Seizure outcome after epilepsy surgery in tuberous sclerosis complex: Results and analysis of predictors from a multicenter study.

Epilepsy surgery is recommended in selected patients with Tuberous Sclerosis Complex (TSC). However, reports on predictive factors of seizure outcome are variable. Here we report on seizure and cognitive outcome of 35 TSC patients who received surgery for refractory epilepsy in 7 Italian centers over a period of 22 years (1997-2019). The rate of seizure-free individuals at last follow-up (mean 7.5 years, range 1-21 years) was 51%. Patients with longer follow-up (≥10 years) had a lower rate of Engel I outcome (11.1%) than those who received surgery in the last 10 years (65.4%, p = 0.003). Factors associated with Engel II, III, IV outcome in our cohort included: high number of cortical tubers (≥5); presence of subependymal nodules (SENs); seizure onset before age 1 year; and multifocal interictal epileptic discharges (IEDs) on electroencephalogram (EEG). A subset of patients evaluated with Vineland Adaptive Behaviour Scales (VABS) showed developmental gains, in line with their developmental trajectories, but no improvement in standard scores after surgery was noted. Our study demonstrates that the rates of successful seizure outcome of epilepsy surgery in TSC have improved in the last 10 years. More than half of the patients achieved seizure freedom, and a high proportion of affected individuals experienced a reduction in seizure burden and in antiseizure medications. A comprehensive assessment after surgery should be performed in TSC patients to evaluate the overall neurodevelopmental outcome, as measures that are based only on seizure control do not adequately identify the benefits of surgery on global functioning in these patients.

Ganglionic Eminence Anomalies and Coexisting Cerebral Developmental Anomalies on Fetal MR Imaging: Multicenter-Based Review of 60 Cases.

BACKGROUND AND PURPOSE: The ganglionic eminences are transient fetal brain structures that produce a range of neuron types. Ganglionic eminence anomalies have been recognized on fetal MR imaging and anecdotally found in association with a number of neurodevelopmental anomalies. The aim of this exploratory study was to describe and analyze the associations between ganglionic eminence anomalies and coexisting neurodevelopmental anomalies. MATERIALS AND METHODS: This retrospective study includes cases of ganglionic eminence anomalies diagnosed on fetal MR imaging during a 20-year period from 7 centers in Italy and England. Inclusion criteria were cavitation or increased volume of ganglionic eminences on fetal MR imaging. The studies were analyzed for associated cerebral developmental anomalies: abnormal head size and ventriculomegaly, reduced opercularization or gyration, and abnormal transient layering of the developing brain mantle. The results were analyzed using χ2 and Fisher exact tests. RESULTS: Sixty fetuses met the inclusion criteria (21 females, 24 males, 15 sex unknown). Thirty-four had ganglionic eminence cavitations (29 bilateral and 5 unilateral), and 26 had increased volume of the ganglionic eminences (19 bilateral, 7 unilateral). Bilateral ganglionic eminence cavitations were associated with microcephaly (P = .01), reduced opercularization, (P < .001), reduced gyration (P < .001), and cerebellar anomalies (P = .01). Unilateral ganglionic eminence cavitations were not significantly associated with any particular feature. Bilateral increased volume of the ganglionic eminences showed an association with macrocephaly (P = .03). Unilateral increased volume was associated with macrocephaly (P = .002), abnormal transient layering (P = .001), unilateral polymicrogyria (P = .001), and hemimegalencephaly (P < .001). CONCLUSIONS: Ganglionic eminence anomalies are associated with specific neurodevelopmental anomalies with ganglionic eminence cavitations and increased ganglionic eminence volume apparently having different associated abnormalities.

DTI and MR Volumetry of Hippocampus-PC/PCC Circuit: In Search of Early Micro- and Macrostructural Signs of Alzheimers's Disease.

Hippocampal damage, by DTI or MR volumetry, and PET hypoperfusion of precuneus/posterior cingulate cortex (PC/PCC) were proposed as biomarkers of conversion from preclinical (MCI) to clinical stage of Alzheimer's disease (AD). This study evaluated structural damage, by DTI and MR volumetry, of hippocampi and tracts connecting hippocampus to PC/PCC (hipp-PC/PCC) in 10 AD, 10 MCI, and 18 healthy controls (CTRL). Normalized volumes, mean diffusivity (MD), and fractional anisotropy (FA) were obtained for grey matter (GM), white matter (WM), hippocampi, PC/PCC, and hipp-PC/PCC tracts. In hippocampi and hipp-PC/PCC tracts, decreased volumes and increased MD were found in AD versus CTRL (P < .001). The same results with lower significance (P < .05) were found in MCI versus CTRL. Verbal memory correlated (P < .05) in AD with left hippocampal and hipp-PC/PCC tract MD, and in MCI with FA of total WM. Both DTI and MR volumetry of hippocampi and hipp-PC/PCC tracts detect early signs of AD in MCI patients.

Duplication of the pituitary stalk in a patient with a heterozygous deletion of chromosome 14 harboring the thyroid transcription factor-1 gene.

Magnetic resonance imaging of the hypothalamic-pituitary region revealed a duplication of the pituitary stalk in a patient with a heterozygous deletion of chromosome 14 harboring the thyroid transcription factor-1 gene.

Nuclear receptors, intestinal architecture and colon cancer: an intriguing link.

The intestinal epithelium is structured in crypt-villus units which are responsible for its continuous renewal. These units are organized in a dynamic scenario in which proliferating progenitor cells are generated from stem cells in the crypts and migrate along the villus axis until their extrusion as differentiated cells at the surface epithelium. The mechanisms controlling cell transition involve transcription factors that switch on and off compartment-specific genes. The Wnt cascade represents the dominant force controlling cell fate in the crypt-villus axis. Mutations in this cascade result in the development of colorectal cancer. Life-style modifications and dietary regimens are epidemiologically recognized contributing factors for intestinal tumorigenesis. Nuclear receptors are a family of transcription factors functioning as sensors of dietary and endogenous molecules, thus translating nutritional and hormonal stimuli into transcriptional modifications. This review presents the role of nuclear receptors in intestinal carcinogenesis and explores their influence in maintenance of intestinal epithelium architecture.

Study of the mitochondrial transcription factor A (Tfam) gene in the primate Presbytis cristata.

The mitochondrial transcription factor A (Tfam) is a member of the HMG-box protein family, necessary for both transcription and maintenance of mitochondrial DNA. The gene is structured in seven exons and six introns and it is estimated to span about 10 kb in mouse, human and rat. In addition to the full length mRNA of Tfam, a shorter mRNA isoform lacking exon 5 has been found to be widely distributed in human and rat tissues. Here we present the isolation and characterization of Tfam gene in the primate Presbytis cristata which belongs to the Cercopithecidae family. We have determined the complete CDS sequence, the size of all the six introns, the complete sequences of the three shorter ones (I, III, VI) and the partial sequences of the long introns (II, IV, V). The comparison with other available Tfam sequences from mammals has revealed a high degree of conservation (above 90%) both in CDS and introns. By in situ hybridization (FISH) experiments we have mapped Tfam gene on chromosome 12 which, according to other cytogenetics studies, is the homologous region of chromosome 10, where human Tfam has been mapped. Moreover we have searched for the presence of alternatively spliced isoforms through several approaches, such as RT-PCR and differential hybridization. In Presbytis cristata we have not detected the presence of any spliced isoforms lacking exons; however we have identified one isoform in which part of the intron I is retained in the mRNA. The inclusion of this portion of intron I would originate an early stop codon if translated.