Preconditioning Exercise in Rats Attenuates Early Brain Injury Resulting from Subarachnoid Hemorrhage by Reducing Oxidative Stress, Inflammation, and Neuronal Apoptosis.

Subarachnoid hemorrhage (SAH) is a catastrophic form of stroke responsible for significant morbidity and mortality. Oxidative stress, inflammation, and neuronal apoptosis are important in the pathogenesis of early brain injury (EBI) following SAH. Preconditioning exercise confers neuroprotective effects, mitigating EBI; however, the basis for such protection is unknown. We investigated the effects of preconditioning exercise on brain damage and sensorimotor function after SAH. Male rats were assigned to either a sham-operated (Sham) group, exercise (Ex) group, or no-exercise (No-Ex) group. After a 3-week exercise program, they underwent SAH by endovascular perforation. Consciousness level, neurological score, and sensorimotor function were studied. The expression of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), 4-hydroxynonenal (4HNE), nitrotyrosine (NT), ionized calcium-binding adaptor molecule 1 (Iba1), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 1ß (IL-1ß), 14-3-3γ, p-ß-catenin Ser37, Bax, and caspase-3 were evaluated by immunohistochemistry or western blotting. The terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end labeling (TUNEL) assay was also performed. After SAH, the Ex group had significantly reduced neurological deficits, sensorimotor dysfunction, and consciousness disorder compared with the No-Ex group. Nrf2, HO-1, and 14-3-3γ were significantly higher in the Ex group, while 4HNE, NT, Iba1, TNF-α, IL-6, IL-1ß, Bax, caspase-3, and TUNEL-positive cells were significantly lower. Our findings suggest that preconditioning exercise ameliorates EBI after SAH. The expression of 4HNE and NT was reduced by Nrf2/HO-1 pathway activation; additionally, both oxidative stress and inflammation were reduced. Furthermore, preconditioning exercise reduced apoptosis, likely via the 14-3-3γ/p-ß-catenin Ser37/Bax/caspase-3 pathway.

Quantitative susceptibility mapping of the rat brain after traumatic brain injury.

The primary lesion arising from the initial insult after traumatic brain injury (TBI) triggers a cascade of secondary tissue damage, which may also progress to connected brain areas in the chronic phase. The aim of this study was, therefore, to investigate variations in the susceptibility distribution related to these secondary tissue changes in a rat model after severe lateral fluid percussion injury. We compared quantitative susceptibility mapping (QSM) and R2 * measurements with histological analyses in white and grey matter areas outside the primary lesion but connected to the lesion site. We demonstrate that susceptibility variations in white and grey matter areas could be attributed to reduction in myelin, accumulation of iron and calcium, and gliosis. QSM showed quantitative changes attributed to secondary damage in areas located rostral to the lesion site that appeared normal in R2 * maps. However, combination of QSM and R2 * was informative in disentangling the underlying tissue changes such as iron accumulation, demyelination, or calcifications. Therefore, combining QSM with R2 * measurement can provide a more detailed assessment of tissue changes and may pave the way for improved diagnosis of TBI, and several other complex neurodegenerative diseases.

The interplay among education, brain metabolism, and cognitive impairment suggests a role of cognitive reserve in Amyotrophic Lateral Sclerosis.

We tested the Cognitive Reserve (CR) hypothesis in Amyotrophic Lateral Sclerosis (ALS), enrolling 111 patients, using education as CR proxy, 18F-FDG-PET to assess brain damage, and ECAS to measure cognition. Education was regressed out against brain metabolism, including age, sex, spinal/bulbar onset, ALSFRS-R, and ECAS as covariates. Clusters showing a significant correlation were used as seed regions in an interregional correlation analysis (IRCA) in the ALS group and in 40 controls. In the ALS group, we found a negative correlation between brain metabolism and education in the right anterior cingulate and bilateral medial frontal gyrus. In the IRCA in the ALS group, the medial frontal cluster metabolism positively correlated with that of frontotemporal regions (right > left), bilateral caudate nuclei, and right insula, and negatively correlated with that of corticospinal tracts, cerebellum, and pons. In controls, the IRCA showed significant positive correlations in the same regions but less extended. Our results agree with the CR hypothesis. The negative correlation between the medial frontal cluster and the cerebellum found only in ALS patients might reflect cerebellar compensation.

Preterm infants with isolated cerebellar hemorrhage show bilateral cortical alterations at term equivalent age.

The cerebellum is connected to numerous regions of the contralateral side of the cerebrum. Motor and cognitive deficits following neonatal cerebellar hemorrhages (CbH) in extremely preterm neonates may be related to remote cortical alterations, following disrupted cerebello-cerebral connectivity as was previously shown within six CbH infants. In this retrospective case series study, we used MRI and advanced surface-based analyses to reconstruct gray matter (GM) changes in cortical thickness and cortical surface area in extremely preterm neonates (median age = 26; range: 24.9-26.7 gestational weeks) with large isolated unilateral CbH (N = 5 patients). Each CbH infant was matched with their own preterm infant cohort (range: 20-36 infants) based on sex and gestational age at birth. On a macro level, our data revealed that the contralateral cerebral hemisphere of CbH neonates did not show less cortical thickness or cortical surface area than their ipsilateral cerebral hemisphere at term. None of the cases differed from their matched cohort groups in average cortical thickness or average cortical surface area in the ipsilateral or contralateral cerebral hemisphere. On a micro (i.e. vertex) level, we established high variability in significant local cortical GM alteration patterns across case-cohort groups, in which the cases showed thicker or bigger volume in some regions, among which the caudal middle frontal gyrus, insula and parahippocampal gyrus, and thinner or less volume in other regions, among which the cuneus, precuneus and supratentorial gyrus. This study highlights that cerebellar injury during postnatal stages may have  widespread bilateral influence on the early maturation of cerebral cortical regions, which implicate complex cerebello-cerebral interactions to be present at term birth.

Is bimanual interference affected in the case of a central proprioceptive loss? New insight from a left-brain-damaged single-case study.

OBJECTIVE: It was suggested that the bimanual coupling effect might be linked to motor intentionality and planning, which are the top-down components of motor execution. However, previous results in pathological and healthy individuals have also underlined the pivotal role of bottom-up sensorimotor information. METHOD: In this single-case study, the Circles-Lines Coupling Task was administered to a left-parietal-brain-damaged individual. The cerebral lesion caused a central proprioceptive loss, relative to the impaired right hand, when out of the visual control. For the 1st time in literature, we sought to investigate whether the movement of the unaffected hand induced an efficient coupling effect on the movement of the affected one. The bimanual task was performed in the presence and absence of visual input. The patient's performance was compared with that of healthy controls. RESULTS: We observed the traditional bimanual coupling effect in healthy controls. Moreover, we also replicated the effect when they performed the task blindfolded. In the case of the patient, both hands showed the typical ovalization of the line trajectory when the task was performed in visual modality. It is interesting that when the patient performed the task blindfolded, the trajectories of the impaired right hand seemed to be not influenced by the concomitant circular movement of the spared left hand. CONCLUSIONS: The movement of the unaffected hand induced a bimanual coupling effect on the movement of the affected one only when the visual input was available. In absence of a visual feedback, the aberrant proprioceptive information might preclude the emerging of bimanual coupling, even in the case of a preserved motor intentionality and planning. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Brain Damage With Heart Failure: Cardiac Biomarker Alterations and Gray Matter Decline.

RATIONALE: Heart failure (HF) following heart damage leads to a decreased blood flow due to a reduced pump efficiency of the heart muscle. A consequence can be insufficient oxygen supply to the organism including the brain. While HF clearly shows neurological symptoms, such as fatigue, nausea, and dizziness, the implications for brain structure are not well understood. Few studies show regional gray matter decrease related to HF; however, the underlying mechanisms leading to the observed brain changes remain unclear. OBJECTIVE: To study the relationship between impaired heart function, hampered blood circulation, and structural brain change in a case-control study. METHODS AND RESULTS: Within a group of 80 patients of the Leipzig Heart Center, we investigated a potential correlation between HF biomarkers and the brain's gray matter density (GMD) obtained by magnetic resonance imaging. We observed a significant positive correlation between cardiac ejection fraction and GMD across the whole frontal and parietal medial cortex reflecting the consequence of HF onto the brain's gray matter. Moreover, we also obtained a relationship between GMD and the NT-proBNP (N-terminal prohormone of brain natriuretic peptide)-a biomarker that is used for screening, diagnosis, and prognosis of HF. Here, we found a significant negative correlation between NT-proBNP and GMD in the medial and posterior cingulate cortex but also in precuneus and hippocampus, which are key regions implicated in structural brain changes in dementia. CONCLUSIONS: We obtained significant correlations between brain structure and markers of heart failure including ejection fraction and NT-proBNP. A diminished GMD was found with decreased ejection fraction and increased NT-proBNP in wide brain regions including the whole frontomedian cortex as well as hippocampus and precuneus. Our observations might reflect structural brain damage in areas that are related to cognition; however, whether these structural changes facilitate the development of cognitive alterations has to be proven by further longitudinal studies.

Increased Functional Connectivity Within Intrinsic Neural Networks in Chronic Stroke Following Treatment with Red/Near-Infrared Transcranial Photobiomodulation: Case Series with Improved Naming in Aphasia.

Objective: To examine effects of four different transcranial, red/near-infrared (NIR), light-emitting diode (tLED) protocols on naming ability in persons with aphasia (PWA) due to left hemisphere (LH) stroke. This is the first study to report beneficial effects from tLED therapy in chronic stroke, and parallel changes on functional magnetic resonance imaging (fMRI). Materials and methods: Six PWA, 2-18 years poststroke, in whom 18 tLED treatments were applied (3 × /week, 6 weeks) using LED cluster heads: 500 mW, red (633 nm) and NIR (870 nm), 22.48 cm2, 22.2 mW/cm2. Results: After Protocol A with bilateral LED placements, including midline, at scalp vertex over left and right supplementary motor areas (L and R SMAs), picture naming was not improved. P1 underwent pre-/postovert, picture-naming task-fMRI scans; P2 could not. After Protocol A, P1 showed increased activation in LH and right hemisphere, including L and R SMAs. After Protocol B with LEDs only on ipsilesional, LH side, naming ability significantly improved for P1 and P2; the fMRI scans for P1 then showed activation only on the ipsilesional LH side. After Protocol C with LED placements on ipsilesional LH side, plus one midline placement over mesial prefrontal cortex (mPFC) at front hairline, a cortical node of the default mode network (DMN), P3 and P4 had only moderate/poor response, and no increase in functional connectivity on resting-state functional-connectivity MRI. After Protocol D, however, with LED placements on ipsilesional LH side, plus over two midline nodes of DMN, mPFC, and precuneus (high parietal) simultaneously, P5 and P6 each had good response with significant increase in functional connectivity within DMN, p < 0.0005; salience network, p < 0.0005; and central executive network, p < 0.05. Conclusions: NIR photons can affect surface brain cortex areas subjacent to where LEDs are applied on the scalp. Improved naming ability was present with optimal Protocol D. Transcranial photobiomodulation may be an additional noninvasive therapy for stroke.

Association between Diffusion Tensor Imaging Findings and Cognitive Outcomes Following Mild Traumatic Brain Injury: A PRISMA-Compliant Meta-Analysis.

Previous diffusion tensor imaging (DTI) research in mild traumatic brain injury (mTBI) patients only concentrated on a limited number of brain regions and a specific cognitive function. Thus, the study aimed to explore the association between DTI findings and cognitive function following mTBI using a meta-analysis. We conducted a search for articles exploring the associations between DTI findings and cognitive outcomes following mTBI published in English in databases (PubMed, Web of Science, EMBASE, Medline, and Google Scholar) before October 2019. The correlations were computed to explore associations between DTI findings and specific cognitive function. Finally, 9 studies (including 293 mTBI patients) were included in the meta-analysis. The study showed that higher fractional anisotropy (FA) values in the longitudinal fasciculus (LF), sagittal stratum (SS), cerebellum, and internal capsule (IC) were associated with better general cognitive function. However, the study showed that higher FA values in the cerebellar peduncles (CP) were associated with worse general cognitive function. Additionally, the present study showed that higher FA values in the mesencephalon, anterior corona radiata (ACR), forceps major (FM), uncinate fasciculus (UF), cingulum, and genu of corpus callosum (gCC) were related to better memory. Higher FA values in the ACR were associated with worse attention, processing speed, and working memory. The study indicated that higher mean diffusivity (MD)/apparent diffusion coefficient (ADC) values in the external capsule (EC) were associated with worse memory. Additionally, higher MD/ADC values in the UF were associated with worse attention, processing speed, and working memory. The present study showed that better white matter integrity (higher FA, lower MD/ADC) might be associated with better cognitive function following mTBI.

Cerebral Damage after Carbon Monoxide Poisoning: A Longitudinal Diffusional Kurtosis Imaging Study.

BACKGROUND AND PURPOSE: Previous DTI cross-sectional studies have showed the cerebral damage feature was different in the three clinical stages after carbon monoxide poisoning. Diffusional kurtosis imaging (DKI) is an advanced diffusion imaging model and considered to better provide microstructural contrast in comparison with DTI parameters. The primary aim of this study was to assess microstructural changes in gray and white matter with diffusional kurtosis imaging in the acute, delayed neuropsychiatric, and chronic phases after acute carbon monoxide (CO) poisoning. The secondary aim was to relate diffusional kurtosis imaging measures to neuropsychiatric outcomes of acute carbon monoxide poisoning. MATERIALS AND METHODS: In all, 17 patients with acute carbon monoxide poisoning and 30 sex- and age-matched healthy volunteers were enrolled in the study. Patients were scanned within 1 week, 3-8 weeks, and 6 months after acute carbon monoxide poisoning. Diffusional kurtosis imaging metrics including mean kurtosis, mean diffusivity, fractional anisotropy, and kurtosis fractional anisotropy were measured in 11 ROIs and then further correlated with neuropsychiatric scores. RESULTS: In WM, mean kurtosis tended to increase from the acute-to-delayed neuropsychiatric phases and then decrease in the chronic phase, while in GM mean kurtosis showed a constant decline. Contrary to mean kurtosis, mean diffusivity first decreased then tended to increase in WM, while in GM, from the acute to chronic phases, mean diffusivity showed a constant increase. In both WM and GM, the fractional anisotropy and kurtosis fractional anisotropy values progressively declined with time. Kurtosis fractional anisotropy showed the best diagnostic efficiency with an area under the curve of 0.812 (P = .000). Along with neuropsychiatric scores, kurtosis fractional anisotropy of the centrum semiovale and Digit Span Backward were most relevant (r = 0.476, P = .000). CONCLUSIONS: Longitudinally, microstructural changes were inconsistent in WM and GM with time after acute carbon monoxide poisoning. Diffusional kurtosis imaging metrics provided important complementary information to quantify the damage to cognitive impairment.

Swallowing progression during the acute phase of cortical and subcortical ischemic stroke and its association with the extension of brain damage and cognitive impairment.

Objective: To assess swallowing progression and its association with the extension of brain damage and cognitive impairment during the acute phase of ischemic stroke. Methods: Cross-sectional, observational study with 50 patients, who were admitted to a Stroke Unit with cerebral ischemia, with a maximum stroke time of 24 h. The following clinical tools were used: National Institutes of Health Stroke Scale, Mini-Mental State Examination, Frontal Battery Assessment, and the Alberta Stroke Program Early CT Score for neuroimaging. The Gugging Swallowing Screen and the Functional Oral Intake Scale were used to assess swallowing. The patients were assessed at three different time-points: at hospital admission, after 72 h of hospitalization, and at hospital discharge. Results: The mean age of patients was 65.5 years. The frequency of dysphagic patients was 50.0%, 18.0%, and 12.0% at admission, after 72 h of hospitalization, and at discharge, respectively. Scores on the Frontal Battery Assessment and the Alberta Stroke Program Early CT Score were associated with dysphagia progression. Conclusion: Dysphagia is a common complication in the acute phase of stroke, and is associated with the extension of brain damage and cognitive impairment.

How often does computed tomography (CT) of the brain demonstrate a cause for psychosis? A 7-year retrospective study at a tertiary metropolitan hospital.

OBJECTIVES: The aim of the study was to determine the diagnostic yield of computed tomography (CT) of the brain for the investigation of psychosis. METHODS: CT brain requests describing psychosis over a 7-year period at a 500-bed major metropolitan hospital were identified retrospectively. Patients were excluded if they were aged greater than 50 years or if the CT request described focal neurological findings on examination, trauma/falls or known brain tumour, demyelinating disorder, encephalopathy, seizure disorder, congenital brain anomaly, stroke or traumatic brain injury. RESULTS: A total of 805 patients meeting the inclusion and exclusion criteria were identified, representing the largest published study on this topic. Only 0.4% of patients (3 out of 805) had a potential cause for psychosis demonstrated on CT. None of these patients had their management altered as a result. An additional 0.6% of patients (5 out of 805) had significant pathology that was deemed unrelated to their psychosis. CONCLUSIONS: The diagnostic value of CT in the setting of psychosis was found to be extremely low in patients meeting the inclusion and exclusion criteria. Given the risk of ionising radiation and the expenditure of time and cost, more judicious use of CT is suggested.

What bilateral damage of the superior parietal lobes tells us about visual attention disorders in developmental dyslexia.

Neuroimaging studies have identified the superior parietal lobules bilaterally as the neural substrates of reduced visual attention (VA) span in developmental dyslexia. It remains however unclear whether the VA span deficit and the deficits in temporal and spatial attention shifting also reported in dyslexic children reflect a unitary spatio-temporal deficit of attention - probably linked to general posterior parietal dysfunction- or the dysfunction of distinct attentional systems that relate to different neural substrates. We explored this issue by testing an adult patient, IG, with a specific damage of the bilateral superior parietal lobules after stroke, on tasks assessing the VA span as well as temporal and spatial attention shifting. IG demonstrated a very severe VA span deficit, but preserved temporal attention shifting. Exogenous spatial orientation shifting was spared but her performance was impaired in endogenous attention. The overall findings show that distinct sub-systems of visual attention can be dissociated within the parietal lobe, suggesting that different attentional systems associated with specific neural networks can be selectively impaired in developmental dyslexia.

Hemispheric language organization after congenital left brain lesions: A comparison between functional transcranial Doppler and functional MRI.

This study investigated whether functional transcranial Doppler ultrasound (fTCD) is a suitable tool for studying hemispheric lateralization of language in patients with pre-perinatal left hemisphere (LH) lesions and right hemiparesis. Eighteen left-hemisphere-damaged children and young adults and 18 healthy controls were assessed by fTCD and fMRI to evaluate hemispheric activation during two language tasks: a fTCD animation description task and a fMRI covert rhyme generation task. Lateralization indices (LIs), measured by the two methods, differed significantly between the two groups, for a clear LH dominance in healthy participants and a prevalent activation of right hemisphere in more than 80% of brain-damaged patients. Distribution of participants in terms of left, right, and bilateral lateralization was highly concordant between fTCD and fMRI values. Moreover, right hemisphere language dominance in patients with left hemispheric lesions was significantly associated with severity of cortical and subcortical damage in LH. This study suggests that fTCD is an easily applicable tool that might be a valid alternative to fMRI for large-scale studies of patients with congenital brain lesions.

Mechanical knowledge does matter to tool use even when assessed with a non-production task: Evidence from left brain-damaged patients.

In the literature on apraxia of tool use, it is now accepted that using familiar tools requires semantic and mechanical knowledge. However, mechanical knowledge is nearly always assessed with production tasks, so one may assume that mechanical knowledge and familiar tool use are associated only because of their common motor mechanisms. This notion may be challenged by demonstrating that familiar tool use depends on an alternative tool selection task assessing mechanical knowledge, where alternative uses of tools are assumed according to their physical properties but where actual use of tools is not needed. We tested 21 left brain-damaged patients and 21 matched controls with familiar tool use tasks (pantomime and single tool use), semantic tasks and an alternative tool selection task. The alternative tool selection task accounted for a large amount of variance in the single tool use task and was the best predictor among all the semantic tasks. Concerning the pantomime of tool use task, group and individual results suggested that the integrity of the semantic system and preserved mechanical knowledge are neither necessary nor sufficient to produce pantomimes. These results corroborate the idea that mechanical knowledge is essential when we use tools, even when tasks assessing mechanical knowledge do not require the production of any motor action. Our results also confirm the value of pantomime of tool use, which can be considered as a complex activity involving several cognitive abilities (e.g., communicative skills) rather than the activation of gesture engrams.

[Meta-Cognitive Ability and Brain Damage in Autoimmune Encephalitis: A Case Report]. / Otoimmün Ensefalitte Beyin Hasari ve Üst Bilissel Beceri: Bir Olgu Sunumu.

Autoimmune encephalitis is an important contributor to rapidly progressive cognitive and behavioral decline. The purpose of this work was to evaluate the effects of cognitive rehabilitation in a patient with autoimmune encephalitis. We also wanted to evaluate the effectiveness of rehabilitative treatment by monitoring the cognitive and metacognitive outcomes over a time interval. We reported a case of 22 year-old female patient with autoimmune encephalitis, cognitive behavioral impairments, and severe reduction in metarepresentational capacity. We performed an assessment of personality, neuropsychological, and meta-cognitive functions at the beginning of the rehabilitative training. The last evaluation was performed six months after the discharge from the rehabilitation unit. We applied a combination of remediation, psycho-educational treatment, and psychotherapy to improve the knowledge and the empathy of the patient, to promote the selfcontrol strategies, and to prompt better behavioral management. Our findings revealed an improvement in the performance of the individual tests after rehabilitative training.

Magnetic resonance spectroscopy of fiber tracts in children with traumatic brain injury: A combined MRS - Diffusion MRI study.

Traumatic brain injury can cause extensive damage to the white matter (WM) of the brain. These disruptions can be especially damaging in children, whose brains are still maturing. Diffusion magnetic resonance imaging (dMRI) is the most commonly used method to assess WM organization, but it has limited resolution to differentiate causes of WM disruption. Magnetic resonance spectroscopy (MRS) yields spectra showing the levels of neurometabolites that can indicate neuronal/axonal health, inflammation, membrane proliferation/turnover, and other cellular processes that are on-going post-injury. Previous analyses on this dataset revealed a significant division within the msTBI patient group, based on interhemispheric transfer time (IHTT); one subgroup of patients (TBI-normal) showed evidence of recovery over time, while the other showed continuing degeneration (TBI-slow). We combined dMRI with MRS to better understand WM disruptions in children with moderate-severe traumatic brain injury (msTBI). Tracts with poorer WM organization, as shown by lower FA and higher MD and RD, also showed lower N-acetylaspartate (NAA), a marker of neuronal and axonal health and myelination. We did not find lower NAA in tracts with normal WM organization. Choline, a marker of inflammation, membrane turnover, or gliosis, did not show such associations. We further show that multi-modal imaging can improve outcome prediction over a single modality, as well as over earlier cognitive function measures. Our results suggest that demyelination plays an important role in WM disruption post-injury in a subgroup of msTBI children and indicate the utility of multi-modal imaging.

Semantic representation in the white matter pathway.

Object conceptual processing has been localized to distributed cortical regions that represent specific attributes. A challenging question is how object semantic space is formed. We tested a novel framework of representing semantic space in the pattern of white matter (WM) connections by extending the representational similarity analysis (RSA) to structural lesion pattern and behavioral data in 80 brain-damaged patients. For each WM connection, a neural representational dissimilarity matrix (RDM) was computed by first building machine-learning models with the voxel-wise WM lesion patterns as features to predict naming performance of a particular item and then computing the correlation between the predicted naming score and the actual naming score of another item in the testing patients. This correlation was used to build the neural RDM based on the assumption that if the connection pattern contains certain aspects of information shared by the naming processes of these two items, models trained with one item should also predict naming accuracy of the other. Correlating the neural RDM with various cognitive RDMs revealed that neural patterns in several WM connections that connect left occipital/middle temporal regions and anterior temporal regions associated with the object semantic space. Such associations were not attributable to modality-specific attributes (shape, manipulation, color, and motion), to peripheral picture-naming processes (picture visual similarity, phonological similarity), to broad semantic categories, or to the properties of the cortical regions that they connected, which tended to represent multiple modality-specific attributes. That is, the semantic space could be represented through WM connection patterns across cortical regions representing modality-specific attributes.

Analysis of brain and spinal cord lesions to occult brain damage in seropositive and seronegative neuromyelitis optica.

OBJECTIVES: According to aquaporin-4 antibody (AQP4-Ab), neuromyelitis optica (NMO) can be divided into seropositive and seronegative subgroups. The purpose of this study was to a) compare the distribution of spinal cord and brain magnetic resonance imaging (MRI) lesions between seropositive and seronegative NMO patients; b) explore occult brain damage in seropositive and seronegative NMO patients; and c) explore the contribution of visible lesions to occult grey and white matter damage in seropositive and seronegative NMO patients. MATERIALS AND METHODS: Twenty-two AQP4-Ab seropositive and 14 seronegative NMO patients and 30 healthy controls were included in the study. Two neuroradiologists independently measured the brain lesion volume (BLV) and the length of spinal cord lesion (LSCL) and recorded the region of brain lesions. The normal-appearing grey matter volume (NAGM-GMV) and white matter fractional anisotropy (NAWM-FA) were calculated for each subject to evaluate occult brain damage. RESULTS: The seropositive patients displayed more extensive damage in the spinal cord than the seronegative patients, and the seronegative group had a higher proportion of patients with brainstem lesions (28.57%) than the seropositive group (4.55%, P=0.064). Both NMO subgroups exhibited reduced NAGM-GMV and NAWM-FA compared with the healthy controls. NAGM-GMV was negatively correlated with LSCL in the seropositive group (rs=-0.444, P=0.044) and with BLV in the seronegative group (rs=-0.768, P=0.002). NAWM-FA was also negatively correlated with BLV in the seropositive group (rs=-0.682, P<0.001). CONCLUSION: Our findings suggest that the occult brain damage in these two NMO subgroups may be due to different mechanisms, which need to be further clarified.

Plasma cytokines associated with febrile status epilepticus in children: A potential biomarker for acute hippocampal injury.

OBJECTIVE: Our aim was to explore the association between plasma cytokines and febrile status epilepticus (FSE) in children, as well as their potential as biomarkers of acute hippocampal injury. METHODS: Analysis was performed on residual samples of children with FSE (n = 33) as part of the Consequences of Prolonged Febrile Seizures in Childhood study (FEBSTAT) and compared to children with fever (n = 17). Magnetic resonance imaging (MRI) was obtained as part of FEBSTAT within 72 h of FSE. Cytokine levels and ratios of antiinflammatory versus proinflammatory cytokines in children with and without hippocampal T2 hyperintensity were assessed as biomarkers of acute hippocampal injury after FSE. RESULTS: Levels of interleukin (IL)-8 and epidermal growth factor (EGF) were significantly elevated after FSE in comparison to controls. IL-1ß levels trended higher and IL-1RA trended lower following FSE, but did not reach statistical significance. Children with FSE were found to have significantly lower ratios of IL-1RA/IL-1ß and IL-1RA/IL-8. Specific levels of any one individual cytokine were not associated with FSE. However, lower ratios of IL-1RA/IL-1ß, IL-1RA/1L-6, and IL-1RA/ IL-8 were all associated with FSE. IL-6 and IL-8 levels were significantly higher and ratios of IL-1RA/IL-6 and IL-1RA/IL-8 were significantly lower in children with T2 hippocampal hyperintensity on MRI after FSE in comparison to those without hippocampal signal abnormalities. Neither individual cytokine levels nor ratios of IL-1RA/IL-1ß or IL-1RA/IL-8 were predictive of MRI changes. However, a lower ratio of IL-1RA/IL-6 was strongly predictive (odds ratio [OR] 21.5, 95% confidence interval [CI] 1.17-393) of hippocampal T2 hyperintensity after FSE. SIGNIFICANCE: Our data support involvement of the IL-1 cytokine system, IL-6, and IL-8 in FSE in children. The identification of the IL-1RA/IL-6 ratio as a potential biomarker of acute hippocampal injury following FSE is the most significant finding. If replicated in another study, the IL-1RA/IL-6 ratio could represent a serologic biomarker that offers rapid identification of patients at risk for ultimately developing mesial temporal lobe epilepsy (MTLE).

Left Anterior Temporal Lobe and Bilateral Anterior Cingulate Cortex Are Semantic Hub Regions: Evidence from Behavior-Nodal Degree Mapping in Brain-Damaged Patients.

The organizational principles of semantic memory in the human brain are still controversial. Although studies have shown that the semantic system contains hub regions that bind information from different sensorimotoric modalities to form concepts, it is unknown whether there are hub regions other than the anterior temporal lobe (ATL). Meanwhile, previous studies have rarely used network measurements to explore the hubs or correlated network indexes with semantic performance, although the most direct supportive evidence of hubs should come from the network perspective. To fill this gap, we correlated the brain-network index with semantic performance in 86 brain-damaged patients. We especially selected the nodal degree measure that reflects how well a node is connected in the network. The measure was calculated as the total number of connections of a given node with other nodes in the resting-state functional MRI network. Semantic ability was measured using the performance of both general and modality-specific (object form, color, motion, sound, manipulation, and function) semantic tasks. We found that the left ATL and the bilateral anterior cingulate cortex could be semantic hubs because the reduced nodal degree values of these regions could effectively predict the deficits in both general and modality-specific semantic performance. Moreover, the effects remained when the analyses were performed only in the patients who did not have lesions in these regions. The two hub regions might support semantic representations and executive control processes, respectively. These data provide empirical evidence for the distributed-plus-hub theory of semantic memory from the network perspective. SIGNIFICANCE STATEMENT: Although the distributed-plus-hub organization of semantic memory has been proposed for several years, it remains unclear which hubs other than the anterior temporal lobe are included in the semantic system. Here, we identified such hubs from an innovative network perspective. The voxelwise nodal degree values were correlated with the performance of general and modality-specific semantic tasks in 86 patients with brain damage. We observed that the left anterior temporal lobe and bilateral anterior cingulate cortex could be semantic hubs because their decreased nodal degree values were significantly correlated with the severity of the deficit in semantic performance. The two hub regions might contribute to semantic representational and control processes, respectively. These findings offer new evidence for the distributed-plus-hub theory.