Clarissa Lin Yasuda

Does Resection of the Medial Temporal Lobe Improve the Outcome of Temporal Lobe Epilepsy Surgery

Summary:  Purpose: Surgical removal of the hippocampus is the standard of care of patients with drug‐resistant medial temporal lobe epilepsy (MTLE). The procedure carries a success rate of ∼75%, but the reasons that some patients fail to achieve seizure control after surgery remain inexplicable. The question of whether the resection of medial temporal lobe structures in addition to the hippocampus would influence the surgical outcome in patients with MTLE was examined.

Antiepileptic drug response in temporal lobe epilepsy A clinical and MRI morphometry study

Objective: To investigate the relationship between brain MRI and clinical characteristics and patterns of antiepileptic drug (AED) response in patients with mesial temporal lobe epilepsy (MTLE). Methods: A total of 165 MTLE patients were divided into seizure-free with AED (AED responders, n = 50), pharmacoresistant (n = 87), and remitting-relapsing seizure control group (n = 28). All groups were evaluated regarding age, frequency of seizures, and age at epilepsy onset, duration of epilepsy, febrile seizures, presence and side of hippocampal atrophy (HA), and initial precipitating injuries. For gray matter (GM) MRI voxel-based morphometry (VBM) we selected only patients with unilateral HA on visual MRI analysis (n = 100). Comparisons were made between all groups and 75 healthy controls. Results: Age at epilepsy onset was lower (p = 0.005) and initial frequency of seizures was higher in the pharmacoresistant compared with the other 2 groups (p = 0.018). All groups showed GM atrophy compared to controls in ipsilateral hippocampus, bilateral parahippocampal gyri, frontal, occipital, parietal, and cerebellar areas. In the AED responders group, such findings were more restricted to areas ipsilateral to the epileptic focus and more widespread in the pharmacoresistant and remitting-relapsing groups. VBM pairwise comparisons showed areas with GM volume reduction in the pharmacoresistant and remitting-relapsing groups compared with AED responders in bilateral periorbital frontal (p < 0.01), cingulum (p < 0.05), and temporal lobe contralateral to the epileptic focus (p < 0.05). Conclusions: Pharmacoresistant and remitting-relapsing groups presented a similar pattern of GM atrophy, which was more widespread compared with AED responders. Conversely, age at epilepsy onset was lower and initial seizure frequency was higher in pharmacoresistant patients.

Dynamic changes in white and gray matter volume are associated with outcome of surgical treatment in temporal lobe epilepsy

BACKGROUND The reasons for surgical failure in 30% of patients with unilateral mesial temporal lobe epilepsy (MTLE) are still unclear. We investigated if different outcomes could be associated to different patterns of subtle gray matter atrophy (GMA) and white matter atrophy (WMA), and searched for postoperative magnetic resonance imaging (MRI) changes. METHODS We studied 69 controls and 67 operated patients with refractory unilateral MTLE. Patients were grouped as seizure-free (SF) group (34 patients Engels IA), worthwhile improvement group (23 patients, Engels IB-IIA) and failure group (10 patients Engels IIB-IV). We created a voxel-based morphometry/MATLAB code to mask the surgical lacuna, and performed t-test and paired t-test to evaluate preoperative and postoperative MRI scans. RESULTS Failure group showed a widespread pattern of preoperative GMA. On SF and improvement groups we identified a more restricted pattern of GMA. The three groups presented a widespread, bilateral pattern of WMA. In contrast, postoperative analyses showed bilateral hemispheric recovery (a relative increase of WM concentration) on SF and improvement groups, but few changes on failure group. We also identified areas with relative postoperative increase of GM on both SF and improvement groups, more widespread on SF group. CONCLUSION Areas of subtle GMA may be related to poorer surgical outcome. In addition, we demonstrated a postoperative relative increase of WM and GM concentration associated with seizure control. These changes may represent neuroplasticity related to improvement of brain function after seizure control. Further studies with a multimodal approach may help to predict surgical outcome and improve selection of patients for surgical treatment of MTLE.

MR Imaging Texture Analysis of the Corpus Callosum and Thalamus in Amnestic Mild Cognitive Impairment and Mild Alzheimer Disease

BACKGROUND AND PURPOSE: TA is a branch of image processing that seeks to reduce image information by extracting texture descriptors from the image. TA of MR images of anatomic structures in mild AD and aMCI is not well-studied. Our objective was to attempt to find differences among patients with aMCI and mild AD and normal-aging subjects, by using TA applied to the MR images of the CC and the thalami of these groups of subjects. MATERIALS AND METHODS: TA was applied to the MR images of 17 patients with aMCI, 16 patients with mild AD, and 16 normal-aging subjects. The TA approach was based on the GLCM. MR images were T1-weighted and were obtained in the sagittal and axial planes. The CC and thalami were manually segmented for each subject, and 44 texture parameters were computed for each of these structures. RESULTS: TA parameters showed differences among the 3 groups for the CC and thalamus. A pair-wise comparison among groups showed differences for AD-control and aMCI-AD for the CC; and for AD-control, aMCI-AD, and aMCI-control for the thalamus. CONCLUSIONS: TA is a useful technique to aid in the detection of tissue alterations in MR images of mild AD and aMCI and has the potential to become a helpful tool in the diagnosis and understanding of these pathologies.

Interferon beta modulates experimental autoimmune encephalomyelitis by altering the pattern of cytokine secretion.

The mechanism of action underlying the beneficial effect of IFNbeta in Multiple Sclerosis is poorly understood. Experimental Autoimmune Encephalomyelitis (EAE) is the experimental model for Multiple Sclerosis; therefore, we investigated the effects of recombinant mouse IFNbeta on the severity of EAE induced in SJL mice and on cytokine production by Th1 and Th2 lymphocytes. The results indicated that rmIFN beta reduced the disease activity with an I.P. dosage of 10,000 U/day every other day, and successfully treated EAE mice revealed reduced amounts of IFN gamma; no changes in the levels of IL4 were observed, although thera was a significant increase in IL10 and TGFbeta production. Beneficial effects on EAE are associated with inhibition of inflammatory cytokines and stimulation of anti-inflammatory cytokines.

Differences in grey and white matter atrophy in amnestic mild cognitive impairment and mild Alzheimer's disease.

Background:  Grey matter (GM) atrophy has been demonstrated in amnestic mild cognitive impairment (aMCI) and mild Alzheimer’s disease (AD), but the role of white matter (WM) atrophy has not been well characterized. Despite these findings, the validity of aMCI concept as prodromal AD has been questioned.

Neocortical Atrophy in Machado-Joseph Disease: A Longitudinal Neuroimaging Study

Previous imaging studies in the Machado‐Joseph disease (MJD/SCA3) have mostly concentrated on the cerebellum and brainstem. Our goal was to perform a whole brain longitudinal evaluation.

The effect of topiramate on cognitive fMRI

Summary Purpose Topiramate (TPM) is known to cause language impairment in healthy volunteers and patients with epilepsy. We assessed the effects of TPM on functional language networks in both patients with focal epilepsies and healthy controls using functional magnetic resonance imaging (fMRI). Methods We obtained fMRI data in 24 controls and 35 patients with frontal lobe epilepsy using a simple verbal fluency (VF) paradigm. Eight of the 35 patients were treated with TPM in polytherapy. We compared cognitive task related activations and de-activations in patients taking TPM with patients taking other AEDs and healthy controls. In a longitudinal pilot study with VF-fMRI paradigm, we studied two patients with focal epilepsies twice, prior to starting and on stable doses of TPM, two patients twice, before and after tapering TPM completely and two healthy controls twice, before and after single doses of 200 mg TPM. Key findings Cross sectional analyses of VF-fMRI showed a reduction in the task-related deactivation of the default mode network (DMN) in patients taking TPM. The longitudinal study corroborated these findings as both chronic administration and a single dose of TPM were associated with impaired categorical verbal fluency and disruption of task-related deactivations. Significance Similar neuropsychological and fMRI findings in patients and healthy controls indicate a specific effect of TPM in default mode network areas that may be essential components of the language network. Our preliminary data suggest a mechanism by which TPM impairs cognitive processing during language function and highlights the sensitivity of fMRI to detect the effects of AEDs on cognitive brain networks.

Structural brain abnormalities are related to retinal nerve fiber layer thinning and disease duration in neuromyelitis optica spectrum disorders

Background: Although aquaporin-4 (AQP4) is widely expressed in the human brain cortex, lesions are rare in neuromyelitis optica (NMO) spectrum disorders (NMOSD). Recently, however, several studies have demonstrated occult structural brain atrophy in NMO. Objective: This study aims to investigate magnetic resonance imaging (MRI) patterns of gray matter (GM) and white matter (WM) abnormalities in patients with NMOSD and to assess the visual pathway integrity during disease duration correlation of the retinal nerve fiber layer (RNFL) and pericalcarine cortex thickness. Methods: Twenty-one patients with NMOSD and 34 matched healthy controls underwent both high-field MRI (3T) high-resolution T1-weighted and diffusion-tensor MRI. Voxel-based morphometry, cortical analyses (Freesurfer) and diffusion-tensor imaging (DTI) analyses (TBSS-FSL) were used to investigate brain abnormalities. In addition, RNFL measurement by optic-coherence tomography (OCT) was performed. Results: We demonstrate that NMOSD is associated with GM and WM atrophy, encompassing more frequently the motor, sensory and visual pathways, and that the extent of GM atrophy correlates with disease duration. Furthermore, we demonstrate for the first time a correlation between RNFL and pericalcarine cortical thickness, with cortical atrophy evolving over the course of disease. Conclusions: Our findings indicate a role for retrograde and anterograde neurodegeneration in GM atrophy in NMOSD. However, the presence atrophy encompassing almost all lobes suggests that additional pathomechanisms might also be involved.

Neuroimaging changes in mesial temporal lobe epilepsy are magnified in the presence of depression

OBJECTIVE The aim of this study was to investigate differences in gray matter volume between patients with mesial temporal lobe epilepsy (MTLE) with and without depression using voxel-based morphometry. METHOD We included 48 adults with refractory MTLE (31 women, 39.18 ± 8.4 years) and 96 healthy controls (75 women, 37.11 ± 8.9 years). For the psychiatric evaluation, the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Axis I, was used for the diagnosis of depression, and the Beck Depression Inventory, for the determination of symptom intensity. All patients underwent an MRI scan. Patients were separated into two groups: those with MTLE with depression (n = 24) and those with MTLE without depression (n = 24). We performed voxel-based morphometric analysis, comparing patients with controls using the t test. RESULTS The number of areas of gray matter volume loss was higher in patients with MTLE with depression than in those with MTLE without depression. CONCLUSIONS The evidence of more widespread gray matter volume loss in patients with MTLE and depression calls our attention to the importance of timely recognition and treatment of depression in patients with MTLE and also to the bidirectional relationship between the two disorders and their frequent co-occurrence.