Neurology International

10 pages, 1177 KiB

Open AccessArticle

Development of a Novel Method of Spinal Electrophysiological Assessment via Intrathecal Administration at Analgesic Doses

by 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

Viewed by 36

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Acute and Chronic Pain: Pathogenesis, Treatment Strategies and Care)

► Show Figures

Graphical abstract

26 pages, 1962 KiB

Open AccessSystematic Review

Medications for Managing Central Neuropathic Pain as a Result of Underlying Conditions—A Systematic Review

by Bjarke Kaae Houlind and Henrik Boye Jensen

Neurol. Int. 2025, 17(5), 77; https://doi.org/10.3390/neurolint17050077 - 20 May 2025

Viewed by 152

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Acute and Chronic Pain: Pathogenesis, Treatment Strategies and Care)

► Show Figures

Figure 1

10 pages, 609 KiB

Open AccessBrief Report

The Second Exteroceptive Suppression Period of the Temporalis Muscle Is Altered in Migraine Patients with Allodynia

by 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

Viewed by 87

Abstract

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 [...] Read more.

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. Full article

► Show Figures

Figure 1

18 pages, 319 KiB

Open AccessReview

The Role of Tau in Neuronal Function and Neurodegeneration

by 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

Viewed by 227

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 [...] Read more.

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. Full article

19 pages, 2194 KiB

Open AccessArticle

Cardiac Autonomic Modulation and Cognitive Performance in Community-Dwelling Older Adults: A Preliminary Study

by 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

Viewed by 183

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 [...] Read more.

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. Full article

(This article belongs to the Collection Advances in Neurodegenerative Diseases)

► Show Figures

Figure 1

18 pages, 2581 KiB

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

Viewed by 231

Abstract

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 [...] Read more.

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. Full article

► Show Figures

Figure 1

20 pages, 7473 KiB

Open AccessArticle

Cerebellar Contributions to Hypokinetic Symptoms in an Acute Lesion Parkinsonism Model

by 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

Viewed by 180

Abstract

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 [...] Read more.

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. Full article

► Show Figures

Figure 1

23 pages, 3022 KiB

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

Viewed by 220

Abstract

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 [...] Read more.

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. Full article

► Show Figures

Figure 1

9 pages, 1107 KiB

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

Viewed by 147

Abstract

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 [...] Read more.

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. Full article

► Show Figures

Figure 1

11 pages, 3540 KiB

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

Viewed by 194

Abstract

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. [...] Read more.

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. Full article

► Show Figures

Figure 1

18 pages, 11479 KiB

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

Viewed by 279

Abstract

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 [...] Read more.

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. Full article

► Show Figures

Figure 1

14 pages, 664 KiB

Open AccessArticle

The Association of Cerebral Blood Flow Measured Using Extracranial Carotid Ultrasound with Functional Outcomes in Patients with Anterior Circulation Large Vessel Occlusion After Endovascular Thrombectomy—A Retrospective Study

by Xin-Hong Lin, Kuan-Wen Chen, Chung-Fu Hsu, Ting-Wei Chang, Chao-Yu Shen and Hsin-Yi Chi

Neurol. Int. 2025, 17(5), 67; https://doi.org/10.3390/neurolint17050067 - 25 Apr 2025

Viewed by 199

Abstract

Background: Endovascular mechanical thrombectomy (EVT) is regarded as the standard treatment for acute ischemic stroke with large vessel occlusion. Few studies have examined the evolution of cerebral flow after the acute stage of ischemic stroke. In this study, we examined the association [...] Read more.

Background: Endovascular mechanical thrombectomy (EVT) is regarded as the standard treatment for acute ischemic stroke with large vessel occlusion. Few studies have examined the evolution of cerebral flow after the acute stage of ischemic stroke. In this study, we examined the association of functional outcomes with cerebral blood flow by extracranial carotid sonography during the subacute phase after EVT and multiple prognostic variables. Methods: We conducted a single-center, retrospective, observational study between January 2018 and June 2023. Patients with acute stroke resulting from anterior circulation large vessel occlusion who underwent EVT were included. All patients underwent carotid sonography in the second week after EVT. Patients with fair (modified Rankin Scale [mRS]: 0–3) and poor outcomes (mRS: 4–6) were compared to determine the association between and identify the predictors of these factors and functional outcomes. Results: A total of 89 patients were included (female: 38 (42.7%); mean age: 69.45 ± 13.59 years). Multivariable logistic regression analysis revealed that three factors were independent predictors of fair outcomes: (1) the Alberta Stroke Program Early CT Score (odds ratio [OR]: 1.79; 95% confidence interval [CI]: 1.16–2.78; p = 0.009); (2) Thrombolysis in Cerebral Infarction 2b to 3 (OR: 4.91; 95%CI: 1.10–21.89; p = 0.037); (3) the ratio of treatment-side blood flow between the internal carotid artery and common carotid artery (QTI/QTC, OR: 45.35; 95% CI: 1.11–1847.51; p = 0.04). Conclusions: The ratio of QTI/QTC is a clinically relevant parameter as a potential predictor of favorable outcomes. This parameter can be used to formulate patient prognostic scores and help clinicians determine whether adequate cerebral perfusion is maintained during the subacute phase. Full article

(This article belongs to the Special Issue Innovations in Acute Stroke Treatment, Neuroprotection, and Recovery)

► Show Figures

Figure 1

24 pages, 5534 KiB

Open AccessReview

Epilepsy Diagnosis When the Routine Ancillary Tests Are Normal

by Boulenouar Mesraoua, Bassel Abou-Khalil, Bernhard Schuknecht, Hassan Al Hail, Musab Ali, Majd A. AbuAlrob, Khaled Zammar and Ali A. Asadi-Pooya

Neurol. Int. 2025, 17(5), 66; https://doi.org/10.3390/neurolint17050066 - 24 Apr 2025

Viewed by 472

Abstract

Background/Objectives: In a patient suspected of having epilepsy, routine EEG primarily contributes to the recording of interictal epileptiform discharges (IEDs). Similarly, magnetic resonance imaging (MRI) has become the gold standard imaging technique for identifying epileptogenic structural brain abnormalities. Various EEG and MRI tools [...] Read more.

Background/Objectives: In a patient suspected of having epilepsy, routine EEG primarily contributes to the recording of interictal epileptiform discharges (IEDs). Similarly, magnetic resonance imaging (MRI) has become the gold standard imaging technique for identifying epileptogenic structural brain abnormalities. Various EEG and MRI tools to improve epilepsy diagnosis will be presented. Methods: When the initial EEG fails to record IEDs, various EEG measures that can improve EEG performance are presented; a comprehensive epilepsy-targeted MRI protocol to identify, localize, and characterize an epileptogenic lesion will also be described. Results: Studies show that the initial routine EEG fails to record IEDs in approximately 47–50% of epileptic patients. To improve the yield of EEG, subsequent EEG recording should include sleep deprivation, sleep recording, prolonged hyperventilation, optimized light stimulation, addition of an inferior temporal electrode chain, extended EEG duration, and continuous video-EEG monitoring, all measures known to activate IEDs. Furthermore, MRI is interpreted as “normal” in many epilepsy patients, even when performed according to an epilepsy-specific protocol and evaluated by a specialized MRI reader. In such case, the use of the Harmonized Epilepsy Structural Sequence Imaging (HARNESS-MRI) protocol and other imaging tools will improve the detection of potential epileptic lesions, as described in this study. Conclusions: In a patient with a clinical diagnosis of epilepsy but a normal EEG and brain MRI, several options can improve the performance of subsequent EEG and MRI examinations, the subjects of this review. Full article

► Show Figures

Graphical abstract

18 pages, 1275 KiB

Open AccessArticle

Variants in Neurotransmitter-Related Genes Are Associated with Alzheimer’s Disease Risk and Cognitive Functioning but Not Short-Term Treatment Response

by Tirso Zúñiga-Santamaría, Blanca Estela Pérez-Aldana, Ingrid Fricke-Galindo, Margarita González-González, Zoila Gloria Trujillo-de los Santos, Marie Catherine Boll-Woehrlen, Rosalía Rodríguez-García, Marisol López-López and Petra Yescas-Gómez

Neurol. Int. 2025, 17(5), 65; https://doi.org/10.3390/neurolint17050065 - 24 Apr 2025

Viewed by 1066

Abstract

Background/Objectives: Several genetic factors are related to the risk of Alzheimer’s disease (AD) and the response to cholinesterase inhibitors (ChEIs) (donepezil, galantamine, and rivastigmine) or memantine. However, findings have been controversial, and, to the best of our knowledge, admixed populations have not [...] Read more.

Background/Objectives: Several genetic factors are related to the risk of Alzheimer’s disease (AD) and the response to cholinesterase inhibitors (ChEIs) (donepezil, galantamine, and rivastigmine) or memantine. However, findings have been controversial, and, to the best of our knowledge, admixed populations have not been previously evaluated. We aimed to determine the impact of genetic and non-genetic factors on the risk of AD and the short-term response to ChEIs and memantine in patients with AD from Mexico. Methods: This study included 117 patients from two specialty hospitals in Mexico City, Mexico. We evaluated cognitive performance via clinical evaluations and neuropsychological tests. Nineteen variants in ABCB1, ACHE, APOE, BCHE, CHAT, CYP2D6, CYP3A5, CHRNA7, NR1I2, and POR were assessed through TaqMan assays or PCR. Results: Minor alleles of the ABCB1 rs1045642, ACHE rs17884589, and CHAT rs2177370 and rs3793790 variants were associated with the risk of AD; meanwhile, CHRNA7 rs6494223 and CYP3A5 rs776746 were identified as low-risk variants in AD. BCHE rs1803274 was associated with worse cognitive functioning. None of the genetic and non-genetic factors studied were associated with the response to pharmacological treatment. Conclusions: We identified potential genetic variants related to the risk of AD; meanwhile, no factor was observed to impact the response to pharmacological therapy in patients with AD from Mexico. Full article

► Show Figures

Figure 1

9 pages, 8524 KiB

Open AccessCase Report

Iatrogenic Cerebral Amyloid Angiopathy After Childhood Brain Surgery: Novel Findings of MRI and CT

by Fumine Tanaka, Maki Umino, Megumi Matsukawa, Seiya Kishi, Ryota Kogue, Norikazu Kawada, Ken Kagawa, Takaya Utsunomiya, Hiroyuki Kajikawa, Hidehiro Ishikawa, Yuichiro Ii, Akihiro Shindo, Hajime Sakuma and Masayuki Maeda

Neurol. Int. 2025, 17(5), 64; https://doi.org/10.3390/neurolint17050064 - 24 Apr 2025

Viewed by 359

Abstract

Background/Objectives: A subtype of cerebral amyloid angiopathy (CAA), iatrogenic CAA (iCAA), has been increasingly reported. iCAA occurs primarily in patients who underwent surgery during childhood and is caused by the prion-like propagation of amyloid beta. This subtype of CAA tends to develop [...] Read more.

Background/Objectives: A subtype of cerebral amyloid angiopathy (CAA), iatrogenic CAA (iCAA), has been increasingly reported. iCAA occurs primarily in patients who underwent surgery during childhood and is caused by the prion-like propagation of amyloid beta. This subtype of CAA tends to develop at a younger age than age-related CAA, usually before the age of 55. After a latency period of 20–40 years following surgery, it manifests as lobar intracerebral hemorrhage (ICH), cognitive impairment, or transient focal neurological episodes. Between 2023 and 2024, we observed four cases of possible iCAA, all of which had a history of neurosurgery during childhood. Case presentation: MRI findings for all cases revealed multiple lobar microbleeds. Two cases also showed cortical superficial siderosis and lobar ICH. Notably, contrast-enhanced 3D FLAIR demonstrated sulcal enhancement in two cases, and CT demonstrated cortical calcification in the bilateral posterior lobes in one case. Conclusions: Sulcal enhancement on contrast-enhanced 3D FLAIR and cortical calcification in the bilateral posterior lobes on CT may suggest advanced CAA in the present cases. Full article

► Show Figures

Figure 1

10 pages, 250 KiB

Open AccessArticle

Functional Mobility Assessment in People with Multiple Sclerosis

by Ivana Sretenović, Srećko Potić, Goran Nedović, Gordana Odović and Ljiljana Šimpraga

Neurol. Int. 2025, 17(5), 63; https://doi.org/10.3390/neurolint17050063 - 23 Apr 2025

Viewed by 267

Abstract

Background/Objectives: Functional mobility includes gait and balance. People with multiple sclerosis often experience gait impairment and difficulties with walking, as well as an increased risk of falling. The aim of the research was to assess functional mobility and to examine the relationship between [...] Read more.

Background/Objectives: Functional mobility includes gait and balance. People with multiple sclerosis often experience gait impairment and difficulties with walking, as well as an increased risk of falling. The aim of the research was to assess functional mobility and to examine the relationship between gait and balance in people with multiple sclerosis, as well as the impact of falls on these two variables. Methods: The study sample consisted of 92 people with multiple sclerosis, with an average age of 45.10 (SD = 9.57) years, and both sexes (82.6% were female). The Activities-specific Balance Confidence Scale was used to assess an individual’s confidence in maintaining balance throughout daily activities, and the 12-item Multiple Sclerosis Walking Scale was employed to evaluate the impact of multiple sclerosis on walking ability. Descriptive statistics, measures of central tendency, Pearson’s correlations, and partial correlations were applied to the data. Results: The results indicated moderate gait impairment and a high level of function in people with multiple sclerosis. There was a correlation between confidence in maintaining balance and walking ability. Conclusions: The results of this study can be used to develop appropriate treatments and support programs for individuals with multiple sclerosis. Full article

11 pages, 795 KiB

Open AccessArticle

Identifying Factors Associated with the Efficacy of Lasmiditan 50 mg as an Acute Treatment for Migraine Attacks Under Various Dosing Conditions in Real-World Clinical Practice

by Takafumi Tanei, Shun Yamamoto, Satoshi Maesawa, Yusuke Nishimura, Tomotaka Ishizaki, Yoshitaka Nagashima, Yoshiki Ito, Miki Hashida, Takahiro Suzuki, Hajime Hamasaki, Toshihiko Wakabayashi and Ryuta Saito

Neurol. Int. 2025, 17(5), 62; https://doi.org/10.3390/neurolint17050062 - 22 Apr 2025

Viewed by 290

Abstract

Background/Objectives: Lasmiditan is a newly developed drug for the acute treatment of migraine attacks, but factors associated with its efficacy remain unclear. This study aimed to confirm the efficacy of lasmiditan started at 50 mg under various dosing conditions and identify factors [...] Read more.

Background/Objectives: Lasmiditan is a newly developed drug for the acute treatment of migraine attacks, but factors associated with its efficacy remain unclear. This study aimed to confirm the efficacy of lasmiditan started at 50 mg under various dosing conditions and identify factors associated with its efficacy. Methods: There are four reasons for prescribing lasmiditan: as an add-on to triptan, if triptan is ineffective, if triptan produces side effects, and when triptan is contraindicated. Lasmiditan was administered at a dose of 50 mg. The efficacy of lasmiditan was defined as the disappearance of headache or a 50% or greater reduction in headache intensity within two hours after dosing. This study included 108 patients with migraines who took lasmiditan. Results: The results for efficacy and the side effects of lasmiditan were as follows: effective without side effects (22), effective with mild side effects (32), ineffective (14), and severe side effects (40). The efficacy rate of lasmiditan 50 mg was 50.0% (54/108). The following factors were found to be associated with lasmiditan’s efficacy: sex, migraine classification, calcium channel blockers, and anti-calcitonin gene-related peptide monoclonal antibody (CGRP-mAb) treatment. The overall incidence of side effects was 66.7%, and the dropout rate was 37.0%. Somnolence was more prevalent in the effective group, and other side effects were more prevalent in patients who dropped out due to the side effects of lasmiditan. Conclusions: Lasmiditan is likely to be effective in males with severe migraine classification and receiving CGRP-mAb treatment. If mild somnolence is a side effect, the drug can be continued and may be effective. Full article

► Show Figures

Figure 1

Journal Menu

Journal Browser

Neurol. Int., Volume 17, Issue 5 (May 2025) – 17 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI