Neurology International

8 pages, 1374 KB

Open AccessCase Report

Bilateral Optic Neuritis Following Acute Glyphosate Inhalation: A Case Report

by Roberta Grasso, Elena Carapelle, Maria Eva Terracciano, Giuseppe Raunich, Antonio Turco, Luigi Longo and Ciro Mundi

Neurol. Int. 2026, 18(2), 39; https://doi.org/10.3390/neurolint18020039 - 23 Feb 2026

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Abstract

Background: Bilateral optic neuritis is a rare condition generally associated with inflammatory, demyelinating, or toxic causes. Its association with glyphosate exposure has rarely been documented. Case Presentation: A 66-year-old man with hypertension, hypercholesterolemia, and hypothyroidism developed rapid bilateral vision loss within hours after [...] Read more.

Background: Bilateral optic neuritis is a rare condition generally associated with inflammatory, demyelinating, or toxic causes. Its association with glyphosate exposure has rarely been documented. Case Presentation: A 66-year-old man with hypertension, hypercholesterolemia, and hypothyroidism developed rapid bilateral vision loss within hours after acute inhalational exposure to glyphosate during agricultural work. MRI showed bilateral optic nerve hyperintensity consistent with optic neuritis. Cerebrospinal fluid and serum anti-NMO antibody tests were negative, while visual evoked potentials demonstrated increased latencies. High-dose corticosteroid therapy led to progressive clinical improvement. At follow-up, MRI revealed no new lesions and the patient experienced near-complete visual recovery. Conclusion: This case suggests a possible link between acute glyphosate exposure and reversible bilateral optic neuritis. Early recognition and corticosteroid therapy may support full functional recovery even in severe presentations. Full article

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19 pages, 3560 KB

Open AccessArticle

Experimental Characterisation of Differently Composed Thrombus Entities with Spectral-Detector-CT

by Schekeb Aludin, Agreen Horr, Lars-Patrick Schmill, Carmen Wolf, Olav Jansen, Bodo Kurz, Julian Andersson, Svea Seehafer, Naomi Larsen, Patrick Langguth and Jens Trentmann

Neurol. Int. 2026, 18(2), 38; https://doi.org/10.3390/neurolint18020038 - 21 Feb 2026

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Abstract

Background/Objectives: Thrombus composition influences the success of endovascular therapy in stroke, but conventional CT is limited in determining it. Spectral-detector-CT (SDCT) can apply material-decomposition and virtual monoenergetic (MonoE) imaging, which may provide a way to gain information on thrombus composition. This experimental [...] Read more.

Background/Objectives: Thrombus composition influences the success of endovascular therapy in stroke, but conventional CT is limited in determining it. Spectral-detector-CT (SDCT) can apply material-decomposition and virtual monoenergetic (MonoE) imaging, which may provide a way to gain information on thrombus composition. This experimental study aimed to evaluate the differentiability of heterogeneous thrombi with variable red blood cell (RBC) content using SDCT. Methods: Ten thrombus entities with different compositions on RBC and plasma, thus fibrin content, were manufactured (volumetric RBC%/Plasma% = 90/10; 80/20; 70/30; 60/40; 50/50; 40/60; 30/70; 20/80; 10/90; 5/95) and scanned in an SDCT. Conventional Hounsfield-unit (HU) values, spectral electron density (ED), effective atomic number (Z-effective) and HU in MonoE maps ranging from 40– to 200 keV were evaluated for thrombus differentiation. Results: Conventional HU increased with RBC content, allowing us to differentiate the entities (p < 0.001). ED values also increased with RBC content and allowed for differentiation too (p < 0.001). Z-effective values showed no differences among the different entities (p > 0.05). Regarding the mass-attenuation curves from 40 to 200 keV the different thrombi showed a similar curve progression with highest HU values at 40 and lowest at 200 keV. The thrombi could be distinguished overall at each monoenergetic level by HU (p < 0.001 for each level). The absolute decrease in HU between 40 and 200 keV was thereby not significantly different between the different entities, but the relative decrease was, as it was more pronounced in thrombi with lower RBC content (p < 0.001). Conclusions: Spectral CT enables differentiation between thrombi with different RBC and fibrin contents by means of ED or analysis of the mass-attenuation curve. This offers alternative possibilities that go beyond characterisation based on CT-density alone. The additional inclusion of spectral parameters in thrombus diagnostics could therefore improve diagnosis and treatment. Full article

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

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25 pages, 3389 KB

Open AccessReview

Alzheimer’s Disease as a Disorder of Neuroimmune Dysregulation

by Gonzalo Emiliano Aranda-Abreu, Fausto Rojas-Durán, María Elena Hernández-Aguilar, Deissy Herrera-Covarrubias, Luis Roberto Tlapa-Monge and Sonia Lilia Mestizo-Gutiérrez

Neurol. Int. 2026, 18(2), 37; https://doi.org/10.3390/neurolint18020037 - 20 Feb 2026

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Abstract

Alzheimer’s disease (AD) is traditionally defined by Amyloid-β (Aβ) plaques and tau neurofibrillary tangles, yet these proteinopathies alone fail to explain disease heterogeneity, progression, and cognitive decline. Emerging evidence identifies chronic neuroinflammation as a central integrator that converts molecular pathology into synaptic failure [...] Read more.

Alzheimer’s disease (AD) is traditionally defined by Amyloid-β (Aβ) plaques and tau neurofibrillary tangles, yet these proteinopathies alone fail to explain disease heterogeneity, progression, and cognitive decline. Emerging evidence identifies chronic neuroinflammation as a central integrator that converts molecular pathology into synaptic failure and neurodegeneration. In this context, Aβ acts as a danger-associated molecular pattern that activates microglial and astrocytic immune programs through receptors such as TREM2, TLRs, and RAGE, leading to inflammasome activation, cytokine release, and oxidative stress. These responses pathologically re-engage developmental complement pathways (C1q–C3–CR3), driving excessive synaptic pruning that correlates more closely with cognitive impairment than neuronal loss. Reactive astrocytes further amplify dysfunction by impairing glutamate and potassium homeostasis, promoting excitotoxic and metabolic stress, while inflammatory glia facilitate prion-like tau propagation via extracellular vesicles. Concurrent neurovascular inflammation disrupts blood–brain barrier integrity and cerebral perfusion, reinforcing immune-metabolic failure. Importantly, neuroinflammatory biomarkers (GFAP, sTREM2, YKL-40, cytokines, complement, and TSPO-PET) provide dynamic readouts of disease activity and therapeutic response. Together, these findings position AD as a disorder of failed immune resolution and support precision immunomodulatory and pro-resolving therapies aimed at restoring neuroimmune homeostasis rather than merely removing protein aggregates. Full article

(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)

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25 pages, 2490 KB

Open AccessReview

Primary and Secondary Prevention of Ischemic Stroke in Elderly Patients with Cardiovascular Disease: The Role of Frailty and Care Pathways

by Fabiana Lucà, Roberto Ceravolo, Michele Massimo Gulizia, Sandro Gelsomino, Carmelo Massimiliano Rao, Nadia Ingianni, Giuseppina Vitale, Giovanna Geraci, Attilio Iacovoni, Pietro Scicchitano, Adriano Murrone, Claudio Bilato, Luigina Guasti, Furio Colivicchi, Fabrizio Oliva, Federico Nardi, Massimo Grimaldi and Iris Parrini

Neurol. Int. 2026, 18(2), 36; https://doi.org/10.3390/neurolint18020036 - 14 Feb 2026

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Abstract

Stroke is a major global health concern, particularly among the elderly, who frequently present with multiple comorbidities, most notably cardiovascular diseases. Importantly, atrial fibrillation confers a nearly fivefold increase in stroke risk and accounts for up to one-quarter of ischemic strokes in older [...] Read more.

Stroke is a major global health concern, particularly among the elderly, who frequently present with multiple comorbidities, most notably cardiovascular diseases. Importantly, atrial fibrillation confers a nearly fivefold increase in stroke risk and accounts for up to one-quarter of ischemic strokes in older adults. Stroke is a neurological disease characterised by a strong cardiovascular interplay, and its multifactorial nature requires an integrated preventive approach. This review focuses on primary and secondary prevention in this population, with a frailty-informed perspective. We synthesise evidence on blood pressure control, lipid-lowering (including LDL-C targets), glycemic management, and antithrombotic strategies—particularly oral anticoagulation for atrial fibrillation—as well as the role of frailty indices in guiding individualised risk–benefit decisions. We also discuss practical care pathways, including structured post-discharge programs, continuity of care, and the need for multidisciplinary collaboration involving cardiologists, neurologists, and primary care. We highlight how frailty indices refine risk–benefit assessments without justifying therapeutic nihilism, and how sex- and age-related factors shape treatment effectiveness and safety. By narrowing scope and emphasising practical, multidisciplinary prevention strategies, this review aims to support clinicians in reducing recurrent events, disability, and mortality in very old patients. Future work should prioritise pragmatic trials, including those involving the oldest old and the use of standardised frailty metrics, to inform prevention decisions. Full article

(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)

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1 pages, 159 KB

Open AccessCorrection

Correction: Astasio-Picado et al. Impact of Stroke Code Activation on Functional Outcomes and the Role of Nursing in Neurorehabilitation: A Systematic Review. Neurol. Int. 2025, 17, 175

by Álvaro Astasio-Picado, Jesus Jurado-Palomo and Clara Fátima Rodriguez-Urbaneja

Neurol. Int. 2026, 18(2), 35; https://doi.org/10.3390/neurolint18020035 - 12 Feb 2026

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Abstract

Missing Supplementary File [...] Full article

16 pages, 841 KB

Open AccessSystematic Review

Medication Adherence Following Stroke and TIA: A Qualitative Synthesis of Patient, Caregiver and Clinician Perspectives

by Erin O’Kane, Rhiannon De Ivey, Katie Pearson, Christa Awad, Khalifa Mohammed, Nathan Williamson, Richard Andrew Lumb, Ami Mehta and Eugene Yee Hing Tang

Neurol. Int. 2026, 18(2), 34; https://doi.org/10.3390/neurolint18020034 - 11 Feb 2026

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Abstract

Background/Objectives: Stroke survivors require life-long secondary prevention to reduce recurrence, but they also often face long-term impairments that may limit medication adherence (MA) including cognitive, physical, and psychological effects. This updated qualitative meta-synthesis aims to descriptively explore and synthesise the experiences and [...] Read more.

Background/Objectives: Stroke survivors require life-long secondary prevention to reduce recurrence, but they also often face long-term impairments that may limit medication adherence (MA) including cognitive, physical, and psychological effects. This updated qualitative meta-synthesis aims to descriptively explore and synthesise the experiences and perspectives of stroke/TIA survivors, informal and formal carers of stroke survivors, and healthcare professionals involved in post-stroke/TIA care, with a focus on factors influencing and hindering MA. Methods: A qualitative meta-synthesis was conducted in accordance with PRISMA guidance. Searches were undertaken across MEDLINE, CINAHL, Embase, PsycINFO, Scopus and Web of Science for studies published from 1 January 2018. Study quality was assessed using the Joanna Briggs Institute checklist and data synthesised using Thomas and Harden’s method. Results: Of 5463 titles and abstracts screened, 212 underwent full-text review with 13 papers meeting inclusion criteria from eight countries with a total of 435 participants. Seven key themes were identified: knowledge and understanding, beliefs and attitudes, practical barriers, social support, healthcare system, psychological factors and medication characteristics. Survivors showed a varied understanding of their condition and prescribed medicines, with unclear communication often contributing to confusion. Beliefs and attitudes shaped adherence, ranging from confidence in treatment to scepticism. Practical barriers included financial costs, physical impairments, and limited access to services. Social support from family, friends, and healthcare professionals was also important. Psychological wellbeing, coping strategies, and medication side effects further influenced adherence, highlighting the challenges faced by this patient group. Conclusions: Medication adherence post-stroke/TIA is shaped by multiple complex factors including knowledge, beliefs, attitudes, and lived experience. As a descriptive synthesis of qualitative evidence, these findings do not permit conclusions regarding causality or intervention effectiveness but provide insight into perceived barriers and facilitators that may inform future intervention development and clinical questioning. Full article

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

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19 pages, 6700 KB

Open AccessArticle

Prevalence of Intracranial and Cervical Artery Abnormalities in Patients with Hypermobile Ehlers–Danlos Syndrome and Hypermobility Spectrum Disorders Presenting to an Academic Headache Clinic

by Todd D. Rozen, Katelyn A. Bruno, Ethan M. Rozen, Frances C. Wilson, Marysia S. Tweet, Raymond C. Shields, Sharonne N. Hayes, Dacre R. T. Knight, Shilpa N. Gajarawala, Sukhwinder J. S. Sandhu, Alok A. Bhatt and DeLisa Fairweather

Neurol. Int. 2026, 18(2), 33; https://doi.org/10.3390/neurolint18020033 - 11 Feb 2026

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Abstract

Background/Objective: It remains unknown whether patients with the more common forms of hypermobility carry an elevated risk for the development of intracranial/cervical artery abnormalities. The objective of this study was to determine the prevalence of unruptured intracranial aneurysms, spontaneous cervical artery dissections, and [...] Read more.

Background/Objective: It remains unknown whether patients with the more common forms of hypermobility carry an elevated risk for the development of intracranial/cervical artery abnormalities. The objective of this study was to determine the prevalence of unruptured intracranial aneurysms, spontaneous cervical artery dissections, and fibromuscular dysplasia in patients with hypermobile Ehlers–Danlos Syndrome (hEDS) and hypermobility spectrum disorders (HSD) who presented to an academic headache clinic. Methods: This is a retrospective cohort study. We used an electronic medical record to look for all patients seen at the Mayo Clinic Florida Headache Center and EDS Clinic between 2019 and 2025 with a diagnosis of hEDS or HSD and neuroimaging of both the intracranial and cervical arteries. Results: There were 103 patients who met the inclusion criteria. There was no statistically significant difference between hEDS and HSD patients in developing cerebral/cervical arterial anomalies. Of the sample, 95% of the hypermobile patients with abnormal neuroimaging also had migraine. A total of eleven (10.7%) patients (hEDS + HSD) were diagnosed with unruptured intracranial aneurysms. Trends included age less than 50 years, small aneurysms in the anterior circulation, and having migraine with aura. Five (4.8%) patients were diagnosed with spontaneous cervical artery dissection with trends for HSD, over the age of 50 years, vertebral artery involvement and a history of migraine without aura. Six (5.8%) patients were diagnosed with fibromuscular dysplasia with trends for HSD, over the age of 50 years, carotid artery involvement and a history of migraine with aura. Conclusions: This is the first study to identify that patients with the more common type of EDS, HSD and hEDS, and a possible concomitant history of migraine have a heightened risk for the development of unruptured intracranial aneurysms, spontaneous cervical artery dissections, and fibromuscular dysplasia. Our findings suggest the need for targeted screening with intracranial and extracranial arterial imaging for this unique patient population. Full article

(This article belongs to the Section Pain Research)

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16 pages, 2274 KB

Open AccessCase Report

Neurophysiological Characteristics of Upper Extremity Neuropathy in Three Young Patients with Mucopolysaccharidosis Type I and II in a Five-Year Observation—A Case Series Study

by Agnieszka Wiertel-Krawczuk, Zofia Krawczuk and Juliusz Huber

Neurol. Int. 2026, 18(2), 32; https://doi.org/10.3390/neurolint18020032 - 11 Feb 2026

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Abstract

Background/Objectives: To date, few studies have reported the use of neurophysiological testing to assess the long-term progression of functional changes in median and ulnar nerve conduction in children and adolescents with mucopolysaccharidosis (MPS). This case series study aimed to perform an electroneurographic (ENG) [...] Read more.

Background/Objectives: To date, few studies have reported the use of neurophysiological testing to assess the long-term progression of functional changes in median and ulnar nerve conduction in children and adolescents with mucopolysaccharidosis (MPS). This case series study aimed to perform an electroneurographic (ENG) assessment of the median and ulnar nerves in three young patients with MPS treated with enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) over a five-year observation period. Methods: Bilateral electroneurography of the motor and sensory fibers in the median and ulnar nerves, recording compound muscle action potential (CMAP) and sensory nerve action potential (SNAP), was performed twice in 5-, 7-, and 19-year-old males at two time points: before and five years after the application of ERT and HSCT. Results: In three MPS patients with Hurler or Hunter syndrome, ENG studies similarly demonstrated decreased amplitudes and prolonged distal latencies in their CMAP recordings, confirming the bilateral progression of axonal degeneration and demyelinating changes in the distal parts of the median nerves. The SNAP recordings revealed more severe degenerative processes of similar types in the sensory fibers of the median nerves. Nerve conduction studies in the ulnar nerve fibers bilaterally revealed analogous pathologies, but with a lesser degree of progression. Conclusions: This study confirms the progression of axonal degeneration and demyelinating changes in the distal parts of the median nerves, which were associated with decreased amplitudes and prolonged distal latencies in the CMAP recordings of the MPS patients. More expressed degeneration processes of a similar type were found in the sensory fibers of the median nerves. Ulnar nerve pathologies of neural conduction are less advanced in patients with Hurler and Hunter syndromes. It seems advisable to implement neurophysiological diagnostics as soon as possible to specify surgical or conservative therapy, which is crucial for maintaining hand function in the case of progressive peripheral neuropathies in patients with MPS. The timing of the treatment and the patient’s age may be factors influencing the effectiveness of treatment. Full article

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11 pages, 1998 KB

Open AccessCase Report

Transcutaneous Spinal Cord Stimulation Improves Upper and Lower Limbs’ Motor and Sensory Function in a Subject with Central Cord Syndrome: A Case Report

by Fernando Reyes, Camila Parker, Tania Turquie, Aldo Chimal, Lorermy Villalobos, Frida Bailey, Antonio Ibarra, Igor Lavrov and Carlos A. Cuellar

Neurol. Int. 2026, 18(2), 31; https://doi.org/10.3390/neurolint18020031 - 10 Feb 2026

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Abstract

Background: Central cord syndrome (CCS) is the most common incomplete spinal cord injury, producing more severe motor deficits in the upper than lower extremities and impairing sensory and autonomic function. Although transcutaneous spinal cord stimulation (tSCS) has shown benefits in motor and sensory [...] Read more.

Background: Central cord syndrome (CCS) is the most common incomplete spinal cord injury, producing more severe motor deficits in the upper than lower extremities and impairing sensory and autonomic function. Although transcutaneous spinal cord stimulation (tSCS) has shown benefits in motor and sensory recovery after spinal cord injury, studies have not explicitly documented whether CCS subjects were included. The aim of this study was to assess the effects of tSCS over 12 weeks on motor and sensory outcomes in a subject with CCS. Methods: A 20-year-old male with a C7 injury was evaluated at baseline and after 12 weeks with the American Spinal Cord Injury Impairment scale, Modified Ashworth Scale, Penn and Spasm Frequency Scale, 3-Meter Walk Test and 6-Minute Walk Test, 9-Hole Peg Test, Box and Block Test, hand dynamometry, and lower-limb EMG. tSCS was applied between T9 and L1 at 30 Hz. Results: At 12 weeks, upper-limb motor and sensory scores improved, while spasm frequency and hand spasticity were reduced. Manual dexterity improved bilaterally in the 9-Hole Peg and Box and Block Tests, with a 2 kg gain in right-hand grip strength. In the 6-Minute Walk Test, the distance covered increased from 224.4 m to 295.2 m, and a 1.36 s reduction in 3-Meter walking time was achieved. Conclusions: tSCS improved motor and sensory function and reduced spasticity and spasms. These findings suggest that tSCS may serve as an effective complementary intervention for motor and sensory rehabilitation in individuals with mild cervical injuries, including CCS. Full article

(This article belongs to the Topic Advances in Neurorehabilitation)

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12 pages, 1530 KB

Open AccessArticle

Risk Factors for Non-Space-Occupying Postoperative Hemorrhages Following Brain Tumor Resection Without the Influence of Anticoagulant or Antiplatelet Therapy: A Ten-Year Single-Center Retrospective Analysis

by Anatoli Pinchuk, Nikolay Tonchev, Anna Schaufler, Claudia A. Dumitru, Belal Neyazi, Klaus-Peter Stein, I. Erol Sandalcioglu and Ali Rashidi

Neurol. Int. 2026, 18(2), 30; https://doi.org/10.3390/neurolint18020030 - 9 Feb 2026

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Abstract

Background/Objectives: Postoperative intracerebral hematomas (POHs) are a common complication following brain tumor surgery and are typically associated with unfavorable outcomes. While extensive hemorrhages have been studied extensively, smaller, Non-Space-Occupying hemorrhages are frequently detected, yet their clinical relevance and associated risk factors remain [...] Read more.

Background/Objectives: Postoperative intracerebral hematomas (POHs) are a common complication following brain tumor surgery and are typically associated with unfavorable outcomes. While extensive hemorrhages have been studied extensively, smaller, Non-Space-Occupying hemorrhages are frequently detected, yet their clinical relevance and associated risk factors remain insufficiently understood. This study aimed to identify predictive factors for the occurrence of Non-Space-Occupying postoperative cerebral hemorrhages in patients undergoing brain tumor resection. Methods: A total of 1481 patients without a history of anticoagulant or antiplatelet therapy underwent brain tumor surgery at our neurosurgical institute over a ten-year period. Non-Space-Occupying postoperative hemorrhages were diagnosed in 84 patients using cranial computed tomography (cCT) or magnetic resonance imaging (cMRI) performed after the tumor resection. Demographic data, pre-existing comorbidities, and tumor characteristics were collected and analyzed. Results: Non-Space-Occupying POHs occurred in 5.6% of patients. The most frequent tumor type associated with POHs was glioblastoma multiforme (N = 33; 39.3%), followed by metastatic lesions (N = 9; 10.7%) and benign primary intracranial neoplasms (N = 31; 38%). None of the affected patients exhibited new neurological deficits or signs of increased intracranial pressure. A multivariate analysis identified the tumor size as an independent risk factor for Non-Space-Occupying POHs (p = 0.002), with patient age emerging as the strongest predictor (p = 0.001). Conclusions: Non-Space-Occupying POHs after a brain tumor resection are significantly associated with the tumor size, an advanced patient age, and the presence of pre-existing liver disease. The recognition of these risk factors may facilitate targeted perioperative monitoring and guide postoperative management strategies. Full article

(This article belongs to the Section Brain Tumor and Brain Injury)

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14 pages, 265 KB

Open AccessArticle

Protein Z and Protein Z Complex in the Acute Phase of Ischemic Stroke: Potential Markers of Coagulation and Prognostic Value in Patients Treated with Thrombolysis or Conservative Therapy

by Małgorzata Wiszniewska, Urszula Włodarczyk, Mariusz Domagalski, Artur Słomka, Inga Dziembowska, Maciej Gawrysiak, Anna Żdanowicz and Ewa Żekanowska

Neurol. Int. 2026, 18(2), 29; https://doi.org/10.3390/neurolint18020029 - 6 Feb 2026

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Abstract

Background/Objectives: Protein Z (PZ) and the protein Z-dependent protease inhibitor (ZPI) are vitamin K-dependent regulators of coagulation that inhibit activated factor Xa. Their relevance in ischemic stroke (IS) remains insufficiently characterized, with inconsistent evidence regarding their association with stroke severity and outcomes. This [...] Read more.

Background/Objectives: Protein Z (PZ) and the protein Z-dependent protease inhibitor (ZPI) are vitamin K-dependent regulators of coagulation that inhibit activated factor Xa. Their relevance in ischemic stroke (IS) remains insufficiently characterized, with inconsistent evidence regarding their association with stroke severity and outcomes. This study aimed to evaluate the concentrations and dynamics of PZ and ZPI in the acute phase of IS in patients treated with intravenous thrombolysis or conservative therapy and to assess their potential prognostic significance. Methods: Eighty-four patients with acute IS were enrolled and divided into two groups: group I treated with intravenous thrombolysis (rt-PA) and group II managed conservatively. PZ and ZPI concentrations were measured using ELISA on admission (day 1) and on day 7. Associations with factor X activity, the modified Rankin Scale (mRS), and the National Institutes of Health Stroke Scale (NIHSS) were analyzed using nonparametric tests and Spearman correlations (p < 0.05). Results: PZ concentrations were significantly higher in thrombolysis-treated patients than in conservatively managed patients both on day 1 (median: 2810.05 vs. 2178.50 ng/mL; p = 0.024) and day 7 (2982.90 vs. 2286.50 ng/mL; p = 0.026). A slight negative correlation between PZ and mRS on day 7 was observed in the conservative group (r = −0.360; p = 0.043). In thrombolysis-treated patients with dyslipidemia, PZ increased from day 1 to day 7, whereas it decreased in those without dyslipidemia. No significant correlations were found between PZ, ZPI, or factor X and NIHSS or ASTRAL scores. Conclusions: Higher PZ concentrations in the acute phase of IS—particularly in rt-PA-treated patients—may reflect differences related to the timing of the acute ischemic process and reperfusion status, suggesting potential utility as markers of stroke severity or outcome. Full article

(This article belongs to the Collection Biomarkers in Stroke Prognosis)

17 pages, 2104 KB

Open AccessSystematic Review

Effectiveness of Pulsed Electromagnetic Field Therapy on Neuropathic Pain: A Systematic Review and Meta-Analysis

by Jesus Antonio Lara-Reyes, Cristofer Zarate-Calderon, Gonzalo E. Aranda-Abreu, Luis I. García and Fausto Rojas-Durán

Neurol. Int. 2026, 18(2), 28; https://doi.org/10.3390/neurolint18020028 - 6 Feb 2026

Cited by 1 | Viewed by 1649

Abstract

Background: Neuropathic pain represents a substantial global burden with limited effective therapeutic options. Pulsed Electromagnetic Field (PEMF) therapy has emerged as a potential non-invasive adjuvant, though clinical evidence remains inconsistent. This systematic review and meta-analysis evaluated PEMF efficacy and safety, specifically analyzing the [...] Read more.

Background: Neuropathic pain represents a substantial global burden with limited effective therapeutic options. Pulsed Electromagnetic Field (PEMF) therapy has emerged as a potential non-invasive adjuvant, though clinical evidence remains inconsistent. This systematic review and meta-analysis evaluated PEMF efficacy and safety, specifically analyzing the influence of etiology and stimulation parameters. Methods: Following PRISMA 2020 guidelines (PROSPERO: CRD420251184151), five databases (Cochrane, PubMed, Scopus, Web of Science, and LILACS) were searched for Randomized Controlled Trials (RCTs) comparing PEMF versus sham. Risk of bias was assessed via Cochrane RoB 2, and heterogeneity was explored through detailed subgroup analyses. Results: Thirteen RCTs met the inclusion criteria (N = 688). While global analysis indicated a statistically significant pain reduction (SMD: −1.01; p = 0.03), it exhibited extreme statistical heterogeneity (I² = 92.8%) and instability. After adjusting for missing studies using the Trim-and-Fill method, global significance disappeared. However, subgroup analysis resolved this inconsistency, revealing a massive, clinically meaningful effect in Spinal/Radicular pain (SMD: −2.35; 95% CI: −4.42 to −0.29), whereas Peripheral Neuropathy showed no significant reduction (SMD: −0.38; 95% CI: −0.86 to 0.10). Conclusions: The PEMF evidence base for neuropathic pain is currently highly fragmented. Extreme heterogeneity and publication bias render “one-size-fits-all” efficacy estimates invalid and potentially misleading. Instead, our data reveals a critical etiological divergence: PEMF appears highly effective for spinal/radicular pathology, likely due to the mechanical nature of the lesion, but demonstrates limited efficacy for diffuse peripheral neuropathy. Future research must abandon generic protocols in favor of etiology-specific trials, prioritizing high-frequency parameters and rigorous bias control. Full article

(This article belongs to the Special Issue Non-Invasive Neuromodulation in Treatment of Chronic Pain)

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15 pages, 443 KB

Open AccessArticle

Longitudinal Evaluation of Polyneuropathy in Atypical Parkinsonian Syndromes

by Eun Hae Kwon, Julia Steininger, Antonia Bieber, Saskia Kools, Teresa Kleinz, Lovis Hilker, Lea Ebner, Louisa Ortmann, Louisa Basner, Christiane Schneider-Gold, Ralf Gold, Raphael Scherbaum, Kalliopi Pitarokoili and Lars Tönges

Neurol. Int. 2026, 18(2), 27; https://doi.org/10.3390/neurolint18020027 - 3 Feb 2026

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Abstract

Background: In Parkinson’s disease (PD), a higher prevalence of polyneuropathy (PNP) is increasingly recognized, although the causal association is still under debate. In contrast, PNP in atypical parkinsonian syndromes (APS) has been insufficiently addressed, despite preliminary evidence suggesting elevated prevalence. Methods: Nerve conduction [...] Read more.

Background: In Parkinson’s disease (PD), a higher prevalence of polyneuropathy (PNP) is increasingly recognized, although the causal association is still under debate. In contrast, PNP in atypical parkinsonian syndromes (APS) has been insufficiently addressed, despite preliminary evidence suggesting elevated prevalence. Methods: Nerve conduction studies were performed on 13 patients with multiple system atrophy (MSA) and 9 patients with progressive supranuclear palsy (PSP) at baseline. PNP was diagnosed according to standard electrophysiological criteria after exclusion of common secondary causes. Comprehensive clinical evaluation included motor and non-motor assessments over two years of follow-up. Results: At baseline, PNP was present in 53.8% of MSA patients and 66.7% of PSP patients. MSA patients with PNP showed greater motor symptom severity (UPDRS III score; p = 0.046) and worse cognitive performance (MoCA; p = 0.044) compared to those without PNP. Over two years, a significant reduction in the tibial nerve amplitude was observed exclusively in MSA patients (p = 0.039), paralleling disease progression. Conclusions: This study provides the first longitudinal evaluation of clinical and electrophysiological PNP progression in MSA and PSP. A high comorbidity of PNP in patients with APS could contribute to motor and sensory impairments in these patients. Our findings indicate that PNP progression may reflect disease progression in MSA. Given the limited sample size, larger-scale longitudinal studies are needed to further investigate biomarker potential of PNP in APS and to clarify differences in peripheral nerve involvement between synucleinopathies and tauopathies. Full article

(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)

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15 pages, 409 KB

Open AccessSystematic Review

Effectiveness of Music Therapy with Personalized Rhythmic Auditory Stimulation Plus Music-Contingent Gait Training in Patients with Parkinson’s Disease: A Systematic Review

by Andrea Demeco, Rosa Cristina Bruno, Raffaele Bonfiglio, Lorenzo Mancini, Federica Pisani, Lorenzo Scozzafava, Chiara Conte, Antonio Ammendolia, Alessandro de Sire and Nicola Marotta

Neurol. Int. 2026, 18(2), 26; https://doi.org/10.3390/neurolint18020026 - 3 Feb 2026

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Abstract

Background: Parkinson’s disease (PD) is characterized by motor disturbances that significantly impact balance, gait, and quality of life. Personalized Rhythmic Auditory Stimulation (pRAS) is an emerging rehabilitative approach that utilizes auditory entrainment to improve step and gait control. The aim of this [...] Read more.

Background: Parkinson’s disease (PD) is characterized by motor disturbances that significantly impact balance, gait, and quality of life. Personalized Rhythmic Auditory Stimulation (pRAS) is an emerging rehabilitative approach that utilizes auditory entrainment to improve step and gait control. The aim of this systematic review is to critically summarize the data from the most recent evidence concerning the use of pRAS in gait rehabilitation for patients with Parkinson’s disease. Methods: A systematic review was conducted following PRISMA guidelines, including records that evaluated music-based or technological interventions based on personalized RAS. Primary outcomes included spatiotemporal gait parameters and distance covered. Results: Ten studies were included in the analysis. All the studies reported clinically relevant improvements: increases in gait speed, step length, and amplitude. Moreover, a reduction in freezing of gait episodes (up to 36%), greater walking distance, and good adherence were reported. Conclusions: Personalized, adaptive, or on-demand solutions proved more effective than traditional forms of cueing. Moreover, the available evidence suggests that pRAS constitutes an effective and safe rehabilitative option for gait disturbances in PD. However, further studies with larger sample sizes and prolonged follow-up periods are necessary to evaluate its long-term impact and transferability into clinical practice. Full article

(This article belongs to the Collection Exclusive Papers from the Editorial Board Members (EBMs) of Neurology International)

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17 pages, 2183 KB

Open AccessArticle

A Comparative Study of Clinical and Demographic Profiles of Multiple Sclerosis Patients in Two Regional Centers in Denmark and Romania

by Oana Vrînceanu, Rodica Bălașa, Smaranda Maier, Luigi Pontieri and Melinda Magyari

Neurol. Int. 2026, 18(2), 25; https://doi.org/10.3390/neurolint18020025 - 29 Jan 2026

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Abstract

Background: Environmental factors are known to influence the clinical presentation of patients with multiple sclerosis. This study aims to compare the demographic and clinical characteristics of multiple sclerosis patients treated at two diverse geographical settings. Methods: A cross-sectional, observational cohort study [...] Read more.

Background: Environmental factors are known to influence the clinical presentation of patients with multiple sclerosis. This study aims to compare the demographic and clinical characteristics of multiple sclerosis patients treated at two diverse geographical settings. Methods: A cross-sectional, observational cohort study was conducted in two MS centers: the Danish Multiple Sclerosis Center (DMSC) in Copenhagen, Denmark and the Regional MS Center in Târgu Mureș, Romania. We compared patients’ demographic and clinical characteristics between MS centers, including sex distribution, current age, MS onset age, latest EDSS scores, symptomatology at disease onset, MS phenotype and type of ongoing DMT. Results: In both cohorts, sex distribution was similar, with females constituting 69.2% in DMSC, and 65.7% in Târgu Mureș. Pyramidal symptoms at MS onset were predominant among Targu Mures patients (32.7%), while sensory symptoms were more frequent among DMSC patients (33%). Progressive forms of MS were more prevalent in Târgu Mureș (22.6%) compared to DMSC (9.9%). High-efficacy DMTs were on use by 58.3% patients in DMSC and only by 29.4% patients in Târgu Mureș, who were mostly on low-efficacy DMTs (54.4% vs. 12.4% in DMSC). Conclusions: The study highlights both shared and distinct characteristics of MS patients treated in these two centers. These findings underscore the importance of regional considerations in the management and treatment of MS. Full article

(This article belongs to the Topic Management of Multiple Sclerosis: Past, Present and Promise)

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31 pages, 889 KB

Open AccessReview

Ketogenic Strategies in Neonatal Hypoxic–Ischemic Encephalopathy—The Road to Opening Up: A Scoping Review

by Raffaele Falsaperla, Vincenzo Sortino, Cristina Malaventura, Silvia Fanaro, Elisa Ballardini, Aloise Martina, Annamaria Sapuppo and Agnese Suppiej

Neurol. Int. 2026, 18(2), 24; https://doi.org/10.3390/neurolint18020024 - 28 Jan 2026

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Abstract

Background: Neonatal hypoxic–ischemic encephalopathy remains a leading cause of neonatal mortality and long-term neurodevelopmental disability worldwide. Despite the widespread adoption of therapeutic hypothermia, a substantial proportion of affected infants experience death or significant neurological impairment. Given their metabolic vulnerability, ketogenic diet strategies and [...] Read more.

Background: Neonatal hypoxic–ischemic encephalopathy remains a leading cause of neonatal mortality and long-term neurodevelopmental disability worldwide. Despite the widespread adoption of therapeutic hypothermia, a substantial proportion of affected infants experience death or significant neurological impairment. Given their metabolic vulnerability, ketogenic diet strategies and ketone bodies have emerged as potential adjunctive neuroprotective interventions. This scoping review aims to critically evaluate the mechanistic rationale, preclinical evidence, and clinical feasibility of ketogenic approaches. Methods: A scoping review of the literature was conducted, including experimental and clinical studies investigating ketogenic diets, endogenous ketosis, and exogenous ketone supplementation in neonatal hypoxia–ischemia. Evidence was synthesized across mechanistic, preclinical, nutritional, and clinical domains, with particular attention to developmental context, timing of intervention, safety considerations, and translational relevance in the contest of therapeutic hypothermia. Results: Preclinical studies consistently demonstrate that ketone bodies enhance cerebral energy metabolism, support mitochondrial function, reduce excitotoxic signaling, and attenuate oxidative stress and neuroinflammation in the immature brain. Neonatal models show preferential utilization of β-hydroxybutyrate over glucose during hypoxic–ischemic stress, suggesting intrinsic metabolic advantages. Emerging evidence also supports potential long-term effects on epigenetic regulation and white matter development, although direct causal validation in neonatal HIE remains limited. Nutritional studies indicate that carefully monitored enteral and parenteral feeding is feasible in critically ill neonates, identifying a potential window for metabolic interventions. Conclusions: Ketogenic strategies represent a plausible, multimodal approach to targeting the metabolic and inflammatory sequelae of neonatal HIE. While current evidence is insufficient to support clinical implementation, this scoping review provides a hypothesis-generating framework to guide future translational research and the design of carefully controlled clinical trials in neonatal neurocritical care. Full article

(This article belongs to the Collection Exclusive Papers from the Editorial Board Members (EBMs) of Neurology International)

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15 pages, 1091 KB

Open AccessReview

Consensus Molecules Associated with Parkinson’s Disease

by Sara Eyal, Shira Alfasi, Karin Ben Zaken, Ibrahim O. Sawaid, Lior Segev, Samuel Mesfin, Pnina Frankel, Rahaf Ezzy, Trishna Saha-Detroja, Shilpa Madhavan, Naamah Bloch, Baruh Polis and Abraham O. Samson

Neurol. Int. 2026, 18(2), 23; https://doi.org/10.3390/neurolint18020023 - 27 Jan 2026

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Abstract

Parkinson’s disease (PD) has been associated with some types of food and drugs. Here, we query PubMed for the association of PD with foods and drugs, using a list of 217,776 compounds derived from the Human Metabolome Database (HMDB). To calculate associations, a [...] Read more.

Parkinson’s disease (PD) has been associated with some types of food and drugs. Here, we query PubMed for the association of PD with foods and drugs, using a list of 217,776 compounds derived from the Human Metabolome Database (HMDB). To calculate associations, a Python script was developed to query PubMed for co-citations of PD with each compound, and adjust this count for compound abundance. Notably, PD is found to be associated with small-molecule drugs, adjunctive therapies, contraindicated drugs, diagnostic agents, biomarkers, conditional essential molecules, and inducers. Drugs include L-dopa (49%), carbidopa (63%), benserazide (50%), entacapone (74%), tolcapone (56%), rasagiline (76%), selegiline (46%), pargyline (4%), ropinirole (61%), pramipexole (56%), lisuride (27%), cabergoline (16%), bromocriptine (12%), and zonisamide (9%). Adjunctive therapies include droxidopa (33%), trihexyphenidyl (28%), biperiden (17%), amantadine (24%), memantine (7%), rivastigmine (13%), donepezil (6%), galantamine (4%), domperidone (6%), clonazepam (4%), tetrabenazine (16%), mazindol (13%), quetiapine (6%), and clozapine (4%). Contraindicated drugs include haloperidol (4%), sulpiride (3%), and methyldopa (6%). Diagnostic agents include FP-CIT (60%) and beta-CIT (43%). Biomarkers include 3-methoxytyrosine (48%) and homovanillic acid (12%). Endogenous cofactors include tetrahydrobiopterin (4%) and Coenzyme Q10 (4%). Chemical inducers of PD include 6-hydroxydopamine (40%), N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 78%), tetrahydropyridine (77%), probenecid (4%), quinolinic acid (4%), 1,2,3,4-tetrahydroisoquinoline (TIQ, 16%), salsolinol (32%), rotenone (25%), and β-Methylamino-L-alanine (BMAA, 29%). Notably, our study highlights conditional essential endogenous cofactors associated with PD and emphasizes rational directions for investigation in PD. Full article

(This article belongs to the Special Issue Advances in Molecular Mechanisms of Neurodegenerative Diseases)

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17 pages, 8025 KB

Open AccessArticle

Quantitative Analysis of Smooth Pursuit and Saccadic Eye Movements in Multiple Sclerosis

by Pavol Skacik, Lucia Kotulova, Ema Kantorova, Egon Kurca and Stefan Sivak

Neurol. Int. 2026, 18(2), 22; https://doi.org/10.3390/neurolint18020022 - 26 Jan 2026

Viewed by 436

Abstract

Introduction: Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system, frequently associated with visual and oculomotor disturbances. Quantitative analysis of eye movements represents a non-invasive method for assessing central nervous system dysfunction beyond conventional imaging; however, [...] Read more.

Introduction: Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system, frequently associated with visual and oculomotor disturbances. Quantitative analysis of eye movements represents a non-invasive method for assessing central nervous system dysfunction beyond conventional imaging; however, the diagnostic and predictive value of oculomotor metrics remains insufficiently defined. Objectives: The aims of this study were to compare smooth pursuit gain and reflexive saccade parameters (latency, velocity, and precision) between individuals with MS and healthy controls, and to evaluate their ability to discriminate disease status. Methods: This cross-sectional study included 46 clinically stable patients with MS (EDSS ≤ 6.5) and 46 age- and sex-matched healthy controls. Oculomotor function was assessed using videonystagmography under standardized conditions. Group differences across horizontal and vertical gaze directions were analyzed using linear mixed-effects models. Random forest models were applied to assess the discriminative performance of oculomotor parameters, with permutation-based feature importance and receiver operating characteristic (ROC) curve analysis. Results: Patients with MS showed significantly reduced smooth pursuit gain across most horizontal and vertical directions compared with controls. Saccadic latency was significantly prolonged in all tested movement directions. Saccadic velocity exhibited selective directional impairment consistent with subtle medial longitudinal fasciculus involvement, whereas saccadic precision did not differ significantly between groups. A random forest model combining pursuit and saccadic parameters demonstrated only moderate discriminative performance between MS patients and controls (AUC = 0.694), with saccadic latency contributing most strongly to classification. Conclusions: Quantitative eye-movement assessment revealed widespread oculomotor abnormalities in MS, particularly reduced smooth pursuit gain and prolonged saccadic latency. Although the overall discriminative accuracy of oculomotor parameters was limited, these findings support their potential role as complementary markers of central nervous system dysfunction. Further longitudinal and multimodal studies are required to clarify their clinical relevance and prognostic value. Full article

(This article belongs to the Special Issue Advances in Multiple Sclerosis, Third Edition)

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9 pages, 653 KB

Open AccessCase Report

Anteromedial Globus Pallidus Internus Deep Brain Stimulation for Gilles de la Tourette Syndrome: A Two-Case Report and Review of the Literature

by Tomislav Felbabić, Rok Berlot, Maja Trošt, Dejan Georgiev and Mitja Benedičič

Neurol. Int. 2026, 18(2), 21; https://doi.org/10.3390/neurolint18020021 - 25 Jan 2026

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Abstract

Background: Gilles de la Tourette syndrome is a neurobehavioral disorder that typically begins in childhood, subsides during puberty, and may reappear in adolescence. Treatment is primarily conservative, involving psychological and pharmacological therapy. Patients who do not respond to conservative therapy may be treated [...] Read more.

Background: Gilles de la Tourette syndrome is a neurobehavioral disorder that typically begins in childhood, subsides during puberty, and may reappear in adolescence. Treatment is primarily conservative, involving psychological and pharmacological therapy. Patients who do not respond to conservative therapy may be treated with deep brain stimulation, although this remains an experimental treatment. Methods: In this two-case report we present the first two cases of patients with Gilles de la Tourette syndrome in Slovenia treated with deep brain stimulation of the anteromedial globus pallidus internus. Results: Over an 18-month follow-up period, we observed an improvement in both cases. In the first case, the Yale Global Tic Severity Scale score decreased from 71 (17 for motor tics, 14 for phonic tics, and 40 on the impairment scale) to 44 points (12 motor, 12 phonic, and 20 impairment). In the second case, the score decreased from 72 (16 motor, 16 phonic, and 40 impairment) to 38 points (8 motor, 10 phonic, and 20 impairment). Conclusions: Deep brain stimulation could be a promising treatment for this disorder. However, further research is needed to determine the most suitable patients and targets. Full article

(This article belongs to the Section Movement Disorders and Neurodegenerative Diseases)

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Neurol. Int., Volume 18, Issue 2 (February 2026) – 19 articles

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