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1.
BMC Geriatr ; 24(1): 347, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38627620

RESUMO

BACKGROUND: The Comprehensive Geriatric Assessment (CGA) records geriatric syndromes in a standardized manner, allowing individualized treatment tailored to the patient's needs and resources. Its use has shown a beneficial effect on the functional outcome and survival of geriatric patients. A recently published German S1 guideline for level 2 CGA provides recommendations for the use of a broad variety of different assessment instruments for each geriatric syndrome. However, the actual use of assessment instruments in routine geriatric clinical practice and its consistency with the guideline and the current state of literature has not been investigated to date. METHODS: An online survey was developed by an expert group of geriatricians and sent to all licenced geriatricians (n = 569) within Germany. The survey included the following geriatric syndromes: motor function and self-help capability, cognition, depression, pain, dysphagia and nutrition, social status and comorbidity, pressure ulcers, language and speech, delirium, and frailty. Respondents were asked to report which geriatric assessment instruments are used to assess the respective syndromes. RESULTS: A total of 122 clinicians participated in the survey (response rate: 21%); after data cleaning, 76 data sets remained for analysis. All participants regularly used assessment instruments in the following categories: motor function, self-help capability, cognition, depression, and pain. The most frequently used instruments in these categories were the Timed Up and Go (TUG), the Barthel Index (BI), the Mini Mental State Examination (MMSE), the Geriatric Depression Scale (GDS), and the Visual Analogue Scale (VAS). Limited or heterogenous assessments are used in the following categories: delirium, frailty and social status. CONCLUSIONS: Our results show that the assessment of motor function, self-help capability, cognition, depression, pain, and dysphagia and nutrition is consistent with the recommendations of the S1 guideline for level 2 CGA. Instruments recommended for more frequent use include the Short Physical Performance Battery (SPPB), the Montreal Cognitive Assessment (MoCA), and the WHO-5 (depression). There is a particular need for standardized assessment of delirium, frailty and social status. The harmonization of assessment instruments throughout geriatric departments shall enable more effective treatment and prevention of age-related diseases and syndromes.


Assuntos
Transtornos de Deglutição , Delírio , Fragilidade , Humanos , Idoso , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Fragilidade/terapia , Avaliação Geriátrica/métodos , Dor , Inquéritos e Questionários
2.
J Neuroeng Rehabil ; 21(1): 112, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38943208

RESUMO

BACKGROUND: Maintaining static balance is relevant and common in everyday life and it depends on a correct intersegmental coordination. A change or reduction in postural capacity has been linked to increased risk of falls. People with Parkinson's disease (pwPD) experience motor symptoms affecting the maintenance of a stable posture. The aim of the study is to understand the intersegmental changes in postural sway and to apply a trend change analysis to uncover different movement strategies between pwPD and healthy adults. METHODS: In total, 61 healthy participants, 40 young (YO), 21 old participants (OP), and 29 pwPD (13 during medication off, PDoff; 23 during medication on, PDon) were included. Participants stood quietly for 10 s as part of the Short Physical Performance Battery. Inertial measurement units (IMU) at the head, sternum, and lumbar region were used to extract postural parameters and a trend change analysis (TCA) was performed to compare between groups. OBJECTIVE: This study aims to explore the potential application of TCA for the assessment of postural stability using IMUs, and secondly, to employ this analysis within the context of neurological diseases, specifically Parkinson's disease. RESULTS: Comparison of sensors locations revealed significant differences between head, sternum and pelvis for almost all parameters and cohorts. When comparing PDon and PDoff, the TCA revealed differences that were not seen by any other parameter. CONCLUSIONS: While all parameters could differentiate between sensor locations, no group differences could be uncovered except for the TCA that allowed to distinguish between the PD on/off. The potential of the TCA to assess disease progression, response to treatment or even the prodromal PD phase should be explored in future studies. TRIAL REGISTRATION: The research procedure was approved by the ethical committee of the Medical Faculty of Kiel University (D438/18). The study is registered in the German Clinical Trials Register (DRKS00022998).


Assuntos
Doença de Parkinson , Equilíbrio Postural , Humanos , Doença de Parkinson/fisiopatologia , Doença de Parkinson/diagnóstico , Doença de Parkinson/tratamento farmacológico , Equilíbrio Postural/fisiologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Adulto , Antiparkinsonianos/uso terapêutico , Adulto Jovem
3.
Neuromodulation ; 26(2): 364-373, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35227581

RESUMO

INTRODUCTION: Patients with advanced Parkinson disease (PD) often experience problems with mobility, including walking under single- (ST) and dual-tasking (DT) conditions. The effects of deep brain stimulation in the subthalamic nucleus (DBS) versus dopaminergic medication (Med) on these conditions are not well investigated. MATERIALS AND METHODS: We used two ST and two DT-gait paradigms to evaluate the effect of DBS and dopaminergic medication on gait parameters in 14 PD patients (mean age 66 ± 8 years) under DBSOFF/MedON, DBSON/MedOFF, and DBSON/MedON conditions. They performed standardized 20-meter walks with convenient and fast speed. To test DT capabilities, they performed a checking-boxes and a subtraction task during fast-paced walking. Quantitative gait analysis was performed using a tri-axial accelerometer (Dynaport, McRoberts, The Netherlands). Dual-task costs (DTC) of gait parameters and secondary task performance were compared intraindividually between DBSOFF/MedON vs DBSON/MedON, and DBSON/MedOFF vs DBSON/MedON to estimate responsiveness. RESULTS: Dopaminergic medication increased gait speed and cadence at convenient speed. It increased cadence and decreased number of steps at fast speed, and improved DTC of cadence during the checking boxes and DTC of cadence and number of steps during the subtraction tasks. DBS only improved DTC of cadence during the checking boxes and DTC of gait speed during the subtraction task. CONCLUSION: Dopaminergic medication showed larger additional effects on temporal gait parameters under ST and DT conditions in advanced PD than DBS. These results, after confirmation in independent studies, should be considered in the medical management of advanced PD patients with gait and DT deficits.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Pessoa de Meia-Idade , Idoso , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/complicações , Estimulação Encefálica Profunda/métodos , Marcha/fisiologia , Caminhada/fisiologia , Núcleo Subtalâmico/fisiologia
4.
Z Gerontol Geriatr ; 56(1): 59-64, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36454314

RESUMO

This case report describes an 82-year-old patient who was treated in a gerontological psychiatric ward due to a multifactorial gait disorder with falls. The main component of the gait disorder was depression, which was accompanied by a pronounced fear of falling. Other factors were polyneuropathy, gonarthrosis and an exercise deficit after previous inactivity. An important part of the multimodal treatment was electroconvulsive therapy (ECT). A total of nine sessions of ECT in right unilateral stimulation were conducted. The treatment resulted in a significant improvement of the depression and the gait disorder, which was impressively reflected in the geriatric assessment. The presented case shows that depression and fear of falling should not be underestimated as (main) components of a gait disorder. Here, a multimodal treatment including treatment of the depression by ECT was successful.


Assuntos
Eletroconvulsoterapia , Humanos , Idoso , Idoso de 80 Anos ou mais , Eletroconvulsoterapia/métodos , Depressão/terapia , Medo , Terapia Combinada , Marcha , Resultado do Tratamento
5.
BMC Geriatr ; 22(1): 668, 2022 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-35963992

RESUMO

BACKGROUND: Mobility deficits are highly prevalent among geriatric patients and have serious impact on quality of life, hospitalizations, and mortality. This study aims to capture predictors of mobility deficits in hospitalized geriatric patients using the International Classification of Functioning, Disability and Health (ICF) model as a framework. METHODS: Data were obtained from n = 397 patients (78 ± 7 years, 15 ± 7 ICD-11 diagnoses) on a geriatric ward at time of admission. Mobility was assessed using the Short Physical Performance Battery (SPPB) total score and gait, static balance and transfer subscores. Parameters from an extensive assessment including medical history, neuropsychological and motor examination, and questionnaires were assigned to the five components of the ICF model. Spearman's Correlation and multiple linear regression analyses were calculated to identify predictors for the SPPB total score and subscores. RESULTS: Use of walking aid, fear of falling (FOF, but not occurrence of previous falls), participation in society, ADL and grip strength were strongly associated with the SPPB total score and all subscores (p < .001). FOF and grip strength were significant predictors for the SPPB total score as well as for gait and transfer subscores. FOF also showed a strong association with the static balance subscore. The clinical parameters of the ICF model could only partially explain the variance in the SPPB total score (24%) and subscores (12-23%), with no parameter from the activities and participation component being significantly predictive. CONCLUSIONS: FOF and reduced grip strength are associated with mobility deficits in a hospitalized geriatric cohort. Further research should focus on interventions to reduce FOF and increase muscle strength in geriatric patients. Moreover, there is a need for ICF-based assessments instruments (especially in the activities and participation components) that allow a holistic view on mobility and further daily life-relevant health aspects in geriatric patients.


Assuntos
Acidentes por Quedas , Avaliação Geriátrica , Idoso , Medo , Hospitalização , Humanos , Qualidade de Vida
6.
Z Gerontol Geriatr ; 55(2): 116-122, 2022 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-35181808

RESUMO

Mobility and its limitations play an important role in the quality of life of geriatric patients and influence activity and participation. The assessment of mobility is therefore of particular importance for treatment and treatment planning in geriatric patients. There is a variety of assessment tools that cannot be used in every patient group, e.g. due to floor effects. This article provides an overview of common assessment tools and facilitates the evaluation and use of these tools. Special consideration is given to performance-oriented aspects and current technical developments such as wearables.


Assuntos
Avaliação Geriátrica , Qualidade de Vida , Idoso , Marcha , Humanos , Limitação da Mobilidade , Equilíbrio Postural , Caminhada
7.
Mov Disord ; 36(11): 2508-2518, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34002893

RESUMO

BACKGROUND: Extracellular vesicles are small vesicles that are released from many cells, including neurons. α-Synuclein has recently been described in extracellular vesicles derived from the central nervous system and may contribute to the spreading of disease pathology in α-synuclein-related neurodegeneration. OBJECTIVES: We aimed to examine the potential diagnostic value of α-synuclein in plasma extracellular vesicles from patients with Parkinson's disease (PD). METHODS: Preanalytical variables were studied to establish an optimized assay for preparation of plasma extracellular vesicles and detection of extracellular vesicle-derived α-synuclein. Plasma samples were obtained from 2 independent cohorts. The Tübingen cohort contained 96 patients with PD, 50 patients with dementia with Lewy bodies, 50 patients with progressive supranuclear palsy (PSP), and 42 healthy controls; the Kassel cohort included 47 patients with PD, 43 patients with dementia with Lewy bodies, and 36 controls with secondary parkinsonian syndromes. Extracellular vesicles were prepared from total plasma by size exclusion chromatography and quantified by nanoparticle tracking analysis, α-synuclein content was measured by an electrochemiluminescence assay. RESULTS: α-Synuclein concentration in plasma extracellular vesicles provided the best discrimination between PD, dementia with Lewy bodies, PSP, and healthy controls, with an area under the curve of 0.804 (PD vs dementia with Lewy bodies), 0.815 (PD vs. PSP), and 0.769 (PD vs healthy controls) in the Tübingen cohort. Results were validated in the Kassel cohort. CONCLUSIONS: The concentration of α-synuclein in plasma extracellular vesicles may serve as a potential diagnostic biomarker for PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Vesículas Extracelulares , Doença de Parkinson , Paralisia Supranuclear Progressiva , Biomarcadores , Vesículas Extracelulares/patologia , Humanos , Doença de Parkinson/patologia , alfa-Sinucleína
8.
Ann Neurol ; 86(3): 357-367, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31294853

RESUMO

OBJECTIVE: Quantification of gait with wearable technology is promising; recent cross-sectional studies showed that gait characteristics are potential prodromal markers for Parkinson disease (PD). The aim of this longitudinal prospective observational study was to establish gait impairments and trajectories in the prodromal phase of PD, identifying which gait characteristics are potentially early diagnostic markers of PD. METHODS: The 696 healthy controls (mean age = 63 ± 7 years) recruited in the Tubingen Evaluation of Risk Factors for Early Detection of Neurodegeneration study were included. Assessments were performed longitudinally 4 times at 2-year intervals, and people who converted to PD were identified. Participants were asked to walk at different speeds under single and dual tasking, with a wearable device placed on the lower back; 14 validated clinically relevant gait characteristics were quantified. Cox regression was used to examine whether gait at first visit could predict time to PD conversion after controlling for age and sex. Random effects linear mixed models (RELMs) were used to establish longitudinal trajectories of gait and model the latency between impaired gait and PD diagnosis. RESULTS: Sixteen participants were diagnosed with PD on average 4.5 years after first visit (converters; PDC). Higher step time variability and asymmetry of all gait characteristics were associated with a shorter time to PD diagnosis. RELMs indicated that gait (lower pace) deviates from that of non-PDC approximately 4 years prior to diagnosis. INTERPRETATION: Together with other prodromal markers, quantitative gait characteristics can play an important role in identifying prodromal PD and progression within this phase. ANN NEUROL 2019;86:357-367.


Assuntos
Diagnóstico Precoce , Análise da Marcha , Doença de Parkinson/diagnóstico , Doença de Parkinson/fisiopatologia , Sintomas Prodrômicos , Caminhada , Dispositivos Eletrônicos Vestíveis , Progressão da Doença , Feminino , Humanos , Modelos Lineares , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo
9.
BMC Geriatr ; 20(1): 45, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32028945

RESUMO

BACKGROUND: Motor and cognitive deficits and consequently mobility problems are common in geriatric patients. The currently available methods for diagnosis and for the evaluation of treatment in this vulnerable cohort are limited. The aims of the ComOn (COgnitive and Motor interactions in the Older populatioN) study are (i) to define quantitative markers with clinical relevance for motor and cognitive deficits, (ii) to investigate the interaction between both motor and cognitive deficits and (iii) to assess health status as well as treatment outcome of 1000 geriatric inpatients in hospitals of Kiel (Germany), Brescia (Italy), Porto (Portugal), Curitiba (Brazil) and Bochum (Germany). METHODS: This is a prospective, explorative observational multi-center study. In addition to the comprehensive geriatric assessment, quantitative measures of reduced mobility and motor and cognitive deficits are performed before and after a two week's inpatient stay. Components of the assessment are mobile technology-based assessments of gait, balance and transfer performance, neuropsychological tests, frailty, sarcopenia, autonomic dysfunction and sensation, and questionnaires to assess behavioral deficits, activities of daily living, quality of life, fear of falling and dysphagia. Structural MRI and an unsupervised 24/7 home assessment of mobility are performed in a subgroup of participants. The study will also investigate the minimal clinically relevant change of the investigated parameters. DISCUSSION: This study will help form a better understanding of symptoms and their complex interactions and treatment effects in a large geriatric cohort.


Assuntos
Acidentes por Quedas , Atividades Cotidianas , Idoso , Brasil , Cognição , Medo , Avaliação Geriátrica , Alemanha , Humanos , Itália , Portugal , Estudos Prospectivos , Qualidade de Vida
10.
Z Gerontol Geriatr ; 53(7): 687-698, 2020 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-32975634

RESUMO

Vascular dementias (VD, due to the various expressions of VD the plural form is used) are the second most common form of dementia after Alzheimer's dementia. These dementias play an important role especially in geriatric patients. They can occur due to acute events (e.g. stroke) and due to slowly progressive cerebrovascular damage. This article focuses on VD due to cortical and strategic infarcts, microangiopathic infarcts with lacunae as well as intracerebral bleeding. In addition to the clinical description and radiological findings, a special focus is on education, prevention and rehabilitation aspects.


Assuntos
Demência Vascular , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/terapia , Demência Vascular/diagnóstico , Demência Vascular/terapia , Escolaridade , Humanos , Acidente Vascular Cerebral
11.
Z Gerontol Geriatr ; 53(4): 340-346, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32430766

RESUMO

Geriatric medicine is a rapidly evolving field that addresses diagnostic, therapeutic and care aspects of older adults. Some disabilities and disorders affecting cognition (e.g. dementia), motor function (e.g. stroke, Parkinson's disease, neuropathies), mood (e.g. depression), behavior (e.g. delirium) and chronic pain disorders are particularly frequent in old subjects. As knowledge about these age-associated conditions and disabilities is steadily increasing, the integral implementation of neurogeriatric knowledge in geriatric medicine and specific neurogeriatric research is essential to develop the field. This article discusses how neurological know-how could be integrated in academic geriatric medicine to improve care of neurogeriatric patients, to foster neurogeriatric research and training concepts and to provide innovative care concepts for geriatric patients with predominant neurological conditions and disabilities.


Assuntos
Demência/terapia , Geriatria , Doenças do Sistema Nervoso/terapia , Doença de Parkinson/terapia , Idoso , Delírio , Humanos
12.
Z Gerontol Geriatr ; 52(2): 172-178, 2019 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-30206742

RESUMO

BACKGROUND: The Geriatrie-Check was developed as a screening tool for the identification of older patients with geriatric treatment requirements in hospitals. It was recommended by the Baden-Wuerttemberg Hospitals Association for routine use in hospitals in 2014 although no published validation studies are available. The test takes 3-5 min. AIM: Validation of the Geriatrie-Check in a prospective cohort of hospitalized neurological patients with and without geriatric characteristics. METHODS: In this prospective cross-sectional observational study at the University Hospital Tübingen, Germany the Geriatrie-Check was compared with a comprehensive geriatric assessment in 107 neurological inpatients aged 70 years and older (41% women, mean age 76.7 years). RESULTS: The Geriatrie-Check classified 61 patients (57%) as geriatric patients. These patients with a positive result in the Geriatrie-Check had a higher percentage of frailty (according to Fried et al.), higher values in the Gérontopôle frailty screening tool, higher values in the geriatric screening according to Lachs et el., slower gait speed, lower grip force, needed longer for the timed up-and-go test, had a greater fear of falling in the Falls Efficacy Scale - International, lower scores in the Mini Mental State Examination, needed more time to perform the Trail Making Test A and B, had higher values in the Beck's Depressions Inventar II and lower values in the visual analogue scale of the EQ-5D. A higher percentage of patients took more than five different drugs. INTERPRETATION AND CONCLUSION: The Geriatrie-Check has been shown to be a useful and valid tool for the identification of geriatric inpatients in neurological wards due to the good agreement with the results of the geriatric assessment.


Assuntos
Acidentes por Quedas , Avaliação Geriátrica , Acidentes por Quedas/prevenção & controle , Idoso , Estudos Transversais , Feminino , Alemanha , Humanos , Masculino , Estudos Prospectivos
13.
BMC Neurol ; 18(1): 114, 2018 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-30115021

RESUMO

BACKGROUND: Deficits in gait and balance are common among neurological inpatients. Currently, assessment of these patients is mainly subjective. New assessment options using wearables may provide complementary and more objective information. METHODS: In this prospective cross-sectional feasibility study performed over a four-month period, all patients referred to a normal neurology ward of a university hospital and aged between 40 and 89 years were asked to participate. Gait and balance deficits were assessed with wearables at the ankles and the lower back. Frailty, sarcopenia, Parkinsonism, depression, quality of life, fall history, fear of falling, physical activity, and cognition were evaluated with questionnaires and surveys. RESULTS: Eighty-two percent (n = 384) of all eligible patients participated. Of those, 39% (n = 151) had no gait and balance deficit, 21% (n = 79) had gait deficits, 11% (n = 44) had balance deficits and 29% (n = 110) had gait and balance deficits. Parkinson's disease, stroke, epilepsy, pain syndromes, and multiple sclerosis were the most common diseases. The assessment was well accepted. CONCLUSIONS: Our study suggests that the use of wearables for the assessment of gait and balance features in a clinical setting is feasible. Moreover, preliminary results confirm previous epidemiological data about gait and balance deficits among neurological inpatients. Evaluation of neurological inpatients with novel wearable technology opens new opportunities for the assessment of predictive, progression and treatment response markers.


Assuntos
Transtornos Neurológicos da Marcha/diagnóstico , Transtornos Neurológicos da Marcha/fisiopatologia , Marcha/fisiologia , Equilíbrio Postural/fisiologia , Dispositivos Eletrônicos Vestíveis , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Estudos de Viabilidade , Feminino , Transtornos Neurológicos da Marcha/epidemiologia , Alemanha/epidemiologia , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Projetos de Pesquisa
14.
Neurodegener Dis ; 17(4-5): 135-144, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28441649

RESUMO

BACKGROUND: For the early diagnosis of Parkinson disease dementia (PDD), objective home-based tools are needed to quantify even mild stages of dysfunction of the activities of daily living (ADL). OBJECTIVES: In this pilot study, home-based physical behavior was assessed to examine whether it is possible to distinguish mild cognitive impairment (PD-MCI) from PDD. METHODS: Fifty-five patients with mild to severe Parkinson disease (PD) participated in this cross-sectional study. Based on comprehensive neuropsychological testing, PD patients were classified as cognitively nonimpaired (PD-NC), PD-MCI or PDD. For physical behavior assessments, patients wore the accelerometer DynaPort® (McRoberts) for 3 days. Ordinal logistic regression models with continuous Y were applied to correct results for motor impairment and depressive symptoms. RESULTS: After excluding 7 patients due to insufficient wearing time, 48 patients with a mean of 2 recorded days were analyzed (17 PD-NC, 22 PD-MCI, 9 PDD). ADL-impaired PDD patients showed fewer sedentary bouts than non-ADL-impaired PD-MCI (p = 0.01, odds ratio [OR] = 8.9, 95% confidence interval [CI] = 1.8-45.2) and PD-NC (p = 0.01, OR = 10.3, CI = 1.6-67.3) patients, as well as a longer sedentary bout length (PD-NC: p = 0.02, OR = 0.1, CI = 0.02-0.65; PD-MCI: p = 0.02, OR = 0.14, CI = 0.03-0.69). These differences were mainly caused by fewer (PD-NC: p = 0.02, OR = 9.6, CI = 1.5-62.4; PD-MCI: p = 0.01, OR = 8.5, CI = 1.5-37.3) but longer sitting bouts (PD-NC: p = 0.03, OR = 0.12, CI = 0.02-0.80; PD-MCI: p = 0.04, OR = 0.19, CI = 0.04-0.93). Tests assessing executive function, visuoconstruction and attention correlated significantly with specific activity parameters (ρ ≥ 0.3; p < 0.05). CONCLUSION: Objective assessment of physical behavior, in particular the detection of sedentary bouts, is a promising contributor to the discrimination between PD-MCI and PDD.


Assuntos
Atividades Cotidianas/psicologia , Disfunção Cognitiva/classificação , Disfunção Cognitiva/diagnóstico , Exercício Físico/fisiologia , Doença de Parkinson/diagnóstico , Acelerometria , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Estudos Transversais , Metabolismo Energético/fisiologia , Feminino , Humanos , Locomoção/fisiologia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Projetos Piloto , Estatística como Assunto , Estatísticas não Paramétricas
15.
Neurodegener Dis ; 17(2-3): 83-88, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27760429

RESUMO

BACKGROUND AND OBJECTIVE: Reduced progranulin levels are a hallmark of frontotemporal dementia (FTD) caused by loss-of-function (LoF) mutations in the progranulin gene (GRN). However, alterations of central nervous progranulin expression also occur in neurodegenerative disorders unrelated to GRN mutations, such as Alzheimer's disease. We hypothesised that central nervous progranulin levels are also reduced in GRN-negative FTD. METHODS: Progranulin levels were determined in both cerebrospinal fluid (CSF) and serum in 75 subjects (37 FTD patients and 38 controls). All FTD patients were assessed by whole-exome sequencing for GRN mutations, yielding a target cohort of 34 patients without pathogenic mutations in GRN (GRN-negative cohort) and 3 GRN mutation carriers (2 LoF variants and 1 novel missense variant). RESULTS: Not only the GRN mutation carriers but also the GRN-negative patients showed decreased CSF levels of progranulin (serum levels in GRN-negative patients were normal). The decreased CSF progranulin levels were unrelated to patients' increased CSF levels of total tau, possibly indicating different destructive neuronal processes within FTD neurodegeneration. The patient with the novel GRN missense variant (c.1117C>T, p.P373S) showed substantially decreased CSF levels of progranulin, comparable to the 2 patients with GRN LoF mutations, suggesting a pathogenic effect of this missense variant. CONCLUSIONS: Our results indicate that central nervous progranulin reduction is not restricted to the relatively rare cases of FTD caused by GRN LoF mutations, but also contributes to the more common GRN-negative forms of FTD. Central nervous progranulin reduction might reflect a partially distinct pathogenic mechanism underlying FTD neurodegeneration and is not directly linked to tau alterations.


Assuntos
Demência Frontotemporal/sangue , Demência Frontotemporal/líquido cefalorraquidiano , Demência Frontotemporal/genética , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Peptídeos e Proteínas de Sinalização Intercelular/líquido cefalorraquidiano , Peptídeos e Proteínas de Sinalização Intercelular/genética , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Mutação de Sentido Incorreto , Fosforilação , Polimorfismo de Nucleotídeo Único , Progranulinas , Proteínas tau/líquido cefalorraquidiano , Proteínas tau/metabolismo
16.
Neurobiol Dis ; 91: 59-68, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26921471

RESUMO

High-mobility group box 1 (HMGB1) is a nuclear and cytosolic protein that is released during tissue damage from immune and non-immune cells - including microglia and neurons. HMGB1 can contribute to progression of numerous chronic inflammatory and autoimmune diseases which is mediated in part by interaction with the receptor for advanced glycation endproducts (RAGE). There is increasing evidence from in vitro studies that HMGB1 may link the two main pathophysiological components of Parkinson's disease (PD), i.e. progressive dopaminergic degeneration and chronic neuroinflammation which underlie the mechanistic basis of PD progression. Analysis of tissue and biofluid samples from PD patients, showed increased HMGB1 levels in human postmortem substantia nigra specimens as well as in the cerebrospinal fluid and serum of PD patients. In a mouse model of PD induced by sub-acute administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), systemic administration of neutralizing antibodies to HMGB1 partly inhibited the dopaminergic cell death, and reduced the increase of RAGE and tumour necrosis factor-alpha. The small natural molecule glycyrrhizin, a component from liquorice root which can directly bind to HMGB1, both suppressed MPTP-induced HMGB1 and RAGE upregulation while reducing MPTP-induced dopaminergic cell death in a dose dependent manner. These results provide first in vivo evidence that HMGB1 serves as a powerful bridge between progressive dopaminergic neurodegeneration and chronic neuroinflammation in a model of PD, suggesting that HMGB1 is a suitable target for neuroprotective trials in PD.


Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Ácido Glicirrízico/farmacologia , Proteína HMGB1/metabolismo , Doença de Parkinson/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Animais , Morte Celular/efeitos dos fármacos , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , Pessoa de Meia-Idade , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
17.
Mov Disord ; 31(9): 1283-92, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27430969

RESUMO

BACKGROUND: The past decade has witnessed a highly dynamic and growing expansion of novel methods aimed at improving the assessment of Parkinson's disease with technology (NAM-PD) in laboratory, clinical, and home environments. However, the current state of NAM-PD regarding their maturity, feasibility, and usefulness in assessing the main PD features has not been systematically evaluated. METHODS: A systematic review of articles published in the field from 2005 to 2015 was performed. Of 9,503 publications identified in PubMed and the Web of Science, 848 full papers were evaluated, and 588 original articles were assessed to evaluate the technological, demographic, clinimetric, and technology transfer readiness parameters of NAM-PD. RESULTS: Of the studies, 65% included fewer than 30 patients, < 50% employed a standard methodology to validate diagnostic tests, 8% confirmed their results in a different dataset, and 87% occurred in a clinic or lab. The axial features domain was the most frequently studied, followed by bradykinesia. Rigidity and nonmotor domains were rarely investigated. Only 6% of the systems reached a technology level that justified the hope of being included in clinical assessments in a useful time period. CONCLUSIONS: This systematic evaluation provides an overview of the current options for quantitative assessment of PD and what can be expected in the near future. There is a particular need for standardized and collaborative studies to confirm the results of preliminary initiatives, assess domains that are currently underinvestigated, and better validate the existing and upcoming NAM-PD. © 2016 International Parkinson and Movement Disorder Society.


Assuntos
Tecnologia Biomédica/normas , Técnicas e Procedimentos Diagnósticos/normas , Doença de Parkinson/diagnóstico , Humanos
18.
BMC Neurol ; 15: 192, 2015 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-26452640

RESUMO

BACKGROUND: Falls frequency increases with age and particularly in neurogeriatric cohorts. The interplay between eye movements and locomotion may contribute substantially to the occurrence of falls, but is hardly investigated. This paper provides an overview of current approaches to simultaneously measure eye and body movements, particularly for analyzing the association of vestibulo-ocular reflex (VOR) suppression, postural deficits and falls in neurogeriatric risk cohorts. Moreover, VOR suppression is measured during head-fixed target presentation and during gaze shifting while postural control is challenged. Using these approaches, we aim at identifying quantitative parameters of eye-head-coordination during postural balance and gait, as indicators of fall risk. METHODS/DESIGN: Patients with Progressive Supranuclear Palsy (PSP) or Parkinson's disease (PD), age- and sex-matched healthy older adults, and a cohort of young healthy adults will be recruited. Baseline assessment will include a detailed clinical assessment, covering medical history, neurological examination, disease specific clinical rating scales, falls-related self-efficacy, activities of daily living, neuro-psychological screening, assessment of mobility function and a questionnaire for retrospective falls. Moreover, participants will simultaneously perform eye and head movements (fixating a head-fixed target vs. shifting gaze to light emitting diodes in order to quantify vestibulo-ocular reflex suppression ability) under different conditions (sitting, standing, or walking). An eye/head tracker synchronized with a 3-D motion analysis system will be used to quantify parameters related to eye-head-coordination, postural balance, and gait. Established outcome parameters related to VOR suppression ability (e.g., gain, saccadic reaction time, frequency of saccades) and motor related fall risk (e.g., step-time variability, postural sway) will be calculated. Falls will be assessed prospectively over 12 months via protocols and monthly telephone interviews. DISCUSSION: This study protocol describes an experimental setup allowing the analysis of simultaneously assessed eye, head and body movements. Results will improve our understanding of the influence of the interplay between eye, head and body movements on falls in geriatric high-risk cohorts.


Assuntos
Acidentes por Quedas , Envelhecimento/fisiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Doença de Parkinson/fisiopatologia , Equilíbrio Postural/fisiologia , Reflexo Vestíbulo-Ocular/fisiologia , Paralisia Supranuclear Progressiva/fisiopatologia , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Movimentos Oculares/fisiologia , Feminino , Seguimentos , Movimentos da Cabeça/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
19.
BMC Neurol ; 15: 89, 2015 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-26059091

RESUMO

BACKGROUND: Currently, assessment of symptoms associated with Parkinson's disease is mainly performed in the clinic. However, these assessments have limitations because they provide only a snapshot of the condition. METHODS: The feasibility and usability of an objective, continuous and relatively unobtrusive system (SENSE-PARK System), which consists of wearable sensors (three worn during the day and one worn at night), a smartphone-based App, a balance board and computer software, was tested 24/7 over 12 weeks in a study including 22 PD patients. During the first four weeks of the study, patients did not get feedback about their performance, during the last eight weeks they did. The study included seven clinical visits with standardized interviews, and regular phone contact. The primary outcome was the number of drop-outs during the study. As secondary outcomes, the Post-Study System Usability Questionnaire (PSSUQ), score and information obtained from the standardized interviews were used to evaluate the usability of the system. RESULTS: All patients completed the study. The participants rated the usability of the SENSE-PARK System with a mean score of 2.67 (±0.49) on the PSSUQ. The interviews revealed that most participants liked using the system and appreciated that it signaled changes in their health condition. CONCLUSIONS: This 12 week controlled study demonstrates that the acceptance level of PD patients using the SENSE-PARK System as a home-based 24/7 assessment is very good. Particular emphasis should be given to a user-friendly design. Motivation to wear such a system can be increased by providing direct feedback about the individual health condition.


Assuntos
Monitorização Ambulatorial/métodos , Doença de Parkinson/diagnóstico , Aceitação pelo Paciente de Cuidados de Saúde , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial/instrumentação , Estudos Multicêntricos como Assunto , Cooperação do Paciente , Satisfação do Paciente , Projetos Piloto
20.
Diagnostics (Basel) ; 13(15)2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37568932

RESUMO

We report the electroencephalography (EEG) showing an intermittent generalized polyspike pattern in EEG due to an aseptic meningoencephalitis in a 71-year-old soporous patient. Initially, she presented with word-finding disturbances and later with generalized tonic-clonic seizures. The cerebrospinal fluid (CSF) showed pleocytosis of 99 leukocytes/µL (primarily neutrophils) and an increased protein level of 1240 mg/L (CSF/serum glucose ratio and lactate unremarkable). Pathogens and autoimmune antibodies in CSF were not found. Brain imaging was unremarkable. After antibiotic, antiviral and anticonvulsive therapy, the pattern in the EEG was no longer detectable. The patient was discharged to go home due to absence of any residues.

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