Subclinical pulmonary dysfunction in spinocerebellar ataxias 1, 2 and 3

Sriranjini, SJ; Pal, Pramod Kumar; Krishna, Nithin; Sathyaprabha, T.N.

doi:10.1111/j.1600-0404.2009.01306.x

Cited by 10 publications

(16 citation statements)

References 22 publications

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“…The present study found a reduced BPV in SCA patients compared to the controls, which could probably be attributed to impaired ventilation in these patients. A previous report shows pulmonary dysfunction and reduced respiratory muscle strength in SCA1 and SCA2 patients . This lack of integrity of respiratory muscles caused by dysfunctional cerebellar coordination (as proved by cerebellectomy) is an important feature in SCA patients .…”

Section: Discussionmentioning

confidence: 92%

Depressed baroreflex sensitivity from spontaneous oscillations of heart rate and blood pressure in SCA1 and SCA2

et al. 2019

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| INTRODUC TI ONSpinocerebellar ataxia (SCA) type 1 and 2 are dominantly inherited neurodegenerative disorders. These SCA subtypes are two of the most widely prevalent SCAs worldwide with a similar pattern found in India as well. SCA1 and SCA2 are caused by the abnormal expansion of CAG trinucleotide repeats in ATXN1 and ATXN2 genes, respectively. This results in progressive neuronal loss in the cerebellum along with certain cortical and subcortical brain regions in SCA subtypes 1,2 which subsequently leads to widespread clinical manifestations. Motor symptoms of SCA comprise cerebellar ataxia, peripheral neuropathy, ophthalmoplegia, pyramidal and extrapyramidal signs. 3 Furthermore, symptoms of autonomic dysfunction have also been observed in SCA patients. Thus, the evaluation of autonomic profile in SCA subtypes has an extensive clinical value. Objectives: To assess the time and frequency domain measures of cardiac autonomic activity/tone in patients of genetically defined spinocerebellar ataxia (SCA) types 1 and 2, as well as to decipher the probable associations among the cardiovascular autonomic parameters and genetic and clinical characteristics. Materials and methods:Simultaneous 5-min recording of RR interval (RRI) and blood pressure (BP) for the calculation of heart rate variability (HRV), blood pressure variability (BPV) and baroreflex sensitivity (BRS) were performed in genotypically confirmed SCA1 (n = 31) and SCA2 (n = 40) patients and healthy controls (n = 40).Additionally, the International Cooperative Ataxia Rating Scale (ICARS) was used for scoring of clinical severity in SCA patients.Results: Time and frequency domain parameters of HRV, BPV and BRS were depressed in SCA1 and SCA2 subtypes as compared to controls, although there was no statistically significant difference in autonomic tone between the two SCA subtypes.On correlation analysis, autonomic tone parameters were found to be associated with the clinical and genetic features of the SCA subtypes. Also, ICARS was associated with the genotype (CAG repeat length) in SCA2 patents. Conclusions:Cardiac autonomic tone is depressed in both SCA1 and 2 as compared to healthy controls while the two SCA subtypes do not differ in terms of autonomic tone. Also, a typical association exists between disease characteristics and autonomic indices. K E Y W O R D Sbaroreflex sensitivity, blood pressure variability, cardiac autonomic activity/tone, heart rate variability, spinocerebellar ataxia

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Section: Discussionmentioning

confidence: 92%

Depressed baroreflex sensitivity from spontaneous oscillations of heart rate and blood pressure in SCA1 and SCA2

et al. 2019

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“…Hence, the mild cortical and hippocampal developmental defects in the 14-3-3ε +/− mice are unlikely to be responsible for the nonrescued life span phenotype in Sca1 154Q/+ ; 14-3-3ε +/− mice. In the course of trying to understand the cause of death, we uncovered a respiratory dysfunction that had not been reported previously in the Sca1 knock-in mice but is documented in human patients (14). While we were investigating this phenotype, four mice (two Sca1 154Q/+ and two Sca1 154Q/+ ; 14-3-3ε +/− mice) died within 2 to 4 d of our last recording.…”

Section: Discussionmentioning

confidence: 99%

“…SCA1 usually causes onset of slowly progressive gait ataxia in midlife to late life, eventually impairing overall motor coordination and producing dysarthria, hypometric saccades, weight loss, respiratory dysfunction, and premature death (13,14). Cerebellar Purkinje cells are the first to be affected, which accounts for the presenting ataxia, but the pons and brainstem are also prominently involved.…”

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confidence: 99%

Regional rescue of spinocerebellar ataxia type 1 phenotypes by 14-3-3 ε haploinsufficiency in mice underscores complex pathogenicity in neurodegeneration

Jafar‐Nejad¹,

Ward²,

Richman

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by the expansion of a CAG repeat encoding a polyglutamine tract in Ataxin-1 (ATXN1). Both WT and mutant ATXN1 interact with 14-3-3 proteins, and 14-3-3 overexpression stabilizes ATXN1 levels in cells and increases ATXN1 toxicity in flies. To determine whether reducing 14-3-3 levels might mitigate SCA1 pathogenesis, we bred Sca1 154Q/+ mice to mice lacking one allele of 14-3-3ε. 14-3-3ε haploinsufficiency rescued cerebellar pathology and motor phenotypes but, surprisingly, not weight loss, respiratory dysfunction, or premature lethality. Biochemical studies revealed that reducing 14-3-3ε levels exerted different effects in two brain regions especially vulnerable in SCA1: Although diminishing levels of both WT and mutant ATXN1 in the cerebellum, 14-3-3ε haploinsufficiency did not alter ATXN1 levels in the brainstem. Furthermore, 14-3-3ε haploinsufficiency decreased the incorporation of expanded ATXN1 into its large toxic complexes in the cerebellum but not in the brainstem, and the distribution of ATXN1's small and large native complexes differed significantly between the two regions. These data suggest that distinct pathogenic mechanisms operate in different vulnerable brain regions, adding another level of complexity to SCA1 pathogenesis.

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“…Even though initial SCA studies have mostly focused on movement disorders, some have addressed pulmonary function in patients with SCAs and other neurodegenerative diseases like Parkinson's disease (PD) and Huntington's disease (HD) 9,20,21 . Sriranjini et al 9 pointed out that the lack of respiratory manifestations in SCA could explain the small number of studies in this area. These authors observed subclinical restrictive pulmonary dysfunction in individuals with ataxia and recommended early management with respiratory physical therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Sriranjini et al 9 showed a prevalence of restrictive pulmonary dysfunction and upper airway obstruction in patients with SCA1, SCA2, and SCA3; compared with controls, these patients presented significantly lower parameters of total lung volume and respiratory muscle strength. The authors observed subclinical pulmonary dysfunction in all subtypes of SCA analyzed, but the correlation between lung function and disease parameters occurred only in patients with SCA3.…”

mentioning

confidence: 98%

Assessment of ventilatory function in patients with spinocerebellar ataxia type 2

Mello

Zonta

Teive

et al. 2020

Arq. Neuro-Psiquiatr.

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Subclinical ventilatory dysfunction is observed in individuals with spinocerebellar ataxias (SCA). No studies have correlated ventilatory dysfunction to clinical and functional decline in SCA2. Objective: To evaluate the relationship between the values of peak expiratory flow (PEF), maximum inspiratory pressure (MIP), and presence of respiratory complaints with age, disease duration, age at onset of symptoms, balance scores, independence in basic (ADL) and instrumental (IADL) Activities of Daily Living (ADLs), and severity of ataxia (SARA) in individuals with SCA2. Methods: Cross-sectional study evaluating age, disease duration, age at onset of symptoms, scores in the Berg Balance Scale and in the SARA, Functional Independence Measure and Lawton’s scale, values of PEF and MIP, and the presence of respiratory complaints. Results: The study included 36 individuals with SCA2, with a mean age of 42.5±2.4 years, disease duration of 7.6±8.2 years, age 33.7±11.5 years at onset of symptoms, and 9.9±10.3 points in the SARA scale. The lowest PEF values correlated with the longer disease duration (p=0.021). The lowest values of PEF and MIP correlated with greater balance impairment (p=0.019 and p=0.045, respectively), increased degree of dependence in the ADL (p=0.006 and p=0.050, respectively) and IADL (p=0.003 and p=0.001, respectively) scales, and highest severity of ataxia (p=0.00 and p=0.017, respectively). Respiratory complaints were observed in 12 (33.3%) individuals and were not related to age, disease duration, age at onset of symptoms, balance, independence, ataxia severity, or PEF and MIP values. Conclusion: Ventilatory dysfunction, even when asymptomatic, is related to balance impairment, independence, and ataxia severity in individuals with SCA2.

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Subclinical pulmonary dysfunction in spinocerebellar ataxias 1, 2 and 3

Abstract: 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.

Cited by 10 publications

References 22 publications

Depressed baroreflex sensitivity from spontaneous oscillations of heart rate and blood pressure in SCA1 and SCA2

Depressed baroreflex sensitivity from spontaneous oscillations of heart rate and blood pressure in SCA1 and SCA2

Regional rescue of spinocerebellar ataxia type 1 phenotypes by 14-3-3 ε haploinsufficiency in mice underscores complex pathogenicity in neurodegeneration

Assessment of ventilatory function in patients with spinocerebellar ataxia type 2

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