Red flags in patients with hereditary transthyretin amyloidosis at diagnosis in a non-endemic area of Spain.

INTRODUCTION: Hereditary transthyretin (hATTR) amyloidosis with polyneuropathy is a rare multisystemic disease characterised by onset during adulthood and associated with poor prognosis if untreated. A set of signs and symptoms, commonly known as "red flags," have been proposed to assist in early detection of the disease; presence of red flags may suggest underlying hATTR amyloidosis in patients with progressive sensorimotor polyneuropathy. MATERIAL AND METHODS: We analysed the frequency of red flags at the time of diagnosis in 30 patients with hATTR amyloidosis in a non-endemic area of Spain; onset was late in the majority of patients. RESULTS: The frequencies of the red flags were as follows: bilateral carpal tunnel syndrome in 15 patients (50%), early autonomic dysfunction in 17 (56%), gastrointestinal problems in 14 (46.6%), unexplained weight loss in 8 (26.6%), heart disease in 12 (40%), asymptomatic cardiac findings in 13 (43.3%), kidney disease in one (3.3%), vitreous opacities in none, family history of neuropathy in 21 (70%), family history of heart disease in 15 (50%), and family history of gastrointestinal problems in 3 (10%). All patients presented at least one red flag at diagnosis, with a median of 4 red flags. CONCLUSION: Red flags were common at the time of diagnosis, even in patients with late-onset hATTR amyloidosis. Presence of red flags in a patient with symmetrical sensorimotor polyneuropathy should serve as a warning sign, and lead to targeted diagnosis to rule out hATTR amyloidosis, independently of age of onset.

Red flags in patients with hereditary transthyretin amyloidosis at diagnosis in a non-endemic area of Spain. / «Red flags¼ en pacientes con polineuropatía amiloidótica familiar relacionada con transtiretina (hATTR) en el momento del diagnóstico en un área no endémica de España.

INTRODUCTION: Hereditary transthyretin (hATTR) amyloidosis with polyneuropathy is a rare multisystemic disease characterised by onset during adulthood and associated with poor prognosis if untreated. A set of signs and symptoms, commonly known as "red flags," have been proposed to assist in early detection of the disease; presence of red flags may suggest underlying hATTR amyloidosis in patients with progressive sensorimotor polyneuropathy. MATERIAL AND METHODS: We analysed the frequency of red flags at the time of diagnosis in 30 patients with hATTR amyloidosis in a non-endemic area of Spain; onset was late in the majority of patients. RESULTS: The frequencies of the red flags were as follows: bilateral carpal tunnel syndrome in 15 patients (50%), early autonomic dysfunction in 17 (56%), gastrointestinal problems in 14 (46.6%), unexplained weight loss in 8 (26.6%), heart disease in 12 (40%), asymptomatic cardiac findings in 13 (43.3%), kidney disease in one (3.3%), vitreous opacities in none, family history of neuropathy in 21 (70%), family history of heart disease in 15 (50%), and family history of gastrointestinal problems in 3 (10%). All patients presented at least one red flag at diagnosis, with a median of 4 red flags. CONCLUSION: Red flags were common at the time of diagnosis, even in patients with late-onset hATTR amyloidosis. Presence of red flags in a patient with symmetrical sensorimotor polyneuropathy should serve as a warning sign, and lead to targeted diagnosis to rule out hATTR amyloidosis, independently of age of onset.

Histological changes in the rat brain and spinal cord following prolonged intracerebroventricular infusion of cerebrospinal fluid from amyotrophic lateral sclerosis patients are similar to those caused by the disease. / La infusión intracerebroventricular prolongada de líquido cefalorraquídeo procedente de pacientes con esclerosis lateral amiotrófica provoca cambios histológicos en el cerebro y la médula espinal de la rata similares a los hallados en la enfermedad.

INTRODUCTION: Cerebrospinal fluid (CSF) from amyotrophic lateral sclerosis (ALS) patients induces cytotoxic effects in in vitro cultured motor neurons. MATERIAL AND METHODS: We selected CSF with previously reported cytotoxic effects from 32 ALS patients. Twenty-eight adult male rats were intracerebroventricularly implanted with osmotic mini-pumps and divided into 3 groups: 9 rats injected with CSF from non-ALS patients, 15 rats injected with cytotoxic ALS-CSF, and 4 rats injected with a physiological saline solution. CSF was intracerebroventricularly and continuously infused for periods of 20 or 43days after implantation. We conducted clinical assessments and electromyographic examinations, and histological analyses were conducted in rats euthanised 20, 45, and 82days after surgery. RESULTS: Immunohistochemical studies revealed tissue damage with similar characteristics to those found in the sporadic forms of ALS, such as overexpression of cystatinC, transferrin, and TDP-43 protein in the cytoplasm. The earliest changes observed seemed to play a protective role due to the overexpression of peripherin, AKTpan, AKTphospho, and metallothioneins; this expression had diminished by the time we analysed rats euthanised on day 82, when an increase in apoptosis was observed. The first cellular changes identified were activated microglia followed by astrogliosis and overexpression of GFAP and S100B proteins. CONCLUSION: Our data suggest that ALS could spread through CSF and that intracerebroventricular administration of cytotoxic ALS-CSF provokes changes similar to those found in sporadic forms of the disease.

[Cell therapy in amyotrophic lateral sclerosis: science and controversy]. / Terapia celular en la esclerosis lateral amiotrófica: ciencia y controversia.

Stem cell therapy is seen as a possible alternative for the treatment of different degenerative diseases, among which includes amyotrophic lateral sclerosis (ALS). Despite there being basic research works with this therapy in ALS, the mechanism of action of the implanted cells are still unclear. It is also unclear which type of cells to use (bone marrow, fat, dental pulp, etc.), or the most ideal administration route. Furthermore, clinical trials with mesenchymal stem cells are not very conclusive, therefore it has not been convincingly established as an alternative therapy in ALS or any other neurodegenerative disease. Despite the scientific evidence, several clinical trials have been conducted in the last few years that offer stem cell treatments for neurodegenerative diseases, giving rise to what is known as "cellular tourism". This phenomenon has set off alarms and reactions in the scientific community. The application of these therapies must be performed following the good clinical practice guidelines in research, evidence based methodology and international ethical and scientific recommendations.

[Toxoplasmosis of the central nervous system in immunodepressed patients. Our experience]. / Toxoplasmosis del sistema nervioso central en enfermos inmunodeprimidos. Nuestra experiencia.

Seven patients carriers of a disease capable of provoking immunodeficiency (six of them suffering AIDS and one case of Hodgkin type lymphoma) are reported. All of them presented neurological complications consisting of toxoplasma Gondii infection of the Central Nervous System. We summarize their evolution and the diagnostic and therapeutical approaches.