Quantitative analysis of brain atrophy in patients with xeroderma pigmentosum group A carrying the founder mutation in Japan

Ueda, Takahiro; Kanda, Fumio; Nishiyama, Masahiro; Nishigori, Chikako; Toda, Tatsushi

doi:10.1016/j.jns.2017.08.3238

Cited by 8 publications

(13 citation statements)

References 17 publications

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“…We used our previously reported brain magnetic resonance imaging (MRI) volumetry data of cerebral gray matter in XP‐A patients to investigate the correlation between severity of neuropathy and gray matter volume (GMV) in XP‐A 19 . T1‐weighted images (T1WI) (TE = 3.3 ms, TR = 7.2 ms, flip angle = 8°, field of view [FOV] = 256 × 256 mm 2 , matrix = 512 × 512, ST = 0.8 mm) were obtained using a 3‐Tesla MRI scanner (Phillips Medical Systems, Eindhoven, Netherlands).…”

Section: Methodsmentioning

confidence: 99%

“…In almost 100% of XP‐A patients, both the central nervous system (CNS) and peripheral nervous system (PNS) are impaired 17 . Some studies have revealed progressive atrophy of the cerebellum, brainstem, and cerebrum starting from infancy 17‐19 . Although It has been proposed that PNS involvement in XP is a sensory dominant axonal neuropathy, the pattern of PNS involvement and its progression with age have not been clearly delineated 17 .…”

Section: Introductionmentioning

confidence: 99%

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Progressive length‐dependent polyneuropathy in xeroderma pigmentosum group A

et al. 2020

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Background: In this study, we aimed to investigate the progression of peripheral nervous system involvement in xeroderma pigmentosum group A (XP-A). Methods: We performed nerve conduction studies in 17 genetically confirmed XP-A patients and conducted follow-ups. Of these patients we also analyzed gray matter volume (GMV) using brain MRI and assessed the severity score of clinical and skin manifestation. Results: We found significant reduction in the motor and sensory nerve action potential amplitude and mild reduction in conduction velocity. These findings were predominant in sensory nerves and the lower limbs, were observed since early childhood, and gradually deteriorated with age. Conclusions: The electrophysiological characteristics of XP-A patients are consistent with length-dependent axonal polyneuropathy and there is progressive deterioration from early childhood.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Progressive length‐dependent polyneuropathy in xeroderma pigmentosum group A

et al. 2020

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“…38 The central nervous system is affected in 25% of XP patients, and an estimated 20% to 30% display sensorineural abnormalities that include ataxia, hearing loss, as well as sensory and sensorimotor peripheral neuropathies (Table 2). 35,[39][40][41][42][43][44][45] Of the XP genetic subtypes, XPA, XPB, XPD, XPF, and XPG are those that have been found to be associated in some cases with neurological symptoms, with XPA and XPD being the genetic subtypes most frequently associated with neurological degeneration. 46 Conversely, patients with XPC and XPE rarely display neurological manifestations, although there is one published case of an XPC patient developing a peripheral neuropathy at age 47.…”

Section: Xpmentioning

confidence: 99%

Peripheral neuropathies associated with DNA repair disorders

et al. 2022

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Repair of genomic DNA is a fundamental housekeeping process that quietly maintains the health of our genomes. The consequences of a genetic defect affecting a component of this delicate mechanism are quite harmful, characterized by a cascade of premature aging that injures a variety of organs, including the nervous system. One part of the nervous system that is impaired in certain DNA repair disorders is the peripheral nerve. Chronic motor, sensory, and sensorimotor polyneuropathies have all been observed in affected individuals, with specific physiologies associated with different categories of DNA repair disorders. Cockayne syndrome has classically been linked to demyelinating polyneuropathies, whereas xeroderma pigmentosum has long been associated with axonal polyneuropathies. Three additional recessive DNA repair disorders are associated with neuropathies, including trichothiodystrophy, Werner syndrome, and ataxia‐telangiectasia. Although plausible biological explanations exist for why the peripheral nerves are specifically vulnerable to impairments of DNA repair, specific mechanisms such as oxidative stress remain largely unexplored in this context, and bear further study. It is also unclear why different DNA repair disorders manifest with different types of neuropathy, and why neuropathy is not universally present in those diseases. Longitudinal physiological monitoring of these neuropathies with serial electrodiagnostic studies may provide valuable noninvasive outcome data in the context of future natural history studies, and thus the responses of these neuropathies may become sentinel outcome measures for future clinical trials of treatments currently in development such as adeno‐associated virus gene replacement therapies.

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“…However, neurological degeneration was also a major cause of death [ 1 ]. Brain atrophy, cerebellar and basal ganglia degeneration leading to ataxia and severe cognitive decline have all been observed in XP-A and XP-D patients [ 7 , 8 ]. In conjunction with central nervous system (CNS) deterioration, these patients have been observed to become areflexic and develop an axonal polyneuropathy as well as sensorineural hearing loss [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Differences in peripheral neuropathy in xeroderma pigmentosum complementation groups A and D as evaluated by nerve conduction studies

et al. 2021

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Background Xeroderma pigmentosum (XP) is a rare autosomal recessive genetic disorder with defective DNA nucleotide excision repair and associated with a high frequency of skin cancer. Approximately 25% of patients develop progressive neurological degeneration. Complementation groups XP-A and XP-D are most frequently associated with neurological disorders. Design/methods This is a retrospective review of patients with XP who were evaluated at NIH from 1986 to 2015 and had nerve conduction studies (NCS). In the complementation groups with peripheral neuropathy, further comparisons of the NCS were made with audiological, brain imaging, neuropsychological assessments that were also performed on most of the patients. Limited neuropathology of XP-A and XP-D patients were examined.. Results The 33 patients had NCS: XP-A (9 patients), XP-C (7 patients), XP-D (10 patients), XP-E (1 patient), XP-V (4 patients), and XP-unknown (2 patients). Peripheral neuropathy based on nerve conduction studies was documented only in two complementation groups: 78% (7/9) of XP-A patients had a sensorimotor neuropathy while 50% (5/10) of XP-D patients had a sensory neuropathy only. Analysis of sural sensory nerve amplitude in both complementation groups XP-A and XP-D correlated with sensorineural hearing loss (SNHL), MRI/CT severity, and Full-scale Intelligence Quotient (IQ). Analysis of fibular motor nerve amplitude in complementation XP-A correlated with SNHL and MRI/CT severity. Limited follow-up studies showed gradual loss of NCS responses compared to an earlier and more rapid progression of the hearing loss. Conclusions Despite similar brain imaging and audiological findings patients, XP-A and XP-D complementation groups differ in the type of neuropathy, sensorimotor versus sensory alone. A few cases suggest that sensorineural hearing loss may precede abnormal NCS in XP and therefore serve as valuable clinical indicators of XP patients that will later develop peripheral neuropathy.

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Quantitative analysis of brain atrophy in patients with xeroderma pigmentosum group A carrying the founder mutation in Japan

Abstract: This is the first quantitative report presenting with the progression of brain atrophy in patients with XP-A. It is revealed that the brain atrophy started from early childhood in Japanese patients with XP-A carrying the homozygous founder mutation.

Cited by 8 publications

References 17 publications

Progressive length‐dependent polyneuropathy in xeroderma pigmentosum group A

Progressive length‐dependent polyneuropathy in xeroderma pigmentosum group A

Peripheral neuropathies associated with DNA repair disorders

Differences in peripheral neuropathy in xeroderma pigmentosum complementation groups A and D as evaluated by nerve conduction studies

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