Objective: The purpose of this study was to assess the prevalence of and to identify epidemiologic, genetic, electrophysiologic, and neuroanatomic risk factors for autism spectrum disorders (ASD) in a cohort of patients with tuberous sclerosis complex (TSC). Methods:A total of 103 patients with TSC were evaluated for ASD. A retrospective review of patients' records was performed, including mutational analysis. EEG reports were analyzed for the presence of ictal and interictal epileptiform features. Brain MRI scans were evaluated for TSC neuropathology, including tuber burden. Results:Of the 103 patients with TSC, 40% were diagnosed with an ASD. On univariate analysis, patients with ASD were less likely to have mutations in the TSC1 gene. Patients with ASD also had an earlier age at seizure onset and more frequent seizures. On EEG, those with ASD had a significantly greater amount of interictal epileptiform features in the left temporal lobe only. On MRI, there were no differences in the regional distribution of tuber burden, although those with TSC2 and ASD had a higher prevalence of cyst-like tubers. Conclusions:The development of ASD in TSC is not well understood. Given our findings, ASD may be associated with persistent seizure activity early in development in particular brain regions, such as those responsible for social perception and communication in the left temporal lobe. The presence of cyst-like tubers on MRI could provide a structural basis or marker for ASD pathology in TSC, although studies assessing their effect on cortical function are needed. Neurology Tuberous sclerosis complex (TSC) is an autosomal dominant disorder resulting from mutations in the TSC1 or the TSC2 gene.1,2 Neurologic involvement occurs in more than 90% of individuals and comprises several distinct lesions.3 Seizure disorders are present in 70%-90% of patients and often develop within the first year of life.4 Developmental and behavioral disorders, including autism spectrum disorders (ASD), are also frequently diagnosed in TSC.ASD are characterized by impaired social interaction, restricted interests, and repetitive behaviors. ASD affects between 17% and 63% of patients with TSC, a prevalence dramatically higher than that of the general population. 5,6 Studies suggest that mental retardation and early onset of epilepsy in TSC, in particular infantile spasms, are associated with the development of ASD in this group. 7,8 In addition, there is evidence of an association between temporal lobe epileptiform foci with ASD in TSC.9 However, investigations seeking to implicate TSC genetics 10 -12 or neuropathology [13][14][15][16][17][18][19] in ASD have yielded inconclusive results. Discrepancies between investigations may result, in part, from varying methods used to diagnose ASD. To date, no

Two familial X-linked dominant syndromes of cortical maldevelopment have recently been described: double cortex/lissencephaly syndrome and bilateral periventricular nodular heterotopia. We report on 12 kindreds with familial perisylvian polymicrogyria (FPP) presenting at 10 centers, examine the clinical presentation in these familial cases, and propose a possible mode of inheritance. The clinical and radiological pattern was variable among the 42 patients, with clinical differences among the families and even within members of the same family. Pseudobulbar signs, cognitive deficits, epilepsy, and perisylvian abnormalities on imaging studies were not found in all patients. When present, they displayed a spectrum of severity. The only clear correlation in this study was between bilateral imaging findings and abnormal tongue movements and/or pronounced dysarthria. Most of the families provided evidence suggestive of, or compatible with, X-linked transmission. On the other hand, the pedigrees of 2 families ruled out X-linked inheritance. The most likely mode of inheritance for these 2 families was autosomal dominant with decreased penetrance; however, autosomal recessive inheritance with pseudodominance could not be ruled out in 1 family. We conclude that FPP appears to be genetically heterogeneous. However, most of the families probably represent a third previously undescribed X-linked syndrome of cortical maldevelopment.

Localized scleroderma en coup de sabre is associated with focal, and in some progressive, brain lesions underlying the skin atrophy. Epilepsy, when present, is related to these brain lesions. Imaging findings and histopathology indicated that the process, most likely focal inflammatory, may be progressive.

No abstract

Developmental language disorder can be associated with polymicrogyria and the clinical manifestation varies according to the extension of cortical abnormality. A subtle form of posterior parietal polymicrogyria presenting as developmental language disorder is a mild form of perisylvian syndrome.

Cyst-like cortical tubers are strongly associated with TSC2 gene mutation and a more aggressive seizure phenotype in patients with tuberous sclerosis complex.

Summary:Purpose: Many patients with focal cortical dysplasia (FCD) continue to have seizures after surgical treatment. The usual explanation for the poor surgical outcome is the presence of residual dysplastic tissue missed by the preoperative neuroimaging investigation and therefore not resected during surgery. We apply a voxel-based morphometry (VBM) analysis to the magnetic resonance imaging (MRI) scans from patients with epilepsy and visually detected FCD to investigate whether (a) VBM is able to detect gray-matter concentration (GMC) abnormalities in patients with FCD, and (b) whether the extent of GMC abnormalities in the brain of these patients differs from the regions observed by using visual inspection.Methods: We studied 11 patients with visually detected FCD (eight of them with histologic confirmation of FCD). The GMC from each one of these patients was compared with the mean GMC from a control group of 96 normal healthy subjects by using an optimized VBM protocol.Results: Ten of 11 patients showed statistically significant GMC excess, and among patients with GMC excess, only one showed GMC excess that was not exactly correspondent to the visually detected FCD. Seven patients exhibited excess in GMC extending beyond the area of visually detected FCD.Conclusions: This preliminary neuroimaging study suggests that (a) VBM can detect GMC excess in patients with FCD, and (b) GMC excess in these patients can extend to brain areas not visually defined as abnormal. Abnormal areas detected by VBM can possibly correspond to mild malformations of cortical development, supporting the notion that the surgical refractoriness observed in patients with FCD can be due to the incomplete resection of the dysplastic tissue.

Our findings support the idea of a spectrum among the different types of MCD. Focal cortical dysplasia (group 1) is associated with more frequent and severe epilepsy and less important genetic and prenatal events, heterotopias and agyria-pachygyria (group 2) are frequently associated with genetic predisposition, and polymicrogyria and schizencephaly (group 3) are less frequently associated with epilepsy but have a stronger association with genetic and detectable prenatal events.