The microstructural integrity of the corpus callosum and associated impulsivity in alcohol dependence: a tractography-based segmentation study using diffusion spectrum imaging

Previous post-mortem and structural magnetic resonance imaging (MRI) studies in patients with alcohol dependence have demonstrated abnormalities of brain white matter. The present study investigated the microstructural integrity in the corpus callosum and the associations of this integrity with neurobehavioral assessments. Twenty-five male cases fulfilling the DSM-IV diagnosis of alcohol dependence and 15 male control subjects were scanned using a 3T MRI system. Callosal fiber tracts were reconstructed by diffusion spectrum imaging tractography and were subdivided into seven functionally distinct segments. The microstructural integrity was quantified in terms of generalized fractional anisotropy (GFA). Compared with normal subjects, men with alcohol dependence showed lower GFA values on all segments of the corpus callosum. The segment interconnecting the bilateral orbitofrontal cortices was the most affected. The score on the Barratt Impulsivity Scale showed an inverse relationship with GFA on the callosal fiber tracts connecting the bilateral orbitofrontal cortices. Furthermore, the duration of regular use was negatively associated with GFA on the callosal fiber tracts connecting the bilateral temporal and parietal cortices. Our findings suggest that a high self-rated impulsivity level was associated with low anisotropy in white matter of corpus callosum sectors extending to the orbitofrontal cortex.     

Corpus callosum signal intensity in patients with bipolar and unipolar disorder

BACKGROUND: Anatomical abnormalities in the corpus callosum have been reported in magnetic resonance imaging (MRI) studies in patients with bipolar but not unipolar disorder. MRI signal intensity can be used as a putative index of corpus callosum myelination. OBJECTIVES: To measure MRI signal intensity in patients with bipolar and unipolar disorder to investigate abnormalities of corpus callosum myelination. METHODS: The study involved 29 DSM-IV bipolar patients (mean (SD) age, 35 (11) years; 16 male, 13 female), 23 DSM-IV unipolar patients (41 (10) years; 4 male, 19 female), and 36 healthy controls (37 (10) years; 23 male, 13 female). A 1.5T GE Signa magnet was employed, with a fast spin echo sequence. Corpus callosum signal intensity was obtained blindly using the semiautomated software NIH Image 1.62. RESULTS: Bipolar patients had lower corpus callosum signal intensity for all callosal subregions (genu, anterior and posterior body, isthmus, splenium) than healthy controls (ANCOVA, age and sex as covariates, p<0.05). No significant differences were found between unipolar and healthy subjects (ANCOVA, age and sex as covariates, p>0.05). CONCLUSIONS: The findings suggest abnormalities in corpus callosum white matter in bipolar but not unipolar patients, possibly because of altered myelination. Such abnormalities could lead to impaired interhemispheric communication in bipolar disorder. Longitudinal MRI studies involving first episode and early onset bipolar patients will be necessary for a better understanding of the potential role of abnormalities of corpus callosum myelination in the pathophysiology of bipolar disorder.     

White matter tract alterations in Parkinson's disease patients with punding

ObjectiveTo assess brain white matter tract alterations in patients with Parkinson's disease and punding (PD-punding) compared with controls and PD cases without any impulsive-compulsive behaviour.MethodsForty-nine PD patients (21 PD-punding and 28 PD with no impulsive-compulsive behaviours) and 28 controls were consecutively recruited. Clinical, cognitive and psychopathological evaluations were performed. Diffusion tensor MRI metrics of the main white matter tracts were assessed using a tractography approach.ResultsCompared with controls, both PD groups showed white matter microstructural alterations of the left pedunculopontine tract and splenium of the corpus callosum. PD-punding patients showed a further damage to the right pedunculopontine tract and uncinate fasciculus, genu of the corpus callosum, and left parahippocampal tract relative to controls. When adjusting for depression and/or apathy severity, a greater damage of the genu of the corpus callosum and the left pedunculopontine tract was found in PD-punding compared with patients with no impulsive-compulsive behaviours.ConclusionsPD-punding is associated with a disconnection between midbrain, limbic and white matter tracts projecting to the frontal cortices. These alterations are at least partially independent of their psychopathological changes. Diffusion tensor MRI is a powerful tool for understanding the neural substrates underlying punding in PD.     

White matter abnormalities in drug-naïve patients with obsessive-compulsive disorder: a diffusion tensor study before and after citalopram treatment

Objective: The aim was to investigate the white matter abnormalities of drug‐naïve patients with obsessive–compulsive disorder (OCD) using diffusion tensor‐imaging and the white matter changes in the patients after pharmacotherapy. Method: Thirteen drug‐naïve OCD patients and 13 age‐ and sex‐matched healthy comparison subjects were examined using diffusion tensor‐imaging and structural magnetic resonance imaging. Measurements were made in OCD patients before and after 12 weeks of citalopram treatment. Results: Compared with controls, the drug‐naïve OCD patients showed significant increases in fractional anisotropy (FA) in the corpus callosum, the internal capsule and white matter in the area superolateral to the right caudate. The increases in FA were mostly no longer observed in patients after 12 weeks of treatment compared with controls. Conclusion: Our findings suggest that white matter alterations are associated with the pathophysiology of OCD, and the abnormalities may be partly reversible with pharmacotherapy.     

White Matter Abnormalities in Late Onset First Episode Mania: A Diffusion Tensor Imaging Study

IntroductionA first manic episode after 50 years of age is uncommon. Late Onset Mania might be indicative of abnormalities in white matter, probably related to vascular, degenerative, or inflammatory processes.ObjectiveTo determine if patients with late onset mania have reduced white matter integrity according to Magnetic Resonance Diffusion Tensor Imaging (DTI) and structural MRI.MethodsTwenty-two patients with late onset mania (>50 years old) and 22 age-paired healthy subjects were included in the study. Fractional anisotropy (FA) was used as a quantitative measure of white matter integrity. Fazekas scale was assessed also to measure white matter abnormalities in the FLAIR sequence. The Frontal Assessment Battery, COGNISTAT and Trail making test A and B were used as cognitive measurements.ResultsAccording to DTI, commissural connections (left corpus callosum), and limbic connections (right and left uncinate fasciculus) were different between the patients and the comparison group. Fractional anisotropy values in the left corpus callosum showed significant correlations with neuropsychological measures, and with the Fazekas scale score. According to Fazekas scale, a pathological score in the FLAIR sequence was significantly more frequent in the patients as compared to the comparison group.ConclusionsPatients with first episode mania in late life have relevant white matter abnormalities not explained by age, affecting interhemispheric and fronto-limbic networks probably related to executive functioning and emotional processing, at the level of the corpus callosum and the uncinate fasciculus. The etiology of this white matter loss of integrity in patients with late-onset mania is yet to be explored.     

MRI signal changes in the white matter after corpus callosotomy

Magnetic resonance imaging (MRI) changes reported after corpus callosotomy include hyperintensity in the corpus callosum, perifalcine hyperintensity caused by surgical retraction, and acute changes associated with surgical complications. The authors have observed MRI signal changes in the cerebral white matter of corpus callosotomy patients that are separate from the sectioned callosum and not clearly related to surgical manipulation or injury. Brain MRI scans were retrospectively reviewed in 25 of 38 patients who underwent anterior, posterior, or total callosotomy for refractory seizures between 1988 and 1995. Nine patients had signal changes in the cerebral white matter on postoperative MRI. Six of these patients had preoperative MRI studies available for comparison, and none of the white matter signal abnormalities were evident preoperatively. T2 prolongation or hyperintensity on proton-density images was observed in areas including the centrum semiovale, forceps major, and forceps minor. Three patients had signal changes that had distinct borders extending only to the posterior limit of the callosotomy. MRI signal changes in the cerebral white matter after corpus callosotomy have not been previously reported and may represent distant effects of callosal section. Wallerian degeneration occurring in the neuronal processes cut during surgery could account for the signal changes.     

Altered white matter integrity in temporal lobe epilepsy: Association with cognitive and clinical profiles

Purpose: Diffusion tensor imaging (DTI) studies have reported substantial white matter abnormalities in patients with temporal lobe epilepsy (TLE). However, limited data exist regarding the extent of white matter tract abnormalities, cognitive effects of these abnormalities, and relationship to clinical factors. The current study examined these issues in subjects with chronic TLE. Methods: DTI data were obtained in 12 TLE subjects and 10 age‐matched healthy controls. Voxel‐wise statistical analysis of fractional anisotropy (FA) was carried out using tract‐based spatial statistics (TBSS). White matter integrity was correlated with cognitive performance and epilepsy‐related clinical parameters. Results: Subjects with TLE, as compared to healthy controls, demonstrated four clusters of reduced FA, in anterior temporal lobe, mesial temporal lobe, and cerebellum ipsilateral, as well as frontoparietal lobe contralateral to the side of seizure onset. Mean FA was positively correlated with delayed memory, in anterior temporal lobe; and immediate memory, in mesial temporal lobe. Lower FA values in the posterior region of corpus callosum were related to earlier age of seizure onset. Conclusion: TLE is associated with widespread disturbances in white matter tracts and these changes have important cognitive and clinical consequences.     

An advanced white matter tract analysis in frontotemporal dementia and early-onset Alzheimer’s disease

Cortical and subcortical nuclei degenerate in the dementias, but less is known about changes in the white matter tracts that connect them. To better understand white matter changes in behavioral variant frontotemporal dementia (bvFTD) and early-onset Alzheimer’s disease (EOAD), we used a novel approach to extract full 3D profiles of fiber bundles from diffusion-weighted MRI (DWI) and map white matter abnormalities onto detailed models of each pathway. The result is a spatially complex picture of tract-by-tract microstructural changes. Our atlas of tracts for each disease consists of 21 anatomically clustered and recognizable white matter tracts generated from whole-brain tractography in 20 patients with bvFTD, 23 with age-matched EOAD, and 33 healthy elderly controls. To analyze the landscape of white matter abnormalities, we used a point-wise tract correspondence method along the 3D profiles of the tracts and quantified the pathway disruptions using common diffusion metrics – fractional anisotropy, mean, radial, and axial diffusivity. We tested the hypothesis that bvFTD and EOAD are associated with preferential degeneration in specific neural networks. We mapped axonal tract damage that was best detected with mean and radial diffusivity metrics, supporting our network hypothesis, highly statistically significant and more sensitive than widely studied fractional anisotropy reductions. From white matter diffusivity, we identified abnormalities in bvFTD in all 21 tracts of interest but especially in the bilateral uncinate fasciculus, frontal callosum, anterior thalamic radiations, cingulum bundles and left superior longitudinal fasciculus. This network of white matter alterations extends beyond the most commonly studied tracts, showing greater white matter abnormalities in bvFTD versus controls and EOAD patients. In EOAD, network alterations involved more posterior white matter – the parietal sector of the corpus callosum and parahipoccampal cingulum bilaterally. Widespread but distinctive white matter alterations are a key feature of the pathophysiology of these two forms of dementia.     

White matter magnetic resonance imaging hyperintensity in Alzheimer's disease: correlations with corpus callosum atrophy

We have previously demonstrated with MRI that as well as marked white matter involvement in late-onset Alzheimer's disease (AD), atrophy of the corpus callosum may also be present. This finding prompted us to study possible correlations between atrophy of the corpus callosum and white matter hyperintensity (WMH) and between white matter lesions and the severity of the disease. We compared the corpus callosum and white matter lesions on MRI from 15 AD patients and 15 controls. The white matter lesions were scored according to the Scheltens' rating scale. We found a significant reduction of the area of the corpus callosum and more severe white matter lesions in AD patients than in controls. Both atrophy of the corpus callosum and the severity of lesions depended mainly on the diagnosis of senile dementia of the Alzheimer type and on age but not on the diagnosis of presenile AD. We demonstrated a negative correlation between white matter lesions scores and areas of corpus callosum in AD patients and no correlation between the white matter lesions and the severity of the disease. We demonstrated that white matter lesions including WMH and atrophy of the corpus callosum are more frequent in AD than in controls. The predominance of white matter lesions in senile AD may be explained by the combination of aging and disease processes.     

Shape differences in the corpus callosum in first-episode schizophrenia and first-episode psychotic affective disorder

OBJECTIVE: The corpus callosum, the largest white matter tract in the brain, is a midline structure associated with the formation of the hippocampus, septum pellucidum, and cingulate cortex, which have been implicated in the pathogenesis of schizophrenia. Corpus callosum shape deformation, therefore, may reflect a midline neurodevelopmental abnormality. METHOD: Corpus callosum area and shape were analyzed in 14 first-episode psychotic patients with schizophrenia, 19 first-episode psychotic patients with affective disorder, and 18 normal comparison subjects. RESULTS: No statistically significant corpus callosum area differences between groups were found, but there were differences in the structure's shape between the patients with schizophrenia and the comparison subjects. A correlation between width and angle of the corpus callosum was found in patients with affective disorder. CONCLUSIONS: Corpus callosum shape abnormalities in first-episode psychotic patients with schizophrenia may reflect a midline neurodevelopmental abnormality.     

Effect of DAOA genetic variation on white matter alteration in corpus callosum in patients with first-episode schizophrenia

D-amino acid oxidase activator (DAOA) gene, which plays a crucial role in the process of glutamatergic transmission and mitochondrial function, is frequently linked with the liability for schizophrenia. We aimed to investigate whether the variation of DAOA rs2391191 is associated with alterations in white matter integrity of first-episode schizophrenia (FES) patients; and whether it influences the association between white matter integrity, cognitive function and clinical symptoms of schizophrenia. Forty-six patients with FES and forty-nine healthy controls underwent DTI and were genotyped for DAOA rs2391191. Psychopathological assessments were performed by Brief Psychiatric Rating Scale (BPRS) and Scale for Assessment of Negative Symptoms (SANS). Cognitive function was assessed by MATRICS Consensus Cognitive Battery (MCCB). Schizophrenia patients presented lower fractional anisotropy (FA) and higher radial diffusivity (RD), mainly spreading over the corpus callosum and corona radiata compared with healthy controls. Compared with patients carrying G allele, patients with AA showed lower FA in the body of corpus callosum, and higher RD in the genu of corpus callosum, right superior and anterior corona radiata, and left posterior corona radiata. In patients carrying G allele, FA in body of corpus callosum was positively correlated with working memory, RD in genu of corpus callosum was negatively associated with the speed of processing, working memory, and the composite score of MCCB, while no significant correlations were found in AA homozygotes. In our study, patients with FES presented abnormal white matter integrity in corpus callosum and corona radiata. Furthermore, this abnormality was associated with the genetic variation of DAOA rs2391191, with AA homozygotes showing less white matter integrity in the corpus callosum. Our findings possibly provide further support to the evidence that DAOA regulates the process of glutamatergic neurotransmission and mitochondrial function in the pathophysiological mechanism of schizophrenia.

     

强迫症患者脑结构异常的多模态研究

目的探讨强迫症患者脑灰质和白质结构改变是否在同一样本中反映了相同环路的异常。方法对54例强迫症患者(强迫症组)和54名健康对照(对照组)进行3D结构磁共振成像扫描和弥散张量成像扫描。基于SPM分析软件,采用基于体素的形态学分析方法分析强迫症组全脑灰质体积与对照组的差异;基于FSL软件,采用基于纤维束示踪的空间统计学探讨强迫症组各向异性分数(fractional anisotropy,FA)与对照组的差异。结果与对照组相比,强迫症组左侧额中回、左侧前扣带和旁扣带脑回、左侧中央前回及右侧颞下回灰质体积减小(P<0.05,Alphasim校正),胼胝体体部和胼胝体膝部FA值减小(P<0.05,FWE校正)。结论强迫症患者的灰质体积和白质完整性均存在异常,且异常区域多位于皮质-纹状体-丘脑-皮质环路相关脑区,强迫症的灰、白质结构异常可能同时出现。     

Reduced interhemispheric connectivity in schizophrenia-tractography based segmentation of the corpus callosum

BACKGROUND: A reduction in interhemispheric connectivity is thought to contribute to the etiology of schizophrenia. Diffusion Tensor Imaging (DTI) measures the diffusion of water and can be used to describe the integrity of the corpus callosum white matter tracts, thereby providing information concerning possible interhemispheric connectivity abnormalities. Previous DTI studies in schizophrenia are inconsistent in reporting decreased Fractional Anisotropy (FA), a measure of anisotropic diffusion, within different portions of the corpus callosum. Moreover, none of these studies has investigated corpus callosum systematically, using anatomical subdivisions. METHODS: DTI and structural MRI scans were obtained from 32 chronic schizophrenic subjects and 42 controls. Corpus callosum cross sectional area and its probabilistic subdivisions were determined automatically from structural MRI scans using a model based deformable contour segmentation. These subdivisions employ a previously generated probabilistic subdivision atlas, based on fiber tractography and anatomical lobe subdivision. The structural scan was then co-registered with the DTI scan and the anatomical corpus callosum subdivisions were propagated to the associated FA map. RESULTS: Results revealed decreased FA within parts of the corpus interconnecting frontal regions in schizophrenia compared with controls, but no significant changes for callosal fibers interconnecting parietal and temporo-occipital brain regions. In addition, integrity of the anterior corpus was statistically significantly correlated with negative as well as positive symptoms, while posterior measures correlated with positive symptoms only. CONCLUSIONS: This study provides quantitative evidence for a reduction of interhemispheric brain connectivity in schizophrenia, involving corpus callosum, and further points to frontal connections as possibly disrupted in schizophrenia.     

Detection of wallerian degeneration in a newborn by diffusion magnetic resonance imaging (MRI)

We present the case of an infant with hypoxic-ischemic encephalopathy in whom wallerian degeneration is demonstrated in white-matter fiber tracts by diffusion magnetic resonance imaging (MRI). MRI was undertaken on days 2 and 9 and then at 9 months of age. On day 2, conventional MRI was normal, but diffusion MRI showed bioccipital abnormalities. On day 9, diffusion MRI showed marked abnormalities in the deep white matter of the occipital regions (left > right), corpus callosum, left posterior limb of the internal capsule, and left cerebral peduncle. Water apparent diffusion coefficient values showed a significant reduction in the left occipital white matter and corpus callosum between days 2 and 9 while demonstrating the expected pseudonormalization in cortical gray matter. Images at 9 months showed left occipital porencephaly and atrophy of the left cerebral peduncle, with the infant displaying right hemiplegia at 18 months of age. In this case, the time course of diffusion changes differed between white and gray matter, with diffusion MRI showing delayed wallerian degeneration of the cerebral white matter. This case characterizes this degeneration with clinical and follow-up MRI at 9 months of age.     

Disrupted white matter integrity of corticopontine-cerebellar circuitry in schizophrenia

Evidence for white matter abnormalities in patients with schizophrenia is increasing. Decreased fractional anisotropy (FA) in interhemispheric commissural fibers as well as long-ranging fronto-parietal association fibers belongs to the most frequent findings. The present study used tract-based spatial statistics to investigate white matter integrity in 35 patients with schizophrenia and 35 healthy volunteers. We found that patients exhibited significantly decreased FA relative to healthy subjects in the corpus callosum, the cerebral peduncle, the left inferior fronto-occipital fasciculus, the anterior thalamic radiation, the right posterior corona radiata, the middle cerebellar peduncle, and the right superior longitudinal fasciculus. Increased FA was detectable in the inferior sections of the corticopontine-cerebellar circuit. Present data indicate extended cortical-subcortical alterations of white matter integrity in schizophrenia using advanced data analysis strategies. They corroborate preceding findings of white matter structural deficits in mainly long-ranging association fibers and provide first evidence for neuroplastic changes in terms of an increased directionality in more inferior fiber tracts.     

Clinical correlates of white-matter abnormalities on head magnetic resonance imaging

We undertook this study to investigate the relationship between white-matter abnormalities (seen on brain magnetic resonance imaging [MRI]) and muscle tone and muscle stretch reflexes on clinical examination. We identified all patients less than 5 years of age who had undergone cranial MRI studies at Riley Hospital for Children between June 30, 1999, and July 1, 2000, whose scans were read as showing white-matter abnormalities. We measured two ratios and the thickness of the corpus callosum as indicators of the quantity of cerebral white matter. The ratios were R1, the ratio of the thickness of the white matter at the level just above the body of the lateral ventricle compared with the width of the hemisphere, and R2, the ratio of the thickness of the white matter to the width of the hemisphere at the level of the trigone of the lateral ventricle. The thickness of the corpus callosum was measured at the junction of the anterior two thirds and the posterior third. We also evaluated the signal intensity of the cerebral white matter by reviewing the fluid-attenuated inversion-recovery images and grading the signal as normal to severely abnormal depending on the degree and extent of high signal intensity seen (0 = normal to 4+). Thirty-eight children less than 5 years of age who underwent MRI scans between June and August 2000 and who were found to have normal tone prospectively and normal MRI scan on review served as a control group. We identified 215 patients who had white-matter abnormalities; of these, only 142 (66%) had documented tone assessments in their medical record. Our study group was divided into three groups: increased (n = 35), decreased (n = 53), and normal tone (n = 54). All three measurements of white matter in each of the three study groups were significantly below values for control children. The children with white-matter abnormalities and decreased tone had significantly less signal intensity abnormality than the other study groups. Children with white-matter abnormalities and increased tone had a greater frequency of increased reflexes and tended to have more signal abnormalities than the other groups. The group of children with white-matter abnormalities and normal tone had the least amount of cerebral white-matter deficiency of the three study groups. In patients with strikingly decreased quantities of cerebral white matter, those with normal signal-intensity white matter are likely to be hypotonic with normal reflexes and those with increased signal intensity in the white matter are likely to be spastic.     

Evaluation of white matter changes in agyria-pachygyria complex using diffusion tensor imaging

Associated abnormalities of the white matter in patients with agyria-pachygyria complex have rarely been investigated using new imaging modalities like diffusion tensor imaging. The present study evaluated the white matter changes of 9 children with agyria-pachygyria complex using diffusion tensor imaging. Regions of interest were placed in 17 white matter tracts. Compared with normal controls, the axial diffusivity of the genu of the corpus callosum, corticospinal tract, and fornix in patients with agyria-pachygyria complex was decreased. In the subcortical white matter without changes in T2-weighted image, there were significant decreases in fractional anisotropy and axial diffusivity and increases in radial diffusivity, indicating significant alterations of the white matter. Since axial diffusivity and radial diffusivity reflect changes in the axon and myelin, respectively, the findings here indicate disturbance in both axonal and myelin development in agyria-pachygyria complex.     

Longitudinal Changes in Diffusion Properties in White Matter Pathways of Children With Tuberous Sclerosis Complex

BackgroundAbnormal white matter development in patients with tuberous sclerosis complex, a multisystem hamartomatous disorder caused by aberrant neural proliferation and axonal maturation, may be associated with poorer neurocognitive outcomes. The purpose of this study is to identify predictors of longitudinal changes in diffusion properties of white matter tracts in patients with tuberous sclerosis complex.MethodsDiffusion magnetic resonance imaging was carried out in 17 subjects with tuberous sclerosis complex (mean age, 7.2 ± 4.4 years) with at least two magnetic resonance imaging scans (mean number of days between scans, 419.4 ± 105.4). There were 10 males; 5 of 17 had autism spectrum disorder and 10 of 17 had epilepsy. Regions of interest were placed to delineate the internal capsule/corona radiata, cingulum, and corpus callosum. The outcomes were mean change in apparent diffusion coefficient and fractional anisotropy. Data were analyzed using Pearson's correlation and multiple linear regression analyses.ResultsGender was a significant predictor of mean change in apparent diffusion coefficient in the left internal capsule, right and left cingulum bundles, and corpus callosum and a significant predictor of mean change in fractional anisotropy in the corpus callosum. Epilepsy was a significant predictor of mean change in apparent diffusion coefficient in the left internal capsule. Autism spectrum disorder was not predictive of diffusion changes in any of the studied pathways.ConclusionClinical variables, including gender and epilepsy, have an effect on the development of white matter pathways. These variables should be taken into consideration when counseling tuberous sclerosis complex patients and in future imaging studies in this population.     

Sexual dimorphic abnormalities in white matter geometry common to schizophrenia and non‐psychotic high‐risk subjects: Evidence for a neurodevelopmental risk marker?

The characterization of neurodevelopmental aspects of brain alterations require neuroimaging methods that reflect correlates of neurodevelopment, while being robust to other progressive pathological processes. Newly developed neuroimaging methods for measuring geometrical features of the white matter fall exactly into this category. Our recent work shows that such features, measured in the anterior corpus callosum in diffusion MRI data, correlate with psychosis symptoms in patients with adolescent onset schizophrenia and subside a reversal of normal sexual dimorphism. Here, we test the hypothesis that similar developmental deviations will also be present in nonpsychotic subjects at familial high risk (FHR) for schizophrenia, due to genetic predispositions. Demonstrating such changes would provide a strong indication of neurodevelopmental deviation extant before, and independent of pathological changes occurring after disease onset. We examined the macrostructural geometry of corpus callosum white matter in diffusion MRI data of 35 non‐psychotic subjects with genetic (familial) risk for schizophrenia, and 26 control subjects, both male and female. We report a reversal of normal sexual dimorphism in callosal white matter geometry consistent with recent results in adolescent onset schizophrenia. This pattern may be indicative of an error in neurogenesis and a possible trait marker of schizophrenia. Hum Brain Mapp 37:254–261, 2016. © 2015 Wiley Periodicals, Inc.     

Complicated hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) and childhood onset

The hereditary spastic paraplegias (HSPs) are a group of rare disorders with the predominant clinical feature of progressive spastic paraplegia. They are subdivided into pure and complicated forms according to whether the disorder is associated with other neurological abnormalities. We report on two unrelated female Caucasian patients with complicated HSP, aged 16 and 24 years, who showed progressive gait disturbance with spasticity and ataxia as well as cognitive impairment. Onset of symptoms was at age 3 and 10 years, respectively. MRI revealed mild diffuse non-progressive T (2)-signal alterations of cerebral white matter and thinning of the body and genu of the corpus callosum. Some similarity of clinical symptoms and MRI patterns with the phenotype of Mast syndrome prompted a mutation analysis of the SPG21 gene, encoding maspardin, which revealed a wild-type sequence in both patients. Clinical and neuroradiological features in our patients are diagnostic for complicated autosomal recessive hereditary spastic paraplegia with thin corpus callosum (HSP-TCC, SPG11). This disorder, characterized by a typical MRI pattern and a progressive spastic paraplegia that may be associated with dementia and ataxia, may have an onset in early childhood and probably is one of the more common forms of complicated HSP.