Clinical trial NCT05075798: Study of Cerebral MRI Anomalies in Mutated Transthyretin Amyloidosis Patients
Official title: A Comprehensive Retrospective Study of Cerebral MRI Anomalies in Mutated Transthyretin Amyloidosis Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Transthyretin Amyloidosis
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2021-10-13
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients followed at the University Hospital of Nîmes between 2017 and 2021 for a TTR neuropathy with proven mutation, having benefited from a brain MRI.

Brief summary: Transthyretin amyloidosis (aTTR) initially described as a rare disease, became the most serious hereditary polyneuropathy of adult onset and family screening has made it possible to identify and follow up many asymptomatic patients and carriers of the mutation in the TTR gene.

Considered as a systemic disease with involvement of target organs (the heart, the eye, the kidney and peripheral nervous system), it seems to be more complex for neurologists according to recent publications raising the issue of central nervous system involvement.

Indeed, TTR amyloid deposits seem to be correlated with the duration of the disease. These deposits can cause cortical damage by different mechanisms: direct TTR toxicity or as a result of pathology related to cerebral amyloid angiopathy (intraparenchymal or subarachnoid hematomas, small infarcts, hemosiderin). A small number of mutations in the TTR gene cause a rare phenotype of systemic amyloidosis, the oculoleptomeningeal form, characterized by clinical neurological symptoms: progressive dementia, epilepsy, ataxia, spastic paraparesis, stroke-like episodes.

Hypothesis of the work: the central nervous system involvement is probably underestimated on the radiological description in patients with TTR mutation.


Eligibility criteria: Inclusion Criteria:

* patients followed at the University Hospital of Nîmes between 2017 and 2021 for a TTR neuropathy with proven mutation, having benefited from a brain MRI.

Exclusion Criteria:

* Patients without TTR neuropathy with proven mutation, or who did not have a brain MRI.

Primary outcomes:
measure: Clinical-radiological characterization
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Nîmes
country: France
facility: CHU de Nîmes
Study officials:
affiliation: Centre Hospitalier Universitaire de Nīmes
name: Anissa MEGZARI
role: STUDY_DIRECTOR
References:
citation: Ikeda SI. [Cerebral amyloid angiopathy with familial transthyretin-derived oculoleptomeningeal amyloidosis]. Brain Nerve. 2013 Jul;65(7):831-42. Japanese.
citation: Vieira M, Saraiva MJ. Transthyretin: a multifaceted protein. Biomol Concepts. 2014 Mar;5(1):45-54. doi: 10.1515/bmc-2013-0038.
citation: Maia LF, Magalhaes R, Freitas J, Taipa R, Pires MM, Osorio H, Dias D, Pessegueiro H, Correia M, Coelho T. CNS involvement in V30M transthyretin amyloidosis: clinical, neuropathological and biochemical findings. J Neurol Neurosurg Psychiatry. 2015 Feb;86(2):159-67. doi: 10.1136/jnnp-2014-308107. Epub 2014 Aug 4.
citation: Nakagawa K, Sheikh SI, Snuderl M, Frosch MP, Greenberg SM. A new Thr49Pro transthyretin gene mutation associated with leptomeningeal amyloidosis. J Neurol Sci. 2008 Sep 15;272(1-2):186-90. doi: 10.1016/j.jns.2008.05.014. Epub 2008 Jun 24.
citation: Charidimou A, Gang Q, Werring DJ. Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry. 2012 Feb;83(2):124-37. doi: 10.1136/jnnp-2011-301308. Epub 2011 Nov 5.