Search Results (266)

This two-case proof-of-concept study evaluated the feasibility and clinical utility of a smartphone-based markerless motion capture system for quantitative gait assessment in pediatric Guillain–Barré syndrome (GBS). Two children with GBS underwent overground gait analysis using a dual-smartphone setup (OpenCap), and three-dimensional hip, knee, and ankle kinematics were computed via OpenSim. Case 1, a boy with treatment-related fluctuation, demonstrated marked abnormalities in swing-phase limb advancement and ankle push-off that improved after six weeks of rehabilitation in parallel with gains in muscle strength, balance, and ambulation. Case 2, a girl recovering from acute inflammatory demyelinating polyneuropathy, exhibited residual reductions in hip and knee flexion and impaired ankle control despite normal strength, consistent with vestibular dysfunction. All assessments were completed within routine clinical time constraints and produced analyzable kinematic data using only two smartphones. These findings indicate that smartphone-based markerless motion capture is a feasible and informative method for detecting gait impairment and recovery patterns in pediatric GBS and may serve as an accessible digital biomarker to complement standard clinical evaluations. Full article

Background: Cutaneous viral infections, defined as viral pathogens that either primarily affect the skin (e.g., herpesviruses, enteroviruses) or frequently produce dermatologic manifestations despite systemic tropism (e.g., HIV, SARS-CoV-2), can trigger systemic inflammatory and neurotropic responses that extend their impact to the nervous system. A growing body of evidence suggests that viruses with dermatologic manifestations may play a significant role in the pathogenesis of neurologic disorders. Summary: Although individual viruses have been studied in isolation, the skin–brain axis in viral infections remains incompletely characterized. This review synthesizes existing knowledge and highlights gaps in understanding the mechanisms linking cutaneous viral infections to neurologic disease. We explore the principal mechanisms linking viral skin infections to central and peripheral nervous system damage, including direct neuroinvasion, immune-mediated injury, and vascular or endothelial dysfunction. Particular attention is given to herpesviruses, retroviruses, enteroviruses, and respiratory viruses, which have been associated with conditions such as dementia, multiple sclerosis, myelopathies, Guillain-Barré syndrome, and the post-acute neurologic sequelae of COVID-19. Furthermore, we discuss the role of neuroinflammation in viral-associated neurodegeneration and highlight emerging evidence supporting the recombinant zoster vaccine (Shingrix) as a potential modulator of neuroinflammatory processes and a protective factor against dementia. Conclusions: Cutaneous viral infections extend beyond local skin pathology, contributing to a broad spectrum of neurologic complications through intertwined infectious and inflammatory mechanisms. A clearer understanding of how peripheral viral activity shapes central nervous system vulnerability remains a major unmet need. A multidisciplinary approach integrating dermatologic and neurologic perspectives is essential for early recognition and prevention. While observational studies suggest that zoster vaccination may reduce viral reactivation and modulate neuroinflammatory pathways, definitive evidence of neuroprotection is still lacking. Future studies should clarify causal relationships, test mechanistic hypotheses regarding skin–brain immune crosstalk, and explore vaccine-mediated neuroprotection as a novel therapeutic strategy. Full article

This study presents an assessment scheme for haptic interaction systems based on Hamiltonian energy prediction, which contributes to procedures applied to neurorehabilitation. It focuses on robotic systems involving human participation in the control loop, where uncertainty may compromise both stability and task performance. To address this, a regression-based model is proposed to predict total mechanical energy using the robot’s position and velocity signals during active interaction. Synthetic data generated via TimeGAN are used to enhance model generalization. Advanced machine learning techniques—particularly Gradient Boosting—demonstrate outstanding accuracy, achieving an MSE of $0.628\times {10}^{-10}$ and $R^2=0.999976$. These results validate the use of synthetic data and passive-mode-trained models for assessing motor performance in active settings. The method is applied to a patient diagnosed with Guillain-Barré Syndrome, using the Hamiltonian function to estimate energy during interaction and objectively assess motor performance changes. The results obtained show that our proposal is of great relevance since it solves a current field of opportunity in the area. Full article

We report the case of a 62-year-old woman with Miller Fisher syndrome (MFS) whose severe bilateral ophthalmoplegia showed no improvement after four weeks of standard care consisting of intravenous immunoglobulin and physiotherapy. High-frequency transcutaneous electrical nerve stimulation (TENS) was applied over the bilateral sternocleidomastoid muscles and immediately followed by eye-movement exercises. Within three days, ocular motility began to improve, and after one month, only minimal left-eye abduction lag remained. Such neuromodulation of TENS might act on central and peripheral tiers of the oculomotor system and may have been temporally associated with faster recovery than expected in the natural course of the disease compared to the median three-month interval. This dramatic, time-associated improvement highlights the novelty of cervical TENS as a potential accelerator for recovery in MFS-related ophthalmoplegia. To the best of our knowledge, research involving the use of TENS in MFS-related ophthalmoplegia is limited, and our case demonstrates the feasibility and safety of TENS for faster recovery. Full article

Introduction. Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) is an autosomal recessive metabolic disorder resulting from mutations in the genes that encode the electron transfer flavoprotein (ETF) or its associated dehydrogenase (ETFDH), resulting in defects in mitochondrial fatty acid oxidation and a broad range of clinical presentations, most notably in the form of muscle weakness; exercise intolerance; and, in some cases, life-threatening metabolic crises. Late-onset MADD represents the most common form of lipid storage myopathy, but its diagnosis can be elusive due to its varied and often nonspecific clinical symptoms and may resemble other neuromuscular conditions, like inflammatory myopathies or other peripheral neuropathies, complicating the diagnostic process and delaying appropriate treatment. Aims. This case series aims to provide additional insights into the clinical presentation of MADD, highlighting diagnostic challenges in differentiating metabolic myopathies and emphasizing the role of muscle biopsy in diagnosing these conditions. Results. We describe five clinical cases of patients who were diagnosed with MADD, their clinical manifestations, and the diagnostic processes undertaken to arrive at this diagnosis. Notably, three patients were initially misdiagnosed with inflammatory myopathy, and one was misdiagnosed with Guillain–Barré syndrome. The correct diagnosis was established following a muscle biopsy, which revealed characteristic findings consistent with lipid storage myopathy and prompted subsequent biochemical analyses and genetic testing that confirmed the diagnosis of MADD. Conclusions. MADD is an underdiagnosed condition, and the description of new patients with various clinical presentations could support the development of clinical tools to promptly recognize this disease and allow physicians to deliver the most appropriate and effective therapy protocol, with Riboflavin and Carnitine supplementations, avoiding inappropriate treatments. The muscle biopsy was essential for a correct diagnostic assessment. Full article

Zika virus (ZIKV) was first identified in Africa in the mid-20th century and circulated for decades with limited and often unnoticed human cases. This situation changed with the emergence of the Asian lineage, responsible for large outbreaks in the Pacific and the Americas and for severe complications such as Guillain–Barré syndrome and Congenital Zika Syndrome (CZS). In contrast, the African lineage, although frequently more efficient in replication, cytopathogenicity, and mosquito transmission in experimental systems, has not been linked to comparable epidemics or congenital disease clusters. This review summarizes current knowledge on the differences between African and Asian lineages at the molecular, cellular, and epidemiological levels. It highlights how genetic variation interacts with host immunity, ecological factors, and human activity to shape epidemic potential. Understanding these interactions is essential for anticipating future outbreaks and for improving strategies to mitigate the impact of emerging arboviruses. Full article

Background: Respiratory syncytial virus (RSV) is a major pathogen of acute lower respiratory tract infection (LRTI) in infants, the elderly, and immunocompromised individuals. This review focuses on the progress of RSV vaccine development, especially subunit vaccines targeting the fusion protein (F) and attachment glycoprotein (G), aiming to summarize key strategies, challenges, and future directions in the field. Methods: The review is based on a comprehensive literature search and analysis of recent studies on RSV vaccine development, with a specific focus on subunit vaccines and related technologies. Results: Approved vaccines such as Abrysvo and Arexvy utilize structural engineering to stabilize the prefusion conformation of the F protein (PreF), thereby exposing neutralizing epitopes. Subunit vaccine candidates such as DS-Cav1 and DT-PreF enhance stability through disulfide bonds and dityrosine linkages, while ADV110 targets the conserved domain of the G protein to elicit cross-strain immunity. Virus-like particle (VLP) vaccines like IVX-A12 combine RSV and human metapneumovirus antigens to provide broad-spectrum immunity. However, challenges exist, including maintaining PreF stability, overcoming immunosenescence in the elderly, and addressing safety concerns like Guillain-Barré syndrome (GBS). Conclusions: Future RSV vaccine development should center on combined PreF-G protein vaccines, VLP technology, and optimizing cold-chain logistics to improve global accessibility and overcome existing challenges, thereby providing more effective prevention and control of RSV infections. Full article

COVID-19 vaccination has played a pivotal role in mitigating the global health crisis and reducing morbidity and mortality associated with SARS-CoV-2 infection. While its public health benefits are unequivocal, the unprecedented scale of vaccination—reaching billions worldwide—has also enabled the detection of rare autoimmune events, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and Guillain–Barré syndrome. Although such events occur in only a small subset of individuals, often influenced by genetic, environmental, or dosage-related factors, they underscore the importance of understanding immune tolerance mechanisms in vaccination. This review synthesizes clinical observations and immunological findings from the COVID-19 vaccination era, highlighting key mechanisms such as molecular mimicry, adjuvant-induced inflammation, bystander activation, epitope spreading, and polyclonal B cell activation. We also consider how novel vaccine platforms, particularly mRNA-based technologies, may influence immune regulation and self-tolerance. Importantly, we discuss the therapeutic management of vaccine-associated autoimmunity, including the use of corticosteroids, intravenous immunoglobulin (IVIG), plasma exchange, disease-modifying anti-rheumatic drugs (DMARDs), and other immunosuppressive agents, many of which have led to favorable clinical outcomes. By integrating mechanistic insights with treatment strategies, this review emphasizes that the overall benefits of COVID-19 vaccination overwhelmingly outweigh the risks, while advocating for continued surveillance, mechanistic research, and risk stratification to inform safer and more targeted vaccination strategies in future pandemics. Full article

Background/Objectives: Respiratory Syncytial Virus (RSV) is a common respiratory tract infection that accounts for significant morbidity and mortality, particularly among older adults. From 1 August 2024, the bivalent RSVpreF vaccine (Abrysvo^®) was introduced in Scotland for eligible older adults. While clinical trials and post-licensure studies showed a good safety profile of the vaccine, post-marketing observational studies in the United States reported a small increased risk of Guillain–Barré Syndrome (GBS) among older adult populations. Methods: We conducted observed versus expected (OE) and self-controlled case series (SCCS) analyses to retrospectively monitor the incidence of hospital admission for 39 conditions, including GBS. This was undertaken in post-RSV-vaccination periods from 1 August to 31 December 2024, among eligible adults aged 74 to 80 years in Scotland. Results: Observed versus expected analyses identified an increased risk of hospitalisation with GBS in the 1–28-day post-vaccination period. From SCCS analyses, six conditions showed an increased risk in post-vaccination periods (acute coronary syndrome, acute myocardial infarction, acute renal failure, GBS, heart failure and stroke (haemorrhagic)). After temporal adjustment, only GBS remained significant. All 10 hospitalised GBS cases occurred in the 10 to 16 days post-vaccination. Excess risk of GBS was estimated to be 46.1 cases per one million doses. Conclusions: Study results indicated a good safety profile of the RSV vaccine for older eligible adults aged 75 to 79 years, although a small increased risk of GBS was identified in both analyses. Excess risk levels of GBS from vaccination align with other studies. Full article

Antibodies are a cornerstone of the adaptive immune response, serving as key defenders against viral infections; however, they can also act as a double-edged sword, contributing to immune-mediated pathologies. This review advances a “Yin-Yang” framework to integrate the dual activities of antibodies. The protective ‘Yin’ functions are driven by high-affinity antibodies generated through processes like somatic hypermutation and class-switch recombination. These antibodies execute viral neutralization, activate the complement system, and engage Fc receptors (FcRs) to drive antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis. These mechanisms form the immunological basis of effective vaccines, which aim to elicit durable and functionally specialized antibody isotypes like IgG and mucosal IgA. Conversely, the pathogenic ‘Yang’ of the response can be detrimental. This includes antibody-dependent enhancement (ADE) of infection, notably observed with flaviviruses, and the development of autoimmunity through mechanisms like molecular mimicry and bystander activation, which can lead to conditions such as multiple sclerosis and Guillain-Barré Syndrome. The balance between protection and pathology is tipped by a confluence of factors. These include viral evasion strategies like antigenic mutation and glycan shielding, as well as host-based determinants such as genetic polymorphisms in FcRs, immune history, and the gut microbiome. Understanding these molecular determinants informs the rational design of next-generation interventions. Promising strategies, such as Fc-region glyco-engineering and the design of tolerogenic vaccines, aim to selectively promote protective functions while minimizing pathological risks, offering a clear path forward in combating viral threats. Full article

Background: Guillain-Barré syndrome (GBS) is an acute immune-mediated polyneuropathy often associated with autonomic dysfunction. Although transient cardiovascular instability is common, severe dysautonomia leading to cardiac arrest is rarely documented in children. Methods: We report the case of an 11-year-old previously healthy boy who initially presented with acute ophthalmoplegia and rapidly progressed to quadriplegia and areflexia. He developed fluctuating blood pressure and bradycardia, culminating in cardiac arrest due to asystole at 24 h after admission, requiring 17 min of resuscitation. Results: Electrophysiological studies confirmed a demyelinating polyneuropathy. Although intravenous immunoglobulin (IVIG) was initiated 5 h after admission, clinical improvement was achieved only after subsequent plasmapheresis on day 20, with the recovery of autonomic function by day 35. He was extubated on day 45 and discharged on day 83 with a near-complete recovery after prolonged intensive care and rehabilitation. Conclusion: This case highlights the potential for rapid and life-threatening autonomic instability in pediatric GBS. Unlike typical cases, the patient progressed to cardiac arrest within 24 h despite IVIG, highlighting the need to consider plasmapheresis for non-responders. Continuous hemodynamic monitoring is essential to prevent fatal outcomes, even in patients with initially mild or atypical presentations. Full article

Human herpesvirus-8 (HHV-8)-associated multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder with systemic and cutaneous manifestations that can be diagnostically challenging, especially in immunocompromised patients. We report the case of a 68-year-old man with HIV and biopsy-proven Kaposi sarcoma (KS), who developed progressive fevers, night sweats, weight loss, and fatigue, accompanied by diffuse lymphadenopathy, splenomegaly, and new erythematous and hyperpigmented lesions shortly after intravenous immunoglobulin therapy for Guillain–Barré syndrome. A laboratory evaluation revealed that the patient had elevated total protein and polyclonal hypergammaglobulinemia, without monoclonality. Imaging demonstrated widespread lymphadenopathy and splenomegaly. A core lymph node biopsy showed polytypic plasmacytosis, but was non-diagnostic. Given the ongoing symptoms, an excisional biopsy was performed, revealing regressed germinal centers with increased interfollicular vascularity, mantle zone “onion skinning,” and HHV-8 LANA-1 nuclear positivity, establishing the diagnosis of HHV-8-associated MCD. Rituximab monotherapy was initiated, resulting in clinical improvement, resolution of the constitutional symptoms, and stabilization of ascites. This case highlights the importance of maintaining a high index of suspicion for MCD in patients with KS who develop new systemic or cutaneous findings, the limitations of a core biopsy, and the value of a timely excisional biopsy in guiding diagnosis and treatment. Full article

Background: Nearly 10% of all community-acquired pneumonias are caused by Chlamydia pneumoniae. This is a Gram-negative intracellular coccus that poses a significant challenge for routine diagnostics due to its poor growth in tissue culture and non-specific clinical presentations. Case Report: This study presents the case of a 61-year-old man whose initial disease manifestation included a non-specific upper respiratory tract infection and reactive pericarditis. A diagnostic work-up of the etiology of pericarditis, with stepwise exclusion of other causative agents, led to confirmation of a possible chronic, recurrent C. pneumoniae infection, with good clinical and laboratory responses to azithromycin across multiple hospitalizations. However, upon initiation of prolonged doxycycline therapy, the disease course was complicated by the development of Guillain–Barré syndrome. With appropriate treatment, the neurological deficit regressed, with near-complete resolution of the syndrome’s clinical picture. Discussion and Conclusions: The development of reactive pericarditis and the patient’s neurological symptoms stemmed from an immune response to bacterial antigens that resemble antigens of the central nervous system and the pericardium. Prolonged doxycycline therapy, together with symptomatic management of the neurological condition and concomitant pericarditis, represents good clinical practice and is one potential management approach for patients with similar presentations. Full article

Neurological disorders significantly affect ocular surface homeostasis, influencing parameters such as blink rate (BR), tear production, corneal nerve density, and sensitivity. This review summarizes recent findings on ocular surface alterations associated with neurological diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Guillain-Barré syndrome (GBS), trigeminal neuralgia (TN), multiple sclerosis (MS), and Charcot–Marie–Tooth disease (CMT). Notably, ocular manifestations such as reduced BR, decreased tear break-up time (TBUT), impaired tear secretion, and corneal nerve fiber loss are consistently reported. In AD, elevated tear amyloid-beta and tau proteins emerge as promising biomarkers for early disease detection. PD patients frequently experience dry eye symptoms attributed to reduced BR and tear film instability. GBS is linked to lagophthalmos and corneal nerve impairment, potentially leading to severe ocular surface damage. TN demonstrates bilateral ocular surface dysfunction despite unilateral neuropathic symptoms. MS is associated with significant ocular surface alterations, reflecting broader neuroinflammatory and autonomic disturbances. Similarly, CMT patients show reduced corneal sensitivity and tear production, underscoring the systemic nature of neurological impacts. Awareness of these ocular manifestations is essential for improving patient care and guiding future research into ocular biomarkers and targeted therapies. Full article

Guillain–Barré syndrome (GBS) is the most common acute inflammatory motor polyneuropathy. It affects all age groups, but the incidence increases with increasing age. Before manifesting with neurological symptoms, it is usually preceded by a prodromal phase of infection, most commonly respiratory or gastrointestinal. Pathologically, it is a post-infection immune disorder. The immune response is due to mimicry between the infecting agent and axolemmal surface molecules, which triggers an acute immune injury that leads to blockade of nerve conduction. Age-related decline in immune function plays a role in the increased prevalence and severity of GBS in older people. Typical neurological manifestations are ascending paralysis, areflexia and cranial nerve involvement, but sensory loss is uncommon. In up to 25% of cases, autonomic dysfunction occurs, which includes cardiovascular, sudomotor, gastrointestinal or genitourinary symptoms. The development of autonomic dysfunction in GBS is associated with poor prognosis. We report a case of a 78-year-old man who presented with a predominant autonomic dysfunction that led to a delay in the diagnosis. Because of the multiple morbidities associated with old age, the diagnosis of GBS presentation with autonomic dysfunction, without the typical neurological clinical pattern, may be attributed to the existing comorbidities. Therefore, clinical suspicion and close monitoring with respect to the development of autonomic dysfunction, from the first day of hospital admission, are important. The main diagnostic tests are cerebrospinal fluid analysis looking for protein–cell dissociation and nerve conduction studies to confirm the neuropathy. Treatment involves general supportive care, specific immunological intervention by intravenous immunoglobulins or plasma exchange courses and neurorehabilitation. Severe cases may require intensive care admission and mechanical ventilation. More than 80% of cases will fully recover, but 10% may have residual disability, with mortality estimated at 3–7%. Older age, multiple morbidities, severe weakness, autonomic dysfunction and the need for mechanical ventilation are poor prognostic factors. Full article