Report of a case of grey matter heterotopia combined with epilepsy due to TUBB2B gene variant and review of literature / 中华神经科杂志

Objective:To report the clinical phenotype and mutation site of a patient with grey matter heterotopia caused by a de novo heterozygous missense mutation in the TUBB2B gene, and to expand the phenotypic and mutational spectrum of TUBB2B mutations. Methods:One patient with TUBB2B mutation who presented to the Department of Neurology, the First Affiliated Hospital of Air Force Medical University in July 2017 was collected and analyzed for clinical features and mutation site, and a review of previous studies was performed. Results:The male patient started at the age of 18 and presented mainly with seizures, poor left-handed fine motor skills and poor spatial imagination. Magnetic resonance imaging showed nodular grey matter heterotopia in the right cerebral hemisphere, right frontoparietal-temporal localized cerebral gyrus, and cerebral sulcus shallow flat.The whole exon gene test suggested a heterozygous missense mutation in the TUBB2B gene: c.776 C>T (p.Pro259Leu), which was wild-type in both of his parents. The mutation site was located between the tubulin and tubulin-c structural domains and did not affect the function of the essential structural domain. After treatment with magnesium valproate in combination with levetiracetam, the patient′s seizure symptoms were significantly controlled and he has been seizure-free for 3 years now. Conclusions:The TUBB2B gene c.776 C>T (p.Pro259Leu) heterozygous missense mutation is a novel missense mutation causing grey matter heterotopia. The patient had a good prognosis, and the combination of two antiepileptic drugs resulted in complete seizure control.

The grey matter volume and fractional amplitude of low-frequency fluctuation alterations in cerebral small vessel disease patients with subcortical ischemic depression and their relationship with brain derived neurotrophic factor gene polymorphism / 中华神经科杂志

Objective:To investigate the relationship between brain derived neurotrophic factor (BDNF) gene polymorphism and the change of grey matter volume (GMV) and fractional amplitude of low-frequency fluctuation (fALFF) in cerebral small vessel disease (CSVD) patients with subcortical ischemic depression (SID).Methods:Eighty-seven CSVD patients in the First Affiliated Hospital of Anhui Medical University were enrolled from July 2017 to November 2020 and divided into CSVD-SID group [Geriatric Depression Scale (GDS) score>10] and CSVD-non - depression group (CSVD-ND group, GDS score≤10) according to GDS. Both GMV and fALFF were calculated based on structural and functional magnetic resonance imaging data, and the interactions between SID diagnosis and BDNF gene on brain function and structure alteration were explored.Results:GMV was significantly increased in the posterior default network (pDMN; such as posterior cingulate gyrus/precuneus and middle temporal gyrus) in the CSVD-SID group compared with the CSVD-ND group. On GMV property, significant interactions between BDNF gene and SID were found in the cuneus ( F=25.50, P<0.001), precuneus lobe ( F=13.61, P<0.001) and cerebellum ( F=17.23, P<0.001). In the aspect of fALFF, the brain functional activity in the superior frontal gyrus was significantly increased in the CSVD-SID group compared with that in the CSVD-ND group (0.363±0.648 vs -0.427±0.514,cluster size=48 voxels, t=5.63, P<0.001). But there was no significant interaction between diagnosis and BDNF genotype on brain function. Conclusions:Both the GMV and fALFF were increased in CSVD-SID, mainly located in the pDMN and frontal lobe. Significant interaction was found between CSVD-SID and BDNF genotype on GMV.

Grey matter alterations in patients with Parkinson′s disease with different sleep disorders / 中华神经科杂志

Objective:To investigate the grey matter alterations of Parkinson′s disease (PD) patients with and without sleep disorders, and to explore the relationship between different sleep-related problems and clinical variables as well as grey matter volume (GMV) in PD.Methods:Forty-six PD patients and 38 healthy controls (HCs) were recruited from January 2018 to December 2021 in the Department of Neurology, Beijing Hospital. PD patients were divided into PD with sleep disorders (PD-S, n=26) and PD without sleep disorders (PD-nS, n=20) subgroups (cutoff points of 82 for Parkinson′s Disease Sleep Scale or less than 5 for each item was considered as an indicator of substantial sleep disorder). The Mini-Mental State Examination (MMSE), the third part of the Unified Parkinson′s Disease Rating Scale (UPDRS-Ⅲ), Hamilton Rating Scale for Anxiety (HAMA), Hamilton Rating Scale for Depression (HAMD), Non-Motor Symptoms Questionnaire (NMSQ), and Parkinson′s Disease Questionnaire-39 (PDQ-39) were used to evaluate cognitive function, motor symptoms, anxious and depressive symptoms, non-motor symptoms, and the quality of life of the patients. Optimized voxel-based morphometry was applied to the magnetic resonance imaging brain images in all participants,and multiple linear regression analysis was used to test the correlation between GMV and sleep quality in patients with PD. Results:Compared with the HCs, PD-nS patients showed decreased GMV in bilateral limbic lobe, parahippocampal gyrus, amygdala, cingulate gyrus, hippocampus, right cerebellum, bilateral frontotemporal lobe, bilateral occipital lobe and the left parietal lobe. PD-S group exhibited reduced GMV in bilateral limbic lobe, parahippocampal gyrus, amygdala, right cerebellum, bilateral frontotemporal lobe and bilateral parietal-occipital lobe, compared to the HCs. Compared with PD-nS, PD-S patients revealed higher depressive (HAMD score: 12.19±5.59 vs 6.95±3.19, t=-4.01, P<0.001), anxious (HAMA score: 12.04±5.32 vs 7.25±4.68, t=-3.18, P=0.003), and non-motor symptoms scores (NMSQ score: 12.92±5.18 vs 9.90±4.10, t=-2.14, P=0.038), poorer quality of life (PDQ-39 score: 35.31±22.01 vs 22.40±9.00, t=-2.71, P=0.010), and reduced GMV in the left insula, frontal, and parietal lobe ( P<0.001, uncorrected, cluster>100). There was a marked relationship between sleep quality and the reduced GMV of the right medial temporal gyrus (β=0.006, 95% CI 0.002-0.010, P=0.003), left middle frontal gyrus (β=0.006, 95% CI 0.002-0.010, P=0.002), the right cerebellum (β=0.014, 95% CI 0.005-0.023, P=0.003), and the right medial occipital gyrus (β=0.017, 95% CI 0.011-0.024, P<0.001). Significant grey matter changes were associated with nocturnal restlessness, mainly within the left limbic lobe, bilateral occipital lobe, the right cerebellum, and parietal lobe (β=0.008, 95% CI 0.006-0.010, P<0.001). Furthermore, nocturia in PD was related to certain grey matter atrophy, including bilateral limbic lobe, the right inferior parietal gyrus, and bilateral frontal lobe (β=0.010, 95% CI 0.008-0.013, P<0.001). The symptom of daytime dozing was correlated with GMV reduction in the right occipital lobe, the left temporal lobe (β=0.014, 95% CI 0.010-0.019, P<0.001). There were also several compensatory brain regions, including bilateral frontal lobe, the left limbic lobe and cingulate ( P<0.001, uncorrected, cluster>60). Conclusions:Sleep disturbance is common in PD, which is related to the anxious and depressive symptoms, non-motor symptoms, and the quality of life. PD patients with different sleep disorders show grey matter alterations in severeal brain regions, which are associated with sleep quality, nocturnal restlessness, psychosis, and daytime dozing.

Cortical and Subcortical Grey Matter Abnormalities in White Matter Hyperintensities and Subsequent Cognitive Impairment / 神经科学通报·英文版

Grey matter (GM) alterations may contribute to cognitive decline in individuals with white matter hyperintensities (WMH) but no consensus has yet emerged. Here, we investigated cortical thickness and grey matter volume in 23 WMH patients with mild cognitive impairment (WMH-MCI), 43 WMH patients without cognitive impairment, and 55 healthy controls. Both WMH groups showed GM atrophy in the bilateral thalamus, fronto-insular cortices, and several parietal-temporal regions, and the WMH-MCI group showed more extensive and severe GM atrophy. The GM atrophy in the thalamus and fronto-insular cortices was associated with cognitive decline in the WMH-MCI patients and may mediate the relationship between WMH and cognition in WMH patients. Furthermore, the main results were well replicated in an independent dataset from the Alzheimer's Disease Neuroimaging Initiative database and in other control analyses. These comprehensive results provide robust evidence of specific GM alterations underlying WMH and subsequent cognitive impairment.

Volume quantification of normal brain tissues based on the magnetic resonance T1 images / 解剖学报

Objective: By manual and automatic segmentation, the total volume, cerebrospinal fluid volume and white matter volume of normal human brain were obtained, and the differences between different genders and the patterns of changes with age were analyzed. At the same time, we give the software and parameters that can get better result. Methods: The rough brain mask was obtained by software automatic segmentation and it would be refined manually. Then the brain masks would be divided into gray matter, white matter and cerebrospinal fluid by FSL-FAST, and finally statistical analysis was performed with SPSS 25.0 software. Results: The total brain volume of normal Chinese adults was about 1263.24 ml, and the total brain volume of males (1313.84 ml) was lager than the total volume of female brain (1173.11 ml). The difference was statistically significant. There were significant differences in total volume, gray matter, white matter and cerebrospinal fluid volume among different age groups. And there was no correlation between the age and the ratio of gray matter white matter. The total brain volume, gray matter, and white matter volume of males were larger than those of females, and as the age increases, the decline trend of these three sets of data is similar. The changes of total brain volume, gray matter volume and white matter volume with age were also similar in females. They reached their maximum at about 50 years of age, and then the volume gradually decreased. Conclusion: The study on the changes of brain volume and the volume of gray matter, white matter and cerebrospinal fluid with age in different sexes can be used as a basis for identifying the changes of brain volume caused by diseases or the age.

Long-Term Grey Matter Changes in First Episode Psychosis: A Systematic Review

OBJECTIVE: To determine possible progressive changes of the grey matter at the first stages of the schizophrenia spectrum disorders, and to determine what regions are involved in these changes. METHODS: We searched the literature concerning studies on longitudinal changes in grey matter in first-episode psychosis using magnetic resonance imaging, especially studies with an interval between scans of more than a year. Only articles published before 2018 were searched. We selected 19 magnetic resonance imaging longitudinal studies that used different neuroimaging analysis techniques to study changes in cerebral grey matter in a group of patients with a first episode of psychosis. RESULTS: Patients with first episode of psychosis showed a decrease over time in cortical grey matter compared with a group of control subjects in frontal, temporal (specifically in superior regions), parietal, and subcortical regions. In addition to the above, studies indicate that patients showed a grey matter decrease in cerebellum and lateral ventricles volume. CONCLUSION: The results suggest a decrease in grey matter in the years after the first episode of psychosis. Furthermore, the results of the studies showed consistency, regardless of the methods used in their analyses, as well as the time intervals between image collections.

Diagnostic value of multimodal MRI in patients with temporal lobe epilepsy caused by dual pathology / 实用放射学杂志

Objective To investigate the diagnostic value of multimodal MRI for dual pathology (DP)in temporal lobe epilepsy (TLE).Methods The methods of voxel based morphometry (VBM)and voxel based analysis (VBA)had been employed to study the difference between 36 patients (20 cases left group and 16 cases right group)with TLE caused by DP and 36 healthy subjects on the grey matter (GM)volume,exponential apparent diffusion coefficient (eADC)and cerebral blood flow (CBF)value.The corresponding statistical study had also been conducted.Results There were significant statistical differences (FDR correction,P=0.001)between healthy subj ects and patients on the GM volume,eADC and CBF value.Those values decreased with diseased laterality and wider range in functional imaging.These overlaying abnormal brain regions were located in the temporal pole (superior temporal gyrus), temporal pole (middle temporal gyrus),middle temporal gyrus,inferior temporal gyrus,fusiform gyrus,hippocampus and parahippocampal gyrus which represented in all examination results.Conclusion The combined findings of multimodal MRI can improve the localization ability of seizure focus in TLE,which caused by DP,before surgery.

Progressive Grey Matter Volume Changes in Patients with Schizophrenia over 6 Weeks of Antipsychotic Treatment and Their Relationship to Clinical Improvement / 神经科学通报·英文版

Cross-sectional and longitudinal studies have identified widespread and progressive grey matter volume (GMV) reductions in schizophrenia, especially in the frontal lobe. In this study, we found a progressive GMV decrease in the rostral medial frontal cortex (rMFC, including the anterior cingulate cortex) in the patient group during a 6-week follow-up of 40 patients with schizophrenia and 31 healthy controls well-matched for age, gender, and education. The higher baseline GMV in the rMFC predicted better improvement in the positive score on the Positive and Negative Syndrome Scale (PANSS), and this might be related to the improved reality-monitoring. Besides, a higher baseline GMV in the posterior rMFC predicted better remission of general symptoms, and a lesser GMV reduction in this region was correlated with better remission of negative symptoms, probably associated with ameliorated self-referential processing and social cognition. Besides, a shorter disease course and higher educational level contributed to better improvement in the general psychopathological PANSS score, and a family history was negatively associated with improvement of the negative and total PANSS scores. These phenomena might be important for understanding the neuropathological mechanisms underlying the symptoms of schizophrenia and for making clinical decisions.

Grey matter concentration revealed by voxel-based morphometry in individuals with cognitive vulnerability to depression / 中南大学学报(医学版)

Objective:To explore the grey matter concentration in individuals with cognitive vulnerability to depression.Methods:Thirty individuals with cognitive vulnerability to depression and thirty age-and gender-matched healthy controls were enrolled in this study,and they were subjected to magnetic resonance imaging (MRI) examination.The grey matter concentration differences were compared between the two groups by using voxel-based morphometry (VBM) following MRI.Results:Individuals with cognitive vulnerability to depression showed significantly lower grey matter density in bilateral insular,left cerebellum,right supplementary motor area,and left precentral gyrus than those in the healthy controls,while the healthy controls showed significantly lower grey density in the right inferior frontal gyrus,right middle frontal gyrus,and left cuneus than those in the individuals with cognitive vulnerability to depression.Conclusion:Structural brain abnormalities in individuals with cognitive vulnerability to depression might be the neural basis for cognitive vulnerability to depression.

Changes of cerebral gray matter pre- and post-treatment in patients with schizophrenia / 上海交通大学学报（医学版）

Objective · To observe the changes of cerebral gray matter pre- and post-treatment with short term drugs in patients with schizophrenia. Methods · T1-weighted brain MRIs were obtained on a 3T scanner in 21 controls and 27 subjects with schizophrenia who were not given antipsychotic medication. The controls and 21 schizophrenia patients received the second scan after 8 weeks of antipsychotic treatment. Voxel-based morphometry (VBM) were used to investigate the differences in gray matter (GM), mainly about the regional GM volumes. Results · GM volumes were significantly smaller in the patient group than those of healthy controls in left cerebellum posterior lobe , left and right parahippocampalgyrus, left middle temporal gyrus(P=0.000, voxels>50). GM volumes extensively decreased after 8 weeks of antipsychotic-treatment compared with pre-treatment in the superior, middle, and inferior temporal gyri, superior,middle and inferior frontal gyri, parahippocampa gyri, cingulate gyri, right supramarginal gyrus, right cerebellum posterior lobe, and right lingual gyrus(P=0.000, voxels>50). Conclusion · Short term antipsychotic treatment (8 weeks) may have adverse effects on the gray matter of patients with acute schizophrenia by reducing the volume of gray matter.

Abnormal gray matter volume and regional homogeneity of resting fMRI in patients with schizophrenia and obsessive-compulsive disorder / 中国心理卫生杂志

Objective:To explore the traits of gray matter volume (GMV) and regional homogeneity (ReHo) in patients with schizophrenia and obsessive-compulsive disorder (OCD) by magnetic resonance imaging technique (MRI).Methods:Twenty-two patients with schizophrenia,20 patients with OCD and 23 normal controls were recruited in this study.All of the patients satisfied diagnostic criteria from the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition (DSM-Ⅳ),patients and the normal controls were well matched for gender,age and years of education.All subjects received structural magnetic resonance imaging (MRI) scans and resting functional MRI scans.The ANOVA and post hoe anolysis were used to compoare the GMV and Relto differences among the subjects.Results:Compared with the normal controls,patients with schizophrenia and OCD had common GMV loss in the right anterior cingulate (P ＜ 0.001,uncorrected),while lower ReHo in the left cuneus(P ＜ 0.001,uncorrected) and higher ReHo in the left upper medial frontal gyrus(P ＜ 0.001,uncorrected) respectively.Conclusion:It suggests that patients with schizophrenia and OCD share common structural changes and functional alterations,which could attribute so many similarities between the two diseases.

Association of Temporal Lobe Atrophy and Psychosis in Patients with Alzheimer's Disease

OBJECTIVE: The purpose of this study is to investigate the difference on regional volume in temporal lobe between Alzheimer's disease patients with psychosis (AD+P) and Alzheimer's disease patients without psychosis (AD-P). METHODS: Altogether, 24 AD+P and 25 AD-P matched age, gender, and clinical dementia rating sum of box (CDR-SOB) were include from a Memory impairment clinics of Pusan National University Hospital in Korea. AD+P were diagnosed according to Jeste and Finkel's proposed diagnostic criteria for psychosis of Alzheimer's disease. Grey matter volume of temporal lobe was measured with 3-tesla magnetic resonance imaging and freesufer analysis. Analysis of variance was used to investigate the association between temporal lobe and AD+P after controlling age, gender, education years, CDR-SOB and total intracranial volume. RESULTS: We found an association between AD+P and reduced grey matter volume in total temporal lobe as well as in specific temporal regions such as left middle temporal lobe, left inferior temporal lobe, both hippocampus and both fusiform. CONCLUSION: Our findings suggest that AD+P are associated with reduced grey matter volume of temporal lobe.

Preliminary voxel-based morphometry analysis of grey matter abnormalities in early stage of bipolar disorder I / 实用放射学杂志

Objective To estimate brain grey matter volume changes and location of abnormal brain regions cerebrum in early stage of bipolar disorder I (BD),in order to provided objective basis for diagnosing early stages BD.Methods 1 7 cases of BD with duration less than 2 years and 1 7 normal controls were recruited in this study.The volumetric difference of grey matter between two groups were analyzed by using voxel-based morphometry(VBM)software.Statistical threshold was voxel> 100,P <0.001 (uncor-rected).Results Compared to the normal controls,the grey matter volume of BD patients decreased in the left dorcial anterior cingu-late cortex(ACC),left insular,right sub-genu ACC,left superior temporal cortex,bilateral hippocampus-parahippocampus-amydala and left posterior lobe of cerebellum(P <0.001).Conclusion The grey matter volume of early stage BD patients is decreased,main-ly locating in the bilateral limbic system,the superior temporal gyrus and the cerebellar cortex,which probably is the morphological appearance of pathomechanism in early stages of BD.

Abnormal grey matter changes in first-episode antipsychotic-na?ve patients with adolescent-onset schizophrenia / 中国神经精神疾病杂志

Objective To investigate gray matter structural damage in first-episode antipsychotic-na?ve patients with adolescent-onset schizophrenia. Methods Twenty-six patients with schizophrenia and 26 healthy controls were scanned by using GE 3.0T magnetic resonance imaging in order to explore brain gray matter volume (GMV) changes with registration techniques based on the latest morphological deformation field theory. The correlation of gray matter volume abnormalities with clinical severity was also analyzed. Results Compared with healthy controls, patients with adoles-cent-onset schizophrenia showed significant reduction in GMV in the left parietal lobe, parahippocampal gyrus and right cerebellar pyramis. GMV of the left parahippocampal gyrus is significantly correlated with PANSS paranoid scores (r=-0.49, P=0.02). Conclusions There is structural abnormality in GM in parahippocampal-parietal-cerebellar in pa-tients with adolescent-onset schizophrenia and the severity of paranoid symptoms is related to the reduced GMV in the left parahippocampal gyrus.

Functional MRI study of the brain with malformations of cortical development / 中华放射学杂志

Objective To explore the patterns of motor and linguistic activation in cortical and its correlations with abnormal gray matter in patients with malformations of cortical development(MCD)and epilepsy.Methods Seven MCD patients with epilepsy(2 patients with focal cortical dysplasia,2 heterotopia,2 schizencephaly,and 1 polymicrogyria)underwent blood-oxygen-level-dependent(BOLD)functional MRI(fMRI)in a 3 T MR scanner when practicing bilateral fingers tapping,toes twisting,verb generation,and picture naming.Functional images were post-processed by using SPM 5 software based on a general linear model(GLM)to generate activations above a uniform threshold with the cluster size (≥30 voxels,P ＜0.001 corrected).The activations were recognized and classified by two experienced neuroradiologists,and then compared with that in abnormal gray matter.Results The clusters and intensities of motor activations were mainly located in the sensormotor cortex(SMC)and premotor area (PMA).In linguistic tasks,activations produced by verb generation were found in language-associated cortical regions and PMA with higher activation in Wemicke area,picture naming significantly in the visual cortex,and language in Broca area.Combination of the two linguistic tasks produced significant clusters and intensities in language cortex.For MCD patients with abnormal cortical abnormalities,motor and language task could produce neuronal activities within normal as well as abnormal cortex regions.In 6 patients who underwent resective surgery,epileptic seizures decreased significantly,and the follow-up images demonstrated no new neurological dysfunctions and cognitive impairments.Conclusions fMRI can visualize neuronal activities in patients with MCD and epilepsy and demonstrate the motor and linguistic activations occurring in normal and abnormal gray matter.It should be cautious for surgery in patient with MCD and epilepsy.