuroinflammatory diseases.
Background and purpose: A quality of life (QoL) questionnaire for neuromuscular diseases was rece... more Background and purpose: A quality of life (QoL) questionnaire for neuromuscular diseases was recently constructed and validated in the United Kingdom in a sample of adult patients with a variety of muscle disorders. Preliminary results suggested it could be a more relevant and practical measure of QoL in muscle diseases than generic health measures of QoL. The purpose of our work was: (i) To validate INQoL in Italy on a larger sample of adult patients with muscle diseases (ii) to compare INQoL to SF-36. Methods: We have translated into Italian and applied language adaptations to the original UK INQoL version. We studied 1092 patients with different muscle disorders and performed (i) test-retest reliability (n = 80); (ii) psychometric (n = 345), knowngroup (n = 1092), external criterion (n = 70), and concurrent validity with SF-36 (n = 183). Results: We have translated and formally validated the Italian version of INQoL confirming and extending results obtained in the United Kingdom. In addition to good results in terms of reliability, known-group and criterion validity, a comparison with the SF-36 scales showed a stronger association between INQoL total index and SF-36 physical (r = )0.72) than mental (r = )0.38) summary health indexes. When considering comparable domains of INQoL and SF-36 with respect to an objective measure of muscle strength assessment (MMRC), regression analysis showed a stronger correlation using INQoL rather than SF-36 scores. Conclusions: INQoL is recommended to assess QoL in muscle diseases because of its ability to capture physical limitations that are specifically relevant to the muscle condition.
Mitochondrial diseases (MD) with respiratory chain defects are caused by genetic mutations that d... more Mitochondrial diseases (MD) with respiratory chain defects are caused by genetic mutations that determine an impairment of the electron transport chain functioning. Diagnosis often requires a complex approach with measurements of serum lactate, magnetic resonance spectroscopy (MRS), muscle histology and ultrastructure, enzymology, genetic analysis, and exercise testing. The ubiquitous distribution of the mitochondria in the human body explains the multiple organ involvement. Exercise intolerance is a common symptom of MD, due to increased dependence of skeletal muscle on anaerobic metabolism, with an excess lactate generation, phosphocreatine depletion, enhanced free radical production, reduced oxygen extraction and electron flux through the respiratory chain. MD treatment has included antioxidants (vitamin E, alpha lipoic acid), coenzyme Q10, riboflavin, creatine monohydrate, dichloroacetate and exercise training. Exercise is a particularly important tool in diagnosis as well as in...
Background: Cognitive reserve (CR) has been defined as a set of skills and repertoires, character... more Background: Cognitive reserve (CR) has been defined as a set of skills and repertoires, characterized by personal lifestyle and habits and is considered a protective factor against cognitive impairment (Scarmeas et al.,2003, Stern et al., 2009), particularly in the earlier stages. Indeed, a higher CR may be associated to a more efficient utilization of brain networks, as suggested by themore focused task-related neural responses found in functional magnetic resonance imaging (fMRI) studies in healthy individuals (Bernardi et al., 2011). Here we aim to determine the correlation between CR scores and patterns of brain response in both subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) subjects, while they perform a spatial attention task. Methods: Thirty-one MCI (14M, 74.0 yr 6 5.2) and 24 SCI (13M, 72.0 yr 6 5.8) patients underwent neuropsychological assessment and a fMRI experimental protocol (GE 1.5 T, GRE-EPI, TR 2.5s, TE 50ms, 33 Axial Slices, 3mm isotropic voxel, FA 90 , 180 volumes) during a visuo-spatial attention task (Bernardi et al., 2011). Cognitive Reserve Index (CRIq, Nucci et al., 2001) scores were correlated (Cox et al., 1996) to task-related brain responses, considering age as a confounding factor, after processing fMRI data at an individual and group level. Results: CRIq scores negatively correlated with neural responses (p<0.05 cluster corrected) in the task-related bilateral parietal areas (R 2 1⁄40.365) within the spatial dorsal stream, the superior, middle and inferior frontal cortex (R 2 1⁄40.373), and the posterior cingulate cortex (R 2 1⁄40.28). Conclusions: Our findings demonstrate that in the early stages of cognitive decline, neural response is inversely related to cognitive reserve both when the mental decline is clinically quantifiable (MCI) and when there is no supporting objective evidence from neuropsychological testing (SCI).
instructed prior to each "nap" to "stay awake as best as you can" as they underwent video/polysom... more instructed prior to each "nap" to "stay awake as best as you can" as they underwent video/polysomnographic monitoring while sitting upright in a bed with the lights turned off. The mean initial sleep latency (ISL) over the 4 "naps" for each subject was then calculated. Scores < 24 minutes are at the 15 th percentile based on normative data, and considered abnormal. Results: Nine DLB patients (8M, 1F) underwent the MWT with a median age of 72 (range 66-80) years and median CDR score of 1 (range 1-2). All subjects were using cholinesterase inhibitors, and none were using medications during the day which could cause significant sedation. The median value across all subjects for the mean ISL was 16.5 minutes (range 3.75 -23.88 minutes), with all scores falling below the cut-off. Conclusions: These data suggest that impairment in the ability to maintain wakefulness exists in at least some DLB subjects. Further assessment of the neurologic mechanisms subserving wakefulness, and the impact of pharmacotherapy on impaired wakefulness, in DLB subjects is warranted.
Objectives: Elevation of serum gamma-glutamyltransferase (GGT), in absence of a clinically signif... more Objectives: Elevation of serum gamma-glutamyltransferase (GGT), in absence of a clinically significant liver damage, is often found in Myotonic Dystrophy type-1 (DM1). In this study we investigated if a specific GGT fraction pattern is present in DM1. Designs and methods: We compared total and fractional GGT values (b-, m-, s-, f-GGT) among patients with DM1 or liver disease (LD) and healthy subjects (HS). Results: The increase of GGT in DM1 and LD, vs HS, was mainly due to s-GGT (median: 32.7; 66.7; and 7.9 U/L, respectively), and b-GGT (8.5; 18.9; and 2.1 U/L). The subset of DM1 patients matched with HS with corresponding serum GGT showed higher b-GGT (6.0 vs 4.2 U/L). Conclusions: DM1 patients with normal total GGT values showed an alteration of the production and release in the blood of GGT fractions. Since increased s-GGT is also found in LD, a sub-clinical liver damage likely occurs in DM1 subjects apparently free of liver disease.
The European journal of neuroscience, Jan 28, 2017
Mild Cognitive Impairment (MCI) is an intermediate condition between normal aging and dementia, a... more Mild Cognitive Impairment (MCI) is an intermediate condition between normal aging and dementia, associated with an increased risk of progression into the latter within months or years. Olfactory impairment, a well-known biomarker for neurodegeneration, might be present in the condition early, possibly representing a signal for future pathological onset. Our study aimed at evaluating olfactory function in MCI and healthy controls in relation to neurocognitive performance and endothelial function. A total of 85 individuals with MCI and 41 healthy controls, matched for age and gender, were recruited. Olfactory function was assessed by Sniffin' Sticks Extended Test (Burghart, Medizintechnik, GmbH, Wedel, Germany). A comprehensive neurocognitive assessment was performed. Endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery by ultrasound. MCI individuals showed an impaired olfactory function compared to controls. The overall olfactory score is able ...
Background: Myotonic dystrophy type 1 (Steinert's disease or DM1), the most common form of autoso... more Background: Myotonic dystrophy type 1 (Steinert's disease or DM1), the most common form of autosomal dominant muscular dystrophy in adults, is a multisystem disorder, affecting skeletal muscle as well as eyes, heart, gastrointestinal tract, endocrine system, and central nervous system, finally responsible of increasing disabilities and secondary social consequences. To date, DM1-related brain involvement represents a challenging field of research. It is well known that DM1 patients frequently present neuropsychological disturbances and psychiatric comorbidities among which reduced awareness of disease burden and its progression, also defined as anosognosia, is common in clinical practice, this leading to secondary misattribution of symptoms, delay in timely diagnostic procedures and low compliance to treatment. Methods: Here we present an observational cross sectional study in which disease-related cognitive dysfunctions and quality of life were assessed by a protocol finally designed to estimate the prevalence of disease awareness in a sample of 65 adult-onset DM1 patients. Results: Our analysis showed that in DM1 patients several cognitive functions, including executive and mnesic domains with visuo-spatial involvement, were affected. The assessment of anosognosia revealed that a high percentage (51.6 %) of DM1 subjects was disease unaware. The reduced illness awareness occurs across different physical and life domains, and it appears more prominent in Activities and Independence domains investigated by the Individualized Neuromuscular Quality Of Life (INQoL) questionnaire. Moreover, the unawareness resulted significantly related (at p <0.05 and p < 0.01) to the performance failure in cognitive tests, specifically in the domains of visuo-spatial memory, cognitive flexibility and conceptualization. Conclusions: The obtained data confirm, by a systematic analysis, what's the common clinical perceiving of disease unawareness in Steinert's disease, this related to the already known cognitive-behavioural impairment of frontal type in affected patients. We believe that a deep knowledge of this aspect will be useful for medical practice in the management of patients with DM1, also for guidance in occupational and social interventions, definition of outcome measures and in preparation of trial readiness.
Polysomnographic (PSG) studies in mild cognitive impairment (MCI) are not conclusive and are limi... more Polysomnographic (PSG) studies in mild cognitive impairment (MCI) are not conclusive and are limited only to conventional sleep parameters. The aim of our study was to evaluate sleep architecture and cyclic alternating pattern (CAP) parameters in subjects with MCI, and to assess their eventual correlation with cognition. Eleven subjects with MCI (mean age 68.5 ± 7.0 years), 11 patients with mild probable Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD; mean age 72.7 ± 5.9 years), referred to the Outpatient Cognitive Disorders Clinic, and 11 cognitively intact healthy elderly individuals (mean age 69.2 ± 12.6 years) underwent ambulatory PSG for the evaluation of nocturnal sleep architecture and CAP parameters. Rapid eye movement sleep, CAP rate, and CAP slow components (A1 index) were decreased in MCI subjects and to a greater extent in AD patients, compared to cognitively intact controls. AD showed also decreased slow wave sleep (SWS) relative to healthy elderly individuals. MCI nappers showed decreased nocturnal SWS and A1 subtypes compared to non-nappers. Several correlations between sleep variables and neuropsychological tests were found. MCI and AD subjects showed a decreased sleep instability correlated with their cognitive decline. Such a decrease may be considered as a potential biomarker of underlying neurodegeneration.
The hereditary peripheral neuropathies are a clinically and genetically heterogeneous group of di... more The hereditary peripheral neuropathies are a clinically and genetically heterogeneous group of diseases of the peripheral nervous system. Foot deformities, including the common pes cavus, but also hammer toes and twisting of the ankle, are frequently present in patients with hereditary peripheral neuropathy, and often represent one of the first signs of the disease. Pes cavus in hereditary peripheral neuropathies is caused by imbalance between the intrinsic muscles of the foot and the muscles of the leg. Accurate clinical evaluation in patients with pes cavus is necessary to exclude or confirm the presence of peripheral neuropathy. Hereditary peripheral neuropathies should be suspected in those cases with bilateral foot deformities, in the presence of family history for pes cavus and/or gait impairment, and in the presence of neurological symptoms or signs, such as distal muscle hypotrophy of limbs. Herein, we review the hereditary peripheral neuropathies in which pes cavus plays a ...
There are currently approximately 45 million people in Europe who report a long standing health p... more There are currently approximately 45 million people in Europe who report a long standing health problem or disability; according to the World Health Organization data the total number of persons chronically ill are 860 million at a worldwide level. Within a person centric health management framework, the modern healthcare systems must move away Assistive and health monitoring technologies can help to automatically identify and address major deficits. In this work we describe a wearable pervasive platform able to monitor the muscular fatigue during his/her daily life. Our system monitors the performance of a subject through the evaluation of sEMG signals using a wearable device aimed to immediately recognize the onset of muscular fatigue.
2010 8th IEEE International Conference on Pervasive Computing and Communications Workshops, PERCOM Workshops 2010, 2010
The profound, pervasive and enduring consequences of the ageing population present enormous chall... more The profound, pervasive and enduring consequences of the ageing population present enormous challenges as well as enormous opportunities for Information and Communication Technology. In this paper we report an architecture designed to monitor, support and manage the physical activities of the elderly. We realized an unobtrusive wireless body area network to ecologically track the lower body parts motion integrated with
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Papers by Leda Volpi