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Aim of this review is to discuss the value of current ongoing research initiatives in Parkinson's disease from the clinicians' point of view. The repeat, recent failures on progress slowing reflect the drifting apart between initially promising experimental and then disappointing clinical outcomes in the translational trials with well selected Parkinson's disease patients. A similar development concerns the emerging gap between novel developed drugs with improved pharmacokinetic behaviour and their limited use in the clinical practice following approval. Restricted regional different worldwide availability and direct, respectively indirect budget limitations for neurologists in private practice are essential hurdles. They prevent the widespread prescription of these compounds. As a result return of investment for the pharmaceutical industry becomes more and more uncertain. The interest for research on novel treatment approaches for the amelioration of motor and non motor symptoms declines. Clinicians crucially scrutinize the claim for an optimum patient care by payers and regulators.
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PURPOSE: Parkinson's disease (PD) is primarily defined by motor symptoms and is associated with alterations of sensorimotor areas. Evidence for network changes of the sensorimotor network (SMN) in PD is inconsistent and a systematic evaluation of SMN in PD yet missing. We investigate functional connectivity changes of the SMN in PD, both, within the network, and to other large-scale connectivity networks. METHODS: Resting-state fMRI was assessed in 38 PD patients under long-term dopaminergic treatment and 43 matched healthy controls (HC). Independent component analysis (ICA) into 20 components was conducted and the SMN was identified within the resulting networks. Functional connectivity within the SMN was analyzed using a dual regression approach. Connectivity between the SMN and the other networks from group ICA was investigated with FSLNets. We investigated for functional connectivity changes between patients and controls as well as between medication states (OFF vs. ON) in PD and for correlations with clinical parameters. RESULTS: There was decreased functional connectivity within the SMN in left inferior parietal and primary somatosensory cortex in PD OFF. Across networks, connectivity between SMN and two motor networks as well as two visual networks was diminished in PD OFF. All connectivity decreases partially normalized in PD ON. CONCLUSION: PD is accompanied by functional connectivity losses of the SMN, both, within the network and in interaction to other networks. The connectivity changes in short- and long-range connections are probably related to impaired sensory integration for motor function in PD. SMN decoupling can be partially compensated by dopaminergic therapy.
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Doença de Parkinson , Córtex Sensório-Motor , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/tratamento farmacológico , Córtex Sensório-Motor/diagnóstico por imagemRESUMO
BACKGROUND: Although deep brain stimulation of the globus pallidus internus (GPi-DBS) is an established treatment for many forms of dystonia, including generalized as well as focal forms, its effects on brain (dys-)function remain to be elucidated, particularly for focal and segmental dystonia. Clinical response to GPi-DBS typically comes with some delay and lasts up to several days, sometimes even weeks, once stimulation is discontinued. OBJECTIVE: This study investigated how neural activity during rest and motor activation is affected by GPi-DBS while excluding the potential confound of altered feedback as a result of therapy-induced differences in dystonic muscle contractions. METHODS: Two groups of patients with focal or segmental dystonia were included in the study: 6 patients with GPi-DBS and 8 without DBS (control group). All 14 patients had cervical dystonia. Using H215 O PET, regional cerebral blood flow was measured at rest and during a motor task performed with a nondystonic hand. RESULTS: In patients with GPi-DBS (stimulation ON and OFF), activity at rest was reduced in a prefrontal network, and during the motor task, sensorimotor cortex activity was lower than in patients without DBS. Within-group contrasts (tapping > rest) showed less extensive task-induced motor network activation in GPi-DBS patients than in non-DBS controls. Reduced sensorimotor activation amounted to a significant group-by-task interaction only in the stimulation ON state. CONCLUSIONS: These findings support previous observations in generalized dystonia that suggested that GPi-DBS normalizes dystonia-associated sensorimotor and prefrontal hyperactivity, indicating similar mechanisms in generalized and focal or segmental dystonia. Evidence is provided that these effects extend into the OFF state, which was not previously demonstrated by neuroimaging. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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Estimulação Encefálica Profunda , Distonia , Córtex Sensório-Motor , Distonia/terapia , Globo Pálido , Humanos , Resultado do TratamentoRESUMO
Akinesia, a cardinal symptom of Parkinson's disease, has been linked to abnormal activation in putamen and posterior medial frontal cortex (pMFC). However, little is known whether clinical severity of akinesia is linked to dysfunctional connectivity of these regions. Using a seed-based approach, we here investigated resting-state functional connectivity (RSFC) of putamen, pMFC and primary motor cortex (M1) in 60 patients with Parkinson's disease on regular medication and 72 healthy controls. We found that in patients putamen featured decreases of connectivity for a number of cortical and subcortical areas engaged in sensorimotor and cognitive processing. In contrast, the pMFC showed reduced connectivity with a more focal cortical network involved in higher-level motor-cognition. Finally, M1 featured a selective disruption of connectivity in a network specifically connected with M1. Correlating clinical impairment with connectivity changes revealed a relationship between akinesia and reduced RSFC between pMFC and left intraparietal lobule (IPL). Together, the present study demonstrated RSFC decreases in networks for motor initiation and execution in Parkinson's disease. Moreover, results suggest a relationship between pMFC-IPL decoupling and the manifestation of akinetic symptoms.
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Imageamento por Ressonância Magnética/métodos , Córtex Motor/diagnóstico por imagem , Movimento/fisiologia , Rede Nervosa/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Análise de Componente Principal/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/fisiopatologia , Rede Nervosa/fisiopatologia , Doença de Parkinson/fisiopatologiaRESUMO
Previous whole-brain functional connectivity studies achieved successful classifications of patients and healthy controls but only offered limited specificity as to affected brain systems. Here, we examined whether the connectivity patterns of functional systems affected in schizophrenia (SCZ), Parkinson's disease (PD), or normal aging equally translate into high classification accuracies for these conditions. We compared classification performance between pre-defined networks for each group and, for any given network, between groups. Separate support vector machine classifications of 86 SCZ patients, 80 PD patients, and 95 older adults relative to their matched healthy/young controls, respectively, were performed on functional connectivity in 12 task-based, meta-analytically defined networks using 25 replications of a nested 10-fold cross-validation scheme. Classification performance of the various networks clearly differed between conditions, as those networks that best classified one disease were usually non-informative for the other. For SCZ, but not PD, emotion-processing, empathy, and cognitive action control networks distinguished patients most accurately from controls. For PD, but not SCZ, networks subserving autobiographical or semantic memory, motor execution, and theory-of-mind cognition yielded the best classifications. In contrast, young-old classification was excellent based on all networks and outperformed both clinical classifications. Our pattern-classification approach captured associations between clinical and developmental conditions and functional network integrity with a higher level of specificity than did previous whole-brain analyses. Taken together, our results support resting-state connectivity as a marker of functional dysregulation in specific networks known to be affected by SCZ and PD, while suggesting that aging affects network integrity in a more global way. Hum Brain Mapp 38:5845-5858, 2017. © 2017 Wiley Periodicals, Inc.
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Envelhecimento/fisiologia , Encéfalo/fisiopatologia , Doença de Parkinson/fisiopatologia , Esquizofrenia/fisiopatologia , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética , Processos Mentais/fisiologia , Metanálise como Assunto , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/tratamento farmacológico , Descanso , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Máquina de Vetores de Suporte , Adulto JovemRESUMO
BACKGROUND: Several morphometric magnetic resonance imaging parameters may serve for differential diagnosis of parkinsonism. The objective of this study was to identify which performs best in clinical routine. METHODS: We acquired multicentric magnetization-prepared rapid gradient echo sequences in patients with Parkinson's disease (n=204), progressive supranuclear palsy (n=106), multiple system atrophy-cerebellar, (n = 21); multiple system atrophy-parkinsonian (n = 60), and healthy controls (n = 73), performed manual planimetric measurements, and calculated receiver operator characteristics with leave-one-out cross-validation to propose cutoff values. RESULTS: The midsagittal midbrain area was reduced in PSP versus all other groups (P < 0.001). The midsagittal pons area was reduced in MSA-cerebellar, MSA-parkinsonian, and PSP versus PD patients and healthy controls (P < 0.001). The midbrain/pons area ratio was lower in PSP (P < 0.001) and higher in MSA-cerebellar and MSA-parkinsonian versus PD and PSP (P < 0.001). CONCLUSIONS: The midsagittal midbrain area most reliably identified PSP, the midsagittal pons area MSA-cerebellar. The midbrain/pons area ratio differentiated MSA-cerebellar and PSP better than the magnetic resonance-Parkinson index. © 2017 International Parkinson and Movement Disorder Society.
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Encéfalo/diagnóstico por imagem , Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Paralisia Supranuclear Progressiva/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/fisiopatologia , Transtornos Parkinsonianos/diagnóstico por imagem , Transtornos Parkinsonianos/fisiopatologia , Curva ROC , Reprodutibilidade dos TestesRESUMO
BACKGROUND: The introduction of deep brain stimulation (DBS) about 25 years ago provided one of the major breakthroughs in the treatment of Parkinson's disease (PD). However, a high percentage of patients are reluctant to undergo DBS. Previous research revealed that the critical step on the patient's path to DBS is the decision whether to undergo further diagnostic assessment for surgery at a specialized DBS-center. The aims of the current study were to evaluate how effective the combination of an outpatient DBS screening tool, STIMULUS, with specially developed educational material was to enhance patient education on DBS and to identify motivational aspects which influenced the patients' willingness to undergo further assessment. METHODS: In total, 264 patients were identified as appropriate candidates for DBS by general neurologists using the electronic preselection tool STIMULUS. Patient-centered information material was designed and handed out to support education on DBS. Further, several clinical characteristics and details of the patient counseling were documented. Refusal or consent to show up at a DBS center was registered over the following 16 months. RESULTS: 114 (43.2%) patients preselected as eligible for DBS (STIMULUS Score ≥ 6) agreed to show up at a specialized DBS center to undergo further diagnostic assessment. The patients' ages, PD classification as an akinetic-rigid type and the talks' topics side-effects of dopaminergic medication and the optimal time frame had a significant influence on the patients' decisions. CONCLUSIONS: The combination of preselection tools as STIMULUS with comprehensive information material is effective to increase DBS-acceptance rate in PD patients. Important topics of the information about DBS cover the optimal time frame for DBS surgery, the side-effects of dopaminergic medication as well as side-effects and complications of DBS surgery.
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Estimulação Encefálica Profunda , Doença de Parkinson/terapia , Educação de Pacientes como Assunto/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Seleção de PacientesRESUMO
A typical feature of Parkinson's disease (PD) is pathological activity in the subthalamic nucleus (STN). Here, we tested whether in patients with PD under dopaminergic treatment functional connectivity of the STN differs from healthy controls (HC) and whether some brain regions show (anti-) correlations between functional connectivity with STN and motor symptoms. We used functional magnetic resonance imaging to investigate whole-brain resting-state functional connectivity with STN in 54 patients with PD and 55 HC matched for age, gender, and within-scanner motion. Compared to HC, we found attenuated negative STN-coupling with Crus I of the right cerebellum and with right ventromedial prefrontal regions in patients with PD. Furthermore, we observed enhanced negative STN-coupling with bilateral intraparietal sulcus/superior parietal cortex, right sensorimotor, right premotor, and left visual cortex compared to HC. Finally, we found a decline in positive STN-coupling with the left insula related to severity of motor symptoms and a decline of inter-hemispheric functional connectivity between left and right STN with progression of PD-related motor symptoms. Motor symptom related uncoupling of the insula, a key region in the saliency network and for executive function, from the STN might be associated with well-known executive dysfunction in PD. Moreover, uncoupling between insula and STN might also induce an insufficient setting of thresholds for the discrimination between relevant and irrelevant salient environmental stimuli, explaining observations of disturbed response control in PD. In sum, motor symptoms in PD are associated with a reduced coupling between STN and a key region for executive function.
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Doença de Parkinson/fisiopatologia , Núcleo Subtalâmico/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Mapeamento Encefálico , Cerebelo/fisiopatologia , Feminino , Movimentos da Cabeça , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Descanso , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Inhibitory oscillatory mechanisms subserving tic compensation have been put forward in Tourette syndrome. Modulation of the beta rhythm (15-25 Hz) as the well-established oscillatory movement execution-inhibition indicator was tested during a cognitive-motor task in patients with Tourette syndrome. METHODS: Performing a Go/NoGo task, 12 patients with Tourette syndrome and 12 matched controls were recorded using whole-head magnetoencephalography. RESULTS: Compared to healthy participants, patients showed less beta suppression in the sensorimotor area and enhanced beta power in parieto-occipital brain regions contralaterally to the response hand. Average beta power and power gain correlated negatively with tic severity. CONCLUSIONS: Increased motor inhibitory as well as visuomotor attentional processes are likely to subserve tic compensation. Correlational results suggest that stronger inhibitory compensation accompanies less tic severity.
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Ritmo beta/fisiologia , Córtex Motor/fisiologia , Movimento/fisiologia , Síndrome de Tourette/fisiopatologia , Adulto , Feminino , Humanos , Inibição Psicológica , Magnetoencefalografia/métodos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Clinical differentiation of parkinsonian syndromes is still challenging. OBJECTIVES: A fully automated method for quantitative MRI analysis using atlas-based volumetry combined with support vector machine classification was evaluated for differentiation of parkinsonian syndromes in a multicenter study. METHODS: Atlas-based volumetry was performed on MRI data of healthy controls (n = 73) and patients with PD (204), PSP with Richardson's syndrome phenotype (106), MSA of the cerebellar type (21), and MSA of the Parkinsonian type (60), acquired on different scanners. Volumetric results were used as input for support vector machine classification of single subjects with leave-one-out cross-validation. RESULTS: The largest atrophy compared to controls was found for PSP with Richardson's syndrome phenotype patients in midbrain (-15%), midsagittal midbrain tegmentum plane (-20%), and superior cerebellar peduncles (-13%), for MSA of the cerebellar type in pons (-33%), cerebellum (-23%), and middle cerebellar peduncles (-36%), and for MSA of the parkinsonian type in the putamen (-23%). The majority of binary support vector machine classifications between the groups resulted in balanced accuracies of >80%. With MSA of the cerebellar and parkinsonian type combined in one group, support vector machine classification of PD, PSP and MSA achieved sensitivities of 79% to 87% and specificities of 87% to 96%. Extraction of weighting factors confirmed that midbrain, basal ganglia, and cerebellar peduncles had the largest relevance for classification. CONCLUSIONS: Brain volumetry combined with support vector machine classification allowed for reliable automated differentiation of parkinsonian syndromes on single-patient level even for MRI acquired on different scanners. © 2016 International Parkinson and Movement Disorder Society.
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Encéfalo/diagnóstico por imagem , Doenças Cerebelares/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Transtornos Parkinsonianos/classificação , Transtornos Parkinsonianos/diagnóstico por imagem , Máquina de Vetores de Suporte , Paralisia Supranuclear Progressiva/diagnóstico por imagem , HumanosRESUMO
OBJECTIVE: To evaluate the striatal presynaptic dopamine transporter (FP-CIT-SPECT) and postsynaptic D2 receptor (IBZM-SPECT) binding in patients with corticobasal syndrome (CBS). BACKGROUND: FP-CIT and IBZM are commercially available and approved SPECT tracers for in vivo molecular imaging of pre- and postsynaptic nigrostriatal neuronal degeneration, but only few data for CBS are available. METHODS: 23 patients meeting clinical criteria for early- to mid-stage CBS (disease duration ≤4 years) were examined with SPECT radiotracers FP-CIT and IBZM. All suspected CBS patients underwent a clinical follow-up examination and were re-evaluated after 19.7 ± 15.2 months (mean ± SD). Postmortem diagnosis was available for 2 patients. In patients who met research criteria for probable CBS at the final follow-up visit (n = 19; disease duration: 1.95 ± 0.91 years), SPECT binding values were compared to those of age- and gender-matched Parkinson's disease (PD) patients (n = 18, disease duration: 1.92 ± 0.91 years; clinical follow-up: 32 ± 29.6 months) and neurologically normal control subjects (n = 19). RESULTS: In comparison to the healthy control subjects, both patient groups showed significant and asymmetric reduction of the striatal presynaptic dopamine transporter binding, but PD patients had significantly lower FP-CIT binding ratios than probable-CBS patients. FP-CIT binding values of probable-CBS patients and healthy controls demonstrated marked overlaps, and in 7 patients (39%) scans revealed no dopaminergic deficit. IBZM uptake did not show significant between-group differences. CONCLUSION: Our data indicate that in the early- to mid-stage CBS the degree of nigrostriatal impairment is only mild with a significant proportion of preserved dopamine transporter binding.
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Corpo Estriado/diagnóstico por imagem , Corpo Estriado/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Transtornos Parkinsonianos/diagnóstico por imagem , Transtornos Parkinsonianos/metabolismo , Receptores de Dopamina D2/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Idoso , Benzamidas , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Parkinsonianos/complicações , Pirrolidinas , TropanosRESUMO
Over 90 percent of patients with Parkinson's disease experience speech-motor impairment, namely, hypokinetic dysarthria characterized by reduced pitch and loudness. Resting-state functional connectivity analysis of blood oxygen level-dependent functional magnetic resonance imaging is a useful measure of intrinsic neural functioning. We utilized resting-state functional connectivity modeling to analyze the intrinsic connectivity in patients with Parkinson's disease within a vocalization network defined by a previous meta-analysis of speech (Brown et al., 2009). Functional connectivity of this network was assessed in 56 patients with Parkinson's disease and 56 gender-, age-, and movement-matched healthy controls. We also had item 5 and 18 of the UPDRS, and the PDQ-39 Communication subscale available for correlation with the voice network connectivity strength in patients. The within-group analyses of connectivity patterns demonstrated a lack of subcortical-cortical connectivity in patients with Parkinson's disease. At the cortical level, we found robust (homotopic) interhemispheric connectivity but only inconsistent evidence for many intrahemispheric connections. When directly contrasted to the control group, we found a significant reduction of connections between the left thalamus and putamen, and cortical motor areas, as well as reduced right superior temporal gyrus connectivity. Furthermore, most symptom measures correlated with right putamen, left cerebellum, left superior temporal gyrus, right premotor, and left Rolandic operculum connectivity in the voice network. The results reflect the importance of (right) subcortical nodes and the superior temporal gyrus in Parkinson's disease, enhancing our understanding of the neurobiological underpinnings of vocalization impairment in Parkinson's disease.
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Encéfalo/fisiopatologia , Doença de Parkinson/fisiopatologia , Voz , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Atividade Motora/fisiologia , Vias Neurais/fisiopatologia , Descanso , Índice de Gravidade de Doença , Voz/fisiologiaRESUMO
OBJECTIVE: Awareness of cognitive deficits is related to executive functions and may, therefore, be sensitive to the effects of lumbar puncture (LP) in idiopathic normal pressure hydrocephalus (iNPH). Although a reduction in awareness of cognitive deficits (RACD) has been previously described in iNPH, there is a lack of systematic, psychometrically validated reports. In this study, we investigated RACD and its LP-related changes in iNPH patients and compared them with those in clinical and healthy control groups. METHODS: RACD was assessed before and after lumbar puncture (LP) in 24 patients (14 iNPH, 10 other age-associated cognitive syndromes; AACS) and compared with 23 healthy controls (HC), employing two RACD measures alongside cognitive examination. Local metacognition was measured using a visual percentile-based rating system and operationalized as the t-scaled distance between the participants' task-specific performance estimations and their objective test performance (ΔTSPE). Global metacognition, targeting broader estimates of cognitive functioning (ECF), was quantified by subtracting self- from informant-obtained sum scores on a questionnaire evaluating participants' dysexecutive problems (DEX-DS). Within-group and between-group differences in ΔTSPE and DEX-DS scores were compared non-parametrically, focusing on post-LP changes. RESULTS: Averaged ΔTSPE was higher in the patient groups and mirrored the groups' lower objective test performance, while averaged DEX-DS showed no group difference. Following LP, group comparisons revealed iNPH-specific decrease in both RACD measures. CONCLUSION: Our study revealed LP-related RACD changes in iNPH patients compared to those in AACS and HC participants. The results suggest a mitigation of impaired metacognitive abilities in iNPH, possibly resulting from LP-induced improvements in (local) metacognitive performance, facilitating ECF adjustment alongside a metacognitively stimulating testing procedure.
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MANAGE-PD is a validated, web-based tool to assist physicians in identifying patients with Parkinson's disease (PD) whose symptoms are inadequately controlled by oral medication. Also, a modified patient version of MANAGE-PD (Parkinson Check) is available in Germany. However, prospective research into the clinical utility of MANAGE-PD is lacking. This non-interventional study aimed to assess the real-world clinical utility of the MANAGE-PD and Parkinson Check in PD patients attending a single visit at specialist clinics and neurologist practices in Germany in 2022. Participants' disease control was rated by the physicians using their own judgment, and by completing the MANAGE-PD, and by the patients completing the Parkinson Check. Concordance was calculated between the unassisted physician's assessment and the outcome of MANAGE-PD, as well as the Parkinson Check. A total of 278 patients from 19 sites were included in the analyses, of whom 160 patients (57.6%) were assigned to the same category of disease control by physicians' judgment and the MANAGE-PD. Concordance was higher in patients treated in specialist clinics (63.9%) than in neurologist practices (43.7%). Concordance between physicians' and patients' responses was high (>80%) for each question in the Parkinson Check. MANAGE-PD proved to be especially valuable for general neurologists in identifying patients who should be referred to specialist clinics. The Parkinson Check self-assessment generated promising outcomes that merit its more widespread use.
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Introduction: Cerebral insults lead in many cases not only to cognitive impairment but also to disturbed emotionality. After stroke, one in three survivors develops a depression which impacts quality of life and rehabilitation. Meta-analyses have identified five main predictors of post-stroke depression (PSD): history of mental disorder, stroke severity, physical disability, cognitive impairment, and social support. However, these five established variables have never been conjointly investigated in a sample of stroke survivors. Therefore, their independent predictive values remain unclear. Moreover, predictors are most often used as time-invariant factors (status scores), neglecting the intraindividual dynamics after stroke. Methods: Our study analyses the data of two prospective longitudinal studies, investigating stroke survivors from two rehabilitation hospitals (N 1 = 273) and one acute care hospital (N 2 = 226). Baseline assessments included the five established predictors and depressive symptoms. After 6 months, depressive symptoms were reassessed in both studies (n 1 = 176, n 2 = 183), and physical disability and social support were reassessed in study 2. The predictivity of the five predictors and the additional predictivity of intraindividual dynamics for PSD were examined in multiple linear regression analyses. Results: History of mental disorder was a risk factor for depressive symptoms after stroke at all measurement times (B = 3.32 to 3.97; p < 0.01). Physical disability was a risk factor at all measurement times (B = -0.09 to -0.03; p < 0.05) except 6 months after rehabilitation. Social support was a protective factor (B = -2.69 to -1.91; p < 0.01) outside the acute phase (R 2 = 0.15-0.39). Intraindividual changes in physical disability and perceived social support were independent predictors of PSD 6 months after the acute phase (B = -0.08/-0.14; p < 0.01), in addition to status scores on established variables (ΔR 2 = 0.08, p < 0.001). Discussion: History of mental disorder, physical disability, and social support are independent predictors of depressive symptoms in the first year post-stroke, also when considered conjointly. Future studies should control for these variables when investigating new predictors of PSD. In addition, intraindividual changes in known predictors after stroke play a relevant role in the pathogenesis of PSD and should be considered in clinical practice and future research.
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Data on the use of device-aided therapies (DATs) in people with Parkinson's disease (PwP) are scarce. Analyzing data from the Care4PD patient survey, we (1) evaluated application frequency and type of DAT in a larger, nationwide, cross-sectoral PwP sample in Germany; (2) analyzed the frequency of symptoms indicative for advanced PD (aPD) and need for DAT amongst the remaining patients and (3) compared the most bothersome symptoms and need for professional long-term care (LTC) of patients with and without suspected aPD. Data from 1269 PwP were analyzed. In total, 153 PwP (12%) received DAT, mainly deep brain stimulation (DBS). Of the remaining 1116 PwP without DAT, >50% fulfilled at least one aPD criterion. Akinesia/rigidity and autonomic problems were most bothersome for PwP with and without suspected aPD, with more tremor in the non-aPD and more motor fluctuations and falls in the aPD group. To recapitulate, the German DAT application rate is rather low, although a large proportion of PwP fulfills aPD criteria indicating a need for intensified treatment strategies. Many reported bothersome symptoms could be overcome with DAT with benefits even for LTC patients. Thus, precise and early identification of aPD symptoms (and therapy-resistant tremor) should be implemented in future DAT preselection tools and educational trainings.
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To explore the influence of bilateral subthalamic deep brain stimulation (STN-DBS) on car driving ability in patients with Parkinson's disease (PD), we prospectively examined two age-matched, actively driving PD patient groups: one group undergone DBS-surgery (PD-DBS, n = 23) and one group that was eligible for DBS but did not undergo surgery (PD-nDBS, n = 29). In PD-DBS patients, investigation at Baseline was done just prior and at Follow-up 6-12 month after DBS-surgery. In PD-nDBS patients, time interval between Baseline and Follow-up was aimed to be comparable. To assess the general PD driving level, driving was assessed once in 33 age-matched healthy controls at Baseline. As results, clinical and driving characteristics of PD-DBS, PD-nDBS and controls did not differ at Baseline. At Follow-up, PD-DBS patients drove unsafer than PD-nDBS patients. This effect was strongly driven by two single PD-DBS participants (9%) with poor Baseline and disastrous Follow-up driving performance. Retrospectively, we could not identify any of the assessed motor and non-motor clinical Baseline characteristics as predictive for this driving-deterioration at Follow-up. Excluding these two outliers, comparable driving performance between PD-DBS and PD-nDBS patients not only at Baseline but also at Follow-up was demonstrated. Age, disease duration and severity as well as Baseline driving insecurity were associated with poorer driving performance at Follow-up. This first prospective study on driving safety in PD after DBS surgery indicates that DBS usually does not alter driving safety but might increase the risk for driving deterioration, especially in single subjects with already unsafe driving prior to DBS surgery.
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BACKGROUND AND OBJECTIVES: Advanced therapies (ATs; deep brain stimulation [DBS] or pump therapies: continuous subcutaneous apomorphine infusion [CSAI], levodopa/carbidopa intestinal gel [LCIG]) are used in later stages of Parkinson disease (PD). However, decreasing efficacy over time and/or side effects may require an AT change or combination in individual patients. Current knowledge about changing or combining ATs is limited to mostly retrospective and small-scale studies. The nationwide case collection Combinations of Advanced Therapies in PD assessed simultaneous or sequential AT combinations in Germany since 2005 to analyze their clinical outcome, their side effects, and the reasons for AT modifications. METHODS: Data were acquired retrospectively by modular questionnaires in 22 PD centers throughout Germany based on clinical records and comprised general information about the centers/patients, clinical (Mini-Mental Status Test/Montréal Cognitive Assessment, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS], side effects, reasons for AT modification), and therapeutical (ATs with specifications, oral medication) data. Data assessment started with initiation of the second AT. RESULTS: A total of 148 AT modifications in 116 patients were associated with significantly improved objective (median decrease of MDS-UPDRS Part III 4.0 points [p < 0.001], of MDS-UPDRS Part IV 6.0 points [p < 0.001], of MDS-UPDRS Part IV-off-time item 1.0 points [p < 0.001]) and subjective clinical outcome and decreasing side effect rates. Main reasons for an AT modification were insufficient symptom control and side effects of the previous therapy. Subgroup analyses suggest addition of DBS in AT patients with leading dyskinesia, addition of LCIG for leading other cardinal motor symptoms, and addition of LCIG or CSAI for dominant off-time. The most long-lasting therapy-until requiring a modification-was DBS. DISCUSSION: Changing or combining ATs may be beneficial when 1 AT is insufficient in efficacy or side effects. The outcome of an AT combination is comparable with the clinical benefit by introducing the first AT. The added AT should be chosen dependent on dominant clinical symptoms and adverse effects. Furthermore, prospective trials are needed to confirm the results of this exploratory case collection. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that, in patients with PD, changing or combining ATs is associated with an improvement in the MDS-UPDRS or subjective symptom reporting.
Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/psicologia , Antiparkinsonianos/uso terapêutico , Estudos Retrospectivos , Estudos Prospectivos , Carbidopa/uso terapêutico , Levodopa/uso terapêutico , Infusões Subcutâneas , Combinação de Medicamentos , Géis/uso terapêuticoRESUMO
Tourette syndrome (TS) is a neuro-psychiatric disorder being characterized by motor and phonic tics typically preceded by sensory urges. Given the latter the role of the sensory system and sensorimotor interaction in TS has recently gained increased attention. 12 TS patients and 12 matched control subjects performed two tasks, requiring simple finger movements: a Go/NoGo task and a self paced movement task. Neurophysiological data was recorded using magnetoencephalography (MEG). Event related responses around movement onset, i.e. motor field (MF) occurring directly prior to the movement and movement evoked field (MEF) immediately after movement onset were analyzed using dipole modeling. MF peak amplitudes did not differ between groups in either task. In contrast, in both tasks MEF peak amplitudes were increased in TS patients. Moreover, larger MEF amplitudes during self paced movements were inversely correlated with motor tic frequency and severity. Enlarged MEF amplitudes as a marker of early sensory feedback of one's own movements probably represent enlarged sensory input from the periphery resulting from altered subcortical gating. We conclude that TS patients exhibit altered sensory-motor processing involved in voluntary movement control, which might also be successful in tic control.