Microstructural Impairments in a Topologically Distinct Prefrontal-Habenular Connection in Cocaine Addiction

Drug addiction is characterized by neuroadaptations in mesocorticolimbic networks regulating reward and inhibitory control. The habenula (Hb) is central to adaptive reward and aversion-driven behaviors, serving as a hub connecting emotion/cognitive processing regions including the prefrontal cortex (PFC). However, its role in human drug addiction has not been fully explored. Using diffusion tractography, we detailed PFC structural connectivity with three regions, namely the Hb, ventral tegmental area (VTA), and anterior thalamus (AT), and quantified the tract-specific microstructural integrity using diffusion tensor imaging within the anterior limb of the internal capsule (ALIC) in healthy and cocaine-addicted individuals. White matter microstructure in cocaine-addicted individuals was uniquely impaired in PFC-Hb projections in the ALIC, distinguishable from adjacent PFC-VTA and PFC-AT projections, with more pronounced abnormalities in short-term abstinence. These findings extend preclinical evidence of PFC-Hb circuit impairments in addiction and contextualize the plausible existence of a similar PFC-Hb connection in the human brain.

Organic Hallucinosis in Non-Hemorrhagic Stroke Caused by Thrombosis Process: A Case Report

Background/aim: Hallucinations are the special ability to experience phenomena that are not visible to normal individuals. Hallucinations, delusions, and confabulations are common symptoms between neurology and psychiatry. Nervous disease that manifests with hallucinatory symptoms like this is one of them due to right hemispheric stroke. The authors report cases of new-onset organic hallucinosis. and stroke in brain regions similar to the salience network (insular cortex, parietal cortex, and striatum). Case: A 43-year-old man comes to the ER Sanglah Hospital Denpasar, Bali Indonesia with complaints of slurred speech using an incomprehensible language, and repeating the same words. Talking about seeing a shadow following him but actually not there. Patients often experience sleep disorders, from the results of neurological physical examination found right eye ptosis, pupil anisokor, nerve III dextra complete lesion, supranuclear left NVII paresis, supranuclear left NXII paresis, left flaccid hemiparesis. Psychiatric status obtained unnatural appearance, looks confused, verbal and visual contact is sufficient, mood dysphoric, confused affect and there is no harmony. The thought process obtained realistic, coherent, preoccupation with pain. Perceptual disturbances in the form of visual and auditory hallucinations. Insomnia mixed type and there is hypobulia. Psychomotor calm on examination, history increases. Narcissistic personality traits and defense mechanisms of ego repression. Grade 4 view. CT scan of the head with and without contrast shows subacute ischemic cerebral infarction in the right internal capsule to the right thalamus and midbrain. Conclusion: Organic hallucinosis occur in non-hemorrhagic stroke caused by thrombosis process if an infarction is found in the right hemisphere. Keywords: organic hallucinations, ischemic cerebral infarction, non-hemorrhagic stroke, right hemisphere.

White Matter Microstructure is Associated with Serum Clusterin and Everyday Functioning in a Sample of Nondemented Older Adults

Background: Although clusterin-a protein involved in lipid metabolism, amyloid beta clearance, and myelination-has been linked to gray matter atrophy within samples of older adults at risk for Alzheimer’s disease, research exploring associations with white matter (WM) micro- and macro- structural markers are largely limited. Objective:: The current study [1] explored associations between serum clusterin protein levels and WM micro- and macro- structural markers, and [2] clarified whether variations in WM fractional anisotropy (FA) were associated with functional abilities within in a racially homogenous sample of relatively well-educated older adults free of dementia. Methods: Participants underwent magnetic resonance imaging (MRI) brain exams and a blood draw and completed a performance-based measure of everyday functioning. Multiple linear regression adjusting for age, sex, APOE e4 positivity, and vascular risk were used to explore serum clusterin associations with WM metrics, as well clarify potential links between WM microstructure and everyday functioning. Results: Higher serum clusterin was associated with lower FA in several thalamocortical (anterior and posterior internal capsule, posterior thalamic radiation; ßs = -.32 to -.37, ps = .01 to .02) and association fiber tracts (external capsule, superior longitudinal fasciculus; ßs = -.32 to -.40, ps = .02). Serum clusterin was not associated with white matter hyperintensity volume (ß = .14, p = .28), but higher FA of several WM tracts was associated with better performance on the Independent Living Scale (ßs = .37 to .53, ps = .006 to .03). Conclusion: Serum clusterin is differentially associated with WM metrics, and WM microstructure is associated with everyday functioning.

The role of MRI-based texture analysis to predict the severity of brain injury in neonates with perinatal asphyxia

Objectives: To evaluate the efficacy of the magnetic resonance imaging (MRI)-based texture analysis (TA) of the basal ganglia and thalami to distinguish moderate-to-severe hypoxic-ischemic encephalopathy (HIE) from mild HIE in neonates. Methods: This study included 68 neonates (15 with mild, 20 with moderate-to-severe HIE, and 33 control) were born at 37 gestational weeks or later and underwent MRI in first 10 days after birth. The basal ganglia and thalami were delineated for TA on the apparent diffusion coefficient (ADC) maps, T1-, and T2-weighted images. The basal ganglia, thalami, and the posterior limb of the internal capsule (PLIC) were also evaluated visually on diffusion-weighted imaging and T1-weighted sequence. Receiver operating characteristic curve and logistic regression analyses were used. Results: Totally 56 texture features for the basal ganglia and 46 features for the thalami were significantly different between the HIE groups on the ADC maps, T1-, and T2-weighted sequences. Using a Histogram_entropy log-10 value as >1.8 from the basal ganglia on the ADC maps (p < 0.001; OR, 266) and the absence of hyperintensity of the PLIC on T1-weighted images (p = 0.012; OR, 17.11) were found as independent predictors for moderate-to-severe HIE. Using only a Histogram_entropy log-10 value had an equal diagnostic yield when compared to its combination with other texture features and imaging findings. Conclusion: The Histogram_entropy log-10 value can be used as an indicator to differentiate from moderate-to-severe to mild HIE. Advances in knowledge: MRI-based TA may provide quantitative findings to indicate different stages in neonates with perinatal asphyxia.

The Value of Diffusion Kurtosis Imaging in Detecting Delayed Brain Development of Premature Infants

Objective: Preterm infants are at high risk of the adverse neurodevelopmental outcomes. Our aim is to explore the value of diffusion kurtosis imaging (DKI) in diagnosing brain developmental disorders in premature infants.Materials and Methods: A total of 52 subjects were included in this study, including 26 premature infants as the preterm group, and 26 full-term infants as the control group. Routine MRI and DKI examinations were performed. Mean kurtosis (MK), radial kurtosis (RK), fractional anisotropy (FA), and mean diffusivity (MD) values were measured in the brain regions including posterior limbs of the internal capsule (PLIC), anterior limb of internal capsule (ALIC), parietal white matter (PWM), frontal white matter (FWM), thalamus (TH), caudate nucleus (CN), and genu of the corpus callosum (GCC). The chi-squared test, t-test, Spearman's correlation analysis, and receiver operating characteristic curve were used for data analyses.Results: In the premature infant group, the MK and RK values of PLIA, ALIC, and PWM were lower than those in the control group (p &lt; 0.05). The FA values of PWM, FWM, and TH were also lower than those of the control group (p &lt; 0.05). The area under curves of MK in PLIC and ALIC, MD in PWM, and FA in FWM were 0.813, 0.802, 0.842, and 0.867 (p &lt; 0.05). In the thalamus and CN, the correlations between MK, RK values, and postmenstrual age (PMA) were higher than those between FA, MD values, and PMA.Conclusion: Diffusion kurtosis imaging can be used as an effective tool in detecting brain developmental disorders in premature infants.

Effect of Neurorepair for Motor Functional Recovery Enhanced by Total Saponins From Trillium tschonoskii Maxim. Treatment in a Rat Model of Focal Ischemia

Trillium tschonoskii Maxim. (TTM), is a perennial herb from Liliaceae, that has been widely used as a traditional Chinese medicine treating cephalgia and traumatic hemorrhage. The present work was designed to investigate whether the total saponins from Trillium tschonoskii Maxim. (TSTT) would promote brain remodeling and improve gait impairment in the chronic phase of ischemic stroke. A focal ischemic model of male Sprague-Dawley (SD) rats was established by permanent middle cerebral artery occlusion (MCAO). Six hours later, rats were intragastrically treated with TSTT (120, 60, and 30 mg/kg) and once daily up to day 30. The gait changes were assessed by the CatWalk-automated gait analysis system. The brain tissues injuries, cerebral perfusion and changes of axonal microstructures were detected by multimodal magnetic resonance imaging (MRI), followed by histological examinations. The axonal regeneration related signaling pathways including phosphatidylinositol 3-kinases (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3 (GSK-3)/collapsin response mediator protein-2 (CRMP-2) were measured by western blotting. TSTT treatment significantly improved gait impairment of rats. MRI analysis revealed that TSTT alleviated tissues injuries, significantly improved cerebral blood flow (CBF), enhanced microstructural integrity of axon and myelin sheath in the ipsilesional sensorimotor cortex and internal capsule. In parallel to MRI findings, TSTT preserved myelinated axons and promoted oligodendrogenesis. Specifically, TSTT interventions markedly up-regulated expression of phosphorylated GSK-3, accompanied by increased expression of phosphorylated PI3K, AKT, but reduced phosphorylated CRMP-2 expression. Taken together, our results suggested that TSTT facilitated brain remodeling. This correlated with improving CBF, encouraging reorganization of axonal microstructure, promoting oligodendrogenesis and activating PI3K/AKT/GSK-3/CRMP-2 signaling, thereby improving poststroke gait impairments.

Heterogeneous immunoreactivity of axonal spheroids in focal symmetrical encephalomalacia produced by Clostridium perfringens type D epsilon toxin in sheep

Since axonal injury (AI) is an important component of many veterinary neurologic disorders, we assessed the relative ability of a panel of antibodies (amyloid precursor protein, 3 subunits of neurofilament protein, protein gene product 9.5, ubiquitin, and synaptophysin) to detect axonal swellings or spheroids. Abundant axonal spheroids found in necrotic internal capsule foci produced in 4 sheep by chronic Clostridium perfringens type D epsilon neurotoxicity provided a model system in which to evaluate this important diagnostic tool. There was heterogeneous labeling of subsets of spheroids by the respective antibodies, suggesting that, in order to detect the complete spectrum of AI in diagnostic cases, a range of antibodies should be used, not only when spheroids are plentiful but also when they are few in number or incompletely developed. The application of insufficient markers in the latter cases can potentially lead to the contribution of AI to lesion pathogenesis being underappreciated.

Hallervorden-Spatz Syndrome: Case Report of a Typical Form

Hallervorden-Spatz syndrome is a rare neurodegenerative disease, related to mutations in a gene located on chromosome 20p13. Hallervorden-Spatz syndrome is characterized by iron accumulation in the basal ganglia, which leads to variable neurologic manifestations. It is reported the case of a 6 years old male patient, with history of neuro psycho motor development involution noticed since 1 year and 5 months of age and progressive development of dystonia, mostly on upper limbs and neck. Brain Magnetic Resonance Imaging (MRI) revealed bilaterally symmetric signal changes in globus pallidus and in the posterior limb of the internal capsule, findings that suggest neurodegenerative disease with iron accumulation or metabolic disease.

STMO-19 Impact of aggressive resection for glioblastoma of the thalamus with histone H3-K27M mutation

Glioblastoma of the thalamus occurs predominantly in childhood and young adulthood, and cases with histone mutations are thought to have a particularly poor prognosis. We studied tumor resection rate, age, type of adjuvant therapy, and histone gene mutations on progression-free survival (PFS) and overall survival (OS) in patients who underwent aggressive removal. Eight cases of thalamic glioblastoma were included in the study. The mean age at surgery was 36.1 years (10–74 years, 3 cases under 18 years). Tumor removal was performed from the parieto-occipital lobe to the thalamus via the lateral ventricles in all cases. In all cases, more than 90% of the contrast-enhancing lesions were removed. Postoperatively, one patient had sensory disturbance of the left upper limb, and the other had incomplete paralysis of the left upper and lower limbs, but both were able to walk with a cane. In the case of the patient with postoperative complications, the tumor was located in the vicinity of the internal capsule. All patients were treated with radiation therapy and temozolomide, and bevacizumab and Novo-TTF were used in cases after approval. All patients were able to return home and return to school or work after initial treatment. The mean progression-free survival (PFS) was 0.87 years, and overall survival (OS) was 1.95 years. Five patients had histone H3-K27M mutations, and three patients had no mutations. PFS and OS were 1.02 years and 0.62 years, respectively, and 2.53 years and 1.20 years, respectively, both of which were longer in patients with mutations (PFS; p=0.16, OS; p=0.23).Aggressive removal of glioblastoma of the thalamus may improve prognosis, especially in patients with histone H3-K27M mutations. In patients with tumors extending to the vicinity of the internal capsule, total removal may cause paralysis and sensory disturbance.