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The use of imaging in epilepsy care is a powerful tool to show a patient why they have epilepsy. You can use it to correlate your semiology history with an imaging finding. Magnetic resonance imaging (MRI) is the most widely used modality for epilepsy care. Ordering an epilepsy protocol MRI on a 3 Tesla (3T) machine increases the likelihood of finding an epilepsy’s etiology. Common findings include stroke, tumor (i.e., ganglioglioma), hippocampal sclerosis, encephalocele, cortical dysplasia, heterotopia, polymicrogyria, or cavernoma. For MRI-negative epilepsy, additional tests to identify the epileptogenic region include PET (positron emission tomography) and SPECT (single photon emission computed tomography). Functional MRI (fMRI) can delineate brain areas critical for specific functions. Lastly, the use of CT (computed tomography) is limited to identification of acute findings like hemorrhage and tumors in new onset seizures.
The basic science of epilepsy made fundamental advances in this period, with the discovery of GABA as the chief inhibitory transmitter and glutamate as the chief excitatory transmitter involved in epilepsy. This spurred intensive research by the pharmaceutical companies and the introduction of a range of new drug treatments, although none were shown to be of superior efficacy to those already existing. Extraordinary progress was made also in the basic science of genetics, although this did not feed into clinical epilepsy. The major investigational advances were CT and then MRI scanning, which transformed clinical practice in epilepsy, and also EEG technologies allowing prolonged monitoring and video-EEG correlation. The number of clinical researchers in epilepsy greatly increased, stimulated by changing university and hospital priorities and the technological advances of the computing era. Advances were made in many clinical fields in epilepsy, including epidemiology, paediatrics, epilepsy syndromes, febrile convulsions and their relationship to temporal lobe epilepsy, SUDEP and status epilepticus. Aided by therapeutic drug monitoring, antiseizure drug monotherapy became commonplace. New drugs and new surgical techniques were introduced. An attempt was made to federate ILAE and IBE under the umbrella of a new organisation, Epilepsy International, but this failed.
Epilepsy is a frequently encountered disease, affecting 1-2% of the population, but one that is often mistreated due to misunderstandings of specific diagnoses and treatments. This practical manual provides a succinct and clinically relevant reference of routine clinical epilepsy care. The book is designed around the four main aspects of an epilepsy patient's care: first seizure, inpatient epilepsy care, outpatient epilepsy care, and diagnostic modalities. These four aspects are carefully delineated to illustrate the key differences in best practice management. Rational use of EEG and imaging testing is thoroughly covered to guide improved utility of these results. Caring for the mental health of epilepsy patients is also covered, as this is pertinent at every stage and location of epilepsy patient care. An excellent resource for neurology trainees at the resident, fellow, and medical student level as well as advanced practice providers.
At present, animal experimentation remains central to our understanding of human disease-related processes and of the biological effects of many substances. Traditional experiments have relied heavily on invasive techniques to monitor changes in blood biochemistry, tissue structure or function, or to phenotype or genotype genetically modified animals. In some cases, a proportion or all of the animals used during the course of a study may be sacrificed for histopathological assessment. In most cases, this is to track the progression or regression of a disease over time, or to determine the levels of toxicity evident in specific organs or tissues. However, many of these techniques fail to provide details of how a disease develops or how a substance elicits its effects. In recent years there has been a gradual increase in the application of imaging techniques that were originally developed and used in fundamental research or in medicine. These non-invasive techniques allow diseases, and responses to exogenous substances, to be monitored in a temporal and spatial manner, therefore allowing a greater amount of information to be derived from smaller numbers of animals, which in turn, increases the statistical validity of the data by reducing the level of experimental variation. Non-invasive imaging also allows more informative and humane endpoints to be used and, perhaps most importantly, allows functional details to be studied in the context of a living animal. Some of the recent developments within the field of non-invasive imaging and their significance with respect to animal welfare and the understanding of human physiology are discussed.
In patients with intracranial steno-occlusive disease (SOD), the risk of hemodynamic stroke depends on the poststenotic vasodilatory reserve. Cerebrovascular reactivity (CVR) is a test for vasodilatory reserve. We tested for vasodilatory reserve by using PETCO2 as the stressor, and Blood Oxygen Level Dependent (BOLD) MRI as a surrogate of blood flow. We correlate the CVR to the incidence of stroke after a 1-year follow-up in patients with symptomatic intracranial SOD.
In this retrospective study, 100 consecutive patients with symptomatic intracranial SOD that had undergone CVR testing were identified. CVR was measured as % BOLD MR signal intensity/mmHg PETCO2. All patients with normal CVR were treated with optimal medical therapy; those with abnormal CVR were offered revascularization where feasible. We determined the incidence of stroke at 1 year.
83 patients were included in the study. CVR was normal in 14 patients and impaired in 69 patients ipsilateral to the lesion. Of these, 53 underwent surgical revascularization. CVR and symptoms improved in 86% of the latter. The overall incidence of stroke was 4.8 % (4/83). All strokes occurred in patients with impaired CVR (4/69; 2/53 in the surgical group, all in the nonrevascularized hemisphere), and none in patients with normal CVR (0/14).
Our study confirms that CO2-BOLD MRI CVR can be used as a brain stress test for the assessment of cerebrovascular reserve. Impaired CVR is associated with a higher incidence of stroke and normal CVR despite significant stenosis is associated with a low risk for stroke.
Electroconvulsive therapy (ECT) is effective for treatment-resistant depression and leads to short-term structural brain changes and decreases in the inflammatory response. However, little is known about how brain structure and inflammation relate to the heterogeneity of treatment response in the months following an index ECT course.
A naturalistic six-month study following an index ECT course included 20 subjects with treatment-resistant depression. Upon conclusion of the index ECT course and again after six months, structural magnetic resonance imaging scans and peripheral inflammation measures [interleukin-6 (IL-6), IL-8, tumor necrosis factor (TNF-α), and C-reactive protein] were obtained. Voxel-based morphometry processed with the CAT-12 Toolbox was used to estimate changes in gray matter volume.
Between the end of the index ECT course and the end of follow-up, we found four clusters of significant decreases in gray matter volume (p < 0.01, FWE) and no regions of increased volume. Decreased HAM-D scores were significantly related only to reduced IL-8 level. Decreased volume in one cluster, which included the right insula and Brodmann's Area 22, was related to increased HAM-D scores over six months. IL-8 levels did not mediate or moderate the relationship between volumetric change and depression.
Six months after an index ECT course, multiple regions of decreased gray matter volume were observed in a naturalistic setting. The independent relations between brain volume and inflammation to depressive symptoms suggest novel explanations of the heterogeneity of longer-term ECT treatment response.
We report a case of congenital giant left ventricular aneurysm with severely depressed systolic cardiac function who underwent early surgical resection with subsequent recovery of left ventricular systolic function.
It is difficult to easily estimate skeletal muscle (SM) volume in children. We aimed to develop regression-based prediction equations to estimate the total body and regional SM volume using calliper measurements of limb circumference and skinfold thickness, and to investigate the validity of these equations. In total, 142 healthy, prepubertal, Japanese children, aged 6–12 years, were divided into 2 groups: the model development group (60 boys, 38 girls) and the validation group (26 boys, 18 girls). Contiguous magnetic resonance images were obtained from the first cervical vertebra to the ankle joints as reference data. SM volume was calculated from the summation of the digitised cross-sectional areas. Limb and waist circumferences were measured at mid-upper arm, mid-thigh, maximal calf, and at the level of umbilicus. Each girth was corrected for subcutaneous adipose tissue thickness, as estimated by skinfold thickness measurements. Skinfold thickness was measured at the posterior upper arm, anterior thigh, medial calf, and lateral to the umbilicus, using callipers. Significant correlations were observed between the site-matched SM volume, measured by magnetic resonance imaging, and each corrected girth × standing height value in the model development group. When these SM volume prediction equations were applied to the validation group, the measured total body and regional SM volume were similar to the predicted values. These results suggest that the anthropometric prediction equations developed in this study provide reliable information about the total and regional SM volume in prepubertal Japanese children, with varying degrees of estimation accuracy for each region.
Right ventricular outflow tract intervention spans transcatheter, surgical, or hybrid pulmonary valve replacement methodologies. Standardised pre-procedure workup includes cardiac MRI to identify an intended valve site (landing zone). Our institutional practice includes measurement of the right ventricular outflow tract perimeter (circumference) of this site in end-systole. Our primary aim was to compare patients by their perimeter values to the palliative interventions performed (transcatheter versus surgical/hybrid methodologies).
Retrospective review of patients undergoing pulmonary valve replacement from January 2017 to 2021. We performed perimeter measurements at the intended valve site on advanced imaging; the outcomes of interventions were outlined via descriptive and statistical analyses.
A total of 37 patients underwent pulmonary valve replacement that met study criteria – 21 transcatheter, 7 surgical, and 9 hybrid. Median age at intervention was 26 years (range 8–70). The mean end-systolic perimeter of the transcatheter cohort was 88.9 ± 8.7 mm and in the surgical/hybrid cohort measured 106.6 ± 7.5 mm. For the transcatheter cohort, the median “circularised” diameter derived from the perimeter measurement (divided by π) was 27.7 mm (range 24.3–32.4). Notably, this correlated (r = 0.93, p < 0.01) with the median diameter of the narrowest region during actual transcatheter right ventricular outflow tract balloon sizing (lateral imaging) of 27.1 mm (range 23.2–30.1).
Right ventricular outflow tract perimeter measurement to determine circularised diameter is useful in planning pulmonary valve replacement in terms of candidacy of transcatheter versus the need for a surgical/hybrid approach. The circularised diameter correlates with transcatheter right ventricular outflow tract balloon sizing.
This study aimed to assess the ventricular anatomy, function of the right ventricle, and the haemodynamic findings of pulmonary artery in children with cystic fibrosis using cardiac MRI.
This prospective study consisted of 32 children with mild cystic fibrosis and 30 age-matched healthy control participants.
Cardiac MRI was used to assess right ventricular volumes, anatomy, and function and to assessment of haemodynamic findings of pulmonary artery in the control and study groups. Haemodynamic findings of pulmonary arteries were determined using pulmonary arteries peak velocity (cm/s), and pulmonary arteries time-to-peak velocity (ms) and pulmonary artery systolic pressure. All data of children with mild cystic fibrosis were compared with those of 30 age-matched healthy control group participants.
Our patients and their age-matched controls were aged from 6 to 17 years and from 7 to 15 years, respectively. We found that ejection fraction (%), cardiac output (L/ml), cardiac output (L/ml/m2), and systolic volume (ml/m2) were significantly lower in children with cystic fibrosis (p < 0.01). Right ventricular anterior wall thickness (mm) was significantly higher in children with cystic fibrosis (p = 0.01). No significant difference was observed between the haemodynamic parameters of pulmonary artery in the patient group.
In our study, cardiac MRI was used to investigate whether the right ventricle was affected functionally and anatomically in children with mild cystic fibrosis. We detected a significant decrease in right ventricular systolic functions and notable alterations in the right ventricular geometry of children with mild cystic fibrosis. These alterations usually manifest themselves as hypertrophy of the right ventricle. Our study’s results demonstrate no relationship between the development of pulmonary hypertension in mild cystic fibrosis children.
Understanding deviations from typical brain development is a promising approach to comprehend pathophysiology in childhood and adolescence. We investigated if cerebellar volumes different than expected for age and sex could predict psychopathology, executive functions and academic achievement.
Children and adolescents aged 6–17 years from the Brazilian High-Risk Cohort Study for Mental Conditions had their cerebellar volume estimated using Multiple Automatically Generated Templates from T1-weighted images at baseline (n = 677) and at 3-year follow-up (n = 447). Outcomes were assessed using the Child Behavior Checklist and standardized measures of executive functions and school achievement. Models of typically developing cerebellum were based on a subsample not exposed to risk factors and without mental-health conditions (n = 216). Deviations from this model were constructed for the remaining individuals (n = 461) and standardized variation from age and sex trajectory model was used to predict outcomes in cross-sectional, longitudinal and mediation analyses.
Cerebellar volumes higher than expected for age and sex were associated with lower externalizing specific factor and higher executive functions. In a longitudinal analysis, deviations from typical development at baseline predicted inhibitory control at follow-up, and cerebellar deviation changes from baseline to follow-up predicted changes in reading and writing abilities. The association between deviations in cerebellar volume and academic achievement was mediated by inhibitory control.
Deviations in the cerebellar typical development are associated with outcomes in youth that have long-lasting consequences. This study highlights both the potential of typical developing models and the important role of the cerebellum in mental health, cognition and education.
Given psychotic illnesses' high heritability and associations with brain structure, numerous neuroimaging-genetics findings have been reported in the last two decades. However, few findings have been replicated. In the present independent sample we aimed to replicate any psychosis-implicated SNPs (single nucleotide polymorphisms), which had previously shown at least two main effects on brain volume.
A systematic review for SNPs showing a replicated effect on brain volume yielded 25 studies implicating seven SNPs in five genes. Their effect was then tested in 113 subjects with either schizophrenia, bipolar disorder, ‘at risk mental state’ or healthy state, for whole-brain and region-of-interest (ROI) associations with grey and white matter volume changes, using voxel-based morphometry.
We found FWER-corrected (Family-wise error rate) (i.e. statistically significant) associations of: (1) CACNA1C-rs769087-A with larger bilateral hippocampus and thalamus white matter, across the whole brain; and (2) CACNA1C-rs769087-A with larger superior frontal gyrus, as ROI. Higher replication concordance with existing literature was found, in decreasing order, for: (1) CACNA1C-rs769087-A, with larger dorsolateral-prefrontal/superior frontal gyrus and hippocampi (both with anatomical and directional concordance); (2) ZNF804A-rs11681373-A, with smaller angular gyrus grey matter and rectus gyri white matter (both with anatomical and directional concordance); and (3) BDNF-rs6265-T with superior frontal and middle cingulate gyri volume change (with anatomical and allelic concordance).
Most literature findings were not herein replicated. Nevertheless, high degree/likelihood of replication was found for two genome-wide association studies- and one candidate-implicated SNPs, supporting their involvement in psychosis and brain structure.
Schizophrenia is associated with disturbances in neurophysiological processes. However, the relation of EEG and ERP parameters to structural supragranular cortical abnormalities, observed in schizophrenia, remains unclear.
The purpose was to characterize EEG and ERP disturbances and their relationship to changes occurring in supragranular cortical layers in subjects with schizophrenia.
43 first-episode schizophrenia (FES) male patients and 43 matched healthy controls (HC) underwent background EEG and standard two-tones oddball ERP recording and structural MRI at 3T Philips scanner. MRI images were processed via FreeSurfer and MATLAB to derive two markers specific to supragranular thickness change: gyral-sulcal thickness differences (GSTD) and gyral-sulcal intrinsic curvature differences on pial surface (GSCD) (github.com/kwagstyl/schizophrenia_gyral_sulcal).
Theta rhythm spectral power was increased in FES while P300 amplitudes and latencies, N100 (to non-targets) amplitudes, alpha rhythm spectral power were not altered compared to HC. GSCD measures were increased in temporal, parietal and occipital cortices, whereas both GSTD and GSCD were increased in the right frontal cortex in FES. No correlations between altered EEG and supragranular thickness markers survived correction for multiple comparisons.
Presumably, theta rhythm has a widespread circuit of generators, including the cortical ones. However, we have not found correlations between EEG and supragranular markers in FES. Considering an absence of correlations between theta and hippocampal volumes (Lebedeva et al., 2020), a speculative interpretation is that the neurophysiological disturbances may be associated with a more complex patterns of more localized structural and functional impairments.
The work was supported by RFBR grant 20-013-00748.
Bipolar disorder has been repeatedly associated with abnormalities of white matter. However, DTI is intrinsically limited and the precise cellular mechanisms that underlie these alterations remains unknown.
Our aim was to investigate microscopical characteristics of white matter using MRI in patients with bipolar and healthy controls.
77 patients and 71 controls from 3 sites had a T1 structural MRI, a multi-shell HARDI MRI and at one site with a T1-weighted VFA-SPGR acquisition, and a T2 MSME acquisition. The volume fraction and the orientation dispersion was extracted using NODDI from DW images in each site. Myelin Water Fraction was extracted in 33 patients and 36 controls to probe myelin characteristics. White matter bundles were reconstructed using deterministic tractography. Statistical analyses were performed after harmonization by the ComBat algorithm and controlled for age, gender and handedness.
We found significant lower axonal density in patients along the short fibers of the left cingulum, the left anterior arcuate and the left inferior fronto-occipital fasciculus. We found lower mean MWF in patients along the short fibers of the right cingulum, the left inferior fronto-occipital fasciculus, the left anterior arcuate and the splenium of the corpus callosum. We found higher mean orientation dispersion in patients only along the left uncinate fasciculus.
We report alterations of limbic and inter-hemispheric white matter tracts in patients with bipolar disorder reflecting axonal loss, demyelination and architecture alterations. These results contribute to better capture the plurality of the mechanisms involved in bipolar disorder that cannot be deciphered with classical diffusion MRI.
The hippocampus is a complex brain structure with key roles in cognitive and emotional processing and with subregion abnormalities associated with a range of disorders and psychopathologies. Here we combine data from two large independent young adult twin/sibling cohorts to obtain the most accurate estimates to date of genetic covariation between hippocampal subfield volumes and the hippocampus as a single volume. The combined sample included 2148 individuals, comprising 1073 individuals from 627 families (mean age = 22.3 years) from the Queensland Twin IMaging (QTIM) Study, and 1075 individuals from 454 families (mean age = 28.8 years) from the Human Connectome Project (HCP). Hippocampal subfields were segmented using FreeSurfer version 6.0 (CA4 and dentate gyrus were phenotypically and genetically indistinguishable and were summed to a single volume). Multivariate twin modeling was conducted in OpenMx to decompose variance into genetic and environmental sources. Bivariate analyses of hippocampal formation and each subfield volume showed that 10%–72% of subfield genetic variance was independent of the hippocampal formation, with greatest specificity found for the smaller volumes; for example, CA2/3 with 42% of genetic variance being independent of the hippocampus; fissure (63%); fimbria (72%); hippocampus-amygdala transition area (41%); parasubiculum (62%). In terms of genetic influence, whole hippocampal volume is a good proxy for the largest hippocampal subfields, but a poor substitute for the smaller subfields. Additive genetic sources accounted for 49%–77% of total variance for each of the subfields in the combined sample multivariate analysis. In addition, the multivariate analyses were sufficiently powered to identify common environmental influences (replicated in QTIM and HCP for the molecular layer and CA4/dentate gyrus, and accounting for 7%–16% of total variance for 8 of 10 subfields in the combined sample). This provides the clearest indication yet from a twin study that factors such as home environment may influence hippocampal volumes (albeit, with caveats).
Nearly one in five children with CHD is born with white matter injury that can be recognised on postnatal MRI by the presence of T1 hyperintense lesions. This pattern of white matter injury is known to portend poor neurodevelopmental outcomes, but the exact aetiology and histologic characterisation of these lesions have never been described. A fetal sheep was cannulated at gestational age 110 days onto a pumpless extracorporeal oxygenator via the umbilical vessels and supported in a fluid environment for 14.5 days. The fetus was supported under hypoxic conditions (mean oxygen delivery 16 ml/kg/day) to simulate the in utero conditions of CHD. At necropsy, the brain was fixed, imaged with MRI, and then stained to histologically identify areas of injury. Under hypoxemic in utero conditions, the fetus developed a T1 hyperintense lesion in its right frontal lobe. Histologically, this lesion was characterised by microvascular proliferation and astrocytosis without gliosis. These findings may provide valuable insight into the aetiology of white matter injury in neonates with CHD.