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INTRODUCTION: Thymectomy remains a mainstay of treatment in Thymomatous (T) and Nonthymomatous (nT) Myasthenia Gravis (MG), with improved clinical outcomes and reduced need for medical treatment, however, there is little research regarding long-term follow-up. We aim to assess the impact of surgery on the long-term outcome of patients with MG at our center. METHODS: Retrospective analyses of MG patients submitted to thymectomy between 2007 and 2017 at the thoracic surgery department of CHUC. Clinical assessment was performed according to the MG Foundation of America (MGFA) Clinical Classification (cMGFA). The follow-up was categorized according to the MGFA Post-intervention Status (MGFA-PIS) and cMGFA. Statistical analysis was performed with SPSS, to a significance level of 5%. RESULTS: Thirty-seven patients underwent extended thymectomy and 67.6% were female. Median age at diagnosis was 46.68±19.2 years. Most patients (83.8%) had anti-acetylcholine receptor antibodies and 81.1% had generalized forms of MG. Many patients (67.6%) had surgery less than 12 months after the clinical diagnosis. TMG was present in 19 (51.4%) patients. Compared to nTMG, these patients were older (54.06±17.9 vs 40.17±19.4 years) and most were men (52.9% vs 16.7%). We obtained a good outcome in most patients in the first (81.1%), second (86.1%), and fifth (84.8%) year of follow-up. There was a shift towards better prognosis categories in the good outcome group: 9.1% CSR, 3.0% PR, and 66,7% MM in the fifth year. Preoperative medical treatment did not influence the long-term follow-up outcome. A shorter time to surgery (< 12 months) correlated with better outcomes at year 5 (p=0.016). CONCLUSION: Thymectomy led to a sustained clinical improvement in our cohort, allowing for a reduced need for medication. A shorter time to surgery seems to have a positive influence on long-term prognosis. We expect that an extended follow-up would improve our results.
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Miastenia Gravis , Timectomia , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Timectomia/métodos , Resultado do Tratamento , Estudos Retrospectivos , Miastenia Gravis/cirurgia , PrognósticoRESUMO
INTRODUCTION AND OBJECTIVES: Childhood offers an excellent window of opportunity to start interventions to promote behavioral changes before unhealthy lifestyles become established, leading to cardiovascular diseases. The goal of this pilot educational project for children is the promotion of healthy lifestyles and cardiovascular health. METHODS: This project was implemented in 4th grade children and included teacher-led classroom activities, a lesson given by a cardiologist and a practical lesson with dietitians. The teacher received a manual containing information on the topics to be discussed in class with the pupils and the children received a book that addresses cardiovascular risk factors and prevention. The components included were diet (D), physical activity (PA) and human body and heart awareness (BH). At the beginning and at the end of the schoolyear, a questionnaire was applied to the children to assess knowledge (K), attitudes (A) and habits (H) on these topics. RESULTS: A total of 73 children from an urban public school in Lisbon, in a low to medium income area, participated in the project. Following the intervention, there was a 9.5% increase in the overall KAH score, mainly driven by the PA component (14.5%) followed by the BH component (12.3%). No improvement was observed for component D. The benefits were also more significant in children from a lower income area, suggesting that socioeconomic status is a determinant in the response obtained. CONCLUSIONS: An educational project for cardiovascular health can be implemented successfully in children aged 9 years, but longer and larger studies are necessary.
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Introduction: Oculopalatal tremor (OPT) is a late manifestation of a Guillain-Mollaret triangle lesion. Memantine has been shown to improve nystagmus in OPT, but its long-term efficacy and putative distinct effects on each plane of nystagmus and on associated phenomena (e.g., gravity perception) are largely unknown. Methods: We conducted a 6-month open-label study to evaluate the effect of memantine in OPT patients. Baseline (visit 1), 2 (visit 2), and 6 months (visit 3) assessments included video-oculography, best corrected visual acuity (BCVA), visual function questionnaire (VFQ25), palatal tremor frequency, and subjective visual vertical (SVV). Memantine was titrated to 20 mg per day and stopped after 6 months. Results: We included six patients (5 females; mean age 68.5+/-9.7). At visit 2, nystagmus improved >50% only along the horizontal plane in two patients, while worsening >50% along the vertical and horizontal planes in 4 and 1 patients, respectively. At visit 3, previous improvement of nystagmus along the horizontal plane in two patients was not sustained, and it further worsened >50% along the vertical plane in 4. The mean vertical velocity and amplitude of nystagmus in the left eye significantly worsened from visit 2 to visit 3 (p = 0.028). Throughout the study, nystagmus frequency remained unchanged (p = 0.074), BCVA improved in both eyes (p = 0.047, p = 0.017), SVV progression was unpredictable (p = 0.513), and the mean VFQ-25 score (p = 0.223) and mean palatal frequency remained unchanged. Conclusion: The long-term use of memantine 20 mg per day in OPT produced a modest and only transient improvement in nystagmus, predominantly along the horizontal plane. Visual acuity improved, albeit without relevant changes in vision-related quality of life.
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Neuromuscular diseases are genetically highly heterogeneous, and differential diagnosis can be challenging. Over a 3-year period, we prospectively analyzed 268 pediatric and adult patients with a suspected diagnosis of inherited neuromuscular disorder (INMD) using comprehensive gene-panel analysis and next-generation sequencing. The rate of diagnosis increased exponentially with the addition of genes to successive versions of the INMD panel, from 31% for the first iteration (278 genes) to 40% for the last (324 genes). The global mean diagnostic rate was 36% (97/268 patients), with a diagnostic turnaround time of 4-6 weeks. Most diagnoses corresponded to muscular dystrophies/myopathies (68.37%) and peripheral nerve diseases (22.45%). The most common causative genes, TTN, RYR1, and ANO5, accounted for almost 30% of the diagnosed cases. Finally, we evaluated the utility of the differential diagnosis tool Phenomizer, which established a correlation between the phenotype and molecular findings in 21% of the diagnosed patients. In summary, comprehensive gene-panel analysis of all genes implicated in neuromuscular diseases facilitates a rapid diagnosis and provides a high diagnostic yield.
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Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive inflammatory vasculopathy characterized by systemic vasculitis, early-onset stroke and livedo racemosa. We report a family cohort of 3 patients with ADA2 compound heterozygous mutation p.[Thr360Ala] and [Gly383Ser]. Two of them had progressive involvement of the peripheral nervous system in the fourth decade, both after stroke. In one patient, clinical and neurophysiological studies showed progression of mononeuritis multiplex to chronic axonal sensorimotor polyneuropathy, nerve biopsy had features of small vessel vasculitic neuropathy, and muscle biopsy disclosed neurogenic atrophy with reinnervation. The second patient presented with progressive sensory symptoms of the lower limbs and chronic axonal sensorimotor polyneuropathy in nerve conduction studies. These two patients had absent plasma ADA2 activity. The third patient had no neurological affection despite low, but not absent, plasma ADA2 activity. Patients were started on a tumor necrosis factor (TNF) inhibitor, which has presumed benefits for the vasculitic phenotype of DADA2.
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Adenosina Desaminase/deficiência , Doenças do Sistema Nervoso Periférico/etiologia , Vasculite/etiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Mutação , Fenótipo , Adulto JovemRESUMO
Myopathies caused by MYH7 gene mutations are clinically and pathologically heterogeneous and, until recently, difficult to diagnose. The availability of NGS panels for hereditary neuromuscular diseases changed our insight regarding their frequency and allowed a better perception of the different phenotypes and morphological abnormalities associated. We present a male Portuguese patient with the classical phenotype of Laing early-onset distal myopathy (MPD1) beginning at 6 years of age, very slowly progressive, and with a mild to moderate impact on daily life by the age of 56. Muscle biopsy showed a myopathic pattern with hyaline bodies and cores. The NGS panel for structural myopathies identified a novel missense heterozygous variant, c.T4652C (p.Leu1551Pro), in the exon 34 of the MYH7 gene.
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Biópsia/métodos , Miosinas Cardíacas/genética , Miopatias Distais , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Músculo Esquelético/patologia , Atrofia Muscular , Cadeias Pesadas de Miosina/genética , Progressão da Doença , Miopatias Distais/diagnóstico , Miopatias Distais/genética , Miopatias Distais/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular , Atrofia Muscular/diagnóstico , Atrofia Muscular/fisiopatologia , Mutação de Sentido Incorreto , Exame Neurológico/métodosRESUMO
CMT disease caused by NEFL gene mutations is rare. The mode of inheritance can be dominant or recessive and nerve conduction velocities can be normal, reduced (demyelinating) or presenting intermediate values. Two Portuguese adult related members in two successive generations were affected by peripheral neuropathy, one with a chronic ataxic peripheral neuropathy and the other with a classical Charcot-Marie-Tooth phenotype. An axonal sensorimotor peripheral neuropathy was described at neurophysiology. A missense heterozygous mutation, c.794A > G (p.Tyr265Cys), in the NEFL gene was found in both patients. This is the first Portuguese family reported with NEFL-related CMT type 2.
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Doença de Charcot-Marie-Tooth/genética , Proteínas de Neurofilamentos/genética , Doenças do Sistema Nervoso Periférico/genética , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Linhagem , Fenótipo , PortugalRESUMO
Inflammatory myopathies comprise a group of rare autoimmune muscle diseases characterized by a variable degree of muscle weakness, elevated creatine kinase levels and necrotic fibres associated with invading inflammatory cells at histologic examination. Although there are several reports about their relationship with malignancy, association with papillary cancer of the thyroid gland is extremely rare. We present a case of a female patientdiagnosed withinflammatory myopathy and apapillary cancer of the thyroid gland, with a remarkable clinical improvement after thyroid cancer surgery and radioactive iodine treatment, supporting a correlation between the two conditions.
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Carcinoma Papilar/complicações , Carcinoma Papilar/diagnóstico , Miosite/etiologia , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/diagnóstico , Carcinoma Papilar/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Miosite/diagnóstico , Miosite/terapia , Neoplasias da Glândula Tireoide/terapiaRESUMO
INTRODUCTION: Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are considered part of the same pathological spectrum. There is an increased risk of ALS in patients who have had melanoma. The risk of FTLD in melanoma (or cancer) patients is unknown. We aimed to study if C9ORF72 expansion is linked to a higher prevalence of melanoma. METHODS: We selected patients with a diagnosis in the ALS-FTLD spectrum who were tested for pathogenic mutations. Medical history was reviewed, to identify those with pathologically documented melanomas. RESULTS: We included 189 patients. Sixty-two had identified pathogenic mutations (39 C9ORF72). C9ORF72 carriers had a significantly higher risk of melanoma (odds ratio = 24.709; P < 0.007). There was no association with phenotype. CONCLUSIONS: These findings suggest that patients with a history of melanoma may have an increased probability of carrying a C9ORF72 repeat expansion. ALS or FTLD carriers of C9ORF72 should undergo surveillance for skin changes. Muscle Nerve 59:362-365, 2019.
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Proteína C9orf72/genética , Melanoma/epidemiologia , Melanoma/genética , Idoso , Esclerose Lateral Amiotrófica/epidemiologia , Esclerose Lateral Amiotrófica/genética , Estudos de Casos e Controles , Expansão das Repetições de DNA/genética , Feminino , Degeneração Lobar Frontotemporal/epidemiologia , Degeneração Lobar Frontotemporal/genética , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , RiscoRESUMO
SIGMAR1 gene encodes a non-opioid endoplasmic reticulum (ER) protein which is involved in a large diversity of cell functions and is expressed ubiquitously in both central and peripheral nervous systems. Alterations of its normal function may contribute to two different phenotypes: juvenile amyotrophic lateral sclerosis (ALS 16) and distal hereditary motor neuropathies (dHMN). We present the case of a female patient, of 37-years-old, with distal muscle weakness and atrophy beginning in childhood and slowly progressive in the first two decades of life. Neurological examination revealed a symmetrical severe muscle wasting and weakness in distal lower and upper limbs, with claw hands, footdrop with equinovarus deformity and hammer toes, generalized areflexia and normal sensory examination. The electrodiagnostic study revealed a pure chronic motor peripheral nerve involvement without signs of demyelination. The molecular study found the deletion c.561_576del on exon 4 and a deletion of all exon 4, in the SIGMAR1 gene.
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Neuropatia Hereditária Motora e Sensorial/genética , Receptores sigma/genética , Adulto , Família , Feminino , Humanos , Mutação , Fenótipo , Portugal , Análise de Sequência de DNA , Receptor Sigma-1RESUMO
Congenital muscular dystrophy type 1A (MDC1A) is one of the main subtypes of early-onset muscle disease, caused by disease-associated variants in the laminin-α2 (LAMA2) gene. MDC1A usually presents as a severe neonatal hypotonia and failure to thrive. Muscle weakness compromises normal motor development, leading to the inability to sit unsupported or to walk independently. The phenotype associated with LAMA2 defects has been expanded to include milder and atypical cases, being now collectively known as LAMA2-related muscular dystrophies (LAMA2-MD). Through an international multicenter collaborative effort, 61 new LAMA2 disease-associated variants were identified in 86 patients, representing the largest number of patients and new disease-causing variants in a single report. The collaborative variant collection was supported by the LOVD-powered LAMA2 gene variant database (https://www.LOVD.nl/LAMA2), updated as part of this work. As of December 2017, the database contains 486 unique LAMA2 variants (309 disease-associated), obtained from direct submissions and literature reports. Database content was systematically reviewed and further insights concerning LAMA2-MD are presented. We focus on the impact of missense changes, especially the c.2461A > C (p.Thr821Pro) variant and its association with late-onset LAMA2-MD. Finally, we report diagnostically challenging cases, highlighting the relevance of modern genetic analysis in the characterization of clinically heterogeneous muscle diseases.
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Estudos de Associação Genética , Laminina/genética , Mutação , Fenótipo , Alelos , Biomarcadores , Encéfalo/anormalidades , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Biologia Computacional/métodos , Bases de Dados de Ácidos Nucleicos , Frequência do Gene , Variação Genética , Genótipo , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética/métodos , Distrofias Musculares/diagnóstico , Distrofias Musculares/genéticaRESUMO
A group of heterogeneous muscle diseases are caused by dystrophin gene (DMD) mutations. We hereby present a male patient with a diagnosis of symptomatic dilated cardiomyopathy at 44 years-old who developed, soon after, weakness of distal right upper limb. At the age of 58, neurological examination revealed severe atrophy of right thenar muscles, flexion contractures on the right elbow, wrist and fingers, bilateral calf hypertrophy, myotatic areflexia in the upper limbs and hyporeflexia in the lower limbs. Manual muscle examination showed distal weakness of right upper limb muscles, severe on abductor pollicis brevis and extensor pollicis longus, and milder on interossei, finger extensors and brachioradialis muscles. Further testing revealed CK of 1500 U/L, a myopathic pattern on electromyography, and myopathic changes on right deltoid muscle biopsy, with immunohistochemistry showing focal sub-expression of dystrophin. Cardiac workup revealed a severe reduction in left ventricular ejection fraction, with a left ventricle of increased dimensions and global hypo-contractibility. A next-generation sequencing based panel for muscular diseases was performed and a nonsense mutation (c.C7525T) was identified in exon 51 of DMD gene, present in 70% of the gene readings (consistent with mosaicism).
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Cardiomiopatia Dilatada/genética , Distrofina/genética , Debilidade Muscular/genética , Códon sem Sentido , Creatina Quinase/sangue , Eletromiografia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Mosaicismo , Músculo Esquelético/patologia , Extremidade Superior/fisiopatologiaRESUMO
Primary biliary cholangitis (PBC) is a rare chronic disease, characterized by progressive cholestasis that could end in end-stage liver disease. Its diagnosis is based in the presence of a cholestatic pattern and antimitochondrial antibodies. Neurological complications of PBC are unusual, but there are descriptions of association with myopathies and neuropathies, being polymyositis the most frequent. We report two cases of patients with the diagnosis of PBC with neurologic complications: one case with asymptomatic PBC and myopathy and another one with demyelinating neuropathy. Neurologic diseases in patients with PBC have been described mainly as case reports. The co-occurrence of both entities suggests the possible existence of a common pathogenic mechanism but the real etiopathogeny is still unknown.
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Cirrose Hepática Biliar/complicações , Doenças Neuromusculares/etiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Pompe disease is a rare metabolic disorder with available enzymatic replacement therapy. Contrasting with the classic infantile form, the others subtypes have a heterogeneous presentation that makes an early and accurate diagnosis difficult. We conducted a prospective, multicenter, observational study to identify undiagnosed patients. During a one-year period, patients followed in Portuguese neuromuscular outpatient clinics with proximal muscle weakness affecting upper and/or lower limbs, hyperCKemia in two or more determinations or hypotonia and hyperCKemia, were screened for acid α-glucosidase deficiency by dried blood spots. Lysosomal acid-alpha-1,4-glucosidase activity was determined by tandem mass spectrometry and positive results were confirmed by molecular study. From the 99 patients screened, Pompe disease was confirmed in 4, with age of onset ranging from 2.5 to 48 years, all with limb girdle muscle weakness, corresponding to a frequency of 4% in our cohort and 4.9% of limb girdle muscle weakness. Screening for Pompe disease in high risk populations, using dried blood spots, was already performed in some European populations. Apart from two negative Scandinavian studies, positive cases were confirmed in 2.8-7.9% of patients presenting with limb girdle muscle weakness and in 0-2.5% with isolated hyperCKemia.
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Teste em Amostras de Sangue Seco , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial , Criança , Pré-Escolar , Feminino , Doença de Depósito de Glicogênio Tipo II/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/diagnóstico , Debilidade Muscular/fisiopatologia , Portugal , Estudos Prospectivos , Risco , Adulto JovemRESUMO
Mutations of the encoding genes of collagen VI (COL6A1, COL6A2 and COL6A3), are responsible for two classical phenotypes (with a wide range of severity), the Ullrich congenital muscular dystrophy (UCMD) and the Bethlem myopathy (BM). We present a male patient of 49 years old, with symptoms of muscle weakness beginning in childhood and of very slowly progression. At the age of 42, the neurological examination revealed proximal lower limb muscle weakness and contractures of fingers flexors muscles, positive Gowers manoeuvre and a waddling gait. Serum creatine kinase (CK) values were slightly elevated, electromyographic study revealed myopathic changes and muscle MRI of the lower limbs showed a specific pattern of muscle involvement, with peripheral fat infiltration in vastus lateralis and intermedius and anterocentral infiltration in rectus femoris. Respiratory and cardiac functions were unremarkable. Whole exome sequencing identified the homozygous mutation c.1970-9G>A in COL6A2 gene.
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Colágeno Tipo VI/genética , Contratura/etiologia , Dedos , Debilidade Muscular/etiologia , Distrofias Musculares/congênito , Contratura/complicações , Contratura/diagnóstico , Contratura/genética , Marcha , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Distrofias Musculares/complicações , Distrofias Musculares/diagnóstico , Distrofias Musculares/genética , Mutação , PortugalRESUMO
Tremor frequency analysis is usually performed by EMG studies but accelerometers are progressively being more used. The iPhone® contains an accelerometer and many applications claim to be capable of measuring tremor frequency. We tested three applications in twenty-two patients with a diagnosis of PD, ET and Holmes' tremor. EMG needle assessment as well as accelerometry was performed at the same time. There was very strong correlation (Pearson >0.8, pâ<â0.001) between the three applications, the EMG needle and the accelerometry. Our data suggests the apps LiftPulse®, iSeismometer® and Studymytremor® are a reliable alternative to the EMG for tremor frequency assessment.
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Acelerometria/normas , Eletromiografia/normas , Tremor Essencial/diagnóstico , Aplicações da Informática Médica , Monitorização Ambulatorial/normas , Doença de Parkinson/diagnóstico , Smartphone , Tremor/diagnóstico , Acelerometria/instrumentação , Idoso , Humanos , Pessoa de Meia-Idade , Monitorização Ambulatorial/instrumentação , Doença de Parkinson/complicações , Reprodutibilidade dos Testes , Tremor/etiologiaRESUMO
Despite elevated incidence and recurrence rates for Primary Spontaneous Pneumothorax (PSP), little is known about its etiology, and the genetics of idiopathic PSP remains unexplored. To identify genetic variants contributing to sporadic PSP risk, we conducted the first PSP genome-wide association study. Two replicate pools of 92 Portuguese PSP cases and of 129 age- and sex-matched controls were allelotyped in triplicate on the Affymetrix Human SNP Array 6.0 arrays. Markers passing quality control were ranked by relative allele score difference between cases and controls (|RASdiff|), by a novel cluster method and by a combined Z-test. 101 single nucleotide polymorphisms (SNPs) were selected using these three approaches for technical validation by individual genotyping in the discovery dataset. 87 out of 94 successfully tested SNPs were nominally associated in the discovery dataset. Replication of the 87 technically validated SNPs was then carried out in an independent replication dataset of 100 Portuguese cases and 425 controls. The intergenic rs4733649 SNP in chromosome 8 (between LINC00824 and LINC00977) was associated with PSP in the discovery (P = 4.07E-03, ORC[95% CI] = 1.88[1.22-2.89]), replication (P = 1.50E-02, ORC[95% CI] = 1.50[1.08-2.09]) and combined datasets (P = 8.61E-05, ORC[95% CI] = 1.65[1.29-2.13]). This study identified for the first time one genetic risk factor for sporadic PSP, but future studies are warranted to further confirm this finding in other populations and uncover its functional role in PSP pathogenesis.
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Estudo de Associação Genômica Ampla/métodos , Pneumotórax/genética , Cromossomos Humanos Par 8/genética , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Fatores de RiscoRESUMO
INTRODUCTION: In this study we estimated the prevalence, incidence, and mortality of myasthenia gravis (MG) in northern Portugal and characterized the clinical features of the patients identified. METHODS: We used 2 data sources: clinical records from the hospitals and pyridostigmine prescription registers. RESULTS: On December 31, 2013, we estimated a point prevalence of 111.7 patients per million population. The highest prevalence was observed in the group >65 years of age, especially in men (288.1 per million). During 2013, we estimated an incidence rate of 6.3 per million per year. Among women, the incidence rate was highest in the 15-49-year age group; in men, incidence increased with age up to 22.1 per million in those >65 years old. The MG-related mortality rate was 0.5 per million. CONCLUSIONS: These figures are in keeping with similar studies and emphasize the importance of diagnosis and management of MG in elderly populations. Muscle Nerve 54: 413-421, 2016.
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Miastenia Gravis/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Anticorpos/sangue , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/sangue , Exame Neurológico , Portugal/epidemiologia , Prevalência , Receptores Proteína Tirosina Quinases/imunologia , Receptores Colinérgicos/imunologia , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Carpal tunnel syndrome is the most common type of peripheral entrapment neuropathy. PATIENTS & METHODS: We performed an exploratory, open-label, multicenter, observational study of 48 patients with peripheral entrapment neuropathy. Patients received a daily capsule of uridine monophosphate, folic acid + vitamin B12 for 2 months and were evaluated using the Pain DETECT questionnaire. RESULTS: The global score for pain decreased from 17.3 ± 5.9 at baseline to 10.3 ± 6.1 at the final evaluation (p < 0.001). Concomitant analgesic and anti-inflammatory treatment was stopped or the dose reduced in 77.4% of patients. CONCLUSION: Uridine monophosphate + folic acid + vitamin B12 reduced total pain score, intensity and characterization of pain and associated symptoms. These results should be tested in a well-designed, adequately powered randomized controlled trial.
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Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Ácido Fólico/uso terapêutico , Síndromes de Compressão Nervosa/tratamento farmacológico , Dor/tratamento farmacológico , Uridina Monofosfato/uso terapêutico , Vitamina B 12/uso terapêutico , Administração Oral , Adulto , Idoso , Síndrome do Túnel Carpal/complicações , Síndrome do Túnel Carpal/tratamento farmacológico , Feminino , Ácido Fólico/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes de Compressão Nervosa/complicações , Dor/etiologia , Medição da Dor , Síndrome do Túnel do Tarso/complicações , Síndrome do Túnel do Tarso/tratamento farmacológico , Resultado do Tratamento , Uridina Monofosfato/administração & dosagem , Vitamina B 12/administração & dosagemRESUMO
Muscular dystrophies (MDs) are a group of hereditary muscle disorders that include two particularly heterogeneous subgroups: limb-girdle MD and congenital MD, linked to 52 different genes (seven common to both subgroups). Massive parallel sequencing technology may avoid the usual stepwise gene-by-gene analysis. We report the whole-exome sequencing (WES) analysis of a patient with childhood-onset progressive MD, also presenting mental retardation and dilated cardiomyopathy. Conventional sequencing had excluded eight candidate genes. WES of the trio (patient and parents) was performed using the ion proton sequencing system. Data analysis resorted to filtering steps using the GEMINI software revealed a novel silent variant in the choline kinase beta (CHKB) gene. Inspection of sequence alignments ultimately identified the causal variant (CHKB:c.1031+3G>C). This splice site mutation was confirmed using Sanger sequencing and its effect was further evaluated with gene expression analysis. On reassessment of the muscle biopsy, typical abnormal mitochondrial oxidative changes were observed. Mutations in CHKB have been shown to cause phosphatidylcholine deficiency in myofibers, causing a rare form of CMD (only 21 patients reported). Notwithstanding interpretative difficulties that need to be overcome before the integration of WES in the diagnostic workflow, this work corroborates its utility in solving cases from highly heterogeneous groups of diseases, in which conventional diagnostic approaches fail to provide a definitive diagnosis.