Heart rate variability in type 2 spinocerebellar ataxia

Montes‐Brown J, Sánchez‐Cruz G, García AM, Báez ME, Velázquez‐Pérez L. Heart rate variability in type 2 spinocerebellar ataxia.
Acta Neurol Scand: 2010: 122: 329–335.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objectives – To explore cardiovascular autonomic regulation in Spinocerebellar ataxia type 2 (SCA2) patients, using heart rate variability (HRV) analysis and neurophysiologic autonomic reflex tests, and determine relations and causal related factors of dysautonomia in SCA2. Materials and methods – Heart rate variability indices for 5 min series of RR intervals were analyzed in 97 SCA2 patients, assessed quantitatively for somatic and autonomic nervous system complaints applying the International Cooperative Ataxia Rating Scale and Scales for Outcomes in Parkinson’s disease (SCOPA‐AUT), respectively. Autonomic testing included: resting control, standing, Valsalva maneuver and deep breathing. Results – Mean RR, long‐ and short‐term variability indices and spectral density power (LF, HF) indices were lower in the patients group, whereas LF/HF ratio and LF (nu) were higher. Highly differences between groups were observed for seven diagnostic autonomic test indices. Significant correlations were found between different clinical and demographic indices and between clinical indices and some HRV indices. Conclusions – We confirm the presence of cardiovascular autonomic dysfunction in a large group of SCA2 patients.     

Spinocerebellar ataxia type 17 in the Yugoslav population

OBJECTIVES: (1) Analysis of Spinocerebellar ataxia type 17 (SCA17) locus in a group of ataxic patients excluded on other known SCAs; (2) assessment of frequency distributions of SCA17 alleles in the Yugoslav population. MATERIAL AND METHODS: Study includes 115 non-related Yugoslav patients belonging to autosomal-dominant cerebellar ataxias or to sporadic idiopathic adult-onset ataxia and 115 controls. Analysis of SCA17 locus was performed using polymerase chain reaction. RESULTS: None of the analyzed patients show the presence of mutation in SCA17 locus. In the group of patients 12 different alleles in the range of 30-42 repeats were observed, while in healthy population eight alleles in the range of 30-40 repeats were detected. CONCLUSION: (1) None of 115 non-related Yugoslav ataxic patients belong to any known SCAs nor to DRPLA gene; (2) the distribution of SCA17 alleles in the Yugoslav population is consistent with the distribution in other populations and (3) the paucity of alleles with more than 39 repeats could suggest that SCA17 is very rare in the Yugoslav population.     

Spinocerebellar ataxias in Asia: Prevalence,phenotypes and management

This paper reviews and summarizes three main aspects of spinocerebellar ataxias (SCA) in the Asian population. First, epidemiological studies were comprehensively reviewed. Overall, the most common subtypes include SCA1, SCA2, SCA3, and SCA6, but there are large differences in the relative prevalence of these and other SCA subtypes between Asian countries. Some subtypes such as SCA12 and SCA31 are rather specific to certain Asian populations. Second, we summarized distinctive phenotypic manifestations of SCA patients of Asian origin, for example a frequent co-occurrence of parkinsonism in some SCA subtypes. Lastly, we have conducted an exploratory survey study to map SCA-specific expertise, resources, and management in various Asian countries. This showed large differences in accessibility, genetic testing facilities, and treatment options between lower and higher income Asian countries.Currently, many Asian SCA patients remain without a final genetic diagnosis. Lack of prevalence data on SCA, lack of patient registries, and insufficient access to genetic testing facilities hamper a wider understanding of these diseases in several (particularly lower income) Asian countries.     

Spinocerebellar ataxias types 2 and 3: degeneration of the precerebellar nuclei isolates the three phylogenetically defined regions of the cerebellum

Summary. The precerebellar nuclei act as a gate for the entire neocortical, brainstem and spinal cord afferent input destined for the cerebellum. Since no pathoanatomical studies of these nuclei had yet been performed in spinocerebellar ataxia type 2 (SCA2) or type 3 (SCA3), we carried out a detailed postmortem study of the precerebellar nuclei in six SCA2 and seven SCA3 patients in order to further characterize the extent of brainstem degeneration in these ataxic disorders. By means of unconventionally thick serial sections through the brainstem stained for lipofuscin pigment and Nissl material, we could show that all of the precerebellar nuclei (red, pontine, arcuate, prepositus hypoglossal, superior vestibular, lateral vestibular, medial vestibular, interstitial vestibular, spinal vestibular, vermiform, lateral reticular, external cuneate, subventricular, paramedian reticular, intercalate, interfascicular hypoglossal, and conterminal nuclei, pontobulbar body, reticulotegmental nucleus of the pons, inferior olive, and nucleus of Roller) are among the targets of both of the degenerative processes underlying SCA2 and SCA3. These novel findings are in contrast to the current neuropathological literature, which assumes that only a subset of precerebellar nuclei in SCA2 and SCA3 may undergo neurodegeneration. Widespread damage to the precerebellar nuclei separates all three phylogenetically and functionally defined regions of the cerebellum, impairs their physiological functions and thus explains the occurrence of gait, stance, limb and truncal ataxia, dysarthria, truncal and postural instability with disequilibrium, impairments of the vestibulo-ocular reaction and optokinetic nystagmus, slowed and saccadic smooth pursuits, dysmetrical horizontal saccades, and gaze-evoked nystagmus during SCA2 and SCA3.     

Cerebellar Allografts Survive and Transiently Alleviate Ataxia in a Transgenic Model of Spinocerebellar Ataxia Type-1

Spinocerebellar ataxia type 1 (SCA-1) is one of several neurodegenerative diseases, including Huntington's disease, spinobulbar muscular atrophy, dentatorubral-pallidoluysian atrophy, and SCA-2, SCA-3, SCA-6, and SCA-7, each caused by an expanded number of CAG repeats in the coding region of their respective genes. The mechanism by which the resulting proteins are pathogenic is unknown. Clinical trials of neural transplants in Huntington's disease patients are under way. While initial reports are encouraging, definitive evidence of graft survival in patients despite the ongoing disease process is not possible with current imaging techniques. Transplants in primates have shown long-term survival of striatal grafts and recovery of function, but have used lesioning to model Huntington's phenotypically. Studies of striatal grafts in a transgenic mouse model of Huntington's have not yet shown a behavioral benefit. We describe a behavioral benefit of cerebellar grafts in a transgenic model of SCA-1 in which the ataxic phenotype results from expression of an expanded ataxin-1 protein. Mice were transplanted at an age when their ataxic phenotype is just becoming evident. Compared with sham-operated littermates, grafted mice showed better performance on multiple behavioral tests of cerebellar function. Differences persisted for 10 to 12 weeks posttransplant, after which there was a progressive decline in motor performance. At 20 weeks postsurgery, donor Purkinje cell survival was evident in 9 of 12 graft recipients. These results indicate that transplants can have behavioral benefits and grafts can survive long-term despite the ongoing pathological process in a brain actively expressing an expanded polyglutamine protein.     

Spinocerebellar ataxia type 6 (SCA6): neurodegeneration goes beyond the known brain predilection sites

Aims:  Spinocerebellar ataxia type 6 (SCA6) is a late onset autosomal dominantly inherited ataxic disorder, which belongs to the group of CAG repeat, or polyglutamine, diseases. Although, it has long been regarded as a 'pure' cerebellar disease, recent clinical studies have demonstrated disease signs challenging the view that neurodegeneration in SCA6 is confined to the well-known lesions in the cerebellum and inferior olive. Methods:  We performed a systematic pathoanatomical study throughout the brains of three clinically diagnosed and genetically confirmed SCA6 patients. Results:  This study confirmed that brain damage in SCA6 goes beyond the known brain predilection sites. In all of the SCA6 patients studied loss of cerebellar Purkinje cells and absence of morphologically intact layer V giant Betz pyramidal cells in the primary motor cortex, as well as widespread degeneration of brainstem nuclei was present. Additional damage to the deep cerebellar nuclei was observed in two of three SCA6 patients. Conclusions:  In view of the known functional role of affected central nervous grey components it is likely that their degeneration at least in part is responsible for the occurrence of a variety of SCA6 disease symptoms.     

Pathogenesis of spinocerebellar ataxias viewed from the RNA perspective

The underlying cause of a number of autosomal dominant spinocerebellar ataxias is the expansion of various types of simple sequence repeats located in diverse functional regions of different single genes. The genetic heterogeneity of these diseases which contrasts with the similarity of their pathology sites and clinical symptoms justifies the search for the shared mechanism of pathogenesis. In this article we discuss the arguments which are in favor of the RNA-mediated pathomechanism.     

脊髓小脑性共济失调2型的分子遗传学诊断及临床分析

目的:研究分析脊髓小脑性共济失调2型(SCA2)的分子遗传学诊断、应用以及临床表现特征。方法:对来自广西地区临床诊断为SCA的1个家系2例患者和8名"健康"家系成员,以及35名正常对照人员,通过聚合酶链式反应、琼脂糖电泳等技术检测SCA2基因位点内CAG三核苷酸重复扩增次数,并对异常等位基因片段进行DNA测序。结果:我国广西正常人群SCA2等位基因CAG重复数为20～29次,1家系中2例患者与1例症状前患者存在SCA2(CAG)n扩展突变,拷贝数分别为42、45、55次。结论:首次发现广西SCA2,利用分子遗传学分析可进行SCA2基因诊断,为症状前诊断及遗传咨询提供依据。     

Spinocerebellar ataxia type 4 (SCA4): Initial pathoanatomical study reveals widespread cerebellar and brainstem degeneration

Summary. Spinocerebellar ataxia type 4 (SCA4), also known as ‘hereditary ataxia with sensory neuropathy’, represents a very rare, progressive and untreatable form of an autosomal dominant inherited cerebellar ataxia (ADCA). Due to a lack of autopsy cases, no neuropathological or clinicopathological studies had yet been performed in SCA4. In the present study, the first available cerebellar and brainstem tissue of a clinically diagnosed and genetically-confirmed German SCA4 patient was pathoanatomically studied using serial thick sections. During this systematic postmortem investigation, along with an obvious demyelinization of cerebellar and brainstem fiber tracts we observed widespread cerebellar and brainstem neurodegeneration with marked neuronal loss in the substantia nigra and ventral tegmental area, central raphe and pontine nuclei, all auditory brainstem nuclei, in the abducens, principal trigeminal, spinal trigeminal, facial, superior vestibular, medial vestibular, interstitial vestibular, dorsal motor vagal, hypoglossal, and prepositus hypoglossal nuclei, as well as in the nucleus raphe interpositus, all dorsal column nuclei, and in the principal and medial subnuclei of the inferior olive. Severe neuronal loss was seen in the Purkinje cell layer of the cerebellum, in the cerebellar fastigial nucleus, in the red, trochlear, lateral vestibular, and lateral reticular nuclei, the reticulotegmental nucleus of the pons, and the nucleus of Roller. In addition, immunocytochemical analysis using the anti-polyglutamine antibody 1C2 failed to detect any polyglutamine-related immunoreactivity in the central nervous regions of this SCA4 patient studied. In view of the known functional role of affected nuclei and related fiber tracts, the present findings not only offer explanations for the well-known disease symptoms of SCA4 patients (i.e. ataxic symptoms, dysarthria and somatosensory deficits), but for the first time help to explain why diplopia, gaze-evoked nystagmus, auditory impairments and pathologically altered brainstem auditory evoked potentials, saccadic smooth pursuits, impaired somatosensory functions in the face, and dysphagia may occur during the course of SCA4. Finally, the results of our immunocytochemical studies support the concept that SCA4 is not a member of the CAG-repeat or polyglutamine diseases. Y. Hellenbroich and K. Gierga are joint first authors C. Zühlke and U. Rüb are joint senior authors     

Spinocerebellar ataxia type 6: CAG trinucleotide expansion, clinical characteristics and sperm analysis

Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant spinocerebellar degeneration caused by CAG repeat expansions in the human α1A voltage-dependent calcium channel subunit gene. We analyzed 16 SCA6 patients in 14 unrelated Japanese families, and documented the clinical and molecular properties correlating with the CAG repeat expansion. Three of them were sporadic. The CAG repeat number of the expanded and normal alleles was 22.7 ± 2.0 (mean ± SD, n = 15) and 13.8 ± 2.0 (n = 15), respectively, and the repeat size of the expanded alleles correlated inversely with age at onset. The patients presented here were clinically characterized by a slowly progressive cerebellar ataxia and nystagmus. In leukocytes, the strict pattern of the peak in the expanded allele on polyacrylamide gel electrophoresis did not show the presence of cell mosaicism in SCA6, in contrast to other trinucleotide disorders. Moreover, in each patient, the number of CAG repeats in sperm was the same as in leukocytes, and the expanded alleles in sperm indicated uniform peaks as well. In our geographic area, the frequency of SCA6 was as high as MJD, in contrast to the low frequency of other autosomal dominant cerebellar ataxias. Thus, a geographic difference in the frequency of autosomal dominant spinocerebellar ataxias may be present in Japan.     

Subclinical pulmonary dysfunction in spinocerebellar ataxias 1, 2 and 3

Sriranjini SJ, Pal PK, Krishna N, Sathyaprabha TN. Subclinical pulmonary dysfunction in spinocerebellar ataxias 1, 2 and 3. Acta Neurol Scand: 2010: 122: 323–328. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives – Evaluation of pulmonary function in patients with spinocerebellar ataxias (SCA) 1, 2 and 3 without clinical evidence of pulmonary dysfunction. Methods – Thirty patients (F:M = 7:23; age: 35 ± 11.3 years; SCA1 – 13, SCA2 – 9 and SCA3 – 8) without clinical manifestations of respiratory dysfunction and 30 controls underwent pulmonary function tests. The percentage predicted values of forced vital capacity (FVC), volume of air exhaled during first second of FVC (FEV1), peak expiratory flow rate (PEFR) and maximal voluntary ventilation (MVV), actual values of maximal inspiratory and expiratory pressures (MIP and MEP in mmHg), and ratios of actual values of FEV1/FVC (%) and FEV1/PEFR (ml/l/min) were analyzed. Results – Compared with controls SCA patients had significant reductions of FVC (71.1 ± 17.5 vs 85.5 ± 18.7; P < 0.01), PEFR (51.5 ± 20.7 vs 77.1 ± 24.9; P < 0.001), MVV (64.4 ± 21.6 vs 97.2 ± 22.7; P < 0.001), MIP (27.7 ± 16.8 vs 50.1 ± 15.1; P < 0.001) and MEP (38.1 ± 18.7 vs 74.7 ± 16.0; P < 0.001), elevation of FEV1/PEFR (10.5 ± 2.8 vs 7.4 ± 2.1; P < 0.001), but no significant change of FEV1 and FEV1/FVC. FEV1/PEFR correlated positively with illness duration and MVV negatively with severity of illness. Conclusions – The present study showed subclinical restrictive type of pulmonary dysfunction in SCA, and possible presence of upper airway obstruction. Chest physiotherapy and breathing exercises should be introduced early in management of SCA.     

Degeneration of ingestion-related brainstem nuclei in spinocerebellar ataxia type 2, 3, 6 and 7

Dysphagia, which can lead to nutritional deficiencies, weight loss and dehydration, represents a risk factor for aspiration pneumonia. Although clinical studies have reported the occurrence of dysphagia in patients with spinocerebellar ataxia type 2 (SCA2), type 3 (SCA3), type 6 (SCA6) and type 7 (SCA7), there are neither detailed clinical records concerning the kind of ingestive malfunctions which contribute to dysphagia nor systematic pathoanatomical studies of brainstem regions involved in the ingestive process. In the present study we performed a systematic post mortem study on thick serial tissue sections through the ingestion-related brainstem nuclei of 12 dysphagic patients who suffered from clinically diagnosed and genetically confirmed spinocerebellar ataxias assigned to the CAG-repeat or polyglutamine diseases (two SCA2, seven SCA3, one SCA6 and two SCA7 patients) and evaluated their medical records. Upon pathoanatomical examination in all of the SCA2, SCA3, SCA6 and SCA7 patients, a widespread neurodegeneration of the brainstem nuclei involved in the ingestive process was found. The clinical records revealed that all of the SCA patients were diagnosed with progressive dysphagia and showed dysfunctions detrimental to the preparatory phase of the ingestive process, as well as the lingual, pharyngeal and oesophageal phases of swallowing. The vast majority of the SCA patients suffered from aspiration pneumonia, which was the most frequent cause of death in our sample. The findings of the present study suggest (i) that dysphagia in SCA2, SCA3, SCA6 and SCA7 patients may be associated with widespread neurodegeneration of ingestion-related brainstem nuclei; (ii) that dysphagic SCA2, SCA3, SCA6 and SCA7 patients may suffer from dysfunctions detrimental to all phases of the ingestive process; and (iii) that rehabilitative swallow therapy which takes specific functional consequences of the underlying brainstem lesions into account might be helpful in preventing aspiration pneumonia, weight loss and dehydration in SCA2, SCA3, SCA6 and SCA7 patients.     

Spinocerebellar ataxias caused by polyglutamine expansions: A review of therapeutic strategies

Six of the spinocerebellar ataxias (SCAs) are caused by expanded CAG trinucleotide repeats encoding polyglutamine tracts in different genes. Together with three other neurodegenerative diseases they represent the polyglutamine repeat disorders. These disorders share many pathological features beyond a common genetic mechanism. They are the subject of considerable research efforts to elucidate their basic pathophysiologies, with the hope of using this knowledge to develop disease modifying treatments. Here we examine the biology that underpins possible therapeutic strategies for the SCAs caused by CAG repeats and review supportive data from cell and animal models. Therapeutic strategies include silencing gene expression, increasing protein clearance, reducing the toxicity of the protein, influencing downstream pathways activated by the mutant protein and transplantation. We also consider strategies which have been tested in other polyglutamine diseases that may generalize to these SCAs. Finally, we review clinical trials and consider the problems of translating the increasing amount of promising laboratory data into human trials.     

Spinocerebellar ataxia type 6: Systematic patho‐anatomical study reveals different phylogenetically defined regions of the cerebellum and neural pathways undergo different evolutions of the degenerative process

Spinocerebellar ataxia type 6 is a late onset autosomal dominantly inherited ataxic disorder, and previous patho‐anatomical studies have only reported neurodegeneration in SCA6 as being confined to the cerebellar cortex, dentate nucleus and inferior olive. However, the characteristics of cerebellar symptoms and many poorly understood “extracerebellar” symptoms reveal the three cerebellar regions and the corresponding precerebellar nuclei may undergo differing evolution of the degenerative process, and a more widespread brainstem degeneration in SCA6. We carried out a detailed immunohistochemical study in two SCA6 patients who had rather early onset and short disease duration with 25 CAG repeats, which is atypical for SCA‐6. We investigated the severity of neurodegeneration in each of the cerebellar regions and the corresponding precerebellar nuclei, and further characterize the extent of brain degeneration. This study confirmed that vestibulocerebellar, spinocerebellum and pontocerebellar are consistent targets of the pathological process of SCA6, but the severity of neurodegeneration in each of them was different. Vestibulocerebellum and the inferior cerebellar peduncle undergo the most severe neurodegeneration, while neurodegeneration in the pontocerebellar is less severe. Furthermore, we observed obvious neurodegeneration in layers II and III of the primary motor cortex, vestibular nuclei, inferior olivary nucleus, nucleus proprius and posterior spinocerebellar tract. Our detailed postmortem findings confirmed that SCA6 was not a simple “pure” cerebellar disease, but a complex neurodegenerative disease in which the three cerebellar regions underwent different evolutions of neurodegeneration process, and the corresponding precerebellar nuclei and the neural pathway were all involved.     

Autonomic dysfunction in presymptomatic spinocerebellar ataxia type-2

Montes‐Brown J, Machado A, Estévez M, Carricarte C, Velázquez‐Pérez L. Autonomic dysfunction in presymptomatic spinocerebellar ataxia type‐2.
Acta Neurol Scand: 2012: 125: 24–29.
© 2011 John Wiley & Sons A/S. Objectives – To explore and quantify possible abnormalities in the autonomic cardiovascular regulation in presymptomatic stage of type 2 spinocerebellar ataxia (PS‐SCA2). Materials & methods – Heart rate variability (HRV) for 5‐min series of RR intervals was analyzed in 48 PS‐SCA2. Autonomic testing included resting recording, standing, Valsalva maneuver, and deep breathing. The results were compared with a group of sex‐ and age‐matched controls. Results – Time‐and‐frequency domain HRV indices were significantly different between PS‐SCA2 and control groups. Using two standard diagnostic procedures were identified 4 (8.33%) subjects with severe and 8 (16.66%) subjects with early cardiac autonomic neuropathy in PS‐SCA2. CAG index significantly correlated with age (?0.35) and HR (0.31). Conclusions – Our results confirm the presence of cardiovascular autonomic dysfunction in PS‐SCA2 subjects.     

脊髓小脑共济失调2型临床和神经影像学特征分析

研究背景脊髓小脑共济失调2型(SCA2)为常染色体显性遗传性疾病,是由致病基因ATXN2编码区胞嘧啶-腺嘌呤-鸟嘌呤(CAG)三核苷酸重复序列扩展突变引起,目前较公认的正常重复范围为13~31次,异常重复范围>34次。主要表现包括小脑共济失调、眼肌麻痹、慢眼动、腱反射减弱,可伴有动作性震颤、智力减退和周围性感觉神经病等;头部MRI显示脑干、小脑明显萎缩(典型的橄榄脑桥小脑萎缩改变)。本研究针对5例经基因检测明确诊断的SCA2家系先证者进行临床和影像学特点,以及表型与基因型相关性分析。方法对708例常染色体显性遗传性SCA家系的先证者和119例临床拟诊SCA的散发患者进行常规基因学检测,分析SCA1~3、6、7、17型和齿状核红核苍白球路易体萎缩致病基因CAG序列重复动态突变。采用聚合酶链反应扩增重复序列、琼脂糖凝胶电泳检测扩增产物,对于出现2个电泳条带的样品通过荧光标记毛细管电泳片段分析方法进行重复序列计数。结合基因学检测结果,对患者临床表型和神经影像学特征进行分析。结果其中45例患者携带SCA2基因CAG重复扩展突变,临床表现为小脑共济失调、眼肌麻痹、慢眼动、腱反射减弱或消失,部分患者可伴有动作性震颤,MRI均显示脑干、小脑明显萎缩。其中5例典型病例的临床表型均与其基因型相符。结论基因学检测可为SCA2的明确诊断提供依据,临床和神经影像学特征有助于诊断与鉴别诊断。对于携带中间重复等位基因个体的诊断,需结合临床和影像学特点以及家系上下代动态突变进行分析。     

Spinocerebellar ataxia type 7 (SCA7): widespread brain damage in an adult-onset patient with progressive visual impairments in comparison with an adult-onset patient without visual impairments

Spinocerebellar ataxia type 7 (SCA7) represents a rare and severe autosomal dominantly inherited ataxic disorder and is among the known CAG-repeat, or polyglutamine, diseases. In contrast to other currently known autosomal dominantly inherited ataxic disorders, SCA7 may manifest itself with different clinical courses. Because the degenerative changes evolving during these different clinical courses are not well known, many neurological disease symptoms still are unexplained. We performed an initial pathoanatomical study on unconventional thick tissue sections of the brain of a clinically diagnosed and genetically confirmed adult-onset SCA7 patient with progressive visual impairments. In this patient we observed loss of myelinated fibres in distinct central nervous fibre tracts, and widespread degeneration of the cerebellum, telencephalon, diencephalon and lower brainstem. These degenerative changes offer appropriate explanations for a variety of less-understood neurological symptoms in adult-onset SCA7 patients with visual impairments: gait, stance and limb ataxia, falls, dysarthria, dysphagia, pyramidal signs, Parkinsonian features, writing problems, impairments of saccades and smooth pursuits, altered pupillary functions, somatosensory deficits, auditory deficits and mental impairments.     

Spinocerebellar ataxias type 1 and 2: comparison of clinical, electrophysiological and magnetic resonance evaluation

BACKGROUND AND PURPOSE: Spinocerebellar ataxias type 1 (SCA1) and type 2 (SCA2) belong to neurodegenerative disorders of autosomal dominant inheritance, genetically and clinically heterogeneous, caused by the expansion of CAG trinucleotides. Trunk and limb ataxia, dysarthria, dysphagia, gaze palsy, sensory and motor axonal neuropathy are the dominant features in both entities. The aim of the study was to evaluate the differences between genotype and phenotype based on clinical and electrophysiological assessment of the visual, auditory pathways, and EEG alterations in comparison with the cerebellar and brain atrophy in MRI. MATERIAL AND METHODS: 44 patients with SCA1 and 24 cases with SCA2 confirmed molecularly were examined neurologically and using the International Cooperative Ataxia Rating Scale (ICARS). A correlation of clinical symptoms and signs, and CAG repeat numbers with EEG, visual (VEP) and brainstem auditory (BAEP) evoked potentials, and MRI alterations were evaluated. RESULTS: A statistically significant negative correlation between the age of disease onset and number of CAG repeats in both types of SCA was found. Examined patients with SCA2 were younger, with longer disease duration and more pronounced cerebellar and brain atrophy in MRI. We found a significant correlation between ICARS and CAG repeats in this group. The dysphagia, pyramidal tract involvement and depressive reaction were significantly frequent in SCA1 patients. However in SCA2 patients, the peripheral nerve damage and extrapyramidal signs were more prominent. The amplitude of P100 visual evoked potentials was significantly lower in SCA1 patients and negatively correlated with CAG repeats. CONCLUSIONS: These results provide further evidence for the phenotypic differences of genetically defined SCA1 and SCA2 patients, expressed by more frequent involvement of the pyramidal tract and depression reaction in SCA1, in contrast to peripheral nerve involvement and extrapyramidal signs in the clinical feature of SCA2 phenotype. Furthermore, atrophy of the brain and cerebellum revealed in MRI was more pronounced than electrophysiological functional alterations, especially in SCA2. The decreased amplitude of P100 VEP in SCA1 patients was the only electrophysiological parameter differentiating between both groups of patients.