Search

Objective Although bipolar II disorder (BD II) is not simply a mitigated form of bipolar I disorder (BD I), their neurobiological differences have not been elucidated. The present study aimed to explore cortical thickness (CT) and surface area (SA) in patients with BD I and BD II and healthy controls (HCs) to investigate the shared and unique neurobiological mechanisms of BD subtypes.Methods We enrolled 30 and 44 patients with BD I and BD II, respectively, and 100 HCs. We evaluated CT and SA using FreeSurfer and estimated differences in CT and SA among the three groups (BD I vs. BD II vs. HC). We adjusted for age, sex, educational level, and intracranial volume as confounding factors.Results We found widespread cortical thinning in the bilateral frontal, temporal, and occipital regions; cingulate gyrus; and insula in patients with BD. Alterations in SA, including increased SA of the pars triangularis and decreased SA of the insula, were noted in patients with BD. Overall, we found BD II patients demonstrated decreased SA in the right long insula compared to BD I patients.Conclusion Our results suggest that decreased SA in the right long insula is crucial for differentiating BD subtypes.

Objectives: Severity of trigonocephaly varies and potentially affects intracranial volume (ICV) and intracranial pressure (ICP). The aim of this study is to measure ICV in trigonocephaly patients and compare it to normative data and correlate ICV with the severity of the skull deformity according to UCSQ (Utrecht Cranial Shape Quantifier). Design: Retrospective study. Setting: Primary craniofacial center. Patients, Participants: Nineteen preoperative patients with nonsyndromic trigonocephaly (age ≤12 months). Intervention: Intracranial volume was measured on preoperative computed tomography (CT) scans by manual segmentation (OsiriX Fondation). Utrecht Cranial Shape Quantifier was used to quantify the severity of the skull deformity. When present, papilledema as sign of elevated ICP was noted. Main Outcome Measures(s): Measured ICV was compared to Lichtenberg normative cranial volume growth curves, and Pearson correlation coefficient was used to correlate UCSQ with the ICV. Results: Mean age at CT scan was 6 months (2-11). Mean measured ICV was 842 mL (579-1124). Thirteen of h19 patients (11/15 boys and 2/4 girls) had an ICV between ±2 SD curves of Lichtenberg, 2 of 19 (1/15 boys and 1/4 girls) had an ICV less than −2 SD and 4 of 19 (3/15 boys and 1/4 girls) had an ICV greater than +2 SD. Mean UCSQ severity of trigonocephaly was 2.40 (−622.65 to 1279.75). Correlation between severity and ICV was negligible (r = −0.11). No papilledema was reported. Conclusions: Measured ICV was within normal ranges for trigonocephaly patients, in both mild and severe cases. No correlation was found between severity of trigonocephaly and ICV.

Background: Differentiation between symptoms of normal pressure hydrocephalus (NPH) and other neurodegenerative disorders such as Brain Atrophy (BA) are usually confusing. Available diagnostic methods are invasive while the few non-invasive methods did not take care of potential factors known to influence intracranial volumes. We, therefore, aim to determine and compare the intracranial volume fractions among patients with NPH and BA. Methods: This was a prospective, cross-sectional age-matched control study among consenting patients that were diagnosed with NPH, BA and healthy control in Aminu Kano Teaching Hospital from March 2018 to November 2020. Each patient was routinely examined with CT-Scan; However, control participants were from other reasons. Participants with a medical history known to influence the intracranial volume were excluded. Volume estimation was based on a stereological Cavalieri method and three volume fractions were determined mathematically for each of the group. Test-point computing was facilitated through a locally developed software (voXas_2018). Ethical approval was sort prior to the study. Results: Patients with NPH have higher total CSF: brain ratio, intraventricular volume: brain ratio and extra-ventricular: brain ratio. Similar pattern was exhibited according to age grouping, except in the older age category where BA volume fractions were higher. Conclusion: Age, gender and statue are known to influence intracranial volumes. We controlled their potential effects through age-matched control of participants between groups and the use of intracranial volume ratios for objective diagnosis of NPH and BA. However, Tcsf:Br and InV:Br volume fraction ratios were found to be reliable indices for distinguishing patients with NPH and BA.

INTRODUCTION The primary outcome metric in patients with craniosynostosis are changes in intracranial volumes (ICVs). In patients who undergo distraction osteogenesis (DO) to treat craniosynostosis, changes are also dependent on the length of distraction. Virtual surgical planning (VSP) has been used to predict anticipated changes in ICV during cranial vault reconstruction. The purpose of this study is to analyze the actual versus predicted ICV changes using VSP in patients who undergo DO for craniosynostosis management. METHODS All patients with craniosynostosis treated with DO at a single institution, Rady Children's Hospital, between December 2013 and May 2019 were identified. Inclusion criteria are as follows: VSP planning with predicted postoperative ICV values and preoperative and postdistraction CT scans to quantify ICV. Postoperative ICV and VSP-estimated ICV were adjusted for age-related ICV growth. The primary outcome measure calculated was age-adjusted percent volume change per millimeter distraction (PVCPD), and results were analyzed using paired Wilcoxon signed rank tests. RESULTS Twenty-seven patients underwent DO for cranial vault remodeling. Nineteen patients were nonsyndromic, and 8 patients were syndromic. The median postoperative PVCPD was 0.30%/mm, and the median VSP-estimated PVCPD was 0.36% per millimeter (P < 0.001). A subanalysis of nonsyndromic patients showed a median postoperative PVCPD of 0.29%/mm in nonsyndromic patients that differed significantly from the VSP estimate of 0.34%/mm (P = 0.003). There was also a significant difference in syndromic patients' observed PVCPD of 0.41%/mm versus VSP estimate of 0.79%/mm (P = 0.012). CONCLUSIONS Virtual surgical planning overestimates the change in ICV attributable to DO in both syndromic and nonsyndromic patients.

Posterior cranial vault distraction is an important modality in the management of craniosynostosis. This surgical technique increases intracranial volume and improves cranial aesthetics. A single procedure is often inadequate in patients with complex multisuture craniosynostosis, as some will go on to develop intracranial hypertension despite the operation. Considering the negative effects of intracranial hypertension, some patients may warrant 2 planned distractions to prevent this scenario from ever occurring. Three patients with complex multiple-suture synostosis and severe intracranial volume restriction (occipital frontal head circumferences [OFCs]

Dementia is the most frequent degenerative sickness in adults where early diagnosis can forestall or prolong progression. In this study, we used a deep learning techniques for classification of dementia. Data were collected from OASIS database of all the patients receiving dementia screening. The data included the patient’s sex, age, education, social economic status, Mini-Mental State Examination, Clinical Dementia Rating, Atlas Scaling Factor, Estimated Total Intracranial Volume and Normalized Whole Brain Volume. The performance of every algorithm is juxtaposed with Generalized Regression Neural Network (GRNN), Radial Basis Neural Network (RBNN), Multilayer Perceptron Neural Network (MPNN) and Long Short Term Memory (LSTM) using Sensitivity, Specificity, Detection Rate. The results show that with 100% efficiency, GRNN, RBNN and LSTM tend to be the best in the classification of dementia. The use of deep learning such as LSTM for early diagnosis of dementia can help improve the process of dementia diagnosis.

Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered ( https://osf.io/73dvy ) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (, Translational Psychiatry, 12 (1), ISSN:2158-3188

This article reports quantitative measurements of intracranial volume, optic canal area, and peripapillary retinal nerve fiber layer (RNFL) for a cohort of 124 patients with craniofacial fibrous dysplasia/McCune-Albright Syndrome (FD/MAS), previously used to determine risks for developing optic disc edema [1] . Of these, 7 subjects were diagnosed with optic disc edema. OSIRIX imaging analysis software was used to collect intracranial volume and optic canal diameter for 107 patients, via 3D multiplanar reconstruction (MPR) of ≤5 mm axial CT slices. Spectral-domain Optical Coherence Tomography (OCT) was performed with the Cirrus-HD OCT (Carl Zeiss Meditec, Inc., Dublin, CA). The Optic Disc Cube 200 × 200 protocol was used for acquisition and analysis of the RNFL for 69 patients. The data can be used to assess typical ranges for intracranial volume, optic canal area, and RNFL in the craniofacial FD/MAS population and to assess ranges concerning for optic disc edema. [1] Raborn LN, Pan KS, FitzGibbon EJ, Collins MT, Boyce AM. Optic disc edema in fibrous dysplasia/McCune-Albright syndrome: Prevalence, etiologies, and clinical implications. Bone. 2021 Feb;143:115661. doi: 10.1016/j.bone.2020.115661. Epub 2020 Sep 24. PMID: 32979536 .

BACKGROUND The impact of metopic craniosynostosis on intracranial volume (ICV) and ICV growth is unclear. In addition, the relationship between head circumference (HC) and ICV in these patients is not previously described. METHODS A retrospective review of 72 patients with metopic craniosynostosis was performed. The ICVs were calculated from manually segmented preoperative computed tomography scans. Magnetic resonance imaging data for 270 healthy children were available. The ICVs were calculated in FreeSurfer.First, a growth curve for metopic patients was generated and a logarithmic best-fit curve was calculated. Second, the impact of metopic craniosynostosis on ICV relative to healthy controls was assessed using multivariate linear regression. Third, the growth curves for metopic patients and healthy children were compared.Pearson's correlation was used to measure the association between HC and ICV. RESULTS Mean metopic ICV was significantly lower than normal ICV within the first 3 to 6 months (674.9 versus 813.2 cm; P = 0.002), 6 to 9 months (646.6 versus 903.9 cm; P = 0.005), and 9 to 12 months of life (848.0 versus 956.6 cm; P = 0.038). There was no difference in ICV after 12 months of age (P = 0.916).The ICV growth in patients with metopic craniosynostosis is defined by a significantly different growth curve than in normal children (P = 0.005).The ICV and HC were highly correlated across a broad range of ICVs and patient age (r = 0.98, P

Background: The dilation of perivascular space (PVS) has been widely used to reflect brain degeneration in clinical brain imaging studies. However, PVS characteristics exhibit large differences in healthy subjects. Such variations need to be better addressed before PVS can be used to reflect pathological changes. In the present study, we aim to investigate the potential influence of several related factors on PVS dilation in healthy elderly subjects.Methods: One-hundred and three subjects (mean age = 59.5) were retrospectively included from a prospectively collected community cohort. Multi-modal high-resolution magnetic resonance imaging and cognitive assessments were performed on each subject. Machine-learning based segmentation methods were employed to quantify PVS volume and white matter hyperintensity (WMH) volume. Multiple regression analysis was performed to reveal the influence of demographic factors, vascular risk factors, intracranial volume (ICV), major brain artery diameters, and brain atrophy on PVS dilation.Results: Multiple regression analysis showed that age was positively associated with the basal ganglia (BG) (standardized beta = 0.227, p = 0.027) and deep white matter (standardized beta = 0.220, p = 0.029) PVS volume. Hypertension was positively associated with deep white matter PVS volume (standardized beta = 0.234, p = 0.017). Furthermore, we found that ICV was strongly associated with the deep white matter PVS volume (standardized beta = 0.354, p < 0.001) while the intracranial artery diameter was negatively associated with the deep white matter PVS volume (standardized beta = −0.213, p = 0.032).Conclusions: Intracranial volume has significant influence on deep white matter PVS volume. Future studies on PVS dilation should include ICV as an important covariate.

Fetal alcohol spectrum disorders (FASD) continue to be the leading preventable cause of intellectual disability in the U.S., Europe, and in endemic areas, such as the Western Cape region of South Africa. Arithmetic is highly sensitive to prenatal alcohol exposure (PAE). The intraparietal sulcus (IPS) is known to play a critical role in number processing. In this study, we investigate whether smaller IPS volumes play a role in the number-processing deficits observed in children with PAE. Participants were 52 9- to 14-year-old children from a historically disadvantaged community in Cape Town, who are participating in our ongoing studies on the effects of PAE on the brain. The IPS was manually parcellated into its medial (MIPS) and lateral (LIPS) walls on magnetic resonance images. The study aimed to examine: (1) the effects of PAE on IPS regional volumes and asymmetry, (2) whether IPS regional volumes are related to number processing performance and, if so, whether these relations are moderated by PAE and (3) potential mediation by regional IPS volumes of the relation between PAE and number processing performance. Total intracranial volume (TIV) was associated with volumes in all regions except the right LIPS. Both left MIPS and left LIPS volumes were significantly smaller in children in the fetal alcohol syndrome (FAS)/partial FAS (PFAS) group compared to controls. The finding in the left LIPS remained significant after controlling for potential confounders and after adjustment for the smaller overall brain size of the children in the FAS/PFAS group. Smaller left LIPS volumes in the FAS/PFAS group may account for the absence of left-right asymmetry in the LIPS in children with FAS/PFAS compared to controls and nonsyndromal heavily exposed (HE) children. Bilaterally, larger MIPS volumes were associated with better WISC IQ Arithmetic scores. These effects, however, were not moderated by the degree of PAE, and regional IPS volumes did not mediate the effect of PAE on WISC Arithmetic scores. Although we found that certain regions of the IPS were smaller in children with FAS and PFAS, these PAE-induced changes in IPS volume did not mediate the alcohol-related deficits in arithmetic.

Aim: To investigate sex differences in the association between cortical thickness and behavioral inhibition of 9-10 years old American children. Materials and methods: This cross-sectional investigation used data from the Adolescent Brain Cognitive Development (ABCD) study. Baseline ABCD data of 10249 American children between ages 9 and 10 were analyzed. The independent variable was cortical thickness measured by structural brain magnetic resonance imaging (sMRI). The primary outcome, behavioral inhibition, was measured based on the behavioral inhibition system (BIS), and behavioral approach system (BAS). Sex was the moderator. Age, race, ethnicity, socioeconomic status indicators, and intracranial volume were covariates. Results: In the overall sample, high cortical thickness was not associated with behavioral inhibition in children. Sex showed a statistically significant interaction with cortical thickness’s effect on children’s behavioral inhibition, net of all confounders. The interaction indicated a statistically stronger positive effect of high cortical thickness on male behavioral inhibition compared to female children. Conclusion: Cortical thickness is a determinant of behavioral inhibition for male but not female American children. Male but not female children show better behavioral inhabitation at higher levels of cortical thickness.

Purpose The aim is to implement Utrecht Cranial Shape Quantificator (UCSQ) for quantification of severity of scaphocephaly and compare UCSQ with the most used quantification method, cranial index (CI). Additionally, severity is linked to intracranial volume (ICV). Methods Sinusoid curves of 21 pre-operative children (age Results Mean UCSQ was 22.00 (2.00–42.00). Mean traditional CI was 66.01 (57.36–78.58), and mean visual score was 9.1 (7–12). Correlations between both traditional CI and CI of UCSQ and overall visual scores were moderate and high (r = − 0.59; p = 0.005 vs. r = − 0.81; p r = 0.26; p > 0.05) and between ICV and CI and visual score (r = − 0.30; p > 0.05 and r = 0.17; p > 0.05, respectively). Conclusion Our current advice is to use traditional CI in clinical practice; it is easy to use and minimally invasive. However, UCSQ is more precise and objective and captures whole skull shape. Therefore, UCSQ is preferable for research. Additionally, more severe scaphocephaly does not result in more deviant skull volumes.

This study aimed to describe the surgical technique of reverse frontal cranioplasty (RFC), the aesthetical modification as well as the modification of intracranial volume (ICV) to assess its potential eligibility for the treatment of the intracranial hypertension (IH).A retrospective monocentric study included the patients with a history of craniosynostosis with a forehead deformity who underwent RFC. A subjective outcome questionnaire (SOQ) was conducted with each patient or their parent to determine their level of satisfaction after RFC. Pre- and postoperative computed tomography (CT) scans were analyzed and compared to investigate the ICV change and fronto-nasal angle.Eleven patients were included in the study (6 female and 5 male) with a mean age of 10.9 years old (range 3-23 years) and an average follow-up of 4.5 years (1-11 years). All patients responded to the questionnaire with a high level of overall satisfaction (mean 9.1/10). The mean preoperative FNA was 134° ± 5° while the mean postoperative angle was 126.4° ± 6, corresponding to an average decrease of 7.6° (95% CI, 4.0-11.2°; p 0.001). One patient with preoperative IH had a clinical recurrence during the follow-up. The ICV was significantly higher after the surgery (p 0.0001), with an average increase of 3.2% (95% CI, 2.3-4.1%).Reverse (RFC) is a useful technique for the correction of the frontal malformations related to craniosynostosis, such as a sloping forehead and/or a lack of the supraorbital projection. Regarding the limited gain of intracranial volume (ICV), it should not be used alone as primary cranial expansion surgery for craniosynostosis with intracranial hypertension (IH).

Background/Aim Migraine-related intracerebral white matter lesions (WMLs) are likely to be microvascular in nature and can be found in all hemispheric lobes. The aim of this study was to investigate migraine patients with or without WMLs to see the effects of these tissue damages on cortical thickness and volume. The role of migraine characteristics (duration of headache, attack frequency, estimated lifetime attack number, aura) was also tested. Methods As study participants, 161 female migraine patients (63 with aura; 52 with WMLs) and 40 age-matched healthy female subjects were enrolled in the study. None of the included migraine patients’ headache or aura (where present) was unilaterally side-locked. Patients and controls were all right handed. Except for migraine, patients were free of any medical comorbidity. Cortical reconstruction and segmentation were performed on the 3D T1-weighted images using Freesurfer 5.3 image analysis suite. The automatic cortical parcellation was based on Freesurfer’s Desikan–Killiany–Tourville atlas, which has 31 cortical regions per hemisphere. The segmented regions were divided into five lobes (frontal, parietal, temporal, occipital, insula). Since the left and right differences in lobar and insular volumes/thicknesses were not different among our groups, volume and cortical thickness were calculated for corresponding bilateral lobes. Results There was no significant difference in age between the whole migraine and the control groups. Migraineurs with WMLs (L+ patients) were significantly older than lesion-free (L-) patients (P = 0.0003) and controls (P = 0.018). Disease duration (P = 0.003), the total number of migraine attacks (P = 0.022) and the rate of aura (P = 0.0003) were significantly higher in L+ patients than in L- patients. Cortical thickness and volume measurements of lobes were not statistically different between the three groups (L+, L-, control). Age showed a significant negative association with both thickness and volume in each examined lobe (P

Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = -0.71 to -1.37; P 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = -0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10

Displacement Encoding with Stimulated Echoes (DENSE) has recently shown potential for measuring cardiac-induced cerebral volumetric strain in the human brain. As such, it may provide a powerful tool for investigating the cerebral small vessels. However, further development and validation are necessary. This study aims, first, to validate a retrospectively-gated implementation of the DENSE method for assessing brain tissue pulsations as a physiological marker, and second, to use the acquired measurements to explore intracranial volume dynamics. We acquired repeated measurements of cerebral volumetric strain in 8 healthy subjects, and internally validated these measurements by comparing them to spinal CSF stroke volumes obtained in the same scan session. Peak volumetric strain was found to be highly repeatable between scan sessions. First/second measured peak volumetric strains were: (6.4 ​± ​1.7)x10−4/(6.7 ​± ​1.6)x10−4 for whole brain, (9.5 ​± ​2.5)x10−4/(9.6 ​± ​2.4)x10−4 for grey matter, and (4.4 ​± ​1.7)x10−4/(4.1 ​± ​0.8)x10−4 for white matter. Grey matter showed significantly higher peak strain (p ​< ​0.001) and earlier time-to-peak strain (p ​< ​0.02) than white matter. An approximately linear relationship was found between CSF and brain tissue volume pulsations over the cardiac cycle (mean slope and R2 of 0.88 ​± ​0.23 and 0.89 ​± ​0.07, respectively). The close similarity between CSF and brain tissue volume pulsations implies limited contributions from large intracranial vessel pulsations, providing further evidence for venous compression as an additional mechanism for maintaining stable intracranial pressures over the cardiac cycle. Cerebral pulsatility showed consistent inter-subject peak values in healthy subjects, and was strongly correlated to CSF stroke volumes. These results strengthen the potential of brain tissue volumetric strain as a means for investigating the intracranial dynamics of the ageing brain in normal or diseased states.

When analyzing intracranial volume gain resulting from operative intervention in craniosynostosis, it is necessary to understand the underlying growth. The authors sought to create comprehensive intracranial volume and occipitofrontal circumference growth charts, as measured on unoperated craniosynostotic children, and aimed to investigate whether intracranial volume and occipitofrontal circumference could act as proxy measures for each other.All preoperative Great Ormond Street Hospital patients with a diagnosis of Apert, Crouzon-Pfeiffer, or Saethre-Chotzen syndrome from the year 2004 onward were considered for this study. A control group of unaffected Great Ormond Street Hospital patients were also measured. Intracranial volume and occipitofrontal circumference were measured on the same scans. To study correlation between intracranial volume and occipitofrontal circumference, logarithmic fits were assessed.One hundred forty-seven craniosynostotic children with 221 preoperative scans were included (81 Apert, 81 Crouzon, 31 Pfeiffer, and 28 Saethre-Chotzen). The control group comprised 56 patients with 58 scans. Apert intracranial volume curves were significantly larger than those of other syndromes from 206 days onward; occipitofrontal circumference curves were not significantly different. The correlation coefficient between intracranial volume and occipitofrontal circumference was R = 0.87 for all syndromes combined and R = 0.91 for the control group.Apert syndrome children have a larger intracranial volume than children with other syndromic craniosynostotic conditions and unaffected children but maintain a similar occipitofrontal circumference. This study demonstrates high correlation between intracranial volume and occipitofrontal circumference with clinical care implications. The authors' reference growth curves can be used to monitor intracranial volume change over time and correct operative change for underlying growth.

OBJECTIVE:Fatigue is a complex, multidimensional phenomenon that commonly occurs following traumatic brain injury (TBI). The thalamus-a structure vulnerable to both primary and secondary injuries in TBI-is thought to play a pivotal role in the manifestation of fatigue. We explored how neuroimaging markers of local and global thalamic morphometry relate to the subjective experience of fatigue post-TBI. METHODS:Sixty-three Veterans with a history of mild TBI underwent structural magnetic resonance imaging and completed questionnaires related to fatigue and psychiatric symptoms. FMRIB's Software (FSL) was utilized to obtain whole brain and thalamic volume estimates, as well as to perform regional thalamic morphometry analyses. RESULTS:Independent of age, sex, intracranial volume, posttraumatic stress disorder, and depressive symptoms, greater levels of self-reported fatigue were significantly associated with decreased right (P = .026) and left (P = .046) thalamic volumes. Regional morphometry analyses revealed that fatigue was significantly associated with reductions in the anterior and dorsomedial aspects of the right thalamic body (P < .05). Similar trends were observed for the left thalamic body (P < .10). CONCLUSIONS:Both global and regional thalamic morphometric changes are associated with the subjective experience of fatigue in Veterans with a history of mild TBI. These findings support a theory in which disruption of thalamocorticostriatal circuitry may result in the manifestation of fatigue in individuals with a history of neurotrauma.

Background Amyloid-beta (Aβ) has a dose-response relationship with cognition in healthy adults. Additionally, the levels of functional connectivity within and between brain networks have been associated with cognitive performance in healthy adults. Aiming to explore potential synergistic effects, we investigated the relationship of inter-network functional connectivity, Aβ burden, and memory decline among healthy individuals and individuals with preclinical, prodromal, or clinical Alzheimer’s disease. Methods In this longitudinal cohort study (ADNI2), participants (55–88 years) were followed for a maximum of 5 years. We included cognitively healthy participants and patients with mild cognitive impairment (with or without elevated Aβ) or Alzheimer’s disease. Associations between memory decline, Aβ burden, and connectivity between networks across the groups were investigated using linear and curvilinear mixed-effects models. Results We found a synergistic relationships between inter-network functional connectivity and Aβ burden on memory decline. Dose-response relationships between Aβ and memory decline varied as a function of directionality of inter-network connectivity across groups. When inter-network correlations were negative, the curvilinear mixed-effects models revealed that higher Aβ burden was associated with greater memory decline in cognitively normal participants, but when inter-network correlations were positive, there was no association between the magnitude of Aβ burden and memory decline. Opposite patterns were observed in patients with mild cognitive impairment. Combining negative inter-network correlations with Aβ burden can reduce the required sample size by 88% for clinical trials aiming to slow down memory decline. Conclusions The direction of inter-network connectivity provides additional information about Aβ burden on the rate of expected memory decline, especially in the preclinical phase. These results may be valuable for optimizing patient selection and decreasing study times to assess efficacy in clinical trials. Electronic supplementary material The online version of this article (10.1186/s13195-018-0420-9) contains supplementary material, which is available to authorized users.

It has astonished neuroscientists since the advent of decompressive craniectomy as to why a seemingly successfully achieved goal of reduction in intracranial pressure (ICP), by removing a portion of the cranial vault and the resultant intracranial volume augmentation, fails to give the desired beneficial clinical outcome in every case and in fact, at times, proves to be deleterious in some conditions with a shared problem of refractory raised ICP. The authors propose a hypothesis based on the understanding of the anatomy and physiology of the brain that can explain the fallacy.

Prader-Willi syndrome is a complex endocrinological and developmental disorder characterized by hyperphagic, autistic, and obsessive behaviors, which have been considered to primarily originate from hypothalamus-pituitary axis system alterations in the brain. While the pituitary gland has been demonstrated to contribute to behavioral phenotypes associated with neuropeptide, e.g., arginine-vasopressin, the relevant alterations in Prader-Willi syndrome remain unknown. This study aimed to investigate developmental abnormalities in the pituitary gland structures and determine whether the structural abnormalities are associated with behavioral characteristics in Prader-Willi syndrome. In total, 21 Japanese individuals with Prader-Willi syndrome and 31 healthy controls with typical development were included. Compared with the control group, the Prader-Willi syndrome group showed reduced anterior and posterior pituitary volume ratios per total intracranial volume with relative T1 shortening in an age-associated manner. Moreover, altered volume ratios and signal intensities were negatively correlated with hyperphagia and autistic questionnaire scores but positively correlated with obsessive scores. The findings suggest that structural and functional alterations, in part due to altered hypothalamus-pituitary function, may contribute to the behavior in Prader-Willi syndrome. The imaging-behavior correlates and in vivo neurochemical visualization of the pituitary gland might be potential intrinsic biomarkers for behavioral phenotypes in Prader-Willi syndrome and other neurodevelopmental disorders.

The aim of this study is to compare the length of synostosis and segmented intracranial volume (SIV) with age in children with non-syndromic sagittal synostosis. Thirty-three consecutive patients (22 boys) who had been operated by cranial vault remodeling because of sagittal synostosis were compared retrospectively from 3D-CT imaging data sets obtained from volumetric CT. The mean age of the patients at preoperative CT imaging was 0.49 (range 0.13-1.3) years and at 1-year postoperative imaging 1.8 (range 1.3-3) years. The mean interval between preoperative CT imaging and surgery was 0.25 (range 0-0.8) years. Pearson's correlation and Student's t test were used in the statistical analyses. Length of sagittal synostosis correlated positively with age at preoperative CT (r = 0.688, p

Continuous monitoring of the intracranial pressure (ICP) detects impending intracranial hypertension resulting from the impaired intracranial volume homeostasis, when expanding volume generates pressure increase. In this study, cellular brain edema (CE) was induced in rats by water intoxication (WI). Methylprednisolone (MP) was administered intraperitoneally (i.p.) before the start of CE induction, during the induction and after the induction. ICP was monitored for 60 min within 20 h after the completion of the CE induction by fibreoptic pressure transmitter. In rats with induced CE, ICP was increased (MeanSEM: 14.25±2.12) as well as in rats with MP administration before the start of CE induction (10.55±1.27). In control rats without CE induction (4.62±0.24) as well as in rats with MP applied during CE induction (5.52±1.32) and in rats with MP applied after the end of CE induction (6.23±0.73) ICP was normal. In the last two groups of rats, though the CE was induced, intracranial volume homeostasis was not impaired, intracranial volume as well as ICP were not increased. It is possible to conclude that methylprednisolone significantly influenced intracranial homeostasis and thus also the ICP values in the model of cellular brain edema.

We recently built normative data for FreeSurfer morphometric estimates of cortical regions using its default atlas parcellation (Desikan-Killiany or DK) according to individual and scanner characteristics. We aimed to produced similar normative values for Desikan-Killianny-Tourville (DKT) and ex vivo-based labeling protocols, as well as examine the differences between these three atlases. Surfaces, thicknesses, and volumes of cortical regions were produced using cross-sectional magnetic resonance scans from the same 2713 healthy individuals aged 18-94 years as used in the reported DK norms. Models predicting regional cortical estimates of each hemisphere were produced using age, sex, estimated intracranial volume (eTIV), scanner manufacturer and magnetic field strength (MFS) as predictors. The DKT and DK models generally included the same predictors and produced similar R2. Comparison between DK, DKT, ex vivo atlases normative cortical measures showed that the three protocols generally produced similar normative values.

Posterior calvarial vault osteodistraction (PCVO) has become increasingly popular in the correction of craniosynostosis. When compared to cranioplasty, PCVO offers a shorter, less invasive operation, greater intracranial volume advancement and a lower rate of relapse. In general, distraction protocols are based primarily on clinical observations rather than systematic research. Faster distraction protocols may reduce complications. However, distraction protocols producing higher forces can increase complications. Thus, we need to understand these forces in order to improve distraction protocols and devices. We developed a force measurement method that can be used on PCVO devices. Here, we present preliminary data about the forces developed during PCVO. We measured the forces in four bicoronal craniosynostosis patients during PCVO. We observed a linear-like trend between the force increase and the distraction distance within distraction sessions. We also observed a step-wise force increase between distraction sessions and found that the distraction force relaxed rapidly shortly after the distraction session. The mean maximum pre distraction force for one distracter was 20.4 N, while the mean maximum end-distraction force for one distracter was 57.6 N. Our data suggests that current treatment protocols might be re-evaluated favouring shorter distraction distances and more frequent distraction sessions. (C) 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Background: Freezing of gait (FoG) is a disabling gait disorder that commonly occurs in advanced stages of Parkinson’s disease (PD). The neuroanatomical mechanisms underlying FoG in PD are still unclear. The present study aims to explore alterations of structural gray matter (GM) in PD patients with FoG. Method: Twenty-four PD patients with FoG (FoG+), 37 PD patients without FoG (FoG-) and 24 healthy controls (HC) were included. All subjects underwent a standardized MRI protocol. The cortical thickness (CTh), segmentation volume without ventricles (BrainSegVolNotVent) and estimated total intracranial volume (eTIV) were analysed using the FreeSurfer pipeline. Results: CTh differences were found in the right middle temporal gyrus (rMTG) generally. Compared to that in HCs, the CTh of the rMTG in both the FoG+ and FoG- groups was smaller, while no significant difference between the FoG+ and FoG- groups. Correlation analyses demonstrated a negative correlation between the CTh of the rMTG and the UPDRS part II score in PD subjects, and a borderline significant correlation between the score of Freezing of Gait Questionnaire (FoGQ) and rMTG CTh. Additionally, receiver operating characteristic curve (ROC) analysis revealed a cut-off point of CTh =3.08 mm in the rMTG that could be used to differentiate PD patients and HCs (AUC =0.79, P

Craniosynostosis is a congenital defect that causes ≥1 suture to fuse prematurely. Cranial expansion surgery which consists of cranial vault reshaping with or without fronto-orbital advancement (FOA) is done to correct the skull to a more normal shape of the head as well as to increase the intracranial volume (ICV). Therefore, it is important to evaluate the changes of ICV after the surgery and the effect of surgery both clinically and radiologically.The aim of this study is to evaluate the ICV in primary craniosynostosis patients after the cranial vault reshaping with or without FOA and to compare between syndromic and nonsyndromic synostosis group, to determine factors that associated with significant changes in the ICV postoperative, and to evaluate the resolution of copper beaten sign and improvement in neurodevelopmental delay after the surgery.This is a prospective observational study of all primary craniosynostosis patients who underwent operation cranial vault reshaping with or without FOA in Hospital Kuala Lumpur from January 2017 until Jun 2018. The ICV preoperative and postoperative was measured using the 3D computed tomography (CT) imaging and analyzed. The demographic data, clinical and radiological findings were identified and analyzed.A total of 14 cases (6 males and 8 females) with 28 3D CT scans were identified. The mean age of patients was 23 months. Seven patients were having syndromic synostosis (4 Crouzon syndromes and 3 Apert syndromes) and 7 nonsyndromic synostosis. The mean preoperative ICV was 880 mL (range, 641-1234 mL), whereas the mean postoperative ICV was 1081 mL (range, 811-1385 mL). The difference was 201 mL which was statistically significant (P 0.001). In comparison, the mean volume increment for syndromic synostosis and nonsyndromic synostosis was 282 mL and 120 mL, respectively. The difference was statistically significant (P 0.004). Three months post-operation, the copper beaten sign was still present in the CT scan which was statistically not significant in this study (P 1.0). However, there was 100% (n = 13) improvement of this copper beaten sign. However, the neurodevelopmental delay showed no improvement which was statistically not significant (P 1.0).Surgery in craniosynostosis patient increases the ICV besides it improves the shape of the head. From this study, the syndromic synostosis had better increment of ICV compared to nonsyndromic synostosis.

Recent studies have shown differences in brain structure between adolescents with type 2 diabetes (T2D) and their nondiabetic peers. Compared to obese controls (OCs), global white matter (WM) and regional gray matter (GM) differences have been found. Our aim was to evaluate further for global and regional differences in GM, WM, and parenchymal (GM and WM combined) brain volume between youth with T2D and nondiabetic OCs. We compared 11 youth with T2D (mean age 17.1 ±2.0 years, mean HbA1c 8.6 ±2.5%) and 11 age, race and sex similar OCs (mean HbA1c 5.3 ±0.2%). Participants underwent high-resolution T1-weighted MRI scans, analyzed using voxel-based morphometry. Tissue volumes were normalized across participants by dividing by each individual’s intracranial volume (ICV). The normalized global volumes were compared between the two groups, and statistical significance was determined at p Disclosure J.M. Redel: None. M.W. DiFrancesco: None. G.R. Lee: None. L.M. Dolan: None. A.S. Shah: None. Funding Endocrine Fellows Foundation; Cincinnati Diabetes and Obesity Center; Cincinnati Children's

Voxel-based morphometry (VBM) studies of Parkinson's disease (PD), have yielded mixed results, possibly due to several studies not accounting for common nuisance variables (age, sex, and total intracranial volume [TICV]). TICV is particularly important because there is evidence for larger TICV in PD. We explored the influence of these covariates on VBM by 1) comparing PD patients and controls before adding covariates, after adding age and sex, and after adding age, sex and TICV, and 2) by comparing controls split into large and small TICV before and after controlling for TICV, with age and sex accounted for in both analyses. Experiment 1 consisted of 40 PD participants and 40 controls. Experiment 2 consisted of 88 controls median split by TICV. All participants completed an MRI on a 3 T scanner. TICV was calculated as gray + white + CSF from Freesurfer. VBM was performed on T1 images using an optimized VBM protocol. Volume differences were assessed using a voxel-wise GLM analysis. Clusters were considered significant at >10 voxels and p

Posterior cranial vault distraction is considered to be more effective for increasing intracranial volume than fronto-orbital advancement or anterior cranial vault expansion, but the changes in intracranial volumes after posterior cranial vault distraction remain unclear. The changes in intracranial volume were investigated in patients of premature craniosynostosis treated by this technique. Seven patients, 3 boys and 4 girls aged from 5 months to 3 years 3 months (mean 23 months) at operation, with craniosynostosis underwent posterior cranial vault distraction at Juntendo University Hospital from 2011 to 2014. Patient characteristics, length of distraction, and pre- and postoperative computed tomography findings were reviewed. Total intracranial volume, including the supratentorial space and posterior cranial fossa, was measured using the workstation functions on three-dimensional computed tomography scans. Posterior distraction was performed without severe complications except in 2 patients requiring additional surgeries. The distraction length was 22.3 to 39 mm (mean 31 mm), the intracranial volume change was 144 to 281 mL (mean 192 mL), and the enlargement ratio of intracranial volume was 113% to 134% (mean 121%). The present quantitative analysis of intracranial volume change after posterior distraction showed greater increases in intracranial volume compared with previous reports. Furthermore, intracranial volumes in our patients became nearly normal and were maintained for the follow-up period (maximum 13 months). Posterior cranial vault distraction is very effective to increase cranial volume, so may be the first choice of treatment in patients of craniosynostosis.

Background The aim of the current study was to determine the intracranial volume (ICV) and cephalic index (CI) in patients operated for sagittal synostosis, and to compare the outcome of 2 different surgical techniques: craniotomy combined with springs and modified pi-plasty. Methods The authors studied all patients who had been operated for isolated sagittal synostosis and registered in the Gothenburg Craniofacial Registry until the end of 2012 and who had undergone a preoperative and/or postoperative (at 3 years of age) computed tomography examination. Sex- and age-matched controls were identified from children who had undergone computed tomography for other reasons. Results Craniotomy combined with springs increased the ICV and CI from 802 ± 127 mL (mean ± SD) and 70.1 ± 4.0 to 1300 ± 158 mL and 73.1 ± 3.3, respectively. The corresponding values for controls were 796 ± 136 mL and 83.6 ± 7.3 preoperatively and 1334 ± 136 mL and 80.0 ± 4.5 at 3 years of age. Pi-plasty increased the ICV and CI from 1014 ± 115 mL and 69.7 ± 3.3 to 1286 ± 122 mL and 74.1 ± 2.6, respectively. Corresponding values for controls were 1043 ± 153 mL and 83.4 ± 7.0 preoperatively and 1362 ± 122 mL and 79.6 ± 3.9 at 3 years of age. Conclusions There was no significant difference between craniotomy combined with springs in children younger than 6 months and pi-plasty in older children regarding the efficacy of improving ICV and CI. Neither of the techniques fully normalized the head shape.

Normal brain-aging occurs at all structural levels. Excessive pathophysiological changes in the brain, beyond the normal one, are implicated in the etiology of brain disorders such as severe forms of the schizophrenia spectrum and dementia. To account for brain-aging in health and disease, it is critical to study the age-dependent trajectories of brain biomarkers at various levels and among different age groups.The intracranial volume (ICV) is a key biological marker, and changes in the ICV during the lifespan can teach us about the biology of development, aging, and gene X environment interactions. However, whether ICV changes with age in adulthood is not resolved.Applying a semi-automatic in-house-built algorithm for ICV extraction on T1w MR brain scans in the Dutch longitudinal cohort (GROUP), we measured ICV changes. Individuals between the ages of 16 and 55 years were scanned up to three consecutive times with 3.32±0.32 years between consecutive scans (N=482, 359, 302). Using the extracted ICVs, we calculated ICV longitudinal aging-trajectories based on three analysis methods; direct calculation of ICV differences between the first and the last scan, fitting all ICV measurements of individuals to a straight line and applying a global linear mixed model fitting. We report statistically significant increases in the ICV in adulthood until the fourth decade of life (average change +0.03%/y, or about 0.5 ml/y, at age 20), and decreases in the ICV afterward (−0.09%/y, or about −1.2 ml/y, at age 55). To account for previous cross-sectional reports of ICV changes, we analyzed the same data using a cross-sectional approach. Our cross-sectional analysis detected ICV changes consistent with the previously reported cross-sectional effect. However, the reported amount of cross-sectional changes within this age range was significantly larger than the longitudinal changes. We attribute the cross-sectional results to a generational effect.In conclusion, the human intracranial volume does not stay constant during adulthood but instead shows a small increase during young adulthood and a decrease thereafter from the fourth decade of life. The age-related changes in the longitudinal setup are smaller than those reported using cross-sectional approaches and unlikely to affect structural brain imaging studies correcting for intracranial volume considerably. As to the possible mechanisms involved, this awaits further study, although thickening of the meninges and skull bones have been proposed, as well as a smaller amount of brain fluids addition above the overall loss of brain tissue.

Sustaining a traumatic brain injury (TBI) during adolescence has a profound effect on brain development and can result in persistent executive functioning deficits in daily life. Cognitive recovery from pediatric-TBI relies on the potential of neuroplasticity, which can be fostered by restorative training-programs. However the structural mechanisms underlying cognitive recovery in the immature brain are poorly understood. This study investigated gray matter plasticity following 2 months of cognitive training in young patients with TBI. Sixteen adolescents in the chronic stage of moderate-severe-TBI (9 male, mean age = 15y8m ± 1y7m) were enrolled in a cognitive computerized training program for 8 weeks (5 times/week, 40 min/session). Pre-and post-intervention, and 6 months after completion of the training, participants underwent a comprehensive neurocognitive test-battery and anatomical Magnetic Resonance Imaging scans. We selected 9 cortical-subcortical Regions-Of-Interest associated with Executive Functioning (EF-ROIs) and 3 control regions from the Desikan-Killiany atlas. Baseline analyses showed significant decreased gray matter density in the superior frontal gyri p = 0.033, superior parietal gyri p = 0.015 and thalamus p = 0.006 in adolescents with TBI compared to age and gender matched controls. Linear mixed model analyses of longitudinal volumetric data of the EF-ROI revealed no strong evidence of training-related changes in the group with TBI. However, compared to the change over time in the control regions between post-intervention and 6 months follow-up, the change in the EF-ROIs showed a significant difference. Exploratory analyses revealed a negative correlation between the change on the Digit Symbol Substitution test and the change in volume of the putamen (r = −0.596, p = 0.015). This preliminary study contributes to the insights of training-related plasticity mechanisms after pediatric-TBI. Keywords: Pediatric traumatic brain injury, Cognitive rehabilitation, Gray matter, Neural plasticity, Executive function, Linear mixed model analyses

OBJECTIVEReduced intracranial volume (ICV) and raised intracranial pressure (ICP) are assumed to be principal pathophysiological mechanisms in childhood craniosynostosis. This study examined the association between ICV and ICP and whether ICV can be used to estimate the ICP.METHODSThe authors analyzed ICV and ICP measurements from children with craniosynostosis without concurrent hydrocephalus and from age-matched individuals without craniosynostosis who underwent diagnostic ICP measurement.RESULTSThe study included 19 children with craniosynostosis (mean age 2.2 ± 1.9 years) and 12 reference individuals without craniosynostosis (mean age 2.5 ± 1.6 years). There was no difference in ICV between the patient and reference cohorts. Both mean ICP (17.1 ± 5.6 mm Hg) and mean wave amplitude (5.9 ± 2.6 mm Hg) were higher in the patient cohort. The results disclosed no significant association between ICV and ICP values in the patient or reference cohorts, and no association was seen between change in ICV and ICP values after cranial vault expansion surgery (CVES) in 5 children in whom ICV and ICP were measured before and after CVES.CONCLUSIONSIn this cohort of children with craniosynostosis, there was no significant association between ICV and ICP values prior to CVES and no significant association between change in ICV and ICP values after CVES in a subset of patients. Therefore, ICV could not reliably estimate the ICP values. The authors suggest that intracranial hypertension in childhood craniosynostosis may not be caused by reduced ICV alone but rather by a distorted relationship between ICV and the volume of intracranial content (brain tissue, CSF, and blood).

ObjectiveWe postulated that cerebral amyloid angiopathy (CAA) is associated with white matter atrophy (WMA) and that WMA can be related to cognitive changes in CAA.MethodsWhite matter volume expressed as percent of intracranial volume (pWMV) of prospectively enrolled patients without dementia diagnosed with probable CAA was compared to age-matched healthy controls (HC) and patients with Alzheimer disease (AD). Cognitive scores were also sought to understand the potential effects of WMA on cognitive function.ResultsPatients with CAA (n = 72) had significantly lower pWMV (27.97% ± 2.63) when compared to age-matched HC (n = 72; mean difference [MD], 2.38%; p < 0.0001) and patients with AD (n = 72; MD, 1.57%; p < 0.0001). Differences were most pronounced in the posterior occipital regions in both comparisons. When comparisons were restricted to groups of patients with CAA but no intracerebral hemorrhage (n = 32) or hypertension (n = 32), and age-matched HC and AD, the significant differences were unaltered. Within the CAA cohort, higher age, lobar microbleed counts, and presence of hypertension were associated with lower pWMV (p = 0.0007, p = 0.031, and p = 0.003, respectively). All associations remained independent in multivariable analyses. Within the CAA cohort, higher pWMV independently correlated with better scores of executive function.ConclusionsPatients with CAA show WMA when compared to age-matched HC and patients with AD. WMA independently correlates with the number of lobar microbleeds, a marker of CAA severity. Consistent spatial patterns of WMA especially in posterior regions might be related to CAA. The association between WMA and measures of executive function suggests that WMA might represent an important mediator of CAA-related neurologic dysfunction.

[Objective] Craniocerebral disproportion (CCD) is a challenging disease, and several expansile procedures have been used for its treatment. This report describes the dynamic chess-table cranial expansion technique and reports on 9 patients with primary and secondary CCD treated with this procedure., [Methods] Nine patients affected by CCD were treated with chess-table cranial expansion and reviewed. Symptoms of increased intracranial pressure (ICP) and radiologic findings were analyzed. ICP was monitored using epidural or telemetric sensors. Intracranial volume was measured using computed tomography image processing tools before the surgery, 24 hours after the surgery, and 1 month later. A mathematical model was developed to explain the clinical and surgical results., [Results] Five patients had secondary CCD and 4 had primary CCD. The mean age for cranial expansion was 16.78 years. The most frequent symptoms were headaches, nausea/vomiting, and decreased consciousness. Slit ventricles and sutural sclerosis were observed in 33.3% and 55.6% of patients. The mean ICP before the procedure was 48.67 mm Hg. Progressive cranial expansion was seen in all patients after surgery. The mean ICP decreased to 11 mm Hg and mean intracranial volume expansion was 85.8 cm3 at 1 month after surgery. There were no serious complications after surgery. All patients improved their symptoms, and no patient needed additional cranial expansion procedures., [Conclusions] Chess-table cranial expansion is a safe and effective procedure and may be used as an alternative treatment for CCD. Progressive expansion of the intracranial volume is related to a decrease in ICP recordings and an improvement of symptoms.

Background Brain reserve is a concept introduced to explain why Alzheimer’s disease (AD) patients with a greater brain volume prior to onset of pathology generally have better clinical outcomes. In this review, we provide a historical background of the emergence of brain reserve and discuss several aspects that need further clarification, including the dynamic or static nature of the concept and its underlying mechanisms and clinical effect. We then describe how brain reserve has been operationalized over the years, and critically evaluate the use of intracranial volume (ICV) as the most widely used proxy for brain reserve. Furthermore, we perform a meta-analysis showing that ICV is associated with higher cognitive performance after adjusting for the presence and amount of pathology. Although we acknowledge its imperfections, we conclude that the use of ICV as a proxy for brain reserve is currently warranted. However, further development of more optimal measures of brain reserve as well as a more clearly defined theoretical framework is essential.

Introduction: Lysosomal storage disorders (LSD) are often characterized by abnormal brain development, reflected by a reduction of intracranial volume (ICV). The aim of our study was to perform a volumetric analysis of intracranial tissues in Fabry Disease (FD), investigating possible reductions of ICV as a potential expression of abnormal brain development in this condition. Materials and Methods: Forty-two FD patients (15 males, mean age 43.3 ± 13.0 years) were enrolled along with 38 healthy controls (HC) of comparable age and sex. Volumetric MRI data were segmented using SPM12 to obtain intracranial tissue volumes, from which ICV values were derived. Results: Mean ICV of FD patients was 8.1% smaller compared to the control group (p < 5·10−5). Unlike what typically happens in neurodegenerative disorders, no significant differences emerged when comparing between the two groups the fractional volumes of gray matter, white matter and CSF (i.e., normalized by ICV), consistent with a harmonious volumetric reduction of intracranial structures. Discussion: The present results suggest that in FD patients an abnormality of brain development is present, expanding the current knowledge about central nervous system involvement in FD, further emphasizing the importance of an early diagnosis.

Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV + HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for low-frequency variants within TP53, with 0.5 cm wider heads in increaser-allele carriers versus non-carriers during mid-childhood, suggesting a previously unrecognized role of TP53 transcripts in human cranial development., Size and shape of the brain are, among others, influenced by the dimensions of the skull. Here, the authors report genome-wide association studies for head circumference and intracranial volume in children and adults and the identification of nine common or low-frequency variants associated with these traits.

Background/Aims: We performed a morphometric analysis of Chiari I malformations to look for predictors of cervical syrinx formation. Methods: Eighteen patients with Chiari I malformation and associated cervical syrinx and 16 patients with Chiari I malformation without associated cervical syrinx were included in the study. Chiari I size was obtained from the radiology report; foramen magnum diameter, cerebellar volume, posterior fossa volume and intracranial volume were calculated using OsiriX software, and average measurements were compared between the two groups. Results and Conclusion: Patients with Chiari I with syrinx had an average tonsillar descent of 13.03 ± 5.31 mm compared to 9.25 ± 3.31 mm in the Chiari I without syrinx group (p < 0.05). Patients with Chiari I and syrinx also showed increased cerebellar crowding with a higher cerebellar volume to posterior fossa volume ratio; however, this difference was not significant (0.83 vs. 0.81; p = 0.1872). No difference between groups was found in posterior fossa volume, intracranial volume and foramen magnum diameter. Therefore, only Chiari I size based on the extent of tonsillar herniation was found to be a determinant of cervical syrinx formation.

There is still disagreement regarding the intracranial volumes of patients with metopic synostosis compared with healthy patients. This study aimed to compare the intracranial volume of children with metopic synostosis before and after surgery to an age- and sex-matched control cohort using three-dimensional (3D) photogrammetry. Eighteen boys with metopic synostosis were operated on using standardized fronto-orbital advancement. Frontal, posterior and total intracranial volumes were measured exactly 1 day pre-operatively and 10 days post-operatively, using 3D photogrammetry. To establish an age- and sex-matched control group, the 3D photogrammetric data of 634 healthy boys between the ages of 3 and 13 months were analyzed. Mean age at surgery was 9 months (SD 1.7). Prior to surgery, boys with metopic synostosis showed significantly reduced frontal and total intracranial volumes compared with the reference group, but similar posterior volumes. After surgery, frontal and total intracranial volumes did not differ statistically from the control group. As children with metopic synostosis showed significantly smaller frontal and total intracranial volumes compared with an age- and sex-matched control group, corrective surgery should aim to achieve volume expansion. Furthermore, 3D photogrammetry provides a valuable alternative to CT scans in the measurement of intracranial volume in children with metopic synostosis, which significantly reduces the amount of radiation exposure to the growing brain.

To develop an algorithm to segment and obtain an estimate of total intracranial volume (tICV) from computed tomography (CT) images. Thirty-six CT examinations from 18 patients were included. Ten patients were examined twice the same day and eight patients twice six months apart (these patients also underwent MRI). The algorithm combines morphological operations, intensity thresholding and mixture modelling. The method was validated against manual delineation and its robustness assessed from repeated imaging examinations. Using automated MRI software, the comparability with MRI was investigated. Volumes were compared based on average relative volume differences and their magnitudes; agreement was shown by a Bland-Altman analysis graph. We observed good agreement between our algorithm and manual delineation of a trained radiologist: the Pearson’s correlation coefficient was r = 0.94, tICVml[manual] = 1.05 × tICVml[automated] - 33.78 (R2 = 0.88). Bland-Altman analysis showed a bias of 31 mL and a standard deviation of 30 mL over a range of 1265 to 1526 mL. tICV measurements derived from CT using our proposed algorithm have shown to be reliable and consistent compared to manual delineation. However, it appears difficult to directly compare tICV measures between CT and MRI. • Automated estimation of tICV is in good agreement with manual tracing. • Consistent tICV estimations from repeated measurements demonstrate the robustness of the algorithm. • Automatically segmented volumes seem less variable than those from manual tracing. • Unbiased and automated tlCV estimation is possible from CT.

Myopia is part of the spectrum of refractive error. Myopia is associated with psychometric intelligence and, the link between brain anatomy and myopia has been hypothesized. Here we aimed to identify the associations between brain structures and refractive error in developed young adults. In a study cohort of 1,319 normal educated young adults, the refractive error showed a significant negative correlation with total intracranial volume and total cerebrospinal fluid (CSF) volume but not with total gray matter volume (GMV) or total white matter volume (WMV). Time spent studying was associated with refractive error but could not explain the aforementioned associations with brain volume parameters. The R2 values of the simple regression between spherical equivalent and outcome variables for each sex in non-whole brain imaging analyses were less than 0.05 in all cases and thus were weak. Psychometric intelligence was not associated with refractive error or total CSF volume, but it weakly positively correlated with total GMV and total WMV in this study population. Thus, refractive error appears to be primarily (weakly) associated with the volume of the cranium, whereas psychometric intelligence was associated with the volume of the brain.

OBJECTIVE: The objective of this study was to investigate whether reduction of thalamic volumes in children with early onset epilepsy (CWEOE) is associated with cognitive impairment.METHODS: This is a nested case-control study including a prospectively recruited cohort of 76 children with newly-diagnosed early onset epilepsy (onset RESULTS: Age, gender, and intracranial volume (ICV)-adjusted left thalamic volumes were significantly reduced in CWEOE with cognitive impairment compared to CWEOE without impairment (5295mm3vs 6418mm3, q=0.008) or healthy controls (5295mm3vs 6410mm3, qSIGNIFICANCE: Reduced left thalamic volume may be a biomarker for cognitive impairment in CWEOE and could help inform the need for further formal cognitive evaluations and interventions.

The brain requires a high cerebral blood flow (CBF) to maintain structure and function. The brain is enclosed within a rigid box together with blood and cerebrospinal fluid (CSF). CSF accounts for around 9% of the intracranial volume and blood 4%. The normal pressure in the head the intracranial pressure (ICP) is between 7 and 15 mm Hg in healthy adults. If a volume of something (including blood) is inserted into the cranium, after blood and CSF have as far as possible been pushed out of the cranium, the ICP will rise. The importance of the ICP relates to the CBF. Within limits of ICP the CBF remains unchanged. If the rise in ICP is too great, the CBF falls which if severe enough can damage the function or even the structure of the brain. A bleed into the head is one of the most rapid volume loadings that can occur. The bleeding is in general a self-limiting process, the effects of which will depend on the volume and location of the hematoma produced.

The effects of premature fusion of one coronal suture cause skull and orbital alterations in term of side-to-side asymmetry. This study aimed to quantify the cranio-orbital complex changes related to the severity of skull base dysmorphology in patients with unicoronal synostosis. Twenty-four infants affected by unicoronal synostosis were subdivided in three subgroups according to the severity of skull base deformity and their high-resolution CT images were quantitatively analyzed (groups IIa, IIb, III). Dimensions of cranial fossae, intracranial volume (ICV), ICV synostotic and ICV non synostotic side, whole brain volume (WBV), orbital volumes (OV), ICV/WBV, ICVsynostotic/ICVnon-synostotic, and OVsynostotic/OVnon-synostotic were evaluated. Asymmetry and reduction in the growth of the anterior and middle fossae were found in all groups while asymmetry of the posterior cranial fossa was found only in IIb and III groups. In all groups, ICV, WBV, and ICV/WBV were not significantly different while ICVsynostotic/ICVnon-synostotic and OVsynostotic/OVnon-synostotic resulted significant difference (p

Vitamin D and folate deficiency are considered risk factors for schizophrenia and bipolar disorders, but it is unknown how vitamin D and folate influence the growing brain, cranium or the clinical phenotype. Serum vitamin D and folate levels are in part genetically regulated. We investigated whether adult vitamin D and folate levels are associated with the intracranial volume (ICV) under the hypothesis that developmental vitamin D or folate levels influence neurodevelopment and that current levels are associated with ICV. Ninety patients with severe mental disorders and 91 healthy controls underwent 3 T magnetic resonance imaging and serum sampling. Multiple linear regression was used to assess the contribution of serum vitamin D, folate and patient-control status on ICV. We show that vitamin D levels were within lower range for patients and controls (48.8 ± 22.1 nmol/l and 53.4 ± 20.0 nmol/l, respectively). A significant positive association was found between vitamin D and ICV (p = 0.003, r = 0.22), folate was trend-significantly associated with ICV. Folate and vitamin D were significantly associated (p = 0.0001, r = 0.28). There were nonsignificant patient-control differences and no interaction effects. The results suggest that Vitamin D is associated with ICV as detected in the adult. Further studies are warranted for replication and to investigate possible mechanisms and genetic associations.

Summary:. Patients with syndromic craniosynostosis often require a large amount of cranial expansion to avoid intracranial hypertension, but the surgical procedure remains controversial. A patient of severe syndromic craniosynostosis with multiple bony defects and anomalous venous drainage at the occipital region was treated by multidirectional cranial distraction osteogenesis (MCDO) at the age of 8 months. Distraction started 5 days after surgery and ceased on postoperative day 16. The distraction devices were removed 27 days after completing distraction. After device removal, the increase of intracranial volume was 155 ml and the cephalic index was improved from 115.5 to 100.5. The resultant cranial shape was well maintained with minimal relapse at postoperative 9 months. In cases of syndromic craniosynostosis with multiple bony defects and/or anomalous venous drainage at the occipital region, expansion of the anterior cranium by MCDO is a viable alternative to conventional methods.

Purpose The aim of this study was to compare the outcome of intracranial volume (ICV) and cephalic index (CI) between two different techniques for surgical therapy of sagittal synostosis. Material and methods Between 2011 and 2015, all patients scheduled for surgical therapy of sagittal synostosis were consecutively enrolled. All patients younger than 6 months underwent early extended strip craniectomy (ESC group), and patients older than 6 months underwent late modified pi-procedure (MPP group). To measure ICV and CI, data acquisition was performed via three-dimensional photogrammetry, 1 day before (T0) and between 10 and 12 weeks after surgery (T1). Results were compared with an age-matched reference group of healthy children. Perioperative parameters, as duration of surgery and the amount of blood loss of both surgical procedures were analyzed. Results A total of 85 patients were enrolled. Of the patients, 48 underwent an extended strip craniotomy with parietal osteotomies and biparietal widening and 37 patients underwent a late modified pi-procedure. There was no significant difference between the ESC group and the MPP group regarding the efficacy of improving CI (p > 0.05). Both techniques were able to normalize CI and to improve head shape. ICV was normal compared to age-matched norm-groups with both techniques, pre- and postoperatively. However, duration of the surgical procedure and calculated blood loss were significantly lower in the ESC group (p Conclusion ESC and MPP were effective techniques to normalize cephalic index (CI) and improve head shape at their recommended time of surgery. Measurement of ICV and CI with 3D photogrammetry is a valid method to objectively evaluate patients before and after surgery without exposing pediatric patients to ionizing radiation.