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1.
Port J Card Thorac Vasc Surg ; 30(4): 31-38, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38345885

RESUMO

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.


Assuntos
Miastenia Gravis , Timectomia , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Timectomia/métodos , Resultado do Tratamento , Estudos Retrospectivos , Miastenia Gravis/cirurgia , Prognóstico
2.
J Neurol ; 270(9): 4219-4234, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37171481

RESUMO

BACKGROUND: Leukodystrophy with vanishing white matter (LVWM) is an autosomal recessive disease with typical pediatric-onset caused by mutations in one of the five EIF2B genes. Adult-onset (AO) cases are rare. METHODS: In this observational study, we reviewed clinical and laboratory information of the patients with AO-LVWM assessed at two referral centers in Italy and Portugal from Jan-2007 to Dec-2019. RESULTS: We identified 18 patients (13 females) with AO-LVWM caused by EIF2B5 or EIF2B3 mutations. Age of neurological onset ranged from 16 to 60 years, with follow-ups occurring from 2 to 37 years. Crucial symptoms were cognitive and motor decline. In three patients, stroke-like events were the first manifestation; in another, bladder dysfunction remained the main complaint across decades. Brain MRI showed white matter (WM) rarefaction in all cases, except two. Diffusion-weighted imaging documented focal hyperintensity in the acute stage of stroke-like events. 1H-spectroscopy primarily showed N-acetyl-aspartate reduction; 18fluorodeoxyglucose-PET revealed predominant frontoparietal hypometabolism; evoked potential studies demonstrated normal-to-reduced amplitudes; neuro-ophthalmological assessment showed neuroretinal thinning, and b-wave reduction on full-field electroretinogram. Interestingly, we found an additional patient with LVWM-compatible phenotype and monoallelic variants in two distinct eIF2B genes, EIF2B1 and EIF2B2. CONCLUSIONS: AO-LVWM presents varying clinical manifestations at onset, including stroke-like events. WM rarefaction is the most consistent diagnostic clue even in the latest onset cases. Spectroscopy and electrophysiological features are compatible with axon, rather than myelin, damage. Cerebral glucose metabolic abnormalities and retinal alterations can be present. LVWM might also be caused by a digenic inheritance affecting the eIF2B complex.


Assuntos
Doenças Desmielinizantes , Leucoencefalopatias , Doenças por Armazenamento dos Lisossomos , Doenças Neurodegenerativas , Acidente Vascular Cerebral , Substância Branca , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Fator de Iniciação 2B em Eucariotos/genética , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/genética , Imageamento por Ressonância Magnética , Mutação/genética , Estudos Observacionais como Assunto , Substância Branca/diagnóstico por imagem
3.
BMJ Case Rep ; 15(11)2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36379630

RESUMO

Familial amyloidosis of the Finnish type (FAF) is a rare multisystemic disorder caused by mutations in the gelsolin gene. The clinical presentation is typically characterised by a triad of ophthalmic, neurological and dermatological findings. FAF has been reported in several countries, primarily in Finland and recently in Portugal. We report the first genetically confirmed cases of FAF from two unrelated families in our neuromuscular outpatient clinic. Gelsolin gene sequencing revealed the heterozygous gelsolin mutation (c.640G>A). The clinical features and the neurophysiological studies of two index patients and their relatives are presented. Obtaining an early diagnosis can be challenging, but FAF should be considered in the differential diagnosis of progressive bilateral facial neuropathy, even if there is no known Finnish ancestor.


Assuntos
Amiloidose Familiar , Gelsolina , Humanos , Gelsolina/genética , Finlândia , Amiloidose Familiar/diagnóstico , Amiloidose Familiar/genética , Mutação , Portugal
4.
Front Neurol ; 13: 921341, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061989

RESUMO

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.

5.
J Pediatr Genet ; 10(3): 253-258, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34504732

RESUMO

A Silver syndrome is a rare autosomal dominant spastic paraparesis in which spasticity of the lower limbs is accompanied by amyotrophy of the small hand muscles. The causative gene is the Berardinelli-Seip congenital lipodystrophy 2 ( BSCL2) , which is related to a spectrum of neurological phenotypes. In the current study, we presented a 14-year-old male with a slowly progressive spastic paraparesis with urinary incontinence that later on exhibited atrophy and weakness in the thenar and dorsal interosseous muscles. Magnetic resonance imaging (MRI) revealed discrete atrophy of the corpus callosum isthmus and an extended next-generation sequencing panel identified a de novo heterozygous mutation in BSCL2 gene, c.269C > T p.(S90L). Various clinical expression and incomplete penetrance of BSCL2 gene mutations complicate the establishment of a genetic etiology for these cases. Therefore, Silver syndrome should be included in the differential diagnosis if the initial presentation is a spastic paraparesis by urinary involvement with childhood-onset, even with MRI atypical findings. This report described the first Iberian Silver syndrome case carrying a de novo c.269C > T p. (S90L) BSCL2 gene mutation.

6.
Neuromuscul Disord ; 31(9): 891-895, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34210540

RESUMO

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.


Assuntos
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 Jovem
7.
Neurohospitalist ; 10(2): 133-138, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32373278

RESUMO

Herpes simplex virus encephalitis (HSVE) usually presents as a monophasic disease. Symptomatic HSVE relapsing with seizures, encephalopathy, or involuntary movements associated with anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis have been recently reported. We report 2 cases of adult post-HSVE anti-NMDAR encephalitis from Portugal. Two female patients aged 50 years and 30 years were diagnosed with herpes simplex virus type 2 and type 1 encephalitis, respectively. After the initial improvement with specific treatment and despite virologic negativization, both patients suffered clinical, electroencephalographic, and imaging deterioration. The autoimmune encephalitis hypothesis was confirmed with the demonstration of anti-NMDAR antibodies in both cerebrospinal fluid and serum. Both responded to human immunoglobulin and methylprednisolone, with progressive gain of autonomy along the follow-up period. Thymectomy for thymic hyperplasia diagnosed during follow-up was performed in 1 patient. Although being rare, post-HSVE anti-NMDAR encephalitis should be considered in all cases of symptomatic recrudescence after HSVE, since adequate immune-modulating treatment improves the outcome. The role of thyme hyperplasia in autoimmune encephalitis pathogenesis needs better understanding.

9.
Muscle Nerve ; 59(3): 362-365, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30447080

RESUMO

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.


Assuntos
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 , Risco
10.
Pract Neurol ; 18(5): 389-390, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29467180

RESUMO

Ocular neuromyotonia is a rare, albeit treatable, ocular motor disorder, characterised by recurrent brief episodes of diplopia due to tonic extraocular muscle contraction. Ephaptic transmission in a chronically damaged ocular motor nerve is the possible underlying mechanism. It usually improves with carbamazepine. A 53-year-old woman presented with a 4-month history of recurrent episodes of binocular vertical diplopia (up to 40/day), either spontaneously or after sustained downward gaze. Between episodes she had a mild left fourth nerve palsy. Sustained downward gaze consistently triggered downward left eye tonic deviation, lasting around 1 min. MR scan of the brain was normal. She improved on starting carbamazepine but developed a rash that necessitated stopping the drug. Switching to lacosamide controlled her symptoms.


Assuntos
Síndrome de Isaacs/complicações , Transtornos da Motilidade Ocular/complicações , Feminino , Fixação Ocular/fisiologia , Humanos , Pessoa de Meia-Idade
11.
Br J Ophthalmol ; 102(1): 102-108, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28487376

RESUMO

BACKGROUND/AIMS: Neurodegeneration with brain iron accumulation (NBIA) type I is a rare disease that can be divided into a classical or atypical variant, according to age of onset and clinical pattern. Neuro-ophthalmological involvement has been documented in the classical variant but only anecdotically in the atypical variant. We sought to describe the visual and ocular motor function in patients with atypical form of NBIA type I. METHODS: Cross-sectional study, including patients with genetically confirmed NBIA type I and classified as atypical variant, who underwent ophthalmological examination with best corrected visual acuity (BCVA), optical coherence tomography (OCT), fundus autofluorescence (FAF), electroretinography (ERG), visual evoked potentials (VEP) and video-oculography. RESULTS: Seven patients with a mean BCVA of 0.12±0.14 logMAR were included. Only two patients showed structural evidence of advanced retinopathy in OCT and FAF, and there were no cases of optic atrophy. ERG data, however, showed abnormal scotopic and/or photopic responses in all patients. VEP were normal in all three patients. Ocular fixation was markedly unstable (eg, increased rate of saccadic pulses) in the majority of patients (5). Additional mild ocular motor disturbances included low gain pursuit (2), hypermetric saccades (1), low gain optokinetic (2) and caloric and rotatory responses (3). CONCLUSION: Functional retinal changes associated with marked instability of ocular fixation should be included in the clinical spectrum of NBIA, particularly in the atypical form.


Assuntos
Potenciais Evocados Visuais/fisiologia , Movimentos Oculares/fisiologia , Distúrbios do Metabolismo do Ferro/complicações , Distrofias Neuroaxonais/complicações , Transtornos da Motilidade Ocular/fisiopatologia , Retina/fisiopatologia , Doenças Retinianas/fisiopatologia , Acuidade Visual , Adulto , Estudos Transversais , Eletrorretinografia , Feminino , Angiofluoresceinografia , Fundo de Olho , Humanos , Distúrbios do Metabolismo do Ferro/diagnóstico , Distúrbios do Metabolismo do Ferro/fisiopatologia , Masculino , Pessoa de Meia-Idade , Distrofias Neuroaxonais/diagnóstico , Distrofias Neuroaxonais/fisiopatologia , Transtornos da Motilidade Ocular/diagnóstico , Transtornos da Motilidade Ocular/etiologia , Retina/diagnóstico por imagem , Doenças Retinianas/diagnóstico , Doenças Retinianas/etiologia , Tomografia de Coerência Óptica , Adulto Jovem
12.
J Parkinsons Dis ; 6(4): 717-721, 2016 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-27662333

RESUMO

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, p < 0.001) 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.


Assuntos
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/etiologia
13.
Acta Med Port ; 29(9): 564-566, 2016 Sep.
Artigo em Português | MEDLINE | ID: mdl-28060695

RESUMO

Neurological manifestations of Lyme disease are reported in 3% - 12% of patients, with the most common form of presentation being meningoradiculitis. Other symptoms involving the central nervous system, such as myelitis or encephalitis, are rare (< 5 %). We report a case of a 66-year-old male, with a subacute extensive transverse myelitis, secondary to Borrelia burgdorferi infection. The patient underwent antibiotic therapy filed for neuroborreliosis with a good clinical outcome. The rareness in clinical symptoms and imaging presentation, based on a treatable infectious disease, highlights the importance of the inclusion of neuroborreliosis in the differential diagnosis of longitudinally extensive transverse myelitis.


As manifestações neurológicas na doença de Lyme ocorrem em 3% - 12% dos doentes, sendo a forma de apresentação mais comum a meningorradiculite. Outros sintomas de envolvimento do sistema nervoso central, como encefalomielite ou mielite são raros (< 5%). Descreve-se um caso clínico de um homem de 66 anos com uma mielite transversa extensa, de instalação subaguda, secundária a infeção por Borrelia burgdorferi. O doente foi submetido a terapêutica antibiótica dirigida, com uma boa evolução clínica. A raridade na forma de apresentação clínica e imagiológica deste caso, tendo como base uma doença infecciosa tratável, destaca a importância da sua inclusão no diagnóstico diferencial da mielite transversa longitudinalmente extensa.


Assuntos
Neuroborreliose de Lyme/diagnóstico , Mielite/microbiologia , Idoso , Humanos , Masculino
14.
BMJ Case Rep ; 20152015 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-25564591

RESUMO

Myasthenia gravis is an autoimmune disorder affecting predominantly women in their reproductive age. The course of the disease during pregnancy is unpredictable, although it is more difficult to manage earlier in the gestation. Myasthenia gravis with antibodies against the muscle-specific receptor tyrosine kinase (anti-MuSK) has been described as a subtype of disease with more localised clinical features and a poorer response to treatment than acetylcholine receptor antibody (anti-AChR)-positive patients. Few cases have been reported in pregnant women, with deliveries being performed mainly by caesarean section. We report a successful case of vaginal delivery and describe our experience providing the first review of the management of this subtype of disease during pregnancy.


Assuntos
Autoanticorpos/sangue , Parto Obstétrico , Miastenia Gravis/complicações , Complicações na Gravidez/imunologia , Receptores Proteína Tirosina Quinases/imunologia , Receptores Colinérgicos/imunologia , Adulto , Feminino , Humanos , Recém-Nascido , Masculino , Músculos , Miastenia Gravis/imunologia , Miastenia Gravis/terapia , Gravidez
15.
Rheumatol Int ; 35(1): 189-92, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24923906

RESUMO

Macrophagic myofasciitis (MMF) characterized by specific muscle lesions assessing long-term persistence of aluminum hydroxide within macrophages at the site of previous immunization has been reported with increasing frequency in the past 10 years. We describe clinical and laboratory findings in patients with MMF. We did a retrospective analysis of 16 cases observed in our Neuropathology Laboratory, between January 2000 and July 2013. The mean age of the 16 patients was 48.8 ± 18.0 years; 80.0 % were female. Chronic fatigue syndrome was found in 8 of 16 patients. Half of the patients had elevated creatinine kinase levels, and 25.0 % had a myopathic electromyogram. Thirteen patients received intramuscular administration of aluminum-containing vaccine prior to the onset of symptoms. MMF may mirror a distinctive pattern of an inflammatory myopathy. The vaccines containing this adjuvant may trigger MMF in some patients.


Assuntos
Adjuvantes Imunológicos/efeitos adversos , Fasciite/etiologia , Miosite/etiologia , Vacinação/efeitos adversos , Adulto , Idoso , Hidróxido de Alumínio/efeitos adversos , Fasciite/patologia , Feminino , Humanos , Injeções Intramusculares/efeitos adversos , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Miosite/patologia
16.
Acta Myol ; 33(3): 144-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25873783

RESUMO

INTRODUCTION: CMT4B2 is a rare subtype of CMT caused by pathogenic mutations in the myotubularin-related protein-13/set binding factor 2 (MTMR13/SBF2) gene. Nerve conduction velocities are markedly reduced and focally folded myelin sheaths are present on nerve biopsies. We presented two patients from two related Portuguese families with peripheral neuropathy caused by a novel mutation in the MTMR13/SBF2 gene. CASE REPORT: Family 1: Patient 1: A 30-year-old woman, with disease onset in early childhood presented pes cavus and hammertoes and walked with a steppage gait. Muscle weakness was present distally, myotactic reflexes were abolished and sensory examination revealed a stocking and glove pattern of hypoesthesia to all sensory modalities. Family 2: Patient 2: A 43-year-old man, second degree cousin of patient 1, born of a consanguineous marriage. At the age of 9 months, he was diagnosed with congenital glaucoma on the left eye, with progressive visual loss up to total blindness. He presented bilateral claw hand deformity, pes cavus and hammertoes and walked with a steppage gait. Myotactic reflexes were abolished and muscle weakness was severe distally in the upper and lower limbs. Sensory examination revealed a stocking and glove pattern of hypoesthesia to all modalities. In both patients electrodiagnostic studies evidenced an uniform and generalized sensorimotor demyelinating polyneuropathy and the molecular study found a frameshift/truncating homozygous novel mutation c.5073_5074del (p.Ser1692Tyrfs*42) in the MTMR13/SBF2 gene. CONCLUSIONS: We report a novel mutation in the MTMR13/SBF2 gene associated with a classical CMT phenotype. Congenital glaucoma associated with a frameshift/truncating mutation in CMT4B2 is reported for the first time.


Assuntos
Doença de Charcot-Marie-Tooth , Glaucoma , Doenças do Sistema Nervoso Periférico/etiologia , Proteínas Tirosina Fosfatases não Receptoras/genética , Adulto , Doença de Charcot-Marie-Tooth/complicações , Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/fisiopatologia , Consanguinidade , Feminino , Glaucoma/congênito , Glaucoma/etiologia , Humanos , Masculino , Mutação , Monitorização Neurofisiológica/métodos , Portugal
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