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

Rüb, Udo; Brunt, Ewout; Seidel, Kay; Gierga, K.; Mooy, Cornelia M.; Kettner, Mattias; Broeckhoven, Christine Van; Bechmann, Ingo; Spada, Albert R. La; Schöls, Lüdger; Dunnen, Wilfred F. A. den; Vos, Rob A. I. de; Deller, Thomas

doi:10.1111/j.1365-2990.2007.00882.x

Cited by 32 publications

(29 citation statements)

References 58 publications

(167 reference statements)

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“…In the present pathoanatomical study, we confirmed the hypothesis that the brainstem auditory system, along with the vestibular, oculomotor, somatosensory, ingestion-related and precerebellar brainstem systems [11,15,21,22,35,36,[38][39][40][41] is among the consistent targets of the degenerative processes of SCA2, SCA3 and SCA7. Such a consistent and severe impairment of the auditory brainstem system, to the best of our knowledge, has never before been reported in other human neurodegenerative diseases.…”

Section: Discussionsupporting

confidence: 86%

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

Hoche

Seidel

Brunt

et al. 2008

Neuropathology Appl Neurobio

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The involvement of the auditory brainstem system offers plausible explanations for the auditory impairments detected in some of our and other SCA2, SCA3 and SCA7 patients upon bedside examination or neurophysiological investigation. However, further clinical studies are required to resolve the striking discrepancy between the consistent involvement of the brainstem auditory system observed in this study and the comparatively low frequency of reported auditory impairments in SCA2, SCA3 and SCA7 patients.

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Section: Discussionsupporting

confidence: 86%

“…The presence of intraneuronal aggregates with an expanded polyglutamine tract in the SCA2 patients and the occurrence of NI in the SCA3 and SCA7 patients was classified as absent (–) or present (+) (Table 2). The neuropathological findings of the two SCA7 patients have been recently reported [35,36].…”

Section: Methodsmentioning

confidence: 99%

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

Hoche

Seidel

Brunt

et al. 2008

Neuropathology Appl Neurobio

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“…Anatomical studies have shown severe cerebellar degeneration and region-specific neocortical atrophy in SCA 7 patients [56]. Functional imaging has shown reduced functional interaction between the cerebellum and the middle and superior frontal gyri, and disrupted functional connectivity between the visual and motor cortices compared with healthy controls.…”

Section: Differential Diagnosesmentioning

confidence: 99%

Central ocular motor disorders, including gaze palsy and nystagmus

et al. 2014

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An impairment of eye movements, or nystagmus, is seen in many diseases of the central nervous system, in particular those affecting the brainstem and cerebellum, as well as in those of the vestibular system. The key to diagnosis is a systematic clinical examination of the different types of eye movements, including: eye position, range of eye movements, smooth pursuit, saccades, gaze-holding function and optokinetic nystagmus, as well as testing for the different types of nystagmus (e.g., central fixation nystagmus or peripheral vestibular nystagmus). Depending on the time course of the signs and symptoms, eye movements often indicate a specific underlying cause (e.g., stroke or neurodegenerative or metabolic disorders). A detailed knowledge of the anatomy and physiology of eye movements enables the physician to localize the disturbance to a specific area in the brainstem (midbrain, pons or medulla) or cerebellum (in particular the flocculus). For example, isolated dysfunction of vertical eye movements is due to a midbrain lesion affecting the rostral interstitial nucleus of the medial longitudinal fascicle, with impaired vertical saccades only, the interstitial nucleus of Cajal or the posterior commissure; common causes with an acute onset are an infarction or bleeding in the upper midbrain or in patients with chronic progressive supranuclear palsy (PSP) and Niemann–Pick type C (NP-C). Isolated dysfunction of horizontal saccades is due to a pontine lesion affecting the paramedian pontine reticular formation due, for instance, to brainstem bleeding, glioma or Gaucher disease type 3; an impairment of horizontal and vertical saccades is found in later stages of PSP, NP-C and Gaucher disease type 3. Gaze-evoked nystagmus (GEN) in all directions indicates a cerebellar dysfunction and can have multiple causes such as drugs, in particular antiepileptics, chronic alcohol abuse, neurodegenerative cerebellar disorders or cerebellar ataxias; purely vertical GEN is due to a midbrain lesion, while purely horizontal GEN is due to a pontomedullary lesion. The pathognomonic clinical sign of internuclear ophthalmoplegia is an impaired adduction while testing horizontal saccades on the side of the lesion in the ipsilateral medial longitudinal fascicule. The most common pathological types of central nystagmus are downbeat nystagmus (DBN) and upbeat nystagmus (UBN). DBN is generally due to cerebellar dysfunction affecting the flocculus bilaterally (e.g., due to a neurodegenerative disease). Treatment options exist for a few disorders: miglustat for NP-C and aminopyridines for DBN and UBN. It is therefore particularly important to identify treatable cases with these conditions.

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“…The copyright holder for this preprint this version posted October 7, 2020. ; https://doi.org/10.1101/2020.10.05.20207340 doi: medRxiv preprint = 300 (10) and b = 1100 (60) s/mm 2 and phase-encode direction anterior-posterior), and T2 weighted (T2W) fast spin-echo volume (62 slices, TR: 7500 ms, TE: 100.74 ms, slice thickness: 2.5 mm, 0.9375 mm × 0.9375 mm in-plane resolution, FoV: 240x180 mm 2 , percent phase FoV: 80, flip angle: 90, matrix size 256x192).…”

Section: Image Acquisitionmentioning

confidence: 99%

In vivo assessment of neurodegeneration in Spinocerebellar Ataxia type 7

Parker

Merchant

Attaripour-Isfahani

et al. 2020

Preprint

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Spinocerebellar Ataxia type 7 (SCA7) is a neurodegenerative disease characterized by progressive cerebellar ataxia and retinal degeneration. Increasing loss of visual function complicates the use of clinical scales to track the progression of motor symptoms, hampering our ability to develop accurate biomarkers of disease progression, and thus test the efficacy of potential treatments. In this cross-sectional study, we aimed to identify imaging measures of neurodegeneration, which may more accurately reflect SCA7 severity and progression. We analyzed diffusion tensor imaging (DTI) data collected from a cohort of 13 SCA7 patients and 14 healthy volunteers using two recent methodological advances: 1) a diffusion tensor-based image registration technique, and 2) a dual-compartment DTI model to control for the potential increase in extracellular CSF-like water due to neurodegeneration. These methodologies allowed us to assess both volumetric and microstructural abnormalities in both white and gray matter brain-wide in SCA7 patients for the first time. To measure tissue volume, we performed diffusion tensor-based morphometry (DTBM) using the tensor-based registration. To assess tissue microstructure, we computed the parenchymal mean diffusivity (pMD) and parenchymal fractional anisotropy (pFA) using the dual compartment model. This model also enabled us to estimate the parenchymal volume fraction (pVF), a measure of parenchymal tissue volume within a given voxel. While DTBM and pVF revealed tissue loss primarily in the brainstem, cerebellum, thalamus, and a subset of cerebral white matter tracts in patients, pMD and pFA detected microstructural abnormalities brain-wide (p < 0.05, FWE corrected; Hedge's g > 1). This distinction was meaningful in terms of motor symptom severity, as we found that patient scores on the Scale for the Assessment and Rating of Ataxia correlated most strongly with cerebellar pVF (r = -0.66, p = 0.015) and global white matter pFA (r = -0.64, p = 0.018). Since this contrast between focal tissue loss and global microstructural abnormality has previously been described in neuropathology, we believe the approach employed here is well suited for the in-vivo assessment of neurodegeneration. Moving forward, this approach could be applied to characterize the full spatiotemporal pattern of neurodegeneration in SCA7, and potentially develop an accurate imaging biomarker of disease progression.

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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

Cited by 32 publications

References 58 publications

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

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

Central ocular motor disorders, including gaze palsy and nystagmus

In vivo assessment of neurodegeneration in Spinocerebellar Ataxia type 7

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