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1.
Rev Neurol (Paris) ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38760282

RESUMO

The term "Gilles de la Tourette syndrome", or the more commonly used term "Tourette syndrome" (TS) refers to the association of motor and phonic tics which evolve in a context of variable but frequent psychiatric comorbidity. The syndrome is characterized by the association of several motor tics and at least one phonic tic that have no identifiable cause, are present for at least one year and appear before the age of 18. The presence of coprolalia is not necessary to establish or rule out the diagnosis, as it is present in only 10% of cases. The diagnosis of TS is purely clinical and is based on the symptoms defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). No additional tests are required to confirm the diagnosis of TS. However, to exclude certain differential diagnoses, further tests may be necessary. Very frequently, one or more psychiatric comorbidities are also present, including attention deficit hyperactivity disorder, obsessive-compulsive disorder, anxiety, explosive outbursts, self-injurious behaviors, learning disorders or autism spectrum disorder. The condition begins in childhood around 6 or 7 years of age and progresses gradually, with periods of relative waxing and waning of tics. The majority of patients experience improvement by the end of the second decade of life, but symptoms may persist into adulthood in around one-third of patients. The cause of TS is unknown, but genetic susceptibility and certain environmental factors appear to play a role. The treatment of TS and severe forms of tics is often challenging and requires a multidisciplinary approach (involving the general practitioner (GP), pediatrician, psychiatrist, neurologist, school or occupational physicians, psychologist and social workers). In mild forms, education (of young patients, parents and siblings) and psychological management are usually recommended. Medical treatments, including antipsychotics, are essential in the moderate to severe forms of the disease (i.e. when there is a functional and/or psychosocial discomfort linked to tics). Over the past decade, cognitive-behavioral therapies have been validated for the treatment of tics. For certain isolated tics, botulinum toxin injections may also be useful. Psychiatric comorbidities, when present, often require a specific treatment. For very severe forms of TS, treatment by deep brain stimulation offers real therapeutic hope. If tics are suspected and social or functional impairment is significant, specialist advice should be sought, in accordance with the patient's age (psychiatrist/child psychiatrist; neurologist/pediatric neurologist). They will determine tic severity and the presence or absence of comorbidities. The GP will take over the management and prescription of treatment: encouraging treatment compliance, assessing side effects, and combating stigmatization among family and friends. They will also play an important role in rehabilitation therapies, as well as in ensuring that accommodations are made in the patient's schooling or professional environment.

2.
Rev Neurol (Paris) ; 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37833205

RESUMO

Chronic pain is a non-motor symptom affecting from 60 to 80% of patients with Parkinson's disease (PD). PD patients can suffer from different types of pain, either specific or not specific of the disease, and depending on various pathophysiological mechanisms (nociceptive, nociplastic or neuropathic), which can be present at any stage of the disease. Non-pharmacological interventions (NPIs) are essential to complement routine care interventions in PD pain management. Moreover, in the literature, it has been shown that 42% of PD patients are already using complementary therapies. Hence, our aim was to investigate the effectiveness and safety of NPIs for pain management in PD. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Eighteen published randomized control trials (RCTs) were included between 2004 and 2021 leading to a total of 976 PD patients. From them, we reported fifteen different NPIs classified in seven categories: physical exercises, balneotherapy, manual therapy, acupuncture, botanical preparation, body-psychological practice and multiprotection care. Our results have shown that NPIs for PD pain management had a low-to-moderate level of evidence showing mainly favourable results, even if some NPIs presented inconclusive results. Moreover, our review highlighted the clinical relevance of some specific NPIs in PD pain management: NPIs consisting of active physical activities, opposed to passive activities. The safety of NPIs was also confirmed since only few minor transient adverse events were reported. Nevertheless, even if some interesting results were found, the methodology of future studies needs to be more robust and to include comprehensive descriptions in order to offer reliable and sound recommendations to clinicians.

3.
Rev Neurol (Paris) ; 179(10): 1086-1094, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37633737

RESUMO

BACKGROUND: Among the workshops of our therapeutic patient education (TPE) program, the medication workshop (TPEM workshop) is very frequently proposed to patients in view of the difficulties they encounter related to the complexity of managing antiparkinsonian treatment. Patients' appropriation of their medications could depend on their social representations. OBJECTIVES: To evaluate the effect of our TPEM workshop on the social representations PD patients have of their medications and to compare it with that of another therapeutic intervention such as a talking group defined as the control group. METHODS: This single-center, prospective, randomized, parallel-group study investigated the social representations of medication through a questionnaire on knowledge about antiparkinsonian medications, a questionnaire on beliefs about medication (BMQ), and a word association task. RESULTS: In the TPEM group (n=16), the workshop induced significant effects over time on the knowledge questionnaire (P=0.01), BMQ specific necessity and concerns scores (P=0.04 and 0.01, respectively), necessity-concerns differential (P=0.04), and BMQ general harm (P=0.04). No significant difference was found in the talking group (n=6). Comparison of the two groups showed a significant difference of the BMQ general harm with a decrease in belief in the harmfulness of the medications in the workshop group (P=0.03). The results of the verbal association task showed a modification in the content and structure of the social representations of medication in the TPEM group. DISCUSSION: The TPEM workshop helped reduce initial negative aspects of medication representations. Improved knowledge of their medication allowed patients to feel more competent and legitimate in communicating with caregivers, modifying their beliefs about medications. Indeed, the medication was perceived as less restrictive, care becoming central as shown by the emergence of the medical team in the social representations of the medication. CONCLUSION: All the results show a specific beneficial effect of the TPEM workshop through an evolution of the social representations of medications, which became more positive in our PD patients.


Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Adesão à Medicação , Estudos Prospectivos , Pacientes , Inquéritos e Questionários , Antiparkinsonianos
4.
Rev Neurol (Paris) ; 178(4): 347-354, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34565624

RESUMO

INTRODUCTION: Non-motor fluctuations (NMF) in Parkinson's disease (PD) remain poorly recognized but have a high impact on patients' quality of life. The lack of assessment tools limits our understanding of NMF, compromising appropriate management. Our objective was to validate a hetero-questionnaire for NMF in PD patients at different stages of the disease: without treatment, without motor fluctuations, with motor fluctuations. METHODS: We included patients in 15 centers in France. Our questionnaire, NMF-Park, resulted from previous studies, allowing us to identify the more pertinent NMF for evaluation. Patients reported the presence (yes or no) of 22 selected NMF, and their link with dopaminergic medications. The assessment was repeated at one and two years to study the progression of NMF. We performed a metrological validation of our questionnaire. RESULTS: We included 255 patients (42 without treatment, 88 without motor fluctuations and 125 with motor fluctuations). After metrological validation, three dimensions of NMF were found: dysautonomic; cognitive; psychiatric. The sensory/pain dimension described in the literature was not statistically confirmed by our study. DISCUSSION: Our questionnaire was validated according to clinimetric standards, for different stages of PD. It was clinically coherent with three homogeneous dimensions. It highlighted a link between fatigue, visual accommodation disorder, and cognitive fluctuations; and the integration of sensory/pain fluctuations as part of dysautonomic fluctuations. It focused exclusively on NMF, which is interesting considering the described differences between non-motor and motor fluctuations. CONCLUSION: Our study validated a hetero-questionnaire of diagnosis for NMF for different stages of PD.


Assuntos
Doença de Parkinson , Disautonomias Primárias , Humanos , Dor , Doença de Parkinson/terapia , Qualidade de Vida , Inquéritos e Questionários
5.
Rev Neurol (Paris) ; 177(8): 919-923, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34154827

RESUMO

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) is an advanced therapy for patients with Parkinson Disease (PD). Weight loss has been pointed out as an adverse event of LCIG infusion. AIMS OF THE STUDY: To compare weight changes between three groups of PD patients: patients treated with LCIG, patients within the first year of subthalamic deep brain stimulation (STN-DBS) and patients treated exclusively with oral treatment during 1 year of follow up. METHODS: Patients treated with LCIG were retrospectively matched by age, gender, disease duration and Hoehn and Yahr to patients undergoing STN-DBS and to patients both receiving the standard of care treatment and unwilling advanced therapies (SOC). Clinical features and weight were collected at baseline, and 12 months after introducing the treatment (LCIG and STN-DBS groups) or for one year of treatment (SOC). RESULTS: Eighteen patients were included in each group. They had no differences in clinical and demographic features, except for cognitive impairment. There was a mean weight (-5.8kg ±6.8) and BMI (-2.1kg/m2±2.6) reduction in the LCIG group after 12 months, while there was a slight weight loss in the SOC (-1.4kg ±3.1) and a weight increase in the STN-DBS group (5.4kg ±4.7). Differences of weight were statistically different between, LCIG and STN-DBS (P<0.001), LCIG and SOC (P=0.002) and STN-DBS and SOC (P<0.001). CONCLUSIONS: The study shows a significant weight reduction after starting LCIG infusion compared to the other groups. Weight loss should be closely monitored in patients treated with LCIG.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Antiparkinsonianos , Índice de Massa Corporal , Carbidopa , Estudos de Casos e Controles , Combinação de Medicamentos , Géis , Humanos , Levodopa/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Estudos Retrospectivos , Padrão de Cuidado
6.
Rev Neurol (Paris) ; 177(4): 394-399, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33019996

RESUMO

Pain is an increasingly recognized non-motor symptom of Parkinson's disease (PD), with significant prevalence and strong impact on quality of life of patients. Moreover, pain can occur with various features in PD and several subtypes may coexist in a same patient, leading to a complex presentation and difficult diagnosis and treatment. In this paper we review the clinical manifestations of painful phenomena in PD, with focus on classifications and algorithms allowing to standardize the diagnosis of pain and PD. We also discuss the pathophysiological mechanisms underlying pain in PD, particularly parkinsonian central pain, in regard to recent clinical, neurophysiological and imaging studies.


Assuntos
Dor Crônica , Neuralgia , Doença de Parkinson , Dor Crônica/etiologia , Humanos , Doença de Parkinson/complicações , Qualidade de Vida
7.
Acta Neurol Scand ; 137(1): 59-66, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28832893

RESUMO

BACKGROUND: Subjective cognitive complaint (SCC) is a criterion recommended by the Movement Disorder Society (MDS) task force for the diagnosis of mild cognitive impairment (MCI). Until now there were few specific tools for detecting SCC in PD. We sought to develop a new tool to assess SCC specifically dedicated for PD. MATERIALS AND METHODS: We set a group of experts in movements disorders and neurocognition to develop an easy-to-use tool based on a visual analogue scale (VAS) for five cognitive domains: memory, executive functions, spatial orientation, attention, and language. We use it to assess SCC twice (at a one-month interval) in PD patients with disease duration of less than 5 years. Comprehensibility of the VAS was assessed. Controls were assessed with the same VAS. Patients with PD also underwent neuropsychological testing. RESULTS: VAS was easily understandable by the 70 patients with PD. We found significant SCC for the patients with PD vs controls in three cognitive domains: executive functions (1.7 ± 1.9 vs 0.8 ± 1.1; P < .001), language (2.3 ± 2.5 vs 1.0 ± 1.3, P < .001), and attention (2.1 ± 2.2 vs 1.2 ± 1.2; P < .01). Reproducibility between the two evaluations of patients with PD was good. There was no relationship between SCC and the results of neuropsychological testing. CONCLUSIONS: SCC seems to appear early in PD, in three cognitive domains (executive functions, language, and attention), and VAS might be a good way to detect SCC in PD, but need to be validated.


Assuntos
Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Doença de Parkinson/psicologia , Escala Visual Analógica , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Projetos Piloto , Reprodutibilidade dos Testes
8.
Parkinsonism Relat Disord ; 48: 28-33, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29254664

RESUMO

INTRODUCTION: Patients with Parkinson's disease or Multiple System Atrophy frequently experience painful sensations. The few studies investigating pain mechanisms in Multiple System Atrophy patients have reported contradictory results. In our study, we compared pain thresholds in Multiple System Atrophy and Parkinson's disease patients and healthy controls and evaluated the effect of l-DOPA on pain thresholds. METHODS: We assessed subjective and objective pain thresholds (using a thermotest and RIII reflex), and pain tolerance in OFF and ON conditions, clinical pain, motor and psychological evaluation. RESULTS: Pain was reported in 78.6% of Multiple System Atrophy patients and in 37.5% of Parkinson's disease patients. In the OFF condition, subjective and objective pain thresholds were significantly lower in Multiple System Atrophy patients than in healthy controls (43.8 °C ± 1.3 vs 45.7 °C ± 0.8; p = 0.0005 and 7.4 mA ± 3.8 vs 13.7 mA ± 2.8; p = 0.002, respectively). They were also significantly reduced in Multiple System Atrophy compared to Parkinson's disease patients. No significant difference was found in pain tolerance for the 3 groups and in the effect of l-DOPA on pain thresholds in Multiple System Atrophy and Parkinson's disease patients. In the ON condition, pain tolerance tended to be reduced in Multiple System Atrophy versus Parkinson's disease patients (p = 0.05). CONCLUSION: Multiple System Atrophy patients had an increase in pain perception compared to Parkinson's disease patients and healthy controls. The l-DOPA effect was similar for pain thresholds in Multiple System Atrophy and Parkinson's disease patients, but tended to worsen pain tolerance in Multiple System Atrophy.


Assuntos
Atrofia de Múltiplos Sistemas/complicações , Percepção da Dor/fisiologia , Limiar da Dor/fisiologia , Dor/etiologia , Idoso , Dopaminérgicos/uso terapêutico , Feminino , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/tratamento farmacológico , Atrofia de Múltiplos Sistemas/psicologia , Dor/psicologia , Medição da Dor , Doença de Parkinson/complicações , Estimulação Física , Escalas de Graduação Psiquiátrica , Testes Psicológicos
9.
Rev Neurol (Paris) ; 170(11): 680-4, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25287732

RESUMO

OBJECTIVES: The purpose of this work was to study the feasibility of an individual Parkinson disease (PD) rehabilitation program based on each patient's prevalent symptoms and to determine the effects of this program on patient's quality of life as well as the level of patient's and physiotherapist's satisfaction with the program. PATIENTS AND METHODS: In association with physiotherapists with expertise in PD, a physical medicine and rehabilitation physician, we elaborated a physical therapy program based on the core areas for physical therapy in PD: transfers; posture; balance and falls; physical capacity and inactivity. Within this program, we selected exercises tailored to each patient's main impairment and proposed this selection to their local physiotherapist for three months. Quality of life was evaluated with PDQ-39 at baseline and after three months of the individualized physical therapy program. We built an anonymous satisfaction questionnaire for patients and physiotherapists that was filled out at the end of the program. RESULTS: One hundred and three individuals with moderately advanced but clinically stable idiopathic PD were included. Significant improvement was found for the emotional well-being, bodily discomfort and stigma domain (P ≤ 0.05). No significant improvement was found for the other PDQ-39 domains. The mean global satisfaction figures for this program were 6.0 ± 2.4 and 7.2 ± 2.1 for patients and physiotherapists respectively. Most of the patients felt improved by the physiotherapy program and especially for transfer, balance, gait, and mobility. CONCLUSION: Our study found evidence of the potential benefits of a patient-tailored physiotherapy program. Such a program was feasible and had a favorable impact on patients' quality of life and on physiotherapists' practices for PD patients. Specific physiotherapy may be effective to limit physical mobility impairment. Our results also pointed out that physiotherapy may be efficient to confine the negative impact of social isolation, pain and emotional reactions. Such a program should be associated with a therapeutic education intervention such as encouraging patients to perform physical therapy exercises alone.


Assuntos
Transtornos Parkinsonianos/reabilitação , Fisioterapeutas , Modalidades de Fisioterapia , Acidentes por Quedas/prevenção & controle , Idoso , Atitude do Pessoal de Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Parkinsonianos/psicologia , Satisfação do Paciente , Equilíbrio Postural , Postura , Medicina de Precisão , Qualidade de Vida , Resultado do Tratamento
10.
Rev Neurol (Paris) ; 170(2): 128-33, 2014 Feb.
Artigo em Francês | MEDLINE | ID: mdl-24267951

RESUMO

We developed a therapeutic educational program in Parkinson's disease (PD). The needs analysis for this program was performed through a survey involving 41 PD patients. This survey questionnaire was elaborated through the analysis of 395 patients' semi-directive interviews, performed in our specialized hospitalisation unit during explanation workshops between 2005 and 2007. We managed to design an educational program tailored to specificities of PD and according to the recommendations of the High Authority of Health in France (HAS). This program was based on individual sessions conducted by a nurse experienced in PD and trained in education. Collective workshops concerning specific themes such as physical therapy, communication, social supports, sleep disorders, stress management, therapies in PD could be proposed to volunteer patients and were performed by the nurse, a physiotherapist and a specialized practitioner. This program focused on skills structured in knowledge, expertise, and learning. It was intended for patients without any motor or cognitive severe impairment. We educated 231 patients between 2008 and 2012 individually and 113 in collective workshops. Patients had an interesting improvement in their self-esteem (6.2±1.4 before and 7.3±1.1 after one year of this educational program). This program has been validated by our regional medical agency and we performed a medico-economic study demonstrating a significant improvement in quality-of-life of educated patients without extra costs.


Assuntos
Promoção da Saúde/métodos , Doença de Parkinson/terapia , Educação de Pacientes como Assunto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , França , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Pessoa de Meia-Idade , Modalidades de Fisioterapia , Qualidade de Vida , Inquéritos e Questionários
11.
N Engl J Med ; 368(7): 610-22, 2013 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-23406026

RESUMO

BACKGROUND: Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS: In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS: For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS: Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).


Assuntos
Terapia por Estimulação Elétrica , Doença de Parkinson/terapia , Qualidade de Vida , Atividades Cotidianas , Adulto , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/uso terapêutico , Terapia Combinada , Agonistas de Dopamina/efeitos adversos , Agonistas de Dopamina/uso terapêutico , Discinesias/etiologia , Terapia por Estimulação Elétrica/efeitos adversos , Feminino , Humanos , Neuroestimuladores Implantáveis/efeitos adversos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Núcleo Subtalâmico , Inquéritos e Questionários , Resultado do Tratamento
13.
Clin Neurophysiol ; 122(5): 1019-26, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-20943434

RESUMO

OBJECTIVE: To investigate the contribution of group II spinal pathways in Parkinsonian upper limb rigidity and the modulation of spinal excitability of group I and group II pathways by L-DOPA and subthalamic nucleus-high-frequency stimulation (STN-HFS). METHODS: The effect of ulnar nerve electrical stimulation on Flexor Carpi Radialis Electromyogram (FCR EMG) was investigated in two groups of patients: patients receiving medication (MED group) and chronically surgically implanted patients (DBS group). Results were compared in patients ON and OFF treatment, and between patients and control subjects. RESULTS: The resulting long-lasting facilitation in FCR EMG had similar characteristics in all groups, and surface area was assessed in analysis windows corresponding to the parts supposed to be mediated by non-monosynaptic spinal pathways to FCR motoneurones, fed by hand muscle group I and group II afferents (Lourenço et al., 2006). In both the MED and DBS groups, the group I excitation was not altered but the group II excitation was particularly enhanced when OFF treatment, compared to controls, and both L-DOPA and STN-HFS restored the group II spinal excitation to normal level. CONCLUSION: Both L-DOPA and STN-HFS influence the metabolism of monoamines in the midbrain, and restore the descending neuromodulation on group II spinal reflex. SIGNIFICANCE: These results further support a group II contribution to the enhanced long latency response (LLR) to muscle stretch observed in wrist muscles of rigid Parkinson's disease (PD) patients.


Assuntos
Antiparkinsonianos/uso terapêutico , Levodopa/uso terapêutico , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Reflexo/fisiologia , Adulto , Idoso , Análise de Variância , Antiparkinsonianos/farmacologia , Estimulação Encefálica Profunda , Eletromiografia , Feminino , Humanos , Levodopa/farmacologia , Masculino , Pessoa de Meia-Idade , Rigidez Muscular/terapia , Reflexo/efeitos dos fármacos
14.
Neurology ; 75(13): 1174-80, 2010 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-20876470

RESUMO

BACKGROUND: Multiple system atrophy (MSA) is an atypical parkinsonian syndrome including cerebellar impairment and poor response to levodopa. We assessed right hand motor activation in patients with MSA before and after an acute levodopa challenge in comparison with patients with PD and healthy volunteers (HVs). METHODS: Eighteen patients with MSA, 8 patients with PD, and 10 age-matched HVs were included. Regional cerebral blood flow measurements with H(2)(15)O PET were performed at rest and during a right hand movement. Statistical parametric mapping was used to analyze motor vs rest in OFF and ON conditions and the effect of levodopa on motor activation. RESULTS: Before levodopa, patients with MSA activated most known cerebral motor areas. Compared with HVs, patients with MSA exhibited less bilateral cerebellar activation and greater left superior parietal activation. They also had less bilateral cerebellar and greater supplementary motor and left superior parietal activation than patients with PD. Conversely, patients with PD had greater activation than HVs in the right cerebellum and less in the supplementary motor cortex. After levodopa, patients with MSA exhibited reduced activation in anterior cingulate, whereas patients with PD had greater activation in the right cerebellum. CONCLUSION: Patients with MSA and patients with PD recruited different motor networks. Patients with PD preferentially activated cerebellar pathways, possibly to compensate for basal ganglia dysfunction. This was not observed in patients with MSA, probably because of cerebellar dysfunction; other frontoparietal cortical areas were recruited.


Assuntos
Movimento/fisiologia , Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Atrofia de Múltiplos Sistemas/fisiopatologia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Idoso , Mapeamento Encefálico , Estudos de Casos e Controles , Óxido de Deutério , Dopaminérgicos/uso terapêutico , Lateralidade Funcional/efeitos dos fármacos , Lateralidade Funcional/fisiologia , Mãos/fisiopatologia , Humanos , Levodopa/uso terapêutico , Córtex Motor/diagnóstico por imagem , Movimento/efeitos dos fármacos , Atrofia de Múltiplos Sistemas/tratamento farmacológico , Atrofia de Múltiplos Sistemas/patologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Tomografia por Emissão de Pósitrons , Estatísticas não Paramétricas
16.
J Med Genet ; 46(7): 458-64, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19357115

RESUMO

BACKGROUND: Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified in families with autosomal dominant Parkinson's disease (ADPD), the most common of which is the p.G2019S substitution that has been found at varying frequencies worldwide. Because of the size of the LRRK2 gene, few studies have analysed the entire gene in large series of ADPD families. METHODS: We performed extensive mutation analyses of all 51 coding exons of the LRRK2 gene in index cases from 226 Parkinson's disease families compatible with autosomal dominant inheritance, mostly from France (n = 182) and North Africa (n = 14). RESULTS: We found 79 sequence variants, 29 of which were novel. Eight potentially or proven pathogenic mutations were found in 22 probands (9.7%). There were four novel amino acid substitutions that are potentially pathogenic (p.S52F, p.N363S, p.I810V, p.R1325Q) and two novel variants, p.H1216R and p.T1410M, that are probably not causative. The common p.G2019S mutation was identified in 13 probands (5.8%) including six from North Africa (43%). The known heterozygous p.R1441H and p.I1371V mutations were found in two probands each, and the p.E334K variant was identified in one single patient. Most potentially or proven pathogenic mutations were located in the functional domains of the Lrrk2 protein. CONCLUSION: This study leads us to conclude that LRRK2 mutations are a common cause of autosomal dominant Parkinson's disease in Europe and North Africa.


Assuntos
Transtornos Parkinsonianos/genética , Proteínas Serina-Treonina Quinases/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , População Negra/genética , Distribuição de Qui-Quadrado , Análise Mutacional de DNA/métodos , Feminino , Frequência do Gene , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Mutação , Transtornos Parkinsonianos/diagnóstico , Linhagem , População Branca/genética
17.
J Neurol Neurosurg Psychiatry ; 78(10): 1140-2, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17504881

RESUMO

BACKGROUND: Patients suffering from Parkinson's disease (PD) describe painful sensations that could be related to neuropathic pain. Experimental data have indicated the involvement of basal ganglia and dopaminergic pathways in central nociceptive processing. AIM: The objective of this study was to assess and compare the effect of levodopa on the objective pain threshold in patients with PD and healthy subjects. METHODS: The objective pain threshold was assessed by the nociceptive flexion reflex (RIII) in 13 PD patients and 10 healthy subjects. Patients and healthy subjects were evaluated under two randomised conditions: with levodopa (ON) and without (OFF). RESULTS: Levodopa significantly increased the RIII threshold of PD patients (6.9 (1.2) mA in the OFF condition vs 8 (1.1) mA in the ON position; p = 0.02). RIII threshold was significantly lower in PD patients than in healthy subjects in the OFF condition (6.9 (1.2) mA vs 9.7 (3.4) mA; p = 0.02). RIII threshold did not change after levodopa administration in healthy subjects. CONCLUSION: These results provide evidence of a dopaminergic modulation of objective pain threshold in PD patients. In addition, the decrease in RIII threshold in PD patients, in the OFF condition, compared with controls, confirms the existence of an objective pain perception disturbance in PD.


Assuntos
Levodopa/uso terapêutico , Limiar da Dor/efeitos dos fármacos , Dor/tratamento farmacológico , Dor/etiologia , Doença de Parkinson/complicações , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/fisiopatologia
18.
Rev Neurol (Paris) ; 163(1): 66-71, 2007 Jan.
Artigo em Francês | MEDLINE | ID: mdl-17304174

RESUMO

OBJECTIVE: To assess levodopa dose effect on pain thresholds in Parkinson's disease (PD) patients using an experimental nociceptive thermal stimulation. PATIENTS AND METHODS: We evaluated pain thresholds in 20 PD patients treated by dopaminergic drugs. We assessed heat and cold pain thresholds by using 2 different methods (method of limits and method of levels), intensity-response curve and tolerance threshold. Each PD patient was evaluated in two conditions: ON (after administration of leovdopa and OFF (after acute levodopa withdrawal). The order was randomized. RESULTS: The mean age of patients was 652+/-9.9 years and the mean duration was 9.3+/-3.3 years. Heat pain thresholds were statistically higher in ON versus OFF condition using both methods (44.1+/-3,6 degrees C versus 42.3+/-3,1 degrees C, method of levels, p=0.02). Cold pain thresholds were statistically higher in ON versus OFF condition only using method of levels (17.9+/-4,4 degrees C versus 19.6+/-4,2 degrees C, p=0.02). Heat pain tolerance was statistically higher in ON versus OFF condition (21.4+/-21.6 seconds versus 14.7+/-20.3 seconds, p=0.02). CONCLUSION: This study showed that levodopa increased heat and cold pain thresholds and heat pain tolrance in PD patients. This suggests that dopaminergic drugs could have an analgesic effects on PD related pain.


Assuntos
Antiparkinsonianos/farmacologia , Levodopa/farmacologia , Limiar da Dor/efeitos dos fármacos , Doença de Parkinson/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Eur J Neurol ; 13(3): 209-14, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16618334

RESUMO

Recent case reports of 'sleep attacks' (SA) in patients with Parkinson's disease (PD) generated concerns about drug-induced daytime somnolence in this population. However, there are nearly no comparative data on sleep and vigilance problems between PD patients and normal controls. We performed a cross-sectional survey in PD patients and age-matched controls using a structured questionnaire on PD history, treatments, co-morbidity, activities of daily living, habits, exercise, sleep pattern, driving, pre-existing nocturnal problems, daytime somnolence, episodes of SA and the circumstances in which such episodes occurred. Daytime somnolence was also measured with the Epworth Sleepiness Scale (ESS) and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). 176 PD patients and 174 controls were included. The same proportion of PD patients (27%) and controls (32%) reported episodes of SA, but these were more frequent in PD patients and occurred more frequently during situations requiring attention (10.8% vs. 1.7%, p<10(-3)). More PD patients had abnormal daytime somnolence (ESS) and poor sleeping quality (PSQI). The most consistent factor associated with SA was the duration of levodopa therapy and the predictive value of an abnormal ESS score was rather poor (40.7%). Abnormal daytime somnolence and poor sleep quality at night are more frequent in PD patients than in normals. However, SA are reported in both groups, although less frequently in the normals during activities that requires attention.


Assuntos
Antiparkinsonianos/efeitos adversos , Distúrbios do Sono por Sonolência Excessiva/induzido quimicamente , Doença de Parkinson/complicações , Transtornos do Sono-Vigília/complicações , Atividades Cotidianas , Idoso , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Estudos Transversais , Exercício Físico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/epidemiologia , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Transtornos do Sono do Ritmo Circadiano , Transtornos do Sono-Vigília/epidemiologia , Inquéritos e Questionários
20.
Neurophysiol Clin ; 36(5-6): 333-6, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17336778

RESUMO

Various drugs have been reported to induce myoclonus. However, this adverse event is not well known because of the difficult diagnosis and the lack of pharmaco-epidemiological or controlled studies. As far as we know, there are only case reports. In the literature, antiparkinsonian medications, antipsychotics, antidepressants, anesthetics, opiates and anti-infectious drugs have been reported in the occurrence of myoclonus. In a French pharmacovigilance database study, only 423 reports (0.2%) involved drug-induced myoclonus. The median age of patients was 55 years and 10% of these patients had a concomitant neurological disease. Only 16% of these reports had a strong imputability score (likely). The most frequently involved drugs were anti-infectious (15%), antidepressants (15%), anxiolytics (14%), and opiates agents (12%). Fifty-six percent of these reports were classified as serious adverse event. Concerning outcome, most patients (84%) recovered without sequels.


Assuntos
Mioclonia/induzido quimicamente , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Idoso , Causalidade , Comorbidade , Bases de Dados Factuais , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mioclonia/epidemiologia , Mioclonia/etiologia , Doenças do Sistema Nervoso/complicações , Preparações Farmacêuticas/classificação
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