Search Results (73)

Background: The arcuate fasciculus (AF) is a critical white matter (WM) tract that connects key cortical language-processing regions, including the so-called Broca’s and Wernicke’s areas. The aim of the present study was to quantitatively assess its radiological–anatomical–morphometric modifications according to different brain tumor histotypes. Methods: A retrospective multicentric Italian study was conducted. AF reconstructions were calculated for both hemispheres for each patient diagnosed with glioblastoma (GBM), low-grade glioma (LGG), brain metastasis, and meningioma using Elements Fibertracking 2.0 software (Brainlab AG, Munich, Germany). A 3D object of each fascicle was evaluated for its volume, average fractional anisotropy (FA), and length. The cerebral healthy hemisphere was compared to the pathological contralateral in different tumor histotypes. Results: In total, 1294 patients were evaluated. A total of 156 met the inclusion criteria. We found a significant difference between healthy hemisphere and the contralateral for AF mean length and volume (p = 0.01 and p < 0.001, respectively). Considering separately the different tumor histotypes, the GBM subgroup (98, 63%) confirmed the results for mean FA and volume (p-value < 0.001); LGG patients (26, 17%) showed no significant difference between healthy and pathological hemisphere for AF mean length, mean FA, and volume (p-value 0.5, p-value 0.3, p-value <0.1, respectively). In patients affected by brain metastasis (18, 12%), Student’s t-test showed a significant difference for FA (p-value 0.003). No differences were found in patients affected by meningiomas (14, 9%) (14). Conclusions: Thorough knowledge of the microscopic anatomy and function of the arcuate fasciculus, as well as the pattern of growth of the different brain tumor histotypes, along with a careful preoperative neuroradiological assessment are mandatory to plan a tailored surgical strategy and perform a safe and effective surgical technique. The AF could be displaced and infiltrated/destructed by the solid component and peritumoral edema, respectively, of GBM. LGG shows a prevalent infiltrative pattern. Metastases account for AF dislocation due to peritumoral edema. Meningiomas do not affect WM anatomy. Full article

Background/Objectives: Olfaction is in many ways the least understood sensory modality. Its organization and connectivity are still under debate. The aim of this study was to investigate the anatomy of the olfactory system by using a cadaver fiber dissection technique and in vivo tractography to attain a deeper understanding of the subcortical connectivity and organization. Methods: Ten cerebral hemispheres were used in this study for white matter dissection according to Klingler’s technique. Measurements of different cortical structures and interhemispheric symmetry were compared. Diffusion tensor imaging sequences from twenty-five healthy individuals from the Human Connectome Project dataset were used to explore the connectivity of the olfactory system using DSI Studio. White matter connectivity between the following were reconstructed in vivo: (1) Olfactory bulb to primary olfactory cortices; (2) Olfactory bulb to secondary olfactory cortices; (3) Primary to secondary olfactory cortices. The DTI metrics of the identified major associative, projection and commissural pathways were subsequently correlated with olfactory function and cognition in seventy-five healthy individuals with Spearman’s rank correlation and the Benjamini–Hochberg method for false discoveries (CI 95%, p < 0.05) using R. Results: 1. The dissection showed that the lateral stria was significantly longer on the left side and projected towards the amygdala, the entorhinal and piriform cortex. 2. The medial stria was not evident as a consistent white matter structure. 3. Both dissection and tractography showed that major associative white matter pathways such as the uncinate fasciculus, the inferior fronto-occipital fasciculus and cingulum supported the connectivity between olfactory areas together with the anterior commissure. 4. No significant correlation was found between DTI metrics and sensory or cognition test results. Conclusions: We present the first combined fiber dissection analysis and tractography of the olfactory system. We propose a novel definition where the primary olfactory network is defined by the olfactory tract/bulb and primary olfactory cortices through the lateral stria only. The uncinate fasciculus, inferior fronto-occipital fasciculus and cingulum are the associative pathways supporting the connectivity between primary and secondary olfactory areas together with the anterior commissure. We suggest considering these structures as a secondary olfactory network. Further work is needed to attain a deeper understanding of the pathological and physiological implications of the olfactory system. Full article

Background/Objectives: Cerebral palsy (CP), often caused by early brain injury such as perinatal stroke or hemorrhage, is the most common lifelong motor disability. Early identification of at-risk infants and timely access to rehabilitation interventions are essential for improving long-term outcomes. The General Movements Assessment (GMA), performed in the first months of life, has high sensitivity and specificity to predict CP; however, the neurological correlates of general movements remain unclear. This analysis aimed to investigate the relationship between white matter integrity and general movements in infants with perinatal brain injury using advanced neuroimaging techniques. Methods: Diffusion-weighted MRI data were analyzed in 17 infants, 12 with perinatal brain injury and 5 typically developing infants. Tractography was used to identify the corticospinal tract, a key motor pathway often affected by perinatal brain injury, and tract-based spatial statistics (TBSS) were used to examine broader white matter networks. Diffusion parameters from the diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) models were compared between infants with and without typical general movements. Results: Corticospinal tract integrity did not differ between groups when averaged across hemispheres. However, infants with asymmetric general movements exhibited greater corticospinal tract asymmetries. A subset of infants with atypical general movement trajectories at <6 weeks and 3–5 months of age showed reduced corticospinal tract integrity compared to those with typical general movements. TBSS revealed significant differences in white matter integrity between infants with typical and atypical general movements in several white matter pathways, including the corpus callosum, the right posterior corona radiata, bilateral posterior thalamic radiations, the left fornix/stria terminalis, and bilateral tapetum. Conclusions: These findings support and expand upon previous research suggesting that white matter integrity across multiple brain regions plays a role in the formation of general movements. Corticospinal integrity alone was not strongly associated with general movements; interhemispheric and cortical-subcortical connectivity appear critical. These findings underscore the need for further research in larger, diverse populations to refine early biomarkers of neurodevelopmental impairment and guide targeted interventions. Full article

Chronic graft-versus-host disease (cGVHD) is a prognostically negative event following hematopoietic stem cell transplant (HSCT). While cGVHD mainly affects the muscles, skin, oral mucosa, eyes, lungs, gastrointestinal tract, and liver, central nervous system (CNS) involvement remains possible and, moreover, is rare when it occurs isolated. CNS-cGVHD can manifest with a wide spectrum of CNS disorders, including cerebrovascular diseases, autoimmune demyelinating diseases, and immune-mediated encephalitis. We present a case of 65-year-old man previously treated with HSCT presenting with progressive cerebrovascular disorder and optic neuropathy without any clear alternative causal processes except for immune-mediated CNS microangiopathy in the context of possible CNS-cGVHD, along with suggestive imaging and instrumental and laboratory findings. Starting one year after HSCT for acute myeloid leukemia, when the first cerebral ischemic event occurred and was then associated with a reduction in visual acuity, an extensive diagnostic work-up had remained inconclusive over many years, leading us to the hypothesis of CNS-cGVHD and, therefore, to the start of immunosuppressive therapy. Our experience highlighted not ignoring the possibility of cGVHD as the underlying mechanism of CNS disorder, even in the absence of other systemic presentations, once more common etiologies of CNS pathological processes have been ruled out. Full article

Background: Perinatal brain injury is a leading cause of developmental disabilities, including cerebral palsy. However, further work is needed to understand early brain development in the presence of brain injury. In this case report, we examine the longitudinal neuromotor development of a term infant following a significant loss of right-hemispheric brain tissue due to a unilateral ischemic stroke. Our analysis focuses on the integrity and development of the corticospinal tract (CST) from the lesioned hemisphere. This case provides a unique opportunity to evaluate CST development after loss of the majority of the motor cortex. Methods: Evaluations were conducted when the infant was 4 (Visit-1), 18 (Visit 2), and 25 (Visit 3) months old. Assessments included magnetic resonance imaging (MRI) to characterize the lesion and quantify CST structural integrity, single-pulse transcranial magnetic stimulation (spTMS) to evaluate CST functional circuitry, and neuromotor assessments. Results: At Visit 1, bilateral CSTs were identified through diffusion-weighted MRI (dMRI) despite an estimated loss of 92.7% (7.3% retained) of age-typical motor cortex from the right hemisphere. Both hemispheres exhibited bilateral motor-evoked potential in response to stimulation with spTMS, which remained when reassessed at Visits 2 and 3. Longitudinal MRI showed distinct developmental trajectories of CST integrity in each hemisphere, with the lesioned hemisphere exhibiting initial increases in integrity between Visits 1 and 2 followed by a decrease in integrity between Visits 2 and 3. The non-lesioned hemisphere showed increased integrity from Visit 1 to Visit 2, which remained stable at Visit 3. Motor assessments at all visits indicated a high risk of cerebral palsy. Conclusions: This report highlights the utility of MRI and spTMS in studying neuromotor development. The findings reveal preserved functional bilateral CST circuitry despite majority loss of the right-hemispheric motor cortex as well as distinct developmental trajectories in CST integrity between hemispheres. These results underscore the potential for neural plasticity after perinatal brain injury. Clinical Trials Registration: NCT05013736. Full article

Objective: To evaluate neurogenic bladder and bowel dysfunction (NBBD) in children with cerebral palsy (CP) and acquired brain injury (ABI), a condition considered less frequent in those patients than in children with spinal cord injury (SCI), and to study the relationship between NBBD and disability grade in this population. Study Design: We retrospectively reviewed the clinical data of all patients (aged 3–18 years old) admitted during a three-month observation in our neurorehabilitation department. Data collected were as follows: demographic parameters; disability status (Wee-FIM Scale, Gross Motor Function Classification System (GMFCS) and the Communication Function Classification System); and gastrointestinal and urological symptoms (diaries, Bristol scale, Pad Test and International Consultation on Incontinence Modular Questionnaire). Results: Sixty patients were enrolled (31 females, 29 males): 30 CP, 17 ABI, 3 SCI, and 10 others with neurological diseases. All presented urinary incontinence without gender differences. CP and ABI had major incidences of bowel dysfunction (50% and 64.7%, respectively) and SCI of urinary tract infections (66.6%) and enuresis (100%). A major incidence of symptoms was recorded in patients with higher GMFCS levels (level 3-4-5). Conclusions: NBBD has a high frequency in children with CP and ABI, as in SCI. More attention is needed from pediatricians and pediatric urologists for this clinical entity. Further studies are needed to better understand clinical relevance and, therefore, to establish specific management. Full article

Introduction: Quantitative spinal cord imaging has facilitated the objective appraisal of spinal cord pathology in a range of neurological conditions both in the academic and clinical setting. Diverse methodological approaches have been implemented, encompassing a range of morphometric, diffusivity, susceptibility, magnetization transfer, and spectroscopy techniques. Advances have been fueled both by new MRI platforms and acquisition protocols as well as novel analysis pipelines. The quantitative evaluation of specific spinal tracts and grey matter indices has the potential to be used in diagnostic and monitoring applications. The comprehensive characterization of spinal disease burden in pre-symptomatic cohorts, in carriers of specific genetic mutations, and in conditions primarily associated with cerebral disease, has contributed important academic insights. Methods: A narrative review was conducted to examine the clinical and academic role of quantitative spinal cord imaging in a range of neurodegenerative and acquired spinal cord disorders, including hereditary spastic paraparesis, hereditary ataxias, motor neuron diseases, Huntington’s disease, and post-infectious or vascular disorders. Results: The clinical utility of specific methods, sample size considerations, academic role of spinal imaging, key radiological findings, and relevant clinical correlates are presented in each disease group. Conclusions: Quantitative spinal cord imaging studies have demonstrated the feasibility to reliably appraise structural, microstructural, diffusivity, and metabolic spinal cord alterations. Despite the notable academic advances, novel acquisition protocols and analysis pipelines are yet to be implemented in the clinical setting. Full article

Background/Objectives: Alzheimer’s disease (AD), a complex neurogenerative disorder, manifests as dementia and concomitant neuropsychiatric symptoms, including apathy, depression, and circadian disruption. The pathology involves a profound degeneration of the hippocampus and cerebral cortex, leading to the impairment of both short-term and long-term memory. The cholinergic hypothesis is among the various theories proposed, that assume the loss of the cholinergic tract contributes to the onset of AD and proves clinically effective in managing mild to moderate stages of the disease. This study explores the potential therapeutic efficacy of sulfonamide-based butyrylcholinesterase inhibitors in mitigating scopolamine-induced amnesia in rats. Methods: Behavioral assessments utilizing Y-maze, Barnes maze, and neurochemical assays were conducted to evaluate the effectiveness of the test compounds. Results: Results demonstrated a significant reduction in the impact of scopolamine administration on behavioral tasks at a dose of 20 mg/kg for both compounds. Correspondingly, neurochemical assays corroborated these findings. In silico docking analysis on rat butyrylcholinesterase (BChE) was performed to elucidate the binding mode of the compounds. Subsequent molecular dynamics studies unveiled the formation of stable complexes between the test compounds and rat BChE. Conclusions: These findings contribute valuable insights into the potential therapeutic role of sulfonamide-based butyrylcholinesterase inhibitors in addressing memory deficits associated with AD, emphasizing their in silico molecular interactions and stability. Full article

Neonatal hypoxia–ischemia is a major cause of infant death and disability. The only clinically accepted treatment is therapeutic hypothermia; however, cooling is less effective in the most severely encephalopathic infants. Here, we wanted to test the neuroprotective effect of the antioxidant dimethyl fumarate after severe hypoxia–ischemia in neonatal rats. We used a modified Rice–Vannucci model to generate severe hypoxic–ischemic brain damage in day 7 postnatal rats, which were randomized into four experimental groups: Sham, Sham + DMF, non-treated HI, and HI + DMF. We analyzed brain tissue loss, global and regional (cortex and hippocampus) neuropathological scores, white matter injury, and microglial and astroglial reactivity. Compared to non-treated HI animals, HI + DMF pups showed a reduced brain area loss (p = 0.0031), an improved neuropathological score (p = 0.0016), reduced white matter injuries by preserving myelin tracts (p < 0.001), and diminished astroglial (p < 0.001) and microglial (p < 0.01) activation. After severe hypoxia–ischemia in neonatal rats, DMF induced a strong neuroprotective response, reducing cerebral infarction, gray and white matter damage, and astroglial and microglial activation. Although further molecular studies are needed and its translation to human babies would need to evaluate the molecule in piglets or lambs, DMF may be a potential treatment against neonatal encephalopathy. Full article

The cerebral small vessel disease (cSVD) is one of the main causes of vascular and mixed cognitive impairment (CI), and it is associated, in particular, with brain ageing. An understanding of structural tissue changes in an intact cerebral white matter in cSVD might allow one to develop the sensitive biomarkers for early diagnosis and monitoring of disease progression. Purpose of the study: to evaluate microstructural changes in the corpus callosum (CC) using diffusion MRI (D-MRI) approaches in cSVD patients with different severity of CI and reveal the most sensitive correlations of diffusion metrics with CI. Methods: the study included 166 cSVD patients (51.8% women; 60.4 ± 7.6 years) and 44 healthy volunteers (65.9% women; 59.6 ± 6.8 years). All subjects underwent D-MRI (3T) with signal (diffusion tensor and kurtosis) and biophysical (neurite orientation dispersion and density imaging, NODDI, white matter tract integrity, WMTI, multicompartment spherical mean technique, MC-SMT) modeling in three CC segments as well as a neuropsychological assessment. Results: in cSVD patients, microstructural changes were found in all CC segments already at the subjective CI stage, which was found to worsen into mild CI and dementia. More pronounced changes were observed in the forceps minor. Among the signal models FA, MD, MK, RD, and RK, as well as among the biophysical models, MC-SMT (EMD, ETR) and WMTI (AWF) metrics exhibited the largest area under the curve (>0.85), characterizing the loss of microstructural integrity, the severity of potential demyelination, and the proportion of intra-axonal water, respectively. Conclusion: the study reveals the relevance of advanced D-MRI approaches for the assessment of brain tissue changes in cSVD. The identified diffusion biomarkers could be used for the clarification and observation of CI progression. Full article

Cerebral palsy (CP) results in non-progressive damage to the central nervous system, leading to functional disorders of the gastrointestinal tract and requiring enteral nutrition via gastrostomy in some patients. The aim of the study was to assess the impact of enteral nutrition on intestinal inflammation expressed by stool calprotectin and intestinal permeability determined by fecal zonulin and IFABP, and to determine whether CP affects these parameters. The study group consisted of 30 children with CP, fed enterally (Cerebral Palsy Enteral Nutrition—CPEN), and two reference groups: 24 children with CP, fed orally with a standard diet (CPC—Cerebral Palsy Controls) and 24 healthy children (HC—healthy controls). The differences between these groups and between the combined CP groups (CPG and CPEN + CPC) and HC were analyzed. Fecal zonulin, calprotectin, and intestinal fatty acid-binding protein 2 (IFABP2) levels were determined by ELISA. The concentrations of fecal calprotectin and zonulin were significantly higher in the CPEN group than in the CPC group (p = 0.012, p = 0.025). When comparing the CPG (n = 53) with the HC group (n = 24), statistically significant differences were observed for calprotectin (p = 0.000018, higher in the CPG) and IFABP (p = 0.021, higher in HC). Enteral nutrition was associated in our cohort with increased fecal calprotectin and zonulin. Children with cerebral palsy presented with increased fecal calprotectin but not increased intestinal permeability expressed by stool zonulin. Full article

The impact of ethanol on the fetus is a significant concern as an estimated 2–5% of live births may be affected by prenatal alcohol exposure. This exposure can lead to various functional and structural abnormalities in the cerebral cortex, basal ganglia, diencephalon, and cerebellum, resulting in region-specific symptoms. The deficits relate to the motor and cognitive domains, affecting, in particular, general intelligence, attention, executive functions, language, memory, visual perception, and social skills—collectively called the fetal alcohol spectrum disorder (FASD). Recent studies suggest that damage to the developing cerebellum (in form of alcohol exposure) can impair the cortical targets of the cerebello-thalamo-cortical tract. This malfunction in the cerebello-cerebral loop optimization may be due to disruptions in the formation of the foundational elements of the internal model within the developing cerebellum. Alcohol exposure targets multiple nodes in the reciprocal loops between the cerebellum and cerebral cortex. Here, we examine the possibility that prenatal alcohol exposure damages the developing cerebellum and disrupts the connectivity within the cerebello-cerebral neuronal circuits, exacerbating FASD-related cortical dysfunctions. We propose that malfunctions between cerebellar internal model (critically involved in predictions) and cerebral regions contribute to the deficits observed in FASD. Given the major role of the cerebellum in motor, cognitive, and affective functions, we suggest that therapies should target these malfunctions to mitigate the burden of FASD. We discuss the concept of therapies oriented towards malfunctioning cerebello-cerebral loops (TOMCCLs), emphasizing anti-inflammatory strategies and treatments aimed at modulating cerebellar myelination to restore optimal and predictive cerebello-cerebral functions. Full article

Objective: To determine whether early structural brain trajectories predict early childhood neurodevelopmental deficits in complex CHD patients and to assess relative cumulative risk profiles of clinical, genetic, and demographic risk factors across early development. Study Design: Term neonates with complex CHDs were recruited at Texas Children’s Hospital from 2005–2011. Ninety-five participants underwent three structural MRI scans and three neurodevelopmental assessments. Brain region volumes and white matter tract fractional anisotropy and radial diffusivity were used to calculate trajectories: perioperative, postsurgical, and overall. Gross cognitive, language, and visuo-motor outcomes were assessed with the Bayley Scales of Infant and Toddler Development and with the Wechsler Preschool and Primary Scale of Intelligence and Beery–Buktenica Developmental Test of Visual–Motor Integration. Multi-variable models incorporated risk factors. Results: Reduced overall period volumetric trajectories predicted poor language outcomes: brainstem ((β, 95% CI) 0.0977, 0.0382–0.1571; p = 0.0022) and white matter (0.0023, 0.0001–0.0046; p = 0.0397) at 5 years; brainstem (0.0711, 0.0157–0.1265; p = 0.0134) and deep grey matter (0.0085, 0.0011–0.0160; p = 0.0258) at 3 years. Maternal IQ was the strongest contributor to language variance, increasing from 37% at 1 year, 62% at 3 years, and 81% at 5 years. Genetic abnormality’s contribution to variance decreased from 41% at 1 year to 25% at 3 years and was insignificant at 5 years. Conclusion: Reduced postnatal subcortical–cerebral white matter trajectories predicted poor early childhood neurodevelopmental outcomes, despite high contribution of maternal IQ. Maternal IQ was cumulative over time, exceeding the influence of known cardiac and genetic factors in complex CHD, underscoring the importance of heritable and parent-based environmental factors. Full article

In recent years, particular attention has been paid to the serotonin 4 receptor, which is well expressed in the brain, but also peripherally in various organs. The cerebral distribution of this receptor is well conserved across species, with high densities in the basal ganglia, where they are expressed by GABAergic neurons. The 5-HT₄ receptor is also present in the cerebral cortex, hippocampus, and amygdala, where they are carried by glutamatergic or cholinergic neurons. Outside the central nervous system, the 5-HT₄ receptor is notably expressed in the gastrointestinal tract. The wide distribution of the 5-HT₄ receptor undoubtedly contributes to its involvement in a plethora of functions. In addition, the modulation of this receptor influences the release of serotonin, but also the release of other neurotransmitters such as acetylcholine and dopamine. This is a considerable asset, as the modulation of the 5-HT₄ receptor can therefore play a direct or indirect beneficial role in various disorders. One of the main advantages of this receptor is that it mediates a much faster antidepressant and anxiolytic action than classical selective serotonin reuptake inhibitors. Another major benefit of the 5-HT₄ receptor is that its activation enhances cognitive performance, probably via the release of acetylcholine. The expression of the 5-HT₄ receptor is also altered in various eating disorders, and its activation by the 5-HT₄ agonist negatively regulates food intake. Additionally, although the cerebral expression of this receptor is modified in certain movement-related disorders, it is still yet to be determined whether this receptor plays a key role in their pathophysiology. Finally, there is no longer any need to demonstrate the value of 5-HT₄ receptor agonists in the pharmacological management of gastrointestinal disorders. Full article

Palmitoylethanolamine (PEA) is an endocannabinoid-like compound first encountered within the lipid fractions of specific foods and has intrigued researchers since the 1950s due to its therapeutic effects. This survey aims to explore the therapeutic promise held by PEA as an anti-inflammatory and immunomodulatory agent. The therapeutic impact of PEA reverberates across diverse physiological systems, such as the central nervous system, gastrointestinal tract, vascular network, and the digestive and respiratory system. Additionally, it is effective in pain management and reducing inflammation and immune responses. These attributes have fostered collaborations targeting conditions such as Alzheimer’s disease, multiple sclerosis, cerebral ischemia, neuroinflammation, general inflammation, pain, coagulopathy, steatohepatitis, and acute lung injury. PEA operates both independently and in synergy with other compounds, like paracetamol, luteolin, and oxymetazoline. This efficacy stems from its interactions with pivotal targets, including PPARα, PPAR-δ, PPAR-γ, CB1, CB2, GPR55, and TRPV1. Additionally, PEA exerts a direct influence on the inflammatory cascade, orchestrating precise adjustments in immune responses. Numerous animal studies have elucidated the inherent potential of PEA. Nevertheless, the imperative of reinforcing clinical investigation is evident. This review notably underscores the pivotal necessity for methodologically rigorous clinical trials to definitively establish the translational efficacy of PEA in ameliorating diverse inflammatory pathologies within the human milieu. Full article