A 31-year-old woman with transthyretin (TTR) amyloidosis secondary to a Thr60Ala mutation developed recurrent stroke-like episodes with fluctuating mental status. Evaluation for stroke and seizures was unrevealing. She was found to have leptomeningeal contrast enhancement on magnetic resonance imaging, which was confirmed to be CNS TTR amyloidosis on histopathology following brain and dura biopsy. While leptomeningeal disease has rarely been known to be associated with TTR amyloidosis, this is the first documented case of leptomeningeal disease secondary to a Thr60Ala mutation in the TTR gene. A literature review of TTR amyloidosis is presented with special focus on the treatment of leptomeningeal TTR amyloidosis.
ShreiberGAldredAJaworowskiANilssonCAchenSegalMB. Thyroxine transport from blood to brain via transthyretin synthesis in the choroid plexus. Am J Physiol. 1990;258:338-345.
6.
RowczenioDMNoorIGillmoreJD, et al.Online registry for mutations in hereditary amyloidosis including nomenclature recommendations. Hum Mutat. 2014;35:2403-2412.
7.
ZhenDBSwiecickiPLZeldenrustSRDispenzieriAMauermannMGertzM. Frequencies and geographic distributions of genetic mutations in transthyretin- and non-transthyretin-related familial amyloidosis. Clin Genet. 2015;88(4):396-400.
8.
CoelhoTMaurerMSSuhrOB. THAOS: The transthyretin amyloidosis outcomes survey: Initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis. Curr Med Res Opin. 2013;29:63-76.
9.
LiKKyleRADyckPJ. Immunohistochemical characterization of amyloid proteins in sural nerves and clinical associations in amyloid neuropathy. Am J Pathol. 1992;141:217-226.
10.
KeppelSBrannaganTHelmkeS, et al.Early-onset of transthyretin amyloidosis in a young Afro-Caribbean woman with Thr60Ala mutation. JACC: Case Rep. 2020;2:2063-2067.
11.
KaufmanHEThomasLB. Vitreous opacities diagnostic of familial primary amyloidosis. N Engl J Med. 1959;261:1267-1271.
12.
KawajiTAndoYEndoENakamuraMHirataATaniharaH. A case of vitreous amyloidosis without systemic symptoms in familial amyloidotic polyneuropathy. Amyloid. 2004;11:257-259.
QuinQWeiCPiaoY, et al.Current review of leptomeningeal amyloidosis associated with transthyretin mutations. Neurologist. 2021;26:189-195.
15.
EllieECamouFVitalA, et al.Recurrent subarachnoid hemorrhage associated with a new transthyretin variant (Gly53Glu). Neurology. 2003;60:1625-1630.
16.
ParmannYAdamsDObiciL, et al.Sixty years of transthyretin familial amyloid polyneuropathy (TTR-FAP) in Europe: Where are we now? A European network approach to defining the epidemiology and management patterns for TTR-FAP. Curr Opin Neurol. 2016;29(suppl 1):S3-S13.
17.
AdamsDKoikeHSlamaMCoelhoT. Hereditary transthyretin amyloidosis: A model of medical progress for a fatal disease. Nat Rev Neurol. 2019;15(7):387-404.
18.
AndradeC. A peculiar form of peripheral neuropathy: Familiar atypical generalized amyloidosis with special involvement of the peripheral nerves. Brain. 1952;75:408-427.
19.
IkedaSHanyuNHongoM, et al.Hereditary generalized amyloidosis with polyneuropathy. Clinicopathological study of 65 Japanese patients. Brain. 1987;110:315-337.
20.
HolmgrenGSteenIEkstedtJ, et al.Biochemical effect of liver transplantation in two Swedish patients with familial amyloidotic polyneuropathy (FAP-met30). Clin Genet. 1991;40:242-246.
21.
MatsunamiHMakuuchiMKawasakiS, et al.A case of familial amyloid polyneuropathy treated with partial liver transplantation using a graft from a living related donor. Transplantation. 1995;60:301-303.
22.
EriczonBGWilczekHELarssonM, et al.Liver transplantation for hereditary transthyretin amyloidosis: After 20 years still the best therapeutic alternative?Transplantation. 2015;99:1847-1854.
23.
TashimaKAndoYTerazakiH, et al.Outcome of liver transplantation for transthyretin amyloidosis: Follow-up of Japanese familial amyloidotic polyneuropathy patients. J Neurol Sci. 1999;171:19-23.
24.
BuxbaumJBrannaganTBuades-ReinesJ, et al.Transthyretin deposition in the eye in the era of effective therapy for hereditary ATTRV30M amyloidosis. Amyloid. 2019;26(1):10-14.
25.
MaiaLFMagalhaesRFreitasJ, et al.CNS involvement in V30M transthyretin amyloidosis: Clinical, neuropathological, and biochemical findings. J Neurol Neurosurg Psychiatry. 2015;86:159-167.
26.
CoelhoTMaiaLFda SilvaAM, et al.Long-term effects of Tafamidis for the treatment of transthyretin familial amyloid polyneuropathy. J Neurol. 2013;260:2802-2814.
27.
MaurerMSSchwartzJHGundapaneniB, et al.Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379:1007-1016.
28.
MonteiroCMartins da SilvaAFerreiraN, et al.Cerebrospinal fluid and vitreous body exposure to orally administered Tafamidis in hereditary ATTRV30M (p.TTRv50M) amyloidosis patients. Amyloid. 2018;25:120-128.
29.
SalviFVolpeRPastorelliF, et al.Failure of Tafamidis to halt progression of Ala36Pro TTR oculomeningovascular amyloidosis. J Stroke Cerebrovasc Dis. 2018;27:212-214.
30.
SekijimaYTojoKMoritaHKoyamaJIkedaSi. Safety and efficacy of long-term Diflunisal administration in hereditary transthyretin (ATTR) amyloidosis. Amyloid. 2015;22:79-83.
31.
GomesJSalvadoMReigN, et al.Transthyretin stabilization activity of the catechol-O-methyltransferase inhibitor tolcapone (SOM0226) in hereditary ATTR amyloidosis patients and asymptomatic carriers: Proof-of-concept study. Amyloid. 2019;26:74-84.
32.
PinheiroFVarejaoNEsperanteS, et al.Tolcapone, a potent aggregation inhibitor for the treatment of familial leptomeningeal amyloidosis. FEBS J. 2021;288:310-324.
33.
AdamsDGonzalez-DuarteAO’RiordanW, et al.Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N Engl J Med. 2018;379(1):11-21.
34.
BensonMWaddington-CruzMBerkJ, et al.Inotersen treatment for patients with hereditary transthyretin amyloidosis. N Engl J Med. 2018;379(1):22-31.
35.
BensonMDSmithRAHungG, et al.Suppression of choroid plexus transthyretin levels by antisense oligonucleotide treatment. Amyloid. 2010;17(2):43-49.
36.
BodinKEllmerichSKahanMC, et al.Antibodies to human serum amyloid P component eliminate visceral amyloid deposits. Nature. 2010;468:93-97.
37.
HigakiJNChakrabarttyAGalantNJ, et al.Novel conformation-specific monoclonal antibodies against amyloidogenic forms of transthyretin. Amyloid. 2016;23:86-97.
38.
HayashiMHandaYKobayashiHKawanoHIshiiHHiroseS. Plateau-wave phenomenon (I). Correlation between the appearance of plateau waves and CSF circulation in patients with intracranial hypertension. Brain. 1991;114(Pt 6):2681-2691.
39.
CharidimouAPeetersAFoxZ, et al.Spectrum of transient focal neurological episodes in cerebral amyloid angiopathy: Multicentre magnetic resonance imaging cohort study and meta-analysis. Stroke. 2012;43(9):2324-2330.
40.
SousaLCoelhoTTaipaR. CNS involvement in hereditary transthyretin amyloidosis. Neurology. 2021;97(24):1111-1119.
