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1.
Mov Disord ; 38(12): 2308-2312, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37877478

RESUMO

BACKGROUND: Carbidopa/levodopa enteral suspension (CLES) is indicated for the treatment of advanced Parkinson's disease (aPD) with severe motor fluctuations. OBJECTIVE: To determine the cost, quality-adjusted life years (QALY), and cost-effectiveness of CLES compared to the standard-of-care (SoC) for aPD patients in the United States (US), using real-world data. METHODS: A published Markov model, comprising of 25 health states and a death state, (defined by a combination of the Hoehn and Yahr scale and waking time spent in OFF-time) was adapted to estimate the benefits for CLES versus oral SoC over a patient's lifetime in the US healthcare setting. Clinical inputs were based on a clinical trial and a registry study; utility inputs were sourced from the Adelphi-Disease Specific Programmes. RESULTS: CLES compared to SoC was associated with incremental costs ($1,031,791 vs. $1,025,180) and QALY gain (4.61 vs. 3.76), resulting in an incremental cost-effectiveness ratio of $7711/QALY. CONCLUSION: CLES is a cost-effective treatment for aPD patients with medication resistant motor fluctuations. © 2023 AbbVie, Inc and The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Levodopa , Doença de Parkinson , Humanos , Estados Unidos , Levodopa/uso terapêutico , Carbidopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos , Análise Custo-Benefício , Combinação de Medicamentos , Géis/uso terapêutico
2.
Neurol Sci ; 44(3): 827-833, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36378365

RESUMO

INTRODUCTION: Tardive dystonia (TD) is a disabling complication of pharmacological therapy with dopaminergic receptor antagonists, usually resistant to oral medications. Several reports have shown that deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) might be effective in TD, but the overall level of evidence remains limited to case reports or small case series. OBJECTIVES: We sought to summarize the collective evidence in support of GPi-DBS for TD using a meta-analytic approach. METHODS: We searched PubMed for human studies reporting tardive dystonia cases treated with GPi-DBS that reported the validated Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) as outcome measure. Data extracted were reviewed for risk of bias. Then, through linear mixed effects modeling of the percent improvement seen on an individual level, we estimated the average improvement effect varying by study. RESULTS: The searching strategy resulted in a total of n = 78 studies, which were screened for eligibility criteria resulting in the inclusion of n = 14 studies, yielding 134 TD patients for the final analyses. The overall estimate improvement in the BFMDRS after GPi-DBS was 66.88 ± 11.96%. The review of individual case reports indicated rare worsening (n = 4) or lack of improvement (n = 3) following GPi-DBS. CONCLUSIONS: Bilateral GPi-DBS can be an effective therapeutic option for severe cases of TD resistant to oral pharmacological therapies, even though rare cases of symptom worsening or lack of improvement have also been reported.


Assuntos
Estimulação Encefálica Profunda , Distonia , Distúrbios Distônicos , Discinesia Tardia , Humanos , Discinesia Tardia/terapia , Globo Pálido , Resultado do Tratamento , Estimulação Encefálica Profunda/métodos , Distúrbios Distônicos/terapia , Antagonistas de Dopamina
3.
Can J Neurol Sci ; 49(1): 19-28, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33875038

RESUMO

Levodopa-carbidopa intestinal gel infusion (LCIG) is an established therapy for advanced Parkinson disease (PD), resulting in a significant improvement of quality of life. With increased LCIG adoption worldwide, potential complications due to abnormal vitamin absorption or metabolism have been reported in these patients. Neurologists are unfamiliar with vitamins physiology and pathophysiological mechanisms in case of their deficiency. Unfortunately, clinical and laboratory guidelines related to vitamin monitoring and supplementation in the context of treatment with LCIG are not available. We herein summarize the current knowledge on three vitamins that are reduced with LCIG therapy reporting on their physiology, laboratory testing, and clinical impact of their deficiency/excess. In addition, we proposed an opinion-based recommendation for clinicians treating LCIG patients. Patients and caregivers should be informed about the risk of vitamin deficiency. Vitamin B12, homocysteine, and methylmalonic acid (MMA) should be tested before starting LCIG, six months after and once/year thereafter. Vitamin B6 and folate testing is not universally available but it should be considered if homocysteine is elevated but MMA and/or total vitamin B12 are normal. Prophylaxis of vitamin deficiency should be started as soon as LCIG is implemented, possibly even before. Dietary recommendations are enough in most patients although a subgroup of patients is at higher risk and should receive Vitamin B12 regularly and cycles of B6. Finally, once diagnosed a vitamin deficiency should be readily treated and accompanied by clinical and laboratory monitoring. Resistant cases should receive non-oral routes of administration and possibly discontinue LCIG, even temporarily.


Assuntos
Carbidopa , Levodopa , Antiparkinsonianos/efeitos adversos , Humanos , Levodopa/efeitos adversos , Qualidade de Vida , Vitaminas/uso terapêutico
4.
Clin Auton Res ; 32(6): 455-461, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36030471

RESUMO

PURPOSE: We sought to estimate the impact of cardiovascular autonomic neuropathy (cAN) on informal caregivers of patients with Parkinson's disease (PD), defined as individuals providing regular care to a friend, partner, or family member with PD, and to evaluate the mutual relationship between caregiver burden and patient health-related quality of life (HRQoL). METHODS: We enrolled 36 consecutive patients with PD and their informal caregivers. Patients underwent a detailed motor, autonomic, cognitive, and functional assessment. Caregivers were assessed using the Zarit Burden Interview (ZBI). Differences in caregiver burden, expressed by the ZBI score, and strength of association between caregiver burden, cAN, and HRQoL were assessed using analysis of covariance (ANCOVA), logistic regression, and linear regression analyses. Analyses were adjusted for patients' age, PD duration, and motor and cognitive disability, as well as caregivers' age. RESULTS: Moderate-severe caregiver burden was reported in 41.7% of PDcAN+ versus 8.7% of PDcAN- (p < 0.001). The ZBI score was increased in PDcAN+ versus PDcAN- (31.5 ± 3.4 versus 15.2 ± 2.3; p < 0.001), with tenfold higher odds (p = 0.012) of moderate-severe caregiver burden in PDcAN+, even after adjusting for potential confounders. The ZBI score correlated with cAN severity (p = 0.005), global autonomic impairment (p = 0.012), and HRQoL impairment (p < 0.001). CONCLUSION: These results highlight the significant impact of cAN on PD caregivers and the need for targeted interventions addressing this frequently overlooked and insufficiently treated source of nonmotor disability in PD.


Assuntos
Doença de Parkinson , Disautonomias Primárias , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Qualidade de Vida , Efeitos Psicossociais da Doença , Cuidadores/psicologia , Disautonomias Primárias/etiologia , Inquéritos e Questionários
5.
Cerebellum ; 20(1): 134-139, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32888184

RESUMO

We report a 52-year-old woman presenting with autosomal dominant progressive cerebellar ataxia and familial hemiplegic migraine type 1 whose genetic evaluation, negative for spinocerebellar ataxia (SCA) types 1, 2, 3, and 6, revealed instead a heterozygous pathogenic missense mutation in CACNA1A (NM_001127221:c.1748G > A:p.Arg583Gln). A systematic literature review showed that Arg583Gln is associated predominantly with progressive ataxia combined with episodic disorders (overwhelmingly hemiplegic migraine) whereas Thr666Met, the other most common CACNA1A missense mutation, with a combination of progressive ataxia and episodic disorders in half the cases and episodic disorders only in the other half. While uncertainties remain in the genotype-phenotype correlation of all CACNA1A mutations, the accumulated evidence suggests that that the co-occurrence of hemiplegic migraine and autosomal dominant progressive cerebellar ataxia should guide the clinician to test for CACNA1A missense mutation rather than CAG expansions or truncating mutations.


Assuntos
Canais de Cálcio/genética , Ataxia Cerebelar/etiologia , Ataxia Cerebelar/genética , Expansão das Repetições de DNA/genética , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/genética , Mutação de Sentido Incorreto/genética , Ataxia Cerebelar/complicações , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Fenótipo
6.
J Neurol Neurosurg Psychiatry ; 91(4): 426-433, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32079672

RESUMO

OBJECTIVE: Genetic subtypes of dystonia may respond differentially to deep brain stimulation of the globus pallidus pars interna (GPi DBS). We sought to compare GPi DBS outcomes among the most common monogenic dystonias. METHODS: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology guidelines. We searched PubMed for studies on genetically confirmed monogenic dystonia treated with GPi DBS documenting pre-surgical and post-surgical assessments using the Burke-Fahn-Marsden Dystonia Rating Scale Motor Score (BFMMS) and Burke-Fahn-Marsden Disability Score (BFMDS). We performed (i) meta-analysis for each gene mutation; (ii) weighted ordinary linear regression analyses to compare BFMMS and BFMDS outcomes between DYT-TOR1A and other monogenic dystonias, adjusting for age and disease duration and (iii) weighted linear regression analysis to estimate the effect of age, sex and disease duration on GPi DBS outcomes. Results were summarised with mean change and 95% CI. RESULTS: DYT-TOR1A (68%, 38.4 points; p<0.001), DYT-THAP1 (37% 14.5 points; p<0.001) and NBIA/DYT-PANK2 (27%, 21.4 points; p<0.001) improved in BFMMS; only DYT-TOR1A improved in BFMDS (69%, 9.7 points; p<0.001). Improvement in DYT-TOR1A was significantly greater than in DYT-THAP1 (BFMMS -31%), NBIA/DYT-PANK2 (BFMMS -35%; BFMDS -53%) and CHOR/DYT-ADCY5 (BFMMS -36%; BFMDS -42%). Worse motor outcomes were associated with longer dystonia duration and older age at dystonia onset in DYT-TOR1A, longer dystonia duration in DYT/PARK-TAF1 and younger age at dystonia onset in DYT-SGCE. CONCLUSIONS: GPi DBS outcomes vary across monogenic dystonias. These data serve to inform patient selection and prognostic counselling.


Assuntos
Estimulação Encefálica Profunda , Distonia/terapia , Distúrbios Distônicos/terapia , Globo Pálido , Idade de Início , Distonia/genética , Distonia/fisiopatologia , Distúrbios Distônicos/genética , Distúrbios Distônicos/fisiopatologia , Humanos , Terapêutica , Fatores de Tempo , Resultado do Tratamento
7.
Mov Disord ; 35(10): 1796-1801, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32562441

RESUMO

BACKGROUND: Limited tools are available for the assessment of orthostatic tremor severity and disability. OBJECTIVES: To develop and validate a self-administered orthostatic tremor scale. METHODS: After expert consensus and literature review generating a list of 42 items, the scale was developed and modified for validation after a patient focus group, multiple rounds of Delphi panels, and cognitive interviews. Clinimetric evaluations included assessing content validity, internal consistency, measurement error and reliability, construct validity, and concurrent validity anchored on the examiner's Clinical Global Impression score. RESULTS: Eleven items ranked on a Likert scale from 0 (no disability/severity) to 5 (maximal disability/severity) were evaluated in 54 orthostatic tremor patients (16 men and 38 women; mean age: 69.17 ± 9.64 years; disease duration: 13.83 ± 11.24 years) to probe severity and disability over the preceding 1-week period. The 11-item scale showed good internal consistency (Cronbach's alpha = 0.863) and acceptable (>0.40) item-to-total correlation. However, one item was removed at the final Delphi panel because of significant floor effect, poor item-to-total correlation, and poor factor-loading, leaving the scale with 10 items (10-item Orthostatic Tremor Severity and Disability Scale). Test-retest reliability at 2 weeks was excellent (two-way random intraclass correlation coefficient > 0.90), and the individual item test-retest reliability showed good agreement, with a threshold weighted kappa >0.60 for all items. Exploratory factor analyses revealed a parsimonious two-factor construct accounting for 57.7% of the scale's variance. The 10-item Orthostatic Tremor Severity and Disability Scale scores correlated with the CGI. CONCLUSIONS: The self-administered 10-item Orthostatic Tremor Severity and Disability Scale scale is valid and reliable for capturing orthostatic tremor-related severity and disability. © 2020 International Parkinson and Movement Disorder Society.


Assuntos
Avaliação da Deficiência , Tremor , Idoso , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários , Tremor/diagnóstico
8.
Ann Neurol ; 84(6): 797-811, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30357892

RESUMO

Levodopa-induced dyskinesia is a common complication in Parkinson disease. Pathogenic mechanisms include phasic stimulation of dopamine receptors, nonphysiological levodopa-to-dopamine conversion in serotonergic neurons, hyperactivity of corticostriatal glutamatergic transmission, and overstimulation of nicotinic acetylcholine receptors on dopamine-releasing axons. Delay in initiating levodopa is no longer recommended, as dyskinesia development is a function of disease duration rather than cumulative levodopa exposure. We review current and in-development treatments for peak-dose dyskinesia but suggest that improvements in levodopa delivery alone may reduce its future prevalence. Ann Neurol 2018;84:797-811.


Assuntos
Antiparkinsonianos/efeitos adversos , Discinesia Induzida por Medicamentos , Levodopa/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Animais , Relação Dose-Resposta a Droga , Esquema de Medicação , Discinesia Induzida por Medicamentos/epidemiologia , Discinesia Induzida por Medicamentos/etiologia , Discinesia Induzida por Medicamentos/terapia , Humanos
9.
J Neurol Neurosurg Psychiatry ; 90(11): 1257-1263, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31142660

RESUMO

OBJECTIVE: Review the effect of orthostatic hypotension (OH) and rapid-eye-movement sleep behavioural disorder (RBD) on survival, cognitive impairment and postural stability, and discuss pathogenic mechanisms involved in the association of these two common non-motor features with relevant clinical outcomes in α-synucleinopathies. METHODS: We searched PubMed (January 2007-February 2019) for human studies of OH and RBD evaluating cognitive impairment, postural instability, and survival in Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA) and pure autonomic failure (PAF). Included studies were analysed for design, key results and limitations as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: OH and RBD showed a positive association with cognitive impairment in PD and DLB, conflicting association in PAF, and no association in MSA. OH was correlated with incident falls and postural instability in PD and DLB but not in MSA. The association between RBD and postural instability was inconclusive; positive in five studies, negative in seven. OH, but not RBD, correlated with reduced survival in PD, DLB and MSA. The combination of OH and RBD was associated with cognitive impairment and more rapid progression of postural instability. CONCLUSIONS: OH and RBD yielded individual and combined negative effects on disability in α-synucleinopathies, reflecting a 'malignant' phenotype of PD with early cognitive impairment and postural instability. Underlying mechanisms may include involvement of selected brainstem cholinergic and noradrenergic nuclei.


Assuntos
Hipotensão Ortostática/complicações , Transtorno do Comportamento do Sono REM/complicações , Sinucleinopatias/complicações , Sinucleinopatias/fisiopatologia , Disfunção Cognitiva/complicações , Disfunção Cognitiva/fisiopatologia , Progressão da Doença , Humanos , Hipotensão Ortostática/fisiopatologia , Equilíbrio Postural , Transtorno do Comportamento do Sono REM/fisiopatologia , Sinucleinopatias/mortalidade
10.
Mov Disord ; 34(5): 657-663, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30901495

RESUMO

Obtaining reliable longitudinal information about everyday functioning from individuals with Parkinson's disease (PD) in natural environments is critical for clinical care and research. Despite advances in mobile health technologies, the implementation of digital outcome measures is hindered by a lack of consensus on the type and scope of measures, the most appropriate approach for data capture (eg, in clinic or at home), and the extraction of timely information that meets the needs of patients, clinicians, caregivers, and health care regulators. The Movement Disorder Society Task Force on Technology proposes the following objectives to facilitate the adoption of mobile health technologies: (1) identification of patient-centered and clinically relevant digital outcomes; (2) selection criteria for device combinations that offer an acceptable benefit-to-burden ratio to patients and that deliver reliable, clinically relevant insights; (3) development of an accessible, scalable, and secure platform for data integration and data analytics; and (4) agreement on a pathway for approval by regulators, adoption into e-health systems and implementation by health care organizations. We have developed a tentative roadmap that addresses these needs by providing the following deliverables: (1) results and interpretation of an online survey to define patient-relevant endpoints, (2) agreement on the selection criteria for use of device combinations, (3) an example of an open-source platform for integrating mobile health technology output, and (4) recommendations for assessing readiness for deployment of promising devices and algorithms suitable for regulatory approval. This concrete implementation guidance, harmonizing the collaborative endeavor among stakeholders, can improve assessments of individuals with PD, tailor symptomatic therapy, and enhance health care outcomes. © 2019 International Parkinson and Movement Disorder Society.


Assuntos
Doença de Parkinson/fisiopatologia , Avaliação de Resultados da Assistência ao Paciente , Smartphone , Telemedicina , Dispositivos Eletrônicos Vestíveis , Segurança Computacional , Análise de Dados , Visualização de Dados , Aprovação de Equipamentos , Necessidades e Demandas de Serviços de Saúde , Humanos , Ciência da Implementação , Aplicativos Móveis , Reprodutibilidade dos Testes
12.
Telemed J E Health ; 25(7): 541-550, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30136898

RESUMO

Introduction: Telemedicine represents an emerging model for the assessment and management of various neurological disorders. Methods: We sought to discuss opportunities and challenges for the integration of telemedicine in the management of common and uncommon neurological disorders by reviewing and appraising studies that evaluate telemedicine as a means to facilitate the access to care, deliver highly specialized visits, diagnostic consultations, rehabilitation, and remote monitoring of neurological disorders. Results: Opportunities for telemedicine in neurological disorders include the replacement of or complement to in-office evaluations, decreased time between follow-up visits, reduction in disparities in access to healthcare, and promotion of education and training through interactions between primary care physicians and tertiary referral centers. Critical challenges include the integration of the systems for data monitoring with an easy-to-use, secure, and cost-effective platform that is both widely adopted by patients and healthcare systems and embraced by international scientific societies. Conclusions: Multiple applications may spawn from a model based on digitalized healthcare services. Integrated efforts from multiple stakeholders will be required to develop an interoperable software platform capable of providing not only a holistic approach to care but also one that reduces disparities in the access to care.


Assuntos
Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/terapia , Tecnologia de Sensoriamento Remoto , Telemedicina/organização & administração , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/terapia , Acessibilidade aos Serviços de Saúde/organização & administração , Humanos , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/terapia , Telerreabilitação/organização & administração , Fatores de Tempo
13.
Ann Neurol ; 82(4): 503-513, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28892572

RESUMO

Idiopathic normal pressure hydrocephalus (NPH) remains both oversuspected on clinical grounds and underconfirmed when based on immediate and sustained response to cerebrospinal fluid diversion. Poor long-term postshunt benefits and findings of neurodegenerative pathology in most patients with adequate follow-up suggest that hydrocephalic disorders appearing in late adulthood may often result from initially unapparent parenchymal abnormalities. We critically review the NPH literature, highlighting the near universal lack of blinding and controls, absence of specific clinical, imaging, or pathological features, and ongoing dependence for diagnostic confirmation on variable cutoffs of gait response to bedside fluid-drainage testing. We also summarize our long-term institutional experience, in which postshunt benefits in patients with initial diagnosis of idiopathic NPH persist in only 32% of patients at 36 months, with known revised diagnosis in over 25% (Alzheimer's disease, dementia with Lewy bodies, and progressive supranuclear palsy). We postulate that previously reported NPH cases with "dual" pathology (ie, developing a "second" disorder) more likely represent ventriculomegalic presentations of selected neurodegenerative disorders in which benefits from shunting may be short-lived, with a consequently unfavorable risk-benefit ratio. Ann Neurol 2017;82:503-513.


Assuntos
Hidrocefalia de Pressão Normal/complicações , Hidrocefalia de Pressão Normal/cirurgia , Doenças Neurodegenerativas/etiologia , Progressão da Doença , Transtornos Neurológicos da Marcha/diagnóstico por imagem , Transtornos Neurológicos da Marcha/etiologia , Humanos , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Imageamento por Ressonância Magnética , Doenças Neurodegenerativas/diagnóstico por imagem , PubMed/estatística & dados numéricos
14.
J Neurol Neurosurg Psychiatry ; 89(6): 566-571, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29549192

RESUMO

OBJECTIVE: To ascertain demographic and clinical features of Parkinson disease (PD) associated with functional neurological features. METHODS: A standardised form was used to extract data from electronic records of 53 PD patients with associated functional neurological disorders (PD-FND) across eight movement disorders centres in the USA, Canada and Europe. These subjects were matched for age, gender and disease duration to PD patients without functional features (PD-only). Logistic regression analysis was used to compare both groups after adjusting for clustering effect. RESULTS: Functional symptoms preceded or co-occurred with PD onset in 34% of cases, nearly always in the most affected body side. Compared with PD-only subjects, PD-FND were predominantly female (68%), had longer delay to PD diagnosis, greater prevalence of dyskinesia (42% vs 18%; P=0.023), worse depression and anxiety (P=0.033 and 0.025, respectively), higher levodopa-equivalent daily dose (972±701 vs 741±559 mg; P=0.029) and lower motor severity (P=0.019). These patients also exhibited greater healthcare resource utilisation, higher use of [(123)I]FP-CIT SPECT and were more likely to have had a pre-existing psychiatric disorder (P=0.008) and family history of PD (P=0.036). CONCLUSIONS: A subtype of PD with functional neurological features is familial in one-fourth of cases and associated with more psychiatric than motor disability and greater use of diagnostic and healthcare resources than those without functional features. Functional manifestations may be prodromal to PD in one-third of patients.


Assuntos
Doenças do Sistema Nervoso/epidemiologia , Doença de Parkinson/complicações , Doença de Parkinson/fisiopatologia , Idoso , Antiparkinsonianos/uso terapêutico , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/diagnóstico , Doença de Parkinson/tratamento farmacológico , Prevalência , Fatores de Risco
15.
Mov Disord ; 33(3): 391-397, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29278286

RESUMO

BACKGROUND: Dysautonomia is a frequent and disabling complication of PD, with an estimated prevalence of 30-40% and a significant impact on the quality of life. OBJECTIVES: To evaluate the rate of progression of dysautonomia and, in particular, orthostatic hypotension, in a cohort of unselected PD patients, and assess the extent to which the progression of dysautonomia affects activities of daily living, health-related quality of life, and health care utilization in PD. METHODS: We recruited 131 consecutive patients into a 12-month, prospective, observational cohort study. Clinical measures included the International Parkinson and Movement Disorder Society/UPDRS, the Scale for Outcomes in Parkinson Disease-Autonomic, the Orthostatic Hypotension Symptoms Assessment, and orthostatic blood pressure measurements. Health care utilization was quantified as the number of hospitalizations, emergency room visits, and outpatient clinic evaluations. RESULTS: The overall severity of autonomic symptoms, as measured by the the Orthostatic Hypotension Symptoms Assessment total score, worsened by 20% over 12 months (P < 0.001), with an overall increase in orthostatic hypotension prevalence from 31.1% to 46.7% (P < 0.001). Worsening of autonomic symptoms was independently associated with deterioration in daily living activities (P = 0.021) and health-related quality of life (P = 0.025) adjusting for disease duration, cognitive impairment, and motor severity. Regardless of symptomatic status, orthostatic hypotension was associated with greater deterioration in daily living activities, health care utilization, and falls (P ≤ 0.009) compared to patients without orthostatic hypotension. CONCLUSIONS: The severity of autonomic symptoms progressed by 20% over 1 year and was independently associated with impairments in daily living activities and health-related quality of life. Symptomatic and asymptomatic orthostatic hypotension were both associated with increased prevalence of falls and health care utilization. © 2017 International Parkinson and Movement Disorder Society.


Assuntos
Doenças do Sistema Nervoso Autônomo/etiologia , Doença de Parkinson/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/fisiologia , Estudos de Coortes , Progressão da Doença , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora/fisiologia , Avaliação de Resultados em Cuidados de Saúde , Doença de Parkinson/psicologia , Qualidade de Vida/psicologia
16.
Mov Disord ; 32(3): 325-331, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28116753

RESUMO

Although essential tremor has been considered the most common movement disorder, it has largely remained a diagnosis of exclusion: many tremor and nontremor features must be absent for the clinical diagnosis to stand. The clinical features of "essential tremor" overlap with or may be part of other tremor disorders and, not surprisingly, this prevalent familial disorder has remained without a gene identified, without a consistent natural history, and without an acceptable pathology or pathophysiologic underpinning. The collective evidence suggests that under the rubric of essential tremor there exists multiple unique diseases, some of which represent cerebellar dysfunction, but for which there is no intrinsic "essence" other than a common oscillatory behavior on posture and action. One approach may be to use the term essential tremor only as a transitional node in the deep phenotyping of tremor disorders based on historical, phenomenological, and neurophysiological features to facilitate its etiologic diagnosis or serve for future gene- and biomarker-discovery efforts. This approach deemphasizes essential tremor as a diagnostic entity and facilitates the understanding of the underlying disorders to develop biologically tailored diagnostic and therapeutic strategies. © 2017 International Parkinson and Movement Disorder Society.


Assuntos
Tremor Essencial/classificação , Tremor Essencial/diagnóstico , Humanos
17.
Mov Disord ; 32(3): 319-324, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28233927

RESUMO

Past clinical trials of putative neuroprotective therapies have targeted PD as a single pathogenic disease entity. From an Oslerian clinicopathological perspective, the wide complexity of PD converges into Lewy bodies and justifies a reductionist approach to PD: A single-mechanism therapy can affect most of those sharing the classic pathological hallmark. From a systems-biology perspective, PD is a group of disorders that, while related by sharing the feature of nigral dopamine-neuron degeneration, exhibit unique genetic, biological, and molecular abnormalities, which probably respond differentially to a given therapeutic approach, particularly for strategies aimed at neuroprotection. Under this model, only biomarker-defined, homogenous subtypes of PD are likely to respond optimally to therapies proven to affect the biological processes within each subtype. Therefore, we suggest that precision medicine applied to PD requires a reevaluation of the biomarker-discovery effort. This effort is currently centered on correlating biological measures to clinical features of PD and on identifying factors that predict whether various prodromal states will convert into the classical movement disorder. We suggest, instead, that subtyping of PD requires the reverse view, where abnormal biological signals (i.e., biomarkers), rather than clinical definitions, are used to define disease phenotypes. Successful development of disease-modifying strategies will depend on how relevant the specific biological processes addressed by an intervention are to the pathogenetic mechanisms in the subgroup of targeted patients. This precision-medicine approach will likely yield smaller, but well-defined, subsets of PD amenable to successful neuroprotection. © 2017 International Parkinson and Movement Disorder Society.


Assuntos
Biomarcadores , Ensaios Clínicos como Assunto , Doença de Parkinson/classificação , Doença de Parkinson/diagnóstico , Humanos , Doença de Parkinson/terapia
18.
Mov Disord ; 32(8): 1240-1244, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28631862

RESUMO

BACKGROUND: We report the accumulated experience with ventral intermediate nucleus deep brain stimulation for medically refractory orthostatic tremor. METHODS: Data from 17 patients were reviewed, comparing presurgical, short-term (0-48 months), and long-term (≥48 months) follow-up. The primary end point was the composite activities of daily living/instrumental activities of daily living score. Secondary end points included latency of symptoms on standing and treatment-related complications. RESULTS: There was a 21.6% improvement (P = 0.004) in the composite activities of daily living/instrumental activities of daily living score, which gradually attenuated (12.5%) in the subgroup of patients with an additional long-term follow-up (8 of 17). The latency of symptoms on standing significantly improved, both in the short-term (P = 0.001) and in the long-term (P = 0.018). Three patients obtained no/minimal benefit from the procedure. CONCLUSIONS: Deep brain stimulation of the ventral intermediate nucleus was, in general, safe and well tolerated, yielding sustained benefit in selected patients with medically refractory orthostatic tremor. © 2017 International Parkinson and Movement Disorder Society.


Assuntos
Estimulação Encefálica Profunda/métodos , Tontura/terapia , Sistema de Registros , Tremor/terapia , Núcleos Ventrais do Tálamo/fisiologia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
19.
Mov Disord ; 31(9): 1272-82, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27125836

RESUMO

The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capture of more and previously inaccessible phenomena in Parkinson's disease (PD). However, more information has not translated into a greater understanding of disease complexity to satisfy diagnostic and therapeutic needs. Challenges include noncompatible technology platforms, the need for wide-scale and long-term deployment of sensor technology (among vulnerable elderly patients in particular), and the gap between the "big data" acquired with sensitive measurement technologies and their limited clinical application. Major opportunities could be realized if new technologies are developed as part of open-source and/or open-hardware platforms that enable multichannel data capture sensitive to the broad range of motor and nonmotor problems that characterize PD and are adaptable into self-adjusting, individualized treatment delivery systems. The International Parkinson and Movement Disorders Society Task Force on Technology is entrusted to convene engineers, clinicians, researchers, and patients to promote the development of integrated measurement and closed-loop therapeutic systems with high patient adherence that also serve to (1) encourage the adoption of clinico-pathophysiologic phenotyping and early detection of critical disease milestones, (2) enhance the tailoring of symptomatic therapy, (3) improve subgroup targeting of patients for future testing of disease-modifying treatments, and (4) identify objective biomarkers to improve the longitudinal tracking of impairments in clinical care and research. This article summarizes the work carried out by the task force toward identifying challenges and opportunities in the development of technologies with potential for improving the clinical management and the quality of life of individuals with PD. © 2016 International Parkinson and Movement Disorder Society.


Assuntos
Tecnologia Biomédica/normas , Doença de Parkinson/diagnóstico , Doença de Parkinson/terapia , Humanos
20.
J Peripher Nerv Syst ; 20(1): 1-6, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25864585

RESUMO

Cases of chronic inflammatory demyelinating poliradiculoneuropathy (CIDP) have been reported in hematopoietic stem cells transplantation complicated by graft versus host disease (GVHD). A systematic review of the CIDP-like neuropathies associated with GVHD was conducted until January 2015, analyzing the clinical presentation and the response to different therapeutic regimens. Nineteen patients have been reported in literature including the present one. Fourteen subjects fulfilled the criteria for CIDP, whereas two cases presented with an asymmetric motor onset and one showed motor involvement only associated with anti-ganglioside antibodies. In addition, two subjects already affected by CIDP developed a significant relapse after GVHD. This study reviews the literature data and reports one additional case of CIDP and GVHD, suggesting that the two clinical entities might share a similar immunological background.


Assuntos
Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa/fisiologia
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