Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
3.7
4.7
Journals
Biomedicines
Special Issues
Immune-Mediated Neurological Disorders
share announcement

Immune-Mediated Neurological Disorders

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 25473

Special Issue Editors

Dr. Carlo Colosimo

E-Mail Website
Guest Editor
Department of Neurology, Santa Maria University Hospital, 05100 Terni, Italy
Interests: movement disorders; parkinsonism; atypical parkinsonian disorders; dystonia; genetics; autoimmune neurology
Dr. Luca Marsili

E-Mail Website
Guest Editor
Department of Neurology and Rehabilitation Medicine, Gardner Family Center for Parkinson’s Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, USA
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The present Special Issue aims to provide an overview of the immune system's role in several neurological diseases, even if not classically considered immune mediated. With recent advances in neuroscience, it is evident that the immune system plays an essential role in affecting how our organism interacts with the external world, including infectious diseases, toxic agents, drugs, and other environmental substances. Several experts in the field of neurology will provide their expertise in describing the most advanced theories on the role of the immune system as the leading player in multiple conditions that may be observed in clinical practice, which general neurologists should know. Further, it is crucial to know the possible effects of new immune-modulating treatments, frequently used in oncology, that may contribute to some of these conditions. Finally, the role of the immune system in neurodegeneration will be explored to see how immune signals could be used as biomarkers for disease progression.

Dr. Carlo Colosimo
Dr. Luca Marsili
Guest Editors

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. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • immune-mediated movement disorders
  • paraneoplastic neurological syndromes
  • immunity and neurodegeneration
  • immune-checkpoint inhibitors and neurological adverse events
  • CAR-T cell therapies and neurological adverse events
  • immune-mediated encephalitis
  • immune-mediated peripheral neurological syndromes
  • genetics and immune system
  • COVID and related neurological syndromes
  • treatments for immune-mediated neurological syndromes

Published Papers (10 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review, Other

4 pages, 187 KiB  
Editorial
Special Issue: Immune-Mediated Neurological Disorders
by Luca Marsili and Carlo Colosimo
Biomedicines 2023, 11(12), 3214; https://doi.org/10.3390/biomedicines11123214 - 4 Dec 2023
Cited by 1 | Viewed by 793
Abstract
For a long time, the immune system has been considered responsible for only a minority of neurological conditions involving the central and peripheral nervous system (CNS, PNS), respectively, namely multiple sclerosis and myasthenia gravis (with myastheniform syndromes) [...] Full article
(This article belongs to the Special Issue Immune-Mediated Neurological Disorders)

Research

Jump to: Editorial, Review, Other

15 pages, 2756 KiB  
Article
Purified Serum IgG from a Patient with Anti-IgLON5 Antibody Cause Long-Term Movement Disorders with Impaired Dopaminergic Pathways in Mice
by Yining Gao, Hongxia Li, Huoqing Luo, You Ni, Yifan Feng, Lu He, Qinming Zhou, Ji Hu and Sheng Chen
Biomedicines 2023, 11(9), 2483; https://doi.org/10.3390/biomedicines11092483 - 7 Sep 2023
Cited by 2 | Viewed by 1112
Abstract
Background: Anti-IgLON5 disease is a rare autoimmune disease of the central nervous system. It typically manifests as a chronic condition, characterized by cognitive impairments, movement disorders, and sleep disorders. The mechanisms underlying movement disorders in this disease remain poorly understood due to [...] Read more.
Background: Anti-IgLON5 disease is a rare autoimmune disease of the central nervous system. It typically manifests as a chronic condition, characterized by cognitive impairments, movement disorders, and sleep disorders. The mechanisms underlying movement disorders in this disease remain poorly understood due to a lack of research. Furthermore, this disease exhibits both neuroimmune and neurodegenerative characteristics. The objective of this study is to explore the underlying mechanisms of movement disorders caused by anti-IgLON5 antibodies for the first time. Methods: Antibodies were purified from the serum of a confirmed patient of anti-IgLON5 disease. The passive transfer animal models were employed, where antibodies were continuously injected into the substantia nigra pars compacta (SNc) of the mouse midbrain using stereotactic injection to explore the mechanism of movement disorder. The effects of anti-IgLON5 antibodies on dopaminergic neurons in the SNc and neurodegeneration were examined through immunohistochemistry. Changes in neurotransmitter levels in the basal ganglia were assessed using high-performance liquid chromatography. Additionally, RNA-seq was employed to identify the differentially expressed genes associated with the short-term and long-term effects of anti-IgLON5 antibody on the SNc. Results: Mice injected with anti-IgLON5 antibodies in the SNc exhibited persistent movement impairments for up to 3 months. One week after antibody injection, the number of TH neurons significantly decreased compared to the control group, accompanied by reduced projection fibers in the basal ganglia and decreased dopamine levels. After 3 months of antibody injection, an increase in phosphorylated Tau was observed in the SNc of the midbrain. Additionally, long-term sustained activation of microglia was detected in the SNc. The differentially expressed genes of long-term effects of IgLON5 antibodies were different from their short-term effects on the SNc. Conclusion: Purified serum IgG from a patient with anti-IgLON5 antibodies can cause long-term movement disorder in mice. The movement disorders appear to be linked to the impaired dopaminergic pathway, and the increased p-Tau showed neurodegenerative changes induced by the anti-IgLON5 antibody. Full article
(This article belongs to the Special Issue Immune-Mediated Neurological Disorders)
►▼ Show Figures

Figure 1

15 pages, 299 KiB  
Article
Autoimmune Encephalitis—A Multifaceted Pathology
by Monica Neațu, Ana Jugurt, Anca Covaliu, Eugenia Irene Davidescu and Bogdan Ovidiu Popescu
Biomedicines 2023, 11(8), 2176; https://doi.org/10.3390/biomedicines11082176 - 2 Aug 2023
Cited by 1 | Viewed by 1379
Abstract
Autoimmune encephalitis is a complex and multifaceted pathology that involves immune-mediated inflammation of the brain. It is characterized by the body’s immune system attacking the brain tissue, leading to a cascade of inflammatory processes. What makes autoimmune encephalitis vast is the wide range [...] Read more.
Autoimmune encephalitis is a complex and multifaceted pathology that involves immune-mediated inflammation of the brain. It is characterized by the body’s immune system attacking the brain tissue, leading to a cascade of inflammatory processes. What makes autoimmune encephalitis vast is the wide range of causes, mechanisms, clinical presentations, and diagnostic challenges associated with the condition. The clinical presentations of autoimmune encephalitis are broad and can mimic other neurological disorders, making it a challenging differential diagnosis. This diverse clinical presentation can overlap with other conditions, making it crucial for healthcare professionals to maintain a high level of suspicion for autoimmune encephalitis when evaluating patients. The diagnostic challenges associated with autoimmune encephalitis further contribute to its vastness. Due to the variable nature of the condition, there is no definitive diagnostic test that can confirm autoimmune encephalitis in all cases. In this context, personalized patient management is crucial for achieving favorable outcomes. Each patient’s treatment plan should be tailored to their specific clinical presentation, underlying cause, and immune response. Our objective is to raise awareness about the frequent yet underdiagnosed nature of autoimmune encephalitis by sharing five cases we encountered, along with a brief literature review. Full article
(This article belongs to the Special Issue Immune-Mediated Neurological Disorders)

Review

Jump to: Editorial, Research, Other

16 pages, 343 KiB  
Review
SARS-CoV-2 and Parkinson’s Disease: A Review of Where We Are Now
by Iro Boura, Mubasher A. Qamar, Francesco Daddoveri, Valentina Leta, Karolina Poplawska-Domaszewicz, Cristian Falup-Pecurariu and K. Ray Chaudhuri
Biomedicines 2023, 11(9), 2524; https://doi.org/10.3390/biomedicines11092524 - 13 Sep 2023
Cited by 1 | Viewed by 1668
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has been discussed in the context of Parkinson’s disease (PD) over the last three years. Now that we are entering the long-term phase of this pandemic, we are intrigued to look [...] Read more.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has been discussed in the context of Parkinson’s disease (PD) over the last three years. Now that we are entering the long-term phase of this pandemic, we are intrigued to look back and see how and why the community of patients with PD was impacted and what knowledge we have collected so far. The relationship between COVID-19 and PD is likely multifactorial in nature. Similar to other systemic infections, a probable worsening of PD symptoms secondary to COVID-19, either transient or persistent (long COVID), has been demonstrated, while the COVID-19-related mortality of PD patients may be increased compared to the general population. These observations could be attributed to direct or indirect damage from SARS-CoV-2 in the central nervous system (CNS) or could result from general infection-related parameters (e.g., hospitalization or drugs) and the sequelae of the COVID-19 pandemic (e.g., quarantine). A growing number of cases of new-onset parkinsonism or PD following SARS-CoV-2 infection have been reported, either closely (post-infectious) or remotely (para-infectious) after a COVID-19 diagnosis, although such a link remains hypothetical. The pathophysiological substrate of these phenomena remains elusive; however, research studies, particularly pathology studies, have suggested various COVID-19-induced degenerative changes with potential associations with PD/parkinsonism. We review the literature to date for answers considering the relationship between SARS-CoV-2 infection and PD/parkinsonism, examining pathophysiology, clinical manifestations, vaccination, and future directions. Full article
(This article belongs to the Special Issue Immune-Mediated Neurological Disorders)
15 pages, 2391 KiB  
Review
Stiff Person Spectrum Disorders—An Update and Outlook on Clinical, Pathophysiological and Treatment Perspectives
by Benjamin Vlad, Yujie Wang, Scott D. Newsome and Bettina Balint
Biomedicines 2023, 11(9), 2500; https://doi.org/10.3390/biomedicines11092500 - 10 Sep 2023
Viewed by 4401
Abstract
Stiff person spectrum disorders (SPSD) are paradigm autoimmune movement disorders characterized by stiffness, spasms and hyperekplexia. Though rare, SPSD represent a not-to-miss diagnosis because of the associated disease burden and treatment implications. After decades as an enigmatic orphan disease, major advances in our [...] Read more.
Stiff person spectrum disorders (SPSD) are paradigm autoimmune movement disorders characterized by stiffness, spasms and hyperekplexia. Though rare, SPSD represent a not-to-miss diagnosis because of the associated disease burden and treatment implications. After decades as an enigmatic orphan disease, major advances in our understanding of the evolving spectrum of diseases have been made along with the identification of multiple associated autoantibodies. However, the most important recent developments relate to the recognition of a wider affection, beyond the classic core motor symptoms, and to further insights into immunomodulatory and symptomatic therapies. In this review, we summarize the recent literature on the clinical and paraclinical spectrum, current pathophysiological understanding, as well as current and possibly future therapeutic strategies. Full article
(This article belongs to the Special Issue Immune-Mediated Neurological Disorders)
►▼ Show Figures

Figure 1

23 pages, 1750 KiB  
Review
Paraneoplastic Neurological Syndromes of the Central Nervous System: Pathophysiology, Diagnosis, and Treatment
by Luca Marsili, Samuel Marcucci, Joseph LaPorta, Martina Chirra, Alberto J. Espay and Carlo Colosimo
Biomedicines 2023, 11(5), 1406; https://doi.org/10.3390/biomedicines11051406 - 9 May 2023
Cited by 15 | Viewed by 5986
Abstract
Paraneoplastic neurological syndromes (PNS) include any symptomatic and non-metastatic neurological manifestations associated with a neoplasm. PNS associated with antibodies against intracellular antigens, known as “high-risk” antibodies, show frequent association with underlying cancer. PNS associated with antibodies against neural surface antigens, known as “intermediate- [...] Read more.
Paraneoplastic neurological syndromes (PNS) include any symptomatic and non-metastatic neurological manifestations associated with a neoplasm. PNS associated with antibodies against intracellular antigens, known as “high-risk” antibodies, show frequent association with underlying cancer. PNS associated with antibodies against neural surface antigens, known as “intermediate- or low-risk” antibodies, are less frequently associated with cancer. In this narrative review, we will focus on PNS of the central nervous system (CNS). Clinicians should have a high index of suspicion with acute/subacute encephalopathies to achieve a prompt diagnosis and treatment. PNS of the CNS exhibit a range of overlapping “high-risk” clinical syndromes, including but not limited to latent and overt rapidly progressive cerebellar syndrome, opsoclonus-myoclonus-ataxia syndrome, paraneoplastic (and limbic) encephalitis/encephalomyelitis, and stiff-person spectrum disorders. Some of these phenotypes may also arise from recent anti-cancer treatments, namely immune-checkpoint inhibitors and CAR T-cell therapies, as a consequence of boosting of the immune system against cancer cells. Here, we highlight the clinical features of PNS of the CNS, their associated tumors and antibodies, and the diagnostic and therapeutic strategies. The potential and the advance of this review consists on a broad description on how the field of PNS of the CNS is constantly expanding with newly discovered antibodies and syndromes. Standardized diagnostic criteria and disease biomarkers are fundamental to quickly recognize PNS to allow prompt treatment initiation, thus improving the long-term outcome of these conditions. Full article
(This article belongs to the Special Issue Immune-Mediated Neurological Disorders)
►▼ Show Figures

Graphical abstract

30 pages, 1288 KiB  
Review
Exploring Pro-Inflammatory Immunological Mediators: Unraveling the Mechanisms of Neuroinflammation in Lysosomal Storage Diseases
by Manoj Kumar Pandey
Biomedicines 2023, 11(4), 1067; https://doi.org/10.3390/biomedicines11041067 - 1 Apr 2023
Cited by 5 | Viewed by 3593
Abstract
Lysosomal storage diseases are a group of rare and ultra-rare genetic disorders caused by defects in specific genes that result in the accumulation of toxic substances in the lysosome. This excess accumulation of such cellular materials stimulates the activation of immune and neurological [...] Read more.
Lysosomal storage diseases are a group of rare and ultra-rare genetic disorders caused by defects in specific genes that result in the accumulation of toxic substances in the lysosome. This excess accumulation of such cellular materials stimulates the activation of immune and neurological cells, leading to neuroinflammation and neurodegeneration in the central and peripheral nervous systems. Examples of lysosomal storage diseases include Gaucher, Fabry, Tay–Sachs, Sandhoff, and Wolman diseases. These diseases are characterized by the accumulation of various substrates, such as glucosylceramide, globotriaosylceramide, ganglioside GM2, sphingomyelin, ceramide, and triglycerides, in the affected cells. The resulting pro-inflammatory environment leads to the generation of pro-inflammatory cytokines, chemokines, growth factors, and several components of complement cascades, which contribute to the progressive neurodegeneration seen in these diseases. In this study, we provide an overview of the genetic defects associated with lysosomal storage diseases and their impact on the induction of neuro-immune inflammation. By understanding the underlying mechanisms behind these diseases, we aim to provide new insights into potential biomarkers and therapeutic targets for monitoring and managing the severity of these diseases. In conclusion, lysosomal storage diseases present a complex challenge for patients and clinicians, but this study offers a comprehensive overview of the impact of these diseases on the central and peripheral nervous systems and provides a foundation for further research into potential treatments. Full article
(This article belongs to the Special Issue Immune-Mediated Neurological Disorders)
►▼ Show Figures

Figure 1

14 pages, 322 KiB  
Review
Immunization with Neural-Derived Peptides in Neurodegenerative Diseases: A Narrative Review
by Germán Rivera Monroy, Renata Murguiondo Pérez, Efraín Weintraub Ben Zión, Oscar Vidal Alcántar-Garibay, Ericka Cristina Loza-López, Emilio Tejerina Marion, Enrique Blancarte Hernández, Lisset Navarro-Torres and Antonio Ibarra
Biomedicines 2023, 11(3), 919; https://doi.org/10.3390/biomedicines11030919 - 16 Mar 2023
Cited by 2 | Viewed by 1468
Abstract
Neurodegenerative diseases (NDDs) are a major health problem worldwide. Statistics suggest that in America in 2030 there will be more than 12 million people suffering from a neurodegenerative pathology. Furthermore, the increase in life expectancy enhances the importance of finding new and better [...] Read more.
Neurodegenerative diseases (NDDs) are a major health problem worldwide. Statistics suggest that in America in 2030 there will be more than 12 million people suffering from a neurodegenerative pathology. Furthermore, the increase in life expectancy enhances the importance of finding new and better therapies for these pathologies. NDDs could be classified into chronic or acute, depending on the time required for the development of clinical symptoms and brain degeneration. Nevertheless, both chronic and acute stages share a common immune and inflammatory pathway in their pathophysiology. Immunization with neural-derived peptides (INDP) is a novel therapy that has been studied during the last decade. By inoculating neural-derived peptides obtained from the central nervous system (CNS), this therapy aims to boost protective autoimmunity, an autoreactive response that leads to a protective phenotype that produces a healing environment and neuroregeneration instead of causing damage. INDP has shown promising findings in studies performed either in vitro, in vivo or even in some pre-clinical trials of different NDDs, standing as a potentially beneficial therapy. In this review, we will describe some of the studies in which the effect of INDP strategies have been explored in different (chronic and acute) neurodegenerative diseases. Full article
(This article belongs to the Special Issue Immune-Mediated Neurological Disorders)
37 pages, 1503 KiB  
Review
Neural Surface Antibodies and Neurodegeneration: Clinical Commonalities and Pathophysiological Relationships
by Maria Pia Giannoccaro, Federico Verde, Luana Morelli, Giovanni Rizzo, Fortuna Ricciardiello and Rocco Liguori
Biomedicines 2023, 11(3), 666; https://doi.org/10.3390/biomedicines11030666 - 22 Feb 2023
Cited by 3 | Viewed by 1870
Abstract
Autoimmune encephalitis and neurodegenerative disorders share several clinical features, including behavioural and psychiatric manifestations, cognitive impairment, sleep and movement disorders. Therefore, it is not surprising that autoimmune encephalitis is one of the main differential diagnoses of rapidly progressive dementia. However, more chronic presentations [...] Read more.
Autoimmune encephalitis and neurodegenerative disorders share several clinical features, including behavioural and psychiatric manifestations, cognitive impairment, sleep and movement disorders. Therefore, it is not surprising that autoimmune encephalitis is one of the main differential diagnoses of rapidly progressive dementia. However, more chronic presentations of autoimmune disorders have been reported and can lead to the misdiagnosis of a neurodegenerative disease. On the other hand, antibodies against neuronal proteins, such as those directed against NMDAR, can occur during established neurogenerative disorders, and their role in this context is still unclear. They might be simple bystanders or modify the disease course and phenotype. Indeed, autoimmune encephalitis can leave long-term cognitive sequelae and specific antibodies to neuronal surface antigens are associated with clinical and pathological neurodegenerative features. Here we review the link between these antibodies and neurodegeneration. In particular we discuss: (a) the possibility that autoimmune encephalitis presents as a neurodegenerative disease, identifying the red flags that can help in the differential diagnosis between antibody-mediated and neurodegenerative disorders; (b) the occurrence of antibodies against neuronal surface antigens in patients with neurodegenerative disorders and their possible role in the disease course; and (c) the long-term cognitive and neuroradiological changes associated with autoimmune encephalitis, as well as the biomarkers that can help to predict the cognitive outcome. Finally, we review the clinical and pathological features of IgLON5 antibodies-related encephalitis, a unique model of the relationship between antibodies and neurodegeneration. Full article
(This article belongs to the Special Issue Immune-Mediated Neurological Disorders)
►▼ Show Figures

Figure 1

Other

8 pages, 1379 KiB  
Case Report
Juvenile Dermatomyositis and Infantile Cerebral Palsy: Aicardi-Gouteres Syndrome, Type 5, with a Novel Mutation in SAMHD1—A Case Report
by Lubov S. Sorokina, Rinat K. Raupov and Mikhail M. Kostik
Biomedicines 2023, 11(6), 1693; https://doi.org/10.3390/biomedicines11061693 - 12 Jun 2023
Viewed by 1380
Abstract
Introduction: Aicardi-Gouteres syndrome (AGS) is a monogenic interferonopathy characterized by early onset, dysregulation of skin (chilblain lesions), brain, and immune systems (fever, hepatomegaly, glaucoma, arthritis, myositis, and autoimmune activity). The disease looks like TORCH (Toxoplasmosis, Others, Rubella, Cytomegalovirus, Herpes) infection with early-onset encephalopathy [...] Read more.
Introduction: Aicardi-Gouteres syndrome (AGS) is a monogenic interferonopathy characterized by early onset, dysregulation of skin (chilblain lesions), brain, and immune systems (fever, hepatomegaly, glaucoma, arthritis, myositis, and autoimmune activity). The disease looks like TORCH (Toxoplasmosis, Others, Rubella, Cytomegalovirus, Herpes) infection with early-onset encephalopathy resulting in severe neuropsychological disability. Case description: A six-year-old girl has been suffering from generalized seizures, fever episodes, severe psychomotor development delay, and spastic tetraparesis since the first year of her life. Her two elder brothers died at a young age from suspected infantile cerebral palsy (ICP). Other siblings (younger brother and two elder sisters) are as healthy as their parents. The girl was diagnosed with juvenile dermatomyositis at 5.5 years. Basal ganglia, periventricular, and cerebellum calcifications; hypoplasia of the corpus callosum; and leukodystrophy were detected on CT. The IFN-I score was 12 times higher than normal. The previously not described nucleotide variant c.434G > C (chr 20:36935104C > G; NM_015474) was detected in exon 4 of the SAMHD1 gene in the homozygous state, leading to amino acid substitution p.R145P. Aicardi-Goutières syndrome 5 was diagnosed. Her treatment included corticosteroids, methotrexate, and tofacitinib 5 mg twice a day and it contributed to health improvements. The following brain CT depicted the previously discovered changes without the sign of calcification spreading. Conclusions: Early diagnosis of AGS is highly important as it allows starting treatment in a timely manner. Timely treatment, in return, can help avoid the development/progression of end-organ damage, including severe neurological complications and early death. It is necessary to spread information about AGS among neurologists, neonatologists, infectious disease specialists, and pediatricians. A multidisciplinary team approach is required. Full article
(This article belongs to the Special Issue Immune-Mediated Neurological Disorders)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-10
Back to TopTop