ABSTRACT
BACKGROUND:Saccadic eye movement abnormalities are common in patients with spinocerebellar ataxia type 2, but it is unclear how these alterations progress over time. The aim of this study was to assess the progression of saccade involvement in spinocerebellar ataxia type 2 patients, identify its main determinants, and evaluate its usefulness as outcome measures in clinical trials.METHODS:A prospective 5-year follow-up study was performed with 30 spinocerebellar ataxia type 2 patients and their matched healthy controls, who were evaluated a total of four times by clinical and electrooculographical assessments of horizontal saccades and by the scoring of ataxia.RESULTS:Patients showed significant decreases in saccade peak velocity and saccade accuracy as well as increases of saccadic latency during the follow-up period. Annual progression rates were significantly higher in patients compared to controls. Faster progression rates of saccade slowing were associated with higher trinucleotide cytosine-adenine-guanine repeat expansions. Sample-size estimates for two-arm trials would require 19 patients per group to detect a 50 percent reduction in disease progression using saccade peak velocity as outcome variable, but 44 and 124 patients using saccade latency and accuracy, respectively (power, 80 percent; alpha = 0.05).CONCLUSIONS:Electrooculographical measures of saccade changes are useful for the objective quantification of disease course in spinocerebellar ataxia type 2. The progression rate of saccade slowing is influenced by the expansion size, providing novel insight into the cumulative polyglutamine neurotoxicity, and supporting the usefulness of saccade peak velocity as a sensitive biomarker during the natural history of the disease, and as suitable outcome measure for therapeutic trials (AU)
Subject(s)
Humans , Male , Female , Adolescent , Young Adult , Adult , Aged , Middle Aged , Spinocerebellar Ataxias/complications , Spinocerebellar Ataxias/physiopathology , Ocular Motility Disorders/etiology , Ocular Motility Disorders/physiopathology , Electrooculography/methods , Electrooculography/standards , Clinical Trials as Topic/methods , Clinical Trials as Topic/standardsABSTRACT
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Subject(s)
Humans , Electromyography , Spinocerebellar Ataxias/diagnosis , Dysarthria/etiology , Gait Ataxia/etiology , SaccadesABSTRACT
Las ataxias cerebelosas autosómicas dominantesautosomal dominant cerebellar ataxias(ADCA)constituyen un grupo heterogéneode enfermedades, caracterizadas clínicamentepor Harding en 1983, quien las dividióen los tipos I, II, III y IV. En la tipo I, laataxia de la marcha es el signo clínico primario,relacionado con oftalmoplejía supranuclear,signos piramidales, extrapiramidales, demenciamoderada y neuropatía periférica. Estegrupo incluye la ataxia espinocerebelosa tipo2 (SCA 2) [1,2], que es una de las 29 formasmoleculares descritas actualmente, en laque se ha comprobado una mutación dinámica[3,4] caracterizada por una expansión intergeneracionaldel triplete CAG (cromosoma 12),que explica el incremento en la gravedad delcuadro clínico y el inicio del cuadro a edadesmás tempranas en generaciones sucesivas...(AU)
Subject(s)
Humans , Spinocerebellar Ataxias/epidemiology , Electromyography , Spinocerebellar AtaxiasABSTRACT
OBJECTIVE: A characteristic feature of spinocerebellar ataxia type 2 (SCA2) is saccadic slowing at early disease stages. We sought to determine whether this sign is detectable before clinical manifestation and quantifies the disease progression throughout life in linear fashion. METHODS: In a specialized ataxia clinic, 54 presymptomatic carriers of SCA2 polyglutamine expansions and 56 relatives without mutation were documented with regard to their maximal saccade velocity (MSV). RESULTS: Among the control individuals, a significant effect of aging on MSV was observed. After elimination of this age influence through a matched-pair approach, a presymptomatic decrease of MSV could be shown. The MSV reduction was stronger in carriers of large expansions. In the years before calculated disease manifestation, the MSV impairment advanced insidiously. CONCLUSION: Saccade velocity is a sensitive SCA2 endophenotype that reflects early pontine degeneration and may be a useful diagnostic parameter before the onset of ataxia. SIGNIFICANCE: Future neuroprotective therapies of polyglutamine neurodegeneration may be assessed by MSV from earliest to prefinal disease stages.
Subject(s)
Ocular Motility Disorders/etiology , Ocular Motility Disorders/physiopathology , Oculomotor Muscles/physiopathology , Saccades/physiology , Spinocerebellar Ataxias/complications , Spinocerebellar Ataxias/physiopathology , Adolescent , Adult , Aged , Ataxins , Cerebellum/physiopathology , Disease Progression , Early Diagnosis , Female , Heterozygote , Humans , Male , Middle Aged , Nerve Tissue Proteins/genetics , Neural Pathways/physiopathology , Ocular Motility Disorders/diagnosis , Oculomotor Muscles/innervation , Predictive Value of Tests , Prognosis , Spinocerebellar Ataxias/diagnosis , Young AdultABSTRACT
La ataxia espinocerebelosa tipo 2 (SCA2) es una enfermedad neurodegenerativa producidapor expansiones del número de repeticiones del trinucleótido CAG en el gen SCA2. Ésta secaracteriza por el síndrome cerebeloso progresivo, el enlentecimiento sacádico y la neuropatíaperiférica, así como por alteracionescognitivas y del sueño [1]. Cuba posee el mayor número de familias afectadas por la SCA2, específicamente en la provincia de Holguín, donde la tasa de prevalencia supera los 40 casospor cada 100.000 habitantes y existen más de 2.000 descendientes directos con riesgo de padecer la enfermedad [2,3]. Hasta el momento,no existe tratamiento farmacológico efectivo contra las ataxias hereditarias, aunque se han descrito numerosos blancos terapéuticos,así como biomarcadores neuroquímicos [4] y electrofisiológicos...(AU)
Subject(s)
Humans , Spinocerebellar Ataxias/epidemiology , Spinocerebellar Ataxias/genetics , ElectromyographyABSTRACT
A characteristic feature of spinocerebellar ataxia type 2 (SCA2) is saccadic slowing at early disease stages. We sought to determine whether this sign is detectable before clinical manifestation and quantifies the disease progression throughout life in linear fashion. In a specialized ataxia clinic, 54 presymptomatic carriers of SCA2 polyglutamine expansions and 56 relatives without mutation were documented with regard to their maximal saccade velocit Spinocerebellar ataxia type 2 Among the control individuals, a significant effect of aging on MSV was observed. After elimination of this age influence through a matched-pair approach, a presymptomatic decrease of MSV could be shown. The MSV reduction was stronger in carriers of large expansions. In the years before calculated disease manifestation, the MSV impairment advanced insidiously.Saccade velocity is a sensitive SCA2 endophenotype that reflects early pontine degenerationPolyglutamine expansion and may be a useful diagnostic parameter before the onset of ataxia. Significance: Future neuroprotective therapies of polyglutamine neurodegeneration may be assessed by MSV from earliest to prefinal disease stages...(AU)
Subject(s)
HumansABSTRACT
Los estudios neurofisiológicos, y entre ellos los de conducción nerviosa motora, suelen ser de gran importanciapor brindar información de gran valor diagnóstico en diferentes patologías como la ataxia espinocerebelosa tipo2, la forma más frecuente en nuestro país, y particularmente en Holguín, y cuya prevalencia es considerada una de lasmás altas del mundo. El propósito del presente trabajo es determinar la posible relación entre la conducción nerviosamotora del nervio facial y el tipo de cara. Pacientes y métodos: Para ello fueron estudiados 101 pacientes con diagnósticoclínico y molecular de ataxia espinocerebelosa tipo 2 (SCA 2) y 36 descendientes presintomáticos. En cada caso serealizaron estudios moleculares, examen bucal, medición de la cara y determinación del tipo facial, previo estudio deconducción nerviosa motora del facial (VII par craneal). Resultados: Éstos mostraron una prolongación de la latencia delpotencial en los enfermos y de la duración tanto en los sujetos enfermos como en los portadores asintomáticos encomparación con el patrón referencial creado en un grupo de sujetos sanos y la no-existencia de relación alguna entre eltipo facial y los parámetros mesurables de la conducción nerviosa del VII par craneal. Conclusiones: La prolongación delos valores de latencia y duración del potencial motor son expresión de la existencia de una lesión de tipo mielínica dedicho par craneal tanto en los enfermos como en los descendientes portadores de la mutación SCA 2.Palabras clave: conducción nerviosa del facial, biotipología facial, tipos de cara, latencia motora distal del facial, ataxiaespinocerebelosa tipo 2, ataxia cerebelosa cubana...(AU)
Neurophysiological studies and particularly motor nerve conduction studies are very important becausethey give us certain diagnostic information of different pathologies including Spinocerebellar Ataxia Type 2, the mostfrequent form in Cuba and in Holguín, whose prevalence is considered as one of the highest in the world. The purpose ofthis study is in order to determine the relationship between motor conduction parameters of facial nerve and facialtypes. Patients and methods: We studied 101 patients with clinical and molecular diagnosis of SCA 2 and 36presimptomatic relatives. In all cases were made molecular studies, oral exam and face measurements to determingfacial type after a previous facial nerve motor conduction study of VII cranial pair. Results: These showed a latencyprolongation of the potential in patients and of the duration both in SCA 2 patients as its relatives in comparison withhealthy subjects and in the asymptomatic bearers as compared to the reference pattern (control group of healthysubjects), and the non-existing relationship between facial type and motor nerve conduction parameters. Conclusions:The facial nerve in SCA 2 patients and their relatives. Theres a positive proof...(AU)
