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BACKGROUND: The EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN-DBS) and best medical treatment (BMT) was superior to BMT alone. OBJECTIVE: This prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility assessment between STN-DBS and BMT over 2 years, and secondary outcomes included non-speech oral movements (maximum phonation time [MPT], oral diadochokinesis), physician- and patient-reported assessments. METHODS: STN-DBS (n = 102) and BMT (n = 99) groups underwent assessments on/off medication at baseline and 24 months (in four conditions: on/off medication, ON/OFF stimulation-for STN-DBS). Words and sentences were randomly presented to blinded listeners, and speech intelligibility rate was measured. Statistical analyses compared changes between the STN-DBS and BMT groups from baseline to 24 months. RESULTS: Over the 2-year period, changes in speech intelligibility and MPT, as well as patient-reported outcomes, were not different between groups, either off or on medication or OFF or ON stimulation, but most outcomes showed a nonsignificant trend toward worsening in both groups. Change in oral diadochokinesis was significantly different between STN-DBS and BMT groups, on medication and OFF STN-DBS, with patients in the STN-DBS group performing slightly worse than patients under BMT only. A signal for clinical worsening with STN-DBS was found for the individual speech item of the Unified Parkinson's Disease Rating Scale, Part III. CONCLUSION: At this early stage of the patients' disease, STN-DBS did not result in a consistent deterioration in blinded speech intelligibility assessment and patient-reported communication, as observed in studies of advanced Parkinson's Disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Doença de Parkinson/complicações , Estudos Prospectivos , Núcleo Subtalâmico/fisiologia , Movimento , Inteligibilidade da Fala/fisiologia , Estimulação Encefálica Profunda/métodos , Resultado do TratamentoRESUMO
BACKGROUND: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic in 2020 outpatient care of neovascular age-related macular degeneration (nAMD) patients was severely reduced due to lockdown. Missed visits are known to be detrimental to patients in need of continued anti-vascular endothelial growth factor (VEGF) intravitreal injections (IVIs). The purpose of the study was to assess the effect of a month-long pause of regular visits and anti-VEGF IVIs in nAMD patients. METHODS: A retrospective study was performed. Patients were treated in a pro re nata ("as needed") scheme. Distance (logMAR) and near (logRAD) visual acuity (VA), optical coherence tomography, delay between planned and actual visit date and the indication for IVI were assessed for 3 continous visits in the 6 months before lockdown (V-3, -2, -1) and the 2 visits after lockdown (V0, V + 1). For analysis of long-term impact, records for visits 1 years before and after lockdown (V-3, V + 2) were gathered. RESULTS: We included 166 patients (120 female, 46 male) with a median (range) age of 80.88 (59.8-99.36) years. Compared to V-1, distance VA was significantly worse at both V0 (0.27 ± 0.21 vs 0.31 ± 0.23 logMAR, p < 0.001) and V + 1 (0.27 ± 0.21 vs 0.30 ± 0.23 logMAR, p = 0.021). Near VA was significantly worse at both V0 (0.31 ± 0.21 vs 0.34 ± 0.22 logRAD, p = 0.037) and V + 1 (0.31 ± 0.21 vs 0.34 ± 0.22 logRAD, p = 0.02). Visit delay (VD) at V0 was significantly longer than at V + 1 (30.81 ± 20.44 vs 2.02 ± 6.79 days, p < 0.0001). Linear regression analysis showed a significant association between visit delay and a reduction of near VA between V-1 and V + 1 (p = 0.0223). There was a significant loss of distance VA (p = 0.02) in the year after the lockdown period (n = 125) compared to the year before. Loss of reading acuity was not significantly increased (p = 0.3). One year post lockdown, there was no correlation between VA change and visit delay after lockdown (p > 0.05). CONCLUSIONS: In nAMD patients whose visits and treatment were paused for a month during the first wave of the COVID-19 pandemic, we found a loss of VA immediately after lockdown, which persisted during follow-up despite re-established anti-VEGF treatment. In the short term, length of delay was predictive for loss of reading VA. The comparison of development of VA during the year before and after the lockdown showed a progression of nAMD related VA loss which may have been accelerated by the disruption of regular visits and treatment. TRIAL REGISTRATION: This article does not report the outcome of a health care intervention. This retrospective study was therefore not registered in a clinical trials database.
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COVID-19 , Degeneração Macular , Degeneração Macular Exsudativa , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Masculino , Pandemias , Ranibizumab/uso terapêutico , Estudos Retrospectivos , Fator A de Crescimento do Endotélio Vascular , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/epidemiologiaRESUMO
BACKGROUND: The pattern and role of microglial activation in multiple system atrophy is largely unclear. The objective of this study was to use [11 C](R)-PK11195 PET to determine the extent and correlation of activated microglia with clinical parameters in MSA patients. METHODS: Fourteen patients with the parkinsonian phenotype of MSA (MSA-P) with a mean disease duration of 2.9 years (range 2-5 years) were examined with [11 C](R)-PK11195 PET and compared with 10 healthy controls. RESULTS: Patients with the parkinsonian phenotype of MSA showed a significant (P ≤ 0.01) mean increase in binding potentials compared with healthy controls in the caudate nucleus, putamen, pallidum, precentral gyrus, orbitofrontal cortex, presubgenual anterior cingulate cortex, and the superior parietal gyrus. No correlations between binding potentials and clinical parameters were found. CONCLUSIONS: In early clinical stages of the parkinsonian phenotype of MSA, there is widespread microglial activation as a marker of neuroinflammatory changes without correlation to clinical parameters in our patient population. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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Encéfalo/diagnóstico por imagem , Microglia/metabolismo , Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Idoso , Encéfalo/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/metabolismo , Tomografia por Emissão de PósitronsRESUMO
The efficient synthesis of tripodal platforms based on tetraphenylmethane with three acetyl-protected thiol groups in either meta or para positions relative to the central sp(3) carbon for deposition on Au (111) surfaces is reported. These platforms are intended to provide a vertical arrangement of the substituent in positionâ 4 of the perpendicular phenyl ring and an electronic coupling to the gold substrate. The self-assembly features of both derivatives are analyzed on Au (111) surfaces by low-temperature ultra-high-vacuum STM, high-resolution X-ray photoelectron spectroscopy, near-edge X-ray absorption fine structure spectroscopy, and reductive voltammetric desorption studies. These experiments indicated that the meta derivative forms a well-ordered monolayer, with most of the anchoring groups bound to the surface, whereas the para derivative forms a multilayer film with physically adsorbed adlayers on the chemisorbed para monolayer. Single-molecule conductance values for both tripodal platforms are obtained through an STM break junction experiment.
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Previous models proposed that the subthalamic nucleus (STN) is critical in the early phase of skill acquisition. We hypothesized that subthalamic deep brain stimulation modulates the learning curve in early classification learning. Thirteen idiopathic Parkinson's disease patients (iPD) with subthalamic deep brain stimulation (STN-DBS), 9 medically treated iPD, and 21 age-matched healthy controls were tested with a probabilistic classification task. STN-DBS patients were tested with stimulation OFF and ON, and medically treated patients with medication OFF and ON, respectively. Performance and reaction time were analyzed on the first 100 consecutive trials as early learning phase. Moreover, data were separated for low and high-probability patterns, and more differentiated strategy analyses were used. The major finding was a significant modulation of the learning curve in DBS patients with stimulation ON: although overall learning was similar to healthy controls, only the stimulation ON group showed a transient significant performance dip from trials '41-60' that rapidly recovered. Further analysis indicated that this might be paralleled by a modulation of the learning strategy, particularly on the high-probability patterns. The reaction time was unchanged during the dip. Our study supports that the STN serves as a relay in early classification learning and directs attention toward unacquainted content. The STN might play a role in balancing the short-term success against strategy optimization for improved long-term outcome.
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Aprendizagem por Associação/fisiologia , Estimulação Encefálica Profunda , Aprendizagem por Probabilidade , Núcleo Subtalâmico/fisiologia , Idoso , Antiparkinsonianos/uso terapêutico , Aprendizagem por Associação/efeitos dos fármacos , Encéfalo/irrigação sanguínea , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Levodopa/farmacologia , Levodopa/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Doença de Parkinson/patologia , Doença de Parkinson/terapia , Índice de Gravidade de DoençaRESUMO
Gait and balance disturbances typically emerge in advanced Parkinson's disease with generally limited response to dopaminergic medication and subthalamic nucleus deep brain stimulation. Therefore, advanced programming with interleaved pulses was put forward to introduce concomittant nigral stimulation on caudal contacts of a subthalamic lead. Here, we hypothesized that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata improves axial symptoms compared with standard subthalamic nucleus stimulation. Twelve patients were enrolled in this 2 × 2 cross-over double-blind randomized controlled clinical trial and both the safety and efficacy of combined subthalamic nucleus and substantia nigra pars reticulata stimulation were evaluated compared with standard subthalamic nucleus stimulation. The primary outcome measure was the change of a broad-scaled cumulative axial Unified Parkinson's Disease Rating Scale score (Scale II items 13-15, Scale III items 27-31) at '3-week follow-up'. Secondary outcome measures specifically addressed freezing of gait, balance, quality of life, non-motor symptoms and neuropsychiatric symptoms. For the primary outcome measure no statistically significant improvement was observed for combined subthalamic nucleus and substantia nigra pars reticulata stimulation at the '3-week follow-up'. The secondary endpoints, however, revealed that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata might specifically improve freezing of gait, whereas balance impairment remained unchanged. The combined stimulation of subthalamic nucleus and substantia nigra pars reticulata was safe, and of note, no clinically relevant neuropsychiatric adverse effect was observed. Patients treated with subthalamic nucleus and substantia nigra pars reticulata stimulation revealed no 'global' effect on axial motor domains. However, this study opens the perspective that concomittant stimulation of the substantia nigra pars reticulata possibly improves otherwise resistant freezing of gait and, therefore, highly warrants a subsequent phase III randomized controlled trial.
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Estimulação Encefálica Profunda/métodos , Transtornos Neurológicos da Marcha/terapia , Doença de Parkinson/terapia , Equilíbrio Postural/fisiologia , Transtornos de Sensação/terapia , Substância Negra/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Cross-Over , Método Duplo-Cego , Feminino , Seguimentos , Transtornos Neurológicos da Marcha/etiologia , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Doença de Parkinson/complicações , Qualidade de Vida , Transtornos de Sensação/etiologia , Índice de Gravidade de Doença , Adulto JovemRESUMO
Learning efficacy depends on its emotional context. The contents learned and the feedback received during training tinges this context. The objective here was to investigate the influence of content and feedback on the efficacy of implicit learning and to explore using functional imaging how these factors are processed in the brain. Twenty-one participants completed 150 trials of a probabilistic classification task (predicting sun or rain based on combinations of playing cards). Smileys or frowneys were presented as feedback. In 10 of these subjects, the task was performed during functional magnetic resonance imaging. Card combinations predicting sun were remembered better than those predicting rain. Similarly, positive feedback fortified learning more than negative feedback. The presentation of smileys recruited bilateral nucleus accumbens, sensorimotor cortex, and posterior cingulum more than negative feedback did. The higher the predictive value of a card combination, the more activation was found in the lateral cerebellum. Both context and feedback influence implicit classification learning. Similar to motor skill acquisition, positive feedback during classification learning is processed in part within the sensorimotor cortex, potentially reflecting the activation of a dopaminergic projection to motor cortex (Hosp et al., 2011). Activation of the lateral cerebellum during learning of combinations with high predictive value may reflect the formation of an internal model.
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Encéfalo/fisiologia , Aprendizagem/fisiologia , Imageamento por Ressonância Magnética , Recompensa , Adulto , Idoso , Idoso de 80 Anos ou mais , Mapeamento Encefálico/métodos , Cerebelo/fisiologia , Dopamina/fisiologia , Retroalimentação Psicológica/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/fisiologia , Núcleo Accumbens/fisiologia , Valor Preditivo dos Testes , Córtex Somatossensorial/fisiologiaRESUMO
Present pathophysiological concepts of neuropathic tremor assume mistimed and defective afferent input resulting in deregulation of cerebello-thalamo-cortical motor networks. Here, we provide direct evidence of central tremor processing in a 76-year-old female who underwent bilateral deep brain stimulation of the ventral intermedial nucleus of the thalamus (Vim-DBS) because of neuropathic tremor associated with IgM paraproteinemia. Electrophysiological recordings of EEG and EMG were performed in three perioperative sessions: (1) preoperatively, (2) intraoperatively, and (3) 4 days after surgery in both rest and postural tremor conditions. Tremor-related synchronization (coherence) between motor cortex (M1) and muscles (M. extensor digitorum, M. flexor digitorum) was assessed, and additional intraoperative local field potential (LFP) recordings from Vim allowed comprehensive coherence mapping in thalamo-cortico-muscular networks. Directionality of information flow was determined by directed transfer function (DTF) and phase analyses. Stimulation effects on tremor and corticomuscular coherence were assessed and the patient was followed for 12 months on clinical outcome measures (Tremor Rating Scale, CADET-Score). Vim-DBS reduced tremor (59%) and improved motor functionality in daily activities (31%, CADET-A) after 12 months. Intraoperative recordings demonstrated significant coherence in the tremor frequency (4 Hz) between M1 and contralateral muscle, Vim and ipsilateral M1, Vim and contralateral muscle, but not between Vim and contralateral M1. Information flow was directed from M1 to Vim and bidirectional between M1 and muscle and between Vim and muscle, respectively. Corticomuscular coherence at tremor frequency was completely suppressed by Vim-DBS. Our case study demonstrates central oscillators underlying neuropathic tremor and implies a strong pathophysiological rationale for Vim-DBS.
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Relógios Biológicos/fisiologia , Encéfalo/fisiopatologia , Paraproteinemias/fisiopatologia , Tremor/fisiopatologia , Idoso , Encéfalo/cirurgia , Estimulação Encefálica Profunda , Eletroencefalografia , Eletromiografia , Feminino , Humanos , Músculo Esquelético/fisiopatologia , Neurônios/fisiologia , Paraproteinemias/complicações , Tremor/etiologia , Tremor/terapiaRESUMO
Reward and punishment are potent modulators of associative learning in instrumental and classical conditioning. However, the effect of reward and punishment on procedural learning is not known. The striatum is known to be an important locus of reward-related neural signals and part of the neural substrate of procedural learning. Here, using an implicit motor learning task, we show that reward leads to enhancement of learning in human subjects, whereas punishment is associated only with improvement in motor performance. Furthermore, these behavioral effects have distinct neural substrates with the learning effect of reward being mediated through the dorsal striatum and the performance effect of punishment through the insula. Our results suggest that reward and punishment engage separate motivational systems with distinctive behavioral effects and neural substrates.
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Encéfalo/fisiologia , Aprendizagem/fisiologia , Atividade Motora/fisiologia , Punição , Recompensa , Encéfalo/irrigação sanguínea , Mapeamento Encefálico , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Modelos Lineares , Masculino , Testes Neuropsicológicos , Oxigênio/sangue , Tempo de Reação/fisiologia , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: Involuntary eyelid closure (IEC) may occur after deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson's disease (PD) and is often categorised as apraxia of lid opening (ALO), albeit the appropriateness of this term is under debate. To gain insight into the hitherto undefined pathophysiology of IEC after STN-DBS, we performed a comprehensive clinical and electrophysiological characterisation of lid function in a total of six PD patients. METHODS: The study was carried out in six PD patients who developed IEC after STN-DBS. They underwent neurological examination and electromyography recording of activity in the orbicularis oculi muscle (OO) upon varying stimulation patterns. Intraoperative studies were performed in one patient. RESULTS: Increasing STN-DBS intensity induced IEC in four patients, whereas it improved the condition in two. Needle EMG showed tonic hyperactivity of the OO in STN-DBS induced IEC, while variable patterns of OO activity (irregular and tonic) were seen in patients with STN-DBS-relieved IEC. Intraoperative analysis in one patient showed evidence for IEC being induced by activation of corticobulbar fibres. CONCLUSIONS: We identified two groups of IEC after STN-DBS based on clinical and EMG patterns: (1) STN-DBS induced IEC associated with tonic OO overactivity and (2) STN-DBS relieved IEC presenting with variable EMG patterns. Our findings provide relevant information on pathophysiology of STN-DBS related IEC and implications for its therapeutic management.
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Estimulação Encefálica Profunda/efeitos adversos , Doenças Palpebrais/fisiopatologia , Pálpebras/fisiopatologia , Doença de Parkinson/terapia , Núcleo Subtalâmico/fisiopatologia , Idoso , Estimulação Encefálica Profunda/métodos , Eletromiografia/métodos , Doenças Palpebrais/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Tratos Piramidais/fisiopatologiaAssuntos
Distonia/genética , Mutação/genética , Proteínas Nucleares/genética , Feminino , Frequência do Gene , Alemanha , Humanos , MasculinoRESUMO
Functional imaging studies in humans and electrophysiological data in animals suggest that corticostriatal circuits undergo plastic modifications during motor skill learning. In motor cortex and hippocampus circuit plasticity can be prevented by protein synthesis inhibition (PSI) which can interfere with certain forms learning. Here, the hypothesis was tested that inducing PSI in the dorsal striatum by bilateral intrastriatal injection of anisomycin (ANI) in rats interferes with learning a precision forelimb reaching task. Injecting ANI shortly after training on days 1 and 2 during 4 days of daily practice (n = 14) led to a significant impairment of motor skill learning as compared with vehicle-injected controls (n = 15, P = 0.033). ANI did not affect the animals' motivation as measured by intertrial latencies. Also, ANI did not affect reaching performance once learning was completed and performance reached a plateau. These findings demonstrate that PSI in the dorsal striatum after training impairs the acquisition of a novel motor skill. The results support the notion that plasticity in basal ganglia circuits, mediated by protein synthesis, contributes to motor skill learning.
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Corpo Estriado/metabolismo , Aprendizagem/fisiologia , Destreza Motora/fisiologia , Biossíntese de Proteínas , Ensino/métodos , Animais , Anisomicina/farmacologia , Antídotos/farmacologia , Comportamento Animal/fisiologia , Corpo Estriado/efeitos dos fármacos , Membro Anterior/fisiologia , Masculino , Biossíntese de Proteínas/efeitos dos fármacos , Inibidores da Síntese de Proteínas/farmacologia , Ratos , Ratos Long-Evans , Fatores de TempoRESUMO
To understand the influence of the molecular dipole moment on the electron transfer (ET) dynamics across the molecular framework, two series of differently fluorinated, benzonitrile-based self-assembled monolayers (SAMs) bound to Au(111) by either thiolate or selenolate anchoring groups were investigated. Within each series, the molecular structures were the same with the exception of the positions of two fluorine atoms affecting the dipole moment of the SAM-forming molecules. The SAMs exhibited a homogeneous anchoring to the substrate, nearly upright molecular orientations, and the outer interface comprised of the terminal nitrile groups. The ET dynamics was studied by resonant Auger electron spectroscopy in the framework of the core-hole clock method. Resonance excitation of the nitrile group unequivocally ensured an ET pathway from the tail group to the substrate. As only one of the π* orbitals of this group is hybridized with the π* system of the adjacent phenyl ring, two different ET times could be determined depending on the primary excited orbital being either localized at the nitrile group or delocalized over the entire benzonitrile moiety. The latter pathway turned out to be much more efficient, with the characteristic ET times being a factor 2.5-3 shorter than those for the localized orbital. The dynamic ET properties of the analogous thiolate- and selenolate-based adsorbates were found to be nearly identical. Finally and most importantly, these properties were found to be unaffected by the different patterns of the fluorine substitution used in the present study, thus showing no influence of the molecular dipole moment.
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OBJECTIVE: The effects of botulinum toxin injections (BoNT) on health-related quality of life along the complex spectrum of spasticity needs further characterization to guide practitioners in a real-life therapeutic environment. METHODS: In this study, we analyzed 50 consecutive and unselected patients with spasticity before and four weeks after re-injection of botulinum toxin. Health-related quality of life in terms of the EuroQol (EQ) as well as further motor and non-motor characteristics were assessed. RESULTS: BoNT improved the EQ visual analog scale (EQ VAS). In addition, state of health and pain maxima improved. The EQ VAS improvement correlated with pre-injection characteristics of the EQ VAS and life satisfaction in the "movement disorders" domain. CONCLUSION: EQ VAS is sensitive for monitoring HR-QoL outcomes in an unselected real life observational cohort. This study may inform future studies intended to validate prediction variables that could inform on HR-QoL effects of BoNT treatment in spasticity.
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Inibidores da Liberação da Acetilcolina/uso terapêutico , Toxinas Botulínicas/uso terapêutico , Espasticidade Muscular/tratamento farmacológico , Qualidade de Vida , Inibidores da Liberação da Acetilcolina/efeitos adversos , Adulto , Idoso , Toxinas Botulínicas/efeitos adversos , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular/diagnóstico , Espasticidade Muscular/fisiopatologia , Satisfação do Paciente , Estudos Prospectivos , Inquéritos e Questionários , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate predictors for improvement of disease-specific quality of life (QOL) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson disease (PD) with early motor complications. METHODS: We performed a secondary analysis of data from the previously published EARLYSTIM study, a prospective randomized trial comparing STN-DBS (n = 124) to best medical treatment (n = 127) after 2 years follow-up with disease-specific QOL (39-item Parkinson's Disease Questionnaire summary index [PDQ-39-SI]) as the primary endpoint. Linear regression analyses of the baseline characteristics age, disease duration, duration of motor complications, and disease severity measured at baseline with the Unified Parkinson's Disease Rating Scale (UPDRS) (UPDRS-III "off" and "on" medications, UPDRS-IV) were conducted to determine predictors of change in PDQ-39-SI. RESULTS: PDQ-39-SI at baseline was correlated to the change in PDQ-39-SI after 24 months in both treatment groups (p < 0.05). The higher the baseline score (worse QOL) the larger the improvement in QOL after 24 months. No correlation was found for any of the other baseline characteristics analyzed in either treatment group. CONCLUSION: Impaired QOL as subjectively evaluated by the patient is the most important predictor of benefit in patients with PD and early motor complications, fulfilling objective gold standard inclusion criteria for STN-DBS. Our results prompt systematically including evaluation of disease-specific QOL when selecting patients with PD for STN-DBS. CLINICALTRIALSGOV IDENTIFIER: NCT00354133.
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Estimulação Encefálica Profunda , Doença de Parkinson/psicologia , Doença de Parkinson/terapia , Qualidade de Vida , Seguimentos , Humanos , PrognósticoRESUMO
OBJECTIVE: Blepharospasm associates with impairment in generic health-related quality of life (HR-QoL). Albeit botulinum toxin is widely used to alleviate the motor symptoms of blepharospasm, its effect on generic health-related quality of life (HR-QoL) is heterogeneous. PATIENTS AND METHODS: In this open-label clinical observational study, we characterized outcomes on HR-QoL in terms of the EuroQol (EQ-5D-5â¯L) from botulinum toxin (BoNT) injection in a prospective cohort of patients with blepharospasm (nâ¯=â¯55). Additionally, we characterized motor and non-motor signs of blepharospasm including motor symptom improvement, life satisfaction, depressive symptoms, pain and sleep quality. Patients were assessed at the end of a regular three-month period from last injection (Timepoint1) and four weeks after the re-injection of BoNT (Timepoint2). RESULTS: There was no improvement of generic HR-QoL on group-level. Individual findings were heterogeneous, dividing patients in three groups of responders (RESP), unchanged outcomes (UNCHN), and worsening (WORSE). We identified, that these subgroups differed at Timepoint 1 with respect to EQ-5D-5â¯L, EQ-VAS, life satisfaction (health and movement disorders domains), Beck's Depression inventory, and sleep quality (One-way ANOVAs, Pâ¯<⯠0.05, adjusted for multiple comparisons). In post-hoc Tuckey tests, RESP or WORSE showed distinct differences from UNCHN that might help to separate the subgroups in future. As such, RESP showed higher impairment in EQ-5D-5L, EQ-VAS, and Beck's Depression Inventory compared to UNCHN (unlike WORSE), whereas WORSE showed higher impairment in life satisfaction 'movement disorders' domain (unlike RESP). CONCLUSION: Our study suggests, that several dependent non-motor, life satisfaction and generic HR-QoL measures associate to individual patient outcomes. The variables identified in this study may be validated in future studies to predict HR-QoL outcomes in patients with blepharospasm.
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Blefarospasmo/tratamento farmacológico , Toxinas Botulínicas/uso terapêutico , Depressão/tratamento farmacológico , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Estudos Prospectivos , Psicometria , Inquéritos e Questionários , Resultado do TratamentoRESUMO
BACKGROUND: Although botulinum neurotoxin (BoNT) injections may alleviate involuntary muscle contractions in hemifacial spasm substantially, it is less clear whether the motor effect would translate into improvements of health-related quality of life (HR-QoL). METHODS: In this open-label clinical observational study, we characterized outcomes on HR-QoL in terms of the EuroQol (EQ-5D-5L) from BoNT in a prospective cohort of patients with hemifacial spasm (n = 73). Additionally, we characterized appendicular motor and nonmotor signs on motor symptom improvement, depressive symptoms, pain and sleep quality. Patients were assessed at the end of a regular 3-month period from last injection (timepoint1) and 4 weeks after the reinjection of BoNT (timepoint2). RESULTS: Patients showed improved HR-QoL on the EQ-VAS (visual analogue scale) at timepoint2 compared with timepoint1. Moreover, we identified, that impairments in HR-QoL at timepoint1 correlated with life satisfaction and depressive symptoms, respectively. However, these associated variables did not predict the therapeutic effect. Instead, EQ-VAS at timepoint1 accounted for 34.5% of the variance of EQ-VAS improvement expressed as the difference between timepoint2 and timepoint1. CONCLUSION: Our study supports HR-QoL improvements in hemifacial spasm and the value of generic HR-QoL measures to estimate therapeutic outcome. However, the findings should be considered descriptive, and future high quality trials are needed for confirmatory purposes in order to refine treatment referral in hemifacial spasm with respect to QoL.
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Botulinumtoxin injection (BoNT) into affected muscles is effective to improve motor symptoms of cervical dystonia (CD) by reducing muscle contraction and involuntary dystonic movement and posturing. However, the understanding of the effect on health-related quality of life (HR-QoL) and patient referral under HR-QoL aspects is incomplete. In this open-label clinical prospective observational study, we characterized the outcomes in CD (n = 159) from botulinumtoxin on both generic HR-QoL (EuroQol; EQ-5D-5L) and disease-specific HR-QoL [craniocervical dystonia questionnaire (CDQ-24)]. Additionally, we characterized motor and non-motor signs of dystonia including motor symptom improvement, depressive symptoms, pain, and sleep quality. We assessed patients at the end of a regular 3-month period from last injection (Timepoint1) and 4 weeks after the re-injection of BoNT (Timepoint2). We aimed to define outcomes on both generic and disease-specific HR-QoL and to evaluate predictors of therapeutic outcome in terms of stepwise multiple regression models. Patients with CD showed a robust improvement of both generic and disease-specific HR-QoL. Furthermore, motor and non-motor signs improved. Multiple regression analyses revealed that EQ-5D-5L and "satisfaction with health" (Fragen zur Lebenszufriedenheit-G) at Timepoint1 predicted treatment response on generic HR-QoL outcome (R2 = 0.284; P = 0.019). Similarly, CDQ-24 and Beck's Depression inventory at Timepoint1 predicted the treatment response on disease-specific HR-QoL (R2 = 0.253; P = 0.026). Our study underscores both generic and disease-specific HR-QoL improvements in CD, and provides useful predictors on HR-QoL outcomes.
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Self-assembled monolayers (SAMs) containing embedded dipolar groups offer the particular advantage of changing the electronic properties of a surface without affecting the SAM-ambient interface. Here we show that such systems can also be used for continuously tuning metal work functions by growing mixed monolayers consisting of molecules with different orientations of the embedded dipolar groups. To avoid injection hot-spots when using the SAM-modified electrodes in devices, a homogeneous mixing of the two components is crucial. We show that a combination of high-resolution X-ray photoelectron spectroscopy with state-of-the-art simulations is an ideal tool for probing the electrostatic homogeneity of the layers and thus for determining phase separation processes in polar adsorbate assemblies down to inhomogeneities at the molecular level.
RESUMO
Tunnelling currents through tunnelling junctions comprising molecules with cross-conjugation are markedly lower than for their linearly conjugated analogues. This effect has been shown experimentally and theoretically to arise from destructive quantum interference, which is understood to be an intrinsic, electronic property of molecules. Here we show experimental evidence of conformation-driven interference effects by examining through-space conjugation in which π-conjugated fragments are arranged face-on or edge-on in sufficiently close proximity to interact through space. Observing these effects in the latter requires trapping molecules in a non-equilibrium conformation closely resembling the X-ray crystal structure, which we accomplish using self-assembled monolayers to construct bottom-up, large-area tunnelling junctions. In contrast, interference effects are completely absent in zero-bias simulations on the equilibrium, gas-phase conformation, establishing through-space conjugation as both of fundamental interest and as a potential tool for tuning tunnelling charge-transport in large-area, solid-state molecular-electronic devices.