ObjectiveTo determine whether objective and quantitative assessment of dysarthria and dysphagia i... more ObjectiveTo determine whether objective and quantitative assessment of dysarthria and dysphagia in spinocerebellar ataxia type 2 (SCA2), specifically at pre-ataxic and early disease phases, can act as sensitive disease markers.MethodsForty-six individuals (16 with pre-ataxic SCA2, 14 with early-stage ataxic SCA2, and 16 healthy controls) were recruited in Holguin, Cuba. All participants underwent a comprehensive battery of assessments including objective acoustic analysis, clinician-derived ratings of speech function and swallowing, and quality of life assessments of swallowing.ResultsReduced speech agility manifest at the pre-ataxic stage was observed during diadochokinetic tasks, with the magnitude of speech deficit augmented in the early ataxic stage. Speech rate was slower in early-stage ataxic SCA2 compared with pre-ataxic SCA2 and healthy controls. Reduced speech agility and speech rate correlated with disease severity and time to ataxia onset, verifying that speech deficits o...
Background: Cognitive decline is a common non-motor feature characterizing Spinocerebellar Ataxia... more Background: Cognitive decline is a common non-motor feature characterizing Spinocerebellar Ataxia type 2 (SCA2) during the prodromal stage, nevertheless a reduced number of surrogate biomarkers of these alterations have been described. Objective: To provide insights into cognitive dysfunction in SCA2 patients using P300 event-related potentials (ERP) and to evaluate these measures as biomarkers of the disease. Methods: A cross-sectional study was performed with 30 SCA2 patients, 20 preclinical carriers and 33 healthy controls, who underwent visual, auditory P300 ERPs, and neurological examinations and ataxia scoring. Results: SCA2 patients showed significant increase in P300 latencies and decrease of P300 amplitudes for visual and auditory stimuli, whereas preclinical carriers exhibit a less severe, but significant prolongation of P300 latencies. Multiple regression analyses disclosed a significant effect of SARA score on visual P300 abnormalities in patients as well as of the time to ataxia onset on visual P300 latencies in preclinical carriers. Conclusions: This paper demonstrated the role of P300 ERP for the study of attentional, discriminative and working memory abnormalities in SCA2 patients and for the search of surrogate biomarkers from prodromal to the symptomatic stages. Moreover, our findings provide psychophysiological evidences supporting the cerebellar involvement in cognitive processes and allows us to identify promising outcome measures for future trials focusing on cognitive dysfunction.
Annals of clinical and translational neurology, 2018
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited neurodegenerative disea... more Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited neurodegenerative disease mainly affecting the cerebellum and brainstem. In this Cuban-German research collaboration, we aimed to characterize atrophy patterns and associations with clinical measures in preclinical and manifest SCA2. In this study, 16 nonmanifest SCA2 mutation carriers, 26 manifest patients with SCA2, and 18 healthy control subjects underwent magnetic resonance imaging, as well as genetic and clinical characterization including assessment of ataxia (Scale for the Assessment and Rating of Ataxia) and saccade velocity in Cuba were enrolled. Semiautomated quantitative volumetry of the cerebellum and brainstem, subdivided into the medulla oblongata, the pontine brainstem, and mesencephalon was performed. Additionally, the anteroposterior diameter of the pontine brainstem was measured. Analysis of volumetric data revealed degeneration of the cerebellum and brainstem, in particular of pontine volume...
Saccade slowing has been proposed as endophenotype marker in Spinocerebellar Ataxia type 2 (SCA2)... more Saccade slowing has been proposed as endophenotype marker in Spinocerebellar Ataxia type 2 (SCA2), nevertheless the heritability of this trait has not been properly demonstrated. Thus the present paper was aimed to assess the heritability of different saccadic parameters in SCA2. Forty-eight SCA2 patients, 25 preclinical carriers and 24 non-SCA2 mutation carriers underwent electronystagmographical assessments of saccadic eye movements as well as neurological examination and ataxia scoring. Estimates of heritability based on the intraclass correlation coefficients were calculated for saccade velocity, accuracy and latency as well as for age at disease onset from 36, 17 and 15 sibling pairs of SCA2 patients, preclinical carriers and controls, respectively. Saccade velocity was significantly reduced in SCA2 patients and preclinical carriers, whereas decreased saccade accuracy and increased saccade latency were only observed in the patients cohort. Intraclass correlation coefficient for...
Spinocerebellar ataxia type 2 (SCA2) is part of a group of at least nine dominantly inherited dis... more Spinocerebellar ataxia type 2 (SCA2) is part of a group of at least nine dominantly inherited disorders characterized by progressive degeneration of specific neuronal populations and a shared mutational mechanism involving the expansion of a CAG repeat tract in coding regions of novel genes. Efforts have been made to identify biomarkers of disease progression, which would allow timely preventive therapeutic interventions. In the present study was assessed the influence of several genome instability biomarkers on SCA2 clinical severity. A case-control design was applied on exfoliated epithelial buccal cells to determine micronuclei frequency and others nuclear anomalies, using 5% Giemsa stains. The slides were analyzed under 1000X magnification and nuclei morphological anomalies were identified according to Tolbert PE, et al. (1992) and Bolognesi C, et al. (2013) criteria. It was found a highly significant increase in micronuclei frequency in cases related to age and sex-matched healthy controls (p !0.001). There was a trend for karyolytic, pyknotic and condensed chromatin cells to be increased in SCA2 cases, and a significant association was found between binucleated cells and disease duration (r 5 0.46; p 5 0.027). Nor the CAG repeat length neither the age at onset correlated significantly with any of the studied markers (p O0.05). Our results are consistent with report previous in similar neurodegenerative diseases, and suggest that micronuclei and binucleated cells constitute potential peripheral biomarkers for SCA2. These results should be validated by other studies.
Revista Cubana De Investigaciones Biomedicas, Jun 1, 2014
Introduction: Spinocerebellar ataxia type 2 (SCA2) is a severe neurodegenerative disease which co... more Introduction: Spinocerebellar ataxia type 2 (SCA2) is a severe neurodegenerative disease which constitutes a serious health problem in Cuba due to its high prevalence and incidence rates and the lack of curative treatments. Objectives: Evaluate the effect and safety of the treatment with high doses of Bcomplex vitamins (Compvit-B) on peripheral neuropathy in patients with SCA2. Methods: A prospective clinical intervention study was conducted of 20 patients in the mild stage of the disease undergoing a therapeutic protocol consisting in intramuscular injection of Compvit-B for 12 weeks. Patients were administered two ampoules weekly in the first 4 weeks and one from the fifth week onwards. Immediately before and after the treatment patients underwent clinical and electrophysiological examination. Results: Upon completion of the treatment patients showed a significant increase in the amplitude of the sensitive action potentials of the median and sural nerves. In the latter case there was also a decrease in latency and an increase in conduction velocity. Motor nerve conduction parameters were not modified. Somatosensory evoked potentials of the median nerve showed a significant reduction in the latency of Erb's potential. A significant decrease was also found in the frequency of painful muscle contractures in 53% of the cases after treatment. Adverse events were not recorded during the study. Conclusions: The study identifies a new therapeutic option for symptomatic SCA2, and provides new evidence of the pathophysiological bases and clinical management of painful muscle contractures. Broader studies should be conducted with patients and carriers of the mutation, who typically present such manifestations long before developing ataxia.
159 relatives of patients suffering from SCA2 (Spinocerebellar ataxia 2) were studied. All of the... more 159 relatives of patients suffering from SCA2 (Spinocerebellar ataxia 2) were studied. All of them were done physical examination in order to value them clinically as well as studies of peripherical nerve conduction were done. Clinical manifestations were found in 13 of this patients. In other 11 patients electrophysiological alterations in lack of symptoms and signs were detected. The others were excluded from the studies. The main electrophysiological alterations detected were reduced amplitude of the sensitive potentials. This is an expression of axonal lesion in sensitive portion of studied nerves.
RESUMEN Introducción Cuba es el país con mayores tasas de prevalencia e incidencia para las ataxi... more RESUMEN Introducción Cuba es el país con mayores tasas de prevalencia e incidencia para las ataxias hereditarias, lo que constituye un problema de salud que motivó la creación del Centro para la Investigación y Rehabilitación de Ataxias Hereditarias en Holguín. Objetivos Describir los principales resultados, aportes científicos, estrategias de intervención e impactos que durante más de 10 años se han obtenido por el citado centro, como modelo para el abordaje integral de las ataxias hereditarias en Cuba. Fuente de datos Se realizó una revisión en las bases de datos Pubmed-Medline y Scopus, analizando todos los artículos relevantes, comprendidos en el periodo 1978-2011. Se utilizó el descriptor «ataxia espinocerebelar», de elevada especificidad y sensibilidad para el tema en análisis. Síntesis de los datos La prevalencia de la enfermedad se ha mantenido constante durante 40 años, extendiéndose a toda la isla. La mutación ataxia espinocerebelosa tipo 2 es responsable del 60 % de la variabilidad fenotípica mientras que el 40 % restante se debe a factores modificadores genéticos y/o ambientales. Se ha descrito la existencia de un daño oxidativo severo, disminución de neuroprotectores y oligoelementos. Los estudios neurofisiológicos permitieron definir etapas evolutivas desde estadios preclínicos de la enfermedad así como biomarcadores de progresión y daño genético. Estos resultados propiciaron el diseño y ejecución de varios ensayos clínicos controlados en busca de un protocolo de tratamiento contra la enfermedad. Adicionalmente se brinda un servicio de diagnostico prenatal y presintomático con un impacto positivo sobre las familias afectadas. Conclusiones Las investigaciones sobre la ataxia espinocerebelosa tipo 2 cubana, como problema de salud, han tenido un enfoque integral. Los nuevos descubrimientos sobre la patogenia, la identificación de biomarcadores, los ensayos clínicos, el diagnóstico prenatal y presintomático permitieron conformar un nuevo modelo cubano para el abordaje de las ataxias hereditarias y el estudio de otras enfermedades neurodegenerativas. Palabras clave: Ataxia espinocerebelosa tipo 2, SCA2, ataxia cubana, Centro para la Investigación y Rehabilitación de las ataxias hereditarias (CIRAH).
Although antisaccadic task is a sensitive research tool in psychopathology, it has not been syste... more Although antisaccadic task is a sensitive research tool in psychopathology, it has not been systematically studied in patients with spinocerebellar ataxia type 2 (SCA2). To identify putative biomarkers of executive dysfunction in SCA2 we assessed the antisaccade performance in 41 SCA2 patients and their sex-and-age matched controls using an electronystagmography device. We studied the relationship between findings in the antisaccade task and CAG repeat length and motor function as assessed using the Scale for the Assessment and Rating of Ataxia (SARA), Nine-Hole Pegboard Test and a validated battery for executive dysfunctions. SCA2 patients showed a significant increase of inhibition and omission antisaccadic error rates, decrease of corrected antisaccadic errors and prolongation of antisaccadic latency and antisaccadic correction latency. Multiple regression predictions identified the expanded CAG repeat as a significant contributing factor on inhibition antisaccadic error rate and percentage of corrected antisaccadic errors. Impaired antisaccadic performance was associated to higher Stroop interference task and verbal fluency test deficits. In conclusion, antisaccadic eye movement abnormalities are a newly recognized association with the genetic abnormality in SCA2 and correlate with executive dysfunction in SCA2. Antisaccade parameters are a promising source of cognitive biomarkers for exploring the disease pathophysiology, and assessing the efficacy of therapeutic options.
The prodromal phase of spinocerebellar ataxias (SCAs) has not been systematically studied. Main f... more The prodromal phase of spinocerebellar ataxias (SCAs) has not been systematically studied. Main findings come from a homogeneous SCA type 2 (SCA2) population living in Cuba. The aim of this study was to characterize extensively the prodromal phase of SCA2 by several approaches. Thirty-seven non-ataxic SCA2 mutation carriers and its age- and sex-matched controls underwent clinical assessments, including standardized neurological exam, structured interviews and clinical scales, and looking for somatic and autonomic features, as well as a neuropsychological battery, antisaccadic recordings, and MRI scans. Main clinical somatic features of non-ataxic mutation carriers were cramps, sensory symptoms, sleep disorders, and hyperreflexia, whereas predominating autonomic symptoms were pollakiuria/nocturia, constipation, and frequent throat clearing. Cognitive impairments included early deficits of executive functions and visual memory, suggesting the involvement of cerebro-cerebellar-cerebral loops and/or reduced cholinergic basal forebrain input to the cortex. Antisaccadic task revealed impaired oculomotor inhibitory control but preserved ability for error correction. Cognitive and antisaccadic deficits were higher as carriers were closer to the estimated onset of ataxia, whereas higher Scale for the Assessment and Rating of Ataxia (SARA) scores were associated most notably to vermis atrophy. The recognition of early features of SCA2 offers novel insights into the prodromal phase and physiopathological base of the disease, allowing the assessment of its progression and the efficacy of treatments, in particular at early phases when therapeutical options should be most effective.
parkinsonism in our group. All subjects were screened for selected exons in LRRK 2 and parkin gen... more parkinsonism in our group. All subjects were screened for selected exons in LRRK 2 and parkin genes using dHPLC and HRM analysis. For the LRRK 2 gene, we analyzed the exons 31, 35, 41 and 48, and for the parkin gene the exons 2, 6 and 7. Results: Analyzing 126 samples, we detected one exonic and four intronic polymorphisms in the exon 48 and one intronic polymorphism in the exon 35 of the LRRK 2 gene. We identified also one intronic polymorphism in the exon 2 of the parkin gene. No pathogenic mutations were found in our patients. Conclusion: Our study indicates that the most common mutations in LRRK 2 gene do not play an important role in the etiology of Parkinson's disease in central Europe. This has been also shown by previous studies. It must be emphasized that the overall sample size is relatively small, particularly for the familial PD cases. A study on larger series is in progress.
parkinsonism in our group. All subjects were screened for selected exons in LRRK 2 and parkin gen... more parkinsonism in our group. All subjects were screened for selected exons in LRRK 2 and parkin genes using dHPLC and HRM analysis. For the LRRK 2 gene, we analyzed the exons 31, 35, 41 and 48, and for the parkin gene the exons 2, 6 and 7. Results: Analyzing 126 samples, we detected one exonic and four intronic polymorphisms in the exon 48 and one intronic polymorphism in the exon 35 of the LRRK 2 gene. We identified also one intronic polymorphism in the exon 2 of the parkin gene. No pathogenic mutations were found in our patients. Conclusion: Our study indicates that the most common mutations in LRRK 2 gene do not play an important role in the etiology of Parkinson's disease in central Europe. This has been also shown by previous studies. It must be emphasized that the overall sample size is relatively small, particularly for the familial PD cases. A study on larger series is in progress.
ObjectiveTo determine whether objective and quantitative assessment of dysarthria and dysphagia i... more ObjectiveTo determine whether objective and quantitative assessment of dysarthria and dysphagia in spinocerebellar ataxia type 2 (SCA2), specifically at pre-ataxic and early disease phases, can act as sensitive disease markers.MethodsForty-six individuals (16 with pre-ataxic SCA2, 14 with early-stage ataxic SCA2, and 16 healthy controls) were recruited in Holguin, Cuba. All participants underwent a comprehensive battery of assessments including objective acoustic analysis, clinician-derived ratings of speech function and swallowing, and quality of life assessments of swallowing.ResultsReduced speech agility manifest at the pre-ataxic stage was observed during diadochokinetic tasks, with the magnitude of speech deficit augmented in the early ataxic stage. Speech rate was slower in early-stage ataxic SCA2 compared with pre-ataxic SCA2 and healthy controls. Reduced speech agility and speech rate correlated with disease severity and time to ataxia onset, verifying that speech deficits o...
Background: Cognitive decline is a common non-motor feature characterizing Spinocerebellar Ataxia... more Background: Cognitive decline is a common non-motor feature characterizing Spinocerebellar Ataxia type 2 (SCA2) during the prodromal stage, nevertheless a reduced number of surrogate biomarkers of these alterations have been described. Objective: To provide insights into cognitive dysfunction in SCA2 patients using P300 event-related potentials (ERP) and to evaluate these measures as biomarkers of the disease. Methods: A cross-sectional study was performed with 30 SCA2 patients, 20 preclinical carriers and 33 healthy controls, who underwent visual, auditory P300 ERPs, and neurological examinations and ataxia scoring. Results: SCA2 patients showed significant increase in P300 latencies and decrease of P300 amplitudes for visual and auditory stimuli, whereas preclinical carriers exhibit a less severe, but significant prolongation of P300 latencies. Multiple regression analyses disclosed a significant effect of SARA score on visual P300 abnormalities in patients as well as of the time to ataxia onset on visual P300 latencies in preclinical carriers. Conclusions: This paper demonstrated the role of P300 ERP for the study of attentional, discriminative and working memory abnormalities in SCA2 patients and for the search of surrogate biomarkers from prodromal to the symptomatic stages. Moreover, our findings provide psychophysiological evidences supporting the cerebellar involvement in cognitive processes and allows us to identify promising outcome measures for future trials focusing on cognitive dysfunction.
Annals of clinical and translational neurology, 2018
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited neurodegenerative disea... more Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited neurodegenerative disease mainly affecting the cerebellum and brainstem. In this Cuban-German research collaboration, we aimed to characterize atrophy patterns and associations with clinical measures in preclinical and manifest SCA2. In this study, 16 nonmanifest SCA2 mutation carriers, 26 manifest patients with SCA2, and 18 healthy control subjects underwent magnetic resonance imaging, as well as genetic and clinical characterization including assessment of ataxia (Scale for the Assessment and Rating of Ataxia) and saccade velocity in Cuba were enrolled. Semiautomated quantitative volumetry of the cerebellum and brainstem, subdivided into the medulla oblongata, the pontine brainstem, and mesencephalon was performed. Additionally, the anteroposterior diameter of the pontine brainstem was measured. Analysis of volumetric data revealed degeneration of the cerebellum and brainstem, in particular of pontine volume...
Saccade slowing has been proposed as endophenotype marker in Spinocerebellar Ataxia type 2 (SCA2)... more Saccade slowing has been proposed as endophenotype marker in Spinocerebellar Ataxia type 2 (SCA2), nevertheless the heritability of this trait has not been properly demonstrated. Thus the present paper was aimed to assess the heritability of different saccadic parameters in SCA2. Forty-eight SCA2 patients, 25 preclinical carriers and 24 non-SCA2 mutation carriers underwent electronystagmographical assessments of saccadic eye movements as well as neurological examination and ataxia scoring. Estimates of heritability based on the intraclass correlation coefficients were calculated for saccade velocity, accuracy and latency as well as for age at disease onset from 36, 17 and 15 sibling pairs of SCA2 patients, preclinical carriers and controls, respectively. Saccade velocity was significantly reduced in SCA2 patients and preclinical carriers, whereas decreased saccade accuracy and increased saccade latency were only observed in the patients cohort. Intraclass correlation coefficient for...
Spinocerebellar ataxia type 2 (SCA2) is part of a group of at least nine dominantly inherited dis... more Spinocerebellar ataxia type 2 (SCA2) is part of a group of at least nine dominantly inherited disorders characterized by progressive degeneration of specific neuronal populations and a shared mutational mechanism involving the expansion of a CAG repeat tract in coding regions of novel genes. Efforts have been made to identify biomarkers of disease progression, which would allow timely preventive therapeutic interventions. In the present study was assessed the influence of several genome instability biomarkers on SCA2 clinical severity. A case-control design was applied on exfoliated epithelial buccal cells to determine micronuclei frequency and others nuclear anomalies, using 5% Giemsa stains. The slides were analyzed under 1000X magnification and nuclei morphological anomalies were identified according to Tolbert PE, et al. (1992) and Bolognesi C, et al. (2013) criteria. It was found a highly significant increase in micronuclei frequency in cases related to age and sex-matched healthy controls (p !0.001). There was a trend for karyolytic, pyknotic and condensed chromatin cells to be increased in SCA2 cases, and a significant association was found between binucleated cells and disease duration (r 5 0.46; p 5 0.027). Nor the CAG repeat length neither the age at onset correlated significantly with any of the studied markers (p O0.05). Our results are consistent with report previous in similar neurodegenerative diseases, and suggest that micronuclei and binucleated cells constitute potential peripheral biomarkers for SCA2. These results should be validated by other studies.
Revista Cubana De Investigaciones Biomedicas, Jun 1, 2014
Introduction: Spinocerebellar ataxia type 2 (SCA2) is a severe neurodegenerative disease which co... more Introduction: Spinocerebellar ataxia type 2 (SCA2) is a severe neurodegenerative disease which constitutes a serious health problem in Cuba due to its high prevalence and incidence rates and the lack of curative treatments. Objectives: Evaluate the effect and safety of the treatment with high doses of Bcomplex vitamins (Compvit-B) on peripheral neuropathy in patients with SCA2. Methods: A prospective clinical intervention study was conducted of 20 patients in the mild stage of the disease undergoing a therapeutic protocol consisting in intramuscular injection of Compvit-B for 12 weeks. Patients were administered two ampoules weekly in the first 4 weeks and one from the fifth week onwards. Immediately before and after the treatment patients underwent clinical and electrophysiological examination. Results: Upon completion of the treatment patients showed a significant increase in the amplitude of the sensitive action potentials of the median and sural nerves. In the latter case there was also a decrease in latency and an increase in conduction velocity. Motor nerve conduction parameters were not modified. Somatosensory evoked potentials of the median nerve showed a significant reduction in the latency of Erb's potential. A significant decrease was also found in the frequency of painful muscle contractures in 53% of the cases after treatment. Adverse events were not recorded during the study. Conclusions: The study identifies a new therapeutic option for symptomatic SCA2, and provides new evidence of the pathophysiological bases and clinical management of painful muscle contractures. Broader studies should be conducted with patients and carriers of the mutation, who typically present such manifestations long before developing ataxia.
159 relatives of patients suffering from SCA2 (Spinocerebellar ataxia 2) were studied. All of the... more 159 relatives of patients suffering from SCA2 (Spinocerebellar ataxia 2) were studied. All of them were done physical examination in order to value them clinically as well as studies of peripherical nerve conduction were done. Clinical manifestations were found in 13 of this patients. In other 11 patients electrophysiological alterations in lack of symptoms and signs were detected. The others were excluded from the studies. The main electrophysiological alterations detected were reduced amplitude of the sensitive potentials. This is an expression of axonal lesion in sensitive portion of studied nerves.
RESUMEN Introducción Cuba es el país con mayores tasas de prevalencia e incidencia para las ataxi... more RESUMEN Introducción Cuba es el país con mayores tasas de prevalencia e incidencia para las ataxias hereditarias, lo que constituye un problema de salud que motivó la creación del Centro para la Investigación y Rehabilitación de Ataxias Hereditarias en Holguín. Objetivos Describir los principales resultados, aportes científicos, estrategias de intervención e impactos que durante más de 10 años se han obtenido por el citado centro, como modelo para el abordaje integral de las ataxias hereditarias en Cuba. Fuente de datos Se realizó una revisión en las bases de datos Pubmed-Medline y Scopus, analizando todos los artículos relevantes, comprendidos en el periodo 1978-2011. Se utilizó el descriptor «ataxia espinocerebelar», de elevada especificidad y sensibilidad para el tema en análisis. Síntesis de los datos La prevalencia de la enfermedad se ha mantenido constante durante 40 años, extendiéndose a toda la isla. La mutación ataxia espinocerebelosa tipo 2 es responsable del 60 % de la variabilidad fenotípica mientras que el 40 % restante se debe a factores modificadores genéticos y/o ambientales. Se ha descrito la existencia de un daño oxidativo severo, disminución de neuroprotectores y oligoelementos. Los estudios neurofisiológicos permitieron definir etapas evolutivas desde estadios preclínicos de la enfermedad así como biomarcadores de progresión y daño genético. Estos resultados propiciaron el diseño y ejecución de varios ensayos clínicos controlados en busca de un protocolo de tratamiento contra la enfermedad. Adicionalmente se brinda un servicio de diagnostico prenatal y presintomático con un impacto positivo sobre las familias afectadas. Conclusiones Las investigaciones sobre la ataxia espinocerebelosa tipo 2 cubana, como problema de salud, han tenido un enfoque integral. Los nuevos descubrimientos sobre la patogenia, la identificación de biomarcadores, los ensayos clínicos, el diagnóstico prenatal y presintomático permitieron conformar un nuevo modelo cubano para el abordaje de las ataxias hereditarias y el estudio de otras enfermedades neurodegenerativas. Palabras clave: Ataxia espinocerebelosa tipo 2, SCA2, ataxia cubana, Centro para la Investigación y Rehabilitación de las ataxias hereditarias (CIRAH).
Although antisaccadic task is a sensitive research tool in psychopathology, it has not been syste... more Although antisaccadic task is a sensitive research tool in psychopathology, it has not been systematically studied in patients with spinocerebellar ataxia type 2 (SCA2). To identify putative biomarkers of executive dysfunction in SCA2 we assessed the antisaccade performance in 41 SCA2 patients and their sex-and-age matched controls using an electronystagmography device. We studied the relationship between findings in the antisaccade task and CAG repeat length and motor function as assessed using the Scale for the Assessment and Rating of Ataxia (SARA), Nine-Hole Pegboard Test and a validated battery for executive dysfunctions. SCA2 patients showed a significant increase of inhibition and omission antisaccadic error rates, decrease of corrected antisaccadic errors and prolongation of antisaccadic latency and antisaccadic correction latency. Multiple regression predictions identified the expanded CAG repeat as a significant contributing factor on inhibition antisaccadic error rate and percentage of corrected antisaccadic errors. Impaired antisaccadic performance was associated to higher Stroop interference task and verbal fluency test deficits. In conclusion, antisaccadic eye movement abnormalities are a newly recognized association with the genetic abnormality in SCA2 and correlate with executive dysfunction in SCA2. Antisaccade parameters are a promising source of cognitive biomarkers for exploring the disease pathophysiology, and assessing the efficacy of therapeutic options.
The prodromal phase of spinocerebellar ataxias (SCAs) has not been systematically studied. Main f... more The prodromal phase of spinocerebellar ataxias (SCAs) has not been systematically studied. Main findings come from a homogeneous SCA type 2 (SCA2) population living in Cuba. The aim of this study was to characterize extensively the prodromal phase of SCA2 by several approaches. Thirty-seven non-ataxic SCA2 mutation carriers and its age- and sex-matched controls underwent clinical assessments, including standardized neurological exam, structured interviews and clinical scales, and looking for somatic and autonomic features, as well as a neuropsychological battery, antisaccadic recordings, and MRI scans. Main clinical somatic features of non-ataxic mutation carriers were cramps, sensory symptoms, sleep disorders, and hyperreflexia, whereas predominating autonomic symptoms were pollakiuria/nocturia, constipation, and frequent throat clearing. Cognitive impairments included early deficits of executive functions and visual memory, suggesting the involvement of cerebro-cerebellar-cerebral loops and/or reduced cholinergic basal forebrain input to the cortex. Antisaccadic task revealed impaired oculomotor inhibitory control but preserved ability for error correction. Cognitive and antisaccadic deficits were higher as carriers were closer to the estimated onset of ataxia, whereas higher Scale for the Assessment and Rating of Ataxia (SARA) scores were associated most notably to vermis atrophy. The recognition of early features of SCA2 offers novel insights into the prodromal phase and physiopathological base of the disease, allowing the assessment of its progression and the efficacy of treatments, in particular at early phases when therapeutical options should be most effective.
parkinsonism in our group. All subjects were screened for selected exons in LRRK 2 and parkin gen... more parkinsonism in our group. All subjects were screened for selected exons in LRRK 2 and parkin genes using dHPLC and HRM analysis. For the LRRK 2 gene, we analyzed the exons 31, 35, 41 and 48, and for the parkin gene the exons 2, 6 and 7. Results: Analyzing 126 samples, we detected one exonic and four intronic polymorphisms in the exon 48 and one intronic polymorphism in the exon 35 of the LRRK 2 gene. We identified also one intronic polymorphism in the exon 2 of the parkin gene. No pathogenic mutations were found in our patients. Conclusion: Our study indicates that the most common mutations in LRRK 2 gene do not play an important role in the etiology of Parkinson's disease in central Europe. This has been also shown by previous studies. It must be emphasized that the overall sample size is relatively small, particularly for the familial PD cases. A study on larger series is in progress.
parkinsonism in our group. All subjects were screened for selected exons in LRRK 2 and parkin gen... more parkinsonism in our group. All subjects were screened for selected exons in LRRK 2 and parkin genes using dHPLC and HRM analysis. For the LRRK 2 gene, we analyzed the exons 31, 35, 41 and 48, and for the parkin gene the exons 2, 6 and 7. Results: Analyzing 126 samples, we detected one exonic and four intronic polymorphisms in the exon 48 and one intronic polymorphism in the exon 35 of the LRRK 2 gene. We identified also one intronic polymorphism in the exon 2 of the parkin gene. No pathogenic mutations were found in our patients. Conclusion: Our study indicates that the most common mutations in LRRK 2 gene do not play an important role in the etiology of Parkinson's disease in central Europe. This has been also shown by previous studies. It must be emphasized that the overall sample size is relatively small, particularly for the familial PD cases. A study on larger series is in progress.
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