Functional neurosurgery is nowadays a recognized treatment for advanced Parkinson’s disease with pharmacologically uncontrolled symptoms. This procedure brings us the unique opportunity to deepen in the knowledge of...Functional neurosurgery is nowadays a recognized treatment for advanced Parkinson’s disease with pharmacologically uncontrolled symptoms. This procedure brings us the unique opportunity to deepen in the knowledge of PD’s physiopathology by recording patients’ neural activity, and possibly in the future it will let us select the appropriate target and the optimal chronic stimulation pattern.展开更多
Objective: The Tower of Hanoi measures executive functions using non-verbal content and requires perception of position in space. The main objective of this study is to standardize the use of the TOH as a measurement ...Objective: The Tower of Hanoi measures executive functions using non-verbal content and requires perception of position in space. The main objective of this study is to standardize the use of the TOH as a measurement tool in Parkinson’s disease. Patients and Methods: Of the Control Group subjects, 192 (59.6%) were women, 223 subjects (69.25%) were able to perform the TOH with 3 discs. In the Parkinson’s Group, there were 57 women (39.3%), and 66 subjects (45.5%) did not get past that level. Results: If we take the TOH (with 3 or 4 discs) as a tool for discriminating between those who have dysexecutive syndrome and those who do not, we find that the Parkinson’s Group presents dysexecutive syndrome significantly more frequently than the Control Group (p ≤ 0.0064). Conclusion: We can conclude that dysexecutive syndrome is frequent in Parkinson’s patients and it is more prevalent than in the general population.展开更多
The core(established)cerebrospinal fluid biomarkers of Alzheimer's disease(AD),namely amyloid-beta peptide,total tau protein and phospho-tau protein,have become a part of the diagnostic workup of patients with cog...The core(established)cerebrospinal fluid biomarkers of Alzheimer's disease(AD),namely amyloid-beta peptide,total tau protein and phospho-tau protein,have become a part of the diagnostic workup of patients with cognitive disorders in many specialized centers,especially for ambiguous cases.Combined,these biomarkers can identify the presence or absence of an AD biochemical process with sensitivities and specificities approaching or exceeding 90%in both dementia and pre-dementia stages of AD.Thus,they have been incorporated in various sets of research or clinical diagnostic criteria and recommendations.Results that are atypical,incompatible with AD,or inconclusive may occur,necessitating the use of other cerebrospinal fluid or imaging biomarkers.展开更多
Background:Parkinson’s disease(PD)is a neurodegenerative disorder whose diagnosis is often challenging because symptoms may overlap with neurodegenerative parkinsonisms.PD is characterized by intraneuronal accumulati...Background:Parkinson’s disease(PD)is a neurodegenerative disorder whose diagnosis is often challenging because symptoms may overlap with neurodegenerative parkinsonisms.PD is characterized by intraneuronal accumulation of abnormalα-synuclein in brainstem while neurodegenerative parkinsonisms might be associated with accumulation of eitherα-synuclein,as in the case of Multiple System Atrophy(MSA)or tau,as in the case of Corticobasal Degeneration(CBD)and Progressive Supranuclear Palsy(PSP),in other disease-specific brain regions.Definite diagnosis of all these diseases can be formulated only neuropathologically by detection and localization ofα-synuclein or tau aggregates in the brain.Compelling evidence suggests that trace-amount of these proteins can appear in peripheral tissues,including receptor neurons of the olfactory mucosa(OM).Methods:We have set and standardized the experimental conditions to extend the ultrasensitive Real Time Quaking Induced Conversion(RT-QuIC)assay for OM analysis.In particular,by using human recombinantα-synuclein as substrate of reaction,we have assessed the ability of OM collected from patients with clinical diagnoses of PD and MSA to induceα-synuclein aggregation,and compared their seeding ability to that of OM samples collected from patients with clinical diagnoses of CBD and PSP.Results:Our results showed that a significant percentage of MSA and PD samples inducedα-synuclein aggregation with high efficiency,but also few samples of patients with the clinical diagnosis of CBD and PSP caused the same effect.Notably,the final RT-QuIC aggregates obtained from MSA and PD samples owned peculiar biochemical and morphological features potentially enabling their discrimination.Conclusions:Our study provide the proof-of-concept that olfactory mucosa samples collected from patients with PD and MSA possess important seeding activities forα-synuclein.Additional studies are required for(i)estimating sensitivity and specificity of the technique and for(ii)evaluating its application for the diagnosis of PD and neurodegenerative parkinsonisms.RT-QuIC analyses of OM and cerebrospinal fluid(CSF)can be combined with the aim of increasing the overall diagnostic accuracy of these diseases,especially in the early stages.展开更多
There has been a growing appreciation for freezing of gait as a disabling symptom that causes a significant burden in Parkinson’s disease. Previous research has highlighted some of the key components that underlie th...There has been a growing appreciation for freezing of gait as a disabling symptom that causes a significant burden in Parkinson’s disease. Previous research has highlighted some of the key components that underlie the phenomenon, but these reductionist approaches have yet to lead to a paradigm shift resulting in the development of novel treatment strategies. Addressing this issue will require greater integration of multi-modal data with complex computational modeling, but there are a number of critical aspects that need to be considered before embarking on such an approach. This paper highlights where the field needs to address current gaps and shortcomings including the standardization of definitions and measurement, phenomenology and pathophysiology, as well as considering what available data exist and how future studies should be constructed to achieve the greatest potential to better understand and treat this devastating symptom.展开更多
文摘Functional neurosurgery is nowadays a recognized treatment for advanced Parkinson’s disease with pharmacologically uncontrolled symptoms. This procedure brings us the unique opportunity to deepen in the knowledge of PD’s physiopathology by recording patients’ neural activity, and possibly in the future it will let us select the appropriate target and the optimal chronic stimulation pattern.
基金Partially funded by the Pontifical Catholic University of Ecuador.
文摘Objective: The Tower of Hanoi measures executive functions using non-verbal content and requires perception of position in space. The main objective of this study is to standardize the use of the TOH as a measurement tool in Parkinson’s disease. Patients and Methods: Of the Control Group subjects, 192 (59.6%) were women, 223 subjects (69.25%) were able to perform the TOH with 3 discs. In the Parkinson’s Group, there were 57 women (39.3%), and 66 subjects (45.5%) did not get past that level. Results: If we take the TOH (with 3 or 4 discs) as a tool for discriminating between those who have dysexecutive syndrome and those who do not, we find that the Parkinson’s Group presents dysexecutive syndrome significantly more frequently than the Control Group (p ≤ 0.0064). Conclusion: We can conclude that dysexecutive syndrome is frequent in Parkinson’s patients and it is more prevalent than in the general population.
文摘The core(established)cerebrospinal fluid biomarkers of Alzheimer's disease(AD),namely amyloid-beta peptide,total tau protein and phospho-tau protein,have become a part of the diagnostic workup of patients with cognitive disorders in many specialized centers,especially for ambiguous cases.Combined,these biomarkers can identify the presence or absence of an AD biochemical process with sensitivities and specificities approaching or exceeding 90%in both dementia and pre-dementia stages of AD.Thus,they have been incorporated in various sets of research or clinical diagnostic criteria and recommendations.Results that are atypical,incompatible with AD,or inconclusive may occur,necessitating the use of other cerebrospinal fluid or imaging biomarkers.
基金This study was supported in part by the Italian Ministry of Health(GR-2013-02355724)the Michael J.Fox Foundation,Alzheimer’s Association,Alzheimer’s Research UK and the Weston Brain Institute(BAND 11035)+1 种基金Associazione Italiana Encefalopatie da Prioni(AIEnP)to FMItalian Ministry of Health(GR-2009-1607326)to AEE,Italian Ministry of Health(NET-2011-02346784)to FT and NIH/NIA(P30 AG10133)to Bernardino Ghetti.
文摘Background:Parkinson’s disease(PD)is a neurodegenerative disorder whose diagnosis is often challenging because symptoms may overlap with neurodegenerative parkinsonisms.PD is characterized by intraneuronal accumulation of abnormalα-synuclein in brainstem while neurodegenerative parkinsonisms might be associated with accumulation of eitherα-synuclein,as in the case of Multiple System Atrophy(MSA)or tau,as in the case of Corticobasal Degeneration(CBD)and Progressive Supranuclear Palsy(PSP),in other disease-specific brain regions.Definite diagnosis of all these diseases can be formulated only neuropathologically by detection and localization ofα-synuclein or tau aggregates in the brain.Compelling evidence suggests that trace-amount of these proteins can appear in peripheral tissues,including receptor neurons of the olfactory mucosa(OM).Methods:We have set and standardized the experimental conditions to extend the ultrasensitive Real Time Quaking Induced Conversion(RT-QuIC)assay for OM analysis.In particular,by using human recombinantα-synuclein as substrate of reaction,we have assessed the ability of OM collected from patients with clinical diagnoses of PD and MSA to induceα-synuclein aggregation,and compared their seeding ability to that of OM samples collected from patients with clinical diagnoses of CBD and PSP.Results:Our results showed that a significant percentage of MSA and PD samples inducedα-synuclein aggregation with high efficiency,but also few samples of patients with the clinical diagnosis of CBD and PSP caused the same effect.Notably,the final RT-QuIC aggregates obtained from MSA and PD samples owned peculiar biochemical and morphological features potentially enabling their discrimination.Conclusions:Our study provide the proof-of-concept that olfactory mucosa samples collected from patients with PD and MSA possess important seeding activities forα-synuclein.Additional studies are required for(i)estimating sensitivity and specificity of the technique and for(ii)evaluating its application for the diagnosis of PD and neurodegenerative parkinsonisms.RT-QuIC analyses of OM and cerebrospinal fluid(CSF)can be combined with the aim of increasing the overall diagnostic accuracy of these diseases,especially in the early stages.
基金a National Health and Medical Research Council Leadership Fellowship(1195830)has received research funding from The Michael J.Fox Foundation and the Australian Research Council.S.A.F.was supported by The Sartain Lanier Family Foundation.He has been a consultant for Lundbeck,Sunovion,Biogen,Impel,Acorda,and CereSpir.He has received education and research grants from Medtronic,Boston Scientific,Sun Pharmaceuticals Advanced Research Company,Biohaven,Impax,Lilly,US World Meds,Sunovion Therapeutics,Neurocrine,Vaccinex,Voyager,Jazz Pharmaceuticals,CHDI Foundation,The Michael J.Fox Foundation,National Institutes of Health(NIH),and Parkinson’s Foundation.He receives royalties from Demos,Blackwell Futura,Springer for textbooks,and UpToDate.Other support was from Signant(Bracket Global LLC)and CNS Ratings LLC.N.G.serves as consultant to Sionara,NeuroDerm,Pharma2B,Denali,Neuron23,Sanofi-Genzyme,Biogen,and AbbVie.He receives royalties from Lysosomal Therapeutics(LTI)and payment for lectures at AbbVie,Sanofi-Genzyme,and Movement Disorder Society.He received research support from The Michael J.Fox Foundation,the National Parkinson Foundation,European Union,and Israel Science Foundation,as well as from Teva NNE program,Biogen,and Ionis.He receives support from the Sieratzki Family Foundation and the Aufzien Academic Center in Tel-Aviv University.A.N.received funding from the European Commission,Research Foundation Flanders,King Baudouin Foundation,The Michael J.Fox Foundation,Jacques and Gloria Gossweiler Foundation,and KU Leuven Internal Research Funds.M.H.is an inventor of patents held by the NIH for an immunotoxin for the treatment of focal movement disorders and the H-coil for magnetic stimulationin relation to the latter,he has received license-fee payments from the NIH(from Brainsway).He is on the Medical Advisory Boards of CALA Health and Brainsway(both unpaid positions).He is on the editorial board of approximately 15 journals and receives royalties and/or honoraria from publishing from Cambridge University Press,Oxford University Press,Springer,Wiley,Wolters Kluwer,and Elsevier.He has research grants from Medtronic,Inc.for a study of deep brain stimulation for dystonia and CALA Health for studies of a device to suppress tremor.
文摘There has been a growing appreciation for freezing of gait as a disabling symptom that causes a significant burden in Parkinson’s disease. Previous research has highlighted some of the key components that underlie the phenomenon, but these reductionist approaches have yet to lead to a paradigm shift resulting in the development of novel treatment strategies. Addressing this issue will require greater integration of multi-modal data with complex computational modeling, but there are a number of critical aspects that need to be considered before embarking on such an approach. This paper highlights where the field needs to address current gaps and shortcomings including the standardization of definitions and measurement, phenomenology and pathophysiology, as well as considering what available data exist and how future studies should be constructed to achieve the greatest potential to better understand and treat this devastating symptom.
