Dementia

This unit presents specific protocols intended to maximize the contribution of MRI to the clinical evaluation of dementia. Each protocol has, as its foundation, a wholeâ brain screen designed to evaluate for treatable causes of dementia. Reflecting the frequent overlap of vascular disease with dementing illness, the screening protocol also serves as an optimal evaluation of the patient with suspected vascular dementia. Additional sequences or modifications are then used to answer specific clinical questions. The parameters given here are derived from experience at 1.5 T and may need to be altered slightly depending on the field strength and the equipment manufacturer.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145357/1/cpmia0503.pd

Clinical profile of vigabatrin as monotherapy for treatment of infantile spasms

Jason T Lerner1, Noriko Salamon2, Raman Sankar1,31Departments of Pediatrics, 2Radiological Sciences, 3Neurology, David Geffen School of Medicine, University of California Los Angeles and Mattel Children’s Hospital at UCLA, Los Angeles, CA, USAAbstract: Vigabatrin, the first therapeutic agent to be approved by the Food and Drug Administration for the treatment of infantile spasms, as well as for adjunctive use in the treatment of refractory complex partial epilepsy, represents an important advance for patients with difficult-to-manage epilepsy. This review summarizes the complex history, chemistry, and pharmacology, as well as the clinical data leading to the approval of vigabatrin for infantile spasms in the US. The long path to its approval reflects the visual system and white matter toxicity concerns with this agent. This review provides a brief description of these concerns, and the regulatory safety monitoring and mitigation systems that have been put in place to enhance benefit over risk.Keywords: vigabatrin, infantile spasms, monotherap

FARS2 mutations presenting with pure spastic paraplegia and lesions of the dentate nuclei.

Mutations in FARS2, the gene encoding the mitochondrial phenylalanine-tRNA synthetase (mtPheRS), have been linked to a range of phenotypes including epileptic encephalopathy, developmental delay, and motor dysfunction. We report a 9-year-old boy with novel compound heterozygous variants of FARS2, presenting with a pure spastic paraplegia syndrome associated with bilateral signal abnormalities in the dentate nuclei. Exome sequencing identified a paternal nonsense variant (Q216X) lacking the catalytic core and anticodon-binding regions, and a maternal missense variant (P136H) possessing partial enzymatic activity. This case confirms and expands the phenotype related to FARS2 mutations with regards to clinical presentation and neuroimaging findings

Evidence for Innate and Adaptive Immune Responses in a Cohort of Intractable Pediatric Epilepsy Surgery Patients.

Brain-infiltrating lymphocytes (BILs) were isolated from resected brain tissue from 10 pediatric epilepsy patients who had undergone surgery for Hemimegalencephaly (HME) (n = 1), Tuberous sclerosis complex (TSC) (n = 2), Focal cortical dysplasia (FCD) (n = 4), and Rasmussen encephalitis (RE) (n = 3). Peripheral blood mononuclear cells (PBMCs) were also isolated from blood collected at the time of the surgery. Cells were immunostained with a panel of 20 antibody markers, and analyzed by mass cytometry. To identify and quantify the immune cell types in the samples, an unbiased clustering method was applied to the entire data set. More than 85 percent of the CD45+ cells isolated from resected RE brain tissue comprised T cells; by contrast NK cells and myeloid cells constituted 80-95 percent of the CD45+ cells isolated from the TSC and the FCD brain specimens. Three populations of myeloid cells made up >50 percent of all of the myeloid cells in all of the samples of which a population of HLA-DR+ CD11b+ CD4- cells comprised the vast majority of myeloid cells in the BIL fractions from the FCD and TSC cases. CD45RA+ HLA-DR- CD11b+ CD16+ NK cells constituted the major population of NK cells in the blood from all of the cases. This subset also comprised the majority of NK cells in BILs from the resected RE and HME brain tissue, whereas NK cells defined as CD45RA- HLA-DR+ CD11b- CD16- cells comprised 86-96 percent of the NK cells isolated from the FCD and TSC brain tissue. Thirteen different subsets of CD4 and CD8 αβ T cells and γδ T cells accounted for over 80% of the CD3+ T cells in all of the BIL and PBMC samples. At least 90 percent of the T cells in the RE BILs, 80 percent of the T cells in the HME BILs and 40-66 percent in the TSC and FCD BILs comprised activated antigen-experienced (CD45RO+ HLA-DR+ CD69+) T cells. We conclude that even in cases where there is no evidence for an infection or an immune disorder, activated peripheral immune cells may be present in epileptogenic areas of the brain, possibly in response to seizure-driven brain inflammation

Residual Tumor Confers a 10-Fold Increased Risk of Regrowth in Clinically Nonfunctioning Pituitary Tumors.

ObjectiveWe evaluated tumor recurrence and regrowth rates following endoscopic transnasal transsphenoidal (TNTS) surgical removal in a consecutive series of clinically nonfunctioning pituitary adenomas (CNFTs).DesignRetrospective chart review of clinical, biochemical, and sellar MRI findings in all TNTS surgeries in patients with CNFT, performed by a single surgeon, between 2008 and 2015 (n = 280).PatientsNinety-three patients met eligibility criteria, with complete clinical, biochemical, and imaging follow-up for a 3-year minimum.ResultsOf 85 patients who were not irradiated, 3-month postsurgical MRI demonstrated no residual tumor in 58 of 85 (68.2%), equivocal findings in 12 of 85 (14.1%), and definite residual tumor in 15 of 85 (17.6%) patients. Six of 85 (7.1%) demonstrated tumor regrowth by 3 years, and 2 further patients demonstrated true tumor recurrence at 3 and 6 years after surgery, respectively, for a total recurrence rate of 9.4% (8 of 85). Eight of the 93 patients were irradiated between 3 months and 4 years after pituitary surgery. In 3 patients with tumor regrowth, 2 exhibited residual tumor and 1 had no residual findings at the 3-month postoperative imaging. Overall, Ki-67 labeling index or Knosp grading did not predict recurrence.ConclusionTumor recurrence at 3 years was low (1 of 58; 1.7%) if the 3-month postoperative MRI showed no residual tumor. The findings support a less frequent imaging schedule for this group. Patients with definite residual tumor visible at 3 months harbor the greatest risk for tumor growth, but regrowth does not occur in all patients (6 of 15; 40%)

Elevated glutamatergic compounds in pregenual anterior cingulate in pediatric autism spectrum disorder demonstrated by 1H MRS and 1H MRSI.

Recent research in autism spectrum disorder (ASD) has aroused interest in anterior cingulate cortex and in the neurometabolite glutamate. We report two studies of pregenual anterior cingulate cortex (pACC) in pediatric ASD. First, we acquired in vivo single-voxel proton magnetic resonance spectroscopy ((1)H MRS) in 8 children with ASD and 10 typically developing controls who were well matched for age, but with fewer males and higher IQ. In the ASD group in midline pACC, we found mean 17.7% elevation of glutamate + glutamine (Glx) (p<0.05) and 21.2% (p<0.001) decrement in creatine + phosphocreatine (Cr). We then performed a larger (26 subjects with ASD, 16 controls) follow-up study in samples now matched for age, gender, and IQ using proton magnetic resonance spectroscopic imaging ((1)H MRSI). Higher spatial resolution enabled bilateral pACC acquisition. Significant effects were restricted to right pACC where Glx (9.5%, p<0.05), Cr (6.7%, p<0.05), and N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (10.2%, p<0.01) in the ASD sample were elevated above control. These two independent studies suggest hyperglutamatergia and other neurometabolic abnormalities in pACC in ASD, with possible right-lateralization. The hyperglutamatergic state may reflect an imbalance of excitation over inhibition in the brain as proposed in recent neurodevelopmental models of ASD

Bimodal coupling of ripples and slower oscillations during sleep in patients with focal epilepsy.

OBJECTIVE: Differentiating pathologic and physiologic high-frequency oscillations (HFOs) is challenging. In patients with focal epilepsy, HFOs occur during the transitional periods between the up and down state of slow waves. The preferred phase angles of this form of phase-event amplitude coupling are bimodally distributed, and the ripples (80-150 Hz) that occur during the up-down transition more often occur in the seizure-onset zone (SOZ). We investigated if bimodal ripple coupling was also evident for faster sleep oscillations, and could identify the SOZ. METHODS: Using an automated ripple detector, we identified ripple events in 40-60 min intracranial electroencephalography (iEEG) recordings from 23 patients with medically refractory mesial temporal lobe or neocortical epilepsy. The detector quantified epochs of sleep oscillations and computed instantaneous phase. We utilized a ripple phasor transform, ripple-triggered averaging, and circular statistics to investigate phase event-amplitude coupling. RESULTS: We found that at some individual recording sites, ripple event amplitude was coupled with the sleep oscillatory phase and the preferred phase angles exhibited two distinct clusters (p \u3c 0.05). The distribution of the pooled mean preferred phase angle, defined by combining the means from each cluster at each individual recording site, also exhibited two distinct clusters (p \u3c 0.05). Based on the range of preferred phase angles defined by these two clusters, we partitioned each ripple event at each recording site into two groups: depth iEEG peak-trough and trough-peak. The mean ripple rates of the two groups in the SOZ and non-SOZ (NSOZ) were compared. We found that in the frontal (spindle, p = 0.009; theta, p = 0.006, slow, p = 0.004) and parietal lobe (theta, p = 0.007, delta, p = 0.002, slow, p = 0.001) the SOZ incidence rate for the ripples occurring during the trough-peak transition was significantly increased. SIGNIFICANCE: Phase-event amplitude coupling between ripples and sleep oscillations may be useful to distinguish pathologic and physiologic events in patients with frontal and parietal SOZ

Validation of vessel size imaging (VSI) in high-grade human gliomas using magnetic resonance imaging, image-guided biopsies, and quantitative immunohistochemistry.

To evaluate the association between a vessel size index (VSIMRI) derived from dynamic susceptibility contrast (DSC) perfusion imaging using a custom spin-and-gradient echo echoplanar imaging (SAGE-EPI) sequence and quantitative estimates of vessel morphometry based on immunohistochemistry from image-guided biopsy samples. The current study evaluated both relative cerebral blood volume (rCBV) and VSIMRI in eleven patients with high-grade glioma (7 WHO grade III and 4 WHO grade IV). Following 26 MRI-guided glioma biopsies in these 11 patients, we evaluated tissue morphometry, including vessel density and average radius, using an automated procedure based on the endothelial cell marker CD31 to highlight tumor vasculature. Measures of rCBV and VSIMRI were then compared to histological measures. We demonstrate good agreement between VSI measured by MRI and histology; VSIMRI = 13.67 μm and VSIHistology = 12.60 μm, with slight overestimation of VSIMRI in grade III patients compared to histology. rCBV showed a moderate but significant correlation with vessel density (r = 0.42, p = 0.03), and a correlation was also observed between VSIMRI and VSIHistology (r = 0.49, p = 0.01). The current study supports the hypothesis that vessel size measures using MRI accurately reflect vessel caliber within high-grade gliomas, while traditional measures of rCBV are correlated with vessel density and not vessel caliber

Grey Matter Reshaping of Language-Related Regions Depends on Tumor Lateralization

Published: 28 July 2023A brain tumor in the left hemisphere can decrease language laterality as assessed through fMRI. However, it remains unclear whether or not this decreased language laterality is associated with a structural reshaping of the grey matter, particularly within the language network. Here, we examine if the disruption of the language hubs exclusively affects the macrostructural properties of the contralateral homologues or whether it affects both hemispheres. This study uses voxel-based morphometry applied to high-resolution MR T1-weighted MPRAGE images from 31 adult patients’ left hemisphere, which is dominant for language. Eighteen patients had brain tumors in the left hemisphere, and thirteen had tumors in the right hemisphere. A cohort of 71 healthy individuals matched with respect to age and sex was used as a baseline. We defined 10 ROIs per hemisphere involved in language function. Two separate repeated-measure ANOVAs were conducted with the volume per region as the dependent variable. For the patients, tumor lateralization (right versus left) served as a between-subject factor. The current study demonstrated that the presence of a brain tumor generates global volumetric changes affecting the left language regions and their contralateral homologues. These changes are mediated by the lateralization of the lesion. Our findings suggest that functional mechanisms are supported by the rearrangement of the grey matter.This research was supported by the Basque Government through the BERC 2022–2025 program; the Spanish State Research Agency through BCBL Severo Ochoa excellence accreditation CEX2020−001010-S; the Fundación Científica AECC (FCAECC) through the project PROYE20005CARR; the Spanish Ministry of Economy and Competitiveness through the Plan Nacional RTI2018 093547 B I00 (LANGCONN) awarded to I.Q.; the Spanish Ministry of Science, Innovation and Universities through the predoctoral grant PRE2019-091492 awarded to L.M.-O.; and the NIH (NIDCD) grant K01DC016904 (Comprehensive presurgical identification of the critical language network in tumor patients) awarded to M.M.P