Abstract Details

Title Neurologic Involvement in Cystinosis: Focus on Brain Lesions and New Evidence of Four-repeat (4R-) Tauopathy

Topic General Neurology

Presentation(s) P6 - Poster Session 6 (8:00 AM-9:00 AM)

Poster/Presentation
Number 4-004

Objective To present a man with cystinosis-related cerebral lesions including a literature review focused on longitudinal clinical, imaging and pathology data.

Background Cystinosis is caused by CTNS mutations leading to autophagy-lysosomal pathway impairment and cystine crystals accumulation. Neurologic involvement is variable and includes both neurodevelopmental and neurodegenerative disturbances, as well as focal neurologic deficits. Compliance to depleting therapy with cysteamine still represents the main treatment option.

Design/Methods We selected studies describing clinical, imaging, and pathological features of patients with cystinosis-related cerebral lesions between 1979 and 2023. Inclusion criteria were one morphological (neuroimaging/neuropathology data) and one clinical criterion (slowly progressive vs acute/subacute neurologic symptoms). Other variables encompassed age, sex, onset of neurologic symptoms, age at cystinosis diagnosis, disease duration since kidney transplantation, age at kidney transplantation, years of cysteamine therapy, lesion topography, presence of epilepsy and lesion load.

Results Eleven cystinosis patients (mean age 24.1 years, male 78.8%) were included. Seven out of 11 patients presented with acute/subacute focal neurological deficits, whereas 4/11 showed a slowly progressive neurological deterioration. Five out of 10 patients had epilepsy. Brain lesions variably showed crystals, inflammation, necrosis and calcification. Furthermore, our patient showed new evidence of 4-repeat-tauopathy and increased serum neurofilament light chains (NfL). Lesion load positively correlated with age of neurological symptoms onset. Two patients showed improvement after steroid therapy. Two patients remained stable at follow-up under cysteamine treatment. The other patients (7/10) encountered neurologic deterioration and death.

Conclusions Cystinosis-related cerebral lesions occur in advanced disease phases and variably show accumulation of crystals, vasculitis-like features, necrosis, and calcification. Epilepsy is a frequent comorbidity. Steroids might play a role in the symptomatic treatment of edematous-inflammatory lesions. New evidence of 4R-tauopathy might suggest concurrent neurodegeneration shedding light on the crosstalk between proteinopathies and autophagy-lysosomal system defects. Biomarkers (e.g. NfL) might influence in future the management of (sub)clinical neurologic involvement in cystinosis.

Authors/Disclosures
Tommaso Nicoletti, MD (Universitätsmedizin Essen) PRESENTER	Dr. Nicoletti has nothing to disclose.
Andrea Bink (Universitätsspital Zürich)	No disclosure on file
Birgit Helmchen	No disclosure on file
Nils Briel, Jr., MD	Dr. Briel has nothing to disclose.
Karl Frontzek	No disclosure on file
Benjamin Vlad	No disclosure on file
Ariana Gaspert (University Hospital Zurich)	No disclosure on file
Elisabeth Boudriot (University Hospital Zurich)	No disclosure on file
Hans Heinrich Jung, MD	Dr. Jung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Jung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Jung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylan. Dr. Jung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi Aventis. Dr. Jung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus. Dr. Jung has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for CSL Behring. Dr. Jung has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Aventis. The institution of Dr. Jung has received research support from Swiss National Science Foundation.
Anna Maria Reuss	No disclosure on file
Michael Weller, MD (University Hospital Zurich)	Dr. Weller has received personal compensation in the range of $0-$499 for serving as a Consultant for Neurosense. Dr. Weller has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medac. Dr. Weller has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Weller has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Philogen. Dr. Weller has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Weller has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Servier. Dr. Weller has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Curevac. Dr. Weller has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Orbus. Dr. Weller has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novocure. The institution of Dr. Weller has received research support from Versameb.
Tibor Hortobagyi	No disclosure on file

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