Hippocampus and amygdala volumes in a random community-based sample of 60–64 year olds and their relationship to cognition

Reduced volumes of the hippocampus (HC) and amygdala (AG) are potential biomarkers for Alzheimer's disease (AD) and other neuropsychiatric disorders. Published studies on HC and AG volumes suffer from methodological limitations, and a valid and reliable normative database does not exist. This study aimed to establish a database of HC and AG volumes from a large community sample of participants 60–64 years old and relate them to cognition. A total of 452 randomly selected participants (from 622 approached) were retained in the study (238 males, 214 females), and all received brain MRI scans, as well as cognitive and physical assessments. HC and AG volumes were estimated from manual tracings on T1-weighted images, and intracranial volume (ICV) was obtained from an automated program. In both sexes, right hippocampi were larger than left, while left amygdalae were larger than right. The only correlation to remain significant after normalization was left HC volume and percent retention of a word list in females. This study provides a HC and AG volumetrics database and describes its relationship with cognitive performance in a representative sample using a standard methodology that will be a reference for future studies. It will therefore have clinical applicability in early AD and other disorders.     

Quantitative MRI in Outpatient Childhood Epilepsy

Summary: Purpose: In adult studies, MRI volumetrics is a proven technique in presurgical assessment of epilepsy. Hippocampal volume loss is maximal in the syndrome of mesial temporal lobe epilepsy. We aimed (a) to validate this methodology in a pediatric outpatient epilepsy population (b) to determine the relationship of hippocampal asymmetry (HA) to epileptic syndromes and risk factors. Methods: Two neurologists classified the epileptic syndrome in 79 pediatric outpatients, according to the International Classification of Epilepsies and Epileptic Syndromes (ILAE). Hippocampal volumetrics were performed in all patients. HA was defined according to adult control values. Results: Inter-rater variability on measurement of HA was very small (Correlation of test retest of 0.97 on 17 children <3 years old). The rate of HA was 44/79 (57%). In 21 patients, (27%) potentially epileptogenic lesions (other than HA) were identified (cerebral dysgenesis n = 11). HA was present in 9/15 (60%) of temporal lobe epilepsy and in 15/28 (54%) extratemporal onset epilepsy and 5/11 (46%) of generalized symptomatic epilepsy. Analysis confined to <13 years also showed HA was not specific for epileptic syndrome. There was no significant association of febrile convulsions (13%) with HA or temporal lobe epilepsy. Conclusions: There is a high incidence of HA in childhood epilepsy. HA was not confined to clinically defined temporal lobe epilepsy. The poor correlation of epileptic syndrome to quantitative MRI findings may be due to the inadequacies of epilepsy classification in the younger child, with the clinical semiology providing misleading localizing information. Normative childhood data for hippocampal volumes and symmetry is needed.     

Angiographic and volumetric effects of mammalian target of rapamycin inhibitors on angiomyolipomas in tuberous sclerosis

AIM: To investigate the angiographic and volumetric effects of mammalian target of rapamycin (mTOR) inhibitors on angiomyolipomas (AMLs) in a case series of patients with tuberous sclerosis complex.METHODS: All patients who underwent catheter angiography prior to and following mTOR inhibitor therapy (n = 3) were evaluated. All cross-sectional imaging studies were analyzed with three-dimensional volumetrics, and tumor volume curves for all three tissue compartments (soft tissue, vascular, and fat) were generated. Segmentation analysis tools were used to automatically create a region of interest (ROI) circumscribing the AML. On magnetic resonance images, the “fat only” map calculated from the in- and opposed-phase gradient recalled echo sequences was used to quantify fat volume within tumors. Tumor vascularity was measured by applying a thresholding tool within the ROI on post-contrast subtraction images. On computed tomography images, volume histogram analysis of Hounsfield unit was performed to quantify tumor tissue composition. The angiography procedures were also reviewed, and tumor vascularity based on pre-embolization angiography was characterized in a semi-quantitative manner.RESULTS: Patient 1 presented at the age of 15 with a 6.8 cm right lower pole AML and a 4.0 cm right upper pole AML. Embolization was performed of both tumors, and after a few years of size control, the tumors began to grow, and the patient was initiated on mTOR inhibitor therapy. There was an immediate reduction in the size of both lesions. The patient then underwent repeat embolization and discontinuation of mTOR inhibition, after which point there was a substantial regrowth in both tumors across all tissue compartments. Patient 2 presented at the age of 18 with a right renal AML. Following a brief period of tumor reduction after embolization, she was initiated on mTOR inhibitor therapy, with successful reduction in tumor size across all tissue compartments. As with patient 1, however, there was immediate rebound growth following discontinuation of inhibitor therapy, without sustained control despite repeat embolization. patient 3 presented at the age of 5 with a left renal AML and underwent two embolization procedures without lasting effect prior to starting mTOR inhibition. As with patients 1 and 2, following discontinuation of therapy, there was immediate rebound growth of the tumor. Repeat embolization, however, was notable for a substantial reduction in intratumoral aneurysms and vascularity.CONCLUSION: AML volume reduction as well as post-treatment rebound growth due to mTOR inhibitors involves all three tissue components of the tumor.     

ILAE-Defined Epilepsy Syndromes in Children: Correlation with Quantitative MRI

Summary: Purpose : The role of quantitative magnetic resonance imaging (MRI) in evaluation of childhood epilepsy remains poorly defined, with minimal published data. Previous work from our center questioned the specificity of hippocampal asymmetry (HA) in an outpatient group whose epilepsy was defined by using clinical and interictal data only. By using childhood volunteer controls and defining epilepsy syndromes using video-EEG monitoring, we readdressed the utility of HA in differentiating mesial temporal lobe epilepsy (M tle ) from other partial and generalized epileptic syndromes in children.
Methods: Seventy children were enrolled; entry criteria were age younger than 18 years with predominant seizure type recorded on video-EEG telemetry with volumetric MRI in all cases. Thirty healthy child volunteers had volumetric MRI. Epilepsy syndrome classification was according to ILAE.
Results: Control data revealed symmetric hippocampi, mean smallernarger ratio of 0.96 (0.95–0.97,95% CI) with no gender or rightneft predominance. Overall 23% of patients had significant HA. Mean hippocampal ratio for M tle was 0.78 (95% CI, 0.70–0.86), significantly lower than controls and from all other epilepsy syndromes. HA was highly specific (85%) to the syndrome of MTLE. Other potential epileptogenic lesions were found in 27 (39%) patients, lowest yield in frontal and mesial temporal syndromes. Dual pathology was present in 10% of patients. There was no significant association between HA and risk factors.
Conclusions: In this study, we found that HA in children with a well-defined epilepsy syndrome is highly sensitive and specific for MTLE. Whether this will correlate with surgical outcome, as in adults, is the subject of ongoing study.     

Computer-Assisted Volumetric Analysis Compared With ABC/2 Method for Assessing Warfarin-Related Intracranial Hemorrhage Volumes

Introduction  Intraparenchymal hemorrhage (IPH) volume is a powerful predictor of 30-day mortality. Warfarin-related intracranial hemorrhage (ICH) has a higher mortality than ICH without anticoagulation, possibly due to continued growth after 24 h, larger average size, and extension to extraparenchymal compartments. We compared 2 methods of measuring ICH volume in patients with warfarin-related ICH. Methods  ICH volume was estimated using the ABC/2 method and a computer-assisted method (Analyze 6.0 software) applied to the initial head computed tomographic scans in a consecutive series of 8 patients with warfarin-related ICH. The 2 methods were compared for relative and absolute differences in estimated hematoma volumes. Results  The ABC/2 method underestimated hematoma volume in 4 of 5 patients with IPH, inaccurately calculated intraventricular hemorrhage volume in 2 patients (overestimated by 9%, underestimated by 23%), and underestimated a complex subdural hematoma in 1 patient by 24% despite use of the Gebel modification. The mean percentage difference between the Analyze and ABC/2 methods was 24% in ellipsoid hemorrhages and 28% in nonellipsoid hemorrhages (P = 0.77). The mean of the absolute difference between the 2 methods was 6.7 cm³ in ellipsoid hemorrhages and 38.0 cm³ in nonellipsoid hemorrhages (P = 0.18). Conclusion  The ABC/2 method accurately and quickly estimates smaller, ellipsoid intraparenchymal hematomas but is inaccurate for larger, complex-shaped warfarin-related intraparenchymal, intraventricular, and subdural hematomas. Warfarin-related ICH mortality may be underestimated by the ABC/2 method because of larger, complex-shaped, and multicompartmental hematomas. Presented in part as a poster at the annual meeting of the Neurocritical Care Society, Baltimore, Maryland, November 6, 2006.     

Longitudinal changes in cortical thickness in children after traumatic brain injury and their relation to behavioral regulation and emotional control

The purpose of this study was to assess patterns of cortical development over time in children who had sustained traumatic brain injury (TBI) as compared to children with orthopedic injury (OI), and to examine how these patterns related to emotional control and behavioral dysregulation, two common post-TBI symptoms. Cortical thickness was measured at approximately 3 and 18 months post-injury in 20 children aged 8.2-17.5 years who had sustained moderate-to-severe closed head injury and 21 children aged 7.4-16.7 years who had sustained OI. At approximately 3 months post-injury, the TBI group evidenced decreased cortical thickness bilaterally in aspects of the superior frontal, dorsolateral frontal, orbital frontal, and anterior cingulate regions compared to the control cohort, areas of anticipated vulnerability to TBI-induced change. At 18 months post-injury, some of the regions previously evident at 3 months post-injury remained significantly decreased in the TBI group, including bilateral frontal, fusiform, and lingual regions. Additional regions of significant cortical thinning emerged at this time interval (bilateral frontal regions and fusiform gyrus and left parietal regions). However, differences in other regions appeared attenuated (no longer areas of significant cortical thinning) by 18 months post-injury including large bilateral regions of the medial aspects of the frontal lobes and anterior cingulate. Cortical thinning within the OI group was evident over time in dorsolateral frontal and temporal regions bilaterally and aspects of the left medial frontal and precuneus, and right inferior parietal regions. Longitudinal analyses within the TBI group revealed decreases in cortical thickness over time in numerous aspects throughout the right and left cortical surface, but with notable "sparing" of the right and left frontal and temporal poles, the medial aspects of both the frontal lobes, the left fusiform gyrus, and the cingulate bilaterally. An analysis of longitudinal changes in cortical thickness over time (18 months-3 months) in the TBI versus OI group demonstrated regions of relative cortical thinning in the TBI group in bilateral superior parietal and right paracentral regions, but relative cortical thickness increases in aspects of the medial orbital frontal lobes and bilateral cingulate and in the right lateral orbital frontal lobe. Finally, findings from analyses correlating the longitudinal cortical thickness changes in TBI with symptom report on the Emotional Control subscale of the Behavior Rating Inventory of Executive Function (BRIEF) demonstrated a region of significant correlation in the right medial frontal and right anterior cingulate gyrus. A region of significant correlation between the longitudinal cortical thickness changes in the TBI group and symptom report on the Behavioral Regulation Index was also seen in the medial aspect of the left frontal lobe. Longitudinal analyses of cortical thickness highlight an important deviation from the expected pattern of developmental change in children and adolescents with TBI, particularly in the medial frontal lobes, where typical patterns of thinning fail to occur over time. Regions which fail to undergo expected cortical thinning in the medial aspects of the frontal lobes correlate with difficulties in emotional control and behavioral regulation, common problems for youth with TBI. Examination of post-TBI brain development in children may be critical to identification of children that may be at risk for persistent problems with executive functioning deficits and the development of interventions to address these issues.     

Bilateral Hippocampal Volume Loss in Patients with a History of Encephalitis or Meningitis

Volumetric analysis of high-quality magnetic resonance imaging (MRI) scans identifies asymmetric hippocampal atrophy in most patients with temporal lobe epilepsy. However, bilateral hippocampal atrophy can be missed by unnormalized volume measures. We considered two patient groups with temporal lobe epilepsy, one with a history of febrile convulsions (FC, n = 14) and one with a history of encephalitis or meningitis (E/M, n = 12), to compare the prevalence of bilateral volume loss between the groups. A volume normalization process defines a normal range of hippocampal volumes in control subjects (n = 32). Normalized volumes indicated that 11 of 14 subjects with a history of FC had unilateral hippocampal atrophy and 9 of 12 subjects with a history of E/M had bilateral hippocampal atrophy as compared with the controls. Visual assessments of unilateral hippocampal atrophy (n = 17) correlated well with measured unilateral volume loss (n = 14), but visual assessment of bilateral hippocampal atrophy (n = 3) correlated poorly with measured bilateral volume loss (n = 12). Mean age at seizure onset was lower in the FC group (7 years) than in the E/M group (13 years), but other clinical features were similar between the two groups. Hippocampal volume normalization is necessary to detect bilateral volume loss, which is common in patients with a history of encephalitis or meningitis.     

Traumatic brain injury, major depression, and diffusion tensor imaging: Making connections

It is common for depression to develop after traumatic brain injury (TBI), yet despite poorer recovery, there is a lack in our understanding of whether post-TBI brain changes involved in depression are akin to those in people with depression without TBI. Modern neuroimaging has helped recognize degrees of diffuse axonal injury (DAI) as being related to extent of TBI, but its ability to predict long-term functioning is limited and has not been considered in the context of post-TBI depression. A more recent brain imaging technique (diffusion tensor imaging; DTI) can measure the integrity of white matter by measuring the directionality or anisotropy of water molecule diffusion along the axons of nerve fibers. Aim: To review DTI results in the TBI and depression literatures to determine whether this can elucidate the etiology of the development of depression after TBI. Method: We reviewed the TBI/DTI (40 articles) and depression/DTI literatures (17 articles). No articles were found that used DTI to investigate depression post-TBI, although there were some common brain regions identified between the TBI/DTI and depression/DTI studies, including frontotemporal, corpus callosum, and structures contained within the basal ganglia. Specifically, the internal capsule was commonly reported to have significantly reduced fractional anisotropy, which agrees with deep brain stimulation studies. Conclusion: It is suggested that measuring the degree of DAI by utilizing DTI in those with or without depression post-TBI, will greatly enhance prediction of functional outcome.     

Systemic inflammation moderates the association of prior concussion with hippocampal volume and episodic memory in high school and collegiate athletes

BackgroundThere is a need to determine why prior concussion has been associated with adverse outcomes in some retired and active athletes. We examined whether serum inflammatory markers moderate the associations of prior concussion with hippocampal volumes and neurobehavioral functioning in active high school and collegiate athletes.MethodsAthletes (N = 201) completed pre-season clinical testing and serum collection (C-reactive protein [CRP]; Interleukin-6 [IL]-6; IL-1 receptor antagonist [RA]) and in-season neuroimaging. Linear mixed-effects models examined associations of prior concussion with inflammatory markers, self-reported symptoms, neurocognitive function, and hippocampal volumes. Models examined whether inflammatory markers moderated associations of concussion history and hippocampal volume and/or clinical measures.ResultsConcussion history was significantly associated with higher symptom severity, p = 0.012, but not hippocampal volume or inflammatory markers (ps > 0.05). A significant interaction of prior concussion and CRP was observed for hippocampal volume, p = 0.006. Follow-up analyses showed that at high levels of CRP, athletes with two or more prior concussions had smaller hippocampal volume compared to athletes without prior concussion, p = 0.008. There was a significant interaction between prior concussion and levels of IL-1RA on memory scores, p = 0.044, i.e., at low levels of IL-1RA, athletes with two or more concussions had worse memory performance than those without prior concussion (p = 0.014).ConclusionFindings suggest that certain markers of systemic inflammation moderate the association between prior concussion and hippocampal volume and episodic memory performance. Current findings highlight potential markers for predicting at-risk individuals and identify therapeutic targets for mitigating the long-term adverse consequences of cumulative concussion.     

Brain structure and aging in chronic temporal lobe epilepsy

Purpose: To characterize differences in brain structure and their patterns of age‐related change in individuals with chronic childhood/adolescent onset temporal lobe epilepsy compared with healthy controls. Methods: Subjects included participants with chronic temporal lobe epilepsy (n = 55) of mean childhood/adolescent onset and healthy controls (n = 53), age 14–60 years. Brain magnetic resonance imaging (MRI) studies (1.5 T) were processed using FreeSurfer to obtain measures of lobar thickness, area, and volume as well as volumes of diverse subcortical structures and cerebellum. Group differences were explored followed by cross‐sectional lifespan modeling as a function of age. Key Findings: Anatomic abnormalities were extensive in participants with chronic temporal lobe epilepsy including distributed subcortical structures (hippocampus, thalamus, caudate, and pallidum), cerebellar gray and white matter, total cerebral gray and white matter; and measures of cortical gray matter thickness, area, or volume in temporal (medial, lateral) and extratemporal lobes (frontal, parietal). Increasing chronologic age was associated with progressive changes in diverse cortical, subcortical, and cerebellar regions for both participants with epilepsy and controls. Age‐accelerated changes in epilepsy participants were seen in selected areas (third and lateral ventricles), with largely comparable patterns of age‐related change across other regions of interest. Significance: Extensive cortical, subcortical, and cerebellar abnormalities are present in participants with mean chronic childhood/adolescent onset temporal lobe epilepsy implicating a significant neurodevelopmental impact on brain structure. With increasing chronologic age, the brain changes occurring in epilepsy appear to proceed in a largely age‐appropriate fashion compared to healthy controls, the primary exception being age‐accelerated ventricular expansion (lateral and third ventricles). These cumulative structural abnormalities appear to represent a significant anatomic burden for persons with epilepsy, the consequences of which remain to be determined as they progress into elder years.