RESUMO
The human brain is increasingly seen as a dynamic neural system, the function of which relies on a diverse set of connections between brain regions. To assess these complex dynamical interactions, formalism of complex networks was suggested as one of the most promising tools to offer new insight into the brain's structural and functional organization, with a potential also for clinical implications. Irrespective of the brain mapping technique, modern network approaches have revealed fundamental aspects of normal brain-network organization, such as small-world and scale-free patterns, hierarchical modularity, and the presence of hubs. Moreover, the utility of these approaches, to gain a better understanding of neurological diseases, is of great interest. In the present contribution, we first describe the basic network measures and how the brain networks are constructed on the basis of brain activity data in order to introduce clinical neurologists to this new theoretical paradigm. We then demonstrate how network formalism can be used to detect changes in EEG-based functional connectivity patterns in six paediatric patients with childhood absence epilepsy. Notably, our results do not only indicate enhanced synchronicity during epileptic episodes but also reveal specific spatial changes in the electrical activity of the brain. We argue that the network-based evaluation of functional brain networks can provide clinicians with more detailed insight into the activity of a pathological brain and can also be regarded as a support for objective diagnosis and treatment for various neurological diseases.
Assuntos
Encéfalo/fisiopatologia , Conectoma , Eletroencefalografia , Epilepsia Tipo Ausência/fisiopatologia , Rede Nervosa/fisiopatologia , Criança , HumanosRESUMO
OBJECTIVES: The adult type of metachromatic leukodystrophy can manifest itself as motor or as psycho-cognitive form, the latter is very similar to schizophrenia. We report on two sisters with adult metachromatic leukodystrophy who display symptoms of both forms. METHODS: Presented are genotype analyses and 4-year follow-up data regarding clinical manifestations as well as neurocognitive and neuroimaging results for two adult sisters with metachromatic leukodystrophy. RESULTS: Whereas the younger sister developed disorganized schizophrenia-like symptoms, the other exhibited schizophrenia-like, negative symptoms. In both sisters, neurological signs were already present at the onset of the disease and progression towards dementia was documented within 1-2 years. In peripheral leukocytes, the activity of arylsulphatase A was reduced to 2 and 5% of the mean normal activity in both women. Genotype analysis revealed compound heterozygosity for a known severe splice site mutation, (c.459+1G>A) together with two known polymorphisms, [(c.937G>T), (p.Trp193Asp)] and [(c.1530C>G), (p.Thr391Ser)], and a novel missense mutation, (c.1194C>T). The latter results in the exchange of a conserved polar amino acid, threonine 279, to hydrophobic isoleucine (Thr279Ileu), which could not be found among >100 control alleles. A family analysis identified T279I as the paternal allele, whereas (c.459+1G>A) as well as the two polymorphisms were inherited from the mother. This is consistent with a disease-causing effect of the novel mutation. CONCLUSIONS: The novel mutation, T279I detected in our patients, correlates with a specific phenotype with schizophrenia-like symptoms, neurological signs and cognitive impairment early in the course of the disease and a relatively fast progression towards dementia. This is in contrast to previous reports on adult metachromatic leukodystrophy patients with the psycho-cognitive phenotype who did not show any neurological signs for decades, however, most of these patients were heterozygous for another specific missense mutation, I179S.
Assuntos
Demência/genética , Leucodistrofia Metacromática/genética , Esquizofrenia/genética , Adulto , Idade de Início , Processamento Alternativo , Cerebrosídeo Sulfatase/sangue , Cerebrosídeo Sulfatase/genética , Primers do DNA , Progressão da Doença , Feminino , Seguimentos , Humanos , Leucócitos/enzimologia , Masculino , Mutação , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo Único , IrmãosRESUMO
PURPOSE OF THE STUDY: To reassess the predictive role of clinical parameters and epileptiform paroxysmal EEG abnormalities for subsequent epilepsy in patients with febrile seizures. PATIENTS AND METHODS: 179 patients with febrile seizures were included in a prospective study investigating the impact of some clinical parameters and EEG abnormalities that could be important for future epilepsy. EEGs were performed in afebrile patients after hospital discharge. The follow-up period from the first presentation ranged from 2.1 to 9.2 years (mean, 6.6 years). The correlation between the development of epileptic seizures and the presence of epileptiform EEG abnormalities in the two groups was evaluated with the Mann-Whitney and chi-square test. Statistical significance was set at p<0.05. RESULTS: Febrile seizures occurred more than once in 58 (32.5%) patients, with one recurrence in 32 (17.9%) patients and multiple recurrences in 26 (14.5%) patients. The incidence of paroxysmal abnormalities was 16.8%. Of these, 15 patients (50%) showed generalized paroxysms only, while in 15 patients (50%), focal abnormalities were found. Epilepsy developed in 12 patients (6.7%). There were 27 patients with clinically focal features of the first febrile seizure, five (18.5%) of whom developed epilepsy. With focal EEG abnormalities included, the incidence of epilepsy increased to 50%. CONCLUSION: Generalized EEG discharges in patients with febrile seizures are not predictive of later epilepsy, but focal discharges are.
Assuntos
Córtex Cerebral/fisiopatologia , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Convulsões Febris/diagnóstico , Convulsões Febris/fisiopatologia , Pré-Escolar , Eletroencefalografia , Epilepsia/complicações , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Convulsões Febris/complicaçõesRESUMO
We describe the cases of 2 sisters with adult metachromatic leukodystrophy (MLD). Whereas one sister presented with disorganized schizophrenia-like symptoms as the initial manifestation of MLD, the other remained symptom free except for a 4-week period of postpartum depression. In both patients, there was some residual activity of leukocyte arylsulfatase A (1.7% and 5.5% of normal), and a marked increase in urinary sulfatides was present, as measured by tandem mass spectrometry. An arylsulfatase A pseudodeficiency was therefore excluded. The most common mutations of the adult phenotype, Ile-179-Ser and Pro-426-Leu, were not found. In the literature, only 1 case of adult MLD manifesting as disorganized schizophrenia-like symptoms has been described, whereas postpartum depression has been so far unknown as a presenting symptom of MLD.