Hemodialysis Catheter Breakage in an Infant.

A 3-month-old male infant was admitted to our unit due to acute decompensation of chronic kidney disease of unknown etiology. Further investigation led to the diagnosis of primary hyperoxaluria type 1. As the patient did not recover, hemodialysis was initiated with a non-tunneled femoral catheter. A tunneled Hickman catheter was placed in the internal jugular vein. The patient experienced moderate intradialytic exit-site bleeding and catheter malfunction, which initially responded to pressure and postural changes. During the third session, the patient suffered cardiopulmonary arrest. After stabilization, a chest hematoma was identified. Fluoroscopy revealed a catheter breakage. Despite initial stabilization, the patient developed septic shock due to Pseudomonas aeruginosa and died several days later. Hemodialysis is sometimes necessary in children under 24 months with chronic kidney disease. Vascular access is a major challenge in these patients due to lack of appropriate catheter sizes and high complication rates. Hemodialysis catheter fracture is an uncommon complication, and diagnosis can be difficult when the breakage involves the subcutaneous segment. Persistent intradialytic bleeding and mechanical malfunction should raise suspicion of this complication and should elicit catheter revision under fluoroscopy. Without prompt diagnosis, catheter breakage may have fatal consequences, as in our case.

Plasma metabolomics of presymptomatic PSEN1-H163Y mutation carriers: a pilot study.

BACKGROUND AND OBJECTIVE: PSEN1-H163Y carriers, at the presymptomatic stage, have reduced 18 FDG-PET binding in the cerebrum of the brain (Scholl et al., Neurobiol Aging 32:1388-1399, 2011). This could imply dysfunctional energy metabolism in the brain. In this study, plasma of presymptomatic PSEN1 mutation carriers was analyzed to understand associated metabolic changes. METHODS: We analyzed plasma from noncarriers (NC, n = 8) and presymptomatic PSEN1-H163Y mutation carriers (MC, n = 6) via untargeted metabolomics using gas and liquid chromatography coupled with mass spectrometry, which identified 1199 metabolites. All the metabolites were compared between MC and NC using univariate analysis, as well as correlated with the ratio of Aß1-42/A ß 1-40 , using Spearman's correlation. Altered metabolites were subjected to Ingenuity Pathway Analysis (IPA). RESULTS: Based on principal component analysis the plasma metabolite profiles were divided into dataset A and dataset B. In dataset A, when comparing between presymptomatic MC and NC, the levels of 79 different metabolites were altered. Out of 79, only 14 were annotated metabolites. In dataset B, 37 metabolites were significantly altered between presymptomatic MC and NC and nine metabolites were annotated. In both datasets, annotated metabolites represent amino acids, fatty acyls, bile acids, hexoses, purine nucleosides, carboxylic acids, and glycerophosphatidylcholine species. 1-docosapentaenoyl-GPC was positively correlated, uric acid and glucose were negatively correlated with the ratio of plasma Aß1-42 /Aß1-40 (P < 0.05). INTERPRETATION: This study finds dysregulated metabolite classes, which are changed before the disease symptom onset. Also, it provides an opportunity to compare with sporadic Alzheimer's Disease. Observed findings in this study need to be validated in a larger and independent Familial Alzheimer's Disease (FAD) cohort.

Buccal Cell Micronucleus Frequency Is Significantly Elevated in Patients with Spinocerebellar Ataxia Type 2.

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 = 0.46; p = 0.027). Nor the CAG repeat length neither the age at onset correlated significantly with any of the studied markers (p >0.05). 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.

Epidemiological, clinical, and molecular characterization of Cuban families with spinocerebellar ataxia type 3/Machado-Joseph disease.

BACKGROUND: Spinocerebellar Ataxia Type 3/Machado-Joseph Disease (SCA3/MJD) is a hereditary neurodegenerative disorder resulting from the expansion of CAG repeats in the ATXN3 gene. It is the most common autosomal dominant ataxia in the world, but its frequency prevalence in Cuba remains uncertain. We undertook a national study in order to characterize the ATXN3 gene and to determine the prevalence of SCA3/MJD in Cuba. RESULTS: Twenty-two individuals belonging to 8 non-related families were identified as carriers of an expanded ATXN3 allele. The affected families come from the central and western region of the country. Ataxia of gait was the initial symptom in all of the cases. The normal alleles ranged between 14 and 33 CAG repeats while the expanded ones ranged from 63 to 77 repeats. The mean age at onset was 40 ± 9 years and significantly correlated with the number of CAG repeats in the expanded alleles. CONCLUSIONS: This disorder was identified as the second most common form of spinocerebellar ataxia (SCA) in Cuba based on molecular testing, and showing a different geographical distribution from that of SCA2. This research constitutes the first clinical and molecular characterization of Cuban SCA3 families, opening the way for the implementation of predictive diagnosis for at risk family members.

Adult-onset Diamond-Blackfan anemia with a novel mutation in the exon 5 of RPL11: too late and too rare.

Diamond-Blackfan anemia (DBA) is a congenital erythroid aplasia usually diagnosed in the early infancy and associated with mutations or large deletions in 11 ribosomal protein (RP) genes. Adult patients with severe, transfusion dependence, aregenerative anemia might have a genetic-in-origin disease with an atypical presentation. Late onset nonclassical DBA should be ruled out and mutations of RP genes studied.

Executive deficit in spinocerebellar ataxia type 2 is related to expanded CAG repeats: evidence from antisaccadic eye movements.

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.

Evolución inmediata y a medio plazo de las dehiscencias paravalvulares cerradas percutáneamente / Immediate and mid-term clinical course after percutaneous closure of paravalvular leakage

Introducción y objetivos: El cierre percutáneo de dehiscencias paravalvulares es una alternativa a la cirugía en pacientes de alto riesgo, pero la falta de dispositivos específicos ha limitado su uso. Recientemente se han desarrollado dispositivos más adecuados, como el Amplatzer Vascular Plug III, pero actualmente hay poca información de su eficacia y su seguridad. El objetivo es estudiar el resultado a medio plazo del cierre de dehiscencias paravalvulares con este dispositivo. Métodos: Se analizó la evolución clínica y ecocardiográfica tanto hospitalaria como a medio plazo (13±9 meses) de una serie de 20 pacientes consecutivos (edad, 68 años; EuroSCORE logístico, 29) con dehiscencias paravalvulares e intento de cierre percutáneo. Resultados: Se intentó el cierre de 23 dehiscencias (17 mitrales y 6 aórticas) durante 22 procedimientos en 20 pacientes. Se logró el éxito del implante en el 87% de las dehiscencias y el éxito del procedimiento con una reducción de ≥ 1 grado de la insuficiencia en el 83%. La supervivencia al año fue del 64,7% y la supervivencia libre de muerte/cirugía, del 58,8%. El grado de insuficiencia valvular residual no se relacionó con la mortalidad, pero sí con el grado funcional. Entre los supervivientes se observó una mejora significativa en la clase funcional. Conclusiones: El cierre percutáneo de dehiscencias con el Amplatzer Vascular Plug III es seguro y eficaz a medio plazo, aunque la mortalidad de los pacientes de alto riesgo es alta independientemente del grado de insuficiencia residual, lo que indica que se realiza en un estadio avanzado de la cardiopatía

Introduction and objectives: Percutaneous closure of paravalvular leakage is an alternative to surgery in high-risk patients, but its use has been limited by a lack of specific devices. More appropriate devices-like the Amplatzer Vascular Plug III-have recently been developed, but information about their efficacy and safety is still scarce. The objective of the present study was to assess the mid-term results of paravalvular leakage closure with this device. Methods: We analyzed the clinical and echocardiographic course both in-hospital and mid-term (13 [9] months) in a series of 20 consecutive patients (age, 68 years; logistic EuroSCORE, 29) with paravalvular leakage and attempted percutaneous closure. Results: Closure was attempted for 23 leaks (17 mitral and 6 aortic) during 22 procedures in 20 patients. Implantation was successful in 87% of the leaks and the procedure was successful in 83%-with success being defined as a reduction in regurgitation of ≥ 1 degree. Survival at 1 year was 64.7% and survival free of the composite event of death/surgery was 58.8%. The degree of residual regurgitation was not associated with mortality but was associated with functional status. Survivors showed significant improvement in functional class. Conclusions: Percutaneous closure of leakage with the Amplatzer Vascular Plug III is safe and efficient in the mid-term. However, mortality among high-risk patients is high independently of the degree of residual regurgitation, indicating that these procedures are performed when heart disease has reached an advanced stage

Immediate and mid-term clinical course after percutaneous closure of paravalvular leakage.

INTRODUCTION AND OBJECTIVES: Percutaneous closure of paravalvular leakage is an alternative to surgery in high-risk patients, but its use has been limited by a lack of specific devices. More appropriate devices-like the Amplatzer Vascular Plug III-have recently been developed, but information about their efficacy and safety is still scarce. The objective of the present study was to assess the mid-term results of paravalvular leakage closure with this device. METHODS: We analyzed the clinical and echocardiographic course both in-hospital and mid-term (13 [9] months) in a series of 20 consecutive patients (age, 68 years; logistic EuroSCORE, 29) with paravalvular leakage and attempted percutaneous closure. RESULTS: Closure was attempted for 23 leaks (17 mitral and 6 aortic) during 22 procedures in 20 patients. Implantation was successful in 87% of the leaks and the procedure was successful in 83%-with success being defined as a reduction in regurgitation of ≥ 1 degree. Survival at 1 year was 64.7% and survival free of the composite event of death/surgery was 58.8%. The degree of residual regurgitation was not associated with mortality but was associated with functional status. Survivors showed significant improvement in functional class. CONCLUSIONS: Percutaneous closure of leakage with the Amplatzer Vascular Plug III is safe and efficient in the mid-term. However, mortality among high-risk patients is high independently of the degree of residual regurgitation, indicating that these procedures are performed when heart disease has reached an advanced stage.

Comprehensive study of early features in spinocerebellar ataxia 2: delineating the prodromal stage of the disease.

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.

Progression of early features of spinocerebellar ataxia type 2 in individuals at risk: a longitudinal study.

BACKGROUND: The effects of ATXN2 expansion on the nervous system arise before the cerebellar syndrome can be diagnosed; however, progression of the underlying early clinical manifestations is unknown. We aimed to assess progression of the main clinical features in early stages of the spinocerebellar ataxia type 2 (SCA2). METHODS: We did this longitudinal study between Aug 12, 1986, and Sept 3, 2013, in carriers and non-carriers of the SCA2 mutation. We enrolled participants aged 6-60 years who were asymptomatic offspring or siblings of patients with SCA2. Participants were repeatedly assessed (two to seven times) until they presented definite cerebellar syndrome. All participants underwent standardised neurological examinations and electrophysiological (nerve conduction tests and somatosensory evoked potentials) and genetic assessments. FINDINGS: We enrolled 40 (73%) of 55 eligible participants to the baseline assessment, of whom 21 (13 women and eight men) were carriers of the SCA2 mutation, and 19 (14 women and five men) were non-carriers. Muscle cramps and sensory abnormalities were the most common clinical features in carriers (n=17 [81%] for both features) compared with controls (n=3 [16%] and n=4 [21%], respectively; χ(2)=84·58; p<0.0001, and χ(2)=72·03; p<0·0001, respectively) Both features showed a notable worsening over time and, in 17 (81%) carriers, age at onset was inversely correlated to CAG repeats (cramps: r -0·76, p=0·0004; sensory abnormalities: r -0·77, p=0·0004). Hyper-reflexia was associated with long time to ataxia onset (mean 5·71 years [SD 5·03]), whereas hyporeflexia was associated with short time (median 1·29 years [range 1-3]). Electrophysiological recordings obtained between 5 and 8 years before ataxia in 11 (52%) carriers showed reduced sensory amplitudes for median nerve (10·34 uV [SD 5·07]) and prolonged mean P40 latency (39·31 ms [2·40]) compared with age-matched and sex-matched controls (20·72 uV [9·08 uV]; p=0·0085, and 35·60 ms [2·05]; p=0·0023, respectively). INTERPRETATION: Early features of SCA2 are detectable before the onset of the cerebellar syndrome, and are associated with expanded CAG repeats and the time to onset of cerebellar syndrome. These findings could aid early diagnosis and genetic counselling, and also offer physiopathological insights that could help in the implementation of clinical trials in early stages of the disease. FUNDING: Cuban Ministry of Public Health.

Genetic features of Huntington disease in Cuban population: implications for phenotype, epidemiology and predictive testing.

Huntington disease is the most frequent polyglutamine disorder with variable worldwide prevalence. Although some Latin American populations have been studied, HD prevalence in Cuban population remains unknown. In order to characterize the disease in Cuba, the relative frequency of HD was determined by studying 130 patients with chorea and 63 unrelated healthy controls, emphasizing in the molecular epidemiology of the disease. Sixty-two patients with chorea belonging to 16 unrelated families carried a pathological CAG expansion in the HTT gene, ranging from 39 to 67 repeats. Eighty-three percent of them come from the eastern region of the country. A significant inverse correlation between age at onset and expanded CAG repeats was seen. Intermediate alleles in affected individuals and controls represented 4.8% and 3.97% respectively, which have been a putative source of de novo mutation. This study represents the largest molecular characterization of Huntington disease in the Cuban population. These results may have significant implications for an understanding of the disease, its diagnosis and prognosis in Cuban patients, giving health professionals the tools to implement confirmatory genetic testing, pre-symptomatic testing and clinical trials in this population.

Cierre percutáneo de fugas perivalvulares mitrales en pacientes con prótesis metálica aórtica / Percutaneous closure of mitral paravalvular leaks in patients with aortic valve prostheses

No disponible

Cierre de comunicación interventricular tras miectomía septal quirúrgica mediante procedimiento híbrido en un paciente adulto / Closure of ventricular septal defect after surgical septal myectomy by hybrid procedure in an adult patient

No disponible

Oral Zinc Sulphate Supplementation for Six Months in SCA2 Patients: A Randomized, Double-Blind, Placebo-Controlled Trial

Cuban patients with Spinocerebellar Ataxia type 2 (SCA2) have reduced concentrations of zinc in serum and cerebrospinal fluid (CSF). To assess the effect and safety of zinc supplementation, 36 Cuban SCA2 patients were randomly assigned to receive daily either 50 mg ZnSO4 or placebo, together with neurorehabilitation therapy in a randomized, double-blind, placebo-controlled clinical trial during 6 months. Outcome measures included the changes of zinc levels in CSF and serum, ataxia score, oxidative stress and saccadic eye movements. At the end of the study, the Zinc-treated group showed: (i) a significant increase of the Zn levels in the CSF, (ii) mild decrease in the ataxia scale subscores for gait, posture, stance and dysdiadochocinesia (iii) reduction of lipids oxidative damage, and (iv) reduction of saccadic latency when compared with the placebo group. The treatment was safe and well tolerated by all subjects. This study demonstrated the efficacy and safety of Zn supplementation, combined with neurorehabilitation for SCA2 patients and therefore it may encourage further studies on the clinical effect of zinc supplementation in SCA2 based in the conduction of future clinical trials with higher number of subjects(AU)

Caracterización integral de la ataxia espinocerebelosa 2 en Cuba y su aplicación en proyectos de intervención / Comprehensive characterization of spinocerebellar ataxia type 2 in Cuba and its application in intervention projects

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 espinocerebelar¼, 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 proiciaron 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.

Introduction Cuba is one of the countries with high rates of prevalence and incidence of hereditary ataxias, which is a health problem that encouraged the foundation of the Center for Research and Rehabilitation of Hereditary Ataxias in Holguín province. Objectives To describe the main results, scientific achievements, intervention strategies and impacts of this institution for more than 10 years, as a sort of pattern to be followed to approach hereditary ataxias in Cuba in a more comprehensive way. Data source Pubmed-Medline and Scopus database were reviewed in which all the relevant articles published from 1978 to 2011 were analyzed. Spinocerebelar ataxia, highly specific and sensitive subject headings, were used for the topic under analysis. Data synthesis The prevalence of this disease has remained unchanged for 40 years, being extended to the whole island. Spinocerebelar ataxia type 2 mutation accounts for 60% of the phenotypical variability whereas the remaining 40% is caused by genetic and/or environmental modifying factors. Severe oxidative damage, reduction of neuroprotectors and of oligoelements have been described. The neurophysiological studies allowed defining evolutionary phases from the preclinical stagings as well as progression and genetic damage biomarkers. These results allowed designing several controlled clinical assays in search of one treatment protocol for the disease. Additionally, prenatal and pre-symptomatic diagnosis service is rendered, with positive impact on affected families. Conclusions The research studies on spinocerebelar ataxia type 2 in Cuba as a health problem have had comprehensive approach. The new breakthroughs on pathogeny, identification of biomarkers, clinical assays, prenatal and presymptomatic diagnosis allowed making a new Cuban model to approach hereditary ataxias and the study of other neurodegenerative diseases.

A Comprehensive Review of Spinocerebellar Ataxia Type 2 in Cuba

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant cerebellar ataxia characterized by a progressive cerebellar syndrome associated to saccadic slowing, peripheral neuropathy, cognitive disorders, and other multisystem features. SCA2 is caused by the abnormal expansion of cytosine-adenine-guanine triplet repeats in the encoding region of the ATXN2 gene and therefore the expression of toxic polyglutamine expansions in the ataxin 2 protein, which cause progressive neuronal death of Purkinje cells in the cerebellum and several pontine, mesencephalic, and thalamic neurons among other cells. Worldwide, SCA2 is the second most frequent type of spinocerebellar ataxia, only surpassed by SCA3. Nevertheless, in Holguin, Cuba, the disease reaches the highest prevalence, resulting from a putative foundational effect. This review discusses the most important advances in the genotypical and phenotypical studies of SCA2, highlighting the comprehensive characterization reached in Cuba through clinical, neuroepidemiological, neurochemical, and neurophysiological evaluation of SCA2 patients and pre-symptomatic subjects, which has allowed the identification of new disease biomarkers and therapeutical opportunities. These findings provide guidelines, from a Cuban viewpoint, for the clinical management of the disease, its diagnosis, genetic counseling, and therapeutical options through rehabilitative therapy and/or pharmacological options (AU)

Oral zinc sulphate supplementation for six months in SCA2 patients: a randomized, double-blind, placebo-controlled trial.

Cuban patients with Spinocerebellar Ataxia type 2 (SCA2) have reduced concentrations of zinc in serum and cerebrospinal fluid (CSF). To assess the effect and safety of zinc supplementation, 36 Cuban SCA2 patients were randomly assigned to receive daily either 50 mg ZnSO(4) or placebo, together with neurorehabilitation therapy in a randomized, double-blind, placebo-controlled clinical trial during 6 months. Outcome measures included the changes of zinc levels in CSF and serum, ataxia score, oxidative stress and saccadic eye movements. At the end of the study, the Zinc-treated group showed: (i) a significant increase of the Zn levels in the CSF, (ii) mild decrease in the ataxia scale subscores for gait, posture, stance and dysdiadochocinesia (iii) reduction of lipid's oxidative damage, and (iv) reduction of saccadic latency when compared with the placebo group. The treatment was safe and well tolerated by all subjects. This study demonstrated the efficacy and safety of Zn supplementation, combined with neurorehabilitation for SCA2 patients and therefore it may encourage further studies on the clinical effect of zinc supplementation in SCA2 based in the conduction of future clinical trials with higher number of subjects.

Sleep disorders in spinocerebellar ataxia type 2 patients.

BACKGROUND: Sleep disturbances are common features in spinocerebellar ataxias (SCAs). Nevertheless, sleep data on SCA2 come from scarce studies including few patients, limiting the evaluation of the prevalence and determinants of sleep disorders. OBJECTIVE: To assess the frequency and possible determinants of sleep disorders in the large and homogeneous SCA2 Cuban population. METHODS: Thirty-two SCA2 patients and their age- and sex-matched controls were studied by video-polysomnography and sleep interviews. RESULTS: The most striking video-polysomnography features were rapid eye movement (REM) sleep pathology and periodic leg movements (PLMs). REM sleep abnormalities included a consistent reduction of the REM sleep percentage and REM density as well as an increase in REM sleep without atonia (RWA). REM sleep and REM density decreases were closely related to the increase in ataxia scores, whereas the RWA percentage was influenced by the cytosine-adenine-guanine (CAG) repeats. PLMs were observed in 37.5% of cases. The PLM index showed a significant association with the ataxia score and disease duration but not with CAG repeats. CONCLUSIONS: REM sleep pathology and PLMs are closely related to SCA2 severity, suggesting their usefulness as disease progression markers. The RWA percentage is influenced by the CAG repeats and might thus be a sensitive parameter for reflecting polyglutamine toxicity. Finally, as PLMs are sensible to drug treatment, they represents a new therapeutic target for the symptomatic treatment of SCA2.