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Mamede de Carvalho

Publications and source records attributed to Mamede de Carvalho.

At least 19 recordsLinked to original sources
PubMed2006

Influence of peer review medical audit on pathophysiological interpretation of nerve conduction studies in polyneuropathies.

OBJECTIVE: To evaluate the possible influence of peer review medical audit on experienced physicians' pathophysiological interpretation of nerve conduction studies in polyneuropathy patients. METHODS: Since 1992, 7 European neurophysiologists have collected samples of their patient examinations for regular review where the physicians interpret each other's cases electronically and subsequently discuss them at regular workshop meetings (i.e. a form of medical audit). Two sets of 100 polyneuropathy examinations interpreted with an interval of 4-6 years were selected. The sets contained 1456 and 1719 nerve conduction studies, each given a pathophysiological test conclusion by each individual physician. Inter-physician agreement on interpretation of demyelination and axonal loss of the nerve, as well as neuropathic and unspecific findings, was estimated using kappa statistics. RESULTS: Increased agreement from set 1 to set 2 was found on interpretation of demyelination of the nerve (set 1: kappa=0.22; set 2: kappa=0.45), and of neuropathic (set 1: kappa=0.46; set 2: kappa=0.64) and unspecific findings (set 1: kappa=0.35; set 2: kappa=0.54). No changes were found on interpretation of axonal loss (set 1: kappa=0.26; set 2: kappa=0.31) and normal findings (set 1 and set 2: kappa=0.90). CONCLUSIONS: Participation in regular peer review medical audit resulted in increased agreement on interpretation of nerve conduction studies for 6 of the 7 participants. The study further highlights the need for better definition of criteria for identification of demyelinating, and in particular, axonal peripheral neuropathies. SIGNIFICANCE: International collaboration involving peer review medical audit may contribute to development of practice guidelines and, in turn, to increased quality of electrodiagnostic medicine.

Axons↗
PubMed2006

Can selection of rapidly progressing patients shorten clinical trials in amyotrophic lateral sclerosis?

BACKGROUND: The marked variability in progression of amyotrophic lateral sclerosis (ALS) requires large numbers of patients to detect a significant effect in current clinical trial designs. OBJECTIVE: To test the utility of a lead-in period to assess rate of progression so that patients with rapidly progressive ALS can be selected for subsequent clinical trials. DESIGN: Prospective study. SETTING: The ALS Center, University of Lisbon, Lisbon, Portugal. PATIENTS: Fifty-seven consecutively recruited patients assessed at diagnosis and 3 months later (end of lead-in period). INTERVENTIONS: Change in ALS Functional Rating Scale (ALS-FRS) score was analyzed to establish a statistically significant cutoff point to define patients with rapid (group 1) or slow (group 2) progression. Patients from both groups were reexamined 1 and 3 months after the lead-in period. MAIN OUTCOME MEASURES: Changes in ALS-FRS score, motor unit number estimation, and neurophysiologic index, and resultant grouping of patients according to rate of progression at 1 and 3 months. RESULTS: Both the 80th percentile and 2 SDs above the mean of the change in ALS-FRS score identified the same patients. Twelve patients showed rapid progression (group 1) and 45 showed slow progression (group 2). One month after the lead-in period there was a significant reduction in ALS-FRS score, motor unit number estimation, and neurophysiologic index in group 1, and after 3 months all these measurements changed significantly in both groups. CONCLUSIONS: This strategy of selecting patients with rapidly progressing ALS for inclusion in exploratory, short phase II clinical trials offers substantial savings in costs and time, and could accelerate the process of testing potentially useful drugs for the treatment of ALS.

Adult↗
PubMed2006

Ventilation in ALS.

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Amyotrophic Lateral Sclerosis↗
PubMed2006

Evidence for central abnormality in respiratory control in primary lateral sclerosis.

Primary lateral sclerosis (PLS) is a very rare disease characterized by pure upper motor neuron findings. Although a number of previous reports have evaluated this condition, no study has addressed the respiratory function in PLS. Six patients meeting previously proposed diagnostic criteria for PLS were submitted to a number of respiratory tests: forced vital capacity, maximal pressures, phrenic nerve responses, needle electromyography of the respiratory muscles, percutaneous nocturnal oximetry (PNO) and polysomnography (two patients). Our results show that the diaphragm is not affected in this condition, but some respiratory function tests (RFT) and PNO had abnormal values. Voluntary muscular activation to perform RFT may be limited in these patients. PNO and polysomnography suggest that respiratory central drive dysfunction can occur when upper motor neurons are severely affected, in PLS. However, we did not verify progression on follow-up.

Adult↗
PubMed2005

Pain and calf hypertrophy associated with spontaneous repetitive discharges treated with botulinum toxin.

OBJECTIVE: To report a case of neurogenic calf hypertrophy associated with root lesion responsive to botulinum toxin (BTX). In addition, we systematically review the literature for cases of muscle hypertrophy associated with radiculopathy. METHODS: A 56-year-old man with a previous history of S1 root lesion presented with marked calf hypertrophy, muscle pain, cramps, fasciculations, and increased CK level. Magnetic resonance imaging and muscle biopsy confirmed true muscle hypertrophy. Electromyography (EMG) showed signs of chronic denervation-reinnervation in the right S1 myotome, with greatly increased spontaneous activity (SA) (fasciculations and complex repetitive discharges). Botox(R) was injected in 3 occasions on 4 sites on the right gastrocnemius (20U per site). Symptoms, CK level and SA on EMG (quantified) were evaluated. RESULTS: The patient improved clinically, CK level and SA steadily decreased. CONCLUSIONS: The literature review failed to identify a unique causative factor for muscle hypertrophy related to neurogenic lesions. BTX treatment was effective in our patient with muscle hypertrophy associated with SA. SIGNIFICANCE: We provide further evidence that spontaneous activity secondary to nerve lesion may cause focal muscle hypertrophy. Treatment with BTX should be considered in these conditions.

Anti-Dyskinesia Agents↗
PubMed2005

Quantitating progression in ALS.

The authors prospectively studied the value of clinical and neurophysiologic measurements in assessing progression in ALS. Motor unit number estimation (MUNE) and the neurophysiologic index (NI) were significantly correlated with ADM strength (maximal voluntary isometric contraction force in the abductor digiti minimi muscle [MVIC-ADM]). MUNE and the NI were reliable, but the NI showed a lower variation. On assessing progression at 3, 6, and 12 months, MUNE, NI, and MVIC-ADM showed the highest rate of change. The NI is a potentially useful new neurophysiologic measurement.

Adult↗
PubMed2005

Influence of medical audit on electrodiagnostic evaluation of polyneuropathy. A multicentre study.

OBJECTIVE: Since 1992, 7 European neurophysiologists have participated in the ESTEEM project concerned with improvements in electrodiagnostic medicine. This study assesses whether the collaboration that includes peer review medical audit has influenced the involved physicians' electrodiagnostic criteria for polyneuropathy (PNP) diagnosing and classification. METHODS: Two sets of each physician's PNP examinations performed early and late in the study were examined for changes in (1) number of studies with abnormal electrophysiological findings required for diagnosing PNP, and (2) agreement between the classifications given by the individual physicians and the peer review group. RESULTS: The average number of abnormal motor nerve segments per patient increased from 4.6 to 6.4 during the study. Although most individual changes were minor, the second set of examinations showed an increased homogeneity among the physicians in the number of abnormal motor nerve segments and abnormal F wave studies, and a tendency towards increased homogeneity in the number of abnormal sensory nerve segments. There was also an increased agreement on pathophysiological PNP classification in the second set of examinations compared to the first set. CONCLUSIONS: The participation in the ESTEEM project seems to have impacted the physicians' clinical routine, possibly as they have accustomed themselves to apply criteria more strictly. SIGNIFICANCE: This study support that international collaboration is a useful step towards improvements in electrodiagnostic medicine.

Analysis of Variance↗
PubMed2005

Pathophysiology inferred from electrodiagnostic nerve tests and classification of polyneuropathies. Suggested guidelines.

OBJECTIVE: To present criteria for pathophysiological interpretation of motor and sensory nerve conduction studies and for pathophysiological classification of polyneuropathies suggested by a group of European neurophysiologists. METHODS: Since 1992 seven neurophysiologists from six European countries have collected random samples of their electrodiagnostic examinations for peer review medical audit in the ESTEEM (European Standardized Telematic tool to Evaluate Electrodiagnostic Methods) project. Based on existing criteria in the literature, the experience with a patient material of 572 peer reviewed electrodiagnostic examinations, and productive discussions between the physicians at workshops, the collaboration has produced a set of criteria now routinely used at the centres involved in the project. RESULTS: The first part of the paper considers pathophysiology of individual nerve segments. For interpretation of motor and sensory nerve conduction studies, figures showing change in amplitude versus change in conduction velocity/distal latency and change in F-wave frequency versus change in F-wave latency are presented. The suggested boundaries delimit areas corresponding to normal, axonal, demyelinated, or neuropathic nerve segments. Criteria for motor conduction block in upper and lower extremities are schematically depicted using the parameters CMAP amplitude and CMAP duration. The second part of the paper suggests criteria for classification of polyneuropathies into axonal, demyelinating, or mixed using the above-mentioned criteria. CONCLUSIONS: The suggested criteria are developed during many years of collaboration of different centres and may be useful for standardization in clinical neurophysiology. SIGNIFICANCE: Consistent interpretation of nerve conduction studies is an important step in optimising diagnosis and treatment of nerve disorders.

Axons↗
PubMed2005

Neurophysiological measures in amyotrophic lateral sclerosis: markers of progression in clinical trials.

In this review we evaluate clinical neurophysiological methods, originally described for use in diagnosis that can be applied to measurement of change during the progress of amyotrophic lateral sclerosis (ALS). Such measurements are potentially important in clinical trials, and also in clinical practice. We have assessed methods for lower and upper motor neuron function, including conventional EMG, nerve conduction and F-wave studies, the derived Neurophysiological Index, motor unit counting methods (MUNE), and transcranial magnetic motor cortex stimulation. We have also addressed the validity of measurements of electromechanical coupling. Methods for measuring muscle strength are beyond the scope of this review. We conclude that MUNE, M-wave amplitude and the Neurophysiological Index are sufficiently reliable, sensitive, and relevant to the clinical problem of ALS, to be used in clinical trials in the disease. Transcranial magnetic stimulation is of limited value, but a combination of the measurements made as part of this technique may also be useful. We conclude that clinical neurophysiological techniques should now be used in measuring change in clinical trials in ALS.

Amyotrophic Lateral Sclerosis↗
PubMed2005

Biochemical characterization of plasma in amyotrophic lateral sclerosis: amino acid and protein composition.

In this work, we have studied the amino acid and protein composition of the plasma from a group of 32 ALS patients. As controls, groups of 10 healthy subjects (HC) and 32 patients with other neuromuscular disorders have been analysed. When the HC group was compared with the ALS group there were significant decreases of His (39+/-18 to 24+/-9 microM, p<0.01) and Ala (313+/-62 to 237+/-66 microM, p<0.05), and a significant increase of Asn (89+/-41 to 118+/-24 microM, p<0.05), for the ALS group. When the three groups were compared, we observed significant decreased concentrations of Ser, His, Thr, Ala, Arg, Tyr, Met, Cys, Ile, and significant increases of Asn, Phe and Lys. An increase of proteolytic products of alpha2-macroglobulin (alpha2-M), an acute-phase serum glycoprotein that functions as a protease inhibitor, has been observed for a subgroup of ALS patients by Western blot. Furthermore, the detection of alpha2-M during disease progression has shown increases of the intact subunit and of a proteolytic product for two of the four patients analysed. Another acute-phase glycoprotein, haptoglobin, which regulates haemoglobin degradation, was not increased for the same group of patients. The results obtained suggested that diet supplementation with His and Ala and modulation of alpha2-M might have some beneficial effects on the course of ALS.

Adult↗
PubMed2005

Clinical trials in ALS: a review of the role of clinical and neurophysiological measurements.

We have reviewed all the published clinical trials of ALS and, from those considered sufficiently large, and containing a control group, we have evaluated their methodology with regard to statistical power. This implies a critical analysis of the endpoint measurements. We have concluded that clinical endpoints used in clinical trials of ALS have frequently been insufficiently sensitive, non-linear, or even not intuitively highly relevant to the disease. We suggest that the ALS-FRS, perhaps also MUNE and the Neurophysiological Index, may be the best measures currently available. These techniques have complementary characteristics that allow them to be used to address different aspects of the disease and its treatment in various trials designs. In the past some trials may have failed to demonstrate a treatment effect because the chosen endpoint measures and the trial design were inappropriate.

Amyotrophic Lateral Sclerosis↗
PubMed2004

Hereditary sensory neuropathy type 1 in a Portuguese family-electrodiagnostic and autonomic nervous system studies.

Hereditary sensory and autonomic neuropathy type 1 (HSAN 1) is a dominantly inherited disorder; its gene locus is mapped on chromosome 9q22. Three different missense mutations (C133Y, C133W and V144D) have been described in 11 families from Australia, England and Austria. Common clinical features have been found in these families. We report the clinical and electrophysiological features of three members of a large Portuguese family with HSAN 1 and the C133Y missense mutation. The affected members showed typical clinical features. Electrophysiological findings were consistent with a distal axonal predominantly sensory neuropathy with motor involvement, in three different severity stages. No autonomic involvement was detected in sudomotor and cardiovascular tests. This report documents the lesion of the motor nerve fibers in this disease, as well as the preservation of the autonomic nervous system function, therefore suggesting that HSNA is an inappropriate name for this disorder.

Action Potentials↗
PubMed2004

Cramps, muscle pain, and fasciculations: not always benign?

Fasciculation and cramps without weakness or muscle atrophy are recognized as a benign syndrome. The authors report a patient with cramp and fasciculation, which persisted for 1 year without abnormal motor unit morphology on EMG before progressive weakness, muscle atrophy, and EMG abnormalities developed. This observation raises the possibility that lower motor neuron hyperexcitability may precede motor neuron death in motor neuron disease.

Accidental Falls↗
PubMed2004

Repetitive nerve stimulation in myasthenia gravis--relative sensitivity of different muscles.

OBJECTIVE: To correlate repetitive nerve stimulation (RNS) decrement in different muscles with the predominant clinical presentation in myasthenia gravis (MG), and to study single fibre EMG (SFEMG) sensitivity in ocular MG. METHODS: Sixty-nine, untreated, consecutive patients suspected for MG were observed prospectively for a minimum of 6 months. Those who improved on medical treatment were diagnosed as MG. The others, in whom the neurophysiological studies were normal and that did not improve on medical treatment served as a control group, from which normative data for RNS and SFEMG was obtained. The MG patients were further classified in 3 subgroups according to the predominant clinical presentation: group I (ocular); group b (bulbar); and group a (axial). We performed RNS in nasalis, trapezius, anconeus, and abductor digiti minimi. All patients with ocular MG underwent jitter determination of the orbicularis oculi muscle. RESULTS: Thirty-seven patients were diagnosed as MG (group I, 15; group b, 13; group a, 9). In group I, RNS was abnormal in 33% of the patients. RNS studies disclosed at least one abnormal muscle response in every patient in groups a and b. Trapezius was significantly more sensitive in group a, and anconeus and nasalis in group b (P < 0.01). Jitter was abnormal in all patients in group I, and the most sensitive parameter was an increased number of unstable pairs, 100%. CONCLUSIONS: Based on these observations, we recommend that a shoulder muscle, as the trapezius, should be studied first in the limb-axial presentation of MG, and the anconeus-nasalis muscles in predominant bulbar MG. In ocular MG, RNS is not sensitive and jitter should be performed in facial muscles. SIGNIFICANCE: This paper shows the unequal sensitivity of several muscles to RNS in different forms of MG.

Adult↗
PubMed2004

Mutant fibrinogen A-alpha-chain associated with hereditary renal amyloidosis and peripheral neuropathy.

A middle age Portuguese woman was investigated for renal amyloidosis. She presented with progressive renal failure, proteinuria, hypertension, and sensory symptoms in the feet. Clinical and neurophysiological evaluation disclosed sensory-autonomic neuropathy. Cardiovascular tests and 123-MIBG investigation showed parasympathetic dysfunction and decrease of myocardial innervation, in accordance with small fiber neuropathy, as usually observed in amyloidosis. Immunohistochemical studies revealed AFib amyloidosis and genetic studies the amino acid exchange Glu526Val of the fibrinogen Aalpha-chain mutation, which was also present in one of her sons. The mutant gene in this patient was associated with the same haplotype as all other reported cases of Glu526Val mutations. This is the first reported AFibamyloidosis in Portugal, and the first case of AFib in which sensory and autonomic nerve fiber dysfunction is described, indicating that small nerve fiber lesion can occur in the fibrinogen Aalpha chain mutation. This can be important for prognosis, in particular when liver transplantation is considered for treatment.

Amino Acid Substitution↗