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2.
Drug Healthc Patient Saf ; 15: 51-62, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36824481

RESUMO

Hereditary amyloid transthyretin (ATTRv) amyloidosis is a devastating hereditary multisystemic disease affecting predominantly the peripheral and autonomic nervous systems and the heart. ATTRv is caused by mutations in the transthyretin (TTR) gene, leading to extracellular deposition of amyloid fibrils in multiple organs including the peripheral nervous system. If untreated, it is associated with a fatal outcome 10-12 years after disease onset. Different treatments are available for patients with ATTRv polyneuropathy. Tafamidis 20 mg is approved in Europe since 2011 for early stages of ATTRv polyneuropathy (stage I - able to walk without support) and it is recommended as first-line therapy in these patients. Tafamidis is a TTR stabilizer that selectively binds to TTR and kinetically stabilizes both wild-type native TTR and mutant TTR. Consequently, it has the potential to prevent the amyloidogenic cascade initiated by TTR tetramer dissociation into its monomers and subsequent misfolding and aggregation. Tafamidis is an oral drug, taken once per day, with proved efficacy, safety and tolerability in ATTRv-PN patients as demonstrated in different clinical trials and open-label extension studies as well in clinical practice setting with around 10 years of experience. Tafamidis treatment started in the earliest stages of the disease is associated with better neurological outcomes. A multidisciplinary approach in referral centres is also fundamental for monitoring patients to assess individual response to treatment.

3.
Front Neurol ; 13: 1064619, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36733448

RESUMO

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 desirable. We analyzed the diagnostic pathway in different countries in order to identify the major challenges. Methods: We studied a cohort of 1,405 ALS patients from five different centers, in four different countries (Turkey, Germany, Poland, and Portugal), which collaborated in a common database. Demographic, disease and sociocultural factors were collected. Time from first symptom onset to first medical evaluation and to diagnosis, the specialist assessment and investigations requested were analyzed. Factors contributing to diagnostic delay were evaluated by multivariate linear regression. Results: The median diagnostic delay from first symptom onset was 11 months and was similar between centers. Major differences were seen in the time from symptom onset to first medical evaluation. An earlier first medical evaluation was associated with a longer time to diagnosis, highlighting that ALS diagnosis is not straightforward in the early stages of the disease. The odds for ALS diagnosis were superior when evaluated by a neurologist and increased over time. Electromyography was decisive in establishing the diagnosis. Conclusions: We suggest that a specific diagnostic test for ALS-a specific biomarker-will be needed to achieve early diagnosis. Early referral to a neurologist and to electromyography is important for early ALS diagnosis.

4.
Front Neurol ; 12: 761355, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803894

RESUMO

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. Methods: We studied a cohort of 580 ALS patients followed up in our ALS clinic in Lisbon. Demographic, disease, and sociocultural factors were collected. Time from first symptom onset to diagnosis, the specialist's assessment, and investigations requested were analyzed. Predictors of diagnostic delay were evaluated by multivariate linear regression, adjusting for potential confounders. Results: The median diagnostic delay from first symptom onset was 10 months. Spinal-onset, slower disease progression, cognitive symptoms at onset, and lower income were associated with increased diagnostic delay. Most patients were first assessed by general practitioners. Patients who were first evaluated by a neurologist were more likely to be correctly diagnosed, decreasing time to diagnosis. Electromyography was decisive in establishing the diagnosis. Conclusions: Late referral from non-neurologists to a neurologist is a potentially modifiable factor contributing to significant diagnostic delay. Educational interventions targeted to non-neurologists physicians, in order to increase awareness of ALS and, consequently, promote early referral to a neurologist at a tertiary center, will be important in reducing diagnostic delay.

5.
Case Rep Neurol Med ; 2019: 5976410, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885962

RESUMO

Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) is a rare autosomal recessive disorder caused by mutations in the gene encoding the Thymidine Phosphorylase (TP). It is clinically characterized by severe gastrointestinal dysmotility, cachexia, palpebral ptosis, ophthalmoparesis, sensorimotor polyneuropathy and leukoencephalopathy. The diagnosis is established by the presence of typical clinical and neuroimaging features, positive family history, and abnormal genetic test. A 19-year-old Cape Verdean patient with a history since childhood of recurrent episodes of nausea, vomiting, diarrhoea and painful abdominal distension associated with progressive motor disability with difficulty in climbing stairs and running and clumsiness with her hands. The diagnostic workup was suggestive of MNGIE. Genetic screening of the TYMP gene identified a novel mutation (c. 1283 G>A). Patients with MNGIE have significant comorbidity and mortality, and they are frequently misdiagnosed. A better acknowledgment of this disorder is essential to permit an earlier diagnosis and to improve disease management.

6.
J Peripher Nerv Syst ; 24(4): 354-358, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31596031

RESUMO

Hereditary sensory autonomic neuropathy (HSAN) type II is a rare, autosomal recessive, and early onset sensory neuropathy, characterized by severe and progressive sensation impairment, leading to ulcero-mutilating complications. FAM134B gene, also known as RETREG1 gene, mutations have been reported to be associated to HSAN-IIB. We report four patients from two unrelated families who developed during childhood a sensory axonal neuropathy with variable severity and pronounced nociception impairment. Complications such as recurrent ulcerations, osteomyelitis, and osteonecrosis leading to distal amputation were noticed. Dysautonomia was mild or even absent in our group of patients. Additionally, either clinical or neurophysiological motor impairment was not uncommon. Presence of upper motor neuron signs was also a distinctive feature in two related patients. After extensive workup, two novel homozygous mutations in the FAM134B gene were identified. This report expands the clinical and genetic spectrum of HSAN type II and emphasizes the phenotype variability even within the same family.


Assuntos
Neuropatias Hereditárias Sensoriais e Autônomas/genética , Neuropatias Hereditárias Sensoriais e Autônomas/fisiopatologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Adulto , Consanguinidade , Feminino , Humanos , Mutação , Linhagem , Irmãos , Adulto Jovem
8.
J Clin Neurosci ; 64: 8-10, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30955949

RESUMO

Distal myopathies are a clinically and genetically heterogeneous group characterized by distal weakness at onset. Distal myopathies are classified according to age of onset, inheritance pattern, clinical features and molecular diagnosis. Inclusion body myopathy with early-onset Paget disease and fronto-temporal dementia is a rare adult late-onset disease related to valosin-containing protein gene mutations with an autosomal dominance inheritance. It is characterized by the triad of progressive myopathy, early-onset Paget disease and premature fronto-temporal dementia We report a severe phenotype in a Portuguese patient, related to a novel mutation in the valosin-containing protein gene, characterized by a severe late-onset distal myopathy and a rapidly progressive cognitive dysfunction suggesting fronto-temporal dementia. The patient did not manifest Paget disease. Family history was negative. This case emphasizes the importance of considering inclusion body myopathy with early-onset Paget disease and fronto-temporal dementia in the differential diagnosis of distal myopathies, even in the absence of family history.


Assuntos
Demência Frontotemporal/diagnóstico , Demência Frontotemporal/genética , Distrofia Muscular do Cíngulo dos Membros/diagnóstico , Distrofia Muscular do Cíngulo dos Membros/genética , Miosite de Corpos de Inclusão/diagnóstico , Miosite de Corpos de Inclusão/genética , Osteíte Deformante/diagnóstico , Osteíte Deformante/genética , Proteína com Valosina/genética , Diagnóstico Diferencial , Miopatias Distais/diagnóstico , Miopatias Distais/genética , Feminino , Humanos , Pessoa de Meia-Idade , Mutação
9.
Neurophysiol Clin ; 49(1): 81-86, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30554965

RESUMO

OBJECTIVES: Myasthenia gravis (MG) is an autoimmune disease associated with antibodies against the nicotinic muscle acetylcholine receptor (AChR) at the neuromuscular junction. Dysautonomia has been previously described in MG. Electrochemical skin conductance (ESC), assessed by Sudoscan®, is a non-invasive method that allows evaluation of sudomotor function. Since sweat glands are innervated by sudomotor, postganglionic, cholinergic sympathetic C-fibers, we hypothesized that ESC could be a reliable method for assessing autonomic dysfunction in MG. METHODS: ESC measurements were prospectively assessed in patients with generalized MG and in healthy controls. Patients with diabetes mellitus, anticholinergic medication or electrophysiological findings of peripheral neuropathy were excluded. Data regarding demographic and disease features were collected. Presence of autonomic symptoms in patients with MG was assessed by Compass-31. For statistical analysis we performed student t-test and Chi2 test for comparison between both groups. RESULTS: We included 24 patients (mean age of 46.4±10.6, 75% women, mean disease duration 12.5 years, 62.5% positive for AChR antibodies) and 37 controls. We found no difference in either foot (P=0.13) or hand (P=0.83) ESC measurements between patients and controls, even after correcting for age. CONCLUSION: We could not prove the presence of autonomic sympathetic dysfunction in our cohort of MG patients when assessed by Sudoscan®. In addition, Compass-31 was not a useful questionnaire in this clinical context.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Mãos/fisiopatologia , Miastenia Gravis/fisiopatologia , Adulto , Diabetes Mellitus Tipo 2/complicações , Feminino , Pé/fisiopatologia , Resposta Galvânica da Pele/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade
11.
J Clin Neurosci ; 45: 153-154, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28867362

RESUMO

Riluzole is the only drug approved for the treatment of patients with Amyotrophic Lateral Sclerosis (ALS). It is well tolerated, being the most frequent adverse effects asthenia, nausea and reversible increase of liver enzymes levels. Severe adverse effects are extremely rare. We report for the first time, two patients with sporadic limb-onset ALS who developed recurrent acute pancreatitis (AP), with portal vein thrombosis as complication, during treatment with riluzole. We suggest that AP should be considered asa probable rare and severe side effect of treatment with riluzole in patients with ALS. We believe that in patients who develop AP during treatment with riluzole, its withdrawn may prevent recurrent AP and should be discussed with patients.


Assuntos
Pancreatite/induzido quimicamente , Riluzol/efeitos adversos , Idoso , Esclerose Lateral Amiotrófica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Neuroprotetores/efeitos adversos , Riluzol/uso terapêutico
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