Neurologic involvement in cystinosis: Focus on brain lesions and new evidence of four-repeat (4R-) Tau immunoreactivity.

Autor: Nicoletti T; Department of Neurology, University Hospital Zurich, Zurich, Switzerland; Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Switzerland. Electronic address: tommasof.nicoletti@gmail.com., Bink A; Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Switzerland; Department of Neuroradiology, University Hospital Zurich, Switzerland., Helmchen B; Department of Pathology, University Hospital Zurich, Zurich, Switzerland., Briel N; Department of Neurology, University Hospital Zurich, Zurich, Switzerland; Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Switzerland; Center for Neuropathology and Prion Research, Ludwig-Maximilians-University, Munich, Germany., Frontzek K; Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland; Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London, UK., Vlad B; Department of Neurology, University Hospital Zurich, Zurich, Switzerland; Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Switzerland., Gaspert A; Department of Pathology, University Hospital Zurich, Zurich, Switzerland., Boudriot E; Department of Neurology, University Hospital Zurich, Zurich, Switzerland; Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Switzerland., Jung HH; Department of Neurology, University Hospital Zurich, Zurich, Switzerland; Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Switzerland., Reuss AM; Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland., Weller M; Department of Neurology, University Hospital Zurich, Zurich, Switzerland; Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Switzerland., Hortobágyi T; Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.
Jazyk: angličtina
Zdroj: Journal of the neurological sciences [J Neurol Sci] 2024 Jan 15; Vol. 456, pp. 122841. Date of Electronic Publication: 2023 Dec 10.
DOI: 10.1016/j.jns.2023.122841
Abstrakt: Nephropathic cystinosis is a rare autosomal recessive storage disorder caused by CTNS gene mutations, leading to autophagy-lysosomal pathway impairment and cystine crystals accumulation. Neurologic involvement is highly variable and includes both neurodevelopmental and neurodegenerative disturbances, as well as focal neurologic deficits. By presenting longitudinal data of a 28-year-old patient with a large infratentorial lesion, we summarized the pathology, clinical and imaging features of neurological involvement in cystinosis patients. Brain damage in form of cystinosis-related cerebral lesions occurs in advanced disease phases and is characterized by the accumulation of cystine crystals, subsequent inflammation with vasculitis-like features, necrosis, and calcification. Epilepsy is a frequent comorbidity in affected individuals. Steroids might play a role in the symptomatic treatment of "stroke-like" episodes due to edematous-inflammatory lesions, but probably do not change the overall prognosis. Lifelong compliance to depleting therapy with cysteamine still represents the main therapeutic option. However, consequences of CTNS gene defects are not restricted to cystine accumulation. New evidence of four-repeat (4R-) Tau immunoreactivity suggests concurrent progressive neurodegeneration in cystinosis patients, highlighting the need of innovative therapeutic strategies, and shedding light on the crosstalk between proteinopathies and autophagy-lysosomal system defects. Eventually, emerging easily accessible biomarkers such as serum neurofilament light chains (NfL) might detect subclinical neurologic involvement in cystinosis patients.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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