Neurological Diseases: Biomarkers, Diagnosis and Prognosis

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Clinical Diagnosis and Prognosis".

Deadline for manuscript submissions: 31 August 2025 | Viewed by 2526

Special Issue Editor


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Guest Editor
Department of Neurosurgery, School of Medicine, Evangelismos Hospital, National and Kapodistrian University of Athens, 10676 Athens, Greece
Interests: neurological disease biomarkers (CNS tumors, hydrocephalus, chronic subdural hematoma, traumatic brain injury); neuroprotection and functional recovery following brain injury; circadian rhythms and sleep disorders; neuroepidemiology (stroke, CNS tumors, epilepsy, traumatic brain injury)
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Special Issue Information

Dear Colleagues,

This Special Issue, “Neurological Diseases: Biomarkers, Diagnosis, and Prognosis”, delves into cutting-edge research on identifying biomarkers, advancing diagnostic techniques, and predicting prognosis for various neurological disorders, aiming to enhance patient outcomes and the understanding of these complex conditions.

Dr. Theodosis Kalamatianos
Guest Editor

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Keywords

  • biomarkers
  • neurological diseases
  • multiple sclerosis
  • traumatic brain injury
  • peripheral neuropathies
  • COVID-19 neurological-associated damage
  • diagnosis
  • prognosis.

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Published Papers (5 papers)

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Research

20 pages, 8277 KiB  
Article
Investigating the Role of Intravoxel Incoherent Motion Diffusion-Weighted Imaging in Evaluating Multiple Sclerosis Lesions
by Othman I. Alomair, Sami A. Alghamdi, Abdullah H. Abujamea, Ahmed Y. AlfIfi, Yazeed I. Alashban and Nyoman D. Kurniawan
Diagnostics 2025, 15(10), 1260; https://doi.org/10.3390/diagnostics15101260 - 15 May 2025
Viewed by 153
Abstract
Background: Multiple sclerosis (MS) is a chronic and heterogeneous disease characterized by demyelination and axonal loss and damage. Magnetic resonance imaging (MRI) has been employed to distinguish these changes in various types of MS lesions. Objectives: We aimed to evaluate intravoxel incoherent [...] Read more.
Background: Multiple sclerosis (MS) is a chronic and heterogeneous disease characterized by demyelination and axonal loss and damage. Magnetic resonance imaging (MRI) has been employed to distinguish these changes in various types of MS lesions. Objectives: We aimed to evaluate intravoxel incoherent motion (IVIM) diffusion and perfusion MRI metrics across different brain regions in healthy individuals and various types of MS lesions, including enhanced, non-enhanced, and black hole lesions. Methods: A prospective study included 237 patients with MS (65 males and 172 females) and 29 healthy control participants (25 males and 4 females). The field strength was 1.5 Tesla. The imaging sequences included three-dimensional (3D) T1, 3D fluid-attenuated inversion recovery, two-dimensional (2D) T1, T2-weighted imaging, and 2D diffusion-weighted imaging (DWI) sequences. IVIM-derived parameters—apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudo-diffusion (D*), and perfusion fraction (f)—were quantified for commonly observed lesion types (2506 lesions from 224 patients with MS, excluding 13 patients due to MRI artifacts or not meeting the diagnostic criteria for RR-MS) and for corresponding brain regions in 29 healthy control participants. A one-way analysis of variance, followed by post-hoc analysis (Tukey’s test), was performed to compare mean values between the healthy and MS groups. Receiver operating characteristic curve analyses, including area under the curve, sensitivity, and specificity, were conducted to determine the cutoff values of IVIM parameters for distinguishing between the groups. A p-value of ≤0.05 and 95% confidence intervals were used to report statistical significance and precision, respectively. Results: All IVIM parametric maps in this study discriminated among most MS lesion types. ADC, D, and D* values for MS black hole lesions were significantly higher (p < 0.0001) than those for other MS lesions and healthy controls. ADC, D, and D* maps demonstrated high sensitivity and specificity, whereas f maps exhibited low sensitivity but high specificity. Conclusions: IVIM parameters provide valuable diagnostic and clinical insights by demonstrating high sensitivity and specificity in evaluating different categories of MS lesions. Full article
(This article belongs to the Special Issue Neurological Diseases: Biomarkers, Diagnosis and Prognosis)
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11 pages, 4649 KiB  
Article
Longitudinal Analysis of P100 Wave Amplitude and Latency in Multiple Sclerosis: A 19-Year Retrospective VEP Study
by Manuela Andreea Ciapă, Vlad Constantin Donica, Claudia Florida Costea and Camelia Margareta Bogdănici
Diagnostics 2025, 15(10), 1189; https://doi.org/10.3390/diagnostics15101189 - 8 May 2025
Viewed by 272
Abstract
Background: The diagnosis of multiple sclerosis (MS) relies on identifying neurological signs and symptoms, supported by evidence of central nervous system (CNS) dissemination of lesions across time and space. The visual pathway is commonly involved in MS, with a frequent involvement of optic [...] Read more.
Background: The diagnosis of multiple sclerosis (MS) relies on identifying neurological signs and symptoms, supported by evidence of central nervous system (CNS) dissemination of lesions across time and space. The visual pathway is commonly involved in MS, with a frequent involvement of optic neuritis (ON) episodes. Our study aims to assess the relationship between neuronal damage and optic nerve demyelination by analyzing the latency and amplitude of the p100 wave complex using visual evoked potentials (VEPs). Methods: We conducted a retrospective longitudinal study, analyzing VEP records of 15 patients with recurrent remissive MS at baseline, 5, 10, 15, and 19 years. Results: In 30 eyes we observed an increase in p100 wave latency at 5-years by 14.35 ± 4.47 ms (p = 0.003), at 10-years by 19.26 ± 4.87 ms (p < 0.0005) and a decrease in amplitude by 2.29 ± 0.52 mV (p < 0.0005) when comparing to baseline values. At 15-years, 24 eyes presented an increase in latency of 31.39 ± 7.8 ms (p = 0.001) and a decrease in amplitude of 2.51 ± 0.6 mV (p < 0.0005) compared to baseline, while at 19-years, 10 eyes presented an increase in p100 wave latency of 53.45 ± 18.42 ms (p = 0.018) and a further decrease in amplitude of 4.06 ± 1.32 mV (p = 0.014). We found correlations between the p100 wave latency and amplitude at baseline, 15-year, and 19-year follow-ups, increasing from a low negative (r = −0.43) to medium negative (r = −0.502) and finally high negative (r = −0.906) correlation. Conclusions: VEPs have long been acknowledged for their ability to detect both clinical and subclinical lesions in MS cases. Our study offers new insight into the relationship between demyelination and axonal degeneration observed when analyzing the latency and amplitude of the p100 wave complex during VEP in a longitudinal analysis. Full article
(This article belongs to the Special Issue Neurological Diseases: Biomarkers, Diagnosis and Prognosis)
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14 pages, 1178 KiB  
Article
Exploratory Analysis of Cerebrospinal Fluid IL-6 and IL-17A Levels in Subcortical Small-Vessel Disease Compared to Alzheimer’s Disease: A Pilot Study
by Georgios Liakakis, Aigli G. Vakrakou, Fotini Boufidou, Vasilios Constantinides, Georgios Velonakis, George P. Paraskevas, Leonidas Stefanis and Elisabeth Kapaki
Diagnostics 2025, 15(6), 669; https://doi.org/10.3390/diagnostics15060669 - 10 Mar 2025
Viewed by 678
Abstract
Background/Objectives: Low-grade inflammation in the form of microglial activation may be involved in neurodegenerative and vascular dementias. Subcortical small-vessel disease (SSVD) is the main form of vascular dementia, associated with brain barrier dysfunction and endothelial and monocyte activation. IL-6 and IL-17A are [...] Read more.
Background/Objectives: Low-grade inflammation in the form of microglial activation may be involved in neurodegenerative and vascular dementias. Subcortical small-vessel disease (SSVD) is the main form of vascular dementia, associated with brain barrier dysfunction and endothelial and monocyte activation. IL-6 and IL-17A are known proinflammatory cytokines that contribute to the disruption of blood–brain barrier integrity and microvascular dysfunction, features that are central to SSVD pathophysiological pathways. We herein compared cerebrospinal fluid (CSF) IL-6 and IL-17A concentrations in SSVD and AD patients as well as control subjects and examined the potential associations among IL-6 and IL-17A levels with cognitive and ΜRΙ changes. The albumin quotient (Qalb) was also calculated. Methods: CSF IL-6 and IL-17A (18 SSVD, 17 AD, and 12 healthy controls) were measured with solid-phase sandwich ELISAs, while albumin levels were measured by immunonephelometry. MMSE, FAB, and the CLOX tests were used for cognitive assessment and MRI was used for atrophy and white matter hyperintensities. Results: Significantly elevated CSF levels of Qalb and IL-6 were found in SSVD patients compared to both AD (p = 0.02) and controls (p = 0.002), respectively. Moreover, CSF IL-6 levels displayed a significant inverse correlation with CLOX2 scores (r = −0.641, p = 0.02), as well as a positive correlation with the total normalized CSF volume (r = 0.7, p = 0.01). CSF IL-17A levels were found to be reduced in SSVD patients, compared to controls and AD patients (p < 0.0001 and p = 0.002, respectively). The IL-6/IL-17A ratio with a cut-off value > 1.004 displayed a sensitivity of 83.33% (95%CI; 60.78% to 94.16%) and a specificity of 68.97% (95%CI; 50.77% to 82.72%) for the discrimination of SSVD from AD patients and controls. Conclusions: In the present pilot single-center study, we found increased CSF IL-6 and IL-6/IL-17A ratio levels in SSVD patients that correlated with reduced scores in the CLOX2 test and increased CSF volume. These preliminary findings deserve further evaluation in larger cohorts in order to elucidate their potential as surrogate biomarkers for the discrimination of SSVD from AD pathology. Full article
(This article belongs to the Special Issue Neurological Diseases: Biomarkers, Diagnosis and Prognosis)
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13 pages, 423 KiB  
Article
Nesfatin-1 as a Potential Biomarker for Ischemic Stroke: A Case-Controlled Study of a Comparative Analysis of Patients with and Without Internal Carotid Artery Stenosis
by Şennur Delibaş Kati, Serkan Özben, Ertan Küçüksayan, Mert Van, Esra Yeğin Cilli, Aylin Yaman and Tomris Özben
Diagnostics 2025, 15(6), 664; https://doi.org/10.3390/diagnostics15060664 - 10 Mar 2025
Viewed by 558
Abstract
Objectives: Recently, the need for early diagnosis of modifiable risk factors involved in the etiology of stroke has been highlighted in the literature. Nesfatin-1 is a peptide expressed in the central nervous system and peripheral tissues and has been used as a biomarker [...] Read more.
Objectives: Recently, the need for early diagnosis of modifiable risk factors involved in the etiology of stroke has been highlighted in the literature. Nesfatin-1 is a peptide expressed in the central nervous system and peripheral tissues and has been used as a biomarker in recent years. This study aimed to determine the association of ischemic stroke with internal carotid artery stenosis according to nesfatin-1 level and whether it could be used as a biomarker. Methods: A total of 118 patients were included in the study. Three groups were defined: acute stroke patients with symptomatic internal carotid artery stenosis, acute stroke patients without internal carotid artery stenosis, and a control group. Nesfatin-1 levels were measured and compared. Results: The median value was 22 pg/mL in acute stroke patients with internal carotid artery stenosis, 24.3 pg/mL in acute stroke patients without internal carotid artery stenosis, and 46.4 pg/mL in the control group. There is a difference between the median values of nesfatin-1 according to the stroke groups with the control group (p < 0.001). When a cut-off value of ≤30.62 was taken for nesfatin-1, an AUC value of 0.773 indicated statistical significance (p < 0.001). Sensitivity was 77.03%, specificity 83.33%, PPV 90.48%, and NPV 63.83%. The main limitations of our study are the small sample size and the fact that the function of nesfatin-1 is not completely known. Conclusions: Although we found that nesfatin-1 levels were lower in ischemic stroke patients compared to controls, its diagnostic potential indicates a moderate discriminatory ability with an AUC value of 0.773. Therefore, whether it is suitable for clinical use will be demonstrated by studies in larger and multicenter cohorts. Full article
(This article belongs to the Special Issue Neurological Diseases: Biomarkers, Diagnosis and Prognosis)
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13 pages, 279 KiB  
Article
Adiponectin and Leptin—Considerations in Adult Patients with Spinal Muscular Atrophy Type 3
by Marija Miletić, Zorica Stević, Stojan Perić, Milina Tančić Gajić, Jelena Rakočević, Miloš Stojanović, Bojan Marković and Miloš Žarković
Diagnostics 2025, 15(5), 529; https://doi.org/10.3390/diagnostics15050529 - 21 Feb 2025
Cited by 1 | Viewed by 537
Abstract
Background: Spinal muscular atrophy (SMA) is a severe neuromuscular disorder characterized by the degeneration of alpha motor neurons in the spinal cord, leading to progressive proximal muscle weakness and paralysis. SMA is clinically categorized into four phenotypes based on age of onset [...] Read more.
Background: Spinal muscular atrophy (SMA) is a severe neuromuscular disorder characterized by the degeneration of alpha motor neurons in the spinal cord, leading to progressive proximal muscle weakness and paralysis. SMA is clinically categorized into four phenotypes based on age of onset and motor function achieved. Patients with SMA type 3 (juvenile, Kugelberg-Welander disease) initially have the ability to walk unaided, but experience a gradual decline in motor abilities over time. However, their lifespan is not affected by the presence of the disease. Leptin, a cytokine-like hormone secreted by adipocytes, has receptors widely distributed in musculoskeletal tissues. Several studies suggest that adiponectin deficiency contributes to the development of insulin resistance, with lower adiponectin levels closely associated with greater insulin resistance and hyperinsulinemia. However, the role of adiponectin in different types of sarcopenia and its connection to insulin sensitivity remains controversial. The purpose of this study was to measure leptin and adiponectin levels in patients with SMA type 3 and explore their association with markers of insulin sensitivity. Methods: This cross-sectional study included 23 adult patients with SMA type 3 (SMA group) and 18 community-based healthy volunteers (control group), conducted from July 2020 to September 2024. Anthropometric parameters, body composition, body fat percentage, surrogate markers of insulin sensitivity (Homeostasis model assessment of insulin resistance index—HOMA-IR and ISI Matsuda), and circulating levels of leptin and adiponectin were measured in all participants. Results: Insulin resistance was present in 91.3% of patients with SMA type 3, as determined by HOMA-IR and ISI Matsuda insulin sensitivity markers. In the control group, 64.7% had insulin resistance (IR) according to HOMA-IR, while 44.4% met the ISI Matsuda criterion for IR, showing a significant difference in peripheral insulin sensitivity between groups. A significant difference in serum adiponectin levels was observed between patients with SMA type 3 and the control group, whereas there was no significant difference in serum leptin concentrations. High adiponectin levels were observed in 50% of patients with SMA type 3. In the healthy control group, adiponectin levels positively correlated with ISI Matsuda and negatively correlated with HOMA-IR, confirming the insulin-sensitizing role of adiponectin. However, this correlation was not observed in patients with SMA type 3. Conclusions: Our results suggest that in this specific type of hereditary neuromuscular disease, the interplay between sarcopenia and insulin leads to adiponectin resistance, challenging the canonical narrative between insulin sensitivity and adiponectin, and indicating a need for further research. Full article
(This article belongs to the Special Issue Neurological Diseases: Biomarkers, Diagnosis and Prognosis)
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