Journal Description
Neurology International
Neurology International
is an international, peer-reviewed, open access journal which provides an advanced forum for studies related to all aspects of neurology and neuroscience, published monthly online by MDPI (from Volume 12 issue 3 - 2020).
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, ESCI (Web of Science), PubMed, PMC, Embase, and other databases.
- Journal Rank: JCR - Q2 (Clinical Neurology)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 26.5 days after submission; acceptance to publication is undertaken in 3.7 days (median values for papers published in this journal in the second half of 2024).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names published annually in the journal.
- Journal Cluster of Neurosciences: Brain Sciences, Neurology International, NeuroSci, Clinical and Translational Neuroscience, Neuroglia, Psychiatry International, Clocks & Sleep and Journal of Dementia and Alzheimer's Disease.
Impact Factor:
3.2 (2023);
5-Year Impact Factor:
2.6 (2023)
Latest Articles
The C/C Genotype of the C-1019G (rs6295) Polymorphism of the 5-HT1A Receptor Gene Is Associated with Lower Susceptibility to Depressive Symptoms in a Rural Population in Mexico
Neurol. Int. 2025, 17(6), 87; https://doi.org/10.3390/neurolint17060087 (registering DOI) - 31 May 2025
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Background: Depression is one of the most prevalent mental health disorders worldwide, affecting a significant proportion of the global population. Its etiology is complex and influenced by the interaction of environmental factors and genetic variations. In Mexico, it has been reported that 41.3%
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Background: Depression is one of the most prevalent mental health disorders worldwide, affecting a significant proportion of the global population. Its etiology is complex and influenced by the interaction of environmental factors and genetic variations. In Mexico, it has been reported that 41.3% of the population exhibits depressive symptoms. Previous studies have suggested that susceptibility to depression may be associated with the C-1019G (rs6295) polymorphism in the serotonin 1A (5-HT1A) receptor gene. Objective: In this study, we aimed to evaluate the association between the C-1019G polymorphism and depressive symptoms in a rural Mexican population. Methods: Using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP), we examined the effect of C-1019G on depression symptoms, as evaluated by the Beck Depression Inventory. Data were obtained from 83 volunteers; individuals with depressive symptoms and those with a healthy mood were compared. Results: The results showed that the homozygous C/C genotype was found significantly more frequently in the control group than in individuals with depressive symptoms, particularly among men, and is thus associated with a decreased risk of depressive symptomatology. Conclusions: The C/C genotype could protect against susceptibility to developing depressive symptoms in a rural population in Mexico.
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Open AccessCase Report
Idiopathic Normal-Pressure Hydrocephalus Revealed by Systemic Infection: Clinical Observations of Two Cases
by
Shinya Watanabe, Yasushi Shibata, Kosuke Baba, Yuhei Kuriyama and Eiichi Ishikawa
Neurol. Int. 2025, 17(6), 86; https://doi.org/10.3390/neurolint17060086 - 30 May 2025
Abstract
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
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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.
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(This article belongs to the Section Brain Tumor and Brain Injury)
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Open AccessArticle
Gender Differences in Obstructive Sleep Apnea: A Preliminary Clinical and Polysomnographic Investigation
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Alessandra Castelnuovo, Sara Marelli, Salvatore Mazzeo, Francesca Casoni, Paola Proserpio, Alessandro Oldani, Alessandro Bombaci, Elisa Bortolin, Giulia Bruschi, Federica Agosta, Massimo Filippi, Luigi Ferini-Strambi and Maria Salsone
Neurol. Int. 2025, 17(6), 85; https://doi.org/10.3390/neurolint17060085 - 29 May 2025
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Background/Objectives: Gender differences influence the clinical manifestations, progression, and treatment response in obstructive sleep apnea (OSA) syndrome, suggesting the existence of distinct gender-related phenotypes potentially driven by anatomical, physiological, and hormonal factors. However, the impact of gender on OSA-related cognitive profiles remains unknown.
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Background/Objectives: Gender differences influence the clinical manifestations, progression, and treatment response in obstructive sleep apnea (OSA) syndrome, suggesting the existence of distinct gender-related phenotypes potentially driven by anatomical, physiological, and hormonal factors. However, the impact of gender on OSA-related cognitive profiles remains unknown. This study aimed to investigate the neuropsychological and polysomnographic (PSG) differences between OSA females and males in order to detect the impact of gender on clinical manifestation and PSG features. Methods: Data were collected from 28 OSA patients (14 females and 14 males matched for age, education, and disease severity). All patients performed a complete neuropsychological evaluation, Epworth sleepiness scale, and whole-night PSG. To evaluate the relationship between specific sleep profiles and cognitive performance, PSG parameters were correlated to scores obtained on neuropsychological tests. Results: Both male and female groups performed within the normal range across all administered neuropsychological tests, according to Italian normative values. Compared with OSA males, female patients showed significantly lower values on the Rey–Osterrieth Complex Figure (ROCF) Recall Test. By contrast, no significant statistical clinical difference emerged between the two OSA groups in terms of clinical manifestation and sleep parameters. Conclusions: This study improves the knowledge on gender-related cognitive impairment in OSA patients. Our preliminary findings demonstrate that the ROCF Recall Test may be altered in OSA females, but not in males. Further longitudinal studies are needed to investigate whether OSA female patients will develop a frank dementia over time.
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Open AccessArticle
Treatment-Associated Neuroplastic Changes in People with Stroke-Associated Ataxia—An fMRI Study
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Patricia Meier, Christian Siedentopf, Lukas Mayer-Suess, Michael Knoflach, Stefan Kiechl, Gudrun Sylvest Schönherr, Astrid E. Grams, Elke R. Gizewski, Claudia Lamina, Malik Galijasevic and Ruth Steiger
Neurol. Int. 2025, 17(6), 84; https://doi.org/10.3390/neurolint17060084 - 29 May 2025
Abstract
Background/Objectives: In consideration of the significance of the pursuit of training-induced neuroplastic changes in the stroke population, who are reliant on neurorehabilitation treatment for the restoration of neuronal function, the objectives of this trial were to investigate fMRI paradigms for acute stroke
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Background/Objectives: In consideration of the significance of the pursuit of training-induced neuroplastic changes in the stroke population, who are reliant on neurorehabilitation treatment for the restoration of neuronal function, the objectives of this trial were to investigate fMRI paradigms for acute stroke patients with ataxic symptoms, to follow up on changes in motor function and balance due to recovery and rehabilitation, and to investigate the different effects of two treatment methods on neuronal plasticity. Methods: Therefore, fMRI-paradigms foot tapping and the motor imagery (MI) of a balancing task (tandem walking) were employed. Results: The paradigms investigated were suitable for ataxic stroke patients to monitor changes in neuroplasticity while revealing increased activity in the primary motor cortex (M1) and the cerebellum over 3 months of treatment. Furthermore, analysis of the more complex balance task revealed augmented activation of association areas due to training. Coordination exercises, constituting a specific treatment of ataxic symptoms, indicate more consolidated brain activations, corresponding to a faster motor learning process. Activation within Brodmann Area 7 has been prominent among all paradigms, indicating a special importance of this region for coordinative functions. Conclusions: Further studies are needed to confirm our results in larger patient groups. Clinical Trial Registration: German Clinical Trials Registry (drks.de). Identifier: DRKS00020825. Registered 16.07.2020.
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(This article belongs to the Topic Advances in Exercise-Induced Neurogenesis, Neuronal and Functional Adaptations in Neurorehabilitation)
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Open AccessReview
Ketamine in Status Epilepticus: How Soon Is Now?
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Giuseppe Magro
Neurol. Int. 2025, 17(6), 83; https://doi.org/10.3390/neurolint17060083 - 28 May 2025
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Status epilepticus (SE) is a neurological emergency. Current evidence dictates a step-by-step approach with a first line of therapy consisting of benzodiazepines (BDZs). In many situations, the currently approved approach does not terminate a BDZ-resistant SE. This happens in Stage 1 Plus, a
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Status epilepticus (SE) is a neurological emergency. Current evidence dictates a step-by-step approach with a first line of therapy consisting of benzodiazepines (BDZs). In many situations, the currently approved approach does not terminate a BDZ-resistant SE. This happens in Stage 1 Plus, a framework designed by the author to recognize cases of probable benzodiazepine-resistant status epilepticus even before treatment initiation. These cases include Prolonged SE (SE lasting > 10 min), the absence of prominent motor phenomena, and acute etiology (primary central nervous system etiologies most of all). BDZ-refractory SE cases (Stage 1 Plus) might require a different approach, one targeting the unresponsive GABA signaling state mediated by NMDA/AMPA receptors, such as combined polytherapy with Ketamine from the start. These considerations stem from the receptor trafficking hypotheses: in prolonged seizure activity and primary central nervous system etiologies, GABA receptors get internalized and move away from synapses, and therefore, SE becomes resistant to BDZ. A rational polytherapy that might restore the unresponsiveness to BDZ in SE should include NMDA antagonists, such as Ketamine. Ketamine has proven effective in many experimental models of status epilepticus, and much evidence is gathering supporting its use in humans, especially in refractory and super-refractory SE. We lack studies evaluating combined polytherapy in SE, especially in the early phases. The author suggests here that Ketamine should be used along with first-line BDZ in the early SE stage falling in the category of Stage 1 Plus and as a first-line anesthetic infusion drug in refractory SE, especially in cases progressing from Stage 1 Plus, eventually adding continuous midazolam/propofol infusion in later phases. This systematic review’s objective is to summarize the presently available evidence of the early use of combined polytherapy that includes Ketamine, along with the currently available evidence of Ketamine use in early, established, and refractory SE. Nine studies were included. Boluses of Ketamine and Midazolam are effective in pediatric convulsive Stage 1 Plus SE. The results show that earlier Ketamine administration (especially within 12 h of SE onset) was significantly associated with improved seizure control, with a more favorable safety profile than Midazolam in refractory SE. Notably, a dosage of less than 0.9 mg/kg/h proves ineffective in terminating SE. Ketamine has the advantage of preventing intubation, possibly shortening the length of stay in the intensive care unit.
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Open AccessArticle
The Impact of Hypertension and Related Risk Factors on the Onset and Resolution Rates of Benign Paroxysmal Positional Vertigo Recurrence: A 6-Year Retrospective Study
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Alessandro Micarelli, Ivan Granito, Riccardo Xavier Micarelli and Marco Alessandrini
Neurol. Int. 2025, 17(6), 82; https://doi.org/10.3390/neurolint17060082 - 25 May 2025
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Background/Objectives: Due to conflicting results about hypertension and the involvement of associated risk factors in the presentation of idiopathic benign paroxysmal positional vertigo recurrence (R-BPPV), this study aimed to explore possible associations between the resolution rate (RR) and recurrence onset (RO) of R-BPPV,
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Background/Objectives: Due to conflicting results about hypertension and the involvement of associated risk factors in the presentation of idiopathic benign paroxysmal positional vertigo recurrence (R-BPPV), this study aimed to explore possible associations between the resolution rate (RR) and recurrence onset (RO) of R-BPPV, as well as hypertension classification and stages and demographic characteristics. Methods: A total of 1201 medical records from patients collected over a 6-year span who first presented with R-BPPV were retrospectively evaluated regarding blood pressure (BP) presentation and associated risk factors. R-BPPV included patients treated with necessary canalith repositioning procedures (CRPs) and followed up with for 12 months. The RO and RR were evaluated when comparing patients sub-grouped by current classification and staging. The association between the RO and RR and many prognostic factors, including the presence of cardio- and neuro-vascular risks, was examined via multiple regression analysis. Results: Among the 857 included patients with R-BPPV, 211 presented with an optimal/normal BP, 210 were found to have a high–normal BP, 222 were classified with Grade 1 hypertension, and 214 were found to have Grade 2 hypertension. Significant (p < 0.05) progressive earlier presentations and increases in needed CRPs were found with the respective increase in BP subgroups. For the RO, the correlation was statistically significant for age and gender, while for the RR, the correlation was statistically significant for age and hypertension stage. Conclusions: This study demonstrates for the first time that clinical consequences of R-BPPV are strongly associated with cardio-, neuro-vascular, and socio-demographic risk factors, which are commonly involved in R-BPPV occurrence.
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Open AccessReview
Reciprocal Interactions Between Periodontal Disease and Alzheimer’s Disease: Implications for Mutual Triggering, Exacerbation, and Treatment Interventions—A Comprehensive Review of the Literature
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Shatha Gharaibeh, Alameen Alsabbah, Ahmad Alloubani and Abeer Gharaibeh
Neurol. Int. 2025, 17(6), 81; https://doi.org/10.3390/neurolint17060081 - 24 May 2025
Abstract
Periodontal health is connected to many systemic diseases, such as cardiovascular, diabetes mellitus, and neurodegenerative diseases. The oral–brain axis has gained increasing interest in the pathogenesis of diseases. Emerging studies have highlighted the potential role of periodontal disease in the development and progression
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Periodontal health is connected to many systemic diseases, such as cardiovascular, diabetes mellitus, and neurodegenerative diseases. The oral–brain axis has gained increasing interest in the pathogenesis of diseases. Emerging studies have highlighted the potential role of periodontal disease in the development and progression of Alzheimer’s disease. However, Alzheimer’s disease also affects periodontal disease and oral health. In this review, we address the correlation between the two diseases and the mechanisms by which one contributes to the other. Exploring the correlation between Alzheimer’s disease and periodontal disease will assist in better understanding the pathophysiology of diseases and pave the way for the development of therapeutic and preventive strategies.
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(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)
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Open AccessArticle
Identifying Clinical Measures Related to Falls in Ambulatory Patients with Spinal and Bulbar Muscular Atrophy
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Joseph A. Shrader, Allison C. Niemic, Rafael Jiménez-Silva, Joshua G. Woolstenhulme, Galen O. Joe, Uma Jacobs, Ashwini Sansare, Angela Kokkinis, Kenneth Fischbeck, Chris Grunseich and Cris Zampieri
Neurol. Int. 2025, 17(6), 80; https://doi.org/10.3390/neurolint17060080 - 23 May 2025
Abstract
Introduction: Spinal and bulbar muscular atrophy (SBMA) is an adult-onset, X-linked, progressive neuromuscular disease caused by abnormal CAG trinucleotide expansion in the androgen receptor gene. Patients with SBMA report difficulty with falls on self-reported activities of daily living scales. To our knowledge, no
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Introduction: Spinal and bulbar muscular atrophy (SBMA) is an adult-onset, X-linked, progressive neuromuscular disease caused by abnormal CAG trinucleotide expansion in the androgen receptor gene. Patients with SBMA report difficulty with falls on self-reported activities of daily living scales. To our knowledge, no study has examined the relationship between falls and common clinical measures of strength, balance, mobility, and disease biomarkers. We performed a cross-sectional analysis of an SBMA cohort. Objectives: The objectives of this study are as follows: (1) compare demographics, clinical measures, and biomarkers between patients who did and did not fall; (2) determine which measures best discriminate fallers from non-fallers; and (3) identify cutoff scores to detect patients with a higher fall risk. Design: Cross-sectional analysis was used. Outcome Measures: Disease biomarkers included blood serum creatinine, and clinical measures included the Timed Up and Go (TUG), the Adult Myopathy Assessment Tool (AMAT), and posturography, including the Modified Clinical Test of Sensory Interaction on Balance and the Motor Control Test. The Maximal Voluntary Isometric Contractions (MVICs) of four lower extremity muscles were captured via fixed-frame dynamometry. Results: We identified three clinical measures that help detect fall risk in people with SBMA. A post hoc receiver operating characteristic curve analysis helped identify cut scores for each test. Impairments of mobility (TUG > 8 s), muscle endurance (AMAT endurance subscale < 14), and muscle strength (ankle plantar flexion MVIC < 45% of predicted) were different between fallers and non-fallers, via independent t-tests. Conclusions: These three clinical tests can help detect fall riskthat may help clinicians implement gait aid use or other fall prevention strategies before catastrophic falls occur.
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(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)
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Open AccessArticle
Evaluation of Sensory and Motor Function in Spinal and Bulbar Muscular Atrophy Using Quiet Stance and Reactive Postural Control
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Joseph A. Shrader, Ashwini Sansare, Allison C. Niemic, Rafael Jiménez-Silva, Joshua G. Woolstenhulme, Galen O. Joe, Uma Jacobs, Angela Kokkinis, Kenneth Fischbeck, Chris Grunseich and Cris Zampieri
Neurol. Int. 2025, 17(6), 79; https://doi.org/10.3390/neurolint17060079 - 22 May 2025
Abstract
Introduction: Spinal and bulbar muscular atrophy (SBMA) is an X-linked neuromuscular disorder characterized by progressive muscle weakness, along with muscle cramps, tremors, and sensory neuropathy. Previous research has shown that patients with SBMA have difficulty with dynamic balance and sensory postural control during
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Introduction: Spinal and bulbar muscular atrophy (SBMA) is an X-linked neuromuscular disorder characterized by progressive muscle weakness, along with muscle cramps, tremors, and sensory neuropathy. Previous research has shown that patients with SBMA have difficulty with dynamic balance and sensory postural control during quiet stance. There have been no reports on automatic postural reactions in SBMA. Objectives: In this study, we aimed (1) to augment previous findings of sensory postural control, (2) to investigate automatic postural reactions in SBMA, and (3) to explore the relationship between strength and balance. Design: A cross-sectional design was used for the analysis. Participants: The participants were fifty male individuals with a confirmed diagnosis of SBMA. Outcome Measures: Balance testing included the NeuroCom modified Clinical Test of Sensory Interaction on Balance (mCTSIB), which measures sway velocity during quiet stance, and the NeuroCom Motor Control Test (MCT), which measures the latency and strength of postural reactions following sudden perturbations. Strength testing included maximal voluntary isometric contractions measured via fixed-frame dynamometry. Results: Forty-seven out of fifty participants were able to complete the mCTSIB test, but only thirty-eight completed the MCT test. Patients who were unable to complete the MCT were significantly weaker in all lower extremity muscles compared to those who were able to complete testing. Compared to normative data, participants showed significantly higher sway velocity during quiet stance across all conditions of the mCTSIB, except when standing on foam with eyes open. They also exhibited significantly slower postural reactions in response to sudden shifts of the force plate on the MCT. Plantarflexor weakness was significantly correlated with poor postural control on the mCTSIB and MCT. Conclusions: This study confirms previously reported abnormalities of sensory postural control in SBMA and highlights patients’ heavy reliance on visual inputs for postural control. Additionally, this study shows that automatic postural corrections are slower than normal in SBMA and provides a unique approach for measuring the combined sensory and motor components of the disease. Both the sensory and automatic balance abnormalities were found to be associated with plantarflexor weakness and may contribute to a higher risk of falls under challenging situations. Therefore, addressing this weakness may be an important step toward fall prevention in this population.
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(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)
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Open AccessArticle
Development of a Novel Method of Spinal Electrophysiological Assessment via Intrathecal Administration at Analgesic Doses
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Daisuke Uta, Takuya Yamane, Sosuke Yoneda, Erika Kasai and Toshiaki Kume
Neurol. Int. 2025, 17(5), 78; https://doi.org/10.3390/neurolint17050078 - 21 May 2025
Abstract
Background/Objectives: Chronic pain is a significant global health challenge and is associated with diverse conditions, such as diabetic neuropathic pain and spinal stenosis. Understanding the mechanisms of pain transmission is crucial, for both the peripheral and central pathways. However, there are limitations
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Background/Objectives: Chronic pain is a significant global health challenge and is associated with diverse conditions, such as diabetic neuropathic pain and spinal stenosis. Understanding the mechanisms of pain transmission is crucial, for both the peripheral and central pathways. However, there are limitations in spinal electrophysiological techniques in terms of the injection method. Traditional methods such as spinal injections may differ in the distributions and concentrations of drugs compared with intrathecal administration during the behavior test. So, we developed a new intrathecal administration method for electrophysiological recordings. Methods: Sprague–Dawley rats were injected with lidocaine intrathecally, and the analgesic effect was evaluated by the von Frey test. In vivo extracellular single-unit recordings of the superficial dorsal horn neurons were performed following a newly developed technique. Lidocaine was intrathecally injected into the arachnoid membrane after laminectomy. After that, the neural responses in the superficial dorsal horn were measured. Results: Newly developed intrathecally administered dye reached the spinal cord and the cauda equina. Intrathecally administrated lidocaine increased the paw withdrawal threshold and suppressed spinal neuronal firing. This suppression correlated with increases in paw withdrawal thresholds. Conclusions: This innovative method provides insights into the central effects of analgesics, which will help the development of therapies for chronic pain.
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(This article belongs to the Special Issue Acute and Chronic Pain: Pathogenesis, Treatment Strategies and Care)
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Open AccessSystematic Review
Medications for Managing Central Neuropathic Pain as a Result of Underlying Conditions—A Systematic Review
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Bjarke Kaae Houlind and Henrik Boye Jensen
Neurol. Int. 2025, 17(5), 77; https://doi.org/10.3390/neurolint17050077 - 20 May 2025
Abstract
Background: This systematic review assessed the current literature regarding the analgesic treatment of central neuropathic pain (CNP) in central nervous system (CNS) conditions, such as spinal cord injuries, multiple sclerosis, post-stroke disorders, and Parkinson’s disease. The aim of this systematic review was to
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Background: This systematic review assessed the current literature regarding the analgesic treatment of central neuropathic pain (CNP) in central nervous system (CNS) conditions, such as spinal cord injuries, multiple sclerosis, post-stroke disorders, and Parkinson’s disease. The aim of this systematic review was to compare the current algorithmic treatment of CNP, which generally does not discriminate among underlying conditions, with RCTs investigating algorithm-recommended and non-algorithm-recommended drugs for differing underlying conditions. Methods: The PubMed and EMBASE databases were used to identify relevant randomized control trials (RCTs). MeSH terms and EmTree terms were searched as well as free text words in the title/abstract of the studies. A risk of bias tool was used to assess all included studies. Results: A total of 903 RCTs were identified from the initial search. Thirty-eight RCTs published between January 2002 and November 2024 fulfilled all the inclusion criteria and none of the exclusion criteria. The review investigated progressive and stable neurological diseases and conditions with associated CNP. Conclusions: From the majority of the included studies, the current recommended treatment algorithm seems to be effective and safe; however, the underlying condition seems to influence how the patient responds to tier-appropriate medication.
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(This article belongs to the Special Issue Acute and Chronic Pain: Pathogenesis, Treatment Strategies and Care)
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Open AccessBrief Report
The Second Exteroceptive Suppression Period of the Temporalis Muscle Is Altered in Migraine Patients with Allodynia
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Eugenia Rota, Paolo Immovilli, Marco Aguggia, Maria Gabriella Saracco, Elisabetta Ghiglione, Antonella Melotti and Nicola Morelli
Neurol. Int. 2025, 17(5), 76; https://doi.org/10.3390/neurolint17050076 - 16 May 2025
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Background/Objectives: Studying the second exteroceptive suppression period (ES2) of the temporalis muscle may well shed some light on the brainstem neural circuits involved in migraine pathophysiology. It is known that allodynia is related to an increased sensitization of second-/third-order neurons both in the
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Background/Objectives: Studying the second exteroceptive suppression period (ES2) of the temporalis muscle may well shed some light on the brainstem neural circuits involved in migraine pathophysiology. It is known that allodynia is related to an increased sensitization of second-/third-order neurons both in the trigeminal nucleus caudalis and sensory thalamus. This pilot, observational study was carried out in the interictal period on female migraineurs with/without allodynia to assess the ES2 of the temporalis muscle compared to controls. Methods: Forty-nine non-consecutive female patients were enrolled, as they met the diagnostic criteria for migraine (26 episodic and 23 chronic), alongside 23 healthy controls. The inclusion criteria encompassed no ongoing pharmacological prophylactic treatment, and the exclusion criteria included any relevant comorbidities. In line with international standards, the exteroceptive suppression of the temporalis muscle activity was registered on the left side, assessing ES2 latency and duration in the interictal period. Results: Allodynia was observed in 24 patients (50%), and 16/24 (67%) were chronic migraineurs. No statistically significant differences in ES2 latency or its duration between the migraine patients and controls were detected. However, there was a significantly longer ES2 duration in allodynic migraineurs than in the controls (p = 0.04; effect size: 0.71) and in allodynic compared to non-allodynic migraineurs (p = 0.04; effect size: 0.63). Conclusions: The increased duration of ES2 observed in allodynic migraineurs might be related to the impaired activity of brainstem circuits and, in our opinion, it seems reasonable to hypothesize that this change may be a neurophysiological correlate of central sensitization in migraine allodynic patients.
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Open AccessReview
The Role of Tau in Neuronal Function and Neurodegeneration
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Gonzalo Emiliano Aranda-Abreu, Fausto Rojas-Durán, María Elena Hernández-Aguilar, Deissy Herrera-Covarrubias, Luis Isauro García-Hernández, María Rebeca Toledo-Cárdenas and Donají Chi-Castañeda
Neurol. Int. 2025, 17(5), 75; https://doi.org/10.3390/neurolint17050075 - 13 May 2025
Abstract
Tau protein plays a pivotal role in maintaining neuronal structure and function through its regulation of microtubule stability and neuronal polarity. Encoded by the MAPT gene, Tau exists in multiple isoforms due to alternative mRNA splicing, with differential expression in the central and
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Tau protein plays a pivotal role in maintaining neuronal structure and function through its regulation of microtubule stability and neuronal polarity. Encoded by the MAPT gene, Tau exists in multiple isoforms due to alternative mRNA splicing, with differential expression in the central and peripheral nervous systems. In healthy neurons, tau mRNA is selectively localized and translated in axons, a process tightly regulated by untranslated regions (UTRs) and RNA-binding proteins such as HuD and FMRP. Pathologically, Tau undergoes hyperphosphorylation, misfolding, and aggregation, which contribute to neurodegeneration in a range of disorders collectively known as tauopathies. Alzheimer’s disease (AD) is the most prevalent tauopathy, where abnormal Tau accumulation in the temporal and frontal lobes correlates with cognitive decline and behavioral symptoms. Other tauopathies, including Progressive Supranuclear Palsy (PSP), Corticobasal Degeneration (CBD), Frontotemporal Dementia with Parkinsonism (FTDP-17), and Pick’s disease, are distinguished by the predominance of specific Tau isoforms (3R or 4R), cellular distribution, and affected brain regions. Notably, astroglial tauopathies highlight the pathological role of Tau accumulation in glial cells, expanding the understanding of neurodegeneration beyond neurons. Despite advances in imaging biomarkers (e.g., Tau-PET) and molecular diagnostics, effective disease-modifying therapies for tauopathies remain elusive. Ongoing research targets Tau through immunotherapies, splicing modulators, kinase inhibitors, and antisense oligonucleotides, aiming to mitigate Tau pathology and its deleterious effects. Understanding the multifaceted roles of Tau in neuronal and glial contexts is critical for developing future therapeutic strategies against tauopathies.
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Open AccessArticle
Cardiac Autonomic Modulation and Cognitive Performance in Community-Dwelling Older Adults: A Preliminary Study
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Paula Andreatta Maduro, Luiz Alcides Ramires Maduro, Polyana Evangelista Lima, Ana Clara Castro Silva, Rita de Cássia Montenegro da Silva, Alaine Souza Lima Rocha, Maria Jacqueline Silva Ribeiro, Juliana Magalhães Duarte Matoso, Bruno Bavaresco Gambassi and Paulo Adriano Schwingel
Neurol. Int. 2025, 17(5), 74; https://doi.org/10.3390/neurolint17050074 - 12 May 2025
Abstract
Background/Objectives: Cognitive decline has been increasingly linked to cardiac autonomic regulation; however, its specific associations with cognitive domains, such as information processing speed and executive function, remain unclear. This preliminary study examined the relationship between cardiac autonomic modulation and cognitive performance in older
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Background/Objectives: Cognitive decline has been increasingly linked to cardiac autonomic regulation; however, its specific associations with cognitive domains, such as information processing speed and executive function, remain unclear. This preliminary study examined the relationship between cardiac autonomic modulation and cognitive performance in older adults. Methods: A cross-sectional study was conducted with 101 older adults (aged ≥60 years) attending a university hospital outpatient clinic. Participants were classified as without cognitive impairment (WCI) or cognitively impaired and not demented (CIND) based on neuropsychological assessments. Heart rate variability (HRV) was measured at rest, focusing on the time-domain parameters (SDNN, rMSSD, and pNN50). Trail making test parts A and B (TMT-A and TMT-B) were used to assess information processing speed and executive function, respectively. Analyses of covariance (ANCOVAs) were performed, adjusting for confounding variables including age, sex, and comorbidities. Results: Participants in the CIND group had significantly lower HRV indices than those in the WCI group (SDNN, p < 0.05, d = 0.44; rMSSD, p < 0.05, d = 0.39; pNN50, p < 0.05, d = 0.40), indicating reduced parasympathetic modulation. Higher HRV values were observed in individuals with preserved processing speed and executive function. Specifically, pNN50 was significantly associated with processing speed (p = 0.04), and SDNN was significantly correlated with executive function (p = 0.02). These associations persisted even after adjusting for confounding factors. Conclusions: Reduced cardiac autonomic modulation, especially lower parasympathetic activity, is significantly associated with cognitive impairment in older adults. Lower pNN50 values were correlated with slower information processing speed, and lower SDNN was associated with poorer executive function. These findings support the potential use of HRV as a physiological biomarker to detect cognitive changes during ageing.
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(This article belongs to the Collection Advances in Neurodegenerative Diseases)
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Open AccessCase Report
Impaired DNAJB2 Response to Heat Shock in Fibroblasts from a Neuropathy Patient with DNAJB2/HSJ1 Mutation: Cystamine as a Potential Therapeutic Intervention
by
Raj Kumar Pradhan, Nikolas G. Kinney, Brigid K. Jensen and Hristelina Ilieva
Neurol. Int. 2025, 17(5), 73; https://doi.org/10.3390/neurolint17050073 - 9 May 2025
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Background and Objectives: Neuropathy is a debilitating disorder characterized by peripheral nerve dysfunction and damage to sensory, motor, and autonomic neurons and their axons. While homozygous mutations in DNAJB2/HSJ1 have been linked to early-onset neuropathy, a heterozygous DNAJB2 c.823+6C>T was discovered in an
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Background and Objectives: Neuropathy is a debilitating disorder characterized by peripheral nerve dysfunction and damage to sensory, motor, and autonomic neurons and their axons. While homozygous mutations in DNAJB2/HSJ1 have been linked to early-onset neuropathy, a heterozygous DNAJB2 c.823+6C>T was discovered in an adult patient with severe sensory–motor polyneuropathy. This mutation is predicted to affect both isoforms of the protein. DNAJB2 (HSP40), a key member of the heat shock protein family, plays a critical role in cellular protection and stress, including response to heat shock. DNAJB2 traffics unfolded proteins to another heat shock protein, HSP70, and activates its ATPase activity to result in a correctly folded protein(s). In this study, we aimed to investigate the effects of the heterozygous DNAJB2 c.823+6C>T mutation on the stress response of DNAJB2 in fibroblasts obtained from the neuropathy patient. Methods: The fibroblasts were subjected to one hour of heat shock at 42 °C, and the time course of expression levels of DNAJB2 was established. Additionally, we evaluated the therapeutic efficacy of Cystamine, which has been shown to modulate DNAJB2 levels in cellular and animal models of Huntington’s disease. Results: Our results revealed reduced baseline levels of DNAJB2 between the mutant and control fibroblasts. Importantly the mutant cells exhibited a diminished response to heat shock. Thus, the mutation affects the upregulation of DNAJB2 under stress, possibly contributing to the pathogenesis of sensory–motor polyneuropathy. A 48-h pretreatment with 150 μM of Cystamine increased the levels of DNAJB2 in both the control and patient’s fibroblasts. Conclusions: To the best of our knowledge, this is the first study to explore this mutant form of DNAJB2 in neuropathy. The study demonstrated that the heterozygous DNAJB2 c.823+6C>T mutation leads to impaired DNAJB2 response to heat shock in the fibroblasts. Cystamine showed promise in restoring DNAJB2 expression, highlighting the need for further research into targeted therapeutic strategies for DNAJB2-related disorders.
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Open AccessArticle
Cerebellar Contributions to Hypokinetic Symptoms in an Acute Lesion Parkinsonism Model
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Cristofer Zarate-Calderon, Gerardo Marín, Iraís Viveros-Martínez, Lizbeth Vásquez-Celaya, Porfirio Carrillo-Castilla, Gonzalo E. Aranda-Abreu, Donaji Chi-Castañeda and Luis I. García
Neurol. Int. 2025, 17(5), 72; https://doi.org/10.3390/neurolint17050072 - 7 May 2025
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Background: Parkinsonism, characterized by motor symptoms, is typically attributed to basal ganglia dysfunction. Recent evidence suggests that the cerebellum may also influence these symptoms. This study investigated Crus II, the dentate nucleus (DN), and the inferior olive (IO) in a rat model of
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Background: Parkinsonism, characterized by motor symptoms, is typically attributed to basal ganglia dysfunction. Recent evidence suggests that the cerebellum may also influence these symptoms. This study investigated Crus II, the dentate nucleus (DN), and the inferior olive (IO) in a rat model of parkinsonism induced by a bilateral ventrolateral striatal (VLS) lesion. Materials and Methods: Twenty-four male Wistar rats were divided into control (n = 12) and experimental (n = 12) groups. Monopolar electrodes were implanted in target structures. The experimental group received a bilateral VLS lesion. Animals underwent four weekly sessions of electrophysiological recordings and blind behavioral assessments (resting, grooming, locomotion, rearing, sniffing) via video tracking. Power spectral density (PSD) in the 300–500 Hz band was computed. Statistical analyses included Mann–Whitney U, Friedman with Wilcoxon post hoc, and Spearman correlation tests. Results: During weeks one and two, there were significant PSD increases in the experimental group compared to the control, particularly in Crus II—grooming (p = 0.005), locomotion (p = 0.007), and rearing (p = 0.026); in IO—sniffing (p = 0.0167); and in DN—grooming (p < 0.001) and locomotion (p = 0.0008). Additionally, intragroup analysis revealed significant PSD elevations relative to baseline in these structures. Significant correlations were observed only for grooming (negative correlations) and sniffing (positive correlations) across all cerebellar regions. Conclusions: These findings suggest compensatory cerebellar hyperactivity induced by VLS lesion, potentially modulating hypokinetic symptoms and highlighting dynamic network interactions. Interpretation warrants caution due to limitations inherent to the acute lesion model and experimental duration.
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Open AccessReview
Neurological Sequelae of Acute Hydrogen Sulfide Poisoning: A Literature Review, Controversies, and Knowledge Gaps
by
Wilson K. Rumbeiha and Dong-Suk Kim
Neurol. Int. 2025, 17(5), 71; https://doi.org/10.3390/neurolint17050071 - 6 May 2025
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Hydrogen sulfide (H2S) is a highly potent toxic gas, and the brain is a primary target organ following acute intoxications. Accidents and misuse of this gas for nefarious purposes, i.e., bioterrorism, are causes for concern regarding acute poisoning. The immediate effects
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Hydrogen sulfide (H2S) is a highly potent toxic gas, and the brain is a primary target organ following acute intoxications. Accidents and misuse of this gas for nefarious purposes, i.e., bioterrorism, are causes for concern regarding acute poisoning. The immediate effects of acute H2S poisoning are well known. Numerous publications have reported neurological sequelae, including insomnia, persistent headaches, ataxia, cognition deficits, hearing impairment, dysarthria, and neuropsychiatric behaviors, among survivors of acute H2S poisoning. However, this subject remains controversial. The goal of this study was to review the literature on acute H2S-poisoning-induced neurological sequelae and on animal models to determine prevalence and knowledge gaps. We also reviewed the literature on cyanide-induced neurological sequelae. The results of large population studies indicate that the majority of victims of acute H2S poisoning survive. There is a lack of patient follow-up and standardized neuropsychological, neurological, and neuroimaging for accurate assessments. We observed flaws in animal models that failed to recapitulate the severe neurotoxicity induced via the inhalation route. We observed a paucity of literature on cyanide-induced neurological sequelae. In contrast to cyanide-induced sequelae, predominantly characterized by Parkinsonian-like motor behavioral deficits, H2S patients exhibit mostly cognition deficits, speech impairment, and neuropsychological effects. This first comprehensive review of neurological sequelae induced by H2S and cyanide poisonings identified knowledge gaps in the prevalence of these sequelae and cellular and molecular mechanisms underlying them. It is unclear whether these sequelae are reversible. There are no FDA-approved drugs for the prevention or treatment of these sequelae. Notably, patients who received life-saving therapy still developed delayed neurological sequelae.
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Open AccessArticle
The Impact of Concurrent Chronic Heart Failure and Chronic Kidney Dysfunction on Post-Stroke Rehabilitation Outcomes
by
Azadeh Fischer, Nadja Jauert, Martin Schikora, Michael Joebges and Wolfram Doehner
Neurol. Int. 2025, 17(5), 70; https://doi.org/10.3390/neurolint17050070 - 3 May 2025
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Background/Objectives: The aim of this study was to evaluate the impact of chronic heart failure (CHF), chronic kidney dysfunction (CKD), and the combined CHF-CKD comorbidity on the outcomes of rehabilitation in stroke patients. Methods: A total of 586 patients who had suffered a
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Background/Objectives: The aim of this study was to evaluate the impact of chronic heart failure (CHF), chronic kidney dysfunction (CKD), and the combined CHF-CKD comorbidity on the outcomes of rehabilitation in stroke patients. Methods: A total of 586 patients who had suffered a stroke (mean age, 70 ± 13; 47.6% female; 72.4% ischemic and 27.6% hemorrhagic strokes) and who were admitted immediately after acute stroke care to a rehabilitation center were included in this cohort study and followed up with until their death or discharge from the rehabilitation center. The clinical characteristics of the patients were obtained from their medical records. The relationship between the background comorbidities (CHF, CKD, and concurrent CHF-CKD) and fatal and non-fatal unfavorable outcomes (emergency readmission to a primary hospital or transfer to a long-term care facility in a vegetative or minimally conscious state) were investigated. Results: Unfavorable outcomes were more common in the groups with background CHF and/or CKD. From the Cox multivariate analysis, both CHF and CKD were independent prognostic factors for the occurrence of unfavorable outcomes, with a hazard ratio (HR) of 2.28 (95% CI = 1.2–4.29; p-value = 0.01) and 2.19 (95% CI = 1.24–3.87; p-value = 0.007), respectively. Moreover, the combined CHF-CKD comorbidity showed a more than 5-fold increased risk of an adverse post-stroke outcome (HR of 5.8; 95% CI = 2.5–13.44; p-value < 0.001). Conclusions: The combined CHF-CKD comorbidity is an important independent complicating factor that, along with other known influencing factors, can affect unfavorable post-stroke outcomes more than CHF or CKD alone, and necessitates critical attention to its diagnosis and management as a separate mixed syndrome.
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Open AccessArticle
Effect of Cilostazol and Aspirin During Hyperacute Stroke Phase in Rats: An Experimental Research Study
by
Christiana Anastasiadou, Anastasios Papapetrou, George Galyfos, Kostas Vekrellis, Patroklos Katafygiotis, Andreas Lazaris, George Geroulakos, Angelos Megalopoulos, Christos Liapis, Nikolaos Kostomitsopoulos and John Kakisis
Neurol. Int. 2025, 17(5), 69; https://doi.org/10.3390/neurolint17050069 - 28 Apr 2025
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Objective: The contralateral hippocampus, a critical region for cognitive function, is often overlooked in everyday clinical practice and stroke research. This study aimed to evaluate the effect of specific antiplatelet agents on the hippocampus (ipsilateral and contralateral) during the hyperacute phase of stroke.
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Objective: The contralateral hippocampus, a critical region for cognitive function, is often overlooked in everyday clinical practice and stroke research. This study aimed to evaluate the effect of specific antiplatelet agents on the hippocampus (ipsilateral and contralateral) during the hyperacute phase of stroke. Materials and Methods: Twelve-week-old rats were randomly assigned to four groups, each containing six rats: a cilostazol group, an aspirin group, an aspirin plus cilostazol group, and a control group. Each substance was administered for four weeks. Permanent brain ischemia was induced over 2 h using intraluminal middle cerebral artery occlusion. A neurologic examination was conducted, followed by euthanasia and histological examination of the CA1 hippocampal region. The hematoxylin and eosin stain was used to assess the total number of intact neuronal cell bodies and pyknotic nuclei, an indicator of early irreversible neuronal injury. Results: In the ipsilateral hippocampus, monotherapy with either aspirin or cilostazol significantly reduced pyknotic nuclei compared with the control group (p = 0.0016 and p = 0.0165, respectively). However, combination therapy showed no significant difference from the controls (p = 0.2375). In the contralateral hippocampus, cilostazol monotherapy demonstrated significantly reduced pyknotic nuclei (p = 0.0098), whereas aspirin monotherapy and combination therapy did not (p = 0.1009 and p = 0.9999, respectively). A cumulative analysis of both hemispheres revealed that monotherapy with aspirin or cilostazol markedly reduced injury markers (p = 0.0002 and p = 0.0001, respectively), whereas combined therapy revealed no significant benefit (p = 0.1984). A neurological assessment indicated that the most severe deficits were in the combination therapy group. Conclusions: To the best of our knowledge, this is the first study to compare acute histopathological changes in the affected and unaffected hippocampus after a stroke in a rat model. Dual antiplatelet therapy resulted in worse outcomes (histopathological and neurological) than monotherapy.
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Open AccessCase Report
Intravascular Large B-Cell Lymphoma Diagnosed After Recurrent Stroke: Case Report and Literature Review
by
Naoko Takaku, Koji Hayashi, Mamiko Sato, Rei Asano, Kouji Hayashi, Toyoaki Miura, Norimichi Shirafuji, Tadanori Hamano and Yasutaka Kobayashi
Neurol. Int. 2025, 17(5), 68; https://doi.org/10.3390/neurolint17050068 - 27 Apr 2025
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Background/Objectives: We describe a case of intravascular large B-cell lymphoma (IVLBCL) presenting with recurrent cerebral infarctions and review similar reported cases. Our aim is to explore potential early diagnostic markers and discuss their prognostic implications. Methods/Results: A 79-year-old man with a
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Background/Objectives: We describe a case of intravascular large B-cell lymphoma (IVLBCL) presenting with recurrent cerebral infarctions and review similar reported cases. Our aim is to explore potential early diagnostic markers and discuss their prognostic implications. Methods/Results: A 79-year-old man with a history of hypertension, hyperuricemia, and postoperative bladder cancer presented with five to six cerebral infarctions over an 11-month period, despite successive changes in antiplatelet and anticoagulant medications. Neurological examination revealed decreased pain sensation, bilateral hearing loss, and right thenar atrophy. Laboratory studies showed elevated inflammatory markers and soluble IL-2 receptor. CSF analysis revealed elevated protein, β2-microglobulin, IL-6, and IL-10 levels. A skin biopsy was performed to investigate suspected IVLBCL. Histopathological examination of the skin biopsy revealed large pleomorphic CD20-positive cells within the vasculature, confirming a diagnosis of IVLBCL. The patient was treated with chemotherapy, including dose-adjusted R-CHOP and high-dose methotrexate, and achieved complete remission. No recurrence of cerebral infarction was observed during a two-year follow-up period. Conclusions: This case highlights the importance of considering IVLBCL in patients with recurrent strokes of unknown etiology, especially when laboratory or imaging findings suggest systemic involvement. Early recognition and appropriate tissue diagnosis, such as skin biopsy, are essential for timely treatment and favorable prognosis.
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