RESUMO
Impulse control disorders (ICD) are common in Parkinson's disease (PD) and are associated with dopaminergic medication. The purpose of this study was to investigate executive function and risk-taking behavior in PD patients with ICD. 17 PD patients with ICD (ICD-PD) were compared to 20 PD patients without ICD (CTRL-PD) using neuropsychological and experimental tasks. Executive functions were assessed using standard executive testing (Conner's Performance Test, Modified Wisconsin Card Sorting Test, Trail Making Test and phonological verbal fluency). Subjects were also submitted to an experimental gambling task consisted of three decks of money cards: neutral deck (equal opportunity for gains as losses), winning deck (small amount of money with a positive balance) and loser deck (high amount of money with a negative balance), evaluating risk-taking behavior (number of cards picked in each deck) and valuation of the reward (subjective appreciation of the value of each deck). There was no significant difference in executive functioning between groups. Both groups selected more cards in the losing deck (high amount of money) as compared to the neutral deck (Mann-Whitney test, ICD-PD, p = 0.02; CTRL-PD, p = 0.003) and to the winning deck (Mann-Whitney test, ICD-PD p = 0.0001; CTRL-PD p = 0.003), suggesting an increased risk-taking behavior. Interestingly, we found that ICD-PD patients estimated the value of decks differently from CTRL-PD patients, taking into account mainly the positive reinforced value of the decks (Mann-Whitney test, p = 0.04). This study showed that executive pattern and risk-taking behavior are similar between ICD-PD and CTRL-PD patients. However, ICD-PD patients showed a specific deficit of the subjective estimation of the reward. Links between this deficit and metacognitive skills are discussed.
Assuntos
Transtornos Disruptivos, de Controle do Impulso e da Conduta/fisiopatologia , Função Executiva/fisiologia , Metacognição/fisiologia , Doença de Parkinson/fisiopatologia , Assunção de Riscos , Adulto , Idoso , Transtornos Disruptivos, de Controle do Impulso e da Conduta/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicaçõesRESUMO
OBJECTIVE: In Parkinson disease (PD), the selective C-O-methyltransferase (COMT) inhibitor entacapone prolongs the effect of levodopa on motor symptoms (ON time) by increasing its bioavailability. The COMT Val158Met polymorphism is equally distributed in PD patients and modulates COMT activity, which can be high (Val/Val, COMT(HH) ), intermediate (Val/Met, COMT(HL) ), or low (Met/Met, COMT(LL) ). The objective of this study was to determine the response to entacapone in COMT(HH) and COMT(LL) PD patients. METHODS: Thirty-three PD patients, homozygous for the COMT alleles COMT(HH) (n = 17) and COMT(LL) (n = 16), were randomized in a double-blind crossover trial consisting of 2 successive acute levodopa challenges associated with 200mg entacapone or placebo. The primary endpoint was the gain in the best ON time. Secondary endpoints were levodopa pharmacokinetics and COMT activity in red blood cells. RESULTS: The gain in the best ON time was higher in COMT(HH) than in COMT(LL) patients (39 ± 10 vs 9 ± 9 minutes, p = 0.04, interaction between treatment and genotype). Area under the concentration over time curve of levodopa increased more after entacapone in COMT(HH) than in COMT(LL) patients (+62 ± 6% vs +34 ± 8%, p = 0.01). COMT inhibition by entacapone was higher in COMT(HH) than in COMT(LL) patients (-0.54 ± 0.07 vs -0.31 ± 0.06 pmol/min/mg protein, p = 0.02). INTERPRETATION: The COMT(HH) genotype in PD patients enhances the effect of entacapone on the pharmacodynamics and pharmacokinetics of levodopa. The response to entacapone after repeated administrations and in heterozygous patients remains to be determined.
Assuntos
Antiparkinsonianos/uso terapêutico , Catecol O-Metiltransferase/genética , Catecóis/uso terapêutico , Nitrilas/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Polimorfismo Genético , Idoso , Antiparkinsonianos/farmacocinética , Disponibilidade Biológica , Inibidores de Catecol O-Metiltransferase , Catecóis/farmacocinética , Estudos Cross-Over , Método Duplo-Cego , Inibidores Enzimáticos/uso terapêutico , Feminino , Genótipo , Humanos , Levodopa/metabolismo , Levodopa/farmacocinética , Levodopa/uso terapêutico , Masculino , Metionina/genética , Pessoa de Meia-Idade , Nitrilas/farmacocinética , Doença de Parkinson/genética , Farmacogenética , Valina/genéticaRESUMO
S90049, a novel sublingual formulation of the non-ergoline D(2)-D(3) agonist piribedil, has a pharmacokinetic profile promising to provide rapid relief on motor signs in Parkinson's disease (PD). We assessed the efficacy and safety of S90049 in aborting OFF episodes responding to subcutaneous apomorphine in PD patients with motor fluctuations. This was a single-dose double-blind double-placebo 3 x 3 cross-over study. Optimal tested doses were determined during a previous open-label titration phase (S90049 median dose: 60 mg, apomorphine: 5 mg). Primary endpoint was the maximal change versus baseline in UPDRS motor score (Delta UPDRS III) assessed after drug administration following an overnight withdrawal of antiparkinsonian medications. Thirty patients (age: 60 +/- 8 years, PD duration: 12 +/- 6 years, UPDRS III OFF: 37 +/- 15) participated. S90049 was superior to placebo on Delta UPDRS III (-13 +/- 12 versus -7 +/- 9 respectively; estimated difference -5.2, 95% Confidence Interval (CI)[-10.4;0.05], P = 0.05). This was also true for secondary outcomes: number of patients switching from OFF to ON (17 on S90049 vs. 8 on placebo, P = 0.03), time to turn ON (P = 0.013) and duration of the ON phase (P = 0.03). In the 17 patients who switched ON on S90049, Delta UPDRS III was similar on S90049 (-21.2 +/- 10.1) and apomorphine (-23.6 +/- 14.1) (estimated difference: 4.0 95% CI [-2.9;10.9]). S90049 was well tolerated: no serious or unexpected adverse event occurred. A single dose of up to 60 mg of S90049 given sublingually was superior to placebo in improving UPDRS III and aborting a practical OFF in patients with advanced PD. Testing greater doses might improve response rate.
Assuntos
Antiparkinsonianos/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Piribedil/administração & dosagem , Administração Sublingual , Apomorfina/administração & dosagem , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Vias de Administração de Medicamentos , França , Humanos , Modelos Logísticos , Modelos de Riscos Proporcionais , Índice de Gravidade de DoençaRESUMO
We assessed the effects of deep brain stimulation of the subthalamic nucleus (STN-DBS) or internal pallidum (GPi-DBS) on health-related quality of life (HrQoL) in patients with advanced Parkinson's disease participating in a previously reported multicenter trial. Sickness Impact Profile (SIP) questionnaires were available for analysis in a subgroup of n = 20/20 patients with GPi-DBS and n = 45/49 patients with STN-DBS at baseline, 6 and 36 months. The SIP provides a physical dimension and a psychosocial dimension sum score and 12 category scores: Alertness/Intellectual Behavior (AIB), Ambulation (A), Body Care and Movement (BCM), Communication (C), Eating (E), Emotional Behavior (EB), Home Management (HM), Mobility (M), Recreation and Pastimes (RP), Sleep and Rest (SR), Social Interaction (SI), and Work (W). Motor functioning was assessed by means of the Unified Parkinson's Disease Rating Scale and diaries. At 6 months significant improvements in off-period motor symptoms and activities of daily living were paralleled by significant reductions in the total, physical, and psychosocial SIP score in both treatment groups. At 3 years, sustained improvements were observed in the physical dimension score, BCM, E, M, RP after STN-DBS and M, SI after GPi-DBS. All other SIP subscores approached baseline values, but were still the same or better (except C) whereas motor functioning remained stable after 36 months. STN-DBS and GPi-DBS led to significant early improvements in HrQoL. Despite sustained motor improvements many of these initial benefits were lost after 3 years. This may reflect either progression of the disease or adaptive changes in the subjective perception of health-related wellbeing over time.
Assuntos
Globo Pálido/fisiologia , Doença de Parkinson/psicologia , Doença de Parkinson/terapia , Qualidade de Vida/psicologia , Núcleo Subtalâmico/fisiologia , Atividades Cotidianas , Idoso , Estimulação Encefálica Profunda , Emoções/fisiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Perfil de Impacto da Doença , Estatísticas não Paramétricas , Inquéritos e Questionários , Fatores de TempoRESUMO
Given the variability of the results found in the literature, the current study is a step toward better clarifying the influence of motor and nonmotor factors on quality of life in Parkinson's disease. A total of 135 participants with Parkinson's disease were selected. Semistructured interviews were carried out, after which their mental and cognitive states were assessed using different scales (MINI, MADRS, EHD, HAMA). Finally, all participants completed 3 self-report questionnaires: 2 assessing coping strategies (WCC, CHIP) and 1, quality of life (Parkinson's disease questionnaire-39). It appears that the presence of dyskinesia, depression, and anxiety were linked to a poor quality of life. Interestingly, some different coping strategies, namely diversion as well as emotional strategies, were associated with a poor quality of life. These results encourage us to develop interventions focused on coping strategies and tailored to the emotional and clinical characteristics of each patient.
Assuntos
Adaptação Psicológica , Discinesias/psicologia , Transtornos do Humor/psicologia , Doença de Parkinson/psicologia , Qualidade de Vida/psicologia , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , Comorbidade , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/psicologia , Discinesias/diagnóstico , Discinesias/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/diagnóstico , Transtornos do Humor/epidemiologia , Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologia , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Psicometria , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To evaluate the clinical features of the working memory (WM) in Parkinson's disease (PD) patients and to test the effect of levodopa on WM. METHOD: The paradigm was based on the 'n-back' tasks, which enables to study the level of executive demand (three levels of difficulty) and the domain of the information being processed (spatial items, faces and letters). The effect of levodopa was studied by testing PD patients in "on" and "off" states. RESULTS: PD patients performed less well in WM tasks than controls. There was no interaction between groups and complexity. Levodopa therapy had a positive effect only on spatial WM tasks but no effect on complexity. CONCLUSION: Our results suggest that impairment observed may result from a maintenance deficit within WM regardless the level of processing and levodopa therapy presents a positive effect on spatial WM.
Assuntos
Antiparkinsonianos/uso terapêutico , Dopaminérgicos/uso terapêutico , Levodopa/uso terapêutico , Memória/efeitos dos fármacos , Doença de Parkinson , Percepção Espacial/efeitos dos fármacos , Idoso , Análise de Variância , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Memória/fisiologia , Memória de Curto Prazo/efeitos dos fármacos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Percepção Espacial/fisiologiaRESUMO
OBJECTIVE: To investigate the prevalence and risk factors of heart valve disease in patients having PD treated with pergolide. DESIGN: Prospective observational study. SETTING: Patients were recruited at the Hôpital de la Pitié-Salpêtrière, Paris, France. Patients Ninety-six patients having PD treated with pergolide for longer than 3 months vs 50 control subjects. Intervention Standardized echocardiography performed by an investigator blinded to treatment status. Main Outcome Measure Moderate to severe regurgitation in at least 1 heart valve. RESULTS: One hundred thirty-three echocardiograms (86 in the pergolide-treated group and 47 in the control group) were analyzed in the study. Moderate to severe regurgitation was found in 15 patients treated with pergolide (17.4%) and in 2 control subjects (4.3%) (odds ratio [OR], 4.75; 95% confidence interval [CI], 1.02-22.1; P = .03). Moderate to severe regurgitation was associated with the cumulative dose of pergolide (OR, 1.37; 95% CI, 1.04-1.81 per 10-mg/kg increase; P =.03). Including the present study, the meta-analysis comprised 7 trials (394 patients treated with pergolide and 280 controls). The overall OR for moderate to severe regurgitation was 3.1 (95% CI, 1.7-5.6; P < .001) in the pergolide-treated group. Risk differences were correlated with the mean cumulative dose of pergolide (r = 0.90, P < .001). DATA SOURCES: Using an end point of moderate to severe heart valve regurgitation, we performed a meta-analysis of patients having Parkinson disease (PD) treated with pergolide mesylate vs control subjects by searching PubMed (January 1, 1966, to April 1, 2007) and the Cochrane databases to identify English-language prospective observational studies that reported echocardiographic data. CONCLUSION: Heart valve disease is independently associated with the use of pergolide treatment in patients having PD and correlates with its cumulative dose. Trial Registration clinicaltrials.gov Identifier: NCT00202657.
Assuntos
Antiparkinsonianos/efeitos adversos , Doenças das Valvas Cardíacas/induzido quimicamente , Doença de Parkinson/complicações , Pergolida/efeitos adversos , Antiparkinsonianos/uso terapêutico , Insuficiência da Valva Aórtica/induzido quimicamente , Insuficiência da Valva Aórtica/epidemiologia , Relação Dose-Resposta a Droga , Ecocardiografia , Feminino , Doenças das Valvas Cardíacas/epidemiologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/induzido quimicamente , Insuficiência da Valva Mitral/epidemiologia , Razão de Chances , Doença de Parkinson/tratamento farmacológico , Pergolida/uso terapêutico , Estudos Prospectivos , Fatores de Risco , Insuficiência da Valva Tricúspide/induzido quimicamente , Insuficiência da Valva Tricúspide/epidemiologiaRESUMO
BACKGROUND: Mutations in leucine-rich repeat kinase 2 gene (LRRK2), particularly the G2019S mutation in exon 41, have been detected in familial and sporadic Parkinson disease (PD) cases. OBJECTIVES: To assess the frequency of LRRK2 exon 41 mutations in a series of sporadic PD cases from Europe and to determine the clinical features of LRRK2 mutation carriers. DESIGN: We analyzed European cases of sporadic PD for the presence of LRRK2 exon 41 mutations. These mutations were screened by denaturing high-performance liquid chromatography, and abnormal chromatograph traces were investigated by direct sequencing to determine the exact nature of the variants. Early-onset sporadic PD cases were also screened for parkin mutations. The haplotypes associated with the G2019S mutation were determined. The clinical characteristics of patients carrying LRRK2 mutations were detailed. SETTING: French Network for the Study of Parkinson Disease Genetics. Patients Three hundred twenty patients with apparently sporadic PD from Europe. MAIN OUTCOME MEASURES: Results of genetic analyses. RESULTS: We found the G2019S mutation in 6 patients and identified 2 new variants (Y2006H and T2031S) in 1 patient each. Their clinical features were similar to those of typical PD. All G2019S mutation carriers shared a common haplotype. CONCLUSIONS: The G2019S mutation is almost as frequent in sporadic cases (1.9%) as in previously reported familial cases (2.9%) in Europe and occurs in the same common founder. We identified 2 novel variants. Although the phenotype of LRRK2 mutation carriers closely resembles that of typical PD, the age at onset was younger (29 years in 1 patient) than previously described, and 3 patients were improved by deep brain stimulation.
Assuntos
Éxons/genética , Mutação , Doença de Parkinson/genética , Proteínas Serina-Treonina Quinases/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA/métodos , Europa (Continente) , Feminino , Histidina/genética , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Serina/genética , Treonina/genética , Tirosina/genéticaRESUMO
OBJECTIVE: To investigate the indications and the outcomes of gastrostomy tube insertion in patients with parkinsonian syndromes. METHODS: Consecutive patients with Parkinson's disease or atypical parkinsonism, seen in two French tertiary referral movement disorders centers, that received gastrostomy tube insertion (GTI) for feeding between 2008 and 2014 were included in this retrospective study. Data regarding clinical status, indications and outcomes were retrieved from medical files. The main outcome measure was survival duration following gastrostomy insertion according to Kaplan-Meier estimate. Cox analysis was also performed to identify factors associated with survival. Finally, we described short term and long term adverse effects occurring during the follow-up period. RESULTS: We identified 33 patients with Parkinsonism that received GTI during the study period. One patient was excluded from the analysis because of missing data. Among 32 patients, 7 (22%) had Parkinson's disease and 25 (78%) had atypical parkinsonism. The median survival following the procedure was 186 days (CI 95% [62-309]). In Cox model analysis, total dependency was the only factor negatively associated with survival (HR 0.1; 95% CI [0.02-0.4], p = 0.001). Pneumonia was the most frequent adverse event. CONCLUSION: In this sample of patients with parkinsonian syndromes, survival after GTI was short particularly in totally dependent subjects. Aspiration pneumonia was not prevented by GTI. A larger prospective study is warranted to assess the potential benefits of gastrostomy, in order to identify the most appropriate indications and timing for the procedure.
Assuntos
Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Gastrostomia/métodos , Transtornos Parkinsonianos , Resultado do Tratamento , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Parkinsonianos/complicações , Transtornos Parkinsonianos/mortalidade , Transtornos Parkinsonianos/cirurgia , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
BACKGROUND: How well the motor symptoms assessed by the motor section of the Unified Parkinson Disease Rating Scale (UPDRS3) reflect the neuronal loss observed in the substantia nigra is not known. OBJECTIVE: To study the relationships among the motor symptoms assessed by the UPDRS3, Lewy body-associated neuronal loss in the substantia nigra, and duration of disease. DESIGN: Longitudinal, prospective, clinicopathological study. SETTING: Long-term care facility of a university hospital. PATIENTS: Eighteen elderly patients with a parkinsonian syndrome, studied prospectively but selected post mortem on the basis of the presence of Lewy bodies, and 5 age-matched control subjects. METHODS: One map of a section of the substantia nigra, indicating the location of all the nucleolated neuronal profiles, was drawn for each case. Neuronal density was estimated using a tessellation method. The relationship between time and neuronal loss and between neuronal loss and motor symptoms (assessed by the UPDRS3) was studied by means of regression analysis, using linear and exponential models. RESULTS: The neuronal density was linearly linked with the UPDRS3 score (r = -0.83 [P<.001]). Each point added to the UPDRS3 score corresponded to an estimated loss of 25 neurons/mm(3). The density of neuronal profiles in the substantia nigra decreased exponentially with time (r = -0.73 [P<.001]). Extrapolation of the curve suggested a presymptomatic phase of 5 years. CONCLUSION: The UPDRS3 score is linearly linked to neuronal density, which, in Lewy body diseases, decreases exponentially with time at a similar pace in this series of elderly patients and in the younger patients described in the literature.
Assuntos
Corpos de Lewy/patologia , Degeneração Neural/patologia , Neurônios/patologia , Transtornos Parkinsonianos/diagnóstico , Transtornos Parkinsonianos/fisiopatologia , Substância Negra/patologia , Idoso , Idoso de 80 Anos ou mais , Contagem de Células , Feminino , Humanos , Corpos de Lewy/metabolismo , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/patologia , Doença por Corpos de Lewy/fisiopatologia , Estudos Longitudinais , Masculino , Movimento/fisiologia , Degeneração Neural/metabolismo , Degeneração Neural/fisiopatologia , Exame Neurológico , Neurônios/metabolismo , Transtornos Parkinsonianos/patologia , Valor Preditivo dos Testes , Estudos Prospectivos , Estatística como Assunto , Substância Negra/fisiopatologiaRESUMO
STUDY DESIGN: Cross-sectional survey. OBJECTIVES: To estimate the extent of back pain in Parkinson's disease (PD). SUMMARY OF BACKGROUND DATA: PD is a common and disabling condition during the course of which back pain may develop. In contrast, the literature on the epidemiology of back pain in PD is poor. METHODS: Patients with PD, seen consecutively in a neurology clinic over a period of 4 months, were inquired about back pain through a self-questionnaire and compared to an age- and sex-matched control group of chronically ill patients. RESULTS: The study involved 104 parkinsonians (mean age: 67.3 years) who had had PD for an average of 11.6 years, and 100 controls (mean age: 65.8 years) who had chronic heart disease or diabetes for an average of 14.2 years. Sixty-two parkinsonians and 23 controls reported back pain. The prevalence was 59.6% in the parkinsonian group and 23.0% in the control group (P < 0.0001). Pain severity was evaluated with a visual analogic scale and averaged 54 +/- 23 mm in parkinsonians and 41 +/- 19 mm in control (P < 0.0001). CONCLUSIONS: Chronic back pain is quite common in PD. It is responsible for a substantial functional impact and needs more attention to reduce disability of such patients.
Assuntos
Dor nas Costas/etiologia , Doença de Parkinson/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Dor nas Costas/diagnóstico , Dor nas Costas/epidemiologia , Estudos de Casos e Controles , Estudos Transversais , Avaliação da Deficiência , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Índice de Gravidade de Doença , Inquéritos e Questionários , Fatores de TempoRESUMO
In the present study, we examined the potential symptomatic and/or disease-modifying effects of monthly bee venom injections compared to placebo in moderatly affected Parkinson disease patients. We conducted a prospective, randomized double-blind study in 40 Parkinson disease patients at Hoehn & Yahr stages 1.5 to 3 who were either assigned to monthly bee venom injections or equivalent volumes of saline (treatment/placebo group: n = 20/20). The primary objective of this study was to assess a potential symptomatic effect of s.c. bee venom injections (100 µg) compared to placebo 11 months after initiation of therapy on United Parkinson's Disease Rating Scale (UPDRS) III scores in the « off ¼ condition pre-and post-injection at a 60 minute interval. Secondary objectives included the evolution of UPDRS III scores over the study period and [123I]-FP-CIT scans to evaluate disease progression. Finally, safety was assessed by monitoring specific IgE against bee venom and skin tests when necessary. After an 11 month period of monthly administration, bee venom did not significantly decrease UPDRS III scores in the « off ¼ condition. Also, UPDRS III scores over the study course, and nuclear imaging, did not differ significantly between treatment groups. Four patients were excluded during the trial due to positive skin tests but no systemic allergic reaction was recorded. After an initial increase, specific IgE against bee venom decreased in all patients completing the trial. This study did not evidence any clear symptomatic or disease-modifying effects of monthly bee venom injections over an 11 month period compared to placebo using a standard bee venom allergy desensitization protocol in Parkinson disease patients. However, bee venom administration appeared safe in non-allergic subjects. Thus, we suggest that higher administration frequency and possibly higher individual doses of bee venom may reveal its potency in treating Parkinson disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT01341431.
Assuntos
Venenos de Abelha/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Venenos de Abelha/administração & dosagem , Venenos de Abelha/imunologia , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Feminino , Humanos , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Injeções , Cinética , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/metabolismo , Resultado do TratamentoRESUMO
[This corrects the article DOI: 10.1371/journal.pone.0158235.].
RESUMO
BACKGROUND: Mutations in the parkin gene, an E3 protein-ubiquitin ligase, cause autosomal recessive early-onset Parkinson disease (PD). The role of polymorphisms in the parkin gene as risk factors for PD is still unclear, as the results in the literature are contradictory. PATIENTS: We compared the allele and genotype frequencies of the Ser167Asn, Arg366Trp, Val380Leu, and Asp394Asn polymorphisms in 194 patients with PD (92 familial and 102 sporadic) and 125 control subjects. RESULTS: Homozygous Val380 was significantly associated with sporadic PD (P =.008). There was also a trend toward an association of homozygous Asp394 with familial PD (P =.07). CONCLUSIONS: Some parkin polymorphisms appear to be risk factors for sporadic or familial PD. The functional effects of these coding polymorphisms need to be established, and further studies on parkin polymorphisms in PD should be undertaken.
Assuntos
Ligases/genética , Doença de Parkinson/genética , Polimorfismo Genético/genética , Ubiquitina-Proteína Ligases , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologiaRESUMO
OBJECTIVE: To study the effects of general anesthesia on the postoperative outcome of patients with Parkinson disease (PD) who underwent surgery using bilateral placement of stimulating electrodes within the subthalamic nucleus (STN). DESIGN: Retrospective analysis. SETTING: Hôpital de la Salpêtrière, Paris, France. PATIENTS: Fifteen PD patients who underwent bilateral implantation of electrodes within the STN received general anesthesia because of severe anxiety, poorly tolerated off-period dystonia, or respiratory difficulties. These patients were compared with 15 patients matched for age, disease duration, and parkinsonian motor disability who underwent the same neurosurgical procedure under local anesthesia. MAIN OUTCOME MEASURE: Motor disability scores. RESULTS: After surgery, the severity of parkinsonian motor disability was markedly improved in both groups of patients. Compared with patients who were under local anesthesia during the operation, the residual parkinsonian motor score under stimulation (with ["on"] or without ["off"] levodopa) and the intensity of stimulation were higher in patients who were under general anesthesia during the operation. CONCLUSIONS: Although the improvement of parkinsonian motor disability is greater in PD patients who receive local anesthesia during surgery, general anesthesia can be performed in patients unable to tolerate prolonged states without levodopa.
Assuntos
Terapia por Estimulação Elétrica/métodos , Doença de Parkinson/terapia , Núcleo Subtalâmico/efeitos da radiação , Idoso , Antiparkinsonianos/uso terapêutico , Estudos de Casos e Controles , Avaliação da Deficiência , Relação Dose-Resposta à Radiação , Eletrodos Implantados , Feminino , Seguimentos , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Atividade Motora/fisiologia , Estudos Retrospectivos , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: High-frequency stimulation of the subthalamic nucleus (STN) is a neurosurgical alternative to medical treatment in levodopa-responsive forms of Parkinson disease. The mechanism of action of STN stimulation remains controversial, although an inhibition of overactive STN neurons has been postulated. OBJECTIVE: To determine the effects of high-frequency STN stimulation on the neuronal activity of STN neurons in Parkinson disease patients. PATIENTS: Single-unit recordings of the neuronal activity of the STN were obtained before, during, and after the application of intra-STN electrical stimulation in 15 Parkinson disease patients. Changes in firing frequency and pattern were analyzed using various combinations of stimulus frequency (range, 14-140 Hz). RESULTS: Stimulation at a frequency greater than 40 Hz applied within the STN significantly decreased the firing frequency and increased the burst-like activity in the firing pattern of STN neurons. An aftereffect was observed in cells that had been totally inhibited during high-frequency stimulation. CONCLUSION: The beneficial effects of high-frequency stimulation result from a change in the firing pattern of cellular discharge and a blockade of the spontaneous overactivity of STN neurons.
Assuntos
Terapia por Estimulação Elétrica , Neurônios/fisiologia , Doença de Parkinson/terapia , Idoso , Eletrofisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Núcleo Subtalâmico/fisiopatologiaRESUMO
BACKGROUND: High-frequency stimulation of the subthalamic nucleus (STN) is an effective treatment for advanced forms of Parkinson disease. Postoperative improvement of motor parkinsonian disability is known to depend on patient selection and surgical targeting. OBJECTIVE: To determine which clinical and electrophysiological variables evaluated during the operation predict the postoperative clinical outcome of patients with Parkinson disease treated by bilateral high-frequency stimulation of the STN. METHODS: Intraoperative clinical and electrophysiological data obtained in 41 patients with Parkinson disease who underwent bilateral implantation of electrodes for STN stimulation were correlated with the improvement in parkinsonian disability assessed 6 months after the operation. RESULTS: The extent of STN neuronal activity recorded along the trajectory of the therapeutic electrode had no effect on the postoperative clinical outcome. The intraoperative improvement in segmental akinesia, but not rigidity, was predictive of the postoperative improvement in parkinsonian motor disability and reduction in daily levodopa-equivalent dosage. Parkinsonian motor disability scores assessed after surgery were lower in patients with intraoperative stimulation-induced dyskinesias than in those without stimulation-induced dyskinesias. CONCLUSION: The improvement of segmental akinesia and the observation of dyskinesias provoked by stimulation during the operation predict the best postoperative effects of bilateral STN stimulation on parkinsonian motor disability.
Assuntos
Terapia por Estimulação Elétrica , Monitorização Intraoperatória , Doença de Parkinson/cirurgia , Doença de Parkinson/terapia , Núcleo Subtalâmico/cirurgia , Avaliação da Deficiência , Discinesias/diagnóstico , Discinesias/cirurgia , Discinesias/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Hallucinations occur in up to 40% of patients with Parkinson's disease (PD) and are mainly of a visual nature. We prospectively studied 8 patients with PD and tactile hallucinations (TH). TH occurred with a clear sensorium, and were long-lasting. In most cases they involved animals, were combined with other types of hallucinations occurring simultaneously (mainly formed visual hallucinations), and predominated in the evening and/or at night. Pharmacological and disease-related factors, including a disorder in rapid-eye-movement sleep mechanisms, could play a part in the pathophysiology of these hallucinations.
Assuntos
Alucinações/complicações , Doença de Parkinson/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Alucinações/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Estudos ProspectivosRESUMO
We have conducted a case-control study in order to test for an association between 8 intragenic polymorphisms of 5 iron-related genes (transferrin, transferrin receptor1, HFE, frataxin and lactoferrin) and Parkinson disease. Comparison of genotypes and allele frequencies did not differ significantly between cases and controls for all studied polymorphisms except the G258S transferrin polymorphism, for which a higher frequency of the G allele was found among cases (p=0.033), particularly among cases with onset older than 60 (p=0.0017) and with negative family history (p=0.022). This finding suggests that genetic variations in the control of iron metabolism may contribute to the pathogenesis of the disease.
Assuntos
Ferro/metabolismo , Doença de Parkinson/genética , Polimorfismo Genético , Transferrina/genética , Idade de Início , Idoso , Estudos de Casos e Controles , Primers do DNA , Genótipo , Humanos , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
BACKGROUND: In Parkinson's disease (PD), the response to L-dopa is highly variable and unpredictable. The major pathway for dopamine synthesis from L-dopa is decarboxylation by aromatic L-amino acid decarboxylase (AAAD, encoded by the DDC gene). OBJECTIVE: To determine the motor response to L-dopa in PD patients as a function of the DDC gene promoter polymorphisms (rs921451 T > C polymorphism (DDC(T/C)) and rs3837091 AGAG del (DDC(AGAG/-))). METHODS: Thirty-three Caucasian PD patients underwent an acute l-dopa challenge together with the peripheral AAAD inhibitor benserazide and were genotyped for rs921451 and rs3837091. The primary efficacy criterion was the motor response to L-dopa, as estimated by the area under the curve for the change in the Unified Parkinson's Disease Rating Scale part III (UPDRS) score relative to baseline (AUCΔUPDRS) in the 4 h following L-dopa administration. Secondary endpoints were pharmacokinetic parameters for plasma levels of L-dopa and dopamine. Investigators and patients were blinded to genotypes data throughout the study. RESULTS: When adjusted for the L-dopa dose, the AUCΔUPDRS was significantly lower in DDC(CC/CT) patients (n = 14) than in DDC(TT) patients (n = 19) and significantly lower in DDC(-/- or AGAG/-) patients (n = 8) than in DDC(AGAG/AGAG) patients (n = 25). There were no significant intergroup differences in plasma pharmacokinetic parameters for L-dopa and dopamine. DISCUSSION: The rs921451 and rs3837091 polymorphisms of the DDC gene promoter influence the motor response to L-dopa but do not significantly change peripheral pharmacokinetic parameters for L-dopa and dopamine. Our results suggest that DDC may be a genetic modifier of the l-dopa response in Parkinson's disease.