Assuntos
Apraxias , Síndrome de Cogan , Ataxias Espinocerebelares , Apraxias/complicações , Apraxias/diagnóstico por imagem , Apraxias/genética , Síndrome de Cogan/complicações , Síndrome de Cogan/diagnóstico por imagem , Síndrome de Cogan/genética , Movimentos Oculares , Humanos , Mutação , Irmãos , Ataxias Espinocerebelares/complicações , Ataxias Espinocerebelares/congênito , Ataxias Espinocerebelares/diagnóstico por imagem , Ataxias Espinocerebelares/genéticaRESUMO
INTRODUCTION: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), previously known as hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) or pigmentary orthochromatic leukodystrophy (POLD), is the most frequent non-vascular adult-onset leukoencephalopathy. It is caused by autosomal dominant mutations in CSF1R gene. Recently, also autosomal recessive mutations in AARS2 gene were found to be the cause of an adult-onset leukodystrophy with axonal spheroids. Our aim was to achieve a genetic diagnosis in a cohort of CSF1R-negative patients, performing a sequence analysis of AARS2 gene. MATERIAL AND METHODS: AARS2 sequencing was performed in 38 CSF1R-negative patients with clinical and magnetic resonance imaging (MRI) findings of adult-onset leukoencephalopathy. RESULTS: Three patients carrying AARS2 compound heterozygous mutations have been found. All patients were female with ovarian failure and leukoencephalopathy. In 2 patients, MRI findings were consistent with previous reports while the third patient showed focal white matter (WM) lesions in the centrum semiovale and the corpus callosum in the absence of extensive involvement and rarefaction of the WM. MRI spectroscopy showed the presence of increased lactate in 2 patients, thus linking AARS2-related leukoencephalopathy with other mitochondrial leukoencephalopathies with high levels of cerebral lactate. CONCLUSION: We recommend screening for mutations in AARS2 gene in CSF1R-negative patients, also in the absence of a clear family history and peculiar MRI findings. Our results also suggest that findings of conventional MRI and MR spectroscopy may be useful in prompting the genetic screening.
Assuntos
Alanina-tRNA Ligase/genética , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/genética , Imageamento por Ressonância Magnética/métodos , Mutação/genética , Doenças Ovarianas/diagnóstico por imagem , Doenças Ovarianas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Corpo Caloso/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodosRESUMO
Mutations in OPA1 are responsible of 32-89% cases of Autosomal Dominant Optic Atrophy (ADOA). OPA1 ADOA usually presents in childhood with bilateral, progressive visual loss due to retinal ganglion cells neurodegeneration, but environmental factors are supposed to influence onset and phenotype. Sixty Italian OPA1 mutations carriers (fifty-two symptomatic), belonging to thirteen families, underwent neuro-ophthalmologic evaluation. Visual acuity (n=60) and Optical Coherence Tomography (OCT) (n=12) were compared in missense mutations (OPA-M) versus haploinsufficiency-inducing mutations (OPA-H) and correlated with age. Presence of plus phenotypes was investigated. We found four known mutations, the most common being missense c.1034G>A, and a new missense mutation, c1193A>C, the latter in a 54-yrs old female with late-onset phenotype. Visual acuity, colour sensitivity, and optic disc atrophy were sensitive indicators of disease. OCT RNFL thickness was reduced in OPA1 compared to controls. OPA-M showed worst visual acuity than OPA-H, but not more frequent plus-phenotype, observed only in four OPA-H patients. In both groups, visual acuity worsened with age. Our data confirm worst vision in OPA-M, but not increased plus-phenotype. Since most patients belonged to nine families from south-eastern Sicily (a famous region for the cult of St. Lucy, patron of the blinds) local genetic and environmental factors might have accounted for the low occurrence of plus-phenotypes.
Assuntos
GTP Fosfo-Hidrolases/genética , Mutação de Sentido Incorreto , Atrofia Óptica Autossômica Dominante/diagnóstico por imagem , Atrofia Óptica Autossômica Dominante/genética , Tomografia de Coerência Óptica , Adulto , Fatores Etários , Estudos de Coortes , Família , Feminino , Estudos de Associação Genética , Heterozigoto , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Atrofia Óptica Autossômica Dominante/fisiopatologia , Fenótipo , Acuidade Visual , Adulto JovemRESUMO
The Forkead Box G1 (FOXG1 in humans, Foxg1 in mice) gene encodes for a DNA-binding transcription factor, essential for the development of the telencephalon in mammalian forebrain. Mutations in FOXG1 have been reported to be involved in the onset of Rett Syndrome, for which sequence alterations of MECP2 and CDKL5 are known. While visual alterations are not classical hallmarks of Rett syndrome, an increasing body of evidence shows visual impairment in patients and in MeCP2 and CDKL5 animal models. Herein we focused on the functional role of FOXG1 in the visual system of animal models (Foxg1(+/Cre) mice) and of a cohort of subjects carrying FOXG1 mutations or deletions. Visual physiology of Foxg1(+/Cre) mice was assessed by visually evoked potentials, which revealed a significant reduction in response amplitude and visual acuity with respect to wild-type littermates. Morphological investigation showed abnormalities in the organization of excitatory/inhibitory circuits in the visual cortex. No alterations were observed in retinal structure. By examining a cohort of FOXG1-mutated individuals with a panel of neuro-ophthalmological assessments, we found that all of them exhibited visual alterations compatible with high-level visual dysfunctions. In conclusion our data show that Foxg1 haploinsufficiency results in an impairment of mouse and human visual cortical function.
Assuntos
Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Transtornos da Visão/genética , Transtornos da Visão/fisiopatologia , Animais , Pré-Escolar , Estudos de Coortes , Modelos Animais de Doenças , Potenciais Evocados Visuais/fisiologia , Feminino , Haploinsuficiência , Humanos , Lactente , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação , Neurônios/patologia , Neurônios/fisiologia , Retina/patologia , Retina/fisiopatologia , Síndrome de Rett/patologia , Síndrome de Rett/fisiopatologia , Acuidade Visual/fisiologia , Córtex Visual/patologia , Córtex Visual/fisiopatologia , Vias Visuais/patologia , Vias Visuais/fisiopatologia , Adulto JovemAssuntos
Transtornos da Motilidade Ocular/complicações , Síndrome de Zellweger/complicações , Humanos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Mutação/genética , Transtornos da Motilidade Ocular/genética , Fator 2 da Biogênese de Peroxissomos , Tempo de Reação/fisiologia , Síndrome de Zellweger/genéticaAssuntos
Doença de Alexander/genética , Variação Genética , Proteína Glial Fibrilar Ácida/genética , Doença de Alexander/patologia , Doença de Alexander/fisiopatologia , Encéfalo/patologia , Medições dos Movimentos Oculares , Movimentos Oculares , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Medula Espinal/patologiaRESUMO
BACKGROUND: Saccades are rapid eye movements used to gather information about a scene which requires both action and perception. These are usually studied separately, so that how perception influences action is not well understood. In a dual task, where the subject looks at a target and reports a decision, subtle changes in the saccades might be caused by action-perception interactions. Studying saccades might provide insight into how brain pathways for action and for perception interact. NEW METHOD: We applied two complementary methods, multifractal detrended fluctuation analysis and Lempel-Ziv complexity index to eye peak speed recorded in two experiments, a pure action task and a combined action-perception task. RESULTS: Multifractality strength is significantly different in the two experiments, showing smaller values for dual decision task saccades compared to simple-task saccades. The normalized Lempel-Ziv complexity index behaves similarly i.e. is significantly smaller in the decision saccade task than in the simple task. COMPARISON WITH EXISTING METHODS: Compared to the usual statistical and linear approaches, these analyses emphasize the character of the dynamics involved in the fluctuations and offer a sensitive tool for quantitative evaluation of the multifractal features and of the complexity measure in the saccades peak speeds when different brain circuits are involved. CONCLUSION: Our results prove that the peak speed fluctuations have multifractal characteristics with lower magnitude for the multifractality strength and for the complexity index when two neural pathways are simultaneously activated, demonstrating the nonlinear interaction in the brain pathways for action and perception.
Assuntos
Dinâmica não Linear , Tempo de Reação/fisiologia , Movimentos Sacádicos/fisiologia , Percepção Visual/fisiologia , Atenção/fisiologia , Humanos , Modelos Lineares , Estimulação LuminosaRESUMO
Saccadic eye movements of a normal subject were assessed through semi-quantitative analysis algorithms based on linear and non-linear test application in order to highlight the dynamics type characterizing saccadic neural system behavior. These movements were recorded during a simple visually-guided saccade test and one with a cognitive load involving button pressing to show a decision. Following the application of specific computational tests, chaotic dynamical trend dominancy was mostly revealed with some differences between the two saccade recording conditions: auto-correlation time was increased from 170 to 240 by cognitive task superposition and the Hurst exponent was enhanced from 0.52 to 0.76, denoting more persistence in the dynamics of saccadic system during increased neural activity related to cognitive task.
RESUMO
Optic atrophy type 1 (OPA1) gene mutation causes autosomal dominant optic atrophy (ADOA, MIM #165500). Prevalence of ADOA ranges from 1:50,000 in most populations to 1:12,000 in Denmark. Seventy members of nine families were analysed for the presence of OPA1 gene mutations by polymerase chain reaction (PCR) and direct sequencing. We identified three OPA1 gene mutations in 48 patients with variable signs of optic atrophy. Two mutations, c.784-21_784-22insAluYb8 and c.876_878delTGT, were found in two different families. The third mutation, c.869G>A, was found in 28 patients from seven families. The haplotype analysis data suggested that the c.869G>A mutation is a founder mutation. Our main result suggests a higher ADOA prevalence in south-eastern Sicily than previously found in Denmark. This is because of not only the founder effect but also to the presence of three different mutations in the geographical area of the study. Our hypothesis is that a combination of social pressure because of blindness and migration factors is involved. In fact, in Siracusa, a provincial capital in south-eastern Sicily, St. Lucy, the patron saint of the blind was born and died.
Assuntos
GTP Fosfo-Hidrolases/genética , Frequência do Gene , Mutação , Atrofia Óptica Autossômica Dominante/epidemiologia , Atrofia Óptica Autossômica Dominante/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Haplótipos , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Linhagem , Prevalência , SicíliaRESUMO
Wernicke encephalopathy (WE) is a neurological emergency due to thiamine deficiency. We aimed to identify clinical course and causes of diagnostic delay or failure of WE in a group of patients who underwent surgery for gastrointestinal tumors. A retrospective review of clinical, laboratory, neuroimaging, and therapeutic features of 10 patients with WE following abdominal surgery for cancer was carried out. Four patients died; in these subjects, diagnosis was delayed and supplementation of vitamin was absent or likely inadequate. Diagnostic delay or failure was also related to the coexistence of several medical complications at presentation masking typical symptoms of WE. In the surviving patients, outcome was influenced by promptness and type of therapy. Postoperative abdominal bleeding and number of subsequent operations may also had an effect. Postsurgical patients with gastrointestinal tumors may develop a subtle WE. The number of subsequent operations and the severity of postoperative complications may increase the risk of unrecognized WE. The disease should be suspected in postsurgical patients who have unexpected mental status changes, even under prophylactic treatment with vitamins. We suggest that prophylaxis with high doses of thiamine should be undertaken in patients with gastrointestinal tumors before surgery.
Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Neoplasias Gastrointestinais/cirurgia , Trato Gastrointestinal/cirurgia , Deficiência de Tiamina/diagnóstico , Deficiência de Tiamina/etiologia , Encefalopatia de Wernicke/diagnóstico , Encefalopatia de Wernicke/etiologia , Idoso , Erros de Diagnóstico/prevenção & controle , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Feminino , Trato Gastrointestinal/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Cuidados Pré-Operatórios/normas , Estudos Retrospectivos , Medição de Risco/métodosRESUMO
The purpose of this pictorial essay is to present the computed tomography (CT) and magnetic resonance imaging (MRI) findings of Wernicke's encephalopathy, a rare, severe, acute neurological syndrome due to thiamine (vitamin B1) deficiency, associated with high morbidity and mortality. The classical clinical triad, which includes ocular signs, altered consciousness and ataxia, can be found in only one-third of patients. Although chronic alcoholic patients are the most commonly affected, Wernicke's encephalopathy may complicate malnutrition conditions in nonalcoholic patients, in whom it is greatly underestimated. CT and above all MRI of the brain play a fundamental role in diagnosing the condition and ruling out other diseases. MRI is the most sensitive technique and is required in all patients with a clinical suspicion of Wernicke's encephalopathy. Medial thalami, mamillary bodies, tegmentum, periaqueductal region, and tectal plate are typical sites of abnormal MRI signal. The dorsal medulla, red nuclei, cranial nerve nuclei, cerebellum, corpus callosum, frontal and parietal cerebral cortex are less common sites of involvement although they are more frequently affected in nonalcoholic patients. Paramagnetic contrast material may help to identify lesions not otherwise visible.
Assuntos
Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Encefalopatia de Wernicke/diagnóstico , Diagnóstico Diferencial , Humanos , Prognóstico , Encefalopatia de Wernicke/diagnóstico por imagemRESUMO
BACKGROUND AND PURPOSE: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disease, because of sterol 27-hydroxylase deficiency. Clinical manifestations of CTX are tendon xanthomas, juvenile cataracts, osteoporosis, diarrhoea and multiple progressive neurological dysfunctions. More than 300 patients with CTX have been reported to date worldwide and about fifty different mutations identified in CYP27A1 gene. This study describes the clinical and laboratory findings of seven new patients. METHODS: We report the molecular and clinical characterization of seven new Italian patients with CTX carrying four novel mutations. RESULTS: We identified four novel mutations located in different exons, in particular in the region of exons 2-5 of the CYP27A1 gene. Phenotypical expression did not differ from classical CTX presentation except for absence of tendon xanthomas in two patients.
Assuntos
Colestanotriol 26-Mono-Oxigenase/deficiência , Colestanotriol 26-Mono-Oxigenase/genética , Predisposição Genética para Doença/genética , Mutação/genética , Xantomatose Cerebrotendinosa/enzimologia , Xantomatose Cerebrotendinosa/genética , Adolescente , Adulto , Feminino , Humanos , Itália , Masculino , Xantomatose Cerebrotendinosa/diagnóstico , Adulto JovemAssuntos
CADASIL/genética , Éxons , Mutação , Fenótipo , Receptores Notch/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Análise Mutacional de DNA , Família , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Linhagem , Receptor Notch3 , População Branca/genéticaRESUMO
BACKGROUND AND PURPOSE: Although sudden death (SD) accounts for numerous cases of premature mortality in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the risk factors responsible for this dramatic event remain unclear. We sought possible differences in the QT variability index (QTVI) -- a well-known index of temporal dispersion in myocardial repolarization strongly associated with the risk of SD -- between a group of patients with CADASIL and healthy controls. METHODS: A total of 13 patients with CADASIL and 13 healthy volunteers underwent a 5-min electrocardiogram recording to calculate the QTVI. All the patients also underwent a clinical assessment, including functional status by Rankin score, and a magnetic resonance imaging (MRI) brain scan for quantitative analysis of T2-weighted (T2-W) and T1-weighted (T1-W) lesion volume (LV). RESULTS: Short-term QT-interval analysis showed significantly higher QTVI (P = 0.029) in patients than in controls. In patients, notwithstanding the limitations of the small sample size, QTVI also well correlated with T1-W LV (r = 0.747, P = 0.003) and T2-W LV (r = 0.731, P = 0.005). CONCLUSION: Because patients with CADASIL have increased temporal cardiac repolarization variability as assessed by QTVI, this mechanism could underlie these patients' risk of SD. Whether this easily assessed, non-invasive marker could be used to stratify the risk of malignant ventricular arrhythmias in patients with CADASIL and, possibly, to guide their therapeutic management warrants confirmation from larger prospective studies.
Assuntos
Arritmias Cardíacas/etiologia , CADASIL/complicações , Morte Súbita Cardíaca/etiologia , Adulto , Idoso , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Encéfalo/fisiopatologia , Artérias Cerebrais/patologia , Eletrocardiografia , Feminino , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca/fisiologia , Ventrículos do Coração/inervação , Ventrículos do Coração/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos TestesRESUMO
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary form of small vessel disease in which the pons may show lacunar infarcts and leukoaraiosis. Acute pure vestibular syndrome may be due to caudal pontine lesions and is probably underestimated. We describe a case of CADASIL with acute vestibular syndrome mimicking peripheral vestibulopathy, and evidence of focal infarction in the ponto-medullary junction at gadolinium-enhanced MRI including diffusion-weighted imaging, involving the area of the right vestibular nucleus and root entry zone of the ipsilateral vestibular nerve bundle. In CADASIL, both focal brainstem lesions and leukoaraiosis may parallel supratentorial white matter changes and may be related to poor outcome. Their actual extent should be evaluated in longitudinal studies that might predict clinical outcome and progression of disability.
Assuntos
CADASIL/complicações , Infarto Cerebral/complicações , Doenças Vestibulares/complicações , Adulto , CADASIL/patologia , Infarto Cerebral/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Doenças Vestibulares/patologiaAssuntos
Colestanotriol 26-Mono-Oxigenase/genética , Predisposição Genética para Doença/genética , Mutação/genética , Xantomatose Cerebrotendinosa/diagnóstico , Xantomatose Cerebrotendinosa/genética , Adolescente , Argentina , Encéfalo/enzimologia , Encéfalo/patologia , Encéfalo/fisiopatologia , Colestanol/sangue , Colesterol/metabolismo , Análise Mutacional de DNA , Feminino , Marcadores Genéticos/genética , Testes Genéticos , Genótipo , Humanos , Deficiência Intelectual/enzimologia , Deficiência Intelectual/genética , Deficiência Intelectual/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Mitocôndrias/enzimologia , Mitocôndrias/genética , Tremor/enzimologia , Tremor/genética , Tremor/fisiopatologia , Xantomatose Cerebrotendinosa/fisiopatologiaRESUMO
Acquired or hereditary prothrombotic risk factors may lead to cerebral venous sinus thrombosis (CVST), particularly when other predisposing factors coexist. A 57-year-old man experienced right leg deep venous thrombosis, severe thrombosis of the haemorrhoid plexus and CVST over a 12-month period during which he was taking sildenafil regularly twice a week. Sildenafil is a phosphodiesterase 5 (PDE5)-inhibitor used for erectile dysfunction (ED). A slight reduction in antithrombin III and free protein S levels was demonstrated. After suspension of sildenafil and six months on oral anticoagulants, clinical improvement was obtained. Recurrent venous thrombosis, including CVST, may complicate prolonged treatment with PDE5-inhibitors in subjects at risk. Periodic monitoring of clotting factors is recommended in these subjects.