Cerebral Gray Matter Research Articles

Abstract 025: Cross-sectional Relations of Serum Cortisol and Cognitive and Structural Brain Measures in Young Adults: The Framingham Heart Study

Introduction: Chronic stress and related changes in serum cortisol have adverse effects on brain structure and cognition in animal models. However, evidence from population-based studies is scant. We assessed the association of early morning serum cortisol with cognition and brain structural integrity in middle-aged adults without dementia. Hypotheses: High or low levels of serum cortisol are associated with lower cognitive performance and brain volumes. Methods: We evaluated dementia-free Framingham Study (Generation 3) participants (mean age 48.5 years; 46.8% men), who underwent cognitive testing of memory, abstract reasoning, visual perception, attention, and executive function (n= 2231), and brain MRI (n=2018) to assess total white matter, lobar gray matter, and white matter hyperintensity volumes and fractional anisotropy (FA) measures. We used linear or logistic (cortisol categorized in tertiles, middle tertile as the reference) regression to assess the relations of cortisol with cognition, MRI volumes and voxel-based microstructural white matter integrity and gray matter density, adjusting for age, sex, APOE and vascular risk factors. Results: Higher cortisol (highest tertile vs. middle tertile) was associated with worse memory and visual perception, as well as lower total cerebral brain, occipital and frontal lobar gray matter volumes (Table ) . Higher cortisol was associated with multiple areas of microstructural changes on voxel-based analyses (gray matter density and FA). The association of cortisol with total cerebral brain volume varied by sex ( Pinteraction =0.048 , highest cortisol tertile inversely associated with cerebral brain volume in women [ P= 0.001] but not in men [ P =0.717]). There was no effect modification by the apoE4 genotype of the relations of cortisol and cognition or imaging traits. Conclusions: Higher serum cortisol was associated with lower brain volumes and impaired memory in asymptomatic young adults in their forties; women may be particularly susceptible to this influence.

Cerebral gray matter volume losses in essential tremor: A case-control study using high resolution tissue probability maps

IntroductionEssential tremor (ET) is increasingly recognized as a multi-dimensional disorder with both motor and non-motor features. For this reason, imaging studies are more broadly examining regions outside the cerebellar motor loop. Reliable detection of cerebral gray matter (GM) atrophy requires optimized processing, adapted to high-resolution magnetic resonance imaging (MRI). We investigated cerebral GM volume loss in ET cases using automated segmentation of MRI T1-weighted images. MethodsMRI was acquired on 47 ET cases and 36 controls. Automated segmentation and voxel-wise comparisons of volume were performed using Statistical Parametric Mapping (SPM) software. To improve upon standard protocols, the high-resolution International Consortium for Brain Mapping (ICBM) 2009a atlas and tissue probability maps were used to process each subject image. Group comparisons were performed: all ET vs. Controls, ET with head tremor (ETH) vs. Controls, and severe ET vs. Controls. An analysis of variance (ANOVA) was performed between ET with and without head tremor and controls. Age, sex, and Montreal Cognitive Assessment (MoCA) score were regressed out from each comparison. ResultsWe were able to consistently identify regions of cerebral GM volume loss in ET and in ET subgroups in the posterior insula, superior temporal gyri, cingulate cortex, inferior frontal gyri and other occipital and parietal regions. There were no significant increases in GM volume in ET in any comparisons with controls. ConclusionThis study, which uses improved methodologies, provides evidence that GM volume loss in ET is present beyond the cerebellum, and in fact, is widespread throughout the cerebrum as well.

Brain gray matter alterations in Chinese patients with chronic knee osteoarthritis pain based on voxel-based morphometry.

Altered cerebral gray matter volume (GMV) is commonly found in patients with chronic pain. Chronic pain is the prominent characteristic of knee osteoarthritis (KOA), yet little is known about its morphological changes in the brain. Here an MRI study was performed to examine the structural brain abnormalities in 30 KOA patients with knee pain and age-matched healthy subjects. We detected that the patients exhibited significant almost 2-fold age-related decreases of GMV compared to healthy controls. Moreover, KOA patients also had significant loss of regional GMV including in the bilateral orbital frontal cortex (OFC), the right lateral prefrontal cortex (lPFC), and precentral and postcentral cortices. In addition, a high proportion of KOA patients exerted abnormal scores of Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Scale (HAMA), Mini Mental State examination (MMSE), and Montreal Cognitive Assessment (MoCA) compare to controls. Our results imply that chronic pain conditions which preferentially involve PFC might consider as a “cognitive state.” And emotion and cognitive function about chronic pain should be highly regarded.

Neurite imaging reveals microstructural variations in human cerebral cortical gray matter

We present distinct patterns of neurite distribution in the human cerebral cortex using diffusion magnetic resonance imaging (MRI). We analyzed both high-resolution structural (T1w and T2w images) and diffusion MRI data in 505 subjects from the Human Connectome Project. Neurite distributions were evaluated using the neurite orientation dispersion and density imaging (NODDI) model, optimized for gray matter, and mapped onto the cortical surface using a method weighted towards the cortical mid-thickness to reduce partial volume effects. The estimated neurite density was high in both somatosensory and motor areas, early visual and auditory areas, and middle temporal area (MT), showing a strikingly similar distribution to myelin maps estimated from the T1w/T2w ratio. The estimated neurite orientation dispersion was particularly high in early sensory areas, which are known for dense tangential fibers and are classified as granular cortex by classical anatomists. Spatial gradients of these cortical neurite properties revealed transitions that colocalize with some areal boundaries in a recent multi-modal parcellation of the human cerebral cortex, providing mutually supportive evidence. Our findings indicate that analyzing the cortical gray matter neurite morphology using diffusion MRI and NODDI provides valuable information regarding cortical microstructure that is related to but complementary to myeloarchitecture.

Changes in Brain Lateralization in Patients with Mild Cognitive Impairment and Alzheimer's Disease: A Resting-State Functional Magnetic Resonance Study from Alzheimer's Disease Neuroimaging Initiative.

To detect changes in brain lateralization in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) using resting-state functional magnetic resonance imaging (fMRI). Data from 61 well-matched right-handed subjects were obtained from the Alzheimer's Disease Neuroimaging Initiative, including 19 healthy controls (HCs), 25 patients with MCI, and 17 patients with AD. First, we divided 256 pairs of seed regions from each hemisphere covering the entire cerebral gray matter. Then, we used the intrinsic laterality index (iLI) approach to quantify the functional laterality using fMRI. One-way ANOVA was employed to estimate the differences in iLI among the three groups. The sum, number and mean value of the iLI were calculated within the thresholds of 0 < |iLI| < 0.2, 0.2 ≤ |iLI| < 0.4, 0.4 ≤ |iLI| < 0.8, and |iLI| ≥ 0.8, to explore the changes in the lateralization of resting-state brain function in patients with MCI and AD. One-way ANOVA revealed that the iLIs of the three groups were significantly different. The HCs showed a significant leftward interhemispheric difference within |iLI| ≥ 0.8. Compared with the HCs, the patients with MCI manifested a distinct abnormal rightward interhemispheric asymmetry, mainly within the thresholds of 0.2 ≤ |iLI| < 0.4 and 0.4 ≤ |iLI| < 0.8; in the patients with AD, the normal leftward lateralization that was observed in the HCs disappeared, and an abnormal rightward laterality was expressed within 0.4 ≤ |iLI| < 0.8. By directly comparing the patients with MCI with the patients with AD, an exclusive abnormal rightward laterality was observed in the patients with MCI within the 0.2 ≤ |iLI| < 0.4 threshold, and the normal leftward asymmetry vanished in the patients with AD within the |iLI| ≥ 0.8 threshold. Global brain lateralization was different among three groups. The abnormal rightward dominance observed in the patients with MCI and AD may indicate that these patients use additional brain resources to compensate for the loss of cognitive function, and the observed disappearance of the leftward laterality in the patients with AD was likely associated with the damage in the left hemisphere. The observed disappearance of the rightward asymmetry in the patients with AD using the 0.2 ≤ |iLI| < 0.4 threshold was likely a sign of decompensation. Our study provides new insights that may improve our understanding of MCI and AD.

18F-FPYBF-2, a new F-18-labelled amyloid imaging PET tracer: first experience in 61 volunteers and 55 patients with dementia

ObjectiveRecently, we developed a benzofuran derivative for the imaging of β-amyloid plaques, 5-(5-(2-(2-(2-18F-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)-N-methylpyridin-2-amine (18F-FPYBF-2) (Ono et al., J Med Chem 54:2971–9, 2011). The aim of this study was to assess the feasibility of 18F-FPYBF-2 as an amyloid imaging PET tracer in a first clinical study with healthy volunteers and patients with various dementia and in comparative dual tracer study using 11C-Pittsburgh Compound B (11C-PiB).Methods61 healthy volunteers (age: 53.7 ± 13.1 years old; 19 male and 42 female; age range 24–79) and 55 patients with suspected dementia [Alzheimer’s Disease (AD); early AD: n = 19 and moderate stage AD: n = 8, other dementia: n = 9, mild cognitive impairment (MCI): n = 16, cognitively normal: n = 3] for first clinical study underwent static head PET/CT scan using 18F−FPYBF-2 at 50–70 min after injection. 13 volunteers and 14 patients also underwent dynamic PET scan at 0–50 min at the same instant. 16 subjects (volunteers: n = 5, patients with dementia: n = 11) (age: 66.3 ± 14.2 years old; 10 males and 6 females) were evaluated for comparative study (50–70 min after injection) using 18F-FPYBF-2 and 11C-PiB on separate days, respectively. Quantitative analysis of mean cortical uptake was calculated using Mean Cortical Index of SUVR (standardized uptake value ratio) based on the established method for 11C-PiB analysis using cerebellar cortex as control.ResultsStudies with healthy volunteers showed that 18F-FPYBF-2 uptake was mainly observed in cerebral white matter and that average Mean Cortical Index at 50–70 min was low and stable (1.066 ± 0.069) basically independent from age or gender. In patients with AD, 18F-FPYBF-2 uptake was observed both in cerebral white and gray matter, and Mean Cortical Index was significantly higher (early AD: 1.288 ± 0.134, moderate AD: 1.342 ± 0.191) than those of volunteers and other dementia (1.018 ± 0.057). In comparative study, the results of 18F-FPYBF-2 PET/CT were comparable with those of 11C-PiB, and the Mean Cortical Index (18F-FPYBF-2: 1.173 ± 0.215; 11C-PiB: 1.435 ± 0.474) showed direct proportional relationship with each other (p < 0.0001).ConclusionsOur first clinical study suggest that 18F-FPYBF-2 is a useful PET tracer for the evaluation of β-amyloid deposition and that quantitative analysis of Mean Cortical Index of SUVR is a reliable diagnostic tool for the diagnosis of AD.

A comparative study on Kapur's and Tsallis entropy for multilevel thresholding of MR images via particle swarm optimisation technique

The present paper explores both the Kapur's and Tsallis entropy for a three level thresholding of brain MR images. The optimal thresholds are obtained by the maximisation of these entropies using a population-based search technique called as particle swarm optimisation (PSO). The algorithm is implemented for the segregation of various tissue constituents, i.e., cerebral spinal fluid (CSF), white matter (WM) and grey matter (GM) region from the simulated images obtained from the brain web database. The efficacy of the thresholding methods was evaluated by the measure of the spatial overlap, i.e., the Dice coefficient (Dice). The experimental results show that: 1) for both the WM and CSF the Tsallis entropy outperforms the Kapur's entropy by achieving an average value of 0.967279 and 0.878031 respectively; 2) for the GM, the Kapur's entropy is more beneficial which is duly justified by the mean value of Dice which was 0.851025 for this case.

Imaging and Genetic Biomarkers Predicting Transition to Psychosis.

The search for diagnostic and prognostic biomarkers in schizophrenia care and treatment is the focus of many within the research community. Longitudinal cohorts of patients presenting at elevated genetic and clinical risk have provided a wealth of data that has informed our understanding of the development of schizophrenia and related psychotic disorders.Imaging follow-up of high-risk cohorts has demonstrated changes in cerebral grey matter of those that eventually transition to schizophrenia that predate the onset of symptoms and evolve over the course of illness. Longitudinal follow-up studies demonstrate that observed grey matter changes can be employed to differentiate those who will transition to schizophrenia from those who will not prior to the onset of the disorder.In recent years our understanding of the genetic makeup of schizophrenia has advanced significantly. The development of modern analysis techniques offers researchers the ability to objectively quantify genetic risk; these have been successfully applied within a high-risk paradigm to assist in differentiating between high-risk individuals who will subsequently become unwell and those who will not.This chapter will discuss the application of imaging and genetic biomarkers within high-risk groups to predict future transition to schizophrenia and related psychotic disorders. We aim to provide an overview of current approaches focussing on grey matter changes that are predictive of future transition to illness, the developing field of genetic risk scores and other methods being developed to aid clinicians in diagnosis and prognosis.

Toward quantitative fast diffusion kurtosis imaging with b-values chosen in consideration of signal-to-noise ratio and model fidelity.

Diffusion kurtosis (DK) imaging is a variant of conventional diffusion magnetic resonance (MR) imaging that allows assessment of non-Gaussian diffusion. Fast DK imaging expedites the procedure by decreasing both scan time (acquiring the minimally required number of b-values) and computation time (obviating least-square curve fitting). This study aimed to investigate the applicability of fast DK imaging for both cerebral gray matter and white matter as a quantitative method. Seventeen healthy volunteers were recruited and each provided written informed consent before participation. On a 3-Tesla clinical MR system, diffusion imaging was performed with 12 b-values ranging from 0 to 4000 s/mm2 . Diffusion encoding was along three orthogonal directions (slice selection, phase encoding, and frequency encoding) in separate series. Candidate b-values were chosen by first determining the maximum b-value (bmax ) in the context of signal-to-noise ratio and then assessing the model fidelity for all b-value combinations within bmax . Diffusion coefficient (D) and diffusion kurtosis coefficient (K) were derived from these candidates and assessed for their dependence on b-value combination. Our data suggested bmax to be 2200 s/mm2 as a trade-off between the percentage (~80%) of voxels statistically detectable against background and the sensitivity to non-Gaussian diffusion in both gray matter and white matter. The measurement dependence on b-value was observed predominantly in areas with a considerable amount of cerebrospinal fluid. In most gray matter and white matter, b-value combinations do not cause statistical difference in the calculated D and K. For fast DK imaging to be quantitatively applicable in both gray matter and white matter, bmax should be chosen to ensure adequate signal-to-noise ratio in the majority of gray/white matter and the two nonzero b-values should be chosen in consideration of model fidelity to mitigate the dependence of derived indices on b-values.

Clinical Perspectives of Lithium's Neuroprotective Effect.

Evidence for a neuroprotective effect of lithium has accumulated over the last 2 decades, and this phenomenon has been regarded as an important mechanism of lithium action in mood disorders. It has been reflected by an increase in cerebral gray matter volume in lithium-treated subjects and by the favorable influence of lithium on cognitive functions. A neuroprotective effect of lithium also makes this ion a possible candidate for use as a therapeutic drug in neurology, especially in neurodegenerative disorders. In this paper, neurochemical mechanisms of neuroprotective action of lithium will be characterized. A possible association between the effect of lithium on brain structures reflected in neuroimaging studies, as well as on cognitive functions, and its neuroprotective action, will be considered. Data from experimental, epidemiological, and clinical studies have also pointed to an antidementia effect of lithium, bringing about some promise of using lithium in the treatment of mild cognitive impairment and Alzheimer's disease. The results of attempts of employing lithium in other neurodegenerative disorders will also be discussed.

PRES in the course of hemato-oncological treatment in children

IntroductionPosterior reversible leukoencephalopathy syndrome (PRES) is a clinical syndrome of varying aetiologies, characterised by acute neurological symptoms of brain dysfunction with MRI abnormalities in posterior cerebral white and grey matter. In most cases, symptoms resolve without neurological consequences.AimThe aim of this paper is the analysis of predisposing factors, clinical outcomes and radiological features of PRES in eight children with hemato-oncological disease.Material and methodsWe analysed the medical records of eight hemato-oncological patients aged from 3.0 to 16.1 years. The mean of age at primary diagnosis was 8.5 years.ResultsAll patients had both clinical and radiological PRES features. Seven out of eight underwent intensive chemotherapy regimens. Time elapsed from start of treatment to the occurrence of PRES ranged from 6 to 556 days. In one case, PRES occurred before chemotherapy and was the first symptom of cancer. Most (six of eight) patients had history of hypertension (> 95pc) and some (two of eight) occurred electrolyte imbalance—mainly hypomagnesaemia. Patients presented headache (seven of eight), disturbances of consciousness (six of eight), seizures (six of eight), visual changes (four of eight) and vomiting (three of eight). MRI demonstrated abnormalities in seven children: typical cerebral oedema in the white matter of the occipital to the parietal lobes. Most patient lesions in the MRI shrunk after 4 weeks, and clinical symptoms of PRES disappeared completely within a few hours to few days.ConclusionPRES may complicate oncological treatment in children. Hypertension is the most important risk factor of PRES. PRES should be included in differential diagnosis in all patients with acute neurological symptoms.

Cerebral gray matter volume in patients with chronic migraine: correlations with clinical features

BackgroundTo date, few MRI studies have been performed in patients affected by chronic migraine (CM), especially in those without medication overuse. Here, we performed magnetic resonance imaging (MRI) voxel-based morphometry (VBM) analyses to investigate the gray matter (GM) volume of the whole brain in patients affected by CM. Our aim was to investigate whether fluctuations in the GM volumes were related to the clinical features of CM.MethodsTwenty untreated patients with CM without a past medical history of medication overuse underwent 3-Tesla MRI scans and were compared to a group of 20 healthy controls (HCs). We used SPM12 and the CAT12 toolbox to process the MRI data and to perform VBM analyses of the structural T1-weighted MRI scans. The GM volume of patients was compared to that of HCs with various corrected and uncorrected thresholds. To check for possible correlations, patients’ clinical features and GM maps were regressed.ResultsInitially, we did not find significant differences in the GM volume between patients with CM and HCs (p < 0.05 corrected for multiple comparisons). However, using more-liberal uncorrected statistical thresholds, we noted that compared to HCs, patients with CM exhibited clusters of regions with lower GM volumes including the cerebellum, left middle temporal gyrus, left temporal pole/amygdala/hippocampus/pallidum/orbitofrontal cortex, and left occipital areas (Brodmann areas 17/18). The GM volume of the cerebellar hemispheres was negatively correlated with the disease duration and positively correlated with the number of tablets taken per month.ConclusionNo gross morphometric changes were observed in patients with CM when compared with HCs. However, using more-liberal uncorrected statistical thresholds, we observed that CM is associated with subtle GM volume changes in several brain areas known to be involved in nociception/antinociception, multisensory integration, and analgesic dependence. We speculate that these slight morphometric impairments could lead, at least in a subgroup of patients, to the development and continuation of maladaptive acute medication usage.

Temporal gradient during famous face naming is associated with lower cerebral blood flow and gray matter volume in aging

ObjectiveEvidence suggests that famous face naming may be a cognitive ability especially sensitive to the early pathological processes of Alzheimer's disease (AD) and that those at risk for AD may demonstrate a Ribot temporal gradient (RTG), characterized by better performance for naming remote famous faces than for naming recent famous faces. Reductions in cerebral blood flow (CBF) and gray matter volume (GMV) have been implicated in the neuropathological cascade of AD and show utility as biomarkers of AD risk. We examined whether a RTG during famous face naming was associated with lower CBF and/or GMV among a group of cognitively normal older adults. MethodsVoxel-wise independent samples t-tests were employed to contrast resting CBF values between those who exhibited a RTG (RTG+) during a famous face naming task and those who did not (RTG-) among a sample of 52 cognitively normal older adults (25 RTG-, 27 RTG+; mean age = 73). Groups were also compared on GMV using a voxel-wise general linear model. ResultsSignificant group differences in CBF and GMV were found, whereby the RTG+ group demonstrated reduced CBF and GMV within medial temporal lobe regions (hippocampus, parahippocampal gyrus), relative to the RTG- group. ConclusionsThis represents the first study to show that cognitively intact older adults who demonstrate a RTG during famous face naming exhibit vascular dysregulation and structural changes similar to that seen in AD risk. Findings suggest that famous face naming ability may be particularly sensitive to the very early brain changes associated with AD.

A two-year study using cerebral gray matter volume to assess the response to fingolimod therapy in multiple sclerosis

BackgroundCerebral gray matter (GM) atrophy has clinical relevance in multiple sclerosis (MS). Fingolimod has known efficacy on clinical and conventional MRI findings in MS; the effect on GM is unknown. ObjectiveTo explore fingolimod's treatment effect on cerebral GM atrophy over two years in patients with relapsing forms of MS. Design/methodsPatients starting fingolimod [n=24, age (mean±SD) 41.2±11.6years, Expanded Disability Status Scale (EDSS) score 1.1±1.4; 58% women] were compared to untreated patients [n=29, age 45.7±8.4years, EDSS 1.0±1.2; 93% women]. Baseline, one and two year MRI was applied to an SPM12 pipeline to assess brain parenchymal fraction (BPF) and cortical GM fraction (cGMF). T2 lesion volume (T2LV) and gadolinium-enhancing lesions were assessed. Change was modeled using a mixed effects linear regression with a random intercept and fixed effects for time, group, and the time-by-group interaction. The group slope difference was assessed using the interaction term. ResultsOver two years, cGMF remained stable in the fingolimod group (p>0.05), but decreased in the untreated group (p<0.001) (group difference p<0.001). BPF change did not differ between groups (all time-points p>0.05). T2LV increased over two years in the untreated group (p<0.001) but not in the fingolimod group (p≥0.44) (group difference p<0.001). ConclusionThese results suggest a treatment effect of fingolimod on cerebral GM atrophy in the first two years. GM atrophy is more sensitive to such effects than whole brain atrophy. However, due to the non-randomized, retrospective design, heterogeneous between-group characteristics, and small sample size, these results require confirmation in future studies.

Aberrant resting-state cerebellar blood flow in major depression

BackgroundAbnormal cortical cerebral blood flow and gray matter volume have been frequently reported in patients with major depressive disorder (MDD). In contrast, although the role of the cerebellum in MDD pathophysiology has attracted considerable interest more recently, studies investigating both functional and structural aspects of cerebellar integrity are scarce. MethodsIn this study, we used structural and functional magnetic resonance imaging (MRI) to investigate cerebellar volume and regional cerebellar blood flow (rCBF) at rest in clinically acute MDD patients (n = 22) and healthy controls (n = 18). We acquired high-resolution structural images at 3 T together with perfusion images obtained with continuous arterial spin labeling. Cerebellar structure and function were investigated using cerebellum-optimized analysis techniques. ResultsMarkedly increased rCBF was found in bilateral cerebellar areas VIIa and VIIIb (p < 0.05 family-wise-error [FWE] corrected). Significant differences in cerebellar volume between patients and controls were not found (p < 0.05, FWE-corrected). Left cerebellar area VIIa perfusion was significantly associated with depressive symptoms, as measured by the Hamilton Depression Rating Scale. LimitationsPotential limitations of this study include the modest sample size, the cross-sectional design, the lack of task-related imaging and the heterogeneity of drug treatment. ConclusionsThe data suggest contributions of “affective” cerebellar regions to MDD pathophysiology and symptom expression. While cerebellar perfusion at rest is compromised in MDD, cerebellar volume seems to be less affected.

Test-retest reliability of 3D spiral fast-spin-echo pseudo-continuous arterial spin labeling for cerebral perfusion imaging of subcortical gray matter in healthy adults

To evaluate the test-retest reliability of 3D spiral fast-spin-echo (FSE) pseudo-continuous arterial spin labeling (3D pc-ASL) for cerebral perfusion imaging of the subcortical gray matter in healthy adults in resting state. 3D spiral FSE ASL and 3D T1-weighted fast spoiled gradient recalled echo (3D T1-FSPGR) sequences were used for cerebral perfusion imaging in 8 healthy adult subjects, and a repeat imaging examination was performed after one week. The subcortical gray matter structures including the putamen, globus pallidus, caudate nucleus, thalamus, amygdala and hippocampus were segmented on the brain structural 3D images to generate the cerebral blood flow (CBF) map. The CBF value was extracted based on the segmented images and the CBF maps. The reliability and reproducibility of the measurements were evaluated using the intraclass correlation coefficient (ICC) and Bland-Altman plot. The mean ICC value of the subcortical gray matter structures was 0.88∓0.04 (range, 0.80-0.93). The Bland-Altman plot analysis demonstrated that the differences between the two measurements at all the points corresponding to the subcortical gray matter structures were within 95% CI of the limits of agreement. 3D spiral FSE pseudo-continuous ASL is a reliable method for assessing the perfusion of the cerebral subcortical gray matter structures.

Editors' Note

Editors' Note: In “Long-term cerebral white and gray matter changes after preeclampsia,” the authors found that preeclampsia was associated with chronic temporal lobe white matter changes and reduced cortical volume in young women; the changes were consistent with persistent inflammation. Dr. Culebras proposes that sleep apnea may be a contributing factor as pregnancy increases the risk of sleep apnea, which leads to inflammation and vascular morbidities, all of which may persist after pregnancy. Authors Siepmann et al. note that recent research shows an increased risk of stroke in patients with obstructive sleep apnea, possibly facilitated by intermittent hypoxia and vascular dysregulation. These mechanisms may relate to the authors' findings given the autonomic neurovascular dysfunction caused by preeclampsia. In “The autism ‘epidemic’: Ethical, legal, and social issues in a developmental spectrum disorder,” the authors emphasized the importance of early screening and diagnosis of autism spectrum disorder (ASD). Machado et al. recommend assessing anatomic brain connectivity using the diffusion-weighted MRI technique and functional brain connectivity using EEG coherence calculations as part of the ASD diagnostic workup. Authors Graf et al. caution against this practice, citing that many studies fail to consistently implicate a specific neural network responsible for autism. The authors conclude that techniques such as those described by Machado et al. have a role in ASD research, but not yet in its routine clinical diagnosis. —Megan Alcauskas, MD, and Steven Galetta, MD Editors' Note: In “Long-term cerebral white and gray matter changes after preeclampsia,” the authors found that preeclampsia was associated with chronic temporal lobe white matter changes and reduced cortical volume in young women; the changes were consistent with persistent inflammation.

Author response: Long-term cerebral white and gray matter changes after preeclampsia.

We thank Dr. Culebras for the comment on our article.1 Sleep apnea might be among the pathophysiologic pathways linking preeclampsia with increased risk of cerebrovascular disease in previously preeclamptic women. In fact, research recently focused on the role of sleep apnea in the etiopathogenesis of cerebrovascular and cardiovascular disease and demonstrated an increased stroke risk in patients with obstructive sleep apnea (OSA).2,3 Intermittent hypoxia with consecutive vascular dysregulation has been identified as a possible mechanism whereby OSA increases risk of stroke. This might be relevant to previously preeclamptic mothers in whom autonomic neurovascular dysfunction, inter alia mediated by functional changes to the sympathetic nervous system, was also demonstrated.4 It remains to be answered whether this similarity among pathologies indeed points to a causative link between preeclampsia and cerebrovascular disease.

Letter re: Long-term cerebral white and gray matter changes after preeclampsia.

The article by Siepmann et al.1 identified long-term cerebral white matter changes and reduced cortical volume, presumably of vascular origin, in young women after pregnancy complicated by preeclampsia. The authors invoked persistent inflammation as the putative agent. Sleep apnea may be a link among pregnancy, preeclampsia, and cerebrovascular disease.

Movement disorders in genetically confirmed mitochondrial disease and the putative role of the cerebellum

Mitochondrial disease can present as a movement disorder. Data on this entity's epidemiology, genetics, and underlying pathophysiology, however, is scarce. The objective of this study was to describe the clinical, genetic, and volumetric imaging data from patients with mitochondrial disease who presented with movement disorders. In this retrospective analysis of all genetically confirmed mitochondrial disease cases from three centers (n = 50), the prevalence and clinical presentation of video-documented movement disorders was assessed. Voxel-based morphometry from high-resolution MRI was employed to compare cerebral and cerebellar gray matter volume between mitochondrial disease patients with and without movement disorders and healthy controls. Of the 50 (30%) patients with genetically confirmed mitochondrial disease, 15 presented with hypokinesia (parkinsonism 3/15), hyperkinesia (dystonia 5/15, myoclonus 3/15, chorea 2/15), and ataxia (3/15). In 3 patients, mitochondrial disease presented as adult-onset isolated dystonia. In comparison to healthy controls and mitochondrial disease patients without movement disorders, patients with hypo- and hyperkinetic movement disorders had significantly more cerebellar atrophy and an atrophy pattern predominantly involving cerebellar lobules VI and VII. This series provides clinical, genetic, volumetric imaging, and histologic data that indicate major involvement of the cerebellum in mitochondrial disease when it presents with hyper- and hypokinetic movement disorders. As a working hypothesis addressing the particular vulnerability of the cerebellum to energy deficiency, this adds substantially to the pathophysiological understanding of movement disorders in mitochondrial disease. Furthermore, it provides evidence that mitochondrial disease can present as adult-onset isolated dystonia. © 2017 International Parkinson and Movement Disorder Society.