Lesions Of Cortex Research Articles

Saturation transfer (CEST and MT) MRI for characterization of U-87 MG glioma in the rat.

The focus of this work was to identify the optimal magnetic resonance imaging (MRI) contrast between orthotopic U-87 MG tumours and normal appearing brain with the eventual goal of treatment response monitoring. U-87 MG human glioblastoma cells were injected into the brain of RNU nude rats (n= 9). The rats were imaged at 7T at three timepoints for all animals: 3-5, 7-9, and 11-13 days after implantation. Whole-brain T1-weighted (before and after gadolinium contrast agent injection), diffusion, and fluid-attenuated inversion recovery scans were performed. In addition, single-slice saturation-transfer-weighted chemical exchange saturation transfer (CEST), magnetization transfer (MT), and water saturation shift referencing (WASSR) contrast Z-spectra and T1 and T2 maps were also acquired. The MT and WASSR Z-spectra and T1 map were fitted to a two-pool quantitative MT model to estimate the T2 of the free and macromolecular-bound water molecules, the relative macromolecular pool size (M0, MT), and the magnetization exchange rate from the macromolecular pool to the free pool (RMT). The T1-corrected apparent exchange-dependent relaxation (AREX) metric to isolate the CEST contributions was also calculated. The lesion on M0, MT and AREX maps with a B1 of 2μT best matched the hyperintensity on the post-contrast T1-weighted image. There was also good separation in Z-spectra between the lesion and contralateral cortex in the 2-μT CEST and 3- and 5-μT MT Z-spectra at all time points. A pairwise Wilcoxon signed-rank tests with Holm-Bonferroni adjustment on MRI parameters was performed and the differences between enhancing lesion and contralateral cortex for the MT ratio with 2μT saturation at 3.6ppm frequency offset (corresponding to the amide chemical group) and M0, MT were both strongly significant (p< 0.001) at all time points. This work has identified that differences between enhancing lesion and contralateral cortex are strongest in MTR with B1=2μT at 3.6ppm and relative macromolecular pool size (M0, MT) images over entire period of 3-13 days after cancer cell implantation.

Cortical drive may facilitate enhanced use of the paretic leg induced by random constraint force to the non-paretic leg during walking in chronic stroke.

The goal of this study was to determine the effects of applying random vs. constant constraint force to the non-paretic leg during walking on enhanced use of the paretic leg in individuals post-stroke, and examine the underlying brain mechanisms. Twelve individuals with chronic stroke were tested under two conditions while walking on a treadmill: random vs. constant magnitude of constraint force applied to the non-paretic leg during swing phase of gait using a custom designed robotic system. Leg kinematics, muscle activity of the paretic leg, and electroencephalography (EEG) were recorded during treadmill walking. Paretic step length and muscle activity of the paretic ankle plantarflexors significantly increased after walking with random and constant constraint forces. Cortico-cortical connectivity between motor cortices and cortico-muscular connectivity from the lesioned motor cortex to the paretic ankle plantarflexors significantly increased for the random force condition but not for the constant force condition. In addition, individuals post-stroke with greater baseline gait variability showed greater improvements in the paretic step length after walking with random force condition but not with the constant force condition. In conclusion, application of random constraint force to the non-paretic leg may enhance the use of the paretic leg during walking by facilitating cortical drive from the lesioned motor cortex to the paretic ankle plantarflexors. Results from this study may be used for the development of constraint induced locomotor intervention approaches aimed at improving locomotor function in individuals after stroke.

Seizure freedom using a regional approach to responsive neurostimulation for multifocal drug-resistant epilepsy: illustrative case.

Responsive neurostimulation (RNS) has emerged as an effective neuromodulatory intervention for patients with medically refractory epilepsy who are not candidates for resective or ablative surgery. However, in patients with multifocal seizures arising from a widely distributed network, optimizing lead placement can be challenging. Here, the authors present the case of a patient with drug-resistant multifocal, nonlateralizing seizures and multiple developmental brain lesions who underwent phase II monitoring with stereoelectroencephalography electrodes targeting the lesion and surrounding cortex as well as the centromedian thalamus. Neurophysiological signals observed during recorded events implicated a seizure network within the left perisylvian polymicrogyria, involving the left parietal operculum, insula, and centromedian thalamic regions rather than a single focus. Using a regional RNS approach to modulate this network, the patient improved from 5 seizures a day to freedom from disabling seizures shortly after lead implantation despite low stimulation parameters. This has implications for understanding the timescale of adaptive mechanisms that occur in response to stimulation and supports the use of RNS as a surgical treatment for drug-resistant epilepsy. https://thejns.org/doi/10.3171/CASE24369.

Brain Ischemic Tolerance Triggered by Preconditioning Involves Modulation of Tumor Necrosis Factor-α-Stimulated Gene 6 (TSG-6) in Mice Subjected to Transient Middle Cerebral Artery Occlusion.

Ischemic preconditioning (PC) induced by a sub-lethal cerebral insult triggers brain tolerance against a subsequent severe injury through diverse mechanisms, including the modulation of the immune system. Tumor necrosis factor (TNF)-α-stimulated gene 6 (TSG-6), a hyaluronate (HA)-binding protein, has recently been involved in the regulation of the neuroimmune response following ischemic stroke. Thus, we aimed at assessing whether the neuroprotective effects of ischemic PC involve the modulation of TSG-6 in a murine model of transient middle cerebral artery occlusion (MCAo). The expression of TSG-6 was significantly elevated in the ischemic cortex of mice subjected to 1 h MCAo followed by 24 h reperfusion, while this effect was further potentiated (p < 0.05 vs. MCAo) by pre-exposure to ischemic PC (i.e., 15 min MCAo) 72 h before. By immunofluorescence analysis, we detected TSG-6 expression mainly in astrocytes and myeloid cells populating the lesioned cerebral cortex, with a more intense signal in tissue from mice pre-exposed to ischemic PC. By contrast, levels of TSG-6 were reduced after 24 h of reperfusion in plasma (p < 0.05 vs. SHAM), but were dramatically elevated when severe ischemia (1 h MCAo) was preceded by ischemic PC (p < 0.001 vs. MCAo) that also resulted in significant neuroprotection. In conclusion, our data demonstrate that neuroprotection exerted by ischemic PC is associated with the elevation of TSG-6 protein levels both in the brain and in plasma, further underscoring the beneficial effects of this endogenous modulator of the immune system.

Local neuronal sleep after stroke: The role of cortical bistability in brain reorganization

BackgroundAcute cerebral ischemia triggers a number of cellular mechanisms not only leading to excitotoxic cell death but also to enhanced neuroplasticity, facilitating neuronal reorganization and functional recovery. ObjectiveTransferring these cellular mechanisms to neurophysiological correlates adaptable to patients is crucial to promote recovery post-stroke. The combination of TMS and EEG constitutes a promising readout of neuronal network activity in stroke patients. MethodsWe used the combination of TMS and EEG to investigate the development of local signal processing and global network alterations in 40 stroke patients with motor deficits alongside neural reorganization from the acute to the chronic phase. ResultsWe show that the TMS-EEG response reflects information about reorganization and signal alterations associated with persistent motor deficits throughout the entire post-stroke period. In the early post-stroke phase and in a subgroup of patients with severe motor deficits, TMS applied to the lesioned motor cortex evoked a sleep-like slow wave response associated with a cortical off-period, a manifestation of cortical bistability, as well as a rapid disruption of the TMS-induced formation of causal network effects. Mechanistically, these phenomena were linked to lesions affecting ascending activating brainstem fibers. Of note, slow waves invariably vanished in the chronic phase, but were highly indicative of a poor functional outcome. ConclusionIn summary, we found evidence that transient effects of sleep-like slow waves and cortical bistability within ipsilesional M1 resulting in excessive inhibition may interfere with functional reorganization, leading to a less favorable functional outcome post-stroke, pointing to a new therapeutic target to improve recovery of function.

Investigating Combined Balance Training and Transcranial Direct Current Stimulation for the Recovery of Postural Control Following Chronic Stroke: A Study Protocol.

Stroke is one of the most debilitating diseases among adults worldwide and leads to persistent rehabilitation needs even at the chronic stage. Achieving good postural control is a critical requirement for daily activities which enhances quality of life (QoL) in patients with stroke. There is increasing evidence that transcranial direct current stimulation (tDCS) can be considered a promising adjunct technique to improve motor recovery after stroke. Evidence of augmented neuroplasticity after tDCS suggests that paired rehabilitation followed by consecutive use of tDCS may optimize recovery outcomes. Although a few randomized controlled trials have been conducted on upper limb rehabilitation in chronic stroke using tDCS, no study focused on balance training in chronic stroke patients. The present randomized, sham-controlled, double-blinded clinical study addresses brain stimulation targeting postural control using tDCS in chronic stroke. The study participants included chronic ischemic stroke individuals with postural control impairments who passed the exclusion criteria. Active or sham anodal tDCS was delivered to the lesioned leg motor cortex combined with balance training. The experimental group received active anodal tDCS stimulation (2 mA) for 20 min, daily for 5 days paired with balance training. Linear and nonlinear approaches were used to analyze postural sway changes pre-and post-intervention. Postural sway fluctuation, functional balance assessment using the Berg balance scale, and timed up-and-go test were conducted to compare the active and sham groups. This trial could have significant implications for balance rehabilitation after stroke in the ambulatory setting. If effective, this novel approach may improve rehabilitation protocol in this population.

The cognitive relevance of non-lesional damage to cortical networks in people with multiple sclerosis.

Cognitive impairment, a common and debilitating symptom in people with multiple sclerosis (MS), is especially related to cortical damage. However, the impact of regional cortical damage remains poorly understood. Our aim was to evaluate structural (network) integrity in lesional and non-lesional cortex in people with MS, and its relationship with cognitive dysfunction. In this cross-sectional study, 176 people with MS and 48 healthy controls underwent MRI, including double inversion recovery and diffusion-weighted scans, and neuropsychological assessment. Cortical integrity was assessed based on fractional anisotropy (FA) and mean diffusivity (MD) within 212 regions split into lesional or non-lesional cortex, and grouped into seven cortical networks. Integrity was compared between people with MS and controls, and across cognitive groups: cognitively-impaired (CI; ≥ two domains at Z ≤ -2 below controls), mildly CI (≥ two at -2 < Z ≤ -1.5), or cognitively-preserved (CP). Cortical lesions were observed in 87.5% of people with MS, mainly in ventral attention network, followed by limbic and default mode networks. Compared to controls, in non-lesional cortex, MD was increased in people with MS, but mean FA did not differ. Within the same individual, MD and FA were increased in lesional compared to non-lesional cortex. CI-MS exhibited higher MD than CP-MS in non-lesional cortex of default mode, frontoparietal and sensorimotor networks, of which the default mode network could best explain cognitive performance. Diffusion differences in lesional cortex were more severe than in non-lesional cortex. However, while most people with MS had cortical lesions, diffusion differences in CI-MS were more prominent in non-lesional cortex than lesional cortex, especially within default mode, frontoparietal and sensorimotor networks.

Mitochondria-targeted cerium vanadate nanozyme suppressed hypoxia-ischemia injury in neonatal mice via intranasal administration

Oxidative stress is a major obstacle for neurological functional recovery after hypoxia-ischemia (HI) brain damage. Nanozymes with robust anti-oxidative stress properties offer a therapeutic option for HI injury. However, insufficiency of nanozyme accumulation in the HI brain by noninvasive administration hinders their application. Herein, we reported a cerium vanadate (CeVO4) nanozyme to realize a noninvasive therapy for HI brain in neonatal mice by targeting brain neuron mitochondria. CeVO4 nanozyme with superoxide dismutase activity mainly co-located with neuronal mitochondria 1 h after administration. Pre- and post-HI administrations of CeVO4 nanozyme were able to attenuate acute brain injury, by inhibiting caspase-3 activation, microglia activation, and proinflammation cytokine production in the lesioned cortex 2 d after HI injury. Moreover, CeVO4 nanozyme administration led to short- and long-term functional recovery following HI insult without any potential toxicities in peripheral organs of mice even after prolonged delivery for 4 weeks. These beneficial effects of CeVO4 nanozyme were associated with suppressed oxidative stress and up-regulated nuclear factor erythroid-2-related factor 2 (Nrf2) expression. Finally, we found that Nrf2 inhibition with ML385 abolished the protective effects of CeVO4 nanozyme on HI injury. Collectively, this strategy may provide an applicative perspective for CeVO4 nanozyme therapy in HI brain damage via noninvasive delivery.

Transcranial Direct Current Stimulation Reverses Stroke-Induced Network Alterations in Mice.

Beyond focal effects, stroke lesions impact the function of distributed networks. We here investigated (1) whether transcranial direct current stimulation (tDCS) alters the network changes induced by cerebral ischemia and (2) whether functional network parameters predict the therapeutic efficacy of tDCS in a mouse model of focal photothrombotic stroke. Starting 3 days after stroke, cathodal tDCS (charge density=39.6 kC/m²) was applied over 10 days in male C57Bl/6J mice under light anesthesia over the lesioned sensory-motor cortex. Functional connectivity (resting-state functional magnetic resonance imaging) was evaluated for up to 28-day poststroke, with global graph parameters of network integration computed. Ischemia induced a subacute increase in connectivity accompanied by a significant reduction in characteristic path length, reversed by 10 days of tDCS. Early measures of functional network alterations and the network configuration at prestroke baseline predicted spontaneous and tDCS-augmented motor recovery. Stroke induces characteristic network changes throughout the brain that can be detected by resting-state functional magnetic resonance imaging. These network changes were, at least in part, reversed by tDCS. Moreover, early markers of a network impairment and the network configuration before the insult improve the prediction of motor recovery.

Outcome Predictors of Lesional Posterior Cortex Epilepsy Surgery.

Lesional posterior cortex epilepsy (PCE) is often drug resistant and may benefit from surgical intervention. In this study, we aimed to identify potential predictive factors associated with seizure recurrence after epilepsy surgery in lesional PCE. We retrospectively reviewed patients with PCE who underwent surgery between 1998 and 2021. They were divided into 2 groups according to seizure outcome; the seizure-free group (group 1) and the non-seizure-free group (group 2). The relationship among clinical factors, electroencephalography (EEG) or cranial magnetic resonance imaging findings, disease, and seizure outcome was investigated. A total of 60 patients, with a mean age of 27.26 ± 12.35 years (range, 9-61 years), were included in the study. There were 31 patients (51.66%) in group 1 (Engel class I) and 29 patients (48.33%) in group 2 (13 [21.66%], 10 [16.66%], and 6 [10%] patients in Engel class II, III, and IV, respectively), with a mean follow-up of 8.95 ± 6.96 years (range, 1-24 years). No difference was observed regarding age, gender, age at seizure onset, operation type, treatment gap, and presence of bilateral lesions between the groups (P > 0.05). However, bilateral findings on interictal EEG and gliosis as the underlying disease were predictors of seizure recurrence (P < 0.05). More than half of the patients (including 2 with bilateral magnetic resonance imaging lesions) were seizure free at long-term follow-up. However, patients with bilateral findings on interictal EEG and gliosis were more likely to have recurrent seizures after surgery. Because lesional PCE is almost always drug resistant and has a potential for favorable outcomes, epilepsy surgery should be considered early.

State-dependent interhemispheric inhibition reveals individual differences in motor behavior in chronic stroke

ObjectiveTo investigate state-dependent interhemispheric inhibition (IHI) in chronic stroke survivors compared to neurotypical older adult controls, and test whether abnormal IHI modulation was associated with upper extremity motor behavior. MethodsDual-coil transcranial magnetic stimulation (TMS) measured IHI bi-directionally, between non-lesioned and lesioned motor cortex (M1) in two activity states: (1) at rest and (2) during contralateral isometric hand muscle contraction. IHI was tested by delivering a conditioning stimulus 8-msec or 50-msec prior to a test stimulus over contralateral M1. Paretic motor behavior was assessed by clinical measures of impairment, strength, and dexterity, and mirroring activity in the non-paretic hand. ResultsStroke survivors demonstrated reduced IHI at rest, and less IHI modulation (active – rest) compared to controls. Individual differences in IHI modulation were related to motor behavior differences where greater IHI modulation was associated with greater motor impairment and more mirroring. In contrast, there were no relationships between IHI at rest and motor behavior. ConclusionsAbnormal state-dependent interhemispheric circuit activity may be more sensitive to post-stroke motor deficits than when assessed in a single motor state. SignificanceCharacterizing state-dependent changes in neural circuitry may enhance models of stroke recovery and inform rehabilitation interventions.

Electric field simulations of transcranial direct current stimulation in children with perinatal stroke.

Perinatal stroke (PS) is a focal vascular brain injury and the leading cause of hemiparetic cerebral palsy. Motor impairments last a lifetime but treatments are limited. Transcranial direct-current stimulation (tDCS) may enhance motor learning in adults but tDCS effects on motor learning are less studied in children. Imaging-based simulations of tDCS-induced electric fields (EF) suggest differences in the developing brain compared to adults but have not been applied to common pediatric disease states. We created estimates of tDCS-induced EF strength using five tDCS montages targeting the motor system in children with PS [arterial ischemic stroke (AIS) or periventricular infarction (PVI)] and typically developing controls (TDC) aged 6-19 years to explore associates between simulation values and underlying anatomy. Simulations were performed using SimNIBS https://simnibs.github.io/simnibs/build/html/index.html using T1, T2, and diffusion-weighted images. After tissue segmentation and tetrahedral mesh generation, tDCS-induced EF was estimated based on the finite element model (FEM). Five 1mA tDCS montages targeting motor function in the paretic (non-dominant) hand were simulated. Estimates of peak EF strength, EF angle, field focality, and mean EF in motor cortex (M1) were extracted for each montage and compared between groups. Simulations for eighty-three children were successfully completed (21 AIS, 30 PVI, 32 TDC). Conventional tDCS montages utilizing anodes over lesioned cortex had higher peak EF strength values for the AIS group compared to TDC. These montages showed lower mean EF strength within target M1 regions suggesting that peaks were not necessarily localized to motor network-related targets. EF angle was lower for TDC compared to PS groups for a subset of montages. Montages using anodes over lesioned cortex were more sensitive to variations in underlying anatomy (lesion and tissue volumes) than those using cathodes over non-lesioned cortex. Individualized patient-centered tDCS EF simulations are prudent for clinical trial planning and may provide insight into the efficacy of tDCS interventions in children with PS.

A Single Episode of Cortical Spreading Depolarization Increases mRNA Levels of Proinflammatory Cytokines, Calcitonin Gene-Related Peptide and Pannexin-1 Channels in the Cerebral Cortex

Cortical spreading depolarization (CSD) is the neuronal correlate of migraine aura and the reliable consequence of acute brain injury. The role of CSD in triggering headaches that follow migraine aura and brain injury remains to be uncertain. We examined whether a single CSD occurring in awake animals modified the expression of proinflammatory cytokines (Il1b, TNF, and Il6) and endogenous mediators of nociception/neuroinflammation-pannexin 1 (Panx1) channel and calcitonin gene-related peptide (CGRP), transforming growth factor beta (TGFb) in the cortex. Unilateral microinjury of the somatosensory cortex triggering a single CSD was produced in awake Wistar rats. Three hours later, tissue samples from the lesioned cortex, intact ipsilesional cortex invaded by CSD, and homologous areas of the contralateral sham-treated cortex were harvested and analyzed using qPCR. Three hours post-injury, intact CSD-exposed cortexes increased TNF, Il1b, Panx1, and CGRP mRNA levels. The strongest upregulation of proinflammatory cytokines was observed at the injury site, while CGRP and Panx1 were upregulated more strongly in the intact cortexes invaded by CSD. A single CSD is sufficient to produce low-grade parenchymal neuroinflammation with simultaneous overexpression of Panx1 and CGRP. The CSD-induced molecular changes may contribute to pathogenic mechanisms of migraine pain and post-injury headache.

Beneficial Effects of Hyaluronan-Based Hydrogel Implantation after Cortical Traumatic Injury

Traumatic brain injury (TBI) causes cell death mainly in the cerebral cortex. We have previously reported that transplantation of embryonic cortical neurons immediately after cortical injury allows the anatomical reconstruction of injured pathways and that a delay between cortical injury and cell transplantation can partially improve transplantation efficiency. Biomaterials supporting repair processes in combination with cell transplantation are in development. Hyaluronic acid (HA) hydrogel has attracted increasing interest in the field of tissue engineering due to its attractive biological properties. However, before combining the cell with the HA hydrogel for transplantation, it is important to know the effects of the implanted hydrogel alone. Here, we investigated the therapeutic effect of HA on host tissue after a cortical trauma. For this, we implanted HA hydrogel into the lesioned motor cortex of adult mice immediately or one week after a lesion. Our results show the vascularization of the implanted hydrogel. At one month after HA implantation, we observed a reduction in the glial scar around the lesion and the presence of the newly generated oligodendrocytes, immature and mature neurons within the hydrogel. Implanted hydrogel provides favorable environments for the survival and maturation of the newly generated neurons. Collectively, these results suggest a beneficial effect of biomaterial after a cortical traumatic injury.

Post-ischemic protection of hepatocyte growth factor requires the type II transmembrane serine protease matriptase-A reciprocal regulation of the two for neuroprotection in stroke brain.

In a rat middle cerebral artery occlusion (MACo) model of ischemic stroke, intracerebroventricular administration of human recombinant hepatocyte growth factor (HGF) mitigated motor impairment and cortical infarction. Recombinant HGF reduced MCAo-induced TNFα and IL1β expression, and alleviated perilesional reactivation of microglia and astrocyte. All of the aforementioned beneficial effects of HGF were antagonized by an inhibitor to the type II transmembrane serine protease matriptase (MTP). MCAo upregulated MTP mRNA and protein in the lesioned cortex. MTP protein, not the mRNA, was increased further by recombinant HGF but reduced when MTP inhibitor (MTPi) was added to the treatment. Changes of the endogenous active HGF by MCAo, HGF or MTPi paralleled with the changes of MTP protein under the same conditions whilst neither HGF mRNA nor the total endogenous HGF protein were altered. These data showed that the therapeutic effects of HGF in stroke brain is attributed to its proteolytic activation and that MTP is a main protease of the event. MCAo enhanced MTP mRNA and thus protein expression; the initial use of the recombinant active HGF stabilized MCAo-induced MTP protein and subsequent activation of endogenous latent HGF which in turn stabilized further MTP protein. A reciprocal regulation between MTP and HGF appears to be present where MTP promotes HGF activation and the active HGF prevents MTP protein turnover. This study, for the first time, shows that MTP can participate in neural protection in stroke brain through activation of HGF. The cycles of HGF-MTP regulation achieved preservation of the neurological activity.

Tremor and Rigidity in Patients with Parkinson’s Disease: Emphasis on Epidemiology, Pathophysiology and Contributing Factors

Parkinson's disease (PD) is the second most prominent neurodegenerative movement disorder after Alzheimer's disease, involving 2-3% of the population aged above 65 years. This is mainly triggered by the depletion of dopaminergic neurons located in substantia nigra pars compacta (SNpc) in the region of basal ganglia. At present, diagnosis for symptoms of PD is clinical, contextual, unspecified and therapeutically incomprehensive. Analysis of various causes of PD is essential for an accurate examination of the disease. Among the different causes, such as tremors and rigidity, unresponsiveness to the current treatment approach contributes to mortality. In the present review article, we describe various key factors of pathogenesis and physiology associated with tremors and rigidity necessary for the treatment of PI (postural instability) in patients with PD. Additionally, several reports showing early tremor and rigidity causes, particularly age, cortex lesions, basal ganglia lesions, genetic abnormalities, weakened reflexes, nutrition, fear of fall, and altered biomechanics, have been explored. By summarizing the factors that contribute to the disease, histopathological studies can assess rigidity and tremor in PD. With a clear understanding of the contributing factors, various prospective studies can be done to assess the incidence of rigidity and tremors.

Diagnostic Accuracy of 99mTc-Sestamibi SPECT/CT for Characterization of Solid Renal Masses.

Our objective was to assess the diagnostic accuracy of 99mTc-sestamibi SPECT/CT for characterizing solid renal masses. Methods: Imaging and clinical records of patients who underwent 99mTc-sestamibi SPECT/CT for clinical work-up of their solid renal masses from September 2018 to October 2021 were retrospectively reviewed. Histopathology formed the reference standard, and the diagnoses were categorized as malignant/concerning (renal cell carcinomas [RCCs] other than chromophobe histology) and benign/nonconcerning (oncocytic tumors including chromophobe RCC, other benign diagnoses) to calculate the sensitivity and specificity of 99mTc-sestamibi SPECT/CT and contrast-enhanced CT (ceCT). The clinical reads of the SPECT/CT images were used for visual classification of the lesions. Additionally, the SPECT images were manually segmented to obtain the maximum and mean counts of the lesion and adjacent renal cortex and maximum and mean lesion Hounsfield units. Results: 99mTc-sestamibi SPECT/CT was performed on 42 patients with 62 renal masses. A histopathologic diagnosis was available for 27 patients (18 male, 9 female) with 36 solid renal masses. ceCT findings were available for 20 of these patients. The most commonly identified single histologic type was clear cell RCC (13/36; 36.1%). Oncocytic tumors were the most common group of nonconcerning lesions (15/36), with oncocytoma as the predominant histologic type (n = 6). The sensitivity and specificity of SPECT/CT for diagnosing a nonconcerning lesion were 66.7% and 89.5%, respectively, compared with 10% and 75%, respectively, for ceCT. The lesion-to-kidney ratios for maximum and mean counts and maximum lesion Hounsfield units showed significant differences between the 2 groups (P < 0.05). The lesion-to-kidney mean count ratio at a cutoff of 0.46 showed a sensitivity and specificity of 87.5% and 86.67%, respectively, for detecting nonconcerning lesions, which was significantly higher than that of ceCT. Conclusion: The current literature on the utility of 99mTc-sestamibi SPECT/CT for characterization of solid renal masses is limited. We offer additional evidence of the incremental value of 99mTc-sestamibi SPECT/CT over ceCT for differentiating malignant or aggressive renal tumors from benign or indolent ones, thereby potentially avoiding overtreatment and its associated complications. Quantitative assessment can further increase the diagnostic accuracy of SPECT/CT and may be used in conjunction with visual interpretation.

Linking lesions in sensorimotor cortex to contralateral hand function in multiple sclerosis: a 7 T MRI study.

Cortical lesions constitute a key manifestation of multiple sclerosis and contribute to clinical disability and cognitive impairment. Yet it is unknown whether local cortical lesions and cortical lesion subtypes contribute to domain-specific impairments attributable to the function of the lesioned cortex.In this cross-sectional study, we assessed how cortical lesions in the primary sensorimotor hand area relate to corticomotor physiology and sensorimotor function of the contralateral hand. Fifty relapse-free patients with relapsing–remitting or secondary–progressive multiple sclerosis and 28 healthy age- and sex-matched participants underwent whole-brain 7 T MRI to map cortical lesions. Brain scans were also used to estimate normalized brain volume, pericentral cortical thickness, white matter lesion fraction of the corticospinal tract, infratentorial lesion volume and the cross-sectional area of the upper cervical spinal cord. We tested sensorimotor hand function and calculated a motor and sensory composite score for each hand. In 37 patients and 20 healthy controls, we measured maximal motor-evoked potential amplitude, resting motor threshold and corticomotor conduction time with transcranial magnetic stimulation and the N20 latency from somatosensory-evoked potentials.Patients showed at least one cortical lesion in the primary sensorimotor hand area in 47 of 100 hemispheres. The presence of a lesion was associated with worse contralateral sensory (P = 0.014) and motor (P = 0.009) composite scores. Transcranial magnetic stimulation of a lesion-positive primary sensorimotor hand area revealed a decreased maximal motor-evoked potential amplitude (P < 0.001) and delayed corticomotor conduction (P = 0.002) relative to a lesion-negative primary sensorimotor hand area. Stepwise mixed linear regressions showed that the presence of a primary sensorimotor hand area lesion, higher white-matter lesion fraction of the corticospinal tract, reduced spinal cord cross-sectional area and higher infratentorial lesion volume were associated with reduced contralateral motor hand function. Cortical lesions in the primary sensorimotor hand area, spinal cord cross-sectional area and normalized brain volume were also associated with smaller maximal motor-evoked potential amplitude and longer corticomotor conduction times. The effect of cortical lesions on sensory function was no longer significant when controlling for MRI-based covariates. Lastly, we found that intracortical and subpial lesions had the largest effect on reduced motor hand function, intracortical lesions on reduced motor-evoked potential amplitude and leucocortical lesions on delayed corticomotor conduction.Together, this comprehensive multilevel assessment of sensorimotor brain damage shows that the presence of a cortical lesion in the primary sensorimotor hand area is associated with impaired corticomotor function of the hand, after accounting for damage at the subcortical level. The results also provide preliminary evidence that cortical lesion types may affect the various facets of corticomotor function differentially.

Patterns of Focal Amyloid Deposition Using 18F-Florbetaben PET in Patients with Cognitive Impairment.

Accumulation of aggregated amyloid-β (Aβ) in the brain is considered the first pathological event within the pathogenesis of Alzheimer’s disease (AD). It is difficult to accurately identify the initial brain regions of Aβ accumulation due to the time-lag between the start of the pathophysiology and symptom onset. However, focal regional amyloid uptake on amyloid PET scans may provide insights into this. Hence, we aimed to evaluate the topographic distribution of amyloid deposition in patients with cognitive impairment and to identify the starting order of amyloid accumulation in the brain using conditional probability. We enrolled 58 patients composed of 9 normal cognition (NC), 32 mild cognitive impairment (MCI), and 17 dementia showing focal regional amyloid deposition corresponding to a brain amyloid plaque load (BAPL) score of 2 among those who visited the Memory Clinic of Asan Medical Center and underwent an 18F-florbetaben PET scan (March 2013 to April 2019). Regions of interest (ROI) included the frontal, parietal, lateral temporal, and occipital cortices, the posterior cingulate/precuneus, and the striatum. The most frequent occurrence of Aβ deposition was in the posterior cingulate/precuneus (n = 41, 68.3%). The second most frequent site was the lateral temporal cortex (n = 24, 40.0%), followed by the lateral parietal cortex (n = 21, 35.6%) and other lesions, such as the frontal and occipital cortices. The striatum was the least frequently affected. Our study found that the posterior cingulate/precuneus and the lateral temporal and parietal cortices may be the earliest areas to be affected by Aβ accumulation. Longitudinal follow-up of focal brain amyloid deposition may help elucidate the evolutionary pattern of Aβ accumulation in the brain of people with AD continuum.

FV 13 Transcranial direct current stimulation modulates stroke-induced secondary thalamic neurodegeneration in mice

Introduction: Transcranial direct current stimulation (tDCS) non-invasively promotes recovery after stroke ( Braun et al. Exp. Neurol. 2016; Hummel et al. Brain 2005 ). Stroke affects entire networks beyond the focal lesion, impacting post-stroke impairment ( Blaschke et al. Stroke 2021 ). The thalamus constitutes a central hub due to its numerous functional connections but is also prone to secondary injury ( Cao et al. Front. Neurol. 2020 ). Under the hypothesis that tDCS promotes recovery by supporting neuroprotection, we investigated the effects of tDCS on secondary thalamic neurodegeneration after stroke. Methods: Cortical stroke was induced in the sensory-motor cortex (photothrombosis model in mice). Starting three days after stroke, cathodal tDCS over the ipsilesional somatosensory cortex was performed daily for ten days (39.6 kC/m 2 ), sham-stimulated mice served as control. Behavioral tests over time assessed functional recovery. Secondary degeneration of the ipsilesional thalamus was evaluated ex vivo 28 days after stroke. Using an atlas-based registration pipeline ( Pallast et al. J. Neurosc. Methods 2019 ), the absolute number of GFAP+ astrocytes and relative number of ipsilesional NeuN+ neurons compared to the contralateral unaffected thalamus were evaluated. Lesion maps based on T2-weighted Magnetic Resonance Imaging (MRI) before tDCS were used for voxel-based lesion-symptom mapping (VBLSM) to evaluate the effect of the lesion location on remote neurodegeneration. Functional connectivity (FC) between the lesioned sensorimotor cortex and the ipsilesional thalamus was measured by resting-state functional MRI. Additionally, glucose metabolism after a likewise tDCS regimen in healthy mice was measured by positron emission tomography compared to sham stimulation. Results: Repetitive tDCS decreased the ipsilateral thalamic glucose metabolism in unlesioned animals, while accelerating motor recovery after stroke. Four weeks after cortical stroke, secondary glial scaring was found in the ipsilesional thalamus, most pronounced in the posterior (Po), ventral posterolateral (VPL), and ventral posteromedial (VPM) nucleus, its extent correlating to the cortical lesion size (R 2 =0.3, p<0.01). Neurodegeneration was associated with a lesion cluster (VSBLM, p<0.05) extending laterally and including the callosal white matter tracts as well as deeper primary somatosensory layers. A decrease in FC between the primary somatosensory area of the lower limb (SS-LL) and the thalamus correlated with secondary neurodegeneration (R 2 =0.25, p<0.01). Intriguingly, in contrast to glial scaring, tDCS reduced thalamic neurodegeneration by over 60% (p<0.05). Conclusion: Cortical stroke induced network changes and led to remote secondary structural impairment of the thalamus, depending on the affection of corticothalamic connections. TDCS mitigated this remote secondary neurodegeneration. Data suggest previously unknown effects of tDCS on remote brain regions after stroke.