Neurologic Manifestations of Rheumatologic Disorders.

OBJECTIVE: This article provides an overview of the neurologic manifestations of sarcoidosis and select rheumatologic disorders. An approach to the assessment and differential diagnosis of characteristic clinical presentations, including meningitis and vasculitis, is also reviewed. A review of treatment options is included as well as discussion of distinct areas of overlap, including rheumatologic disease in the setting of neuromyelitis spectrum disorder and demyelinating disease in the setting of tumor necrosis factor-α inhibitors. LATEST DEVELOPMENTS: An increased understanding of the immune mechanisms involved in sarcoidosis and rheumatologic diseases has resulted in a greater diversity of therapeutic options for their treatment. Evidence directing the treatment of the central nervous system (CNS) manifestations of these same diseases is lacking, with a paucity of controlled trials. ESSENTIAL POINTS: It is important to have a basic knowledge of the common CNS manifestations of rheumatologic diseases and sarcoidosis so that they can be recognized when encountered. In the context of many systemic inflammatory diseases, including systemic lupus erythematosus, IgG4-related disease, and sarcoidosis, CNS disease may be a presenting feature or occur without systemic manifestations of the disease, making familiarity with these diseases even more important.

HSCT for systemic autoimmune diseases with neurologic involvement.

Over the past 25 years, hematopoietic stem cell transplantation (HSCT) has been evolving as specific treatment for patients with severe and refractory systemic autoimmune diseases, where mechanistic studies have provided evidence for a profound immune renewal facilitating the observed beneficial responses. In addition to autoimmune neurologic diseases, such as multiple sclerosis (MS) or neuromyelitis optica (NMO), rheumatic diseases with central or peripheral nervous system involvement and insufficient response to conventional immunosuppressive or biologic therapies represent a growing indication for autologous HSCT. They most commonly include connective tissue diseases, such as systemic lupus erythematosus (SLE), vasculitides, or rarer diseases from the autoinflammatory spectrum, such as Behçet's disease, where neurologic manifestations may represent the greatest disease burden. Neurologic manifestations may resemble those of MS, including myelitis optic neuropathy, stroke, or seizures. Outcomes of such manifestations are variable after autologous HSCT but most frequently improve or even resolve with the underlying disease, especially in SLE. This article will provide the current evidence and summarize the outcomes of HSCT for rheumatic autoimmune diseases with neurologic manifestations.

Post-SARS-CoV-2 infection and post-vaccine-related neurological complications share clinical features and the same positivity to anti-ACE2 antibodies.

Introduction: A potential overlap in symptoms between post-acute COVID-19 syndrome and post-COVID-19 vaccination syndrome has been noted. We report a paired description of patients presenting with similar manifestations involving the central (CNS) or peripheral nervous system (PNS) following SARS-CoV-2 infection or vaccination, suggesting that both may have triggered similar immune-mediated neurological disorders in the presence of anti-idiotype antibodies directed against the ACE2 protein. Patients and methods: Four patients exhibited overlapping neurological manifestations following SARS-CoV-2 infection or vaccination: radiculitis, Guillain-Barré syndrome, and MRI-negative myelitis, respectively, sharing positivity for anti-ACE2 antibodies. Autoantibodies against AQP-4, MOG, GlyR, GAD, and amphiphysin, onconeural antibodies for CNS syndromes, and anti-ganglioside antibodies for PNS syndromes tested negative in all patients. Discussion: Anti-idiotype antibodies against ACE2 have been detected in patients who recovered from COVID-19 infection, and it has been hypothesized that such antibodies may mediate adverse events following SARS-CoV-2 infection or vaccination, resulting in the activation of the immune system against cells expressing ACE2, such as neurons. Our data reveal clinically overlapping syndromes triggered by SARS-CoV-2 infection or vaccination, sharing positivity for anti-ACE2 antibodies. Their presence, in the absence of other classic autoimmune markers of CNS or PNS involvement, suggests that they might play an active role in the context of an aberrant immune response. Conclusion: Anti-idiotype antibodies directed against ACE2 may be triggered by both SARS-CoV-2 infection and vaccination, possibly contributing to neurological autoimmune manifestations. Their pathogenic role, however, remains to be demonstrated in large-scale, more structured studies.

Neurofilament light chain in serum of cancer patients with acute neurological complications.

Aim: Neurofilament light chain (NfL) is a nonspecific sensitive biomarker of axonal damage.Methods: This case series identified cancer patients with neurological complications who had serum NfL measurements and paired these results to outcomes.Results: NfL serum levels were available in 15 patients with hematological malignancies or solid tumors. The neurological complications studied were immune effector cell-associated neurotoxicity syndrome, immune checkpoint inhibitor-related encephalopathy, anoxic brain injury, Guillain-Barre syndrome, hemophagocytic lymphohistiocytosis, transverse myelitis, paraneoplastic syndrome, central nervous system demyelinating disorder and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. All patients but one with serum NfL >900 pg/ml died during hospitalization.Conclusion: Serum NfL levels consistently corresponded to death, disease severity or recovery in this series.

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Neurologic complications in patients receiving aortic versus subclavian versus femoral arterial cannulation for post-cardiotomy extracorporeal life support: results of the PELS observational multicenter study.

BACKGROUND: Cerebral perfusion may change depending on arterial cannulation site and may affect the incidence of neurologic adverse events in post-cardiotomy extracorporeal life support (ECLS). The current study compares patients' neurologic outcomes with three commonly used arterial cannulation strategies (aortic vs. subclavian/axillary vs. femoral artery) to evaluate if each ECLS configuration is associated with different rates of neurologic complications. METHODS: This retrospective, multicenter (34 centers), observational study included adults requiring post-cardiotomy ECLS between January 2000 and December 2020 present in the Post-Cardiotomy Extracorporeal Life Support (PELS) Study database. Patients with Aortic, Subclavian/Axillary and Femoral cannulation were compared on the incidence of a composite neurological end-point (ischemic stroke, cerebral hemorrhage, brain edema). Secondary outcomes were overall in-hospital mortality, neurologic complications as cause of in-hospital death, and post-operative minor neurologic complications (seizures). Association between cannulation and neurological outcomes were investigated through linear mixed-effects models. RESULTS: This study included 1897 patients comprising 26.5% Aortic (n = 503), 20.9% Subclavian/Axillary (n = 397) and 52.6% Femoral (n = 997) cannulations. The Subclavian/Axillary group featured a more frequent history of hypertension, smoking, diabetes, previous myocardial infarction, dialysis, peripheral artery disease and previous stroke. Neuro-monitoring was used infrequently in all groups. Major neurologic complications were more frequent in Subclavian/Axillary (Aortic: n = 79, 15.8%; Subclavian/Axillary: n = 78, 19.6%; Femoral: n = 118, 11.9%; p < 0.001) also after mixed-effects model adjustment (OR 1.53 [95% CI 1.02-2.31], p = 0.041). Seizures were more common in Subclavian/Axillary (n = 13, 3.4%) than Aortic (n = 9, 1.8%) and Femoral cannulation (n = 12, 1.3%, p = 0.036). In-hospital mortality was higher after Aortic cannulation (Aortic: n = 344, 68.4%, Subclavian/Axillary: n = 223, 56.2%, Femoral: n = 587, 58.9%, p < 0.001), as shown by Kaplan-Meier curves. Anyhow, neurologic cause of death (Aortic: n = 12, 3.9%, Subclavian/Axillary: n = 14, 6.6%, Femoral: n = 28, 5.0%, p = 0.433) was similar. CONCLUSIONS: In this analysis of the PELS Study, Subclavian/Axillary cannulation was associated with higher rates of major neurologic complications and seizures. In-hospital mortality was higher after Aortic cannulation, despite no significant differences in incidence of neurological cause of death in these patients. These results encourage vigilance for neurologic complications and neuromonitoring use in patients on ECLS, especially with Subclavian/Axillary cannulation.

The Spectrum of Neurological Manifestations in Scrub Typhus.

BACKGROUND: Scrub typhus is a mite-borne zoonotic disease caused by Orientia tsutsugamushi and commonly presents with fever, rash, and eschar. Systemic complications develop later in the illness including, meningoencephalitis, pericardial effusion, myocarditis, and pneumonitis. In this article, we will be presenting different neurological manifestations of scrub typhus along with functional outcomes studied at a tertiary care center in New Delhi. METHODS: This ambispective observational study was conducted at Army Hospital Research and Referral, New Delhi, during January 2018- January 2020. Febrile illness, serologically confirmed as scrub typhus and developing neurological complications were included. A predesigned clinical proforma was recorded for demographics, clinical features, neurological examination, supported with laboratory and/or radiology evaluation, and functional outcomes using the modified Rankin Scale (mRS). RESULTS: In our cohort of 7 patients' majority were male (71%) with mean age at presentation being 42.5 years. Eschar was present in only 2 cases (28%) and a syndromic clinical diagnosis of meningoencephalitis was made in 3 (43%), acute flaccid quadriparesis in 2 (28%); and symptomatic seizure and parkinsonism in 1 patient each (14%). CSF showed lymphocytic pleocytosis with protein elevation in 57% cases. Systemic dysfunction was noted in the form of thrombocytopenia (57%), hyponatremia (42%), elevated transaminases (57%). Symptoms resolved with Doxycycline ± Rifampicin therapy in all cases, with good functional outcomes in majority of (89%) cases. CONCLUSION: Neurological complications in scrub typhus have a wide spectrum involving meninges, encephalon, basal ganglia, cranial, and peripheral nerves. High index of suspicion with early serological testing (ELISA) is a must in undifferentiated fevers. Timely initiation of appropriate therapy leads to good clinical outcomes, in majority of cases with neurological involvement.

Neurological manifestations of Flaviviridae, Togaviridae, and Peribunyaviridae as vector-borne viruses.

Vector-borne viruses pose a significant health problem worldwide, as they are transmitted to humans through the bite of infected arthropods such as mosquitoes and ticks. In recent years, emerging and re-emerging vector-borne diseases have gained attention as they can cause a wide spectrum of neurological manifestations. The neurological manifestations of vector-borne viruses encompass a board spectrum of clinical manifestations, ranging from mild and self-limiting symptoms to severe and life-threatening conditions. Common neurological complications include viral encephalitis, acute flaccid paralysis, aseptic meningitis, and various neuromuscular disorders. The specific viruses responsible for these neurological sequelae vary by geographic region and include Orthoflavivirus nilense, Zika virus, dengue virus, chikungunya virus, Japanese encephalitis virus, and tick-borne encephalitis virus. This review focuses on the pathogenesis of these neurologic complications and highlights the mechanisms by which vector-borne viruses invade the central nervous system and trigger neuroinflammatory responses. Diagnostic challenges and strategies for early detection of neurological manifestations are discussed, emphasising the importance of clinical suspicion and advanced laboratory testing.

Acupuncture, an effective treatment for post-stroke neurologic dysfunction.

Stroke episodes represent a significant subset of cerebrovascular diseases globally, often resulting in diverse neurological impairments such as hemiparesis, spasticity, dysphagia, sensory dysfunction, cognitive impairment, depression, aphasia, and other sequelae. These dysfunctions markedly diminish patients' quality of life and impose substantial burdens on their families and society. Consequently, the restoration of neurological function post-stroke remains a primary objective of clinical treatment. Acupuncture, a traditional Chinese medicine technique, is endorsed by the World Health Organization (WHO) for stroke treatment due to its distinct advantages in managing cerebrovascular diseases, including ischemic stroke. Numerous clinical studies have substantiated the efficacy of acupuncture in ameliorating neurological dysfunctions following stroke. This review systematically examines the improvements in post-stroke neurological dysfunction attributable to acupuncture treatment and elucidates potential mechanisms of action proposed in recent years. Additionally, this article aims to present novel therapeutic concepts and strategies for the clinical management of post-stroke neurological dysfunction.

Neurological and Psychiatric Clinical Manifestations of Sjögren Syndrome.

PURPOSE OF REVIEW: Sjögren Syndrome is a systemic autoimmune disorder that presents mainly with sicca symptoms, but frequently affects other body systems which can lead to a wide variety of manifestations. Understanding the neurological and psychiatric manifestations of Sjögren Syndrome can help with an earlier diagnosis of this disease and leads to better clinical outcomes. RECENT FINDINGS: We provide an updated overview of the central neurological manifestations, peripheral neurological manifestations and psychiatric manifestations and their diagnosis when associated with primary Sjögren Syndrome. The epidemiology and clinical features of the neurological and psychiatric manifestations are derived from different cohort studies and review articles that were selected from PubMed searches conducted between January 2024 and March 2024. The absence of diagnostic criteria and the scarcity of large, robust studies makes the recognition of the neurological and psychiatric manifestations of Sjögren Syndrome more difficult. Maintaining a high index of suspicion in clinical practice and a close collaboration between the Neurologist and the Rheumatologist will facilitate the diagnosis and management of these patients.

Indications for a brain biopsy in neurological diseases of unknown etiology: The role of magnetic resonance imaging findings and liquid biopsy in yielding definitive pathological diagnoses.

Brain biopsies are often considered for patients who cannot be diagnosed with various laboratory test results. However, physicians tend to be hesitant regarding their application in possibly non-neoplastic brain diseases, due to the invasiveness and risks. The aim was to determine the indications for brain biopsies in cases of neurological diseases of unknown etiology. We retrospectively evaluated diagnostic accuracy, laboratory findings (including a liquid biopsy for malignant lymphoma), magnetic resonance imaging (MRI) characteristics and the post-treatment outcomes of patients undergoing brain biopsies for neurological diseases of unknown etiology. The data of patients who had undergone a brain biopsy during their admission to Niigata University Hospital, between 2011 and 2024, were reviewed. Moreover, the laboratory data and MRI findings between patients with definitive and nonspecific biopsy diagnoses were compared. Twenty-six patients underwent a brain biopsy, and a definitive diagnosis was obtained in 14 patients (53.8%). Even in cases where a nonspecific diagnosis was made, biopsy findings helped rule out malignancy and guide clinical diagnosis and treatment decisions. The liquid biopsy for malignant lymphoma was performed in eight patients, with one yielding a positive result, consistent with primary central nervous system lymphoma. The sensitivity and specificity of liquid biopsy were 0.5 and 1, respectively. Diffusely contrasted cortical lesions and the presence of mass effects on MRI, were significantly associated with a definitive diagnosis, compared to a nonspecific diagnosis. In conclusion, brain MRI and liquid biopsies can assist in determining the appropriate indications for brain biopsies in neurological diseases of unknown etiology.

Varicella-zoster virus-related neurological complications: From infection to immunomodulatory therapies.

The Varicella-zoster virus (VZV), classified as a neurotropic member of the Herpesviridae family, exhibits a characteristic pathogenicity, predominantly inducing varicella, commonly known as chickenpox, during the initial infectious phase, and triggering the reactivation of herpes zoster, more commonly recognized as shingles, following its emergence from a latent state. The pathogenesis of VZV-associated neuroinflammation involves a complex interplay between viral replication within sensory ganglia and immune-mediated responses that contribute to tissue damage and dysfunction. Upon primary infection, VZV gains access to sensory ganglia, establishing latent infection within neurons. During reactivation, the virus can spread along sensory nerves, triggering a cascade of inflammatory mediators, chemokines, and immune cell infiltration in the affected neural tissues. The role of both adaptive and innate immune reactions, including the contributions of T and B cells, macrophages, and dendritic cells, in orchestrating the immune-mediated damage in the central nervous system is elucidated. Furthermore, the aberrant activation of the natural defence mechanism, characterised by the dysregulated production of immunomodulatory proteins and chemokines, has been implicated in the pathogenesis of VZV-induced neurological disorders, such as encephalitis, myelitis, and vasculopathy. The intricate balance between protective and detrimental immune responses in the context of VZV infection emphasises the necessity for an exhaustive comprehension of the immunopathogenic mechanisms propelling neuroinflammatory processes. Despite the availability of vaccines and antiviral therapies, VZV-related neurological complications remain a significant concern, particularly in immunocompromised individuals and the elderly. Elucidating these mechanisms might facilitate the emergence of innovative immunomodulatory strategies and targeted therapies aimed at mitigating VZV-induced neuroinflammatory damage and improving clinical outcomes. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of VZV infections.

Dengue versus COVID-19: comparing the incidence of cardiovascular, neuropsychiatric and autoimmune complications.

BACKGROUND: While persistence of chronic symptoms following dengue infection has been documented in small prospective cohorts, population-based studies are limited. The post-acute risk of new-incident multi-systemic complications following dengue infection was contrasted against that following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a multi-ethnic adult Asian population. METHODS: National testing and healthcare claims that databases in Singapore were utilized to build a retrospective population-based adult cohort with laboratory-confirmed infection during overlapping waves of SARS-CoV-2 and dengue transmission (1 July 2021 to 31 October 2022). Risks of new-incident cardiovascular/neuropsychiatric/autoimmune complications 31-300 days of post-dengue infection, contrasted with SARS-CoV-2 infection, were estimated using Cox regression with overlap weights. Risks were reported in terms of adjusted hazard ratio (aHR) and excess burden per 1000 persons. RESULTS: 11 707 dengue-infected individuals and 1 248 326 contemporaneous coronavirus disease 2019 (COVID-19) cases were included; the majority had mild initial infection not requiring hospitalization. Amongst dengue-infected individuals, there was 21% [aHR = 1.21 (1.06-1.38)] increased risk of any sequelae, with 55% [aHR = 1.55 (1.27-1.89)] increased risk of cardiovascular sequelae. Specifically, increased risk of dysrhythmias [aHR = 1.79(1.35-2.37)], ischemic heart disease [aHR = 1.45(1.12-1.89)], other cardiac disorders [aHR = 2.21(1.54-3.16)] and thrombotic disorders [aHR = 2.55(1.50-4.35)] was noted. Elevated risk of individual neuropsychiatric sequelae, including cerebrovascular disorders [aHR = 1.49(1.09-2.13)], cognition/memory disorders [aHR = 2.13(1.55-2.93)], extrapyramidal/movement disorders [aHR = 1.98(1.33-2.94)] and anxiety disorders [aHR = 1.61(1.01-2.56)], was observed in dengue-infected individuals compared to COVID-19 cases. Elevated risks of post-acute sequelae in dengue survivors were observed when contrasted against COVID-19 survivors infected during Delta/Omicron predominance, as well as across vaccination strata. CONCLUSION: Increased risk of post-acute cardiovascular/neuropsychiatric complications was observed in dengue survivors, when contrasted against COVID-19 survivors infected during Delta/Omicron predominance.

Blood-borne viruses and neurological manifestations: An overview.

Infections caused by blood-borne viruses, such as human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), hepatitis C virus (HCV), and hepatitis B virus (HBV), are systemic diseases that can lead to a wide range of pathological manifestations. Besides causing severe immune and hepatic disorders, these viral pathogens can also induce neurological dysfunctions via both direct and indirect mechanisms. Neurological dysfunctions are one of the most common manifestations caused by these viruses that can also serve as indicators of their infection, impacting the clinical presentation of the disease. The main neurological manifestations of these blood-borne viral pathogens consist of several central and peripheral nervous system (CNS and PNS, respectively) dysfunctions. The most common neurological manifestations of HIV, HTLV, HCV, and HBV include HIV-associated peripheral neuropathy (PN), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and HCV-/HBV-associated PN, respectively. Nonetheless, patients infected with these viruses may experience other neurological disorders, either associated with these conditions or manifesting in isolation, which can often go unnoticed or undiagnosed by physicians. The present review aims to provide an overview of the latest evidence on the relationship between blood-borne viruses and neurological disorders to highlight neurological conditions that may be somewhat overlooked by mainstream literature and physicians.

Fuzzy-Based Bioengineering System for Predicting and Diagnosing Diseases of the Nervous System Triggered by the Interaction of Industrial Frequency Electromagnetic Fields.

The study aims to enhance the standard of medical care for individuals working in the electric power industry who are exposed to industrial frequency electromagnetic fields and other relevant risk factors. This enhancement is sought through the integration of fuzzy mathematical models with contemporary information and intellectual technologies. The study addresses the challenges of forecasting and diagnosing illnesses within a specific demographic characterized by a combination of poorly formalized issues with interconnected conditions. To tackle this complexity, a methodological framework was developed for synthesizing hybrid fuzzy decision rules. This approach combines clinical expertise with artificial intelligence methodologies to promote innovative problem-solving strategies. Additionally, the researchers devised an original method to evaluate the body's protective capacity, which was integrated into these decision rules to enhance the precision and efficacy of medical decision-making processes. The research findings indicate that industrial frequency electromagnetic fields contribute to illnesses of societal significance. Additionally, it highlights that these effects are worsened by other risk factors such as adverse microclimates, noise, vibration, chemical exposure, and psychological stress. Diseases of the neurological, immunological, cardiovascular, genitourinary, respiratory, and digestive systems are caused by these variables in conjunction with unique physical traits. The development of mathematical models in this study makes it possible to detect and diagnose disorders in workers exposed to electromagnetic fields early on, especially those pertaining to the autonomic nervous system and heart rhythm regulation. The results can be used in clinical practice to treat personnel in the electric power industry since expert evaluation and modeling showed high confidence levels in decision-making accuracy.

Neurological Manifestations of Acute SARS-CoV-2 Infection in Pediatric Patients: A 3-Year Study on Differences between Pandemic Waves.

This study analyzed the neurological manifestation profiles of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across pandemic waves in pediatric patients. The study collected data on patients aged between 0 and 18 years, diagnosed with acute SARS-CoV-2 infection, admitted to a pediatric tertiary hospital between 1 March 2020 and 28 February 2023. This study included 1677 patients. Neurological manifestations were noted in 10% (n = 168) of patients with a median age of 3.2 years (interquartile range: 1-11.92). Neurological manifestations were significantly associated with the pandemic waves (p = 0.006) and age groups (p < 0.001). Seizures were noted in 4.2% of cases and reached an increasing frequency over time (p = 0.001), but were not associated with age groups. Febrile seizures accounted for the majority of seizures. Headache was reported in 2.6% of cases and had similar frequencies across the pandemic waves and age groups. Muscular involvement was noted in 2% of cases, reached a decreasing frequency over time (p < 0.001), and showed different frequencies among the age groups. Neurological manifestations of acute SARS-CoV-2 infection exhibit distinct patterns, depending on the pandemic wave and patient age group. The Wuhan and Omicron waves involved the nervous system more often than the other waves.