Diagnosis Of Spinocerebellar Ataxia Research Articles

Clinical value of vestibulo-ocular reflex in the differentiation of spinocerebellar ataxias

The diagnosis of spinocerebellar ataxia (SCA) currently depends upon genetic testing. Although genetic testing for SCA is highly specific, clinical parameters for the differentiation of SCAs are still insufficient. We aimed to assess the vestibulo-ocular reflex (VOR) parameters of various SCA subtypes to determine whether they have substantial value in differential diagnosis. We consecutively enrolled 33 genetically confirmed SCA patients (SCA2 = 8, SCA3 = 6, SCA6 = 10, SCA7 = 9). Normative data were obtained from 36 age- and gender-matched healthy controls. Quantitative indicators of VOR were measured using video head impulse test (HIT) and combined ocular motor dysfunctions were investigated using video-oculography. Compared with the control group, the VOR gains in SCA2 were relatively spared, but were markedly decreased for all six canals in SCA3. The VOR gains for the posterior canals (PCs) were significantly decreased in SCA6, and for both vertical canals were decreased in SCA7. The VOR gains for the horizontal canals in SCA3 were negatively correlated with disease severity (R = -0.900, p = 0.037). Abnormal catch-up saccades were common in SCA3 and SCA6, rare in SCA7 and absent in SCA2. Spontaneous, headshaking-induced, and positional nystagmus were only documented in SCA6. SCA3 and SCA6 commonly showed horizontal gaze-evoked nystagmus, but SCA2 and SCA7 had characteristic saccadic slowing without gaze-evoked nystagmus. VOR impairments are common in SCAs, but their patterns vary depending on subtype. In addition to ocular motor characteristics, distinctive VOR performance for each subtype using video HIT may aid the differential diagnosis of the SCA genotypes.

Functionality and disease severity in spinocerebellar ataxias.

Spinocerebellar ataxias (SCAs) are a group of neurodegenerative diseases characterized by deterioration of balance and functionality that tends to follow disease progression. There is no established link between formal clinical markers for severity and functional/balance scores that could guide rehabilitation teams. To evaluate the relationship between functional scales and ataxia severity in order to identify cutoff landmarks for functional loss and estimate the mean SARA (Scale for Assessment and Rating of Ataxia) score for the risk ratings for falls on the BBS (Berg Balance Scale). Consecutive patients with a molecular diagnosis of SCA (total 89: 31 with SCA2 and 58 with SCA3) were assessed for functionality FIM-ADL (Functional Independence Measure-activities of daily living and Lawton-IADL (instrumental activities of daily living), balance (BBS) and disease severity (SARA). The main disability cutoff landmarks were that the need for supervision for FIM-ADL starts with 12 points on SARA and the need for supervision for Lawton-IADL starts with 14 points on SARA. The first items to require assistance were "expression" and "shopping", respectively. At 20 points on SARA, patients were dependent on all FIM and Lawton items. The item with the greatest impact on distinguishing dependents from independents was "means of transport" in Lawton-IADL and the domain "locomotion" in FIM-ADL. The mean SARA score for patients classified as low risk in the BBS was 9.9 points, and it was 17.4 for medium risk and 25.2 for high risk. Analysis on the correlation between the severity of ataxia and functional scales can form an important guide for understanding the progression of functional dependence among individuals with SCAs.

Molecular spectrum, family screening and genetic counselling of Spinocerebellar Ataxia (SCA) cases in an Indian scenario

Spinocerebellar Ataxia (SCA) is a heterogeneous adult-onset disorder with an autosomal dominant inheritance pattern mainly caused by triplet repeat expansions. Clinical diagnosis of SCA is based on phenotypic features followed by confirmation through molecular diagnosis. To identify status of repeat range in Indian SCA cases and provide extended family screening, we enrolled 70 clinical SCA suspects. For molecular diagnosis, multiplex PCR (M-PCR) was used for common Indian SCA subtypes 1, 2, 3, 6, 7, 10, 12 and 17. TP-PCR was further used in SCA2, 7 and 10 to identify larger expansions. Eighteen out of 70 SCA suspects (25%) were found to be positive for various SCA subtypes- (5 SCA1 (28%), 6 SAC2 (34%), 2 SCA3 (12%), 3 SCA7 (16%) and one each for SCA6 (1%) and SCA17 (1%) subtypes). Genetic counselling and extended family screening were offered to all positive cases and yielded additional nine cases. We have established M-PCR and TP-PCR to detect the CAG repeat expansion in SCA suspects. This method can confirm SCA subtypes in a reliable, rapid and cost-effective way. Genetic characterization of SCA-related genes has great clinical relevance, as it could provide additional information and guidance to clinicians and family members regarding prognosis.

A Brief Review on Spinocerebellar Ataxia and its Treatment

Ataxia is defined as a neurological sign including the lack of muscle movement coordination particularly of gait abnormality, talking changes, and also abnormality in eye actions. In ataxia, a part of nervous system is dysfunction which is also coordinate movement such as the cerebellum. In adults, ataxia can be acquired or genetic disorder. The Spinocerebellar ataxia is hereditary, progressive, degenerative, genetic disease or often fatel. There are no effective treatment and cure for Spinocerebellar ataxia (SCA). Spinocerebellar ataxia is a progressive disorders in which the cerebellum slowly degenerates. An average results estimated that 150,000 peoples in the United States have a diagnosis of Spinocerebellar ataxia (SCA) at any given time periods. Spinocerebellar ataxia (SCA) can affects anybody persons of at all ages. A current systemic review shows that the global prevalence of Spinocerebellar ataxia (SCA) is 3 in 100,000 people. However, a wide regional variation exists. SCA3 is common subtype around the world, SCA2 is additional prevalent in Cuba than SCA3 whilst SCA7 is the most frequent subtype in Venezuela due to strong founder’s effect. SCA6 is 1 of the most general ADCA in the North of England, with a global prevalence of 5.2/100,000.There are many different types of spinocerebellar ataxia (SCA) and each may have unique signs and symptoms. And these includes: Problems with coordination and balance (ataxia), Uncoordinated walk, poor hand eye coordination, Abnormal speech, Involuntary eye movement, Vision problems, Difficulty processing, Learning and remembering information. The hereditary ataxias are categorized by mode of inheritance and causative gene or chromosomal locus. The hereditary ataxias can be inherited in an autosomal dominant, autosomal recessive,or X-linked manner. Some types of SCA inherited in an autosomal dominant manner are caused by trinucleotide repeat expansions. A trinucleotide repeat is a segment of DNA that is repeated a number of times. It is normal for these repeats to exist and they typically do not cause any problems. Some Spinocerebellar ataxia SCAs remain unspecified and cannot be precisely diagnosed, but in the previous decades genetic testing has permissible precise identification of dozens of different SCAs and extra tests are being added each year. The spinocerebellar ataxia are classified SCA1 to SCA35for the treatment of SCA. There are no effective and cure treatment available for the spinocerebellar ataxia (SCA). But there are some methods; therapies and treatment are available which will be fruitful for the SCA. And these included the following: Meditation, Zolpidem, N-acetyl leucine, Rehabilitation

Spinocerebellar Ataxia Patient Perceptions Regarding Reproductive Options.

In vitro fertilization with preimplantation genetic testing is a growing reproductive option for people who want to avoid passing a single-gene condition on to their offspring. The spinocerebellar ataxias are a group of rare, autosomal-dominant neurodegenerative disorders which are strong candidates for the use of this technology. This study aimed to assess knowledge of genetic risk and perceptions of reproductive options in individuals with a diagnosis of spinocerebellar ataxia. We administered an online survey to U.S. residents of reproductive age who have been clinically or genetically diagnosed with spinocerebellar ataxia. We assessed their understanding of inheritance and their reproductive opinions. Of 94 participants, 70.2% answered all four inheritance questions correctly. The majority felt they could describe each reproductive option except prenatal diagnosis. Individuals were most interested in in vitro fertilization with preimplantation genetic testing: 48.4% (45 of 93) said they would consider it. They were least interested in prenatal diagnosis and donated embryos or gametes. Having spinocerebellar ataxia with anticipation and choosing inheritance risk as an important factor were both significantly associated with interest in preimplantation genetic testing. Choosing religion/morality as an important factor was associated with less interest in preimplantation genetic testing and prenatal diagnosis. Our population displayed basic knowledge of inheritance risk, and the majority wanted to avoid having affected children. Consistent with literature for other autosomal-dominant adult-onset conditions, individuals showed a preference for preimplantation genetic testing. Health care providers should continue to educate patients about reproductive options and their risks and limitations.

Safe Use of Epidural Analgesia in a Parturient With Spinocerebellar Ataxia: A Case Report.

A 28-year-old, gravida 7, para 4 woman with medical history of sickle cell trait presented to labor and delivery at 39 weeks of gestation for rupture of membranes. The patient had a history of suspected spinocerebellar ataxia with incomplete workup before the current admission. The patient requested epidural analgesia for labor. Epidural was placed at L3-L4 interspace without any complications and the rest of the labor was uneventful. Magnetic resonance imaging of the brain was performed after the delivery and the diagnosis of spinocerebellar ataxia was confirmed. The patient's neurological status remained stable after the procedure.

Diagnosis of Spinocerebellar Ataxia in the West Indies

Diagnosis of Spinocerebellar Ataxia in the West Indies

Diagnosis of Spinocerebellar Ataxia in the West Indies.

BackgroundAccess to medical care in many regions is limited by socioeconomic status, at both the individual and the community level. This report describes the diagnostic process of a family residing on an underserved Caribbean island where routine neurological care is typically addressed by general practitioners, and genetic diagnosis is not available through regular medical channels. The diagnosis and management of neurodegenerative disorders is especially challenging in this setting.Case ReportWe diagnosed a family with spinocerebellar ataxia type 3 (SCA3) in an underdeveloped nation with limited access to genetic medicine and no full-time neurologist.DiscussionMolecular diagnosis of the SCAs can be challenging, even in developed countries. In the Caribbean, genetic testing is generally only available at a small number of academic centers. Diagnosis in this family was ultimately made by utilizing an international, pro bono, research-based collaborative process. Although access to appropriate resources, such as speech, physical, and occupational therapies, is limited on this island because of economic and geographical factors, the provision of a diagnosis appeared to be ultimately beneficial for this family. Identification of affected families highlights the need for access to genetic diagnosis in all communities, and can help direct resources where needed.

Ethical considerations in presymptomatic diagnosis of autosomal dominant spinocerebellar ataxias

IntroductionInformation on achieving presymptomatic diagnosis of spinocerebellar ataxia (SCA) is limited. The advent of molecular diagnosis makes it possible to identify the carriers of different diseases and has also introduced the prospect of detecting diseases even before their onset. This has drawn attention to the ethical implications that must be considered in these subjects with a view to preserving their physical and psychological well-being. DevelopmentSCA is composed of a group of neurodegenerative disorders with autosomal dominant inheritance. Only a few publications have described the genetic counselling processes and guidelines to be followed during the process of presymptomatic diagnosis (PSD). The size of the multidisciplinary teams, their areas of expertise, and the number of counselling sessions are different for each of the studies analysed here. However, the basis of presymptomatic diagnosis originates in common guidelines to which members of our team have contributed recently. ConclusionPresymptomatic diagnosis should be performed according to guidelines that safeguard the subjects’ welfare. The diagnostic process is only recommended for patients over 18 years old with symptoms suggesting SCA, and a minimum risk of 50%. Genetic counselling programmes must be available in all centres that offer presymptomatic diagnosis of SCA.

Diagnosis of Spinocerebellar Ataxias Caused by Trinucleotide Repeat Expansions.

Spinocerebellar ataxias (SCAs) are a group of disorders that are both clinically and genetically heterogeneous. They usually demonstrate onset in adulthood, but some forms may have juvenile or infantile onset. There are many different types of SCA, demonstrating different modes of inheritance and types of mutation. The most common forms are due to dominantly inherited expansions in trinucleotide repeat sequences located within the coding region of the relevant genes, and these are readily identifiable by molecular genetic testing. In general, it is possible to test for these disorders using PCR-based assays, amplifying across the trinucleotide repeat regions and sizing the PCR products to determine the number of repeats. Larger expansions are generally associated with a more severe presentation of the disorder, and alternative methods may be necessary to detect these alleles. This protocol describes methods for detecting normal and expanded triplet repeat alleles in the most common SCA genes. © 2017 by John Wiley & Sons, Inc.

Successful Diagnosis of Spinocerebellar Ataxia in a Patient Presenting with Progressive Incoordination of Movements

A number of disorders cause ataxia which are the determinants of the choice of treatment for the patients affected by it. Correct diagnosis of the underlying disorder depends, not only on the qualification of the attending doctor but also on the accurate communication of the patient with the doctor. History thus plays a vital role in the diagnosis. Proper management might follow counselling sessions at times just to highlight the importance of history to a patient who is unaware about it. Here we present the case of a 32-year-old male who was experiencing progressive motor impairment. This report highlights the value of proper history in the diagnosis of the disease our patient is affected with.

Consideraciones éticas en el diagnóstico presintomático de ataxias espinocerebelosas autosómico dominantes

IntroductionInformation on achieving presymptomatic diagnosis of spinocerebellar ataxia (SCA) is limited. The advent of molecular diagnosis makes it possible to identify the carriers of different diseases and has also introduced the prospect of detecting diseases even before their onset. This has drawn attention to the ethical implications that must be considered in these subjects with a view to preserving their physical and psychological well-being. DevelopmentSCA is composed of a group of neurodegenerative disorders with autosomal dominant inheritance. Only a few publications have described the genetic counselling processes and guidelines to be followed during the process of presymptomatic diagnosis (PSD). The size of the multidisciplinary teams, their areas of expertise, and the number of counselling sessions are different for each of the studies analysed here. However, the basis of presymptomatic diagnosis originates in common guidelines to which members of our team have contributed recently. ConclusionPresymptomatic diagnosis should be performed according to guidelines that safeguard the subjects’ welfare. The diagnostic process is only recommended for patients over 18 years old with symptoms suggesting SCA, and a minimum risk of 50%. Genetic counselling programmes must be available in all centres that offer presymptomatic diagnosis of SCA.

Mutation analysis of 6 spinocerebellar ataxia (SCA) types in patients from southern Turkey.

Spinocerebellar ataxias (SCAs) are complex clinical and genetically heterogeneous, mostly autosomal dominant neurodegenerative diseases. At present, more than 30 hereditary SCA types have been associated with different gene mutations. In this study, the frequency distribution of the 6 SCA types 1, 2, 3, 6, 7, and 17 in the Turkish population was investigated with respect to clinical features. 159 patients who received a diagnosis of SCA and 42 healthy controls from Adana, Mersin, Gaziantep, Hatay, and Osmaniye provinces were included in the study. DNA samples were isolated from 2 mL blood samples and the number of trinucleotide repeats (TNRs) for each SCA type was detected using PCR-RFLP technique and sequencing. Of the 6 SCA types that were studied, 4 types, SCA 1, 3, 7, and 17, were positive and all heterozygous for expansions. SCA types 1 and 17 had higher frequencies, 4.4% and 3.8%, respectively, than SCA types 3 and 7. The clinical data of patients were also evaluated to correlate with the increased TNR numbers. This study, being the first mutation record of SCAs in this area, indicated that 9.4% of cases belonged to 4 types, SCA 1, 3, 7, and 17.

Distribution of five common subtypes of spinocerebellar ataxia in the Korean population

Purpose: Spinocerebellar ataxia (SCA) is a genetically heterogeneous disease for which more than 30 subtypes have been identified. However, 5 subtypes, SCA1, SCA2, SCA3, SCA6, and SCA7, account for more than 60% of cases. In this study, we report the distribution of these 5 subtypes in Korean patients. Materials and Methods: Six hundred and thirty-eight unrelated patients with a presumptive diagnosis of SCA were included in this study. Trinucleotide (CAG) repeat number (TNR) repeat number was determined using fluorescently labeled primers and fragment analysis. Results: A total of 128 unrelated patients (20.1% of all individuals tested) tested positive for SCA subtypes, including SCA1 (5 patients, 3.9% of those testing positive), SCA2 (38 patients, 29.7%), SCA3 (30 patients, 23.4%), SCA6 (39 patients, 30.5%), and SCA7 (16 patients, 12.5%). The mean copy number of pathogenic TNR alleles was 45±8.5 for SCA1, 42±3.1 for SCA2, 72±5.4 for SCA3, 23±1.5 for SCA6, and 50±11.4 for SCA7. TNR copy number was inversely correlated with onset age in SCA2, SCA6, and SCA7. Conclusion: SCA2, SCA3, and SCA6 are common SCA subtypes in Korean patients and could be screened as a first-line test. Expanded pathogenic allele size was associated with early onset age.

Clinical relevance of "bulging eyes" for the differential diagnosis of spinocerebellar ataxias

To investigate the relevance of the clinical finding of bulging eyes (BE) in a large Brazilian cohort of spinocerebellar ataxias (SCA), to assess its importance in clinical differential diagnosis among SCA. Three hundred sixty-nine patients from 168 Brazilian families with SCA were assessed with neurological examination and molecular genetic testing. BE was characterized by the presence of eyelid retraction. Genetically ascertained SCA3 was detected in 167 patients, SCA10 in 68 patients, SCA2 in 20, SCA1 in 9, SCA7 in 6, and SCA6 in 3 patients. BE was detected in 123 patients with SCA (33.3%), namely 109 of the 167 SCA3 patients (65.3%) and in 5 of the others SCA patients (1 SCA10 patient, 2 SCA1 patients and 2 SCA2 patients). BE was detected in the majority of patients with SCA3 (65.3%) and could be used with a clinical tool for the differential diagnosis of SCA.

Optic Atrophy Differentially Diagnosed as Spinocerebellar Ataxia from Leber Hereditary Optic Neuropathy by Gene Mutation Analysis

Optic atrophy describes a group of diseases of retinal ganglion cells and axons that eventually lead to loss of vision. Optic atrophy has both congenital and acquired causes, and its diagnosis (or differential diagnosis) is complicated. This case report describes a 20-year-old man who presented with a 1-year history of progressive vision loss in both eyes and no obvious systemic symptoms. Fundus examination revealed bilateral optic atrophy. Based on clinical characteristics, visual field analysis and pattern visual evoked potential examination, the presumptive diagnosis was Leber hereditary optic neuropathy (LHON). Analysis of mitochondrial DNA indicated the absence of all of three common mutations associated with LHON (m.3460G>A, m.11778G>A, m.14484T>C). Detailed questioning of the patient revealed a history of prolonged language development and poor balance. Neurological examination indicated abnormal co-ordination, suggesting the presence of inherited spinocerebellar ataxia (SCA). Analysis of the SCA7 gene revealed a high number of trinucleotide repeats [(CAG)(n), n > 64], confirming the diagnosis of SCA. The aetiology of optic atrophies is complicated and the molecular genetic detection approach provides the best information for diagnosing these diseases.

Essential tremor with ubiquitinated Purkinje cell intranuclear inclusions

Essential tremor with ubiquitinated Purkinje cell intranuclear inclusions

Frequencies of spinocerebellar ataxia subtypes in Thailand: window to the population history?

Spinocerebellar ataxias (SCAs) are a heterogeneous group of disorders with almost 30 subtypes. The prevalence and relative frequency of each subtype vary among different populations. In this article, we report the relative frequency of six SCA subtypes in the Thai population and attempt to explain the observed pattern when compared with other populations in this region. We searched for SCA type 1, SCA2, SCA3, SCA6, SCA7 and dentatorubral-pallidoluysian atrophy mutations using GeneScan analysis in 340 patients from 182 families, in which at least one person had a clinical diagnosis of SCA. We analyzed the relative frequencies of SCA subtypes on a family basis, and compared these with the data in the Chinese and Indian populations. SCA3 was found in 19.2% of the patients (Agresti-Coull 95% confidence interval: 14.1-25.6%), SCA1 in 11.5% (7.6-17.1%) and SCA2 in 10.4% (6.7-15.8%). SCA6 was found in three families, with a relative frequency of 1.6% (0.3-5.0%). Compared with the related populations, the Thai SCA3 frequency was less than that of the Chinese, whereas it was higher than that in most of the Indian studies. The reverse is true for the SCA1/SCA2 frequency. A similar study in Singapore, where there was a clear history of population admixture, also showed the frequencies between those of the Chinese and the Indian populations. Although SCA3 was the most common identifiable SCA subtype in Thailand, SCA1 and SCA2 were also relatively common. Our results also supported some degree of admixture with the Indians in the Thai population and justify further study in the area.

Ataxia espinocerebelosa tipo 7: descripción de una familia mexicana

Spinocerebellar ataxias (SCA) constitute a group of neurodegenerative diseases characterized by cerebellar disfunction alone or associated with other neurological anomalies. The combination of progressive cerebellar ataxia, macular pigment dystrophy, ophtalmoplegia, spasticity and an autosomal dominant pattern of transmission is characteristic of SCA 7. Genome wide linkage analysis mapped the defective gene to 3p12 13. To describe a Mexican family with SCA 7. We present a family pedigree of 13 individuals with ataxia and other neurologic findings in 3 generations. The evaluation consisted of a complete clinical and neurologic examination; neuropsychologic, neurophysiologic, ophthalmologic, neuroradiologic assessments and a molecular genetic study. The first 2 generations had a history of gait disturbance and visual loss. We objectively found a global cerebellar syndrome, pyramidal signs, visual impairment and ophtalmoparesis in variable grades in all members of the third generation All had progressive retinal degeneration, cerebellar, brainstem and hemispheric atrophy. We observed anticipation phenomena. Genetic analysis of the father of the third generation showed expansion of CAG triplet repeats at the SCA 7 gene. The clinical and genetic findings confirmed the diagnosis of SCA 7, and this is the first report in a Mexican family.

Extreme expansion detection in spinocerebellar ataxia type 2 and type 7.

The autosomal dominant cerebellar ataxias are each defined by progressive ataxia and variable association with other clinical findings (). Numerous spinocerebellar ataxia (SCA) loci have been identified and several of the SCA genes have expansion of a CAG-repeat as the underlying mutation (,). Assays that determine the CAG-repeat length in SCA1, SCA2, SCA3, SCA6, and SCA7 are used for both diagnostic and predictive testing purposes. Molecular genetic testing is necessary to establish a diagnosis of the SCAs that do not have unique clinical features. It is also a valuable tool in confirming a clinical diagnosis of SCAs that have characteristic clinical findings (such as retinal dystrophy in SCA7) (,). Assays typically utilize polymerase chain reaction (PCR) amplification of the repeat region, separation of PCR products by gel electrophoresis or capillary electrophoresis, and visualization of products by incorporation of radioactivity or dye into PCR products or staining with dye after product separation (, , ).