Cerebellar cognitive disorder parallels cerebellar motor symptoms in Friedreich ataxia

Naeije, Gilles; Rai, Myriam; Allaerts, Nick; Sjøgård, Martin; Tiège, Xavier De; Pandolfo, Massimo

doi:10.1002/acn3.51079

Cited by 40 publications

(35 citation statements)

References 32 publications

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“…Dysarthria and upper limb dysmetria point to more global cerebellar dysfunction, but do not allow distinction between cortical and DN pathology. However, the concomitant progression of cerebellar ataxia and CCAS in FRDA 31 contrasts with the dichotomy between cerebellar motor and nonmotor symptoms reported in other cerebellar pathologies where functional and anatomical studies point to a segregation between the cerebellar anterior lobe, responsible for motor functions, and the cerebellar posterior lobe, responsible for cognitive processes. These findings point to involvement of the DN, the axons of which form the dentatothalamic pathway connecting the cerebellum with many neocortical areas, affecting motor control as well as perceptual and cognitive processes.…”

Section: Affected Systems In Frdamentioning

confidence: 69%

“…Although cognitive disorders in FRDA are relatively subtle and less prominent than in other ataxias, and do not cause obvious functional impairment, evidence has accumulated that FRDA patients show features of CCAS, 30 the severity of which correlates with cerebellar impairment. 31 Two additional remarks need to be made about cerebellar signs and symptoms in an FRDA patient. First, some cerebellar signs and symptoms, in particular kinetic or ''intentional'' tremor, are absent or minimal in many or most individuals with FRDA.…”

Section: Cerebellar Systemmentioning

confidence: 99%

Section: Affected Systems In Frdamentioning

confidence: 99%

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Central Nervous System Therapeutic Targets in Friedreich Ataxia

et al. 2020

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Friedreich ataxia (FRDA) is an autosomal recessive inherited multisystem disease, characterized by marked differences in the vulnerability of neuronal systems. In general, the proprioceptive system appears to be affected early, while later in the disease, the dentate nucleus of the cerebellum and, to some degree, the corticospinal tracts degenerate. In the current era of expanding therapeutic discovery in FRDA, including progress toward novel gene therapies, a deeper and more specific consideration of potential treatment targets in the nervous system is necessary. In this work, we have reexamined the neuropathology of FRDA, recognizing new issues superimposed on classical findings, and dissected the peripheral nervous system (PNS) and central nervous system (CNS) aspects of the disease and the affected cell types. Understanding the temporal course of neuropathological changes is needed to identify areas of modifiable disease progression and the CNS and PNS locations that can be targeted at different time points. As most major targets of longterm therapy are in the CNS, this review uses multiple tools for evaluation of the importance of specific CNS locations as targets. In addition to clinical observations, the conceptualizations in this study include physiological, pathological, and imaging approaches, and animal models. We believe that this review, through analysis of a more complete set of data derived from multiple techniques, provides a comprehensive summary of therapeutic targets in FRDA.

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Section: Affected Systems In Frdamentioning

confidence: 69%

Section: Cerebellar Systemmentioning

confidence: 99%

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Central Nervous System Therapeutic Targets in Friedreich Ataxia

et al. 2020

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“…These neuro-ECD aspects remain unclear and are the subject of a prospective study (NCT03127709), but a possible diagnosis of ECD should be considered in the presence of progressive cognitive deterioration occurring in adult patients with no risk factors for early-onset dementia. Progressive cerebellar cognitive affective syndrome has been associated with DN and dentato-thalamic pathway degeneration in FRDA disease [24]. Hearing loss has been reported in up to 8% of ECD patients with skull base lesions [25].…”

Section: Discussionmentioning

confidence: 99%

Cerebellar ataxia and exercise intolerance in Erdheim-Chester disease

et al. 2021

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Background Erdheim-Chester disease (ECD), a rare disorder of monocyte/macrophage lineage, has been related to cerebellar dysfunction. To increase the awareness of this rare, protean disease, an unusual, myasthenia-like onset of ECD is reported. Case presentation A 42-year-old man presented with a 6-year history of mild evening fatigability in his four limbs followed by motor and cognitive symptoms associated with cerebellar atrophy, dentate nuclei and dentato-thalamic pathway degeneration. Magnetic resonance imaging revealed hyperintense signals in T2 and fluid-attenuated inversion recovery sequences within the pons, cerebellar white matter, dentate nuclei and globi pallidi in the absence of any contrast enhancement. Whole-body bone scintigraphy with 99Technetium - methylene diphosphonate and fluorodeoxyglucose-positron emission tomography both revealed symmetric uptake in the lower extremities a finding suggestive of a diagnosis of ECD. Histological examination revealed diffuse infiltration of CD 68+ histiocytes with foamy cytoplasms in the presence of B-type of Rapidly Accelerated Fibrosarcoma protein kinase (BRAF)V600E activating mutation in tumor cells. Conclusion In patients with myasthenia-like symptoms who test negatively for myasthenia gravis, neurodegenerative diseases, and disorders of the hypothalamus, a diagnosis of ECD should be taken into consideration.

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“…These neuro-ECD aspects remain unclear and are the subject of a prospective study (NCT03127709), but a possible diagnosis of ECD should be considered in the presence of progressive cognitive deterioration occurring in adult patients with no risk factors for early-onset dementia. Progressive cerebellar cognitive affective syndrome has been associated with DN and dentatothalamic pathway degeneration in FRDA disease (14). Hearing loss has been reported in up to 8% of ECD patients with skull base lesions (15).…”

Section: Discussionmentioning

confidence: 99%

An Unusual Case of Myasthenia-Like Presentation in Erdheim-Chester Disease

Lauricella

d’Amati

Ingravallo

et al. 2020

Preprint

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Background: Erdheim-Chester disease (ECD), a rare disorder of monocyte/macrophage lineage, has been related to cerebellar dysfunction. To increase the awareness of this rare, protean disease, an unusual, myasthenia-like onset of ECD is reported.Case presentation: A 42-year-old man presented with a 6-year history of mild evening fatigability in his four limbs followed by motor and cognitive symptoms associated with cerebellar atrophy, dentate nuclei and dentato-thalamic pathway degeneration. Magnetic resonance imaging revealed hyperintense signals in T2 and fluid-attenuated inversion recovery sequences within the pons, cerebellar white matter, dentate nuclei and globi pallidi in the absence of any contrast enhancement. Whole-body bone scintigraphy with 99Technetium - methylene diphosphonate and fluorodeoxyglucose-positron emission tomography both revealed symmetric uptake in the lower extremities a finding suggestive of a diagnosis of ECD. Histological examination revealed diffuse infiltration of CD 68+ histiocytes with foamy cytoplasms in the presence of B-type of Rapidly Accelerated Fibrosarcoma protein kinase (BRAF)V600E activating mutation in tumor cells.Conclusion: In patients with myasthenia-like symptoms who test negatively for myasthenia gravis, neurodegenerative diseases, and disorders of the hypothalamus, a diagnosis of ECD should be taken into consideration.

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Cerebellar cognitive disorder parallels cerebellar motor symptoms in Friedreich ataxia

Cited by 40 publications

References 32 publications

Central Nervous System Therapeutic Targets in Friedreich Ataxia

Central Nervous System Therapeutic Targets in Friedreich Ataxia

Cerebellar ataxia and exercise intolerance in Erdheim-Chester disease

An Unusual Case of Myasthenia-Like Presentation in Erdheim-Chester Disease

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