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INTRODUCTION: A large percentage of patients with Parkinson's disease (PD) develop motor fluctuations, dyskinesias, and severe non-motor symptoms within 3 to 5 years of starting dopaminergic therapy, and these motor complications are refractory to treatment. Several authors refer to this stage of the disease as advanced Parkinson's disease. OBJECTIVE: To define the clinical manifestations of advanced PD and the risk factors for reaching this stage of the disease. DEVELOPMENT: This consensus document has been prepared by using an exhaustive literature search and by discussion of the contents by an expert group on movement disorders of the Sociedad Española de Neurología (Spanish Neurology Society), coordinated by two of the authors (JK and MRL). CONCLUSIONS: Severe motor fluctuations and dyskinesias, axial motor symptoms resistant to levodopa, and cognitive decline are the main signs in the clinical phenotype of advanced PD.
Assuntos
Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Adulto , Fatores Etários , Idoso , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/uso terapêutico , Biomarcadores , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/psicologia , Consenso , Demência/etiologia , Progressão da Doença , Discinesias/etiologia , Feminino , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/psicologia , Fenótipo , Qualidade de Vida , Fatores de Risco , Caracteres SexuaisRESUMO
INTRODUCTION: Many patients who have had Parkinson's disease (PD) for several years will present severe motor fluctuations and dyskinesias which require more aggressive therapies. The different approaches which are now available include deep brain stimulation of the subthalamic nucleus or medial globus pallidus, subcutaneous infusion of apomorphine, and intestinal infusion of levodopa-carbidopa. OBJECTIVE: To define the indications and results for the 3 available therapies for advanced PD. DEVELOPMENT: Exhaustive review of the literature concerning the indications and results of deep brain stimulation, subcutaneous apomorphine infusion and duodenal infusion of levodopa/carbidopa gel to treat patients with advanced Parkinson disease. CONCLUSIONS: Although numerous studies have confirmed the efficacy of the 3 different therapies in advanced PD, there are no comparative studies that would allow us to define the best candidate for each technique.
Assuntos
Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/uso terapêutico , Apomorfina/administração & dosagem , Apomorfina/efeitos adversos , Apomorfina/uso terapêutico , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/terapia , Estimulação Encefálica Profunda , Progressão da Doença , Humanos , Infusões Intravenosas , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/psicologia , Transtornos Psicóticos/etiologia , Transtornos Psicóticos/terapiaRESUMO
BACKGROUND: Different types of therapies were proven effective for the medical management of motor and non-motor symptoms in Parkinson's disease (PD). We aimed to gain consensus on the dopamine agonist (DA) therapy use in different clinical scenarios of Parkinson's disease (PD) patients. METHODS: This consensus study was based on the nominal group technique. Initially, a consensus group comprising 12 expert neurologists in the PD field identified the topics to be addressed and elaborated different evidence-based preliminary statements. Next, a panel of 48 Spanish neurologists expressed their opinion on an internet-based systematic voting program. Finally, initial ideas were reviewed and rewritten according to panel contribution and were ranked by the consensus group using a Likert-type scale. The analysis of data was carried out by using a combination of both qualitative and quantitative methods. The consensus was achieved if the statement reached ≥ 3.5 points in the voting process. RESULTS: The consensus group produced 76 real-world recommendations. The topics addressed included 12 statements related to DA therapy in early PD, 20 statements concerning DA treatment strategy in patients with motor complications, 11 statements associated with DA drugs and their side effects, and 33 statements regarding DA therapy in specific clinical scenarios. The consensus group did not reach a consensus on 15 statements. CONCLUSION: The findings from this consensus method represent an exploratory step to help clinicians and patients in the appropriate use of DA in different stages and clinical situations of PD.
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Safinamide is a new add-on drug to levodopa for the treatment of Parkinson's disease (PD) with motor fluctuations. Due to the recent incorporation of safinamide into routine clinical practice, no post-authorisation phase IV studies on the safety of safinamide have been conducted to date. This study provides clinical management guidelines for safinamide based on the opinion of a group of experts in movement disorders. This project was developed in 2 phases: 16 local meetings in phase 1 and a national meeting in phase 2. The meetings followed a pre-established agenda. The present clinical practice guidelines are based on the main conclusions reached during the national meeting. The group concluded that safinamide is effective in reducing motor and non-motor fluctuations. PD patients with mild-to-moderate fluctuations benefit most from treatment, although the drug may also improve the clinical status of patients with advanced PD. The dose of other dopaminergic drugs may be reduced after introducing safinamide, which would contribute to reducing such adverse reactions as impulse control disorder. At doses higher than those usually prescribed, safinamide may also improve dyskinesia. The experts agreed that safinamide is well tolerated and causes few adverse reactions when compared with placebo.
Assuntos
Antiparkinsonianos/uso terapêutico , Benzilaminas/uso terapêutico , Doença de Parkinson , Alanina/análogos & derivados , Antiparkinsonianos/efeitos adversos , Benzilaminas/efeitos adversos , Consenso , Humanos , Doença de Parkinson/tratamento farmacológico , EspanhaRESUMO
BACKGROUND AND PURPOSE: The question whether patients with essential tremor (ET) have slowed movements as part of their clinical manifestations is still a matter of controversy. We analyzed basic motor function in patients with ET and in healthy matched controls. METHODS: We studied 61 patients with ET and 122 age- and sex-matched controls. Evaluation included four timed tests (pronation-supination, finger tapping and movement between two points, all with both hands, and walking test); and three tests performed on a personal computer (speed for pressing repetitively a key - frequency, visual reaction time and movement time, all with both hands). RESULTS: Essential tremor patients showed higher mean values for right and left finger tapping, left movement between two points; and with right and left frequency and reaction time. In the logistic regression study, ET patients showed significantly higher values than controls for right and left finger tapping; mean, SD, maximum and rank values of right and left frequency; and mean, SD, minimum, maximum and rank values of right and left visual reaction time. Tremor severity was not correlated with the altered values. CONCLUSIONS: Patients with ET showed impaired motor performance, at least in some tasks, such as rapid repetitive finger movements (finger tapping and frequency) and visual reaction time (impairment was not related with tremor severity). This probably means that patients with ET have some degree of bradykinesia.
Assuntos
Tremor Essencial/diagnóstico , Tremor Essencial/fisiopatologia , Dedos/fisiologia , Destreza Motora/fisiologia , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/fisiopatologia , Idoso , Sistema Nervoso Central/fisiopatologia , Avaliação da Deficiência , Vias Eferentes/fisiopatologia , Tremor Essencial/complicações , Feminino , Dedos/inervação , Humanos , Hipocinesia/diagnóstico , Hipocinesia/etiologia , Hipocinesia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/etiologia , Músculo Esquelético/inervação , Músculo Esquelético/fisiopatologia , Exame Neurológico , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Análise e Desempenho de Tarefas , Fatores de Tempo , Percepção Visual/fisiologiaRESUMO
Independent deletion of the PARK2 gene and hTauVLW over-expression in mice produce mild alterations in the brain. However, the presence of both mutations in a parkin-deficient and hTauVLW double mutant mouse causes a tau neuropathology, reactive astrocytosis, and neuronal loss in the cortex and hippocampus, as well as lesions in nigrostriatal and motor neurons. Moreover, these mutants display some memory and exploratory defects that reflect a functional link between parkin and tau proteins. We have tested the motor activity and coordination of these double mutant mice to determine the effects of parkin deletion in mice over-expressing the hTauVLW transgene. While the loss of parkin alone produces increased exploration and alterations in gait and motor coordination, in hTauVLW transgenic mice the absence of parkin causes less prominent motor impairments. These effects suggest the existence of some compensatory mechanisms that are activated when the hTauVLW transgene is over-expressed in the absence of parkin. This mouse model will hopefully help to study the causes of the motor deficits associated with certain neuropathologies related to the tau and parkin proteins, and to find appropriate treatments.
Assuntos
Mutação , Sequências Repetitivas de Ácido Nucleico/genética , Ubiquitina-Proteína Ligases/deficiência , Proteínas tau/genética , Análise de Variância , Animais , Comportamento Animal , Comportamento Exploratório/fisiologia , Regulação da Expressão Gênica , Humanos , Camundongos , Camundongos Transgênicos , Atividade Motora/genética , Desempenho Psicomotor/fisiologia , Tempo de Reação/genética , Fatores de TempoRESUMO
INTRODUCTION: Reduced facial expression or amimia is one of the most typical characteristics of Parkinson's disease (PD). Despite being described in classic texts, its significance, physiopathology and correlation with motor and non-motor symptoms is largely unknown. PATIENTS AND METHODS: We have studied facial bradykinesia in a group of 84 de novo PD patients prospectively evaluated for five years. We also studied the relationship of facial bradykinesia with depression in a subgroup of 30 patients. RESULTS: Baseline and follow-up assessments were performed with the Unified Parkinson's Disease Rating Scale (UPDRS). Baseline facial bradykinesia was rated according to item 19 of UPDRS. Baseline facial bradykinesia correlated with total and motor baseline UPDRS. In addition, baseline bradykinesia correlated with total and motor UPDRS at five years. However baseline bradykinesia did not influence the presence of motor (motor fluctuation, dyskinesias and freezing of gait) or non-motor complications (delusion, behavior abnormalities and dementia) at five years. Finally a subgroup of 30 patients completed the self-report version of the Quick Inventory of Depressive Symptoms (QIDS-SR16) questionnaire, facial bradykinesia did not correlate with QIDS-SR16 scores. CONCLUSION: Our study suggests that baseline facial bradykinesia correlates with general baseline situation in PD and even might predict the motor and functional status at five years.
TITLE: Amimia en la enfermedad de Parkinson. Significado y correlacion con la clinica.Introduccion. La amimia o reduccion de la expresion facial es una de las caracteristicas mas tipicas de la enfermedad de Parkinson (EP), y se puede definir como bradicinesia facial. A pesar de ser un elemento clasico, la amimia no se conoce bien, no se sabe con precision su fisiopatologia, su significado patologico ni su correlacion con otros sintomas motores o no motores, incluyendo la depresion. Pacientes y metodos. Se ha analizado la amimia en un grupo de 84 pacientes con EP evaluados de forma prospectiva desde su diagnostico hasta el quinto año de evolucion, y tambien la correlacion entre la amimia basal y la depresion en un subgrupo de 30 pacientes con EP. Resultados. La valoracion basal (antes del tratamiento) y las evaluaciones de seguimiento se realizaron mediante la Unified Parkinson's Disease Rating Scale (UPDRS). La amimia se evaluo mediante el item 19 de la UPDRS. La amimia basal se correlaciono con la UPDRS basal total y motora. Ademas, la amimia basal se correlaciono con la UPDRS total y motora a los cinco años de evolucion. Sin embargo, la amimia basal no se relaciono con la presencia de complicaciones motoras (fluctuaciones motoras, discinesias o bloqueos) o no motoras. La correlacion entre amimia y depresion se analizo mediante el Quick Inventory of Depressive Symptoms (QIDS-SR16). La amimia no se correlaciono con las puntuaciones del QIDS-SR16. Conclusion. Este estudio sugiere que la amimia basal se correlaciona con la situacion basal general (UPDRS) e incluso con la valoracion clinica a los cinco años, aunque no predice la tasa de complicaciones a medio plazo.
Assuntos
Expressão Facial , Hipocinesia/etiologia , Doença de Parkinson/complicações , Humanos , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Doença de Parkinson/fisiopatologia , Estudos ProspectivosRESUMO
INTRODUCTION: Botulinum toxin type A (BTA) is a bacterial endotoxin, whose therapeutic use has had a dramatic impact on different neurological disorders, such as dystonia and spasticity. AIM: To analyze and summarize different questions about the use of BTA in our clinical practice. DEVELOPMENT: A group of experts in neurology developed a list of topics related with the use of BTA. Two groups were considered: neuropharmacology and dystonia. A literature search at PubMed, mainly for English language articles published up to June 2016 was performed. The manuscript was structured as a questionnaire that includes those questions that, according to the panel opinion, could generate more controversy or doubt. The initial draft was reviewed by the expert panel members to allow modifications, and after subsequent revisions for achieving the highest degree of consensus, the final text was then validated. Different questions about diverse aspects of neuropharmacology, such as mechanism of action, bioequivalence of the different preparations, immunogenicity, etc. were included. Regarding dystonia, the document included questions about methods of evaluation, cervical dystonia, blepharospasm, etc. CONCLUSION: This review does not pretend to be a guide, but rather a tool for continuous training of residents and specialists in neurology, about different specific areas of the management of BTA.
TITLE: Mitos y evidencias en el empleo de la toxina botulinica: neurofarmacologia y distonias.Introduccion. La toxina botulinica de tipo A (TBA) ha supuesto una verdadera revolucion terapeutica en neurologia, y en la actualidad es el tratamiento rutinario en las distonias focales y la espasticidad. Objetivo. Plantear, revisar y responder cuestiones controvertidas en relacion con la neurofarmacologia de la TBA y su uso en las distonias en la practica clinica habitual. Desarrollo. Un grupo de expertos en trastornos del movimiento reviso una lista de temas controvertidos relacionados con la farmacologia de la TBA y su uso en las distonias. Revisamos la bibliografia e incluimos articulos relevantes especialmente en ingles, pero tambien, si su importancia lo merece, en castellano y en frances, hasta junio de 2016. El documento se estructuro como un cuestionario que incluyo las preguntas que podrian generar mayor controversia o duda. El borrador inicial del documento fue revisado por los miembros del panel y se realizaron las modificaciones necesarias hasta alcanzar el mayor grado de consenso. Incluimos preguntas sobre diferentes aspectos de la neurofarmacologia, especialmente el mecanismo de accion, la bioequivalencia de los diferentes preparados y la inmunogenicidad. En relacion con el subapartado de las distonias, se incluyeron aspectos sobre la evaluacion y el tratamiento de las distonias focales. Conclusiones. Esta revision no pretende ser una guia, sino una herramienta practica destinada a neurologos y medicos internos residentes interesados en esta area, dentro de diferentes ambitos especificos del manejo de la TBA.
Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Distúrbios Distônicos/tratamento farmacológico , Antitoxina Botulínica/biossíntese , Toxinas Botulínicas Tipo A/efeitos adversos , Toxinas Botulínicas Tipo A/imunologia , Toxinas Botulínicas Tipo A/farmacologia , Gerenciamento Clínico , Relação Dose-Resposta a Droga , Esquema de Medicação , Resistência a Medicamentos , Estabilidade de Medicamentos , Distúrbios Distônicos/diagnóstico por imagem , Humanos , Espasticidade Muscular/tratamento farmacológico , Guias de Prática Clínica como Assunto , Índice de Gravidade de Doença , Inquéritos e Questionários , Equivalência TerapêuticaRESUMO
Safinamide is a new add-on drug to levodopa for the treatment of Parkinson's disease (PD) with motor fluctuations. Due to the recent incorporation of safinamide into routine clinical practice, no post-authorisation phase IV studies on the safety of safinamide have been conducted to date. This study provides clinical management guidelines for safinamide based on the opinion of a group of experts in movement disorders. This project was developed in 2 phases: 16 local meetings in phase 1 and a national meeting in phase 2. The meetings followed a pre-established agenda. The present clinical practice guidelines are based on the main conclusions reached during the national meeting. The group concluded that safinamide is effective in reducing motor and non-motor fluctuations. PD patients with mild-to-moderate fluctuations benefit most from treatment, although the drug may also improve the clinical status of patients with advanced PD. The dose of other dopaminergic drugs may be reduced after introducing safinamide, which would contribute to reducing such adverse reactions as impulse control disorder. At doses higher than those usually prescribed, safinamide may also improve dyskinesia. The experts agreed that safinamide is well tolerated and causes few adverse reactions when compared with placebo.
RESUMO
AIMS AND DEVELOPMENT: Spasticity is an important medical problem with a high rate of incidence both in childhood, mainly as a result of cerebral palsy, and in adults, which is frequently brought about by traumatic brain injuries, strokes and spinal cord injuries. Spasticity is part of upper motoneuron syndrome, which gives rise to important problems, such as limited joint movement, abnormal postures that can produce pain, impaired functional capacity, aesthetic or hygiene disorders, among others. It progresses naturally towards chronicity, accompanied by static phenomena due to alterations affecting the properties of soft tissues (elasticity, plasticity and viscosity). Numerous therapeutic options are available for the treatment of spasticity, including medication, physiotherapy, orthopaedic aid, surgery, and so forth. Moreover, treatment should be individualised and realistic, with goals that have been agreed between the patient or caregiver and the medical team. The aim of the following guide is to further our knowledge of this condition, its causes, epidemiology and progression, as well as to outline an approach that is both rational and global from the point of view of pharmacological, rehabilitation and surgical treatment. CONCLUSIONS: Spasticity is a complex problem that requires specialists (neurologist, rehabilitation doctor, occupational therapist, orthopaedic surgeon, general practitioner, etc.) to work as a team in order to achieve the goals set out when treatment is begun. Early treatment is important to avoid or reduce, as far as possible, the severe complications stemming from this condition.
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Espasticidade Muscular/terapia , Baclofeno/uso terapêutico , Paralisia Cerebral/fisiopatologia , Paralisia Cerebral/terapia , Progressão da Doença , Humanos , Relaxantes Musculares Centrais/uso terapêutico , Espasticidade Muscular/epidemiologia , Espasticidade Muscular/etiologia , Espasticidade Muscular/fisiopatologia , Fármacos Neuromusculares/uso terapêutico , Modalidades de FisioterapiaRESUMO
AIMS: The introduction of botulinum toxin has been a significant step forward in the treatment of spasticity in children and is now considered to be the preferred treatment in focal spasticity. With the aim of optimising this therapeutic resource, a group of Spanish neurologists and specialists in rehabilitation have drawn up these therapeutic guidelines based on the currently available evidence on its use and indications, and on their own experience. DEVELOPMENT: Spasticity in childhood is mainly caused by infantile cerebral palsy. Its natural history is not favourable due to the negative effect of growth and it should be treated before permanent deformities in bones and joints appear. Treatment with botulinum toxin diminishes hyperactivity and muscle tone, and allows the muscle to grow longitudinally, which prevents permanent contractions. The advantages of botulinum toxin are obvious (ease of use and dosing, long-lasting effects, reversibility in case of adverse responses, and so forth) and outnumber by far the few drawbacks it offers. Before it can be used patients, treatment goals and the muscle areas to be treated must all be selected correctly and, at the same time, a tailored rehabilitation scheme must also be developed. The growing body of experience suggests that its early administration is effective in preventing or reducing the severe complications of spasticity. CONCLUSIONS: Botulinum toxin type A is very effective in the treatment of spasticity. These guidelines offer the well-documented experience gained from its use and our knowledge about its indications, effects and safety in clinical practice.
Assuntos
Antidiscinéticos/uso terapêutico , Toxinas Botulínicas Tipo A/uso terapêutico , Espasticidade Muscular/tratamento farmacológico , Antidiscinéticos/administração & dosagem , Toxinas Botulínicas Tipo A/administração & dosagem , Criança , Humanos , Resultado do TratamentoRESUMO
INTRODUCTION: Spasticity is a medical problem with a high incidence that significantly impact on the quality of life of patients and their families. AIM: To analyze and to answer different questions about the use of botulinum toxin type A (BTA) in our clinical practice. DEVELOPMENT: A group of experts in neurology develop a list of topics related with the use of BTA. Two big groups were considered: spasticity in adults and in children with cerebral palsy. A literature search at PubMed for English, French, and Spanish language articles published up to June 2016 was performed. The manuscript was structured as a questionnaire that includes those questions that, according to the panel opinion, could generate more controversy or doubt. The initial draft was reviewed by the expert panel members to allow for modifications, and after subsequent revisions for achieving the highest degree of consensus, the final text was then validated. Different questions about diverse aspects of spasticity in adults, such as methods for evaluating spasticity, infiltration techniques, doses, number of infiltration points, etc. Regarding spasticity in children with cerebral palsy, the document included questions about minimum age of infiltration, methods of analgesia, etc. CONCLUSIONS: This review is a tool for continuous training for neurologist and rehabilitation specialist and residents of both specialties, about different specific areas of the management of BTA.
TITLE: Mitos y evidencias en el empleo de la toxina botulinica: espasticidad del adulto y del nintilde;o con paralisis cerebral.Introduccion. La espasticidad es un problema medico frecuente que impacta de forma significativa en la calidad de vida de los pacientes y sus familias. Objetivo. Analizar y dar respuesta a diferentes cuestiones en el uso de la toxina botulinica tipo A (TBA) en nuestra practica clinica habitual. Desarrollo. Un grupo de expertos en neurologia elaboro una lista de temas relacionados con el uso de la TBA. Se consideraron dos grandes bloques: espasticidad del adulto y del nintilde;o con paralisis cerebral. Se realizo una revision de la bibliografia que incluyo los diferentes articulos publicados en espantilde;ol, ingles y frances hasta junio de 2016. El documento se estructuro como un cuestionario que incluyo las preguntas que, segun el criterio del panel, podrian generar mayor controversia o duda. El borrador inicial del documento fue revisado por los miembros del panel y se realizaron las modificaciones necesarias hasta alcanzar el mayor grado de consenso. A continuacion, el texto final fue validado. Se incluyeron diferentes preguntas sobre diferentes aspectos de la espasticidad en adultos: evaluacion de la espasticidad, tecnicas de infiltracion, dosis, numero de puntos, etc. En cuanto a la espasticidad en los nintilde;os con paralisis cerebral, se analizaron preguntas como: edad minima de infiltracion, metodos de sedoanalgesia, etc. Conclusiones. Esta revision constituye una herramienta para neurologos, medicos rehabilitadores y residentes de ambas especialidades, dentro de diferentes ambitos especificos del manejo de la TBA.
Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Paralisia Cerebral/tratamento farmacológico , Fármacos Neuromusculares/uso terapêutico , Adolescente , Adulto , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/efeitos adversos , Paralisia Cerebral/reabilitação , Paralisia Cerebral/terapia , Criança , Pré-Escolar , Terapia Combinada , Consenso , Gerenciamento Clínico , Feminino , Objetivos , Humanos , Lactente , Masculino , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/terapia , Fármacos Neuromusculares/administração & dosagem , Fármacos Neuromusculares/efeitos adversos , Modalidades de Fisioterapia , Inquéritos e Questionários , Avaliação de Sintomas , Adulto JovemRESUMO
Huntington disease (HD) is characterized by several hyperkinesias though motor slowness is also another cardinal in this disease. In addition, self-paced timing movements are also disturbed in HD, which may also affect several rhythmic voluntary movements such as gait. Motor slowness can be measured with clinical scales such as the Unified Huntington's Disease Rating Scale (UHDRS) and timed tests, but also with the reaction time (RT) paradigm. We evaluated RT as a measure of motor slowness in 30 patients with genetically confirmed Huntington's disease and 24 control subjects. We also evaluated self-paced timing precision (SPTP) by applying a simple software program devised by our group. Clinical assessment was performed according to the UHDRS, including motor section, total functional capacity (TFC) and cognitive section (verbal fluency test, symbol digit, and Stroop test) The mean values obtained for RT and SPTP were statistically different in HD as compared with those from controls (p<0.0005). We observed a statistically significant correlation between RT and TFC scores (rs=-0.57, p<0.005 Spearman's correlation) and also between SPTP values and TFC scores (rs=-0.40, p<0.05 Spearman's correlation). In addition, RT and SPTP significantly correlated with cognitive scores (including digit symbol, verbal fluency and Stroop tests). Simple tests such as RT and SPTP provide an objective evaluation of motor impairment in HD yielding measures that correlate with clinical assessment and functional disability.
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Doença de Huntington/fisiopatologia , Periodicidade , Tempo de Reação/fisiologia , Percepção do Tempo/fisiologia , Adulto , Feminino , Humanos , Doença de Huntington/genética , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Estatística como Assunto , Repetições de Trinucleotídeos/genéticaRESUMO
OBJECTIVES: To compare the severity of cognitive impairment among groups of patients with different age ranges at the onset of Huntington disease (HD) and to evaluate the variable influence of motor and cognitive deficits on functional disability across different ages at the onset of HD. DESIGN: Cross-sectional multidisciplinary evaluation of patients referred to our institution for care related to a possible diagnosis of HD. SETTING: The Huntington disease program in the Departments of Neurology and Genetics at the Fundación Jimenez Diaz, Madrid, Spain. PARTICIPANTS: Seventy-one patients with Huntington disease were classified into 3 groups depending on age at onset of motor symptoms: juvenile onset, 25 years of age or younger (group 1, n = 15); adult onset, from 26 to 50 years (group 2, n = 43); and late onset, 51 years or older (group 3, n = 13). Age- and education-matched controls (n=50) were included to compare cognitive performance with patients in groups 1 and 3. MEASURES: Cognitive evaluation encompassed a wide neuropsychological battery to assess global cognitive functioning and visuospatial, prefrontal, and memory functions. Clinical data included motor and functional variables measured by using the Unified Huntington's Disease Rating Scale. Genetic analysis determined the number of CAG trinucleotide repeats. RESULTS: Patients in group 1 scored 2.9 points and patients in group 3 scored 4.2 points below their respective controls on the Mini-Mental State Examination. Patients in groups 1 and 3 were similarly impaired in verbal memory. Visual function was much more impaired in patients in group 3, and prefrontal functions were slightly worse in patients in group 1. Cognitive scores were correlated only with time of evolution for patients in group 2. Functional scores were not significantly different among the 3 groups, but 11 (85%) of the patients in group 3 were in stage I or II vs 10 (67%) of the patients in group 1. Total functional capacity correlated better with the Mini-Mental State Examination score for patients in group 3 and with motor deficits (akinesia) and prefrontal dysfunction for patients in group 1. The mean+/-SD CAG repeat length decreased from 59.9+/-12.6 for patients in group 1 to 46.2+/-3.5 for patients in group 2 and 41.7+/-2.6 for patients in group 3. Longer CAG repeats in the HD study population correlated with akinetic features but not with cognitive performance. CONCLUSIONS: Despite the much greater genetic defect, cognitive status is slightly better preserved in patients with juvenile-onset HD. Cognitive impairment in patients with juvenile- and late-onset HD differs in the severity of visual and prefrontal deficits. Functional disability in patients with late-onset HD depends more on global cognitive status, while in patients with juvenile-onset HD, it is conditioned more by motor deficits and prefrontal dysfunction.
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Transtornos Cognitivos/etiologia , Doença de Huntington/psicologia , Adolescente , Adulto , Idade de Início , Idoso , Criança , Estudos Transversais , Feminino , Humanos , Doença de Huntington/genética , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/fisiopatologia , Índice de Gravidade de Doença , Repetições de TrinucleotídeosRESUMO
To elucidate the possible role of vitamin E in the pathogenesis of Parkinson's disease (PD), we compared serum levels of alpha-tocopherol (vitamin E), measured by high-performance liquid chromatography, and the vitamin E/cholesterol ratio of 42 Parkinson's disease (PD) patients using their spouses as the control group. The serum levels of vitamin E did not differ significantly between the groups (13.84 +/- 0.56 micrograms/ml for PD and 14.80 +/- 0.57 micrograms/ml for controls), nor did the vitamin E/cholesterol ratio (0.64 +/- 0.03 for both groups). There was no influence of antiparkinsonian therapy on vitamin E or the vitamin E/cholesterol ratio. Serum levels of the vitamin E and vitamin E/cholesterol ratio did not correlate with age, age at onset, scores of the Unified Parkinson's Disease Rating Scale or the Hoehn and Yahr staging in the PD group. These results suggest that serum vitamin E concentrations do not play a role in the pathogenesis of PD.
Assuntos
Doença de Parkinson/sangue , Vitamina E/sangue , Idoso , Análise de Variância , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , MasculinoRESUMO
Tourette's disorder is a neuropsychiatric disorder characterised clinically by motor and vocal tics, which may be associated to conductual disorders such as obsessive-compulsive disorder (OCD) and attention-deficit hyperactivity disorder (ADHD). Although the neurochemistry of Tourette's disorder is not well known, there are some effective therapies for tics, OCD and ADHD. However, these are not devoid of adverse effects. Tics only require treatment when they interfere with the functioning of the patient. If therapy is needed, monotherapy at the minimal effective dose is desirable, but some patients may require two or more drugs. The most frequently used drugs for tics are antipsychotics (mainly pimozide and haloperidol) and clonidine. The potential usefulness of atypical antipsychotic drugs (risperidone, olanzapine, clozapine, ziprasidone) and other dopaminergic drugs (fluphenazine, sulpiride, tiapride, metoclopramide, piquindone, tetrabenazine), clonazepam, calcium channel antagonists, botulinum toxin, dopamine agonists, selegiline, and other drugs is discussed. The drugs of choice for OCD in patients with Tourette's disorder are the selective serotonin reuptake inhibitors (SSRIs), although the tricyclic antidepressant clomiplamine, which inhibits both serotonin and noradrenaline uptake, has also been found to be useful. ADHD can be treated with some psychostimulants, mainly methylphenidate, although these drugs must be used with caution. Other potentially useful drugs for the treatment of ADHD in patients with Tourette's disorder are clonidine, guanfacine, selegiline, some tricyclic antidepressants, sertraline, pimozide and clonazepam. Finally, the potential value of some nonpharmacological therapies (hypnotherapy, biofeedback, conductual therapies, electroconvulsive therapy, acupuncture and surgery) is briefly reviewed.
Assuntos
Agonistas alfa-Adrenérgicos/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Clonidina/uso terapêutico , Transtorno da Conduta/tratamento farmacológico , Antagonistas de Dopamina/uso terapêutico , Síndrome de Tourette/etiologia , Agonistas alfa-Adrenérgicos/farmacologia , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Benzodiazepinas/farmacologia , Benzodiazepinas/uso terapêutico , Toxinas Botulínicas/farmacologia , Toxinas Botulínicas/uso terapêutico , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Clonidina/farmacologia , Transtorno da Conduta/etiologia , Antagonistas de Dopamina/farmacologia , Humanos , Inibidores da Monoaminoxidase/farmacologia , Inibidores da Monoaminoxidase/uso terapêutico , Selegilina/farmacologia , Selegilina/uso terapêutico , Síndrome de Tourette/complicações , Síndrome de Tourette/psicologiaRESUMO
Parkinsonism, tremor, chorea-ballismus, dystonia, tardive dyskinesia, myoclonus, tics and akathisia can be induced by many drugs. The drugs that are most frequently implicated in movement disorders are antipsychotics, calcium antagonists, orthopramides and substituted benzamides (e.g. metoclopramide, sulpiride, clebopride, domperidone), CNS stimulants, antidepressants, anticonvulsants, antiparkinsonian drugs and lithium. It is possible for a single drug to induce 2 or more types of movement disorders in the same patient. Movement disorders are not always reversible after drug withdrawal.