RESUMO
BACKGROUND: Levodopa-carbidopa intestinal gel (designated as carbidopa-levodopa enteral suspension in the United States) provides stable plasma levodopa concentrations and reduces motor fluctuations in advanced Parkinson's disease patients through continuous delivery of levodopa via percutaneous endoscopic gastrojejunostomy. We report long-term safety and efficacy outcomes from an open-label phase 3 treatment program. METHODS: PD patients (n = 262) who completed a 12-week double-blind study and its 52-week open-label extension or a separate 54-week open-label study were enrolled in this ongoing phase 3 open-label, multinational study (NCT00660673). Safety and efficacy assessments were collected every 6 months. RESULTS: Mean total duration of exposure to levodopa-carbidopa intestinal gel was 4.1 years (range, 1.2 to 6.9 years). The overall discontinuation rate was 34% (average annual discontinuation rate, 10%). Although most patients (94%) reported an adverse event, the rate of adverse events decreased over time; 53% experienced a serious adverse event. Of patients in this extension study, 54% required jejunal tube replacement during the study, and 37% required percutaneous endoscopic gastrostomy tube replacement. Most patients were on levodopa monotherapy. Patients maintained reductions in "off" time and increases in mean "on" time without dyskinesia from initial levodopa-carbidopa intestinal gel infusion to he study end point (P < 0.001; n = 81). Activities of daily living and quality-of-life assessments demonstrated significant improvements that persisted through the study. CONCLUSIONS: This long-term study demonstrates sustained and clinically meaningful benefits from levodopa-carbidopa intestinal gel in advanced PD patients. Although adverse event rates decreased over time, vigilance is required for device-related complications and adverse events. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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Antiparkinsonianos/uso terapêutico , Carbidopa/uso terapêutico , Géis/uso terapêutico , Intestinos/fisiologia , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Comportamento Compulsivo/induzido quimicamente , Comportamento Compulsivo/epidemiologia , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Cooperação Internacional , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Polineuropatias/induzido quimicamente , Polineuropatias/epidemiologia , Redução de Peso/efeitos dos fármacosRESUMO
BACKGROUND: Continuous administration of levodopa-carbidopa intestinal gel (carbidopa-levodopa enteral suspension) through a percutaneous endoscopic gastrojejunostomy is a treatment option for advanced Parkinson disease (PD) patients with motor fluctuations resistant to standard oral medications. Safety data from 4 prospective studies were integrated to assess the safety of this therapy. METHODS: Safety data from 4 studies were summarized using 2 overlapping data sets, permitting the separation of procedure/device-associated (n = 395) from non-procedure/device adverse events (n = 412). RESULTS: At the data cutoff, median exposure to levodopa-carbidopa intestinal gel was 911 days (range, 1-1980 days) with 963 total patient-years of exposure. Procedure/device adverse events occurred in 300 patients (76%), and serious adverse events occurred in 68 (17%); most frequently reported procedure/device adverse events and serious adverse events were complications of device insertion (41% and 8%, respectively) and abdominal pain (36% and 4%, respectively). Non-procedure/device adverse events occurred in 92% (379), with most frequently reported being insomnia (23%) and falls (23%); 42% (171) had non-procedure/device serious adverse events, with most frequently reported being pneumonia (5%) and PD symptoms (2%). Adverse events led to discontinuation in 17% (72), most frequently because of complication of device insertion (2.4%). There were 34 treatment-emergent deaths (8.3%) in the overlapping data sets, 2 of which (0.5%) were considered "possibly related" to the treatment system. CONCLUSION: In the largest collection of levodopa-carbidopa intestinal gel safety data from prospective clinical studies, procedure/device events were frequently reported and occasionally life threatening. Most non-procedure/device events were typical for levodopa treatment and an elderly population. These factors combined with high treatment efficacy led to a relatively low discontinuation rate in advanced PD patients.
Assuntos
Antiparkinsonianos/efeitos adversos , Carbidopa/efeitos adversos , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Derivação Gástrica/efeitos adversos , Infusões Parenterais/efeitos adversos , Levodopa/efeitos adversos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Doença de Parkinson/tratamento farmacológico , Idoso , Antiparkinsonianos/administração & dosagem , Carbidopa/administração & dosagem , Combinação de Medicamentos , Feminino , Géis , Humanos , Levodopa/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Estudos ProspectivosRESUMO
INTRODUCTION: The aim of this study was to test the clinimetric properties of the Comprehensive Cervical Dystonia Rating Scale. This is a modular scale with modifications of the Toronto Western Spasmodic Torticollis Rating Scale (composed of three subscales assessing motor severity, disability, and pain) now referred to as the revised Toronto Western Spasmodic Torticollis Scale-2; a newly developed psychiatric screening instrument; and the Cervical Dystonia Impact Profile-58 as a quality of life measure. METHODS: Ten dystonia experts rated subjects with cervical dystonia using the comprehensive scale. Clinimetric techniques assessed each module of the scale for reliability, item correlation, and factor structure. RESULTS: There were 208 cervical dystonia patients (73% women; age, 59 ± 10 years; duration, 15 ± 12 years). Internal consistency of the motor severity subscale was acceptable (Cronbach's alpha = 0.57). Item to total correlations showed that elimination of items with low correlations (<0.20) increased alpha to 0.71. Internal consistency estimates for the subscales for disability and pain were 0.88 and 0.95, respectively. The psychiatric screening scale had a Cronbach's alpha of 0.84 and satisfactory item to total correlations. When the subscales of the Toronto Western Spasmodic Torticollis Scale-2 were combined with the psychiatric screening scale, Cronbach's alpha was 0.88, and construct validity assessment demonstrated four rational factors: motor; disability; pain; and psychiatric disorders. The Cervical Dystonia Impact Profile-58 had an alpha of 0.98 and its construction was validated through a confirmatory factor analysis. CONCLUSIONS: The modules of the Comprehensive Cervical Dystonia Rating Scale are internally consistent with a logical factor structure.
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Exame Neurológico/normas , Índice de Gravidade de Doença , Torcicolo/diagnóstico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Clinical characteristics of isolated idiopathic cervical dystonia such as onset site and spread to and from additional body regions have been addressed in single-site studies with limited data and incomplete or variable dissociation of focal and segmental subtypes. The objectives of this study were to characterize the clinical characteristics and demographics of isolated idiopathic cervical dystonia in the largest standardized multicenter cohort. METHODS: The Dystonia Coalition, through a consortium of 37 recruiting sites in North America, Europe, and Australia, recruited 1477 participants with focal (60.7%) or segmental (39.3%) cervical dystonia on examination. Clinical and demographic characteristics were evaluated in terms of the body region of dystonia onset and spread. RESULTS: Site of dystonia onset was: (1) focal neck only (78.5%), (2) focal onset elsewhere with later segmental spread to neck (13.3%), and (3) segmental onset with initial neck involvement (8.2%). Frequency of spread from focal cervical to segmental dystonia (22.8%) was consistent with prior reports, but frequency of segmental onset with initial neck involvement was substantially higher than the 3% previously reported. Cervical dystonia with focal neck onset, more than other subtypes, was associated with spread and tremor of any type. Sensory tricks were less frequent in cervical dystonia with segmental components, and segmental cervical onset occurred at an older age. CONCLUSIONS: Subgroups had modest but significant differences in the clinical characteristics that may represent different clinical entities or pathophysiologic subtypes. These findings are critical for design and implementation of studies to describe, treat, or modify disease progression in idiopathic isolated cervical dystonia. © 2016 International Parkinson and Movement Disorder Society.
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Torcicolo/epidemiologia , Torcicolo/fisiopatologia , Adulto , Idoso , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Torcicolo/classificaçãoRESUMO
BACKGROUND: Fatigue affects 40% to 50% of all PD patients and is a leading cause of disability, with no clearly established or efficacious established treatments. METHODS: In this double-blinded, placebo-controlled, pilot trial, we investigated whether rasagiline improved fatigue among PD patients. Subjects were randomized to 1 mg daily of rasagiline or placebo for 12 weeks. The primary endpoint was a change in the Modified Fatigue Impact Scale from baseline to week 12. RESULTS: Thirty PD subjects (16 men), with Modified Fatigue Impact Scale baseline score of 67 ± 15, were randomized (16 to rasagiline vs. 14 to placebo). Significant improvement was noted in the mean Modified Fatigue Impact Scale score of the rasagiline group (12 points) as compared to placebo (8.5 points) from baseline to week 12 (P = 0.003). CONCLUSION: In this pilot study, rasagiline at a dose of 1 mg per day improved fatigue. Larger randomized studies are needed to confirm this finding.
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Fadiga/tratamento farmacológico , Fadiga/etiologia , Indanos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
Global attention requires disengagement from focal elements of stimuli. Since people with Parkinson's disease (PD) may reveal impaired disengagement, this study attempted to learn if people with PD may be impaired at allocating global attention. Healthy adults and people with PD attempted to bisect lines of uniform thickness and lines composed of two segments of unequal thickness and length. When the longer line segment was to the right of the shorter segment, the group with PD demonstrated an increased deviation toward the longer segment, supporting the postulate that people with PD have an impaired ability to disengage focal attention and engage global spatial attention.
Assuntos
Atenção , Doença de Parkinson/psicologia , Transtornos da Percepção/psicologia , Percepção Espacial , Idoso , Feminino , Humanos , Masculino , Doença de Parkinson/complicações , Transtornos da Percepção/etiologia , Estimulação LuminosaRESUMO
BACKGROUND: Dystonia is a movement disorder characterized by involuntary sustained muscle contractions causing twisting and repetitive movements or abnormal postures. Some cases of primary and neurodegenerative dystonia have been associated with mutations in individual genes critical to the G1-S checkpoint pathway (THAP1, ATM, CIZ1 and TAF1). Secondary dystonia is also a relatively common clinical sign in many neurogenetic disorders. However, the contribution of structural variation in the genome to the etiopathogenesis of dystonia remains largely unexplored. CASE PRESENTATION: Cytogenetic analyses with the Affymetrix Genome-Wide Human SNP Array 6.0 identified a chromosome 13q34 duplication in a 36 year-old female with global developmental delay, facial dysmorphism, tall stature, breast cancer and dystonia, and her neurologically-normal father. Dystonia improved with bilateral globus pallidus interna (GPi) deep brain stimulation (DBS). Genomic breakpoint analysis, quantitative PCR (qPCR) and leukocyte gene expression were used to characterize the structural variant. The 218,345 bp duplication was found to include ADPRHL1, DCUN1D2, and TMCO3, and a 69 bp fragment from a long terminal repeat (LTR) located within Intron 3 of TFDP1. The 3' breakpoint was located within Exon 1 of a TFDP1 long non-coding RNA (NR_026580.1). In the affected subject and her father, gene expression was higher for all three genes located within the duplication. However, in comparison to her father, mother and neurologically-normal controls, the affected subject also showed marked overexpression (2×) of the transcription factor TFDP1 (NM_007111.4). Whole-exome sequencing identified an SGCE variant (c.1295G > A, p.Ser432His) that could possibly have contributed to the development of dystonia in the proband. No pathogenic mutations were identified in BRCA1 or BRCA2. CONCLUSION: Overexpression of TFDP1 has been associated with breast cancer and may also be linked to the tall stature, dysmorphism and dystonia seen in our patient.
Assuntos
Anormalidades Múltiplas/genética , Neoplasias da Mama/genética , Cromossomos Humanos Par 13 , Distonia/genética , Deficiência Intelectual/genética , Atrofia Muscular/genética , Fator de Transcrição DP1/genética , Adulto , Duplicação Cromossômica/genética , Cromossomos Humanos Par 13/genética , Anormalidades Craniofaciais , Deficiências do Desenvolvimento/genética , Fácies , Feminino , Regulação da Expressão Gênica/genética , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Transtornos Psicóticos/genéticaRESUMO
OBJECTIVES: To screen for potentially underreported behavioral changes in patients with idiopathic Parkinson's disease (PD) pre- and post-deep brain stimulation (DBS), a retrospective data base review was performed. METHODS: In total, 113 patients who underwent unilateral or bilateral DBS at the University of Florida in either subthalamic nucleus or globus pallidus internus for PD were screened for behavioral issues by asking about the presence or absence of seven neuropsychiatric symptoms (panic, fear, paranoia, anger, suicidal flashes, crying, and laughing). RESULTS: There was a high prevalence of fear (16.3%), panic (14.0%), and anger (11.6%) at baseline in this cohort. In the first six months following DBS implantation, anger (32.6%), fear (26.7%), and uncontrollable crying (26.7%) were the most frequent symptoms reported. Those symptoms also were present following six months of DBS surgery (30.2%, 29.1%, and 19.8%, respectively). New uncontrollable crying occurred more in the acute postoperative stage (less than or equal to six months) (p = 0.033), while new anger occurred more in the chronic postoperative stage (greater than six months) (p = 0.017). The frequency of uncontrollable laughing significantly increased with bilateral DBS (p = 0.033). CONCLUSIONS: Many of the neuropsychiatric issues were identified at preoperative baseline and their overall occurrence was more than expected. There was a potential for worsening of these issues post-DBS. There were subtle differences in time course, and in unilateral vs. bilateral implantations. Clinicians should be aware of these potential behavioral issues that may emerge following DBS therapy, and should consider including screening questions in preoperative and postoperative interviews. Standardized scales may miss the presence or absence of these clinically relevant issues.
Assuntos
Estimulação Encefálica Profunda/efeitos adversos , Estimulação Encefálica Profunda/psicologia , Doença de Parkinson/psicologia , Doença de Parkinson/terapia , Humanos , Estudos RetrospectivosRESUMO
Apathy is a common neuropsychiatric feature of Parkinson's disease (PD), but little is known of relationships between apathy and specific medications in PD. Following a retrospective database and chart review of 181 Parkinson's patients, relationships between Apathy Scale scores and use of psychotropic and antiparkinsonian medications were examined with multiple regression. Controlling for age, sex, education, and depression, the use of selective serotonin reuptake inhibitors (SSRIs), but not other antidepressants, was associated with greater apathy. Use of monoamine oxidase B inhibitors was associated with less apathy. Longitudinal studies are needed to evaluate a potential SSRI-induced apathy syndrome in PD.
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Antidepressivos/efeitos adversos , Apatia/efeitos dos fármacos , Depressão/tratamento farmacológico , Doença de Parkinson/psicologia , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Depressão/epidemiologia , Depressão/etiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/epidemiologia , Análise de Regressão , Estudos RetrospectivosRESUMO
OBJECTIVE: The objective of this study is to compare a computerized deep brain stimulation (DBS) screening module (Comparing Private Practice vs. Academic Centers in Selection of DBS Candidates [COMPRESS], NeuroTrax Corp., Bellaire, TX, USA) with traditional triage by a movement disorders specialized neurologist as the gold standard. METHODS: The COMPRESS consists of a combination of the Florida Surgical Questionnaire for Parkinson disease (FLASQ-PD), a cognitive assessment battery provided by MindStreams® (NeuroTrax Corp.), and the Geriatric Depression Scale and the Zung Anxiety Self-Assessment Scale. COMPRESS resulted in the classification of patients into three categories: "optimal candidate,""probable candidate," and "not a good candidate." Similar categorical ratings made by a referring private practice neurologist and by a trained movement disorders specialist were compared with the ratings generated by COMPRESS. RESULTS: A total of 19 subjects with Parkinson's disease were enrolled from five private neurological practices. The clinical impressions of the private practice neurologist vs. those of the movement disorders specialist were in agreement approximately half the time (10/19 cases). The movement disorders specialist and COMPRESS agreed on 15/19 cases. A further comparison between outcomes from the entire COMPRESS module and the FLASQ-PD questionnaire by itself resulted in high agreement (18/19 cases in agreement). CONCLUSIONS: The COMPRESS agreed with an in-person evaluation by a movement disorders neurologist approximately 80% of the time. The computerized COMPRESS did not provide any screening advantage over the short FLASQ-PD paper questionnaire. Larger studies will be needed to assess the utility and cost effectiveness of this computerized triage method for DBS.
Assuntos
Estimulação Encefálica Profunda , Diagnóstico por Computador/métodos , Doença de Parkinson/terapia , Seleção de Pacientes , Triagem/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurologia/métodos , Doença de Parkinson/diagnóstico , Prática Privada , Encaminhamento e ConsultaRESUMO
The objective of this study is to learn if participants with Parkinson disease (PD), when compared to normal controls, are impaired in making simultaneous but independent right and left hand movements. Participants were tested with Luria's Alternating Hand Postures (AHP) test and modified AHP tests. Twelve PD participants without dementia and twelve matched controls were assessed for their ability to perform the parallel AHP test (both hands remaining in the same coronal plane) and with modifications of this test into swimming (alternative arm extension with finger extension and arm flexion with finger flexion) and reverse swimming (alternative arm extension-finger flexion and arm flexion-finger extension) movements. The participants with PD were significantly impaired when performing the parallel and the reverse swimming movements AHP tests, but not impaired on the swimming movements AHP test. Swimming movements may be phylogenetically and ontogenetically more primitive and not as heavily dependent on frontal-basal ganglia networks; thus performance of swimming movements during the parallel AHP test may decrease this test's sensitivity.
Assuntos
Função Executiva/fisiologia , Destreza Motora/fisiologia , Testes Neuropsicológicos , Doença de Parkinson/psicologia , Natação/fisiologia , Idoso , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/psicologia , Demografia , Feminino , Lateralidade Funcional/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Movimento/fisiologia , Doença de Parkinson/complicaçõesRESUMO
Of 96 Parkinson's disease patients surveyed at the University of Florida Movement Disorders Center, one (1%) met diagnostic criteria for binge-eating disorder. Eight (8.3%) exhibited subthreshold binge eating. Psychometric criteria classified problem gambling in 17.8%, hoarding in 8.3%, compulsive buying in 11.5%, hypersexuality in 1.0%, and mania in 1.0% of patients. More overeaters met psychometric criteria for at least one additional impulse-control disorder (67% versus 29%). No more overeaters than non-overeaters were taking a dopamine agonist (44% versus 41%). More overeaters had a history of subthalamic deep brain stimulation (DBS; 44% versus 14%). History of DBS was the only independent predictor of overeating.
Assuntos
Bulimia/epidemiologia , Bulimia/etiologia , Estimulação Encefálica Profunda/efeitos adversos , Doença de Parkinson/epidemiologia , Doença de Parkinson/terapia , Idoso , Bulimia/psicologia , Transtornos Disruptivos, de Controle do Impulso e da Conduta/epidemiologia , Transtornos Disruptivos, de Controle do Impulso e da Conduta/etiologia , Transtornos Disruptivos, de Controle do Impulso e da Conduta/psicologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/psicologia , Prevalência , Psicometria , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Non-motor symptoms are well established phenotypic components of adult-onset idiopathic, isolated, focal cervical dystonia (AOIFCD). However, improved understanding of their clinical heterogeneity is needed to better target therapeutic intervention. Here, we examine non-motor phenotypic features to identify possible AOIFCD subgroups. METHODS: Participants diagnosed with AOIFCD were recruited via specialist neurology clinics (dystonia wales: n = 114, dystonia coalition: n = 183). Non-motor assessment included psychiatric symptoms, pain, sleep disturbance, and quality of life, assessed using self-completed questionnaires or face-to-face assessment. Both cohorts were analyzed independently using Cluster, and Bayesian multiple mixed model phenotype analyses to investigate the relationship between non-motor symptoms and determine evidence of phenotypic subgroups. RESULTS: Independent cluster analysis of the two cohorts suggests two predominant phenotypic subgroups, one consisting of approximately a third of participants in both cohorts, experiencing increased levels of depression, anxiety, sleep impairment, and pain catastrophizing, as well as, decreased quality of life. The Bayesian approach reinforced this with the primary axis, which explained the majority of the variance, in each cohort being associated with psychiatric symptomology, and also sleep impairment and pain catastrophizing in the Dystonia Wales cohort. CONCLUSIONS: Non-motor symptoms accompanying AOIFCD parse into two predominant phenotypic sub-groups, with differences in psychiatric symptoms, pain catastrophizing, sleep quality, and quality of life. Improved understanding of these symptom groups will enable better targeted pathophysiological investigation and future therapeutic intervention.
Assuntos
Distúrbios Distônicos , Torcicolo , Adulto , Teorema de Bayes , Humanos , Fenótipo , Qualidade de Vida , Torcicolo/epidemiologiaRESUMO
OBJECTIVE: Our aim was to compare in a prospective blinded study the cognitive and mood effects of subthalamic nucleus (STN) vs. globus pallidus interna (GPi) deep brain stimulation (DBS) in Parkinson disease. METHODS: Fifty-two subjects were randomized to unilateral STN or GPi DBS. The co-primary outcome measures were the Visual Analog Mood Scale, and verbal fluency (semantic and letter) at 7 months post-DBS in the optimal setting compared to pre-DBS. At 7 months post-DBS, subjects were tested in four randomized/counterbalanced conditions (optimal, ventral, dorsal, and off DBS). RESULTS: Forty-five subjects (23 GPi, 22 STN) completed the protocol. The study revealed no difference between STN and GPi DBS in the change of co-primary mood and cognitive outcomes pre- to post-DBS in the optimal setting (Hotelling's T(2) test: p = 0.16 and 0.08 respectively). Subjects in both targets were less "happy", less "energetic" and more "confused" when stimulated ventrally. Comparison of the other 3 DBS conditions to pre-DBS showed a larger deterioration of letter verbal fluency in STN, especially when off DBS. There was no difference in UPDRS motor improvement between targets. INTERPRETATION: There were no significant differences in the co-primary outcome measures (mood and cognition) between STN and GPi in the optimal DBS state. Adverse mood effects occurred ventrally in both targets. A worsening of letter verbal fluency was seen in STN. The persistence of deterioration in verbal fluency in the off STN DBS state was suggestive of a surgical rather than a stimulation-induced effect. Similar motor improvement were observed with both STN and GPi DBS.
Assuntos
Transtornos Cognitivos , Estimulação Encefálica Profunda/métodos , Globo Pálido/fisiologia , Transtornos do Humor , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Núcleo Subtalâmico/fisiologia , Adulto , Idoso , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/terapia , Método Duplo-Cego , Estimulação Elétrica/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/etiologia , Transtornos do Humor/terapia , Atividade Motora/fisiologia , Testes Neuropsicológicos , Estudos Prospectivos , Escalas de Graduação PsiquiátricaRESUMO
To test whether the synucleinopathies Parkinson's disease and multiple system atrophy (MSA) share a common genetic etiology, we performed a candidate single nucleotide polymorphism (SNP) association study of the 384 most associated SNPs in a genome-wide association study of Parkinson's disease in 413 MSA cases and 3,974 control subjects. The 10 most significant SNPs were then replicated in additional 108 MSA cases and 537 controls. SNPs at the SNCA locus were significantly associated with risk for increased risk for the development of MSA (combined p = 5.5 x 10(-12); odds ratio 6.2) [corrected].
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Predisposição Genética para Doença , Atrofia de Múltiplos Sistemas/genética , Polimorfismo de Nucleotídeo Único/genética , alfa-Sinucleína/genética , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Masculino , Razão de Chances , RiscoRESUMO
BACKGROUND: X-linked dystonia-parkinsonism (XDP; DYT3; Lubag) is an adult-onset hereditary progressive dystonia/parkinsonism which is typically minimally responsive to pharmacological treatment. CASE REPORT: We report a 63- year-old man with a diagnosis of XDP who underwent bilateral globus pallidus internus deep brain stimulator (GPi-DBS) placement. His course initially began with right hand tremor and dystonia at age 57 and progressed to also include bradykinesia and rigidity. The patient tolerated the procedure without significant complications. GPi-DBS improved his right hand dystonia, but did not significantly improve his parkinsonism. CONCLUSION: DBS may be a therapeutic option for select cases of XDP, but its specific indications must be carefully discussed, as the available cases have had mixed responses. Whether other targets may be more effective is not known.
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Estimulação Encefálica Profunda , Distonia/terapia , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Globo Pálido/cirurgia , Transtornos Parkinsonianos/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Autonomic symptomatology is prevalent in Parkinson's disease (PD) and impacts quality of life, yet little data exist on the presentation of autonomic dysregulation. This study measures orthostasis, constipation, and anosmia in 58 PD patients and 51 age-matched controls enrolled in the University of Florida's Movement Disorders Center. Patients had their blood pressure measured while seated and in standing position, performed the University of Pennsylvania Smell Identification Test (UPSIT), and completed a constipation survey. Our PD patients had a significantly different average decrease in systolic BP from a seated to standing position compared with their age-matched controls (5.90 mmHg (SD 17.03) vs. 2.6 mmHg (SD 11.28); p = .05). The difference in heart rate from seated to standing positions was not significant. Reflexive tachycardia was inversely proportional to levodopa equivalent daily dose (LEDD) score (p = .002). Anosmia occurred in 96.4% of the PD group and 49% of the controls (p < .001). Constipation was also more prevalent in the PD population than in the controls (67.3% vs. 21.6%; p < .001). Both anosmia and constipation were correlated with disease duration (p = .038 and .04 respectively). Our study suggests that increasing levels of dopaminergic therapy inhibits reflexive tachycardia. Furthermore, our study suggests that anosmia and constipation progress with the primary disease process.
Assuntos
Constipação Intestinal/etiologia , Tontura/etiologia , Transtornos do Olfato/etiologia , Doença de Parkinson/complicações , Idoso , Pressão Sanguínea/fisiologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Seguimentos , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/psicologia , Projetos Piloto , Qualidade de Vida , Análise de Regressão , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
PURPOSE: The purpose of this study is to compare the prevalence of idiopathic rhinorrhea in PD patients versus controls, to determine the correlation between rhinorrhea and anosmia, and the factors associated with rhinorrhea. SCOPE: A cohort of 61 PD patients and 51 age-matched controls completed a survey about rhinorrhea and underwent the University of Pennsylvania Smell Identification Test (UPSIT). We compared the prevalence of idiopathic rhinorrhea in the PD patients versus controls, the correlation between rhinorrhea and anosmia in PD patients, and the factors associated with rhinorrhea in the PD patients. The results of the study are that 6% of controls versus 24% of PD patients had rhinorrhea (p = .03); moreover, only 2% of controls versus 15% of PD patients had severe rhinorrhea. CONCLUSION: Rhinorrhea is more prevalent in PD patients compared to controls and it does not significantly impact performance on a smell test.
Assuntos
Doenças Nasais/etiologia , Doença de Parkinson/complicações , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/etiologia , Projetos Piloto , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
Consecutive patients in a Movement Disorders Center with Parkinson disease (PD) were offered to undergo complete neuropsychological testing and to complete the Beck Depression Inventory (BDI), regardless of their cognitive and behavioral status. A total of 82 patients were included in this cross-sectional study and had a mean age of 67.7 years, formal education of 14.8 years, PD duration of 101 months, Unified Parkinson Disease Rating Scale-Motor ''off'' score of 36.96, Mini-Mental State Examination (MMSE) score of 27.8 (range 19-30), and BDI score of 10.23 (SD 8.65). Beck Depression Inventory scores did not correlate with disease duration or motor scores but inversely correlated with the MMSE scores (r = -0.40; P < .001) and total Dementia Rating Scale (DRS) scores (r = -0.33; P < .01). Using a univariate regression analysis controlling for age, gender, education, and total Unified Parkinson Disease Rating Scales (UPDRS) score, the BDI scores had a significant and unique relationship with MMSE scores. However, when the BDI scores were correlated with specific cognitive domains, only the Boston Naming Test and the Hopkins Verbal Learning Test (HVLT) delayed recall remained significant after Bonferroni correction. Similarly, when comparing the cognitive performance of patients with PD who scored >14 on the BDI versus those who scored <14, only the mean score of the Boston Naming Test was different between the 2 groups. Our study shows that while depressive symptoms correlated with global cognitive performance, naming, verbal memory, and language are the most susceptible cognitive domains affected with depressive symptoms.
Assuntos
Transtornos Cognitivos/psicologia , Depressão , Doença de Parkinson/psicologia , Idoso , Cognição , Transtornos Cognitivos/complicações , Estudos de Coortes , Estudos Transversais , Discinesias/complicações , Discinesias/psicologia , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Doença de Parkinson/complicações , Análise de Regressão , Índice de Gravidade de Doença , Fatores de TempoRESUMO
We describe late diagnosis of an adult with L-2-hydroxyglutaric aciduria (MIM 236792) on the basis of characteristic metabolite data and mutation analysis in the L2HGDH gene. The patient lacked MRI abnormalities which have been purported to be constant or typical findings in this disease. We further report the genetic status of his parents and his one living sibling. Our observations underline the clinical heterogeneity of the syndrome of L-2-hydroxyglutaric aciduria. This report emphasizes the diagnostic benefit of the assessment of urinary organic acids not only in children, but also in adult patients with unexplained neurological symptoms. The patient was determined to be compound heterozygous for two novel missense mutations in exon 4 of the gene (c.418G>C, c.446T>G), resulting in amino acid exchanges from alanine to proline (p.Ala140Pro) and leucine to arginine (p.Leu149Arg), respectively. The mother of our patient was heterozygous for Ala140Pro, and the father heterozygous for Leu149Arg only. Mutation analysis of a healthy 49-year-old third son of the non-consanguineous parents revealed a normal exon 4.