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1.
Stereotact Funct Neurosurg ; : 1-10, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38657586

RESUMO

INTRODUCTION: Magnetic resonance-guided focused ultrasound (MRgFUS) is an effective treatment option for essential tremor (ET) and tremor dominant Parkinson's disease (TDPD), which is often performed with sedation or in the presence of an anesthesiologist in an effort to minimize adverse events and maximize patient comfort. This study explores the safety, feasibility, and tolerability of performing MRgFUS without an anesthesiologist. METHODS: This is a single academic center, retrospective review of 180 ET and TDPD patients who underwent MRgFUS treatment without anesthesiologist support. Patient demographics, intra-procedural treatment parameters, peri-procedural adverse events, and 3-month Clinical Rating Scale for Tremor Part B (CRST-B) scores were compared to MRgFUS studies that utilized varying degrees of anesthesia. RESULTS: There were no anesthesia related adverse events or unsuccessful treatments. There were no early treatment terminations due to patient discomfort, regardless of skull density ratio. 94.6% of patients would repeat the procedure again. The most common side effects during treatment were facial/tongue paresthesia (26.3%), followed by nausea (22.3%), dysarthria (8.6%), and scalp pain (8.0%). No anxiolytic, pain, or antihypertensive medications were administered. The most common early adverse event after MRgFUS procedure was gait imbalance (58.3%). There was a significant reduction of 83.1% (83.4% ET and 80.5% TDPD) of the mean CRST-B scores of the treated hand when comparing 3-month and baseline scores (1.8 vs. 10.9, n = 109, p < 0.0001). CONCLUSION: MRgFUS without intra-procedural anesthesiologist support is a safe, feasible, and well-tolerated option, without an increase in peri-procedural adverse events.

2.
J Neurol ; 271(2): 852-863, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37839041

RESUMO

OBJECTIVE: To determine longitudinal predictors of health-related quality of life (HR-QoL) in an international multicenter cohort of patients with isolated dystonia. METHODS: Out of 603 dystonia patients prospectively enrolled in the Natural History Dystonia Coalition study, 155 were assessed three times within 2 years for HR-QoL, symptoms of depression, generalized anxiety disorder (GAD), and social anxiety disorder (SAD), as well as dystonia severity and dystonic tremor. In addition, the impact of botulinum neurotoxin (BoNT) injections on HR-QoL was evaluated after 1 year. RESULTS: Depressive symptoms at baseline predicted lower HR-QoL on all subscales after 2 years (all p ≤ 0.001). Higher GAD scores at baseline predicted lower HR-QoL related to general health, pain and emotional well-being, whereas higher SAD scores predicted higher pain-related QoL after 2 years (all p ≤ 0.006). Dystonia severity at baseline predicted social functioning (p = 0.002). Neither dystonic tremor, age, or sex predicted HR-QoL at 2 years. Two latent categories were revealed across the three-time points: Category 1 with higher total HR-QoL scores (mean HR-QoL = 74.4% ± 16.1), susceptible to symptoms of depression and SAD, and Category 2 with lower total HR-QoL scores (mean HR-QoL = 45.5% ± 17.6), susceptible to symptoms of GAD. HR-QoL improved over the course of 1 year irrespective of the use of BoNT. CONCLUSION: The longitudinal impact of psychiatric symptoms on HR-QoL emphasizes the importance of incorporating mental health treatment, in particular also the therapy of anxiety disorders, into treatment regimens for dystonia.


Assuntos
Distonia , Distúrbios Distônicos , Humanos , Pré-Escolar , Qualidade de Vida/psicologia , Tremor/diagnóstico , Distúrbios Distônicos/tratamento farmacológico , Dor
3.
Dysphagia ; 38(5): 1421-1429, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37071189

RESUMO

Cervical dystonia (CD) is the most common form of focal dystonia with Botulinum neurotoxin (BoNT) being a frequent method of treatment. Dysphagia is a common side effect of BoNT treatment for CD. Instrumental evaluation of swallowing in CD using standardized scoring for the videofluoroscopic swallowing study (VFSS) and validated and reliable patient-reported outcomes measures is lacking in the literature. (1) to determine if BoNT injections change instrumental findings of swallowing function using the Modified Barium Swallow Impairment Profile (MBSImP) in individuals with CD; (2) to determine if BoNT injections change self-perception of the psychosocial handicapping effects of dysphagia in individuals with CD, using the Dysphagia Handicap Index (DHI); (3) to determine the effect of BoNT dosage on instrumental swallowing evaluation and self-reported swallowing outcomes measures. 18 subjects with CD completed a VFSS and the DHI before and after BoNT injection. There was a significant increase in pharyngeal residue for pudding consistency after BoNT injection, p = 0.015. There were significant positive associations between BoNT dosage and self-perception of the physical attributes of the handicapping effect of dysphagia, the grand total score and patient self-reported severity of dysphagia on the DHI; p = 0.022; p = 0.037; p = 0.035 respectively. There were several significant associations between changes in MBSImP scores and BoNT dose. Pharyngeal efficiency of swallowing may be affected by BoNT for thicker consistencies. Individuals with CD perceive greater physical handicapping effects of dysphagia with increased amounts of BoNT units and have greater self-perceptions of dysphagia severity with increased amounts of BoNT units.


Assuntos
Toxinas Botulínicas Tipo A , Toxinas Botulínicas , Transtornos de Deglutição , Torcicolo , Humanos , Torcicolo/complicações , Torcicolo/tratamento farmacológico , Toxinas Botulínicas/efeitos adversos , Deglutição , Faringe , Toxinas Botulínicas Tipo A/efeitos adversos
4.
Stereotact Funct Neurosurg ; 101(2): 101-111, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36863325

RESUMO

INTRODUCTION: Magnetic resonance-guided focused ultrasound (MRgFUS) represents an incisionless treatment option for essential or parkinsonian tremor. The incisionless nature of this procedure has garnered interest from both patients and providers. As such, an increasing number of centers are initiating new MRgFUS programs, necessitating development of unique workflows to optimize patient care and safety. Herein, we describe establishment of a multi-disciplinary team, workflow processes, and outcomes for a new MRgFUS program. METHODS: This is a single-academic center retrospective review of 116 consecutive patients treated for hand tremor between 2020 and 2022. MRgFUS team members, treatment workflow, and treatment logistics were reviewed and categorized. Tremor severity and adverse events were evaluated at baseline, 3, 6, and 12 months post-MRgFUS with the Clinical Rating Scale for Tremor Part B (CRST-B). Trends in outcome and treatment parameters over time were assessed. Workflow and technical modifications were noted. RESULTS: The procedure, workflow, and team members remained consistent throughout all treatments. Technique modifications were attempted to reduce adverse events. A significant reduction in CRST-B score was achieved at 3 months (84.5%), 6 months (79.8%), and 12 months (72.2%) post-procedure (p < 0.0001). The most common post-procedure adverse events in the acute period (<1 day) were gait imbalance (61.1%), fatigue and/or lethargy (25.0%), dysarthria (23.2%), headache (20.4%), and lip/hand paresthesia (13.9%). By 12 months, the majority of adverse events had resolved with a residual 17.8% reporting gait imbalance, 2.2% dysarthria, and 8.9% lip/hand paresthesia. No significant trends in treatment parameters were found. CONCLUSIONS: We demonstrate the feasibility of establishing an MRgFUS program with a relatively rapid increase in evaluation and treatment of patients while maintaining high standards of safety and quality. While efficacious and durable, adverse events occur and can be permanent in MRgFUS.


Assuntos
Tremor Essencial , Tremor , Humanos , Fluxo de Trabalho , Resultado do Tratamento , Tremor/diagnóstico por imagem , Tremor/terapia , Parestesia , Disartria , Tremor Essencial/terapia , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Tálamo
6.
Front Neurol ; 13: 927573, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35989908

RESUMO

Background: There is limited information on optimization of symptomatic management of cervical dystonia (CD) after implantation of pallidal deep brain stimulation (DBS). Objectives: To describe the long-term, "real-world" management of CD patients after DBS implantation and the role of reintroduction of pharmacologic and botulinum toxin (BoNT) therapy. Methods: A retrospective analysis of patients with focal cervical or segmental craniocervical dystonia implanted with DBS was conducted. Results: Nine patients were identified with a mean follow-up of 41.7 ± 15.7 months. All patients continued adjuvant oral medication(s) to optimize symptom control post-operatively. Three stopped BoNT and four reduced BoNT dose by an average of 22%. All patients remained on at least one medication used to treat dystonia post-operatively. Conclusion: Optimal symptom control was achieved with DBS combined with either BoNT and/or medication. We suggest utilization of adjuvant therapies such as BoNT and/or medications if DBS monotherapy does not achieve optimal symptom control.

7.
Parkinsonism Relat Disord ; 96: 38-42, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35151948

RESUMO

INTRODUCTION: Outcomes after deep brain stimulation (DBS) therapy are dependent on good surgical placement in the target nucleus and optimized stimulation parameters through multiple programming sessions. This often requires frequent travel to a specialized DBS center, which presents a challenge for those with limited access. Recently, the FDA approved a remote tele-programming solution for DBS. To determine if remote tele-programming of DBS systems is beneficial and useful for Parkinson's Disease (PD) patients, Parkinson's Foundation hosted a survey in collaboration with Abbott Labs. METHODS: The survey was conducted to assess the need for telemedicine among PD patients with DBS and the usability of the telehealth interface for DBS teleprogramming. The survey included two validated instruments: The Effective Accessibility and Accommodation survey (EAA) and the Telehealth Usability Questionnaire (TUQ). RESULTS: 47 patients completed the EAA and 41 completed the TUQ. Results from the EAA revealed more than a third of PD patients cannot easily get to a clinic for various reasons, and more than a quarter reported difficulty contacting their clinic for advice. Results from the TUQ revealed overall satisfaction with the DBS remote programming telehealth interface and care provided. The majority of respondents reported that remote tele-programming visits are similar in quality to in-person visits. CONCLUSION: This study provides support for the use of telehealth and tele-programming for DBS management in PD patients. The ability to use remote technologies for care will increase access to DBS and mitigate the disparities that currently prevent access to care.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Telemedicina , Estimulação Encefálica Profunda/métodos , Estudos de Viabilidade , Humanos , Doença de Parkinson/terapia , Telemedicina/métodos , Resultado do Tratamento
8.
J Pharm Technol ; 37(2): 89-94, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34752556

RESUMO

Background: Currently, there are no guidelines regarding the optimal daily timing of inpatient warfarin administration. Objective: The purpose of this study was to determine whether dosing warfarin in the morning will have a significant impact on therapeutic international normalized ratio (INR) achievement compared with evening administration in mechanical mitral valve patients initiated on warfarin following cardiac surgery. Methods: This was a single-center, pre- and post-retrospective cohort conducted between 2014 and 2018. One-hundred fifty-four adult patients who underwent a mechanical mitral valve replacement or alternative cardiac surgery with a history of a mechanical mitral valve were enrolled. The primary outcome was achievement of therapeutic INR at any time point after initiation of warfarin. Pre-intervention administration timing was 6 pm and post-intervention timing was 10 am. Results: Baseline characteristics including age, sex, and race were similar between the 2 groups (P = NS for each characteristic). Therapeutic INR achievement was significantly improved at all time points following 10 am warfarin administration compared with 6 pm (hazard ratio = 1.69; P = .005). Mean time-to-therapeutic INR was 7.37 days in the post-intervention group and 8.39 days in the pre-intervention group (P = .073). There were no significant differences in INR >4, bleeding, or thrombotic complications between groups. Conclusion and Relevance: This retrospective analysis suggests that there may be a postoperative benefit in therapeutic INR achievement in mechanical valve patients when dosing warfarin in the morning compared with evening administration. Large-scale studies should be conducted to further elucidate the potential benefit across more heterogeneous populations.

9.
Parkinsonism Relat Disord ; 92: 41-45, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34688029

RESUMO

BACKGROUND: The initial COVID-19 pandemic shutdown led to the canceling of elective surgeries throughout most of the USA and Canada. OBJECTIVE: This survey was carried out on behalf of the Parkinson Study Group (PSG) to understand the impact of the shutdown on deep brain stimulation (DBS) practices in North America. METHODS: A survey was distributed through RedCap® to the members of the PSG Functional Neurosurgical Working Group. Only one member from each site was asked to respond to the survey. Responses were collected from May 15 to June 6, 2020. RESULTS: Twenty-three sites participated; 19 (83%) sites were from the USA and 4 (17%) from Canada. Twenty-one sites were academic medical centers. COVID-19 associated DBS restrictions were in place from 4 to 16 weeks. One-third of sites halted preoperative evaluations, while two-thirds of the sites offered limited preoperative evaluations. Institutional policy was the main contributor for the reported practice changes, with 87% of the sites additionally reporting patient-driven surgical delays secondary to pandemic concerns. Pre-post DBS associated management changes affected preoperative assessments 96%; electrode placement 87%; new implantable pulse generator (IPG) placement 83%; IPG replacement 65%; immediate postoperative DBS programming 74%; and routine DBS programming 91%. CONCLUSION: The COVID-19 pandemic related shutdown resulted in DBS practice changes in almost all North American sites who responded to this large survey. Information learned could inform development of future contingency plans to reduce patient delays in care under similar circumstances.


Assuntos
COVID-19/prevenção & controle , Estimulação Encefálica Profunda/estatística & dados numéricos , Neuroestimuladores Implantáveis/estatística & dados numéricos , Transtornos dos Movimentos/terapia , Doença de Parkinson/terapia , Cuidados Pós-Operatórios/estatística & dados numéricos , Cuidados Pré-Operatórios/estatística & dados numéricos , Quarentena/estatística & dados numéricos , Telemedicina/estatística & dados numéricos , Centros Médicos Acadêmicos , Canadá , Pesquisas sobre Atenção à Saúde , Humanos , Neurologistas/estatística & dados numéricos , Neurocirurgiões/estatística & dados numéricos , Estados Unidos
10.
Mov Disord ; 36(12): 2795-2801, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34320236

RESUMO

BACKGROUND: Several monogenic causes for isolated dystonia have been identified, but they collectively account for only a small proportion of cases. Two genome-wide association studies have reported a few potential dystonia risk loci; but conclusions have been limited by small sample sizes, partial coverage of genetic variants, or poor reproducibility. OBJECTIVE: To identify robust genetic variants and loci in a large multicenter cervical dystonia cohort using a genome-wide approach. METHODS: We performed a genome-wide association study using cervical dystonia samples from the Dystonia Coalition. Logistic and linear regressions, including age, sex, and population structure as covariates, were employed to assess variant- and gene-based genetic associations with disease status and age at onset. We also performed a replication study for an identified genome-wide significant signal. RESULTS: After quality control, 919 cervical dystonia patients compared with 1491 controls of European ancestry were included in the analyses. We identified one genome-wide significant variant (rs2219975, chromosome 3, upstream of COL8A1, P-value 3.04 × 10-8 ). The association was not replicated in a newly genotyped sample of 473 cervical dystonia cases and 481 controls. Gene-based analysis identified DENND1A to be significantly associated with cervical dystonia (P-value 1.23 × 10-6 ). One low-frequency variant was associated with lower age-at-onset (16.4 ± 2.9 years, P-value = 3.07 × 10-8 , minor allele frequency = 0.01), located within the GABBR2 gene on chromosome 9 (rs147331823). CONCLUSION: The genetic underpinnings of cervical dystonia are complex and likely consist of multiple distinct variants of small effect sizes. Larger sample sizes may be needed to provide sufficient statistical power to address the presumably multi-genic etiology of cervical dystonia. © 2021 International Parkinson and Movement Disorder Society.


Assuntos
Estudo de Associação Genômica Ampla , Torcicolo , Proteínas Adaptadoras de Sinalização de Receptores de Domínio de Morte/genética , Frequência do Gene , Predisposição Genética para Doença/genética , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Polimorfismo de Nucleotídeo Único/genética , Reprodutibilidade dos Testes , Torcicolo/genética
11.
Artigo em Inglês | MEDLINE | ID: mdl-33563813

RESUMO

OBJECTIVE: To evaluate the relationship between health-related quality of life (HR-QoL) and both physical and psychiatric factors in a large, international, multicentre cohort of patients with isolated dystonia, the Dystonia Coalition. METHODS: Natural history data from 603 patients with isolated dystonia (median age 57 years (IQR: 48 to 64 years), 67.0% women) were prospectively acquired and analysed. HR-QoL (RAND 36-Item Health Survey), severity of depressive symptoms, generalised anxiety (Hospital Anxiety and Depression Scale) and social anxiety (Liebowitz Social Anxiety Scale) were assessed. Dystonia severity (Burke-Fahn-Marsden Dystonia Rating Scale) and dystonic tremor were examined. Statistical predictors of HR-QoL were calculated using saturated path analysis. RESULTS: Reduced HR-QoL was strongly associated with the degree of depressive symptoms and generalised and social anxiety (8/8 RAND 36 subscales, p≤0.001). Increased dystonia severity was associated with worse physical functioning, physical and emotional role functioning and social functioning (all p≤0.001). The presence of tremor correlated with worse physical functioning and pain (all p≤0.006). Younger age was associated with reduced emotional well-being and vitality (all p≤0.006). There were no HR-QoL differences between sexes. CONCLUSION: HR-QoL in isolated dystonia is strongly associated with psychiatric and physical features. While current standard of care focus on motor aspects of dystonia, comprehensive care should address both physical and mental aspects of health.

12.
Neurology ; 96(4): e563-e574, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33046615

RESUMO

OBJECTIVE: To assess the clinical manifestations and predictors of different types of tremors in individuals with different types of isolated dystonia. METHODS: Clinical manifestations of tremor were assessed in a multicenter, international cross-sectional, cohort study of 2,362 individuals with all types of isolated dystonia (focal, segmental, multifocal, and generalized) recruited through the Dystonia Coalition. RESULTS: Methodical and standardized assessments of all participants in this cohort revealed the overall prevalence of any type of tremor was 53.3%. The prevalence of dystonic tremor varied from 36.9% to 48.4%, depending on criteria used to define it. To identify the factors associated with tremors in dystonia, the data were analyzed by generalized linear modeling and cluster analyses. Generalized linear modeling indicated 2 of the strongest factors associated with tremor included body region affected by dystonia and recruitment center. Tremor was also associated with severity of dystonia and duration of dystonia, but not with sex or race. The cluster analysis distinguished 8 subgroups within the whole cohort; defined largely by body region with dystonia, and secondarily by other clinical characteristics. CONCLUSION: The large number of cases evaluated by an international team of movement disorder experts facilitated the dissection of several important factors that influence the apparent prevalence and phenomenology of tremor in dystonia. These results are valuable for understanding the many differences reported in prior studies, and for guiding future studies of the nosology of tremor and dystonia.


Assuntos
Distonia/diagnóstico , Distonia/epidemiologia , Internacionalidade , Tremor/diagnóstico , Tremor/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
Drugs Context ; 8: 212592, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31516532

RESUMO

Motor complications are responsible for the large burden of disability and poor quality of life in Parkinson's disease (PD). The pulsatile nature of stimulation with oral dopaminergic therapies due to relatively short pharmacokinetic profiles and dysfunctional gastrointestinal absorption have been attributed to the development of PD motor complications. In this review, we will provide an overview of the pharmacologic and surgical therapies currently available and under investigation for the treatment of motor fluctuations and dyskinesia.

14.
Clin Neuropharmacol ; 41(6): 210-215, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30303817

RESUMO

INTRODUCTION: Impaired nocturnal sleep and excessive daytime sleepiness are common problems for patients with Parkinson's disease, and patients with Parkinson's disease with sleep dysfunction are 5 times more likely to experience psychotic symptoms. Pimavanserin, a 5-HT2A inverse agonist approved to treat Parkinson's disease psychosis, may improve sleep quality in patients with Parkinson's disease experiencing sleep disturbances. METHODS: Scales for Outcomes in Parkinson's Disease nighttime sleep (SCOPA-NS) and SCOPA-daytime sleepiness (DS) data obtained during 2 double-blind placebo-controlled studies of pimavanserin in persons with Parkinson's disease psychosis were evaluated. Data from the placebo and pimavanserin 34 mg groups in the 2 studies were pooled to provide further information on the effect of pimavanserin 34 mg on sleep. Additional analyses on the pooled study data were performed on participants with significantly impaired nighttime sleep and daytime sleepiness, defined as SCOPA-NS ≥7 and SCOPA-DS ≥5, respectively. RESULTS: In the pooled analysis, treatment effects, expressed as least squares mean reductions in SCOPA-NS at week 6, were -1.4 for pimavanserin 34 mg and -0.5 for placebo. At week 6, the decrease from baseline in SCOPA-DS for the pimavanserin 34 mg group was -1.7 and -1.2 for the placebo group (P = 0.108). When evaluating participants with impaired nighttime sleep and daytime sleepiness at baseline, the SCOPA-NS score change was -4.4 for the pimavanserin 34 mg group and -2.3 for the placebo group (P = 0.002), whereas the SCOPA-DS change was -2.9 and -1.9 for the pimavanserin 34 mg and placebo groups (P = 0.120), respectively. CONCLUSION: The data from the trials suggest that nighttime sleep improved with administration of pimavanserin, a novel 5-HT2A receptor inverse agonist/antagonist.


Assuntos
Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/psicologia , Piperidinas/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Antagonistas do Receptor 5-HT2 de Serotonina/uso terapêutico , Sono/efeitos dos fármacos , Ureia/análogos & derivados , Antiparkinsonianos/uso terapêutico , Método Duplo-Cego , Humanos , Transtornos Psicóticos/etiologia , Transtornos Psicóticos/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Ureia/uso terapêutico
15.
Brain Sci ; 8(9)2018 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-30135369

RESUMO

BACKGROUND: Cervical dystonia (CD) patients have impaired working memory, processing speed and visual-motor integration ability. We used magnetoencephalography (MEG) to investigate changes in cerebral oscillations in CD patients during an executive function test, before and after administration of botulinum toxin. METHODS: MEG data were collected from five CD patients while they performed a visual continuous performance task (CPT), before and after they received a botulinum toxin injection. MEG data was also collected on five controls matched for age and gender. Coherence source imaging was performed to quantify network connectivity of subjects. RESULTS: Controls demonstrated two errors with visual CPT; CD patients demonstrated six and three errors pre- and post-botulinum toxin respectively. After botulinum toxin, mean time from cue to correct response was 0.337 s in controls, 0.390 s in patients before botulinum toxin injection, and 0.366 s after the injection. Differences in coherence between controls and patients were found in the following brain regions: Fronto-frontal, fronto-parietal, fronto-striatal, fronto-occipital, parieto-parietal and temporo-parietal. Intrahemispheric and interhemispheric networks were affected. Post injection, there was minimal change in coherence in the above-mentioned networks. DISCUSSION: Neuropsychological testing suggests difference in coherence in frontal circuits between CD cases and controls during the visual CPT, which may reflect subjects' increased difficulty with the task. Botulinum toxin is associated with minimal improvement with executive function in CD.

16.
Neurol Sci ; 39(10): 1767-1771, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30032332

RESUMO

BACKGROUND: Parkinson's disease psychosis (PDP) is a disabling non-motor symptom of Parkinson's disease (PD) that is challenging to treat. Dopamine receptor blockers (DRB) are used to treat PDP, though these may be associated with adverse effects, including worsening of Parkinsonism. Pimavanserin, a selective 5-HT2A receptor inverse agonist, was recently FDA-approved for treatment of PDP; however, there is limited information on its long-term use in PDP patients. METHODS: A retrospective chart review of patients prescribed pimavanserin was performed in August, 2017. Data on demographics, psychotic features, sleep, and adverse effects was collected using a semi-structured telephone interview with patients or caregivers. Hallucination severity (HS) was quantified as mild (< 1 episode/week), moderate (1/week to < 1/day), or severe (daily/continuous). RESULTS: Seventeen patients consented to participate in the study; 16 were diagnosed with PDP, 1 with Lewy body dementia. Fourteen had co-morbid cognitive impairment/dementia. The mean duration of Parkinsonism was 11.8 ± 8.0 years, with 2.6 ± 1.9 years of psychosis. Eleven of the seventeen patients reported improvement of hallucinations of which 5/8 were initiated on pimavanserin monotherapy, and 6/9 reported improvement of HS with combination of DRB. Six of nine patients prescribed DRB were able to discontinue this medication after introduction of pimavanserin. Four patients discontinued medications (2, no benefit; 1, spontaneous resolution; 1, cost). No major side effects were reported, and two patients noted subjective improvement of sleep. CONCLUSION: In our series based on a small sample size, pimavanserin is well-tolerated and effective as both monotherapy and adjuvant treatment for moderate to severe. This medication can facilitate reduction or cessation of DRB medication.


Assuntos
Transtornos dos Movimentos/tratamento farmacológico , Piperidinas/uso terapêutico , Agonistas do Receptor 5-HT2 de Serotonina/uso terapêutico , Ureia/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do Tratamento , Ureia/uso terapêutico
17.
J Neuropsychiatry Clin Neurosci ; 30(3): 214-219, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29505320

RESUMO

Pseudobulbar affect (PBA) is a syndrome of affective disturbance associated with inappropriate laughter and crying, independent of mood. PBA is common in amyotrophic lateral sclerosis (ALS) and increasingly recognized in Parkinson's disease (PD) and atypical parkinsonism (aP). Correlates of PBA have not been systematically studied. The purpose of this study was to determine whether cognitive and psychiatric comorbidities correlated with patient-reported symptoms of PBA by using the Center for Neurological Study-Lability Scale among patients with ALS, PD, and aP. A total of 108 patients (PD, N=53; aP, N=29; ALS, N=26) completed a cognitive screener and self-reported measures of lability, depression, anxiety, apathy, and quality of life. Statistical analyses included one- and two-way analyses of covariance to evaluate group differences, Pearson's correlations to determine relationships between PBA symptoms and comorbidities, multiple regression for predicting PBA symptom severity in clinical correlates, and chi-square t tests for predicting demographic variables. PBA symptom severity did not vary between the three groups. Younger age and worse anxiety correlated with PBA symptom severity in all three groups, whereas depression and poor mental health/quality of life only correlated with PBA symptom severity in the PD and aP groups. PD and aP patients may be more likely to benefit from treatment with antidepressants. Increased PBA symptoms were associated with declines in cognitive functioning in the aP group, but sufficient numbers of PD and ALS patients with cognitive dysfunction may not have been recruited. The results suggest the possibility of an alternate pathophysiologic mechanism for PBA, which may vary between neurological disorders and disease progression. Mood and cognition are of particular relevance and should be evaluated when symptoms of PBA are suspected.


Assuntos
Esclerose Lateral Amiotrófica/psicologia , Transtornos do Humor/complicações , Transtornos Parkinsonianos/complicações , Transtornos Parkinsonianos/psicologia , Idoso , Análise de Variância , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/epidemiologia , Transtornos Parkinsonianos/epidemiologia , Escalas de Graduação Psiquiátrica , Análise de Regressão , Autorrelato , Índice de Gravidade de Doença
18.
J Neurol ; 265(4): 970-975, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29569175

RESUMO

OBJECTIVE: To investigate the prevalence of substance abuse (SA) in patients with cervical dystonia (CD) and to correlate it with prevalence of psychiatric disorders. METHODS: Data on anxiety, depression, dystonia severity, and substance abuse were collected from ten sites participating in the Dystonia Coalition. Patients were divided into two groups according to the presence of SA, utilizing Structured Clinical Interview for DSM-4 criteria. Wilcoxon Rank-Sum test was used to analyze the difference in median scores on the questionnaires between the groups. Chi-square test was used to analyze association between opiate and benzodiazepine use and SA. Association between TWSTRS severity and SA and medication use was assessed. A two-tailed p value of < 0.05 was considered significant. SAS 9.3 (SAS Institute Inc., Cary, NC, USA) was used for all analyses. RESULTS: Of 208 CD patients, 23 (11%) were identified with SA; 26.3% of patients with SA were on opiates compared to 7.2% of CD patients without SA (p = 0.006). Compared to non-SA patients, those experiencing SA were more likely male (88.9%; p = 0.0007), younger (median age 55; p = 0.031), and scored worse on questionnaires assessing depression (p = 0.044, p = 0.005), anxiety (p = 0.003), and dystonia psychiatric severity (p = 0.033). The median TWSTRS motor severity scores were higher in SA patients compared to non-SA patients (20 versus 16, p = 0.0339). The median TWSTRS total disability, motor, and pain scores were higher in patients on opiates than patients who were not (12 versus 8, p = 0.0071; 18.5 versus 16, p = 0.0243; 12.4 versus 6.7, p = 0.0052, respectively). CONCLUSIONS: Potential risk factors for SA in CD patients include younger age and male gender with comorbid anxiety, depression and other psychiatric problems. Caution should be exercised when prescribing drugs with potential for abuse in these patients.


Assuntos
Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Torcicolo/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Ansiedade , Comorbidade , Depressão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto Jovem
19.
Parkinsons Dis ; 2017: 3410820, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28706748

RESUMO

Deep Brain Stimulation (DBS) has revolutionized the lives of patients of Parkinson disease, offering therapeutic options to those not benefiting entirely from medications alone. With its proven track record of outperforming the best medical management, the goal is to unlock the full potential of this therapy. Currently, the Globus Pallidus Interna (GPi) and Subthalamic Nucleus (STN) are both viable targets for DBS, and the choice of site should focus on the constellation of symptoms, both motor and nonmotor, which are key determinants to quality of life. Our article sheds light on the specific advantages and drawbacks of the two sites, highlighting the need for matching the inherent properties of a target with specific desired effects in patients. UT Southwestern Medical Center has a robust and constantly evolving DBS program and the narrative from our center provides invaluable insight into the practical realities of DBS. The ultimate decision in selecting a DBS target is complex, ideally made by a multidisciplinary team, tailored towards each patient's profile and their expectations, by drawing upon scientific evidence coupled with experience. Ongoing research is expanding our knowledge base, which should be dynamically incorporated into an institute's DBS paradigm to ensure that patients receive the optimal therapy.

20.
Drugs Aging ; 33(12): 855-863, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27830568

RESUMO

Parkinson disease psychosis (PDP) is a common phenomenon in Parkinson disease (PD) patients treated with dopaminergic drugs, and is associated with high morbidity and mortality. It also correlates with depression and dementia, and can contribute to considerable caregiver stress and burnout. While symptoms can be relieved by decreasing doses or number of anti-PD medications, this may lead to an unacceptable worsening of motor function. When general medical or psychiatric conditions have been ruled out, and decreasing dopaminergic agents is not effective in treating psychosis, therapies include atypical antipsychotics, primarily clozapine and quetiapine. Of these, clozapine is effective but is associated with a poor side-effect profile and the necessity for frequent blood draws. Clinicians prefer quetiapine for its theoretically better safety profile, although there is no evidence for efficacy in treating psychosis. All atypical antipsychotics are associated with increased mortality in this patient population. Cholinesterase inhibitors can ameliorate psychosis symptoms. The serotonin 5-HT2A receptor inverse agonist pimavanserin was recently approved by the US FDA for the treatment of PDP and may prove to be a more targeted therapy without the downsides of atypical antipsychotics.


Assuntos
Antipsicóticos/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Transtornos Psicóticos/tratamento farmacológico , Antipsicóticos/farmacologia , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Clozapina/farmacologia , Clozapina/uso terapêutico , Humanos , Terapia de Alvo Molecular , Neurotransmissores/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Transtornos Psicóticos/metabolismo , Transtornos Psicóticos/fisiopatologia , Fumarato de Quetiapina/farmacologia , Fumarato de Quetiapina/uso terapêutico , Ureia/análogos & derivados , Ureia/farmacologia , Ureia/uso terapêutico
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