A pioneering FreeSurfer volumetric study of a series of patients with mesial temporal lobe epilepsy and hippocampal sclerosis with comorbid depression.

Depression is the most frequent psychiatric comorbidity in patients with mesial temporal lobe epilepsy (MTLE) and hippocampal sclerosis (HS). This study aimed to confirm whether patients with comorbid depression have different volumetric patterns on magnetic resonance imaging, analysing the influence of HS sides. Psychiatrists conducted semi-structured interviews with 75 patients, who were divided into non-depression group (NDG, n = 52) and depression group (DG, n = 23), and compared with 98 controls. The FreeSurfer software was used in the volumetric analysis of the estimated total intracranial volume (eTIV), bilateral cortical and subcortical regions of interest (ROIs), and for presence of left (L-, n = 41) or right (R-, n = 34) MTLE-HS. Twenty-three (30.7%) patients had depression, of whom 14 (34.1%) had l-MTLE-HS and 9 (26.5%) had R-MTLE-HS. No difference was observed between DG and NDG vs. controls in terms of eTIV and cortical ROIs, regardless of the severity of depression. In patients with l-MTLE-HS, the eTIV in the DG was reduced in comparison with that in the NDG and control group, with a small effect size. Hippocampal reduction occurred ipsilateral to HS in the l-MTLE-HS and R-MTLE-HS subgroups when DG and NDG were compared with controls, as expected according to Enhancing Neuro Imaging Genetics through Meta-Analysis (2018).

Is treatment-resistant schizophrenia associated with distinct neurobiological callosal connectivity abnormalities?

BACKGROUND: Resistance to antipsychotic treatment affects up to 30% of patients with schizophrenia. Although the time course of development of treatment-resistant schizophrenia (TRS) varies from patient to patient, the reasons for these variations remain unknown. Growing evidence suggests brain dysconnectivity as a significant feature of schizophrenia. In this study, we compared fractional anisotropy (FA) of brain white matter between TRS and non-treatment-resistant schizophrenia (non-TRS) patients. Our central hypothesis was that TRS is associated with reduced FA values. METHODS: TRS was defined as the persistence of moderate to severe symptoms after adequate treatment with at least two antipsychotics from different classes. Diffusion-tensor brain MRI obtained images from 34 TRS participants and 51 non-TRS. Whole-brain analysis of FA and axial, radial, and mean diffusivity were performed using Tract-Based Spatial Statistics (TBSS) and FMRIB's Software Library (FSL), yielding a contrast between TRS and non-TRS patients, corrected for multiple comparisons using family-wise error (FWE) < 0.05. RESULTS: We found a significant reduction in FA in the splenium of corpus callosum (CC) in TRS when compared to non-TRS. The antipsychotic dose did not relate to the splenium CC. CONCLUSION: Our results suggest that the focal abnormality of CC may be a potential biomarker of TRS.

DGCR2 influences cortical thickness through a mechanism independent of schizophrenia pathogenesis.

We investigated the role of DGCR2, a corticogenesis-related gene, on schizophrenia (SZ) and its subphenotypes, including brain morphology. A total of 221 SZ patients, 263 controls and 70 antipsychotic-naïve first episode of psychosis (FEP) were genotyped for 17 DGCR2 polymorphisms. While no association between DGCR2 polymorphisms and SZ was found, the missense variant rs2072123 was associated to left rostral anterior cingulate thickness, showing that DGCR2 seems not to be associated directly with the SZ but might be influencing the brain morphology. We also showed a DGCR2 downregulation in SZ patients when compared to controls and FEP.

The impact of epilepsy duration in a series of patients with mesial temporal lobe epilepsy due to unilateral hippocampal sclerosis.

PURPOSE: To evaluate if the duration of epilepsy influences MRI volumes of the hippocampus, amygdala, parahippocampal gyrus, entorhinal cortex and temporal pole of both hemispheres and epileptogenic hippocampus neuronal cell density and dentate gyrus granular cells distribution in patients with refractory mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE/HS). METHODS: Seventy-seven patients with refractory MTLE/HS submitted to surgery were included. Histopathological analysis included: (1) quantitative: hippocampal subfields and total estimated hippocampal cell density (HCD), thickness of the dentate gyrus - normal, thinning or dispersion; (2) qualitative: type of HS and granule cells pathology in the dentate gyrus (normal, neuronal cell loss, dispersion and bilamination). Automated MRI-derived measurements from bilateral temporal structures (hippocampus, amygdala, parahippocampal gyrus, temporal pole, entorhinal cortex) were obtained for 58 subjects. Histopathological and imaging findings were compared with data from specimens obtained in autopsies of age-matched individuals and living controls, respectively, and the data were adjusted for the age at epilepsy onset and the frequency of focal impaired awareness seizures/month. RESULTS: Forty-two (54.5%) patients presented right HS. The greater the duration of epilepsy, the smaller the total estimated HCD (p = 0.025; r = -0.259). Patients with a normal distribution of the granular cells had a shorter epilepsy duration than those with dispersion (p = 0.018) or thinning (p = 0.031). A reduced ipsilateral hippocampal volume (r = -0.551, p = 0.017) and a smaller hippocampal asymmetry index (r = -0.414, p = 0.002) were correlated to a longer epilepsy duration. The estimated HCD was correlated to the volume of the ipsilateral hippocampus (r = 0.420, p = 0.001). CONCLUSION: Our study showed an increasing atrophy of the ipsilateral hippocampus in patients with a longer epilepsy duration. Our data suggest that this reduction in hippocampal volume is related to neuronal loss. Besides that, we also showed an increased probability of exhibiting an abnormal distribution of the granular cells in the dentate gyrus in patients with longer epilepsy duration.

Morphometric MRI features are associated with surgical outcome in mesial temporal lobe epilepsy with hippocampal sclerosis.

PURPOSE: Corticoamygdalohippocampectomy (CAH) improves seizure control, quality of life, and decreases mortality for refractory mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). One-third of patients continue having seizures, and it is pivotal to determine structural abnormalities that might influence the postoperative outcome. Studies indicate that nonhippocampal regions may play a role in the epileptogenic network in MTLE-HS and could generate seizures postoperatively. The aim of this study is to analyze areas of atrophy, not always detected on routine MRI, comparing patients who became seizure free (SF) with those non seizure free (NSF) after CAH, in an attempt to establish possible predictors of surgical outcome. METHODS: 105 patients with refractory MTLE-HS submitted to CAH (59 left MTLE; 46 males) and 47 controls were enrolled. FreeSurfer was performed for cortical thickness and volume estimation comparing patients to controls and SF versus NSF patients. The final sample after post processing procedures resulted in 99 patients. RESULTS: Cortical thickness analyses showed reductions in left insula in NSF patients compared to those SF. Significant volume reductions in SF patients were present in bilateral thalami, hippocampi and pars opercularis, left parahippocampal gyrus and right temporal pole. In NSF patients reductions were present bilaterally in thalami, hippocampi, entorhinal cortices, superior frontal and supramarginal gyri; on the left: superior and middle temporal gyri, temporal pole, parahippocampal gyrus, pars opercularis and middle frontal gyrus; and on the right: precentral, superior, middle and inferior temporal gyri. Comparison between SF and NSF patients showed ipsilateral gray matter reductions in the right entorhinal cortex (p=0.003) and contralateral parahippocampal gyrus (p=0.05) in right MTLE-HS. Patients NSF had a longer duration of epilepsy than those SF (p=0.028). CONCLUSION: NSF patients exhibited more extensive areas of atrophy than SF ones. As entorhinal cortex and parahippocampal gyrus are reduced in NSF patients compared to those SF these structures might be implicated in the network responsible for the maintenance of postoperative seizures. Duration of epilepsy is a predictor of seizure outcome.

Is there an association between cortical thickness, age of onset, and duration of illness in schizophrenia?

OBJECTIVE: Several studies have shown cortical volume loss in frontotemporal regions in schizophrenia patients, and it is known that these reductions may be associated with disease symptoms and cognitive deficits. The aim of this study was to investigate possible cortical thickness correlations in frontotemporal regions in relation to age at onset and duration of illness. METHODS: One hundred forty-eight schizophrenia patients (97 males; age and SD 36.30 ± 10.06) and 87 (57 males; age and SD 36.48 ± 10.10) age-matched healthy subjects underwent a brain MRI scan. Cortical segmentation and surface statistical analysis were performed using the FreeSurfer software package. Results were corrected for multiple comparisons using the Monte Carlo method considering a cluster-corrected Type I Error of 5%. RESULTS: Compared to controls, schizophrenia patients presented significant cortical thinning in the frontotemporal, parietal, and occipital cortices. No correlation between prefrontal cortex thickness and duration of illness in patients with schizophrenia or between frontotemporal cortical thickness and age at onset was found. However, a significant interaction between age and diagnosis was observed on frontal cortical thickness with patients presenting a thinner cortex than expected for age. CONCLUSION: Although there was no correlation between age of onset and duration of illness with brain volume, our findings suggest that there is an accelerated cortical loss in schizophrenia, thus reinforcing the progressive processes of the disease.