scholarly journals Gray Matter Atrophy And Corresponding Impairments In Connectivity In Patients With Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Author(s):  
Yuanyuan Guo ◽  
Xinyi Lv ◽  
Juanjuan Zhang ◽  
Chenglong Li ◽  
Ling Wei ◽  
...  

Abstract Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune disease that is commonly accompanied by cognitive impairment and various neurological and psychiatric symptoms, advanced image analyses help explore the pathogenesis of this disease. Therefore, this study aimed to explore specific structural and functional alterations and their relationship with the clinical symptoms of anti-NMDAR encephalitis. In this study, twenty-two patients with anti-NMDAR encephalitis after the acute stage and 29 controls received cognitive assessments and magnetic resonance imaging. Grey matter atrophy was measured using voxel-based morphometry, and functional alterations in abnormal regions were subsequently investigated using resting state functional connectivity (RSFC). Finally, correlation analyses were performed to explore the associations between imaging alterations and cognitive assessments. The patients demonstrated significant gray matter atrophy in the bilateral triangle part of the inferior frontal gyrus (triIFG.L and triIFG.R) and right precuneus, decreased RSFC between triIFG.L and bilateral Heschl gyrus (HES), decreased RSFC between triIFG.R and HES.R, decreased RSFC between right precuneus and left cerebellum, and increased RSFC between triIFG.R and left superior frontal gyrus. Further correlation analyses showed that the gray matter volume in triIFG.R and decreased RSFC between triIFG.L and HES.R were associated with decreased memory scores, whereas decreased RSFC between triIFG.R and HES.R was marginally correlated with the disease course in patients. In conclusion, this study suggests that cognitive impairments in patients with anti-NMDAR encephalitis may be mainly associated with gray matter atrophy and abnormal RSFC in the triIFG. These findings provide new insights into anti-NMDAR encephalitis pathogenesis and help explore potential treatments.

2021 ◽  
Vol 39 (4) ◽  
pp. 340-342
Author(s):  
Seok-Yeol Yang ◽  
Wooryang Byun ◽  
Sung-Pa Park ◽  
Jong-Geun Seo

Anti-N-methyl-D aspartate receptor (NMDAR) encephalitis is often accompanied with ovarian teratomas. It has a variety of clinical manifestations including psychiatric symptoms, seizure, and motor dysfunctions. The diagnosis can be definite when clinical symptoms are present and anti-NMDAR antibodies in cerebrospinal fluid are detected. However, in patients with suspected anti-NMDAR encephalitis with teratomas, early surgery may help the clinical outcome even if the antibodies are initially negative. The authors report a patient whose clinical symptoms improved significantly after early removal of teratoma.


2020 ◽  
Author(s):  
Paul Faulkner ◽  
Susanna Lucini Paioni ◽  
Petya Kozhuharova ◽  
Natasza Orlov ◽  
David J. Lythgoe ◽  
...  

AbstractCigarette smoking is still the largest contributor to disease and death worldwide. Successful cessation is hindered by decreases in prefrontal glutamate concentrations and gray matter volume due to daily smoking. Because non-daily, intermittent smoking also contributes greatly to disease and death, understanding whether infrequent tobacco use is associated with reductions in prefrontal glutamate concentrations and gray matter volume may aid public health. Eighty-five young participants (41 non-smokers, 24 intermittent smokers, 20 daily smokers, mean age ~23 years old), underwent 1H-magnetic resonance spectroscopy of the medial prefrontal cortex, as well as structural MRI to determine whole-brain gray matter volume. Compared to non-smokers, both daily and intermittent smokers exhibited lower concentrations of glutamate, creatine, N-acetylaspartate and myo-inositol in the medial prefrontal cortex, and lower gray matter volume in the right inferior frontal gyrus; these measures of prefrontal metabolites and structure did not differ between daily and intermittent smokers. Finally, medial prefrontal metabolite concentrations and right inferior frontal gray matter volume were positively correlated, but these relationships were not influenced by smoking status. This study provides the first evidence that both daily and intermittent smoking are associated with low concentrations of glutamate, creatine, N-acetylaspartate and myo-inositol, and low gray matter volume in the prefrontal cortex. Future tobacco cessation efforts should not ignore potential deleterious effects of intermittent smoking by considering only daily smokers. Finally, because low glutamate concentrations hinder cessation, treatments that can normalize tonic levels of prefrontal glutamate, such as N-acetylcysteine, may help intermittent and daily smokers to quit.


2020 ◽  
Vol 11 ◽  
Author(s):  
Jiao Liu ◽  
Liyan Chen ◽  
Jing Yang ◽  
Lan Wang ◽  
Huifang Shang ◽  
...  

Objectives: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and sporadic Creutzfeldt–Jakob disease (sCJD) share similar clinical features. Here, we present two unusual cases of anti-NMDAR encephalitis who were misdiagnosed as sCJD at first.Methods: We described two patients' clinical manifestations, as well as the string of symptomatological evolution, treatments, and follow-up results.Results: Our patients presented with rapidly progressive dementia, memory problems, psychiatric symptoms, and movement disorders, and we considered all these symptoms as a presenting feature of sCJD at first, but the cerebrospinal fluid examination showed positive results for both the 14-3-3 protein and antibodies against NMDAR. Immunomodulatory treatment led to a resolution of these deficits, and both of them remained in remission after treatment.Conclusion: Anti-NMDAR encephalitis can present with rapidly progressive cognitive decline, and sometimes laboratory investigations can be misleading. The examination for the presence of NMDAR antibodies is necessary, even with the presence of 14-3-3 protein. Early immunomodulatory therapy should be considered, especially for patients with high titers of NMDAR antibodies.


Author(s):  
Kai-Lun Cheng ◽  
Li-Han Lin ◽  
Po-Cheng Chen ◽  
Pi-Ling Chiang ◽  
Yueh-Sheng Chen ◽  
...  

Purpose: Risk of falls is a common sequela affecting patients with Parkinson’s disease (PD). Although motor impairment and dementia are correlated with falls, associations of brain structure and cognition deficits with falls remain unclear. Material and Methods: Thirty-five PD patients with dementia (PDD), and 37 age- and sex-matched healthy subjects were recruited for this study. All participants received structural magnetic resonance imaging (MRI) scans, and disease severity and cognitive evaluations. Additionally, patient fall history was recorded. Regional structural differences between PDD with and without fall groups were performed using voxel-based morphometry processing. Stepwise logistic regression analysis was used to predict the fall risk in PDD patients. Results: The results revealed that 48% of PDD patients experienced falls. Significantly lower gray matter volume (GMV) in the left calcarine and right inferior frontal gyrus in PDD patients with fall compared to PDD patients without fall were noted. The PDD patients with fall exhibited worse UPDRS-II scores compared to PDD patients without fall and were negatively correlated with lower GMV in the left calcarine (p/r = 0.004/−0.492). Furthermore, lower GMV in the left calcarine and right inferior frontal gyrus correlated with poor attention and executive functional test scores. Multiple logistic regression analysis showed that the left calcarine was the only variable (p = 0.004, 95% CI = 0.00–0.00) negatively associated with the fall event. Conclusions: PDD patients exhibiting impaired motor function, lower GMV in the left calcarine and right inferior frontal gyrus, and notable cognitive deficits may have increased risk of falls.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Chiun-Chieh Yu ◽  
Hsiu-Ling Chen ◽  
Meng-Hsiang Chen ◽  
Cheng-Hsien Lu ◽  
Nai-Wen Tsai ◽  
...  

Introduction. Systemic inflammation with elevated oxidative stress causing neuroinflammation is considered a major factor in the pathogenesis of Parkinson’s disease (PD). The interface between systemic circulation and the brain parenchyma is the blood-brain barrier (BBB), which also plays a role in maintaining neurovascular homeostasis. Vascular cell adhesion molecule-1 (VCAM-1) and microRNAs (miRNAs) regulate brain vessel endothelial function, neoangiogenesis, and, in turn, neuronal homeostasis regulation, such that their dysregulation can result in neurodegeneration, such as gray matter atrophy, in PD. Objective. Our aim was to evaluate the associations among specific levels of gray matter atrophy, peripheral vascular adhesion molecules, miRNAs, and clinical disease severity in order to achieve a clearer understanding of PD pathogenesis. Methods. Blood samples were collected from 33 patients with PD and 27 healthy volunteers, and the levels of VCAM-1 and several miRNAs in those samples were measured. Voxel-based morphometry (VBM) analysis was performed using 3 T magnetic resonance imaging (MRI) and SPM (Statistical Parametric Mapping software program). The associations among the vascular parameter, miRNAs, gray matter volume, and clinical disease severity measurements were evaluated by partial correlation analysis. Results. The levels of VCAM-1, miRNA-22, and miRNA-29a expression were significantly elevated in the PD patients. The gray matter volume atrophy in the left parahippocampus, bilateral posterior cingulate gyrus, fusiform gyrus, left temporal gyrus, and cerebellum was significantly correlated with increased clinical disease severity, the upregulation of miRNA levels, and increased vascular inflammation. Conclusion. Patients with PD seem to have abnormal levels of vascular inflammatory markers and miRNAs in the peripheral circulation, and these levels are correlated with specific brain volume changes. This study reinforces the associations among peripheral inflammation, the BBB interface, and gray matter atrophy in PD and further demonstrates that BBB dysfunction with neurovascular impairment may play an important role in PD progression.


SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A116-A116
Author(s):  
C E Meinhausen ◽  
J R Vanuk ◽  
M A Grandner ◽  
W D Killgore

Abstract Introduction Sleep deprivation has often been associated with decreased cognitive control, including deficits in the ability to sustain attention. Psychomotor vigilance speed slows following a period of fatigue, and can lead to disastrous results in daily life. In order to determine the brain areas correlated with reduced psychomotor vigilance speed, as a result of diminished sleep, a voxel-based morphometry analysis was performed prior to a period of monitored sleep deprivation. The mean speed of response time during the final 17 hours of a 29-hour sleep deprivation was then measured with the Psychomotor Vigilance Test (PVT), a reaction-timed task that measures the speed participants respond to a visual stimulus. Methods 45 healthy individuals (male=23 female=22) between the ages of 20-43 years (M=25.4 SD=5.6) participated in the study. Structural neuroimaging data were collected using a T3 magnetic resonance imaging scanner following a typical night’s sleep. Mean PVT speed was monitored with an hourly 10-minute PVT assessment during a monitored overnight sleep deprivation session. Speed was defined as the reciprocal of reaction time (1/RT). Results PVT speed was negatively correlated with grey matter volume (P<.05 FWE-corrected) in the prefrontal cortex, specifically the right posterior inferior frontal gyrus (p=.030; MNI coordinates = 36, 12, 26). Conclusion Our findings indicate that gray matter within the right posterior inferior frontal gyrus is greater in individuals who are more vulnerable to slowing of PVT responses during an overnight period of sleep deprivation. These findings suggest that inter-individual differences in the ability to sustain psychomotor vigilance during sleep loss may be related to increased gray matter in the right lateral prefrontal cortex and could have implications for understanding the neurobiological substrates of vulnerability and resilience to sleep loss. Support  


2021 ◽  
Vol 14 ◽  
Author(s):  
Junyan Wang ◽  
Penghong Liu ◽  
Aixia Zhang ◽  
Chunxia Yang ◽  
Sha Liu ◽  
...  

To identify the common and specific structural basis of bipolar depression (BD) and unipolar depression (UD) is crucial for clinical diagnosis. In this study, a total of 85 participants, including 22 BD patients, 36 UD patients, and 27 healthy controls, were enrolled. A voxel-based morphology method was used to identify the common and specific changes of the gray matter volume (GMV) to determine the structural basis. Significant differences in GMV were found among the three groups. Compared with healthy controls, UD patients showed decreased GMV in the orbital part of the left inferior frontal gyrus, whereas BD patients showed decreased GMV in the orbital part of the left middle frontal gyrus. Compared with BD, UD patients have increased GMV in the left supramarginal gyrus and middle temporal gyrus. Our results revealed different structural changes in UD and BD patients suggesting BD and UD have different neurophysiological underpinnings. Our study contributes toward the biological determination of morphometric changes, which could help to discriminate between UD and BD.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yiran Zhang ◽  
Yun Yang ◽  
Licheng Zhu ◽  
Qing Zhu ◽  
Yuxi Jia ◽  
...  

Background: Depression is a major psychiatric disorder and the leading cause of disability worldwide. Previous evidence suggested certain pattern of structural alterations were induced by major depression disorder (MDD) with heterogeneity due to patients' clinical characteristics and proposed that early impairment of fronto-limbic-striatal circuit was involved. Yet the hypothesis couldn't be replicated fully. Accordingly, this study aimed to validate this hypothesis in a new set of first-episode, drug naïve MDD patients and further explore the neuroimaging biomarker of illness severity using whole-brain voxel-based morphometry (VBM).Materials and Methods: A total of 93 participants, 30 patients with first-episode medication-naïve MDD, and 63 healthy controls were enrolled in the study. VBM was applied to analyze differences in the gray matter volume (GMV) between these two groups. The correlation between the GMV of the identified brain regions and the severity of clinical symptoms quantified by the Hamilton Depression Scale (HAMD) was further conducted in the post-hoc analysis to confirm the role of GMV structural alteration in clinical symptoms.Results: Our results revealed that the brain gray matter volume of the prefrontal lobe, limbic system, striatum, cerebellum, temporal lobe, and bilateral lingual gyri were significantly decreased in MDD patients compared with healthy controls. Besides, the HAMD scores were negatively correlated with GMV of the right insula and positively correlated with that of the right lingual gyrus.Conclusions: Our findings provide robust evidence that gray matter structural abnormalities within the prefronto-limbic-striatal circuit are implicated in the pathophysiology of MDD at an early stage without confounding influence of medication status. Besides, our data suggest that the cerebellum, lingual gyrus, and fusiform gyrus should also be integrated into the brain alterations in MDD. Future synthesis of individual neuroimaging studies and more advanced statistical analysis comparing subfields of the aforementioned regions are warranted to further shed light on the neurobiology of the disease and assist in the diagnosis of this burdensome disorder.


2021 ◽  
Author(s):  
MJ Grubisha ◽  
T Sun ◽  
SL Erickson ◽  
L Eisenman ◽  
S Chou ◽  
...  

ABSTRACTNormally, dendritic size is established prior to adolescence then remains relatively constant into adulthood due to a homeostatic balance between growth and retraction pathways. However, schizophrenia is characterized by accelerated reductions of cerebral cortex gray matter volume and onset of clinical symptoms during adolescence, with reductions in layer 3 pyramidal neuron dendritic length, complexity, and spine density identified in multiple cortical regions postmortem. Nogo receptor 1 (NGR1) activation of the GTPase RhoA is a major pathway restricting dendritic growth in the cerebral cortex. We show that the NGR1 pathway is stimulated by OMGp and requires the Rho guanine nucleotide exchange factor, Kalirin-9 (KAL9). Using a genetically encoded RhoA sensor, we demonstrate that a naturally occurring missense mutation in Kalrn, KAL-PT, that was identified in a schizophrenia cohort, confers enhanced RhoA activitation in neuronal dendrites compared to wildtype KAL. In mice containing this missense mutation at the endogenous locus there is an adolescent-onset reduction in dendritic length and complexity of layer 3 pyramidal neurons in the primary auditory cortex. Tissue density of dendritic spines was also reduced. Early adult mice with these structural deficts exhibited impaired detection of short gap durations. These findings provide a neuropsychiatric model of disease capturing how a mild genetic vulnerability may interact with normal developmental processes such that pathology only emerges around adolescence. This interplay between genetic susceptibility and normal adolescent development, both of which possess inherent individual variability, may contribute to heterogeneity seen in phenotypes in human neuropsychiatric disease.SIGNIFICANCE STATEMENTDendrites are long branching processes on neurons that contain small processes called spines that are the site of connections with other neurons, establishing cortical circuitry. Dendrites have long been considered stable structures, with rapid growth prior to adolescence followed by maintenance of size into adulthood. However, schizophrenia is characterized by accelerated reductions of cortical gray matter volume and onset of clinical symptoms during adolescence, with reductions in dendritic length present when examined after death. We show that dendrites retain the capacity for regression, and that a mild genetic vulnerability in a regression pathway leads to onset of structural impairments in previously formed dendrites across adolescence. This suggests that targeting specific regression pathways could potentially lead to new therapeutics for schizophrenia.


Sign in / Sign up

Export Citation Format

Share Document