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Advances in the Diagnosis of Nervous System Diseases—2nd Edition

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A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: 31 March 2025 | Viewed by 12785

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Dr. Vasileios T. Papaliagkas

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Department of Biomedical Sciences, School of Health Sciences, International Hellenic University, Thessaloniki, Greece
Interests: Alzheimer’s disease; neurodegenerative diseases; clinical neurophysiology; event-related potentials
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Dear Colleagues,

The diagnosis of neurological diseases is one of the most difficult challenges for medical professionals, due to the complexity of the nervous system. Currently, more than 600 diseases have been identified, including neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, cerebrovascular diseases and others, such as multiple sclerosis, migraines, neuroinfections and neuromuscular diseases [1]. According to the World Health Organization report, nervous system diseases affect up to one billion people worldwide [2]. Several methods, such as magnetic resonance imaging, CSF biomarkers, and genetic and neurophysiological tests, provide useful information for the diagnosis of neurological diseases.

In this Special Issue entitled “Advances in the Diagnosis of Nervous System Diseases—2nd Edition”, we invite investigators to contribute original research or review articles that focus on the role of tests or biomarkers (molecular, neuroimaging, genetic and neurophysiological) in the diagnosis of nervous system diseases.

References

Mott, M.; Koroshetz, W. Bridging the Gap in Neurotherapeutic Discovery and Development: The Role of the National Institute of Neurological Disorders and Stroke in Translational Neuroscience. Neurotherapeutics 2015, 12, 651–654. https://doi.org/10.1007/s13311-015-0366-6.
World Health Organisation. Neurological Disorders: Public Health Challenges; World Health Organization: Geneva, Switzerland, 2007.

Dr. Vasileios T. Papaliagkas
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

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Published Papers (11 papers)

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Research

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13 pages, 2669 KiB

Open AccessArticle

A Morphological Study of HLA-DR-Immunopositive Cells in Multiple Sclerosis Lesions and Their Implications for Pathogenesis

by Murad Alturkustani and Lee-Cyn Ang

Diagnostics 2024, 14(19), 2240; https://doi.org/10.3390/diagnostics14192240 - 8 Oct 2024

Viewed by 512

Abstract

Background: Multiple sclerosis (MS) is characterized by white matter demyelinating plaques, which can be classified as active, chronic active, or chronic inactive based on the extent of demyelination, cellularity, and inflammation. Microglia and macrophages play a central role in these processes. This study aimed to investigate the morphological characteristics of HLA-DR-immunopositive cells in these plaques to improve our understanding of the roles of these cells in MS plaques. Methods: This study is a retrospective post-mortem histopathological study. We analyzed 90 plaques from 6 MS cases. Of the plaques studied, 77 were grouped into three categories: 28 active, 34 chronic active, and 15 chronic inactive. Additionally, five vacuolated white matter lesions, two axonal degeneration lesions, and six lesions with mixed histological features were included. Six control cases were also examined to assess HLA-DR-immunopositive cell expression across various age groups. The cells were classified based on their morphology into two types: round cells without processes (macrophages) and cells with varying processes and shapes (ramified microglia). Results: Both macrophages and ramified microglia were present in all lesion types, with a focus on identifying the predominant cell type. Of the 28 active plaques, macrophages were the primary cell type in 25 plaques, while ramified microglia predominated in 3. In the center of 49 chronic plaques, scattered ramified microglia were observed in 46, with three plaques showing a predominance of macrophages. Among the 34 chronic active lesions, ramified microglia were the main cell type in the periphery of 32 plaques, with the remaining two predominantly exhibiting macrophages. Conclusions: The predominance of macrophages in active lesions and the presence of scattered ramified microglia in the center of chronic plaques are consistent with the phagocytic role of macrophages. Meanwhile, the prevalence of ramified microglia at the periphery of chronic active lesions suggests a potential protective function in maintaining lesion stability. Full article

(This article belongs to the Special Issue Advances in the Diagnosis of Nervous System Diseases—2nd Edition)

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15 pages, 1361 KiB

Open AccessArticle

Dynamics of Cognitive Impairment in MCI Patients over a Three-Year Period: The Informative Role of Blood Biomarkers, Neuroimaging, and Genetic Factors

by Irina Morozova, Yana Zorkina, Alexander Berdalin, Anna Ikonnikova, Marina Emelyanova, Elena Fedoseeva, Olga Antonova, Dmitry Gryadunov, Alisa Andryushchenko, Valeriya Ushakova, Olga Abramova, Angelina Zeltser, Marat Kurmishev, Victor Savilov, Natalia Osipova, Irina Preobrazhenskaya, Georgy Kostyuk and Anna Morozova

Diagnostics 2024, 14(17), 1883; https://doi.org/10.3390/diagnostics14171883 - 28 Aug 2024

Viewed by 725

Abstract

Given the high growth rates of cognitive decline among the elderly population and the lack of effective etiological treatments, early diagnosis of cognitive impairment progression is an imperative task for modern science and medicine. It is of particular interest to identify predictors of an unfavorable subsequent course of cognitive disorders, specifically, rapid progression. Our study assessed the informative role of various risk factors on the dynamics of cognitive impairment among mild cognitive impairment (MCI) patients. The study included patients with MCI (N = 338) who underwent neuropsychological assessment, magnetic resonance imaging (MRI) examination, blood sampling for general and biochemical analysis, APOE genotyping, and polygenic risk score (PRS) evaluation. The APOE ε4/ε4 genotype was found to be associated with a diminished overall cognitive scores initial assessment and negative cognitive dynamics. No associations were found between cognitive changes and the PRS. The progression of cognitive impairment was associated with the width of the third ventricle and hematological parameters, specifically, hematocrit and erythrocyte levels. The absence of significant associations between the dynamics of cognitive decline and PRS over three years can be attributed to the provided suitable medical care for the prevention of cognitive impairment. Adding other risk factors and their inclusion in panels assessing the risk of progression of cognitive impairment should be considered. Full article

(This article belongs to the Special Issue Advances in the Diagnosis of Nervous System Diseases—2nd Edition)

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15 pages, 3898 KiB

Open AccessArticle

Cognitive Impairment in Cerebral Small Vessel Disease Is Associated with Corpus Callosum Microstructure Changes Based on Diffusion MRI

by Larisa A. Dobrynina, Elena I. Kremneva, Kamila V. Shamtieva, Anastasia A. Geints, Alexey S. Filatov, Zukhra Sh. Gadzhieva, Elena V. Gnedovskaya, Marina V. Krotenkova and Ivan I. Maximov

Diagnostics 2024, 14(16), 1838; https://doi.org/10.3390/diagnostics14161838 - 22 Aug 2024

Viewed by 658

Abstract

The cerebral small vessel disease (cSVD) is one of the main causes of vascular and mixed cognitive impairment (CI), and it is associated, in particular, with brain ageing. An understanding of structural tissue changes in an intact cerebral white matter in cSVD might allow one to develop the sensitive biomarkers for early diagnosis and monitoring of disease progression. Purpose of the study: to evaluate microstructural changes in the corpus callosum (CC) using diffusion MRI (D-MRI) approaches in cSVD patients with different severity of CI and reveal the most sensitive correlations of diffusion metrics with CI. Methods: the study included 166 cSVD patients (51.8% women; 60.4 ± 7.6 years) and 44 healthy volunteers (65.9% women; 59.6 ± 6.8 years). All subjects underwent D-MRI (3T) with signal (diffusion tensor and kurtosis) and biophysical (neurite orientation dispersion and density imaging, NODDI, white matter tract integrity, WMTI, multicompartment spherical mean technique, MC-SMT) modeling in three CC segments as well as a neuropsychological assessment. Results: in cSVD patients, microstructural changes were found in all CC segments already at the subjective CI stage, which was found to worsen into mild CI and dementia. More pronounced changes were observed in the forceps minor. Among the signal models FA, MD, MK, RD, and RK, as well as among the biophysical models, MC-SMT (EMD, ETR) and WMTI (AWF) metrics exhibited the largest area under the curve (>0.85), characterizing the loss of microstructural integrity, the severity of potential demyelination, and the proportion of intra-axonal water, respectively. Conclusion: the study reveals the relevance of advanced D-MRI approaches for the assessment of brain tissue changes in cSVD. The identified diffusion biomarkers could be used for the clarification and observation of CI progression. Full article

(This article belongs to the Special Issue Advances in the Diagnosis of Nervous System Diseases—2nd Edition)

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17 pages, 12697 KiB

Open AccessArticle

Brain Glucose Metabolism and COMT Val 158 Met Polymorphism in Female Patients with Work-Related Stress

by Saga Steinmann Madsen, Thomas Lund Andersen, Jesper Pihl-Thingvad, Lars Brandt, Birgitte Brinkmann Olsen, Oke Gerke and Poul Videbech

Diagnostics 2024, 14(16), 1730; https://doi.org/10.3390/diagnostics14161730 - 9 Aug 2024

Viewed by 883

Abstract

Stress is a ubiquitous challenge in modern societies. Symptoms range from mood swings and cognitive impairment to autonomic symptoms. This study explores the link between work-related stress and the neurobiological element of brain processing, testing the hypothesis that patients with occupational stress have altered cerebral glucose consumption compared to healthy controls. The participants’ present conditions were evaluated using an adapted WHO SCAN interview. Neural activity at rest was assessed by positron emission tomography (PET) with the glucose analogue [18F]fluorodeoxyglucose. Participants were genotyped for the Val158Met polymorphism of the COMT gene, believed to influence stress resilience. This study included 11 women with work-related stress and 11 demographically comparable healthy controls aged 28–62 years, with an average of 46.2 years. The PET scans indicated clusters of decreased glucose consumption primarily located in the white matter of frontal lobe sub-gyral areas in stress patients. COMT Val158Met polymorphism detection indicated no immediate relation of the homozygous alleles and stress resilience; however, healthy controls mainly had the heterozygous allele. In conclusion, the results support that work-related stress does affect the brain in the form of altered glucose metabolism, suggesting neurobiological effects could be related to white matter abnormalities rather than gray matter deterioration. Genotyping indicates a more complex picture than just that of the one type being more resilient to stress. Further studies recruiting a larger number of participants are needed to confirm our preliminary findings. Full article

(This article belongs to the Special Issue Advances in the Diagnosis of Nervous System Diseases—2nd Edition)

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12 pages, 1892 KiB

Open AccessArticle

Cranial Computer Tomography with Photon Counting and Energy-Integrated Detectors: Objective Comparison in the Same Patients

by Anna Klempka, Alexander Schröder, Philipp Neumayer, Christoph Groden, Sven Clausen and Svetlana Hetjens

Diagnostics 2024, 14(10), 1019; https://doi.org/10.3390/diagnostics14101019 - 15 May 2024

Cited by 1 | Viewed by 890

Abstract

This study provides an objective comparison of cranial computed tomography (CT) imaging quality and radiation dose between photon counting detectors (PCCTs) and energy-integrated detectors (EIDs). We retrospectively analyzed 158 CT scans from 76 patients, employing both detector types on the same individuals to ensure a consistent comparison. Our analysis focused on the Computed Tomography Dose Index and the Dose-Length Product together with the contrast-to-noise ratio and the signal-to-noise ratio for brain gray and white matter. We utilized standardized imaging protocols and consistent patient positioning to minimize variables. PCCT showed a potential for higher image quality and lower radiation doses, as highlighted by this study, thus achieving diagnostic clarity with reduced radiation exposure, underlining its significance in patient care, particularly for patients requiring multiple scans. The results demonstrated that while both systems were effective, PCCT offered enhanced imaging and patient safety in neuroradiological evaluations. Full article

(This article belongs to the Special Issue Advances in the Diagnosis of Nervous System Diseases—2nd Edition)

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13 pages, 50931 KiB

Open AccessArticle

Diagnostic Insights into Pediatric Pleomorphic Xanthoastrocytoma through DNA Methylation Class and Pathological Diagnosis Analysis

by Murad Alturkustani

Diagnostics 2023, 13(22), 3464; https://doi.org/10.3390/diagnostics13223464 - 17 Nov 2023

Cited by 1 | Viewed by 1211

Abstract

This study adopts an innovative approach to utilize the DNA methylation class (MC) by prioritizing the understanding of discrepancies over traditional direct comparisons with the pathological diagnosis (PD). The aim is to clarify the morphological criteria for pleomorphic xanthoastrocytoma (PXA). Using the Children’s Brain Tumor Network online database, PXA-diagnosed cases were sourced. MCs and CDKN2A/B statuses were ascertained using the Heidelberg methylation brain tumor classifier v12.5 (v12.8 for selected cases). Three distinct groups emerged: Group 1 confirmed PXA through both PD and MC (7 cases); Group 2 identified PXA via PD alone (7 cases); and Group 3 diagnosed PXA using MC (5 cases). Key insights from the study include the frequent local infiltration of PXA into gray matter structures, mirroring infiltrative astrocytoma. The MC for PXA stands out for its sensitivity. Cases with a PXA morphological diagnosis diverging from the DNA class warrant attention to newer differential diagnoses such as high-grade astrocytoma with piloid features, pilocytic astrocytoma NF1-associated, and NET-PATZ1. Tumors with a MC indicative of PXA but lacking its typical features may, if high-grade, behave as grade 4 gliomas. In contrast, their low-grade counterparts could belong to the PXA morphological continuum. Further research is pivotal for cementing these findings. Full article

(This article belongs to the Special Issue Advances in the Diagnosis of Nervous System Diseases—2nd Edition)

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Review

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29 pages, 1182 KiB

Open AccessReview

Cardiovascular and Neurological Diseases and Association with Helicobacter Pylori Infection—An Overview

by Vlad Pădureanu, Dalia Dop, Daniel Cosmin Caragea, Dumitru Rădulescu, Rodica Pădureanu and Mircea-Cătălin Forțofoiu

Diagnostics 2024, 14(16), 1781; https://doi.org/10.3390/diagnostics14161781 - 15 Aug 2024

Viewed by 1062

Abstract

This article investigates the link between Helicobacter pylori (H. pylori) infection and cardiovascular and neurological disorders. Recent research suggests that H. pylori may play a role in cardiovascular diseases like atherosclerosis, myocardial infarction, and stroke, as well as neurological diseases including Alzheimer’s disease, multiple sclerosis, and Parkinson’s disease. Cardiovascular Diseases: H. pylori induces endothelial dysfunction and chronic inflammation, promoting atherosclerotic plaque formation and other cardiac complications. High infection prevalence in cardiovascular patients implies that systemic inflammation from H. pylori accelerates disease progression. Eradication therapies combined with anti-inflammatory and lipid-lowering treatments may reduce cardiovascular risk. Neurological Diseases: H. pylori may contribute to Alzheimer’s, multiple sclerosis, and Parkinson’s through systemic inflammation, neuroinflammation, and autoimmune responses. Increased infection prevalence in these patients suggests bacterial involvement in disease pathogenesis. The eradication of H. pylori could reduce neuroinflammation and improve outcomes. Discussions and Future Research: Managing H. pylori infection in clinical practice could impact public health and treatment approaches. Further research is needed to clarify these relationships. Longitudinal and mechanistic studies are essential to fully understand H. pylori’s role in these conditions. Conclusions: H. pylori infection is a potential risk factor for various cardiovascular and neurological conditions. Additional research is critical for developing effective prevention and treatment strategies. Targeted therapies, including H. pylori eradication combined with anti-inflammatory treatments, could improve clinical outcomes. These findings highlight the need for an integrated clinical approach to include H. pylori evaluation and treatment. Full article

(This article belongs to the Special Issue Advances in the Diagnosis of Nervous System Diseases—2nd Edition)

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23 pages, 5207 KiB

Open AccessReview

Central Vein Sign and Paramagnetic Rim Lesions: Susceptibility Changes in Brain Tissues and Their Implications for the Study of Multiple Sclerosis Pathology

by Carolina de Medeiros Rimkus, Fábio Seiji Otsuka, Douglas Mendes Nunes, Khallil Taverna Chaim and Maria Concepción Garcia Otaduy

Diagnostics 2024, 14(13), 1362; https://doi.org/10.3390/diagnostics14131362 - 27 Jun 2024

Cited by 1 | Viewed by 1577

Abstract

Multiple sclerosis (MS) is the most common acquired inflammatory and demyelinating disease in adults. The conventional diagnostic of MS and the follow-up of inflammatory activity is based on the detection of hyperintense foci in T2 and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) and lesions with brain–blood barrier (BBB) disruption in the central nervous system (CNS) parenchyma. However, T2/FLAIR hyperintense lesions are not specific to MS and the MS pathology and inflammatory processes go far beyond focal lesions and can be independent of BBB disruption. MRI techniques based on the magnetic susceptibility properties of the tissue, such as T2*, susceptibility-weighted images (SWI), and quantitative susceptibility mapping (QSM) offer tools for advanced MS diagnostic, follow-up, and the assessment of more detailed features of MS dynamic pathology. Susceptibility-weighted techniques are sensitive to the paramagnetic components of biological tissues, such as deoxyhemoglobin. This capability enables the visualization of brain parenchymal veins. Consequently, it presents an opportunity to identify veins within the core of multiple sclerosis (MS) lesions, thereby affirming their venocentric characteristics. This advancement significantly enhances the accuracy of the differential diagnostic process. Another important paramagnetic component in biological tissues is iron. In MS, the dynamic trafficking of iron between different cells, such as oligodendrocytes, astrocytes, and microglia, enables the study of different stages of demyelination and remyelination. Furthermore, the accumulation of iron in activated microglia serves as an indicator of latent inflammatory activity in chronic MS lesions, termed paramagnetic rim lesions (PRLs). PRLs have been correlated with disease progression and degenerative processes, underscoring their significance in MS pathology. This review will elucidate the underlying physical principles of magnetic susceptibility and their implications for the formation and interpretation of T2*, SWI, and QSM sequences. Additionally, it will explore their applications in multiple sclerosis (MS), particularly in detecting the central vein sign (CVS) and PRLs, and assessing iron metabolism. Furthermore, the review will discuss their role in advancing early and precise MS diagnosis and prognostic evaluation, as well as their utility in studying chronic active inflammation and degenerative processes. Full article

(This article belongs to the Special Issue Advances in the Diagnosis of Nervous System Diseases—2nd Edition)

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12 pages, 494 KiB

Open AccessReview

The Genetic Landscape of Sleep Disorders in Parkinson’s Disease

by Kallirhoe Kalinderi, Vasileios Papaliagkas and Liana Fidani

Diagnostics 2024, 14(1), 106; https://doi.org/10.3390/diagnostics14010106 - 3 Jan 2024

Cited by 4 | Viewed by 2044

Abstract

Parknson’s disease (PD) is the second most common neurodegenerative disease, affecting 1% of people aged over 60. PD is characterized by a wide range of motor symptoms, however the clinical spectrum of PD covers a wide range of non-motor symptoms, as well. Sleep disorders are among the most common non-motor symptoms of PD, can occur at any stage of the disease and significantly affect quality of life. These include rapid eye movement sleep behavior disorder (RBD), restless legs syndrome (RLS), excessive daytime sleepiness (EDS), insomnia, obstructive sleep apnea (OSA) and circadian rhythm disturbances. One of the main challenges in PD research is identifying individuals during the prodromal phase of the disease. Combining genetic and prodromal data may aid the early identification of individuals susceptible to PD. This review highlights current data regarding the genetic component of sleep disorders in PD patients, focusing on genes that have currently been associated with this PD co-morbidity. Full article

(This article belongs to the Special Issue Advances in the Diagnosis of Nervous System Diseases—2nd Edition)

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9 pages, 6617 KiB

Open AccessCase Report

Congenital Heart Malformations Masked by Infantile Gangliosidosis—Case Report and Growing Evidence for Metabolic Disease-Associated Aortopathies

by Dana Elena Mîndru, Elena Țarcă, Elena Emanuela Braha, Alexandrina-Ștefania Curpăn, Solange Tamara Roșu, Dana-Teodora Anton-Păduraru, Heidrun Adumitrăchioaiei, Valentin Bernic, Ioana-Alexandra Pădureț and Alina Costina Luca

Diagnostics 2024, 14(5), 491; https://doi.org/10.3390/diagnostics14050491 - 24 Feb 2024

Viewed by 1134

Abstract

Gangliosidosis (ORPHA: 79255) is an autosomal recessive lysosomal storage disease (LSD) with a variable phenotype and an incidence of 1:200000 live births. The underlying genotype is comprised GLB1 mutations that lead to β-galactosidase deficiency and subsequently to the accumulation of monosialotetrahexosylganglioside (GM1) in the brain and other organs. In total, two diseases have been linked to this gene mutation: Morquio type B and Gangliosidosis. The most frequent clinical manifestations include dysmorphic facial features, nervous and skeletal systems abnormalities, hepatosplenomegaly, and cardiomyopathies. The correct diagnosis of GM1 is a challenge due to the overlapping clinical manifestation between this disease and others, especially in infants. Therefore, in the current study we present the case of a 3-month-old male infant, admitted with signs and symptoms of respiratory distress alongside rapid progressive heart failure, with minimal neurologic and skeletal abnormalities, but with cardiovascular structural malformations. The atypical clinical presentation raised great difficulties for our diagnostic team. Unfortunately, the diagnostic of GM1 was made postmortem based on the DBS test and we were able to correlate the genotype with the unusual phenotypic findings. Full article

(This article belongs to the Special Issue Advances in the Diagnosis of Nervous System Diseases—2nd Edition)

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5 pages, 4055 KiB

Open AccessInteresting Images

CNS Involvement of DLBCL Presenting with an Unusual Non-Enhancing Infiltrative Mass

by Fu-Sheng Hsueh, Hung-Chieh Chen and Huey-En Tzeng

Diagnostics 2023, 13(22), 3424; https://doi.org/10.3390/diagnostics13223424 - 10 Nov 2023

Viewed by 1244

Abstract

Central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL) is relatively uncommon, occurring in approximately 5% of cases, with the majority of instances manifesting during relapse and often associated with poor prognoses. The aim of this case report is to present a unique occurrence of non-enhancing relapse of CNS lymphoma. Significantly, the patient had recently encountered a disease involvement in the axilla region, and subsequent to scheduled chemotherapy, she developed persistent neurological symptoms, leading to the discovery of a relapse of the CNS lymphoma. Our focus will be on delineating the clinical presentation, elucidating the findings observed in clinical imaging, and detailing the therapeutic approaches employed in this specific case. By highlighting these aspects, we aim to provide valuable insights into the diagnosis of the atypical presentation of CNS lymphoma. Full article

(This article belongs to the Special Issue Advances in the Diagnosis of Nervous System Diseases—2nd Edition)

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