Albert Stezin1, Soumya D Venkatesh2, Kandavel Thennarasu3, Meera Purushottam2, Sanjeev Jain4, Ravi Yadav5, Pramod Kumar Pal6. 1. Department of Neurology, National Institute of Mental Health & Neurosciences (NIMHANS), Hosur Road, Bangalore 560029, Karnataka, India; Department of Clinical Neurosciences, National Institute of Mental Health & Neurosciences (NIMHANS), Hosur Road, Bangalore 560029, Karnataka, India. 2. Department of Molecular genetics, National Institute of Mental Health & Neurosciences (NIMHANS), Hosur Road, Bangalore 560029, Karnataka, India. 3. Department of Biostatistics, National Institute of Mental Health & Neurosciences (NIMHANS), Hosur Road, Bangalore 560029, Karnataka, India. 4. Department of Molecular genetics, National Institute of Mental Health & Neurosciences (NIMHANS), Hosur Road, Bangalore 560029, Karnataka, India; Department of Psychiatry, National Institute of Mental Health & Neurosciences (NIMHANS), Hosur Road, Bangalore 560029, Karnataka, India. 5. Department of Neurology, National Institute of Mental Health & Neurosciences (NIMHANS), Hosur Road, Bangalore 560029, Karnataka, India. 6. Department of Neurology, National Institute of Mental Health & Neurosciences (NIMHANS), Hosur Road, Bangalore 560029, Karnataka, India. Electronic address: pal.pramod@rediffmail.com.
Abstract
INTRODUCTION: To evaluate the non-ataxic clinical manifestations in genetically proven Spinocerebellar ataxia 2 (SCA2) and identify their determinants and predictors. METHODS: Seventy-three subjects with genetically proven SCA2 were evaluated clinically for the common non-ataxic manifestations. Based on the presence or absence of non-ataxic manifestations, patients were classified into groups and then compared for significant differences in the CAG repeat length, age at onset (AAO), duration of disease, and ataxia rating score. Predictors of non-ataxic symptoms were identified using multivariable binary logistic regression. RESULTS: The most common non-ataxic clinical manifestations were peripheral neuropathy, extrapyramidal features, pyramidal signs, cognitive impairment and lower motor neuron signs. The CAG repeat length was inversely related to the AAO of symptoms (r = -0.46, p < .001). Patients with peripheral neuropathy and psychiatric symptoms had earlier AAO. Patients with cognitive impairment and extrapyramidal symptoms had higher CAG repeat length whereas presence of lower motor neuron signs was more common in patients with lower CAG repeat length. CONCLUSION: The lower strength of association between CAG repeat length and AAO in our cohort suggests the presence of additional factors underlying the variability in AAO. Both CAG repeat length and AAO were identified as significant determinants and predictors of non-ataxic symptoms.
INTRODUCTION: To evaluate the non-ataxic clinical manifestations in genetically proven Spinocerebellar ataxia 2 (SCA2) and identify their determinants and predictors. METHODS: Seventy-three subjects with genetically proven SCA2 were evaluated clinically for the common non-ataxic manifestations. Based on the presence or absence of non-ataxic manifestations, patients were classified into groups and then compared for significant differences in the CAG repeat length, age at onset (AAO), duration of disease, and ataxia rating score. Predictors of non-ataxic symptoms were identified using multivariable binary logistic regression. RESULTS: The most common non-ataxic clinical manifestations were peripheral neuropathy, extrapyramidal features, pyramidal signs, cognitive impairment and lower motor neuron signs. The CAG repeat length was inversely related to the AAO of symptoms (r = -0.46, p < .001). Patients with peripheral neuropathy and psychiatric symptoms had earlier AAO. Patients with cognitive impairment and extrapyramidal symptoms had higher CAG repeat length whereas presence of lower motor neuron signs was more common in patients with lower CAG repeat length. CONCLUSION: The lower strength of association between CAG repeat length and AAO in our cohort suggests the presence of additional factors underlying the variability in AAO. Both CAG repeat length and AAO were identified as significant determinants and predictors of non-ataxic symptoms.
Authors: Daniel R Scoles; Warunee Dansithong; Lance T Pflieger; Sharan Paul; Mandi Gandelman; Karla P Figueroa; Frank Rigo; C Frank Bennett; Stefan M Pulst Journal: Hum Mol Genet Date: 2020-06-27 Impact factor: 6.150
Authors: Adriana Marcelo; Inês T Afonso; Ricardo Afonso-Reis; David V C Brito; Rafael G Costa; Ana Rosa; João Alves-Cruzeiro; Benedita Ferreira; Carina Henriques; Rui J Nobre; Carlos A Matos; Luís Pereira de Almeida; Clévio Nóbrega Journal: Cell Death Dis Date: 2021-11-29 Impact factor: 8.469