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1.
J Neural Transm (Vienna) ; 130(6): 783-791, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36609737

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disorder, with increasing numbers of affected patients. Many patients lack adequate care due to insufficient specialist neurologists/geriatricians, and older patients experience difficulties traveling far distances to reach their treating physicians. A new option for these obstacles would be telemedicine and wearables. During the last decade, the development of wearable sensors has allowed for the continuous monitoring of bradykinesia and dyskinesia. Meanwhile, other systems can also detect tremors, freezing of gait, and gait problems. The most recently developed systems cover both sides of the body and include smartphone apps where the patients have to register their medication intake and well-being. In turn, the physicians receive advice on changing the patient's medication and recommendations for additional supportive therapies such as physiotherapy. The use of smartphone apps may also be adapted to detect PD symptoms such as bradykinesia, tremor, voice abnormalities, or changes in facial expression. Such tools can be used for the general population to detect PD early or for known PD patients to detect deterioration. It is noteworthy that most PD patients can use these digital tools. In modern times, wearable sensors and telemedicine open a new window of opportunity for patients with PD that are easy to use and accessible to most of the population.


Assuntos
Transtornos Neurológicos da Marcha , Doença de Parkinson , Dispositivos Eletrônicos Vestíveis , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/terapia , Hipocinesia/diagnóstico , Tremor
2.
Eur J Neurol ; 30(5): 1465-1480, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36757008

RESUMO

Levodopa is the gold standard for the symptomatic treatment of Parkinson's disease (PD). There are well documented motor and non-motor fluctuations, however, that occur almost inevitably once levodopa is started after a variable period in people with PD. Whilst brain neurodegenerative processes play a part in the pathogenesis of these fluctuations, a range of barriers across the gastrointestinal (GI) tract can alter levodopa pharmacokinetics, ultimately contributing to non-optimal levodopa response and symptoms fluctuations. GI barriers to levodopa transport and absorption include dysphagia, delayed gastric emptying, constipation, Helicobacter pylori infection, small intestinal bacterial overgrowth and gut dysbiosis. In addition, a protein-rich diet and concomitant medication intake can further alter levodopa pharmacokinetics. This can result in unpredictable or sub-optimal levodopa response, 'delayed on' or 'no on' phenomena. In this narrative review, we provided an overview on the plethora of GI obstacles to levodopa transport and absorption in PD and their implications on levodopa pharmacokinetics and development of motor fluctuations. In addition, management strategies to address GI dysfunction in PD are highlighted, including use of non-oral therapies to bypass the GI tract.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Doença de Parkinson , Humanos , Levodopa/efeitos adversos , Doença de Parkinson/complicações , Antiparkinsonianos/uso terapêutico , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Trato Gastrointestinal
3.
J Neurol Neurosurg Psychiatry ; 92(12): 1313-1318, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510000

RESUMO

BACKGROUND: The effects of subthalamic stimulation (subthalamic nucleus-deep brain stimulation, STN-DBS) on impulsive and compulsive behaviours (ICB) in Parkinson's disease (PD) are understudied. OBJECTIVE: To investigate clinical predictors of STN-DBS effects on ICB. METHODS: In this prospective, open-label, multicentre study in patients with PD undergoing bilateral STN-DBS, we assessed patients preoperatively and at 6-month follow-up postoperatively. Clinical scales included the Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale (QUIP-RS), PD Questionnaire-8, Non-Motor Symptom Scale (NMSS), Unified PD Rating Scale in addition to levodopa-equivalent daily dose total (LEDD-total) and dopamine agonists (LEDD-DA). Changes at follow-up were analysed with Wilcoxon signed-rank test and corrected for multiple comparisons (Bonferroni method). We explored predictors of QUIP-RS changes using correlations and linear regressions. Finally, we dichotomised patients into 'QUIP-RS improvement or worsening' and analysed between-group differences. RESULTS: We included 55 patients aged 61.7 years±8.4 with 9.8 years±4.6 PD duration. QUIP-RS cut-offs and psychiatric assessments identified patients with preoperative ICB. In patients with ICB, QUIP-RS improved significantly. However, we observed considerable interindividual variability of clinically relevant QUIP-RS outcomes as 27.3% experienced worsening and 29.1% an improvement. In post hoc analyses, higher baseline QUIP-RS and lower baseline LEDD-DA were associated with greater QUIP-RS improvements. Additionally, the 'QUIP-RS worsening' group had more severe baseline impairment in the NMSS attention/memory domain. CONCLUSIONS: Our results show favourable ICB outcomes in patients with higher preoperative ICB severity and lower preoperative DA doses, and worse outcomes in patients with more severe baseline attention/memory deficits. These findings emphasise the need for comprehensive non-motor and motor symptoms assessments in patients undergoing STN-DBS. TRIAL REGISTRATION NUMBER: DRKS00006735.


Assuntos
Comportamento Compulsivo/psicologia , Estimulação Encefálica Profunda , Comportamento Impulsivo/fisiologia , Doença de Parkinson/terapia , Núcleo Subtalâmico/fisiopatologia , Idoso , Comportamento Compulsivo/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Doença de Parkinson/psicologia , Estudos Prospectivos , Qualidade de Vida
4.
J Neural Transm (Vienna) ; 128(3): 305-314, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33146753

RESUMO

Non-motor symptoms (NMS) occur in patients with cervical dystonia (CD) but with variable frequencies and impact on health-related quality of life (HRQoL). To define non-motor and motor profiles and their respective impact on HRQoL in CD patients using the newly validated Dystonia Non-Motor Symptoms Questionnaire (DNMSQuest). In an observational prospective multicentre case-control study, we enrolled 61 patients with CD and 61 age- and sex-matched healthy controls (HC) comparing demographic data, motor and non-motor symptoms and HRQoL measurements. 95% CD patients reported at least one NMS. Mean total NMS score was significantly higher in CD patients (5.62 ± 3.33) than in HC (1.74 ± 1.52; p < 0.001). Pain, insomnia and stigma were the most prevalent NMS and HRQoL was significantly impaired in CD patients compared to HC. There was strong correlation of NMS burden with HRQoL (CDQ-24: r = 0.72, EQ-5D: r = - 0.59; p < 0.001) in CD patients. Regression analysis between HRQoL and NMS suggested that emotional well-being (standardized beta = - 0.352) and pain (standardized beta = - 0.291) had a major impact on HRQoL while, in contrast motor severity had no significant impact in this model. Most NMS with the exception of pain, stigma and ADL did not correlate with motor severity. NMS are highly prevalent in CD patients and occur independent of age, sex, disease duration, duration of botulinum neurotoxin therapy and socio-economic status. Specific NMS such as emotional well-being and pain have a major impact on HRQoL and are more relevant than motor severity.


Assuntos
Qualidade de Vida , Torcicolo , Estudos de Casos e Controles , Humanos , Dor , Estudos Prospectivos
5.
Stereotact Funct Neurosurg ; 98(6): 416-423, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32966999

RESUMO

BACKGROUND: Deep brain stimulation (DBS) is an established method of treatment for Parkinson's disease (PD). A stimulation sweet spot at the interface between the motor and associative clusters of the subthalamic nucleus (STN) has recently been postulated. The aim of this study was to analyze the available clustering methods for the STN and their correlation to outcome. METHODS: This is a retrospective analysis of a group of 20 patients implanted with a DBS device for PD. Atlas-based and diffusion tractography-based parcellation of the STN was performed. The distances of the electrode to the obtained clusters were compared to each other and to outcome parameters, which included levodopa equivalent dose (LED) reduction, Unified Parkinson's Disease Rating Scale (UPDRS)-III scores, and reduction in scores for items 32 and 36 of the UPDRS-IV. RESULTS: The implanted electrodes were located nearest to the motor clusters of the STN. The following significant associations with postoperative LED reduction were found: (1) distance of the electrode to the motor cluster in the Accolla and DISTAL atlases (p < 0.01) and (2) distance of the electrode to the supplementary motor area cluster (p = 0.02). There was no association with either the UPDRS-III or the UPDRS-IV score. CONCLUSIONS: The results of this study suggest the possibility that atlas-based clustering, as well as diffusion tractography-based parcellation, can be useful in estimating the stimulation target ("sweet spot") for STN-DBS in PD patients. Atlas-based as well as diffusion-based clustering might become a useful tool in DBS trajectory planning.


Assuntos
Atlas como Assunto , Estimulação Encefálica Profunda/métodos , Imagem de Tensor de Difusão/métodos , Doença de Parkinson/diagnóstico por imagem , Núcleo Subtalâmico/diagnóstico por imagem , Idoso , Análise por Conglomerados , Eletrodos Implantados , Feminino , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/terapia , Estudos Retrospectivos , Núcleo Subtalâmico/anatomia & histologia , Resultado do Tratamento
6.
Stereotact Funct Neurosurg ; 97(3): 195-201, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31553992

RESUMO

BACKGROUND: The Six Sigma concept allows for the evaluation of quality changes after the implementation of new technical equipment or adjustment of perioperative procedures. Exemplarily, we applied this method for quality assessment in deep brain stimulation surgery (DBS) for Parkinson's disease. METHODS: The medical procedure and possible errors were registered. Then, 6 critical-to-quality characteristics regarding clinical outcome, surgical precision, and the surgical process were measured. The surgical procedure was then optimized in 2 steps, and its measurement, along with the analysis, was repeated twice. RESULTS: By optimizing perioperative settings, the operation time could be reduced, and the precision of the lead placement could be increased. Clinical outcome, as measured by improvement in UPDRS-III, IV, and reduction of medication could also be improved with smaller required stimulation voltage. With directional leads considerable reduction of medication was achieved in 97% of patients (σ-value 3.39) compared to 83.7% (σ-value 2.53) with nondirectional leads. CONCLUSION: This study shows that the Six Sigma concept is a suitable quality tool to analyze and improve treatment quality of complex medical procedures such as lead positioning in DBS surgery in clinical routine. Our results suggest that directional leads in subthalamic nucleus DBS may have a favorable impact on patients' outcome.


Assuntos
Estimulação Encefálica Profunda/normas , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/terapia , Melhoria de Qualidade/normas , Núcleo Subtalâmico/diagnóstico por imagem , Núcleo Subtalâmico/cirurgia , Idoso , Estimulação Encefálica Profunda/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Reprodutibilidade dos Testes , Gestão da Qualidade Total/métodos , Gestão da Qualidade Total/normas , Resultado do Tratamento
7.
Int J Qual Health Care ; 30(10): 760-768, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29917085

RESUMO

BACKGROUND: For quality analysis, we applied the Six Sigma concept to define quality indicators and their boundaries as well as to compare treatment-dependent outcome data of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD). METHODS: The Unified Parkinson Disease Rating Scale (UPDRS) III with on medication and on stimulation, the reduction of daily levodopa equivalence doses (LED), and the stimulation amplitude 1 year after surgery were registered. Regarding the results of the EARLYSTIM study, sigma values for applicable studies were calculated and compared. Further, the impact of perioperative conditions on patients' outcomes was analyzed. RESULTS: Forty-one studies with 2184 patients were included. The bleeding risk was 1.36%. In median, UPDRS III on/on improved by 19.9% while the LED was reduced by 45.2%. The median stimulation amplitude was 2.84 V. With the Six Sigma principle, a comparison between different centers was possible. Microelectrode recordings (MER) did not correlate with occurrence of bleedings and did not impact patient outcome. CONCLUSIONS: The Six Sigma principle can be simply used to analyze, improve and compare complex medical processes, particularly, the DBS surgery. Based on these data, higher sigma values were reached for clinical improvement in UPDRS III on/on for patients who underwent surgery in local anesthesia with intraoperative test stimulation compared to surgery in general anesthesia. However, the difference was not statistically significant. Application of MER was found to be optional with no increased bleeding risk and no improvement on patient's outcome.


Assuntos
Estimulação Encefálica Profunda/métodos , Garantia da Qualidade dos Cuidados de Saúde/métodos , Gestão da Qualidade Total/métodos , Idoso , Estimulação Encefálica Profunda/efeitos adversos , Humanos , Hemorragias Intracranianas , Levodopa/administração & dosagem , Levodopa/uso terapêutico , Pessoa de Meia-Idade , Doença de Parkinson/cirurgia , Doença de Parkinson/terapia , Núcleo Subtalâmico , Resultado do Tratamento
8.
Neuroepidemiology ; 49(1-2): 1-17, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28803229

RESUMO

BACKGROUND: Ethnic variations have been described in medical conditions, such as hypertension, diabetes, and multiple sclerosis. Whether ethnicity plays a role in Parkinson's disease (PD), particularly with regard to non-motor symptoms (NMS), remains unclear. Existing literature is diverse, controversial, and inadequately documented. This review aims to analyse and report the currently available literature on NMS, specifically in Asian PD patients. SUMMARY: We conducted a literature review using PubMed, searching for articles and currently available publications that reference and assess NMS in PD patients living in Asia using the validated NMS Questionnaire (NMS Quest) and NMS Scale (NMSS). In total, 24 articles were included: 12 using the NMS Quest and 12 using the NMSS. Symptoms of constipation, memory impairment, and nocturia were the most frequently self-reported symptoms (NMS Quest) in selected Asian populations, while symptoms within the domains sleep/fatigue, attention/memory, and mood/apathy were most prevalent when applying the health-professional completed NMSS. Key Messages: NMS are generally prevalent and highly burdensome within selected Asian PD populations living in countries included in this review. Our review suggests that NMS-driven phenotypic heterogeneity is present in Asian patients, and compared to Western PD populations there might be variations in assessed NMS.


Assuntos
Povo Asiático/etnologia , Doença de Parkinson/diagnóstico , Doença de Parkinson/etnologia , Ásia/etnologia , Humanos , Doença de Parkinson/complicações , Inquéritos e Questionários
9.
J Neural Transm (Vienna) ; 124(6): 709-713, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28155133

RESUMO

This article summarises the noteworthy contribution of Professor Jellinger to the understanding of Parkinson's disease (PD) as a disease affecting multiple body- and neurotransmitter-systems. Phosphorylated alpha-synuclein and the formation of Lewy pathology as neuropathological hallmarks of PD seem to spread from the enteric nervous system and the olfactory bulb in a rostrocranial direction to the CNS. Subsequently, a progressive degeneration of the dopaminergic-nigrostriatal system and widespread extranigral pathology affecting different anatomical structures and neurotransmitters are induced causing the various non-motor and motor symptoms of PD.


Assuntos
Doença de Parkinson/fisiopatologia , Animais , Encéfalo/fisiopatologia , Humanos
10.
Curr Opin Neurol ; 29(4): 467-73, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27262147

RESUMO

PURPOSE OF REVIEW: In recent years progress has been made in the detection and evaluation of nonmotor symptoms in Parkinson's disease. The pathophysiology is better understood and new treatment is available, which will be discussed in this review. RECENT FINDINGS: The most intriguing recent finding is the fact that Parkinson's disease may be a spreading disease. From the environment a toxin, bacteria, or virus may start in genetically susceptible patients a cascade of α-synuclein aggregation which reaches via the olfactory and the enteric system of the gut the brain where further spreading causes symptoms, such as sleep disturbances, motor impairment, and neuropsychiatric symptoms. New treatment should address the abnormal α-synuclein folding. If this would be achieved premotor signs, such as hyposmia, rapid eye movement-sleep behavior disorder, constipation, or depression may be a kind of biomarkers which allow together with other diagnostic tools, such as parenchymal sonography, iodobenzamide-scintigraphy and dopamine transporter scans the prediction whether somebody might be under way to develop the full-blown Parkinson's disease syndrome. SUMMARY: Parkinson's disease seems to be a spreading disease which causes not only a dopaminergic deficit as major cause for the movement disorder but also impairs function of many other brain centers which leads to a multitransmitter malfunction.


Assuntos
Doenças do Sistema Nervoso Autônomo/fisiopatologia , Doença de Parkinson/diagnóstico , Doença de Parkinson/fisiopatologia , alfa-Sinucleína/fisiologia , Doenças do Sistema Nervoso Autônomo/etiologia , Doenças Cardiovasculares/fisiopatologia , Discinesias/fisiopatologia , Diagnóstico Precoce , Disfunção Erétil/etiologia , Fadiga/etiologia , Gastroenteropatias/fisiopatologia , Humanos , Masculino , Transtornos Mentais/etiologia , Transtornos dos Movimentos/fisiopatologia , Transtornos do Olfato/fisiopatologia , Dor/etiologia , Doença de Parkinson/complicações , Transtornos do Sono-Vigília/fisiopatologia , Doenças Urológicas/fisiopatologia
11.
Acta Neurochir (Wien) ; 157(3): 479-86, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25596640

RESUMO

BACKGROUND: Successful deep brain stimulation is mostly dependent on accurate positioning of the leads at the optimal target points. We investigated whether the identification of the subthalamic nucleus in T2-weighted 3-T MRI, fluid-attenuated inversion recovery 3-T MRI and susceptibility-weighted 3-T MRI is confirmed by intraoperative neurological microelectrode recording. METHODS: We evaluated 182 microelectrode recording leads in 21 patients with bilateral deep brain stimulation, retrospectively. Consequently, 728 electrode contact positions in T2-weighted 3-T MRI, 552 electrode contact positions in fluid-attenuated inversion recovery 3-T MRI and 490 electrode contact positions in susceptibility-weighted 3-T MRI were evaluated for a positive nucleus subthalamicus signal. RESULTS: The highest sensitivity was measured for fluid-attenuated inversion recovery 3-T MRI with 82.5 %, while the highest specificity was observed for susceptibility-weighted 3-T MRI with 90.6 %. The negative predictive value was nearly equal for susceptibility-weighted MRI and fluid-attenuated inversion recovery MRI with 87.5 % vs. 87.1 %, but the positive predictive value was higher in susceptibility-weighted 3-T MRI (86.0 %) than in the other MRI sequences. CONCLUSIONS: The susceptibility-weighted 3-T MRI-based subthalamic nucleus localization shows the best accuracy compared with T2-weighted and fluid-attenuated inversion recovery 3-T MRI. Therefore, the susceptibility-weighted 3-T MRI should be preferred for surgical planning when the operation procedure is performed under general anesthesia without microelectrode recordings.


Assuntos
Estimulação Encefálica Profunda/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Doença de Parkinson/terapia , Núcleo Subtalâmico/fisiopatologia , Idoso , Estimulação Encefálica Profunda/instrumentação , Imagem de Difusão por Ressonância Magnética/instrumentação , Feminino , Humanos , Masculino , Microeletrodos , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Estudos Retrospectivos , Sensibilidade e Especificidade
12.
J Neural Transm (Vienna) ; 121 Suppl 1: S25-31, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24696217

RESUMO

Sleep disturbances in Parkinson's disease and parkinsonism (such as atypical parkinsonian disorders like multiple system atrophy, progressive supranuclear palsy, dementia with Lewy bodies and corticobasal degeneration) are multifactorial and as such treatment needs to be tailored to the specific patient case and sleep dysfunction. One also has to consider drug-related effects on sleep architecture. This article provides an overview of the therapeutic options for nocturnal problems in Parkinson`s disease and atypical parkinsonian disorders.


Assuntos
Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Transtornos Parkinsonianos/fisiopatologia , Transtornos Parkinsonianos/terapia , Transtornos do Sono-Vigília/fisiopatologia , Transtornos do Sono-Vigília/terapia , Humanos
13.
NPJ Parkinsons Dis ; 10(1): 14, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195715

RESUMO

Different stages of Parkinson's disease (PD) are defined by clinical criteria, while late-stage PD is marked by the onset of morbidity milestones and rapid clinical deterioration. Based on neuropathological evidence, degeneration in the dopaminergic system occurs primarily in the early stage of PD, raising the question of what drives disease progression in late-stage PD. This study aimed to investigate whether late-stage PD is associated with increased neurodegeneration dynamics rather than functional decompensation using the blood-based biomarker serum neurofilament light chain (sNfL) as a proxy for the rate of neurodegeneration. The study included 118 patients with PD in the transition and late-stage (minimum disease duration 5 years, mean (SD) disease duration 15 (±7) years). The presence of clinical milestones (hallucinations, dementia, recurrent falls, and admission to a nursing home) and mortality were determined based on chart review. We found that sNfL was higher in patients who presented with at least one clinical milestone and increased with a higher number of milestones (Spearman's ρ = 0.66, p < 0.001). Above a cutoff value of 26.9 pg/ml, death was 13.6 times more likely during the follow-up period (95% CI: 3.53-52.3, p < 0.001), corresponding to a sensitivity of 85.0% and a specificity of 85.7% (AUC 0.91, 95% CI: 0.85-0.97). Similar values were obtained when using an age-adjusted cutoff percentile of 90% for sNfL. Our findings suggest that the rate of ongoing neurodegeneration is higher in advanced PD (as defined by the presence of morbidity milestones) than in earlier disease stages. A better understanding of the biological basis of stage-dependent neurodegeneration may facilitate the development of neuroprotective means.

14.
Mov Disord Clin Pract ; 10(4): 569-578, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37070057

RESUMO

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for Parkinson's disease (PD). The long-term benefit in PD patients with STN-DBS in comparison to medical treatment (MT) alone has not yet been demonstrated conclusively. Objectives: To judge the long-term outcome of patients with STN-DBS. Methods: To assess the evolution of PD symptoms and health-related quality of life (HRQoL) after deep brain stimulation (DBS) surgery, we conducted a cross-sectional analysis of 115 patients with STN-DBS with rater-based scales and self-reported questionnaires. In addition, we screened records of all our STN-DBS patients (2001-2019, n = 162 patients) for the onset of the morbidity milestones (falls, hallucinations, dementia, and nursing home placement) to assess disability-free life expectancy. Results: In the first year of STN-DBS, levodopa equivalent dose was reduced and motor function improved. Nonmotor symptoms and cognition remained stable. These effects were similar to previous studies. Morbidity milestones occurred 13 ± 7 years after diagnosis. Motor function, cognition, and HRQoL significantly worsened after the occurrence of any milestone, confirming the clinical relevance of these milestones. After onset of the first milestone, mean survival time was limited to 5 ± 0.8 years, which is comparable with patients with PD but without STN-DBS. Conclusions: On average, PD patients with STN-DBS live with their disease for a longer time, and morbidity milestones occur later in the disease course than in PD patients with MT. As judged by morbidity milestones, morbidity remains compressed into the final 5 years of life in PD patients with STN-DBS.

15.
Front Neurol ; 14: 1149604, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37056364

RESUMO

Objective: A total of 48% of patients with Parkinson's disease (PD) present symptoms of gastrointestinal dysfunction, particularly constipation. Furthermore, gastrointestinal tract (GIT)-related non-motor symptoms (NMSs) appear at all stages of PD, can be prodromal by many years and have a relevant impact on the quality of life. There is a lack of GIT-focused validated tools specific to PD to assess their occurrence, progress, and response to treatment. The aim of this study was to develop and evaluate a novel, disease- and symptom-specific, self-completed questionnaire, titled Gut Dysmotility Questionnaire (GDQ), for screening and monitoring gastrointestinal dysmotility of the lower GIT in patients with PD. Methods: In phase 1, a systematic literature review and multidisciplinary expert discussions were conducted. In phase 2, cognitive pretest studies comprising standard pretests, interviews, and evaluation questionnaires were performed in patients with PD (n = 21), age- and sex-matched healthy controls (HC) (n = 30), and neurologists (n = 11). Incorporating these results, a second round of cognitive pretests was performed investigating further patients with PD (n = 10), age- and sex-matched HC (n = 10), and neurologists (n = 5). The questionnaire was adapted resulting in the final GDQ, which underwent cross-cultural adaptation to the English language. Results: We report significantly higher GDQ total scores and higher scores in five out of eight domains indicating a higher prevalence of gastrointestinal dysmotility in patients with PD than in HC (p < 0.05). Cognitive pretesting improved the preliminary GDQ so that the final GDQ was rated as relevant (100/100%), comprehensive (100/90%), easy to understand concerning questions and answer options (100/90%), and of appropriate length (80/100%) by neurologists and patients with PD, respectively. The GDQ demonstrated excellent internal consistency (Cronbach's alpha value of 0.94). Evidence for good construct validity is given by moderate to high correlations of the GDQ total score and its domains by intercorrelations (r s = 0.67-0.91; p < 0.001) and with validated general NMS measures as well as with specific items that assess gastrointestinal symptoms. Interpretation: The GDQ is a novel, easy, and quick 18-item self-assessment questionnaire to screen for and monitor gastrointestinal dysmotility with a focus on constipation in patients with PD. It has shown high acceptance and efficacy as well as good construct validity in cognitive pretests.

16.
Sci Rep ; 12(1): 1446, 2022 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-35087088

RESUMO

Deep brain stimulation (DBS) is a potent symptomatic therapy for Parkinson's disease, but it is debated whether it causes or prevents neurodegeneration. We used serum neurofilament light chain (NFL) as a reporter for neuronal damage and found no difference between 92 patients with chronic STN-DBS and 57 patients on best medical treatment. Serum NFL transiently increased after DBS surgery whereas the initiation of STN stimulation did not affect NFL levels, suggesting that DBS surgery can be associated with neuronal damage whereas stimulation itself is not.


Assuntos
Estimulação Encefálica Profunda/efeitos adversos , Proteínas de Neurofilamentos/sangue , Procedimentos Neurocirúrgicos/efeitos adversos , Doença de Parkinson/terapia , Núcleo Subtalâmico/patologia , Idoso , Estimulação Encefálica Profunda/métodos , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neurônios/patologia , Núcleo Subtalâmico/citologia , Núcleo Subtalâmico/cirurgia
17.
IEEE Trans Biomed Eng ; 69(5): 1573-1584, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34596531

RESUMO

OBJECTIVE: Parkinson's Disease (PD) is a progressive neurodegenerative disorder, manifesting with subtle early signs, which, often hinder timely and early diagnosis and treatment. The development of accessible, technology-based methods for longitudinal PD symptoms tracking in daily living, offers the potential for transforming disease assessment and accelerating diagnosis. METHODS: A privacy-aware method for classifying patients and healthy controls (HC), on the grounds of speech impairment present in PD, is proposed. Voice features from running speech signals were extracted from passively-captured recordings over voice calls. Language-aware training of multiple- and single-instance learning classifiers was employed to fuse and predict on voice features and demographic data from a multilingual cohort of 498 subjects (392/106 self-reported HC/PD patients). RESULTS: By means of leave-one-subject-out cross-validation, the best-performing models yielded 0.69/0.68/0.63/0.83 area under the Receiver Operating Characteristic curve (AUC) for the binary classification of PD patient vs. HC in sub-cohorts of English/Greek/German/Portuguese-speaking subjects, respectively. Out-of sample testing of the best performing models was conducted in an additional dataset, generated by 63 clinically-assessed subjects (24/39 HC/early PD patients). Testing has resulted in 0.84/0.93/0.83 AUC for the English/Greek/German-speaking sub-cohorts, respectively. CONCLUSIONS: The proposed approach outperforms other methods proposed for language-aware PD detection considering the ecological validity of the voice data. SIGNIFICANCE: This paper introduces for the first time a high-frequency, privacy-aware and unobtrusive PD screening tool based on analysis of voice samples captured during routine phone calls.


Assuntos
Doença de Parkinson , Corrida , Diagnóstico Precoce , Humanos , Doença de Parkinson/diagnóstico , Curva ROC , Fala
18.
Sci Rep ; 11(1): 1632, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452324

RESUMO

Parkinson's disease (PD) is a neurodegenerative disorder with both motor and non-motor symptoms. Despite the progressive nature of PD, early diagnosis, tracking the disease's natural history and measuring the drug response are factors that play a major role in determining the quality of life of the affected individual. Apart from the common motor symptoms, i.e., tremor at rest, rigidity and bradykinesia, studies suggest that PD is associated with disturbances in eating behavior and energy intake. Specifically, PD is associated with drug-induced impulsive eating disorders such as binge eating, appetite-related non-motor issues such as weight loss and/or gain as well as dysphagia-factors that correlate with difficulties in completing day-to-day eating-related tasks. In this work we introduce Plate-to-Mouth (PtM), an indicator that relates with the time spent for the hand operating the utensil to transfer a quantity of food from the plate into the mouth during the course of a meal. We propose a two-step approach towards the objective calculation of PtM. Initially, we use the 3D acceleration and orientation velocity signals from an off-the-shelf smartwatch to detect the bite moments and upwards wrist micromovements that occur during a meal session. Afterwards, we process the upwards hand micromovements that appear prior to every detected bite during the meal in order to estimate the bite's PtM duration. Finally, we use a density-based scheme to estimate the PtM durations distribution and form the in-meal eating behavior profile of the subject. In the results section, we provide validation for every step of the process independently, as well as showcase our findings using a total of three datasets, one collected in a controlled clinical setting using standardized meals (with a total of 28 meal sessions from 7 Healthy Controls (HC) and 21 PD patients) and two collected in-the-wild under free living conditions (37 meals from 4 HC/10 PD patients and 629 meals from 3 HC/3 PD patients, respectively). Experimental results reveal an Area Under the Curve (AUC) of 0.748 for the clinical dataset and 0.775/1.000 for the in-the-wild datasets towards the classification of in-meal eating behavior profiles to the PD or HC group. This is the first work that attempts to use wearable Inertial Measurement Unit (IMU) sensor data, collected both in clinical and in-the-wild settings, towards the extraction of an objective eating behavior indicator for PD.


Assuntos
Comportamento Alimentar/fisiologia , Boca/fisiologia , Doença de Parkinson/fisiopatologia , Idoso , Área Sob a Curva , Estudos de Casos e Controles , Discinesias , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento , Curva ROC , Máquina de Vetores de Suporte , Dispositivos Eletrônicos Vestíveis
19.
CNS Drugs ; 35(2): 215-231, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33559846

RESUMO

Motor and non-motor symptoms (NMS) have a substantial effect on the health-related quality of life (QoL) of patients with Parkinson's disease (PD). Transdermal therapy has emerged as a time-tested practical treatment option, and the rotigotine patch has been used worldwide as an alternative to conventional oral treatment for PD. The efficacy of rotigotine on motor aspects of PD, as well as its safety and tolerability profile, are well-established, whereas its effects on a wide range of NMS have been described and studied but are not widely appreciated. In this review, we present our overall experience with rotigotine and its tolerability and make recommendations for its use in PD and restless legs syndrome, with a specific focus on NMS, underpinned by level 1-4 evidence. We believe that the effective use of the rotigotine transdermal patch can address motor symptoms and a wide range of NMS, improving health-related QoL for patients with PD. More specifically, the positive effects of rotigotine on non-motor fluctuations are also relevant. We also discuss the additional advantages of the transdermal application of rotigotine when oral therapy cannot be used, for instance in acute medical emergencies or nil-by-mouth or pre/post-surgical scenarios. We highlight evidence to support the use of rotigotine in selected cases (in addition to general use for motor benefit) in the context of personalised medicine.


Assuntos
Agonistas de Dopamina/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Tetra-Hidronaftalenos/administração & dosagem , Tiofenos/administração & dosagem , Administração Cutânea , Agonistas de Dopamina/efeitos adversos , Humanos , Doença de Parkinson/fisiopatologia , Qualidade de Vida , Síndrome das Pernas Inquietas/tratamento farmacológico , Tetra-Hidronaftalenos/efeitos adversos , Tiofenos/efeitos adversos , Adesivo Transdérmico
20.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 494-497, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018035

RESUMO

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder after Alzheimer's disease, associated, among others, with motor symptoms such as resting tremor, rigidity and bradykinesia. At the same time, early diagnosis of PD is hindered by a high misdiagnosis rate and the subjective nature of the diagnosis process itself. Recent developments in mobile and wearable devices, such as smartphones and smartwatches, have allowed the automated detection and objective measurement of PD symptoms. In this paper we investigate the hypothesis that PD motor symptom degradation can be assessed by studying the in-meal behavior and modeling the food intake process. To achieve this, we use the inertial data from a commercial smartwatch to investigate the in-meal eating behavior of healthy controls and PD patients. In addition, we define and provide a methodology for calculating Plate-to-Mouth (PtM), an indicator that relates with the average time that the hand spends transferring food from the plate towards the mouth during the course of a meal. The presented experimental results, using our collected dataset of 28 participants (7 healthy controls and 21 PD patients), support our hypothesis. Results initially point out that PD patients have a higher PtM value than the healthy controls. Finally, using PtM we achieve a precision/recall/F1 of 0.882/0.714/0.789 towards classifying the meals from the PD patients and healthy controls.


Assuntos
Doença de Parkinson , Humanos , Hipocinesia , Refeições , Boca , Movimento
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