Bilateral Occipital Regions Research Articles

Case of Dementia with Lewy Bodies in Young Patient with Family History

AbstractBackgroundDementia with Lewy bodies (DLB) is a neurodegenerative disorder characterized by cognitive decline, fluctuating attention, visual hallucinations, and sleep disorders, sometimes with signs of parkinsonism. Pathological evaluation reveals deposition of abnormally metabolized alpha‐synuclein, termed Lewy bodies. Clinical signs of DLB may be misdiagnosed in young patients with coexisting psychiatric disorders. A 43‐year‐old left‐handed man with a history of chronic paranoid schizophrenia, controlled with haloperidol, paroxetine, quetiapine, and clonazepam, presented with a 3‐year history of declining short‐term memory and concentration. He had a twin brother who was diagnosed with DLB and passed away at 40 years of age.MethodsThe patient was evaluated with serum laboratory tests to evaluate for metabolic abnormalities, infection, and heavy metal toxicity, including complete blood count, comprehensive metabolic panel, vitamin B12, folate, thyroid stimulating hormone, copper, and zinc. MRI Brain and subsequent PET‐FDG Brain were also conducted.ResultsThe results of the serum laboratory tests were all normal. MRI Brain was notable for bilateral parieto‐occipital atrophy and minimal chronic microvascular changes. PET‐FDG Brain revealed hypometabolism in bilateral parietal and occipital regions, with a cingulate island sign, indicative of advanced dementia with Lewy bodies.ConclusionDementia with Lewy bodies is a form of dementia that can sometimes present at an early age, and can be associated with psychological comorbidities and genetic risk factors. Further study of this case will include screening for mutations in the GBA gene, which encodes the enzyme beta‐glucocerebrosidease, which is the most frequent genetic association with dementia with Lewy bodies. Counseling on diagnosis and prognosis has been provided to the patient and his family, and he is being managed with rivastigmine 1.5mg twice daily to help slow down cognitive decline.

Characteristic features of electroencephalogram in a pediatric patient with GRIN1 encephalopathy

BackgroundThe number of reports on GRIN1 variants associated with neurodevelopmental phenotypes has increased in recent years. However, there are only two detailed reports on electroencephalography findings. Case studyWe had a case with severe global developmental delay, and exome sequencing revealed a novel de novo heterozygous variant of GRIN1. The patient's electroencephalography showed unique findings: paroxysmal fast activity—20–30 Hz beta waves, independently in the bilateral occipital regions, sometimes in a continuous manner—and prolonged alpha activity in the bilateral frontal regions, observed mainly during sleep, those findings were observed persistently. DiscussionThe electroencephalography findings of our case have not been reported in the past. Receptor hypofunction due to the GRIN1 variant and imbalance in excitatory/inhibitory transmission owing to the dysfunction of the N-methyl-D-aspartate receptors may be the mechanism for the global developmental delay, stereotyped movements, and development of paroxysmal fast activity in our case. Accumulation of additional case reports is needed to confirm the reproducibility of the electroencephalography findings for disease specificity.

Source Localization of Normal Variants Seen on EEG.

The EEG is an essential neurological diagnostic tool. EEG abnormalities can guide diagnosis and management of epilepsy. There are also distinctive EEG waveforms that are seen in healthy individuals. It is critical not to misinterpret these as abnormal. To emphasize the importance of these waveforms, we analyzed different normal variants via the source localization technology. This is a retrospective analysis of EEGs performed at the Duke University Hospital between June 2014 and Dec 2019. We selected samples of vertex waves, Mu, lambda, POSTS, wickets, and sleep spindles for analysis. EEG were imported to Curry 8 (Compumedics) to calculate the dipole and current density. The averaged head model from the Montreal Neurological Institute database was used for reconstruction. Thirty-four patient EEG samples were selected including five vertex, six Mu, four wicket, seven lambda, five POSTS, and seven spindles. Results from source localization showed that vertex waves are localized in the frontocentral area, whereas spindles in the deep midline central region. Mu were identified in the ipsilateral somatosensory cortex. Lambda and POSTS, on the other hand, had maximum results over the bilateral occipital region and wickets in the ipsilateral temporal lobe. Our results confirm and expand previous hypotheses. This allows us to speculate on the origin of these normal EEG variants. Although this study is limited by small sample size, lack of high-density EEG, and patient-specific MRI, our analysis provides an easily replicable three-dimensional visualization of these waveforms.

Altered gamma oscillations and beta–gamma coupling in drug-naive first-episode major depressive disorder: Association with sleep and cognitive disturbance

ObjectiveGamma oscillations contribute to the pathogenesis mechanisms of major depressive disorder (MDD) have been proposed, but gamma activity is not well characterized. This study is the first attempt to investigate the altered gamma oscillations in first-episode MDD, particularly the beta–gamma coupling, and to determine the potential symptomatic relationship with the identified gamma dysregulation. MethodsResting electroencephalography was recorded for 43 drug-naive first-episode MDD and 57 healthy control (HC) subjects. Integrated analysis of relative spectral power, weighted phase lag index, and phase–amplitude coupling (PAC) were utilized to reveal the alterations of gamma activities. Pearson's correlation was implemented to identify the relationship between altered gamma activities and the clinical depressive symptoms, which were categorized into four factors: anxiety somatization, retardation, cognitive disturbance, and sleep disturbance. ResultsCompared with HC subjects, MDD patients showed not only significantly decreased gamma powers in the left temporal and the bilateral occipital regions but also weakened gamma connectivity between the left hemisphere and the right frontal region. Furthermore, attenuated beta–gamma PAC of MDD patients was observed in the left temporal regions. Importantly, the suppression of left occipital mid- and high gamma oscillations were negatively correlated with sleep disturbance, while the deficits in left temporal beta–mid-gamma PAC and beta–high gamma PAC showed negative correlations with cognitive disturbance. LimitationsImportant limitations are the small sample size and the possible inclusion of bipolar depression in the MDD group. ConclusionsOur findings provide the first evidence that in first-episode MDD, aberrant gamma powers and beta–gamma coupling are associated with sleep and cognitive impairments, respectively, deepening our understanding of the physiological mechanisms underlying sleep and cognitive symptoms in first-episode MDD. Altered gamma oscillations emerge as promising biomarkers for diagnosing MDD.

Load-dependent functional connectivity deficits during visual working memory in first-episode psychosis

IntroductionAberrant network connectivity is a core deficit in schizophrenia and may underlie many of its associated cognitive deficits. Previous work in first-episode schizophrenia spectrum illness (FESz) suggests preservation of working memory network function during low-load conditions with dysfunction emerging as task complexity increases. This study assessed visual network connectivity and its contribution to load-dependent working memory impairments. MethodsMagnetoencephalography was recorded from 35 FESz and 28 matched controls (HC) during a lateralized change detection task. Impaired alpha desynchronization was previously identified within bilateral dorsal occipital (Occ) regions. Here, whole-brain alpha-band connectivity was examined using phase-locking (PLV) and bilateral Occ as connectivity seeds. Load effects on connectivity were assessed across participants, and PLV modulation within networks was compared between groups. ResultsOcc exhibited significant load modulated connectivity with six regions (FDR-corrected). HC exhibited PLV enhancement with load in all connections. FESz failed to show PLV modulation between right Occ and left inferior frontal gyrus, lateral occipito-temporal sulcus, and anterior intermediate parietal sulcus. Smaller PLVs in all three network connections during both memory load conditions were associated with increased reality distortion in FESz (FDR-corrected.) ConclusionExamination of functional connectivity across the visual working memory network in FESz revealed an inability to enhance communication between perceptual and executive networks in response to increasing cognitive demands. Furthermore, the degree of network communication impairment was associated with positive symptoms. These findings provide insights into the nature of brain dysconnectivity and its contribution to symptoms in early psychosis and identify potential targets for future interventions.

Correlations Between Structural Brain Abnormalities, Cognition and Electroclinical Characteristics in Patients With Juvenile Myoclonic Epilepsy.

ObjectiveTo explore the structural brain abnormality and its relationship with neuropsychological disorders and electroclinical characteristics in juvenile myoclonic epilepsy (JME) patients.MethodsSixty-seven patients diagnosed with JME and 56 healthy controls were enrolled. All subjects underwent MRI using T1-weighted 3D brain structural images with 1 mm thickness. Voxel-based morphometry (VBM) and surface-based morphometry (SBM) analyses were performed. They also underwent a series of neuropsychological tests to assess cognitive function. The correlation analyses were conducted between structural changes, neuropsychological outcomes, and electroclinical features.ResultsThe gray matter concentration (GMC) was decreased in the bilateral pre-central and post-central gyrus, right anterior cingulate gyrus, left posterior orbital region, bilateral occipital regions, bilateral hippocampus and bilateral caudate nucleus in the JME groups (corrected P < 0.05). The evaluation of gray matter volume (GMV) showed significant decrease respectively in bilateral pre-central and post-central gyrus, left paracentral lobule, left orbital gyrus, left amygdala, left basal ganglia and left thalamus of JME patients (P < 0.05). The cortex thicknesses of the right inferior temporal gyrus, right insular gyrus, and right cingulate gyrus had negative correlations with the disease duration significantly. At the same time, the whole-brain white matter volume was positively associated with the course of the disease (P < 0.05). Patients with persistent abnormal EEG discharges had significantly less whole-brain gray matter volume than JME patients with normal EEG (P = 0.03). Correlation analyses and linear regression analyses showed that, in addition to the gray matter volumes of frontal and parietal lobe, the temporal lobe, as well as the basal ganglia and thalamus, were also significantly correlated with neuropsychological tests' results (P < 0.05).ConclusionThe JME patients showed subtle structural abnormalities in multiple brain regions that were not only limited to the frontal lobe but also included the thalamus, basal ganglia, parietal lobe, temporal lobe and some occipital cortex, with significant involvement of the primary somatosensory cortex and primary motor cortex. And we significantly demonstrated a correlation between structural abnormalities and cognitive impairment. In addition, the course of disease and abnormal discharges had a specific negative correlation with the structural changes.

EEG-based investigation of the impact of room size and window placement on cognitive performance

This study investigated changes in scalp electroencephalography (EEG) features associated with short-term exposure to four virtual classroom designs, with different window placement and room dimensions. Participants engaged in five cognitive tests in each design condition: the Stroop Test, the Digit Span Test, the Benton Test, a Visual Memory Test, and an Arithmetic Test. Performance on the cognitive tests and EEG data were analyzed by contrasting various classroom design conditions. The cognitive test performance results showed no significant differences related to the design changes in the room studied. We computed frequency band-power and connectivity EEG features to identify changes in neural patterns associated to the different design conditions. A leave-one-out machine-learning classification scheme was implemented to assess the robustness of the EEG features, with the classification accuracy evaluation of the trained model iteratively performed against an unseen participant’s data for the test set. The feature selection and classification results located consistent differences in the EEG features that held predictive power (p<0.003) across participants in the different classroom design conditions: a. Neural vs One-Window, b. Neutral vs Two-Windows, c. Neutral vs Wide room. This effect was observed for the tasks that required short-term memory encoding, including the Digit Span Test (median test set classification accuracy: a. 53.8%, b. 51.3%), the Benton Test (a. 61.3%, b. 56.3%), and the Visual Memory Test (a. 55.0%, b. 57.5%, c. 61.3%). The most discriminative EEG features were primarily frequency band-power features, observed in bilateral occipital, parietal, and frontal regions in the theta (4-8 Hz) and alpha (8-12 Hz) frequency bands. The connectivity features reinforced these findings by showing that there were changes in the transfer of information from centro-parietal to frontal electrodes in the different classroom conditions. This study provides rigorous evidence that brain activity features during cognitive tasks are affected by the design elements of window placement and room dimensions in a virtual classroom. The ongoing development of this EEG-based approach has the potential to strengthen evidence-based design through evaluation of robust neurophysiological evidence.

Comprehensive Analysis of Brain Volume in REM Sleep Behavior Disorder with Mild Cognitive Impairment.

Rapid-eye-movement sleep behavior disorder (RBD) is a major risk factor for Parkinson's disease and dementia with Lewy bodies. More than a third of RBD patients have mild cognitive impairment (MCI), but their specific structural brain alterations remain poorly understood. This study aimed to investigate the local deformation and volume of gray and white matter tissue underlying MCI in RBD. Fifty-two idiopathic RBD patients, including 17 with MCI (33%), underwent polysomnography, neuropsychological, neurological, and magnetic resonance imaging assessments. MCI diagnosis was based on a subjective complaint, cognitive impairment on the neuropsychological battery, and preserved daily functioning. Forty-one controls were also included. Deformation-based morphometry (DBM), voxel-based morphometry (VBM), and regional volume analyses of the corpus callosum and cholinergic basal forebrain were performed. Multiple regression models were also computed using anatomical, cognitive (composite z scores), and motor parameters. Globally, patients with MCI displayed a widespread pattern of local deformation and volume atrophy in the cortical (bilateral insula, cingulate cortex, precuneus, frontal, temporal and occipital regions, right angular gyrus, and mid-posterior segment of the corpus callosum) and subcortical (brainstem, corona radiata, basal ganglia, thalamus, amygdala, and right hippocampus) regions compared to patients without MCI (DBM) or controls (DBM and VBM). Moreover, brain deformation (DBM) in patients were associated with lower performance in attention and executive functions, visuospatial abilities, and higher motor symptoms severity. The present study identified novel brain structural alterations in RBD patients with MCI which correlated with poorer cognitive performance. These results are consistent with those reported in patients with synucleinopathies-related cognitive impairment.

Abstract- Poster

1)Subdural hygromas are fluid collections within the subdural space that are clear or only slightly xanthochromic or blood tinged. They can be caused by mechanical trauma, meningeal or parameningeal infection, or venous congestion. Common presentation of SDH are fever, headache, nausea,vomiting, confusion.2)Here we report a 48 year old male who came with complaints of aggressiveness, forgetfulness, disturbed sleep. Further patient started developing dysarthria,inattention and memory was impaired.3)Neuroimaging- MRI brain showed subdural hygroma in bilateral fronto temporal parieto occipital region.4)Neurosurgery opinion obtained which is unremarkable5)Patient then started regaining his verbal fluency,memory and aggression settled in a span of 3 weeks.Although SDH is common among 1/3rd of patients with head injury/trauma,it is very rare that SDH presents with such features.References 1) SUBDURAL HYGROMA PRESENTING AS DEMENTIA WITH KLUVER-BUCY SYMPTOMS HARPREET S. DUGGAL, CHRISTODAY R.J.KHESS & S. HAQUE NIZAMIE2) Cognitive Impairment in the Elderly with Chronic Subdural Hematoma Hyun Hee Ye, MD, Jeong Ho Kim, MD, Yoon Suk Kim, MD,

Association of body mass index with brain structure and biomarkers of inflammation in cognitively unimpaired middle‐aged adults with and without evidence of β‐amyloid pathology

AbstractBackgroundObesity has been linked to brain atrophy and peripheral inflammation. However, the association between body mass index (BMI) and brain structure can be confounded by Alzheimer’s disease (AD) pathology‐related weight loss, and its association with neuroinflammation remains unknown. We explored associations of BMI with brain structure and biomarkers of peripheral and central nervous system inflammation in cognitively unimpaired middle‐aged adults with and without evidence of β‐amyloid (Aβ) pathology.MethodWe analyzed data from 385 ALFA+ study participants. We measured plasma C‐reactive protein (CRP), CSF p‐tau and t‐tau with the Elecsys® immunoassays and CSF Aβ42, Aβ40 and neuroinflammation biomarkers (sTREM2, GFAP, YKL40, S100 and IL6) with the exploratory Roche NeuroToolKit robust prototype assays. We used separated linear regression models to analyze associations of BMI with plasma CRP, CSF AD and neuroinflammation biomarkers, and mean cortical thickness (CTh) in a composite AD signature region. We explored voxelwise associations (p&lt;0.001, k=100) between BMI and gray matter volume (GMv) with SPM12. We stratified all analyses by Aβ status (defining positivity as Aβ42/40&lt;0.071) and adjusted by age, sex, systolic blood pressure, triglyceride, glycated hemoglobin and physical exercise levels.ResultBMI was positively associated with CRP levels in Aβ‐ and Aβ+ groups (p&lt;0.001). We found no significant associations between BMI and CSF AD or neuroinflammation biomarkers. BMI was negatively associated with mean CTh in the AD signature region in the Aβ‐ (p&lt;0.001), but not in the Aβ+ group (p=0.543). Voxel‐based morphometry analyses showed widespread negative associations between BMI and GMv in Aβ‐ participants involving bilateral prefrontal, medial temporal, parietal, occipital, thalamic and cerebellar regions (Figure 1), without positive associations. Among Aβ+ participants, we found positive associations with BMI in small clusters in the cerebellum, middle frontal and anterior cingulate gyri (Figure 2), without negative associations.ConclusionIn the absence of Aβ pathology, higher BMI is associated with brain atrophy involving AD‐related areas, suggesting that midlife obesity may increase dementia risk by mechanisms unrelated to AD pathology. Conversely, among individuals on the AD continuum, higher BMI appears to be associated with more preserved brain structure. We found no evidence of an association between higher BMI and neuroinflammation.

Reduced Regional Cerebral Blood Flow Measured by 99mTc-Hexamethyl Propylene Amine Oxime Single-Photon Emission Computed Tomography in Microgravity Simulated by 5-Day Dry Immersion.

Microgravity induces a cephalad fluid shift that is responsible for cephalic venous stasis that may increase intracranial pressure (ICP) in astronauts. However, the effects of microgravity on regional cerebral blood flow (rCBF) are not known. We therefore investigated changes in rCBF in a 5-day dry immersion (DI) model. Moreover, we tested thigh cuffs as a countermeasure to prevent potential microgravity-induced modifications in rCBF. Around 18 healthy male participants underwent 5-day DI with or without a thigh cuffs countermeasure. They were randomly allocated to a control (n=9) or cuffs (n=9) group. rCBF was measured 4days before DI and at the end of the fifth day of DI (DI5), using single-photon emission computed tomography (SPECT) with radiopharmaceutical 99mTc-hexamethyl propylene amine oxime (99mTc-HMPAO). SPECT images were processed using statistical parametric mapping (SPM12) software. At DI5, we observed a significant decrease in rCBF in 32 cortical and subcortical regions, with greater hypoperfusion in basal ganglia (right putamen peak level: z=4.71, puncorr<0.001), bilateral occipital regions (left superior occipital peak level: z=4.51, puncorr<0.001), bilateral insula (right insula peak level: 4.10, puncorr<0.001), and bilateral inferior temporal (right inferior temporal peak level: 4.07, puncorr<0.001). No significant difference was found between the control and cuffs groups on change in rCBF after 5days of DI. After a 5-day DI, we found a decrease in rCBF in cortical and subcortical regions. However, thigh cuffs countermeasure failed to prevent hypoperfusion. To date, this is the first study measuring rCBF in DI. Further investigations are needed in order to better understand the underlying mechanisms in cerebral blood flow (CBF) changes after exposure to microgravity.

Neuro-Cognitive Differences in Semantic Processing Between Native Speakers and Proficient Learners of Mandarin Chinese.

The present study aimed to investigate the neural mechanism underlying semantic processing in Mandarin Chinese adult learners, focusing on the learners who were Indo-European language speakers with advanced levels of proficiency in Mandarin Chinese. We used functional magnetic resonance imaging technique and a semantic judgment task to test 24 Mandarin Chinese adult learners (L2 group) and 26 Mandarin Chinese adult native speakers (L1 group) as a control group. In the task, participants were asked to indicate whether two-character pairs were related in meaning. Compared to the L1 group, the L2 group had greater activation in the bilateral occipital regions, including the fusiform gyrus and middle occipital gyrus, as well as the right superior parietal lobule. On the other hand, less activation in the bilateral temporal regions was found in the L2 group relative to the L1 group. Correlation analysis further revealed that, within the L2 group, increased activation in the left middle temporal gyrus/superior temporal gyrus (M/STG, BA 21) was correlated with higher accuracy in the semantic judgment task as well as better scores in the two vocabulary tests, the Assessment of Chinese character list for grade 3 to grade 9 (A39) and the Peabody Picture Vocabulary Test-Revised. In addition, functional connectivity analysis showed that connectivity strength between the left fusiform gyrus and left ventral inferior frontal gyrus (IFG, BA 47) was modulated by the accuracy in the semantic judgment task in the L1 group. By contrast, this modulation effect was weaker in the L2 group. Taken together, our study suggests that Mandarin Chinese adult learners rely on greater recruitment of the bilateral occipital regions to process orthographic information to access the meaning of Chinese characters. Also, our correlation results provide convergent evidence that the left M/STG (BA 21) plays a crucial role in the storage of semantic knowledge for readers to access to conceptual information. Moreover, the connectivity results indicate that the left ventral pathway (left fusiform gyrus-left ventral IFG) is associated with orthographic-semantic processing in Mandarin Chinese. However, this semantic-related ventral pathway might require more time and language experience to be developed, especially for the late adult learners of Mandarin Chinese.

A multiparametric MRI study of structural brain damage in dementia with lewy bodies: A comparison with Alzheimer's disease

IntroductionDifferential diagnosis between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) is crucial for an adequate patients' management but might be challenging. We investigated with advanced MRI techniques gray (GM) and white matter (WM) damage in DLB patients compared to those with AD. Methods24 DLB patients, 26 age- and disease severity-matched AD patients, and 20 age and sex-matched controls performed clinical and neuropsychological assessment, and brain structural and diffusion-tensor MRI. We measured GM atrophy using voxel-based morphometry, WM hyperintensities (WMH) using a local thresholding segmentation technique, and normal-appearing WM (NAWM) damage using tract-based spatial statistic. ResultsDLB and AD patients exhibited mild-to-moderate-stage dementia. Compared to controls, GM damage was diffuse in AD, while limited to bilateral thalamus and temporal regions in DLB. Compared to DLB, AD patients exhibited GM atrophy in bilateral fronto-temporal and occipital regions. DLB and AD patients showed higher WMH load than controls, with no differences among each other. WMH in DLB were diffuse with relative prevalence in posterior parietal-occipital regions. Compared to controls, both DLB and AD patients showed reduced microstructural integrity of the main supratentorial and infratentorial NAWM tracts. AD patients exhibited greater posterior NAWM damage than DLB. ConclusionsDLB showed prominent WM degeneration compared to the limited GM atrophy, while in AD both tissue compartments were severely involved. In DLB, NAWM microstructural degeneration was independent of WMH, thus revealing two possible underlying processes. Different pathophysiological mechanisms are likely to drive GM and WM damage distribution in DLB and AD.

Cortical Thickness and Surface Area Abnormalities in Bipolar I and II Disorders.

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

P-PN013. Charcot-Marie-Tooth with transient leukodystrophy: A case report

Introduction . Charcot-Marie-Tooth (CMT), a chronic hereditary peripheral neuropathy, in some rare cases is associated with transient leukodystrophy, making its diagnosis difficult. Results . A 14-year-old boy, after playing football, had a sudden onset of crisis of stiff, numb jaw and tip of tongue, causing drooling, difficulty swallowing and speaking; this numbness spread to his arms. This crisis lasted for 1 to 2 hours; with the daily frequency of 2-3 attacks, at fixed hours. Sometimes he had incontinence. Diagnosed as having epilepsy, he was admitted. Symptoms self ameliorated 3 days later, then discharged. No symptoms recurrence during 4 months follow-up. Two years before admission, his feet were overturned while walking; he was unable to sit straight and had to raise his buttocks. Family history was unremarkable. Neurology examination: Normal sensory function, slight distal weakness of feet, absent tendon reflexes, no pyramid signs, no bladder sphincter disorder. He had pes cavus, and he said he had this deformity for 3 years. Laboratory tests and imaging diagnosis: Normal CBC, CRP, ionogram, glycemia, CPK, and CSF, chest X-ray, and cardiac ultrasound. Brain MRI showed high T2–weighted signal in splenium area of corpus callosum, in white matter behind bilateral centrum ovale, parietal, and occipital regions. These lesions improved on follow-up brain MRI performed 2 months later. Electrodiagnostic studies (EDx) highlighted sensorimotor polyneuropathy, with low SNAP and CMAP of upper and lower limbs. Needle test showed fibrillation, MUP polyphases. Gene panel (Diagsure) for typing CMT shows a homozygous missence mutation (c589 G>C, p.Ala197Pro) in the GJB1 gene of chromosome X. This mutation related to Charcot-Mare-Tooth, has not been reported in ClinVar. Conclusion . Based on history, clinical symptoms, EMG, and gene panel, this is a typical case of CMT1X causing peripheral symptoms and signs. Though transient central symptoms might cause confusion, typing of CMT1X supported transient leucodystrophy.

Cortical Structural Connectivity Alterations and Potential Pathogenesis in Mid-Stage Sporadic Parkinson's Disease.

Many clinical symptoms of sporadic Parkinson’s disease (sPD) cannot be completely explained by a lesion of the simple typical extrapyramidal circuit between the striatum and substantia nigra. Therefore, this study aimed to explore the new potential damaged pathogenesis of other brain regions associated with the multiple and complex clinical symptoms of sPD through magnetic resonance imaging (MRI). A total of 65 patients with mid-stage sPD and 35 healthy controls were recruited in this study. Cortical structural connectivity was assessed by seed-based analysis using the vertex-based morphology of MRI. Seven different clusters in the brain regions of cortical thickness thinning derived from the regression analysis using brain size as covariates between sPD and control were selected as seeds. Results showed that the significant alteration of cortical structural connectivity mainly occurred in the bilateral frontal orbital, opercular, triangular, precentral, rectus, supplementary-motor, temporal pole, angular, Heschl, parietal, supramarginal, postcentral, precuneus, occipital, lingual, cuneus, Rolandic-opercular, cingulum, parahippocampal, calcarine, olfactory, insula, paracentral-lobule, and fusiform regions at the mid-stage of sPD. These findings suggested that the extensive alteration of cortical structural connectivity is one of possible pathogenesis resulting in the multiple and complex clinical symptoms in sPD.

Intracranial Traumatic Hematoma Detection in Children Using a Portable Near-infrared Spectroscopy Device.

IntroductionWe sought to validate a handheld, near-infrared spectroscopy (NIRS) device for detecting intracranial hematomas in children with head injury.MethodsEligible patients were those <18 years old who were admitted to the emergency department at three academic children’s hospitals with head trauma and who received a clinically indicated head computed tomography (HCT). Measurements were obtained by a blinded operator in bilateral frontal, temporal, parietal, and occipital regions. Qualifying hematomas were a priori determined to be within the brain scanner’s detection limits of >3.5 milliliters in volume and <2.5 centimeters from the surface of the brain. The device’s measurements were positive if the difference in optical density between hemispheres was >0.2 on three successive scans. We calculated diagnostic performance measures with corresponding exact two-sided 95% Clopper-Pearson confidence intervals (CI). Hypothesis test evaluated whether predictive performance exceeded chance agreement (predictive Youden’s index > 0).ResultsA total of 464 patients were enrolled and 344 met inclusion for primary data analysis: 10.5% (36/344) had evidence of a hematoma on HCT, and 4.7% (16/344) had qualifying hematomas. The handheld brain scanner demonstrated a sensitivity of 58.3% (21/36) and specificity of 67.9% (209/308) for hematomas of any size. For qualifying hematomas the scanner was designed to detect, sensitivity was 81% (13/16) and specificity was 67.4% (221/328). Predictive performance exceeded chance agreement with a predictive Youden’s index of 0.11 (95% CI, 0.10 – 0.15; P < 0.001) for all hematomas, and 0.09 (95% CI, 0.08 – 0.12; P < 0.001) for qualifying hematomas.ConclusionThe handheld brain scanner can non-invasively detect a subset of intracranial hematomas in children and may serve an adjunctive role to head-injury neuroimaging decision rules that predict the risk of clinically significant intracranial pathology after head trauma.

Altered regional homogeneity and connectivity in cerebellum and visual-motor relevant cortex in Parkinson's disease with rapid eye movement sleep behavior disorder

ObjectiveRapid eye movement sleep behavior disorder (RBD) frequently occurs in Parkinson's disease (PD), however, the exact pathophysiological mechanism underlying its occurrence is not clear. In this study, we explored whether there is abnormal spontaneous neuronal activities and connectivity maps in some brain areas under resting-state in PD patients with RBD. MethodsWe recruited 38 PD patients (19 PD with RBD and 19 PD without RBD), and 20 age- and gender-matched normal controls. We used resting-state functional magnetic resonance imaging (RS-fMRI) to analyze regional homogeneity (ReHo) and functional connectivity (FC), and further to reveal the neuronal activity in all subjects. ResultsCompared with the PD without RBD patients, the PD with RBD patients showed a significant increase in regional homogeneity in the left cerebellum, the right middle occipital region and the left middle temporal region, and decreased regional homogeneity in the left middle frontal region. The REM sleep behavioral disorders questionnaire scores were significantly positively correlated with the ReHo values of the left cerebellum. The functional connectivity analysis in which the four regions described above were used as regions of interest revealed increased functional activity between the left cerebellum and bilateral occipital regions, bilateral temporal regions and bilateral supplementary motor area. ConclusionThe pathophysiological mechanism of PD with RBD may be related to abnormal spontaneous neuronal activity patterns with strong synchronization of cerebellar and visual-motor relevant cortex, and the increased connectivity of the cerebellum with the occipital and motor regions.

Plasma Apolipoprotein E3 and Glucose Levels Are Associated in APOE ɛ3/ɛ4 Carriers

Background:Altered cerebral glucose metabolism, especially prominent in APOE ɛ4 carriers, occurs years prior to symptoms in Alzheimer’s disease (AD). We recently found an association between a higher ratio of plasma apolipoprotein E4 (apoE4) over apoE3, and cerebral glucose hypometabolism in cognitively healthy APOE ɛ3/ɛ4 subjects. Plasma apoE does not cross the blood-brain barrier, hence we speculate that apoE is linked to peripheral glucose metabolism which is known to affect glucose metabolism in the brain.Objective:Explore potential associations between levels of plasma insulin and glucose with previously acquired plasma apoE, cerebral metabolic rate of glucose (CMRgl), gray matter volume, and neuropsychological test scores.Methods:Plasma insulin and glucose levels were determined by ELISA and a glucose oxidase assay whereas apoE levels were earlier quantified by mass-spectrometry in 128 cognitively healthy APOE ɛ3/ɛ4 subjects. Twenty-five study subjects had previously undergone FDG-PET and structural MRI.Results:Lower plasma apoE3 associated with higher plasma glucose but not insulin in male subjects and subjects with a body mass index above 25. Negative correlations were found between plasma glucose and CMRgl in the left prefrontal and bilateral occipital regions. These associations may have functional implications since glucose levels in turn were negatively associated with neuropsychological test scores.Conclusion:Plasma apoE3 but not apoE4 may be involved in insulin-independent processes governing plasma glucose levels. Higher plasma glucose, which negatively affects brain glucose metabolism, was associated with lower plasma apoE levels in APOE ɛ3/ɛ4 subjects. High plasma glucose and low apoE levels may be a hazardous combination leading to an increased risk of AD.

A de novo frameshift variant of ANKRD11 (c.1366_1367dup) in a Chinese patient with KBG syndrome

BackgroundKBG syndrome is a rare autosomal dominant genetic disease mainly caused by pathogenic variants of ankyrin repeat domain-containing protein 11 (ANKRD11) or deletions involving ANKRD11. Herein, we report a novel de novo heterozygous frameshift ANKRD11 variant via whole exome sequencing in a Chinese girl with KBG syndrome.Case presentationA 2-year-2-month-old girl presented with a short stature and developmental delay. Comprehensive physical examinations, endocrine laboratory tests and imaging examination were performed. Whole‐exome sequencing and Sanger sequencing were used to detect and confirm the variant associated with KBG in this patient, respectively. The pathogenicity of the variant was further predicted by several in silico prediction tools. The patient was diagnosed as KBG syndrome with a short stature and developmental delay, as well as characteristic craniofacial abnormalities, including a triangular face, long philtrum, wide eyebrows, a broad nasal bridge, prominent and protruding ears, macrodontia of the upper central incisors, dental crowding, and binocular refractive error. Her skeletal anomalies included brachydactyly, fifth finger clinodactyly, and left-skewed caudal vertebrae. Electroencephalographic results generally showed normal background activity with sporadic spikes and slow wave complexes, as well as multiple spikes and slow wave complexes in the bilateral parietal, occipital, and posterior temporal regions during non-rapid-eye-movement sleep. Brain MRI showed a distended change in the bilateral ventricles and third ventricle, as well as malformation of the sixth ventricle. Whole exome sequencing revealed a novel heterozygous frameshift variant in the patient, ANKRD11 c.1366_1367dup, which was predicted to be pathogenic through in silico analysis. The patient had received physical therapy since 4 months of age, and improvement of gross motor dysfunction was evident.ConclusionsThe results of this study expand the spectrum of ANKRD11 variants in KBG patients and provide clinical phenotypic data for KBG syndrome at an early age. Our study also demonstrates that whole exome sequencing is an effective method for the diagnosis of rare genetic disorders.