Familial amyloid polyneuropathy (FAP): clinical features, pathophysiology and treatment

In the literature, concepts of “polyneuropathy”, “peripheral neuropathy” and “neuropathy” are often mistakenly used as synonyms. Polyneuropathy is a specific term that refers to a relatively homogenous process that affects multiple peripheral nerves. Most of these tend to present as symmetric polyneuropathies that first manifest in the distal portions of the affected nerves. Many of these distal symmetric polyneuropathies are due to toxic-metabolic causes such as alcohol abuse and diabetes mellitus. Other distal symmetric polyneuropathies may result from an overproduction of substances that result in nerve pathology such as is observed in anti-MAG neuropathy and monoclonal gammopathy of undetermined significance. Other “overproduction” disorders are hereditary such as noted in the Portuguese type of familial amyloid polyneuropathy (FAP). FAP is a manifestation of a group of hereditary amyloidoses; an autosomal dominant, multisystemic disorder wherein the mutant amyloid precursor, transthyretin, is produced in excess primarily by the liver. The liver accounts for approximately 98% of all transthyretin production. FAP is confirmed by detecting a transthyretin variant with a methionine for valine substitution at position 30 [TTR (Met30)]. Familial Amyloidotic Polyneuropathy (FAP) – Portuguese type was first described by a Portuguese neurologist, Corino de Andrade in 1939 and published in 1951. Most persons with this disorder are descended from Portuguese sailors who sired offspring in various locations, primarily in Sweden, Japan and Mallorca. Their descendants emigrated worldwide such that this disorder has been reported in other countries as well. More than 2000 symptomatic cases have been reported in Portugal. FAP progresses rapidly with an average time course from symptom onset to multi-organ involvement and death between ten and twenty years. Treatments directed at removing this aberrant protein such as plasmapheresis and immunoadsorption proved to be unsuccessful. Liver transplantation has been the only effective solution as evidenced by almost 2000 liver transplants performed worldwide. A therapy for FAP with a novel agent, “Tafamidis” has shown some promise in ongoing phase III clinical trials. It is well recognized that regular physical activity of moderate intensity has a positive effect on physical fitness as gauged by body composition, aerobic capacity, muscular strength and endurance and flexibility. Physical fitness has been reported to result in the reduction of symptoms and lesser impairment when performing activities of daily living. Exercise has been advocated as part of a comprehensive approach to the treatment of chronic diseases. Therefore, this chapter concludes with a discussion of the role of exercise training on FAP.

Validação do dispositivo automático de medição da pressão arterial, OMRON® M6 Comfort, segundo o Protocolo Internacional da Sociedade Europeia de Hipertensão (2010)

Introdução – A medição da pressão arterial (PA), utilizando dispositivos automáticos, é frequentemente realizada na prática clínica e na automedição, permitindo adquirir informação fiável para o diagnóstico, controlo e tratamento da hipertensão arterial. Porém, muitos dos dispositivos automáticos disponíveis no mercado não estão validados segundo protocolos existentes para o efeito. O objetivo do estudo foi confirmar a validação do dispositivo de medição automática da PA, OMRON® M6 Comfort, segundo o Protocolo Internacional da European Society of Hypertension (ESH), de 2010, para a validação de dispositivos de medição automática da PA em adultos. Metodologia – Foram estudados 33 indivíduos, aos quais foram realizadas 9 medições sequenciais da PA, no braço esquerdo, com um esfignomanómetro aneróide alternando com o dispositivo automático. Seguidamente avaliaram-se as diferenças entre os valores obtidos pelos dispositivos para a pressão arterial sistólica (PAS) e diastólica (PAD), classificando-as em três níveis (≤ 5, ≤ 10 ou ≤ 15 mmHg). O número das diferenças em cada nível foi comparado ao requerido pelo Protocolo (fase 1.1). Para cada sujeito foi ainda determinado o número de diferenças com valores ≤ 5 mmHg. Pelo menos 24 dos 33 indivíduos devem ter 2 ou 3 diferenças com valores ≤ 5 mmHg e no máximo 3 dos 33 indivíduos podem apresentar as 3 diferenças com valores > 5 mmHg (fase 1.2). Resultados – O dispositivo OMRON® M6 Comfort foi aprovado nas fases 1.1 e 1.2 para a PAS e PAD. A média das diferenças entre as medições da PA, determinada pelos dispositivos automático e manual, foi de -0,82 ± 5,62 mmHg para a PAS e 2,14 ± 5,15 mmHg para a PAD. Considerações Finais – O dispositivo OMRON® M6 Comfort é válido para a medição da PA em adultos, de acordo com o Protocolo Internacional da ESH, de 2010. - ABSTRACT - Introduction – The measurement of blood pressure (BP) using automatic devices is often performed in clinical practice and self-measurement allowing the acquisition of reliable information for the diagnosis, monitoring and treatment of hypertension. However not all of the automated devices available in the market are validated in accordance with the existing protocols for this purpose. The purpose of this study was to confirm the validation of the automatic measuring device of the BP, OMRON® M6 Comfort, according to the “European Society of Hypertension International Protocol revision 2010 for the validation of blood pressure measuring devices in adults”. Methodology – The study involved 33 subjects, in each one of them, 9 sequential measurements of BP were performed, in the left arm, with the aneroid sphygmomanometer alternating with the automatic device. Afterwards, the differences on the values obtained by the different devices were evaluated, for systolic blood pressure (SBP) and diastolic (DBP), and these differences were then classified into three levels (≤ 5, ≤ 10 or ≤ 15 mmHg). The number of differences at each level was compared to the number required by the protocol (phase 1.1). For each subject the number of differences with values ≤ 5 mmHg was also determined. At least 24 of the 33 subjects should have 2 or 3 differences with values ≤ 5 mmHg and a maximum of 3 of the 33 subjects may have all differences with values > 5 mmHg (phase 1.2). Results – The device OMRON M6 Comfort ® was approved in phases 1.1 and 1.2 for SBP and DBP. The average difference between measurements of BP, as determined by automatic and manual devices, was -0.82 ± 5.62 mmHg for SBP and 2.14 ± 5.15 mmHg for DBP. Conclusion – The device OMRON M6 Comfort® is valid for measuring BP in adults, according to the ESH International Protocol of 2010.