Search Results (76)

Diffuse axonal brain injury (DAI) is a common, debilitating consequence of traumatic brain injury, yet its detection and severity grading remain challenging in clinical and experimental settings. This study evaluated the sensitivity of diffusion tensor imaging (DTI), histology, and neurological severity scoring (NSS) in assessing injury severity in a rat model of isolated DAI. A rotational injury model induced mild, moderate, or severe DAI in male and female rats. Neurological deficits were assessed 48 h after injury via NSS. Magnetic resonance imaging, including DTI metrics, such as fractional anisotropy (FA), relative anisotropy (RA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD), was performed prior to tissue collection. Histological analysis used beta amyloid precursor protein immunohistochemistry. Sensitivity and variability of each method were compared across brain regions and the whole brain. Histology was the most sensitive method, requiring very small groups to detect differences. Anisotropy-based MRI metrics, especially whole-brain FA and RA, showed strong correlations with histology and NSS and demonstrated high sensitivity with low variability. NSS identified injury but required larger group sizes. Diffusivity-based MRI metrics, particularly RD, were less sensitive and more variable. Whole-brain FA and RA were the most sensitive MRI measures of DAI severity and were comparable to histology in moderate and severe groups. These findings support combining NSS and anisotropy-based DTI for non-terminal DAI assessment in preclinical studies. Full article

Background: Enteroviruses, members of the Picornaviridae family, typically cause asymptomatic or mild infections. However, they can also result in central nervous system (CNS) involvement, with transverse myelitis (TM) occurring only on rare occasions. TM is a syndrome characterized by acute or subacute spinal cord dysfunction, leading to neurological deficits below the level of the lesion. Case report: We report a case series of eight pediatric patients admitted over a three-month period, June to August 2024. All patients presented with ataxia and/or other neurological symptoms, alongside abnormal cerebrospinal fluid (CSF) findings. Although ataxia is commonly associated with cerebellitis, magnetic resonance imaging (MRI) in this cohort revealed findings consistent with TM. Notably, all patients demonstrated similar MRI abnormalities. The onset of symptoms occurred over a short time during an enterovirus epidemic. Enteroviral RNA was detected, or the virus was isolated in seven patients, while one patient had a close epidemiological link to the virus. All patients achieved full recovery following immunomodulatory therapy. Conclusions: This case series underscores that ataxia may be an atypical symptom associated with TM. Furthermore, there was a notable distinction between the clinical presentation and neuroradiological findings. Immunomodulatory therapy with immunoglobulins and corticosteroids has been shown to be effective and safe, supporting the hypothesis of an immune-mediated pathogenesis in these patients. Full article

Background/Objectives: Idiopathic normal-pressure hydrocephalus (iNPH) is a potentially reversible neurological disorder characterized by gait disturbance, cognitive impairment, and urinary incontinence. Its pathophysiology involves impaired cerebrospinal fluid (CSF) absorption, and recent research has highlighted the role of the glymphatic and meningeal lymphatic systems in this process. However, the factors that trigger the clinical manifestations of iNPH in subclinical cases remain poorly understood. Case Presentation: Herein, we report two rare cases of iNPH in which clinical symptoms only became apparent following systemic infections. An 82-year-old man presented with transient neurological deficits during a course of sepsis caused by Klebsiella pneumoniae. Neuroimaging revealed periventricular changes and mild ventricular enlargement. Shunting and a tap test led to significant improvements to both his gait and cognition. An 80-year-old man with a history of progressive gait disturbance and cognitive decline developed worsening urinary incontinence and acute cerebral infarction caused by Staphylococcus haemolyticus bacteremia. Magnetic resonance imaging revealed a ventriculomegaly with features of disproportionally enlarged subarachnoid space hydrocephalus and a corona radiata infarct. Clinical improvement was achieved after a ventriculoperitoneal shunt was placed. Conclusions: Our two present cases suggest that systemic inflammatory states may act as catalysts for the manifestation of iNPH in patients with predisposing cerebral ischemia or subclinical abnormalities in CSF flow, highlighting the need for higher clinical awareness of iNPH in older patients who present with neurological deterioration during systemic infections. Early diagnosis and timely shunting after appropriate infection control may facilitate significant functional recovery in such patients. Full article

Background: Mild traumatic brain injury (mTBI) is a prevalent neurological condition that results in various physical, emotional, and cognitive impairments. The most common are visual impairments, which affect vision’s perceptual, motor, and sensory aspects. Objective: This paper analyzes the pathophysiology of mild traumatic brain injury (mTBI) and its effects on visual and oculomotor functions, focusing on the deficits of the accommodative system and their underlying mechanism. Findings: mTBI frequently causes diffuse axonal injury, resulting in abnormalities of the neurometabolic cascade that impact the brain’s visual regions. Accommodative anomalies, including insufficiency, infacility, and spasm, are markedly more common in mTBI patients than in the general population. These deficiencies present as a notable delay in accommodation response, diminished peak velocity, and compromised dynamic responses, possibly due to sensory and motor disturbances. Conclusions: Accommodation disorder is a significant but under-examined component of visual sequelae related to mTBI. Future research should concentrate on the sensory and motor factors contributing to these deficiencies to enhance diagnostic precision and customize rehabilitative strategies. Full article

Background/Objectives: Mild traumatic brain injury (mTBI) is a leading cause of pediatric emergency department visits, particularly among children under three years old. Although computed tomography (CT) is the gold standard for diagnosing intracranial injuries, its use in young children poses radiation risks. Identifying reliable clinical indicators that justify CT imaging is essential for optimizing both patient safety and resource utilization. Objective: This study aimed to evaluate CT findings in children under three years of age with mTBI and no focal neurological deficits, as well as to identify clinical predictors associated with skull fractures and intracranial injuries. Methods: A retrospective analysis was conducted on 224 children under 36 months who presented with mTBI to a tertiary pediatric hospital from July 2019 to July 2024. Demographic data, injury mechanisms, clinical presentation and CT findings were evaluated. Univariate and multivariate regression analyses were performed to identify risk factors associated with skull fractures and intracranial injuries. Results: Falls accounted for 96.4% of injuries, with the majority occurring from heights of 0.5–1 m. The parietal region was the most frequently affected site (38%). Skull fractures were present in 46% of cases and were primarily linear (92.8%). Intracranial hematomas were identified in 13.8% of cases, while brain edema was observed in 7.6%. Significant predictors of skull fractures included age under 12 months (p < 0.001), falls from 0.5–1 m (p = 0.005), somnolence (p = 0.030), scalp swelling (p = 0.001) and indentation of the scalp (p = 0.016). Parietal bone involvement was the strongest predictor of both skull fractures (OR = 7.116, p < 0.001) and intracranial hematomas (OR = 4.993, p < 0.001). Conversely, frontal bone involvement was associated with a lower likelihood of fractures and hematomas. Conclusions: The findings highlight key clinical indicators that can guide decision-making for CT imaging in children with mTBI. Infants under 12 months, falls from moderate heights and parietal bone involvement significantly increase the risk of fractures and intracranial injuries. A more refined diagnostic approach could help reduce unnecessary CT scans while ensuring the timely identification of clinically significant injuries. Full article

Acute ischemic stroke outcomes depend on various factors. We investigated whether the outcome-relevant factor (ORF) profiles differ between different vascular territories and different therapeutic strategies. In this retrospective study, we analyzed 410 comprehensive stroke center patients [median age of 70 years (IQR 57–80), 125 women (30%)] by analyzing five groups: all patients, patients with infratentorial infarctions only (n = 80), all patients with supratentorial infarctions (n = 330), patients with supratentorial infarctions without (n = 269), and with mechanical thrombectomy (n = 61). Outcomes were classified with the modified Rankin scale as ≤2 (good) or >2 (poor) after three months. The patient group with infratentorial strokes was compared to the group of patients with supratentorial strokes using the Kruskal–Wallis test or chi-squared statistics. Within each of the five stroke groups, univariate logistic regression analysis was used to identify the ORF of a poor outcome; if more than one ORF was identified, all identified factors were included in one multinomial logistic regression analysis model. Compared to the patients with supratentorial strokes, the patients with infratentorial stroke exhibited a less severe neurological deficit at entry and lower rates of ischemic heart disease, thrombolytic intervention, and cardio-embolism but a higher rate of large vessel disease. After multinomial logistic regression analysis, a poor outcome in the infratentorial group was associated with atrial fibrillation [odds ratio (OR) 13.73 (95% confidence interval 1.05–181.89), p = 0.04], estimated glomerular filtration rate [OR 0.96 (0.91–0.99)], p = 0.02], and marginally with diabetes mellitus [OR 7.69 (0.96–62.63), p = 0.05]. In all three supratentorial stroke groups, the neurological deficit as scored by the National Institute of Health Stroke Scale [OR 1.32 (1.22–1.44), p < 0.0001] was predominantly associated with a poor outcome, accompanied by age only in the group of all supratentorial strokes [OR 1.04 (1.01–1.08), p = 0.01]. In this cohort of mild to moderate stroke patients, the ORFs differed between the supra- and infratentorial stroke populations. Full article

Mild traumatic brain injury (mTBI) is a leading cause of morbidity in children with both short- and long-term neurological, cognitive, cerebrovascular, and emotional deficits. These deficits have been attributed to ongoing pathophysiological cascades that occur acutely and persist post-injury. Given our limited understanding of the transcriptional changes associated with these pathophysiological cascades, we studied formalin-fixed paraffin-embedded (FFPE) tissues from the frontal cortex (FC) and the hippocampus + amygdala (H&A) regions of swine (N = 40) after a sagittal rapid non-impact head rotation (RNR). We then sequenced RNA to define transcriptional changes at 1 day and 1 week after injury and investigated the protective influence of cyclosporine A (CsA) treatment. Differentially expressed genes (DEGs) were classified into five temporal patterns (Early, Transient, Persistent, Intensified, Delayed, or Late). DEGs were more abundant at 1 week than 1 day. Shared significant gene ontology annotations in both regions included terms associated with neuronal distress at 1 day and neurorecovery at 1 week. CsA (20 mg/kg/day) infused for 1 day (beginning at 6 h after injury) accelerated 466 DEGs in the FC and 2794 DEGs in the H&A, such that the CsA-treated transcriptional profile was associated with neurorecovery. Overall, our data reveal the effects of anatomic region and elapsed time on gene expression post-mTBI and motivate future studies of CsA treatment. Full article

Fragile-X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurodegenerative disorder associated with the FMR1 gene premutation, characterized by the presence of 55 to 200 CGG triplet repeat expansions. Although the initial symptoms of FXTAS typically manifest in males around the age of 60 with motor symptoms and cognitive deficits, the presentation and progression in females differ. Women, in fact, exhibit a higher prevalence of neuropsychiatric symptoms, with an earlier onset compared to the motor symptoms observed in men. The following article reports on ten cases of women with a diagnosis of FMR1 gene premutation, originating from two medical centers. All the women in the study exhibited neuropsychiatric symptoms and subtle neurological signs as common features. Symptoms typically observed in the male population, such as tremors and cerebellar ataxia, were either absent or significantly reduced in the female cohort. Conversely, there was a higher prevalence of neuropsychiatric symptoms among the women. Neurocognitive impairment was only minimally evident, with mild executive dysfunction and memory complaints noted in a subset of cases. For this reason, we propose the terminology preFXTAS or prodromic FXTAS to define a clinical presentation in women characterized by early manifestations of FXTAS that do not entirely fulfill the established diagnostic criteria but exhibit MRI evidence of white matter alterations suggesting the initiation of the disease process. The study underscores the importance of establishing new diagnostic criteria for FXTAS and, at the same time, developing new biomarkers and interview checklists/assessment scales dedicated to females. Full article

Background: The Zika virus (ZIKV) is an arbovirus linked to “Congenital Zika Syndrome” and a range of neurodevelopmental disorders (NDDs), with microcephaly as the most severe manifestation. Milder NDDs, such as autism spectrum disorders and delays in neuropsychomotor and language development, often go unnoticed in neonates, resulting in long-term social and academic difficulties. Murine models of ZIKV infection can be used to mimic part of the spectrum of motor and cognitive deficits observed in humans. These can be evaluated through behavioral tests, enabling comparison with gene expression profiles and aiding in the characterization of ZIKV-induced NDDs. Objectives: This study aimed to identify genes associated with behavioral changes following a subtle ZIKV infection in juvenile BALB/c mice. Methods: Neonatal mice were subcutaneously inoculated with ZIKV (MH544701.2) on postnatal day 1 (DPN) at a dose of 6.8 × 10³ PFU. Viral presence in the cerebellum and cortex was quantified at 10- and 30-days post-infection (DPI) using RT-qPCR. Neurobehavioral deficits were assessed at 30 DPI through T-maze, rotarod, and open field tests. Next-Generation Sequencing (NGS) was performed to identify differentially expressed genes (DEGs), which were analyzed through Gene Ontology (GO) and KEGG enrichment. Gene interaction networks were then constructed to explore gene interactions in the most enriched biological categories. Results: A ZIKV infection model was successfully established, enabling brain infection while allowing survival beyond 30 DPI. The infection induced mild cognitive behavioral changes, though motor and motivational functions remained unaffected. These cognitive changes were linked to the functional repression of synaptic vesicles and alterations in neuronal structure, suggesting potential disruptions in neuronal plasticity. Conclusions: Moderate ZIKV infection with circulating strains from the 2016 epidemic may cause dysregulation of genes related to immune response, alterations in cytoskeletal organization, and modifications in cellular transport mediated by vesicles. Despite viral control, neurocognitive effects persisted, including memory deficits and anxiety-like behaviors, highlighting the long-term neurological consequences of ZIKV infection in models that show no apparent malformations. Full article

Background: Healthy cognitive functioning is a primary component of well-being, independence, and successful aging. Cognitive deficits can arise from various conditions, such as brain injury, mental illness, and neurological disorders. Rehabilitation is a highly specialized service limited to patients who have access to institutional settings. In response to this unmet need, telehealth solutions are ideal for triggering the migration of care from clinics to patients’ homes. Objectives: The aim of EARLY-COGN^3 will be threefold: (1) to test the efficacy of a digital health at-home intervention (tele@cognitive protocol) as compared to an unstructured cognitive at-home rehabilitation in a cohort of patients with Chronic Neurological Diseases (CNDs); (2) to investigate its effects on the biomolecular and neurophysiological marker hypothesizing that people with CNDs enrolled in this telerehabilitation program will develop changes in biological markers and cortical and subcortical patterns of connectivity; (3) to analyze potential cognitive, neurobiological, and neurophysiological predictors of response to the tele@cognitive treatment. Method: In this single-blind, randomized, and controlled pilot study, we will assess the short- and long-term efficacy of cognitive telerehabilitation protocol (tele@cognitive) as compared to an unstructured cognitive at-home rehabilitation (Active Control Group—ACG) in a cohort of 60 people with Mild Cognitive Impairment (MCI), Subjective Cognitive Complaints (SCCs), or Parkinson’s Disease (PD). All participants will undergo a clinical, functional, neurocognitive, and quality of life assessment at the baseline (T0), post-treatment (5 weeks, T1), and at the 3-month (T2) follow-up. Neurophysiological markers and biomolecular data will be collected at T0 and T1. Conclusions: EARLY-COGN^3 project could lead to a complete paradigm shift from the traditional therapeutic approach, forcing a reassessment on how CNDs could take advantage of a digital solution. (clinicaltrials.gov database, ID: NCT06657274) Full article

Background and Clinical Significance: Aceruloplasminemia (ACP), a member of the neurodegeneration with brain iron accumulation (NBIA) spectrum of disorders, is a rare disorder caused by mutations in the ceruloplasmin (CP) gene. Iron accumulation in various organs, including the brain, liver, eyes, and heart, can lead to a broad clinical spectrum. Here, we report the first case of ACP in Greece. Case Presentation: Our patient was a 53-year-old male who was referred to our movement disorders center for a 6-month history of mild, unspecific, episodic dizziness and postural instability, and attention and memory deficits. Brain MRI revealed significant iron accumulation in multiple brain regions, including the dentate nuclei, cerebellar cortex, basal ganglia, thalamus, brainstem nuclei, and hypothalamus. These findings were particularly evident in susceptibility-weighted images. Fundoscopy revealed a normal retina, optic nerve, and macula. Whole-exome sequencing revealed a novel homozygous frameshift mutation in the CP gene [NM_000096.3:p.Thr3232fs (c.9695delC)]. This mutation has not been previously reported and is predicted to result in premature protein termination, supporting its pathogenic nature. Laboratory tests showed no anemia but revealed significantly elevated serum ferritin and low serum iron. Subsequent testing revealed extremely low serum CP and low serum copper. Despite less involvement of the myocardium, our patient succumbed to cardiac arrest. Conclusions: ACP should be considered in cases with minor neurological signs and symptoms. Brain MRI plays a significant role in early diagnosis. Close cardiac monitoring is also important. Full article

Eye-movement assessment is a key component of neurological evaluation, offering valuable insights into neural deficits and underlying mechanisms. This narrative review explores the emerging subject of digital eye-movement outcomes (DEMOs) and their potential as sensitive biomarkers for neurological impairment. Eye tracking has become a useful method for investigating visual system functioning, attentional processes, and cognitive mechanisms. Abnormalities in eye movements, such as altered saccadic patterns or impaired smooth pursuit, can act as important diagnostic indicators for various neurological conditions. The non-invasive nature, cost-effectiveness, and ease of implementation of modern eye-tracking systems makes it particularly attractive in both clinical and research settings. Advanced digital eye-tracking technologies and analytical methods enable precise quantification of eye-movement parameters, complementing subjective clinical evaluations with objective data. This review examines how DEMOs could contribute to the localisation and diagnosis of neural impairments, potentially serving as useful biomarkers. By comprehensively exploring the role of eye-movement assessment, this review aims to highlight the common eye-movement deficits seen in neurological injury and disease by using the examples of mild traumatic brain injury and Parkinson’s Disease. This review also aims to enhance the understanding of the potential use of DEMOs in diagnosis, monitoring, and management of neurological disorders, ultimately improving patient care and deepening our understanding of complex neurological processes. Furthermore, we consider the broader implications of this technology in unravelling the complexities of visual processing, attention mechanisms, and cognitive functions. This review summarises how DEMOs could reshape our understanding of brain health and allow for more targeted and effective neurological interventions. Full article

Objective: We present the case of a 26-year-old male with severe spinal tuberculosis of the thoracolumbar region. The patient suffered from worsening back pain over five years, initially responding to over-the-counter analgesics. Despite being proposed surgery in 2019, the patient refused the intervention and subsequently experienced significant disease progression. Methods: Upon re-presentation in 2022, mild involvement of the T12-L1 vertebrae was recorded by imaging, leading to a percutaneous needle biopsy which confirmed tuberculosis. Despite undergoing anti-tuberculous therapy for one year, the follow-up in 2024 revealed extensive infection from T10 to S1, with large psoas abscesses and a pseudo-tumoral mass of the right thigh. The patient was ultimately submitted to a two-stage surgical intervention: anterior resection and reconstruction of T11-L1 with an expandable cage, followed by posterior stabilization from T8-S1. Results: Postoperative recovery was uneventful, with significant pain relief and no neurological deficits. The patient was discharged on a continued anti-tuberculous regimen and remains under close surveillance. Conclusions: This paper presents details on the challenges of diagnosis and management of severe spinal tuberculosis, with emphasis on the importance of timely intervention and multidisciplinary care. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19), induced a global pandemic with a diverse array of clinical manifestations. While the acute phase of the pandemic may be waning, the intricacies of COVID-19′s impact on neurological health remain a crucial area of investigation. Early recognition of the spectrum of COVID-19 symptoms, ranging from mild fever and cough to life-threatening respiratory distress and multi-organ failure, underscored the significance of neurological complications, including anosmia, seizures, stroke, disorientation, encephalopathy, and paralysis. Notably, patients requiring intensive care unit (ICU) admission due to neurological challenges or due to them exhibiting neurological abnormalities in the ICU have shown increased mortality rates. COVID-19 can lead to a range of neurological complications such as anosmia, stroke, paralysis, cranial nerve deficits, encephalopathy, delirium, meningitis, seizures, etc., in affected patients. This review elucidates the burgeoning landscape of neurological sequelae associated with SARS-CoV-2 infection and explores the underlying neurobiological mechanisms driving these diverse manifestations. A meticulous examination of potential neuroinvasion routes by SARS-CoV-2 underscores the intricate interplay between the virus and the nervous system. Moreover, we dissect the diverse neurological manifestations emphasizing the necessity of a multifaceted approach to understanding the disease’s neurological footprint. In addition to elucidating the pathophysiological underpinnings, this review surveys current therapeutic modalities and delineates prospective avenues for neuro-COVID research. By integrating epidemiological, clinical, and diagnostic parameters, we endeavor to foster a comprehensive analysis of the nexus between COVID-19 and neurological health, thereby laying the groundwork for targeted therapeutic interventions and long-term management strategies. Full article

Mild traumatic brain injuries (mTBIs) are highly prevalent and can lead to chronic behavioral and cognitive deficits often associated with the development of neurodegenerative diseases. Oxidative stress and formation of reactive oxygen species (ROS) have been implicated in mTBI-mediated axonal injury and pathogenesis. However, the underlying mechanisms and contributing factors are not completely understood. In this study, we explore these pathogenic mechanisms utilizing a murine model of repetitive mTBI (r-mTBI) involving five closed-skull concussions in young adult C57BL/6J mice. We observed a significant elevation of Na⁺/H⁺ exchanger protein (NHE1) expression in GFAP⁺ reactive astrocytes, IBA1⁺ microglia, and OLIG2⁺ oligodendrocytes across various brain regions (including the cerebral cortex, corpus callosum, and hippocampus) after r-mTBI. This elevation was accompanied by astrogliosis, microgliosis, and the accumulation of amyloid precursor protein (APP). Mice subjected to r-mTBI displayed impaired motor learning and spatial memory. However, post-r-mTBI administration of a potent NHE1 inhibitor, HOE642, attenuated locomotor and cognitive functional deficits as well as pathological signatures of gliosis, oxidative stress, axonal damage, and white matter damage. These findings indicate NHE1 upregulation plays a role in r-mTBI-induced oxidative stress, axonal damage, and gliosis, suggesting NHE1 may be a promising therapeutic target to alleviate mTBI-induced injuries and restore neurological function. Full article