Involvement of the auditory brainstem system in spinocerebellar ataxia type 2 (SCA2), type 3 (SCA3) and type 7 (SCA7)

Hoche, Franziska; Seidel, Kay; Brunt, Ewout; Auburger, Georg; Schöls, Lüdger; Bürk, Katrin; Vos, R A de; Dunnen, Wilfred F. A. den; Bechmann, Ingo; Egensperger, Rupert; Broeckhoven, Christine Van; Gierga, K.; Deller, Thomas; Rüb, Udo

doi:10.1111/j.1365-2990.2007.00933.x

Cited by 38 publications

(45 citation statements)

References 55 publications

(136 reference statements)

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“…In addition, their clinical symptoms showed no substantial differences to those of their affected family members and other described SCA2 patients. Together with the fact that the brain pathology of the monozygous SCA2 patient studied here included exclusively brain gray matter areas known to be regularly involved in heterozygous SCA2 patients [1,2,5,7,[12][13][14][15][16][17][18][19][20], this favors the view that the pathoanatomical results and conclusions of the present study not only are valid for monozygous SCA2 patients but can also be generalized to the situation of heterozygous SCA2 patients as well.…”

Section: Discussionsupporting

confidence: 53%

“…a-f Aldehydefuchsin Darrow red staining, 100 μm PEG sections. CP cerebral peduncle, ICP inferior cerebellar peduncle, IO inferior olive, LV lateral vestibular nucleus, RD red nucleus, SN Substantia nigra has been described in detail by recent studies, which could show that this polyglutamine disorder is among the neurodegenerative diseases associated with a very severe telencephalic, cerebellar, and brainstem neuronal loss [1,2,5,7,[12][13][14][15][16][17][18][19][20]. Despite these detailed analysis, up to now it has been impossible to reconstruct the spatiotemporal spread of the pathological process and to identify its early targets in SCA2 brains.…”

Section: Discussionmentioning

confidence: 99%

“…Investigation of the brain of a SCA2 patient in the initial clinical stage and such a comparatively short disease duration, to the best of our knowledge, could not be performed so far. Upon pathoanatomical investigation, the brain of this SCA2 patient showed degeneration of distinct brain gray matter areas, all of which are known to undergo severe neurodegeneration until the advanced clinical stages of SCA2 [1,2,5,7,[12][13][14][15][16][17][18][19][20].…”

Section: Discussionmentioning

confidence: 99%

“…Recent pathoanatomical studies revealed the widespread and consistent degeneration of a variety of brain structures in clinically diagnosed and genetically confirmed heterozygous SCA2 patients [1,2,4,5,[12][13][14][15][16][17][18][19][20]. These studies were confined to brains of SCA2 patients in the advanced clinical stages and with disease durations of more than 10 years.…”

Section: Introductionmentioning

confidence: 99%

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Spinocerebellar Ataxia Type 2 (SCA2): Identification of Early Brain Degeneration in One Monozygous Twin in the Initial Disease Stage

et al. 2010

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Spinocerebellar ataxia type 2 (SCA2) is a progressive autosomal dominantly inherited cerebellar ataxia and is assigned to the CAG repeat or polyglutamine diseases. Recent morphological studies characterized the pathoanatomical features in heterozygous SCA2 patients and revealed severe neuronal loss in a large variety of cerebellar and extra-cerebellar brain sites. In the present study, we examined the brain pathoanatomy of a monozygous twin of a large Hungarian SCA2 family with pathologically extended CAG repeats in both SCA2 alleles. This unique patient was in the initial clinical stage of SCA2 and died almost 3 years after SCA2 onset. Upon pathoanatomical investigation, we observed loss of giant Betz pyramidal cells in the primary motor cortex, degeneration of sensory thalamic nuclei, the Purkinje cell layer, and deep cerebellar nuclei, as well as select brainstem nuclei (i.e., substantia nigra, oculomotor nucleus, reticulotegmental nucleus of the pons, facial, lateral vestibular, and raphe interpositus nuclei, inferior olive). All of these degenerated brain gray matter structures are known as consistent targets of the underlying pathological process in heterozygous SCA2 patients. Since they were already involved in our patient within 3 years after disease onset, we think that we were for the first time able to identify the early brain targets of the pathological process of SCA2.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Spinocerebellar Ataxia Type 2 (SCA2): Identification of Early Brain Degeneration in One Monozygous Twin in the Initial Disease Stage

et al. 2010

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“…Parallel fibers are sparse and no climbing fibers are observed in the Purkinje cell dendritic trunks [44]. In the brainstem, the most noteworthy microscopic findings are the marked loss of inferior olive neurons and the widespread involvement of the auditory brainstem nuclei, in addition to the degeneration of pontine and other pre-cerebellar brainstem nuclei [70,71]. Another important neuropathological marker of SCA2 is the notable reduction of neurons of the substantia nigra in the mesencephalon and the extensive degeneration of several thalamic nuclei, such as the reticular, fasciculosus, ventral anterior, lateral geniculate body, and the anterior nuclei [72].…”

Section: Neuropathology and Morphometric Analysesmentioning

confidence: 98%

A Comprehensive Review of Spinocerebellar Ataxia Type 2 in Cuba

et al. 2011

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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 presymptomatic 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.

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Standardized Assessment of Hereditary Ataxia Patients in Clinical Studies

Paap

Roeske

Dürr

et al. 2016

Movement Disord Clin Pract

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Background Hereditary ataxias are a heterogeneous group of degenerative diseases of the cerebellum, brainstem, and spinal cord. They may present with isolated ataxia or with additional symptoms going beyond cerebellar deficits. There are an increasing number of clinical studies with the goal to define the natural history of these disorders, develop biomarkers, and investigate therapeutic interventions. Especially, early and preclinical disease stages are currently of particular interest. Methods and Results Evidence‐based, we review standards for sampling and storage of biomaterials, clinical and neuropsychological assessment, as well as neurophysiology and neuroimaging and recommendations for standardized assessment of ataxia patients in multicenter studies. Conclusions DNA, RNA, serum, and, if possible, cerebrospinal fluid samples should be processed following established standards. Clinical assessment in ataxia studies must include use of a validated clinical ataxia scale. There are several validated clinical ataxia scales available. There are no instruments that were specifically designed for assessing neuropsychological and psychiatric symptoms in ataxia disorders. We provide a list of tests that may prove valuable. Quantitative performance tests have the potential to supplement clinical scales. They provide additional objective and quantitative information. Posturography and quantitative movement analysis—despite valid approaches—require standardization before implemented in multicenter studies. Standardization of neurophysiological tools, as required for multicenter interventional trials, is still lacking. Future multicenter neuroimaging studies in ataxias should implement quality assurance measures as defined by the ADNI or other consortia. MRI protocols should allow morphometric analyses.

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Involvement of the auditory brainstem system in spinocerebellar ataxia type 2 (SCA2), type 3 (SCA3) and type 7 (SCA7)

Cited by 38 publications

References 55 publications

Spinocerebellar Ataxia Type 2 (SCA2): Identification of Early Brain Degeneration in One Monozygous Twin in the Initial Disease Stage

Spinocerebellar Ataxia Type 2 (SCA2): Identification of Early Brain Degeneration in One Monozygous Twin in the Initial Disease Stage

A Comprehensive Review of Spinocerebellar Ataxia Type 2 in Cuba

Standardized Assessment of Hereditary Ataxia Patients in Clinical Studies

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