The frequency of central nervous system complications in the Cypriot cohort of ATTRV30M neuropathy transplanted patients

Dardiotis, Efthimios; Andreou, Savanna; Aloizou, Athina‐Maria; Panayiotou, Elena; Siokas, Vasileios; Ioannou, Mihaela Nedea; Vounou, Emmelia; Christodoulou, Kyproula; Tanteles, George A.; Michaelides, Demos; Kyriakides, Theodoros

doi:10.1007/s10072-019-04176-9

Cited by 8 publications

(11 citation statements)

References 65 publications

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“…In rare patients with symptomatic hemorrhages, imaging or neuropathologic evaluation detected cerebellar and supratentorial microbleeds. 7,22 In 1 case, MRI evidence of microbleeds was temporally related to repeated TFNEs. 57 On the other hand, in the Japanese posttransplant cohort, brain MRIs from 5 patients with TFNEs showed no parenchymal lesions, despite the presence of substantial amyloid deposition, as measured by 11 C-Pittsburgh compound B PET ( 11 C-PiB-PET).…”

Section: Imaging and Other Biomarkersmentioning

confidence: 99%

“…Since 2015, several studies have shown that CNS symptoms arise as a very late and frequent complication in ATTRV30M patients, starting after at least 14 years of symptomatic systemic disease. [5][6][7] Symptoms include transient focal neurologic episodes (TFNEs), intracerebral hemorrhages, ischemic stroke, and cognitive deterioration. Before liver transplant was available, mean survival of ATTTRV30M patients after diagnosis was 7-10 years.…”

Section: Early or Late Cns Manifestations In Attrv: 2 Phenotypesmentioning

confidence: 99%

“…As for symptoms, 3 independent studies have reviewed neurologic events in posttransplant ATTRV30M patients and found TFNEs in 12%-31%. [5][6][7] Considering that more ATTRv amyloidosis is a systemic disease with multiorgan involvement. While some mutations most often present with "pure" phenotypes with a predominant involvement of the CNS, peripheral nervous system, or heart, most mutations can have "mixed" phenotypes or present with variable symptoms.…”

Section: Epidemiologymentioning

confidence: 99%

“…20 On average, TFNEs start 14-17 years after disease onset and their frequency increases with time (Table 2). [5][6][7] Cerebrovascular events in ATTRV30M patients include ischemic stroke, intracerebral lobar hemorrhages, and subarachnoid hemorrhages. 5,14,[21][22][23][24] Another potential effect of CNS amyloid deposition in ATTRV30M amyloidosis is cognitive deficit.…”

Section: Glossarymentioning

confidence: 99%

“…As for symptoms, 3 independent studies have reviewed neurologic events in posttransplant ATTRV30M patients and found TFNEs in 12%–31%. 5-7 Considering that more than 2,000 transplanted patients exist worldwide, hundreds of patients could be at risk for CNS manifestations. 13…”

Section: Epidemiologymentioning

confidence: 99%

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CNS Involvement in Hereditary Transthyretin Amyloidosis

2021

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Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is predominantly a disease of the peripheral nerves, heart, kidney, and eye. CNS involvement has been a marginal issue in research and the clinical setting until recently. Growing evidence shows that leptomeningeal amyloid accumulation is frequent and present from early stages of ATTRv amyloidosis. Several recent studies show CNS symptoms arise as a common late complication in patients with the V30M mutation after at least 14 years of symptomatic peripheral nerve disease. Conversely, in non-V30M patients, there are several descriptions, mostly case reports, of patients presenting with severe phenotypes of ocular and CNS dysfunction (oculoleptomeningeal amyloidosis), with little systemic involvement. This phenotype is found in rare families worldwide, associated with at least 14 mutations. In both patients with late and early onset CNS dysfunction, symptoms include transient focal neurologic episodes, hemorrhagic and ischemic stroke, cognitive decline, and cranial nerve dysfunction. Pathologically, there is severe amyloid deposition in the leptomeninges and cerebral amyloid angiopathy of leptomeningeal and penetrating vessels. These amyloid aggregates are formed mostly by CSF-produced transthyretin (TTR) and seem resistant to the available ATTRv therapies that increase the stability or reduce the production of plasma TTR. This indicates that CNS involvement will become a meaningful issue in patient management in upcoming years.

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