Mamede de carvalho

Faculty of Medicine- University of Lisbon- Portugal · Institute of Physiology

Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS) are chronic diseases characterized by progressive or alternate impairment of neurological functions (motor, sensory, visual, cognitive). Patients have to manage alternated periods in hospital with care at home, experiencing a constant uncertainty regarding the timing of the disease acu...

Introduction: Caveolin-1 and Caveolin-2 (CAV1 and CAV2) are proteins associated with intercellular neurotrophic signalling. There is converging evidence that CAV1 and CAV2 (CAV1/2) genes have a role in amyotrophic lateral sclerosis (ALS). Disease-associated variants have been identified within CAV1/2 enhancers, which reduce gene expression and lead...

Background: Respiratory insufficiency and its complications are the main cause of death in amyotrophic lateral sclerosis (ALS). Respiratory symptoms are scored in questions Q10 (dyspnoea) and Q11 (orthopnoea) of the revised ALS functional rating scale (ALSFRS-R). The association of respiratory test alterations with respiratory symptoms is unclear....

Mirror activity is an involuntary activation of a muscle when the respective contralateral muscle is contracting. This phenomenon has been described primarily in children and in disease states, and, more recently, also in healthy adults. Different ways of assessing mirror activity have been described. In this work we propose a simple protocol for q...

Amyotrophic lateral sclerosis (ALS) and myopathy have been already described as part of a common genetic syndrome called multisystem proteinopathy. They may occur together or not, and can be associated with other clinical features such as frontotemporal dementia and Paget’s bone disease. In addition, primary skeletal muscle involvement has been als...

Objectives: We investigated the cutaneous silent period (CutSP) as a measure of upper motor neuron (UMN) dysfunction in amyotrophic lateral sclerosis. Methods: The onset latency, duration, and amount of EMG suppression of the CutSP were compared with clinical UMN signs in 24 patients with amyotrophic lateral sclerosis (ALS). UMN signs were quant...

Background Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with a median survival of 2–5 years. An early diagnosis is essential for providing ALS patients the finest management possible. Studies from different countries report a similar median diagnostic delay of around 12 months, which is still far from desir...

Objective: The flail-arm syndrome (FAS), one of the Amyotrophic lateral sclerosis (ALS) phenotypes, is characterized by slow progression and predominantly lower motor neuron (LMN) involvement with proximal upper limb (UL) weakness. We aim to characterize the clinical features, progression and survival of FAS associated with distal or proximal onset...

Amyotrophic Lateral Sclerosis (ALS) is a fast-progressing disease with no cure. Nowadays, needle electromyography (nEMG) is the standard practice for electrodiagnosis of ALS. Surface electromyography (sEMG) is emerging as a more practical and less painful alternative to nEMG but still has analytical and technical challenges. The objective of this w...

Objectives: Transcranial magnetic stimulation (TMS) is a technique to assess motor system function which has been used extensively in amyotrophic lateral sclerosis (ALS). Information on the changes during disease progression is scarce. We aimed to collect this information in a single source. Methods: Literature search tools and personal searching w...

Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of upper and lower motor neurons, leading to progressive weakness of voluntary muscles, with death following from neuromuscular respiratory failure, typically within 3 to 5 years. There is a strong genetic contribution to ALS risk. In 10% or more...

Introduction: The excitability of spinal motor neurons (MN) can be altered through subthreshold currents, such as transcutaneous spinal direct-current stimulation (tsDCS). Current evidence shows that tsDCS can interfere with ascending somatosensory pathways and lower motor neurons' (LMN) excitability, which points to its therapeutic potential for...

We describe four male patients with wasted-leg syndrome, with predominant asymmetric thigh atrophy and weakness that stabilized after a period of slow progression (follow-up 7–18 years). Two patients had an Indian ethnic background and two were Portuguese, without known Indian ancestry. Other mimicking disorders were excluded, but one Indian patien...

Transcutaneous Spinal Direct Current Stimulation (tsDCS) is a neuromodulatory technique that applies low intensity (2–4 mA) direct currents to the spinal cord through electrodes placed above or near the vertebral column. As in transcranial electric stimulation, tsDCS induces an electric field in the spinal cord that can transiently change the trans...

Objective Genetic variation in the neurofilament heavy chain gene ( NEFH ) has been convincingly linked to the pathogenesis of multiple neurodegenerative diseases, however, the relationship between NEFH mutations and ALS susceptibility has not been robustly explored. We therefore wanted to determine if genetic variants in NEFH modify ALS risk. Met...

Caveolin-1 and Caveolin-2 (CAV1 and CAV2) are proteins associated with intercellular neurotrophic signalling. There is converging evidence that CAV1 and CAV2 (CAV1/2) genes have a role in ALS. Disease-associated variants have been identified within CAV1/2 enhancers, which reduce gene expression and lead to disruption of membrane lipid rafts. Using...

Amyotrophic lateral sclerosis is a heterogeneous, fatal neurodegenerative disease, characterized by motor neuron loss and in 50% of cases also by cognitive and/or behavioral changes. Mendelian forms of ALS comprise approximately 10-15% of cases. The majority is however considered sporadic, but also with a high contribution of genetic risk factors....

Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative syndrome. In up to 20% of cases, a family history is observed. Although Mendelian disease gene variants are found in apparently sporadic ALS, genetic testing is usually restricted to those with a family history or younger patients with sporadic disease. With the advent of ther...

Background : Multiple Sclerosis’ (MS) disease-modifying therapy (DMT) have allowed a longer life expectancy, so patients are at higher risk of having a neurodegenerative disorder. Muscular atrophy can happen in MS, but can also indicate other entities. Case report : We report a 52-year-old woman with relapse-remitting MS since 1999, with a recent...

Background Some amyotrophic lateral sclerosis (ALS) patients on continuous non-invasive ventilation (NIV) develop dysphagia demanding a clinical decision regarding gastrostomy. Material and methods We have analyzed a cohort of seventy-four ALS patients dependent on continuous NIV (>22 h/day) and without feeding tube. Results Three patients underw...

Amyotrophic Lateral Sclerosis (ALS) is a severe chronic disease characterized by progressive or alternate impairment of neurological functions, characterized by high heterogeneity both in symptoms and disease progression. As a consequence its clinical course is highly uncertain, challenging both patients and clinicians. Indeed, patients have to man...

Longitudinal cohort studies to study disease progression generally combine temporal features produced under periodic assessments (clinical follow-up) with static features associated with single-time assessments, genetic, psychophysiological, and demographic profiles. Subspace clustering, including biclustering and triclustering stances, enables the...

A new longitudinal study involving carriers of amyotrophic lateral sclerosis (ALS)-associated mutations has identified a prodromal phase of ALS characterized by mild motor impairment. The findings could help us to define a time window during which neuroprotective interventions might be effective in patients with genetic forms of ALS.

Objective Amyotrophic lateral sclerosis (ALS) pathogenesis is still unclear, its course is considerably variable, and prognosis is hard to determine. Despite much research, there is still a lack of easily accessible markers predicting prognosis. We investigated routine blood parameters in ALS patients regarding correlations with disease severity, p...

Introduction: Thyroid hormones influence neuromuscular function, and it has been thought that this might contribute to degeneration of motor neurons. Methods: We used case-control methods to investigate the prevalence of thyroid dysfunction (hyperthyroidism and hypothyroidism) in ALS patients followed in our centre, between 2015 and 2020. Data f...

Objective To describe the clinical features and progression of patients with respiratory onset amyotrophic lateral sclerosis (ALS). Methods: We analyzed the clinical features, including respiratory tests, functional score, noninvasive ventilation (NIV) time and survival of ALS patients with respiratory-onset in our database consisting of 1688 patie...

Background and purpose: Progression rate is quite variable in amyotrophic lateral sclerosis (ALS); thus, tools for profiling disease progression are essential for timely interventions. The objective was to apply dynamic Bayesian networks (DBNs) to establish the influence of clinical and demographic variables on disease progression rate. Methods:...

Hereditary transthyretin amyloidosis (ATTRv) is a severe, adult-onset autosomal dominant inherited systemic disease predominantly affecting the peripheral and autonomic nervous system, heart, kidney and the eyes. ATTRv is caused by mutations of the transthyretin (TTR) gene, leading to extracellular deposition of amyloid fibrils in multiple organs i...

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide a...

Background: Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA). Objective: To assess the feasibility of clinical stu...

We describe three unrelated patients with sporadic motor neuron disease (MND) and hereditary amyloid transthyretin (ATTRv) amyloidosis family history, who were asymptomatic carriers of the pVal50Met mutation of transthyretin (TTR) gene. Patients 1 and 2 were a 43-year-old man with a spinal-onset of ALS and a 37-year-old woman with a bulbar-onset of...

There is a strong genetic contribution to Amyotrophic lateral sclerosis (ALS) risk, with heritability estimates of up to 60%. Both Mendelian and small effect variants have been identified, but in common with other conditions, such variants only explain a little of the heritability. Genomic structural variation might account for some of this otherwi...

Amyotrophic lateral sclerosis (ALS) is a complex disease that leads to motor neuron death. Despite heritability estimates of 52%, genome-wide association studies (GWASs) have discovered relatively few loci. We developed a machine learning approach called RefMap, which integrates functional genomics with GWAS summary statistics for gene discovery. W...

Background Pulmonary function tests are routinely used to measure progression in ALS. This study aimed to assess the change of various respiratory tests, in particular maximal voluntary ventilation (MVV), which evaluates respiratory endurance. Methods A group of 51 patients were assessed 3 times (T1, T2, T3, separated by 5.4 months), including slo...

Introduction/Aims Age can affect hand muscles non-uniformly. We investigated the influence of age on the compound muscle action potential (CMAP) amplitude of the hand muscles and the derived split-hand index (SHI). Methods We studied 244 subjects investigated for myasthenia gravis but without neuromuscular disorders. Abductor pollicis brevis (APB)...

Objectives The excitability of lower motor neurons can be explored non-invasively by several neurophysiological techniques, e.g., F-wave and H-reflex studies after a period of immobility and then after subsequent exercise. The aim of this study is to investigate the impact of exercise and high frequency repetitive nerve stimulation (RNS) following...

Objectives To assess the influence of age and gender on sensory nerve axonal excitability parameters. Methods Thirty-three healthy subjects (21 women) were included, with a mean age of 34.6 (range 21–76). Median sensory nerve excitability measurements (index finger) were performed using the TRONDNF nerve excitability protocol of the QTRAC program....

A number of conditions can mimic amyotrophic lateral sclerosis (ALS), which are in general excluded by neurophysiological and neuroimaging investigation. We present a novel mimicking disorder. A 58-year-old male, without relevant past medical history, presented with a 7-year history of progressive paraparesis. On examination, he had bilateral thigh...

Background: The impact of SARS-CoV-2 infection among neuromuscular diseases with respiratory involvement, including amyotrophic lateral sclerosis (ALS), is still to be elucidated. Objectives: We aim to characterize the clinical outcome of ALS patients non-invasive ventilated (NIV), following SARS-CoV-2 infection. Methods: We analyzed retrospec...

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 indi...

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 indi...

[This corrects the article DOI: 10.3389/fcvm.2021.715842.].

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with unsatisfactory treatment options. Best management and recruitment into clinical trials requires early diagnosis. However, diagnosis is often delayed. Analysis of the diagnostic pathway and identification of the causes of diagnostic delay are imperative....

We read with great interest the letter of Drs Gazulla and collaborators, who suggested that the continuum between primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) is not straightforward.1 They indicated that PLS can be associated to other central nervous system disorders related to known or unknown rare mutations.

Objective To characterize electromyographic (EMG) findings in patients with primary lateral sclerosis (PLS) during the disease course. Methods In PLS patients we scored spontaneous activity and motor unit action potential (MUP) pattern on EMG. We compared patients according to lower (group A) and higher (group B) EMG scores. EMG studies were repea...

Introduction: The motor unit size index (MUSIX) may provide insight into reinnervation patterns in diseases such as amyotrophic lateral sclerosis (ALS). However, it is not known if MUSIX detects clinically relevant changes in reinnervation, or if all muscles manifest changes in MUSIX in response reinnervation following motor unit loss. Methods:...

Amyotrophic lateral sclerosis (ALS) is an aggressive neurodegenerative disorder related to neuroinflammation that is associated with increased risk of thrombosis. We aimed to evaluate γ' fibrinogen plasma level (an in vivo variant of fibrinogen) as a biomarker in ALS, and to test its role as a predictor of disease progression and survival. Sixty-se...

Introduction/Aims Fasciculations can be symptomatic, yet not progress to amyotrophic lateral sclerosis (ALS), a condition categorized as benign fasciculation syndrome (BFS). We aimed to assess electrodiagnostic changes and clinical course over time in patients with BFS. Methods This was a retrospective review of medical records of patients who wer...

Objective This study evaluates diagnostic accuracy of the proposed ‘Gold Coast’ (GC) diagnostic criteria for amyotrophic lateral sclerosis (ALS). Methods Five European centres retrospectively sampled consecutive patients referred for electromyography on suspicion of ALS. Patients were classified according to the GC criteria, the revised El Escoria...

Background and purpose: Primary lateral sclerosis (PLS) is a motor neuron disorder characterized by a pure upper motor neuron degeneration in the bulbar and spinal regions. The key difference with amyotrophic lateral sclerosis (ALS) is the lower motor neuron system integrity. Despite important literature on this disease, the pathophysiology of PLS...

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting the upper and lower motor neurons. A key clinical feature of ALS is the absence of accurate, early-stage diagnostic indicators. ‘Split-hand syndrome’ was first described in ALS at the end of the last century and a considerable body of literature suggests that...

Objective: To study disease characteristics, progression and outcome in a group of motor neuron disease (MND) patients beginning with frontotemporal dementia (FTD) by comparing them with patients with the typical motor-onset. Methods: 849 patients recruited from tertiary centers were studied according to FTD-onset and motor-onset. We studied clinic...

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative neuromuscular disease that affects motor neurons controlling voluntary muscles. Survival is usually 2–5 years after onset, and death occurs due to respiratory failure. The identification of biomarkers would be very useful to help in disease diagnosis and for patient stratification based on,...

Amyotrophic lateral sclerosis (ALS) causes dysphagia and consequent poor nutrition. Sometimes enteral feeding is offered. Percutaneous endoscopic gastrostomy (PEG) is currently the technique of choice for enteral nutrition of these patients. This systematic review addresses the role of PEG and other enteral feeding techniques in maintaining ALS pat...

Background: Short-interval intracortical inhibition by threshold tracking (T-SICI) has been proposed as a diagnostic tool for amyotrophic lateral sclerosis (ALS), but has not been compared directly with conventional amplitude measurements (A-SICI). This study compared A-SICI and T-SICI for sensitivity and clinical usefulness as biomarkers for ALS....

Background and Objectives Deep neural networks recently become a popular tool in medical research to predict disease progression and unveil its underlying temporal phenotypes. While being well suited to study longitudinal clinical data and learn disease progression models, its application in clinical setting is challenged by the importance of model...

Primary Lateral Sclerosis (PLS) is a motor neuron disorder characterized by a pure UMN degeneration in bulbar and spinal regions. The key difference with Amyotrophic Lateral Sclerosis (ALS) is the lower motor neuron system integrity. Despite important literature on this disease, pathophysiology of PLS remains unknown and the link with ALS still bal...

Objective Amyotrophic lateral sclerosis (ALS) is now recognized as a multisystem neurodegenerative disorder, comprising autonomic dysfunction. We aimed to assess sudomotor function in ALS by measuring the electrochemical skin conductance (ESC). Methods Thirty-one ALS patients [median age of 62 years (1st-3rd interquartile range – IQR, 56-72), male...

Objectives To investigate the use of a set of dynamical features, extracted from surface electromyography, to study upper motor neuron (UMN) degeneration in amyotrophic lateral sclerosis (ALS). Methods We acquired surface EMG signals from the upper limb muscles of 13 ALS patients and 20 control subjects and classified them according to a novel set...

Amyotrophic Lateral Sclerosis is a devastating neurodegenerative disease causing rapid degeneration of motor neurons and usually leading to death by respiratory failure. Since there is no cure, treatment's goal is to improve symptoms and prolong survival. Non-invasive Ventilation (NIV) is an effective treatment, leading to extended life expectancy...

Introduction The spinal cord (SC) is a complex structure containing several neuronal circuits related with motor function of the upper and lower limbs, operating under the influence of higher centres. Central nervous diseases can change the responses of the spinal motor circuits leading to its dysfunction. Over the last decade, there has been a gro...