Article Text

PDF
Research paper
CNS involvement in V30M transthyretin amyloidosis: clinical, neuropathological and biochemical findings
  1. Luís F Maia1,2,3,
  2. Rui Magalhães4,
  3. Joel Freitas2,
  4. Ricardo Taipa5,
  5. Manuel Melo Pires5,
  6. Hugo Osório6,
  7. Daniel Dias7,
  8. Helena Pessegueiro8,
  9. Manuel Correia2,
  10. Teresa Coelho1,9
  1. 1Unidade Corino de Andrade, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal
  2. 2Serviço de Neurologia, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal
  3. 3Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, Tübingen, Germany
  4. 4Departamento de Estudos Populacionais, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
  5. 5Unidade de Neuropatologia, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal
  6. 6Instituto de Patologia e Imunologia Molecular da Universidade do Porto, IPATIMUP, Porto, Portugal
  7. 7Serviço de Neuroradiologia, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal
  8. 8Departamento de Medicina, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal
  9. 9Serviço de Neurofisiologia, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal
  1. Correspondence to Dr Luís F Maia, Serviço de Neurologia, Hospital de Santo António—CHP, Largo Prof. Abel Salazar, Porto 4099-001, Portugal; luis.lf.maia{at}gmail.com

Abstract

Objectives Since liver transplant (LT) was introduced to treat patients with familial amyloid polyneuropathy carrying the V30M mutation (ATTR-V30M), ocular and cardiac complications have developed. Long-term central nervous system (CNS) involvement was not investigated. Our goals were to: (1) identify and characterise focal neurological episodes (FNEs) due to CNS dysfunction in ATTR-V30M patients; (2) characterise neuropathological features and temporal profile of CNS transthyretin amyloidosis.

Methods We monitored the presence and type of FNEs in 87 consecutive ATTR-V30M and 35 non-ATTR LT patients. FNEs were investigated with CT scan, EEG and extensive neurovascular workup. MRI studies were not performed because all patients had cardiac pacemakers as part of the LT protocol. We characterised transthyretin amyloid deposition in the brains of seven ATTR-V30M patients, dead 3–13 years after polyneuropathy onset.

Results FNEs occurred in 31% (27/87) of ATTR-V30M and in 5.7% (2/35) of the non-ATTR transplanted patients (OR=7.0, 95% CI 1.5 to 33.5). FNEs occurred on average 14.6 years after disease onset (95% CI 13.3 to 16.0) in ATTR-V30M patients, which is beyond the life expectancy of non-transplanted ATTR-V30M patients (10.9, 95% CI 10.5 to 11.3). ATTR-V30M patients with FNEs had longer disease duration (OR=1.24; 95% CI 1.07 to 1.43), renal dysfunction (OR=4.65; 95% CI 1.20 to 18.05) and were men (OR=3.57; 95% CI 1.02 to 12.30). CNS transthyretin amyloidosis was already present 3 years after polyneuropathy onset and progressed from the meninges and its vessels towards meningocortical vessels and the superficial brain parenchyma, as disease duration increased.

Conclusions Our findings indicate that CNS clinical involvement occurs in ATTR-V30M patients regardless of LT. Longer disease duration after LT can provide the necessary time for transthyretin amyloidosis to progress until it becomes clinically relevant. Highly sensitive imaging methods are needed to identify and monitor brain ATTR. Disease modifying therapies should consider brain TTR as a target.

  • Amyloid
  • Neuropathy
  • Clinical Neurology
  • Neuropathology

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles