RESUMO
OBJECTIVE: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, disimmune disease of the central nervous system whose etiology and pathogenesis remain poorly understood, due to its complex and multifactorial nature. Evidence of a bidirectional connection linking the gut microbiome with the intestinal barrier and the immune system (the gut-brain axis) may have implications for the pathogenesis of inflammatory demyelinating diseases such as MS. This narrative review summarizes the evidence for the gut-brain axis involvement in the pathogenesis of MS and examines the role of gut-oriented interventions in MS. PATIENTS AND METHODS: We reviewed all available studies in PubMed concerning gut-directed interventions and MS. This research was conducted using different combinations of pertinent keywords (multiple sclerosis, immune-mediated inflammatory diseases, autoimmune diseases, first demyelinating event, neurocognition, neurological disorders, neurology practice, risk factors, taxonomic biomarkers, nutrition, diet, dietary additives, complementary treatment, gut bacteria, gut microbiome, microbiome, gut-brain axis, epidemiology, alpha-linolenic acid, fermentative metabolites, fat, saturated fat, monounsaturated fat, polyunsaturated fat, omega-3 fatty acids, calorie restricted diet, fasting, fecal microbiome, fecal microbiota transplantation, animal testing). RESULTS: There is an emerging evidence that alterations in the gut microbiome and increased intestinal permeability may be causative factors in the complex interplay between nutrition, metabolic status and the immune-inflammatory response in patients with MS. This suggests the possibility that modification of lifestyle and the microbiome, for example by specific diets or fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers, may positively influence the pathogenesis of MS. CONCLUSIONS: Although the role of nutritional factors in the pathogenesis of MS remains to be established, there is evidence that appropriate gut-directed interventions such as diet, nutritional supplementation or fecal transplantation may modulate the inflammatory response and improve the course of MS as a complementary treatment in the disease.
Assuntos
Microbioma Gastrointestinal , Esclerose Múltipla , Animais , Ácidos e Sais Biliares , Sistema Nervoso Central , Transplante de Microbiota Fecal , HumanosRESUMO
OBJECTIVE: Aim of the research was to define the quality of life of Italian neurologists and nurses' professional caring for multiple sclerosis, to understand their living the clinical practice and identify possible signals of compassion fatigue. MATERIAL AND METHODS: One hundred five neurologists and nurses from 30 Italian multiple sclerosis centres were involved in an online quali-quantitative survey on the organization of care, combined with the Satisfaction and Compassion Fatigue Test and a collection of narratives. Descriptive statistics of the quantitative data were integrated with the results obtained by the narrative medicine methods of analysis. RESULTS: Most of the practitioners were neurologists, 46 average years old, 69% women, 43% part time dedicated to multiple sclerosis. An increased number of patients in the last 3 years were referred in 29 centres. Differences were found between neurologists and nurses. Physicians showed higher risks of burnout, reporting intensive working paces, lack of medical personnel, and anxiety caused by the precarious employment conditions. Nurses appeared more satisfied, although the reference to the lack of spaces, and the cross professional roles risk of compassion fatigue. Both positive and negative relationships of care were depicted as influencing the professional quality of life. CONCLUSION: The interviewed neurological teams need to limit the risk of compassion fatigue, which appeared from the first years of the career. The prevalence of the risk among neurologists suggests more awareness among scientific societies and health care managers on the risk for this category, as first step to prevent it.
Assuntos
Esclerose Múltipla , Qualidade de Vida , Estudos Transversais , Empatia , Feminino , Humanos , Itália/epidemiologia , Satisfação no Emprego , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/terapia , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To assess, by using quantitative MRI metrics, structural and metabolic brain abnormalities in subjects with preclinical cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL). BACKGROUND: Brain MRI abnormalities have been occasionally reported in preclinical CADASIL subjects. However, very little is known as to when the brain tissue damage starts to accumulate, what brain regions are primarily involved and whether the brain damage is significant in subjects who have no overt clinical manifestations of the disease. METHODS: Twelve subjects (mean age 40 years; range 26-55 years; males/females 6/6) with genetically proven CADASIL and no clinical signs of the disease underwent conventional MRI and proton MR spectroscopic imaging ((1)H-MRSI) to measure white matter (WM) lesion volume (LV), global and regional cerebral volumes, and WM levels of N-acetylaspartate (NAA) normalised to creatine (Cr). MR values were compared with those of 13 age- and sex-matched healthy controls. RESULTS: All preclinical CADASIL showed WM lesions (range 0.2 to 26 cm(3)). They were mostly distributed in the frontal and parietal regions, with the highest probability in the corona radiata. On (1)H-MRSI examination, NAA/Cr values were lower in preclinical CADASIL than in HC, particularly in the corona radiata (p<0.01). Normalised brain and cortical volumes were also lower in preclinical CADASIL than in HC (p<0.01), particularly in the frontal cortex. CONCLUSIONS: The pathological process occurring in CADASIL leads to damage of WM and neocortex much before the evidence of clinical symptoms. At this preclinical stage, this seems to take place prevalently in the frontal brain region.
Assuntos
CADASIL/metabolismo , CADASIL/patologia , Infarto Cerebral/metabolismo , Infarto Cerebral/patologia , Imageamento por Ressonância Magnética , Adulto , Fatores Etários , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Creatina/metabolismo , Feminino , Lobo Frontal/metabolismo , Lobo Frontal/patologia , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , PrótonsRESUMO
Autosomal dominant chronic progressive external ophthalmoplegia (AdPEO) is a muscle mitochondrial disorder due to multiple large scale rearrangements of the mitochondrial DNA. This disorder is probably due to a nuclear defect which causes genetic instability or an impairment in the replication of mitochondrial DNA. X-linked ichthyosis (XLI) is a skin disorder caused by a deletion in the steroid-sulphatase gene. Here we report the clinical, biochemical, morphologic and molecular genetic findings in a patient affected by both AdPEO, inherited by the father, and steroid-sulphatase-deficiency, inherited by the mother. The association in the same patient of the two inherited diseases is merely casual and does not seem to influence the phenotypic expression of the two diseases.
Assuntos
DNA Mitocondrial/genética , Ictiose , Oftalmoplegia Externa Progressiva Crônica , Cromossomo X , Idoso , Feminino , Genes Dominantes , Ligação Genética , Humanos , Ictiose/complicações , Ictiose/genética , Ictiose/patologia , Ictiose/fisiopatologia , Masculino , Oftalmoplegia Externa Progressiva Crônica/complicações , Oftalmoplegia Externa Progressiva Crônica/genética , Oftalmoplegia Externa Progressiva Crônica/patologia , Oftalmoplegia Externa Progressiva Crônica/fisiopatologia , Linhagem , Deleção de SequênciaRESUMO
Premature atherosclerosis and cardiac complications have been reported among the systemic manifestations of cerebrotendinous xanthomatosis (CTX), a rare bile acid disorder with predominantly neurological features. In some cases, myocardial infarction has been the cause of sudden death. We examined nine CTX patients to determine whether they also had clinical or subclinical signs of cardiovascular disorders. In four of them, transthoracic echocardiography showed thickening of the interatrial septum compatible with lipomatous hypertrophy. The unexpected association of the two abnormalities is unlikely to be coincidental and suggests that careful cardiac examination should be considered, even in the absence of clinical manifestations.
Assuntos
Cardiomegalia/etiologia , Lipomatose/etiologia , Xantomatose Cerebrotendinosa/complicações , Adulto , Cardiomegalia/patologia , Feminino , Átrios do Coração/patologia , Septos Cardíacos/patologia , Humanos , Lipomatose/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
The main mutation in fragile X patients is the expansion of the CGG repeat in the first exon of the FMR1 gene, associated with hypermethylation of the proximal CpG island. An increasing number of atypical cases have been reported showing the coexistence of full mutation and premutated or normal-sized alleles. These genotypes are more difficult to detect, and if a PCR strategy alone is adopted, they can be incorrectly identified. We report on a fragile X man with severe phenotype and mosaicism for full mutation and a (CGG)7 normal allele, the shortest fragment reported as yet in mosaics. This case of mosaicism, as other similar cases previously reported, suggests that the normal-length allele can derive from a deletion during the same early stage of development in which the full mutation expansion also arose.
Assuntos
Síndrome do Cromossomo X Frágil/genética , Mosaicismo , Mutação , Proteínas do Tecido Nervoso/genética , Proteínas de Ligação a RNA , Adulto , Alelos , Southern Blotting , Ilhas de CpG/genética , Metilação de DNA , Éxons/genética , Proteína do X Frágil da Deficiência Intelectual , Testes Genéticos , Humanos , Masculino , Reação em Cadeia da Polimerase , Deleção de Sequência , Expansão das Repetições de Trinucleotídeos/genética , Repetições de Trinucleotídeos/genéticaRESUMO
Perineurial cell ensheathment of muscle fibers has been reported only in one patient. Here we describe a new case with identical morphologic features and a similar, but milder clinical course characterized by progressive muscle weakness and bilateral palpebral ptosis. EMG examination (including repetitive stimulation) and antibodies against acetylcholine receptors were normal. Muscle biopsy revealed several muscle fibers encircled by stratified rings of homogeneous material in which elongated nuclei were visible; this material was positively stained by antibodies directed at epithelial membrane antigen. On ultrastructural examination these encircling-fiber spirals had the characteristics of perineurial cells. It is not clear yet whether perineurial cell ensheathment of muscle fibers is an occasional feature, or whether it has a pathogenetic role in the clinical picture of both cases. The perineurial sheaths might alter the correct neuromuscular transmission mimicking a myasthenia-like disease, either by interfering with the neuromuscular junction, or by changing the microenvironment, and, thus, altering the general excitability of the muscle fibers.
Assuntos
Blefaroptose/diagnóstico , Músculos Faciais/fisiopatologia , Debilidade Muscular/diagnóstico , Junção Neuromuscular/fisiopatologia , Biópsia , Blefaroptose/etiologia , Blefaroptose/patologia , Eletromiografia , Músculos Faciais/inervação , Músculos Faciais/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Fadiga Muscular/fisiologia , Fibras Musculares Esqueléticas/patologia , Debilidade Muscular/etiologia , Debilidade Muscular/patologia , Miastenia Gravis/complicações , Miastenia Gravis/diagnóstico , Junção Neuromuscular/patologiaRESUMO
Myasthenia gravis and mitochondrial myopathy may present with similar clinical symptoms as inconstant palpebral ptosis, ophthalmoparesis, and muscle weakness. A few case initially diagnosed as myasthenia gravis by a positive decremental response on EMG and successful anticholinesterase therapy revealed to be affected by mitochondrial disease. We report a new case initially found to be affected by myasthenia gravis in whom muscle biopsy, performed because of symptom worsening, disclosed a mitochondrial myopathy. It is not clear if the association of mitochondrial myopathy and myasthenia gravis is coincidental or if there is a pathogenic link between the two pathologies. We suggest that muscle biopsy should be performed in cases with atypical myasthenia gravis signs.