Search Results (114)

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is characterized by the predominance of optic neuritis, myelitis, acute disseminated encephalomyelitis (ADEM), and cortical encephalitis, and can be diagnosed by the presence of pathogenic immunoglobulin G (IgG) antibodies targeting the extracellular domain of MOG in the serum and cerebrospinal fluid (CSF). Initially considered a variant of multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD), it is now widely recognized as a separate entity, supported by converging evidence from serological, pathological, and clinical studies. Patients with MOGAD often exhibit better recovery from acute attacks; however, their clinical and pathological features vary based on the immunological role of MOG-IgG via antibody- or complement-mediated perivenous demyelinating pathology, in addition to MOG-specific cellular immunity, resulting in heterogeneous demyelinated lesions from vanishing benign forms to tissue necrosis, even though MOGAD is not a mild disease. The key is the immunological mechanism of devastating lesion coalescence and long-term degenerating mechanisms, which may still accrue, particularly in the relapsing, progressing, and aggressive clinical course of encephalomyelitis. The warning features of the severe clinical forms are: (1) fulminant acute multifocal lesions or multiphasic ADEM transitioning to diffuse (Schilder-type) or tumefactive lesions; (2) cortical or subcortical lesions related to brain atrophy and/or refractory epilepsy (Rasmussen-type); (3) longitudinally extended spinal cord lesions severely affected with residual symptoms. In addition, it is cautious for patients refractory to acute stage early 1st treatment including intravenous methylprednisolone treatment and apheresis with residual symptoms and relapse activity with immunoglobulin and other 2nd line treatments including B cell depletion therapy. Persistent MOG-IgG high titration, intrathecal production of MOG-IgG, and suggestive markers of higher disease activity, such as cerebrospinal fluid interleukin-6 and complement C5b-9, could be identified as promising markers of higher disease activity, worsening of disability, and poor prognosis, and used to identify signs of escalating treatment strategies. It is promising of currently ongoing investigational antibodies against anti-interleukin-6 receptor and the neonatal Fc receptor. Moreover, due to possible refractory issues such as the intrathecal production of autoantibody and the involvement of complement in the worsening of the lesion, further developments of other mechanisms of action such as chimeric antigen receptor T-cell (CAR-T) and anti-complement therapies are warranted in the future. Full article

Acute transverse myelitis (ATM) is a rare, immune-mediated disorder of the spinal cord characterized by sensory, motor, and autonomic dysfunction. Although the human papillomavirus (HPV) vaccine is widely regarded as safe, isolated reports have suggested a potential temporal association with autoimmune neurological events, including ATM. We present a case of a 21-year-old woman who developed ATM two weeks following administration of the first dose of the HPV vaccine (Cervarix). The clinical presentation included rapid-onset paraparesis, sensory deficits, and sphincter dysfunction. An MRI revealed a T2-hyperintense lesion at the Th10–Th12 level. A cerebrospinal fluid analysis showed elevated protein levels. The patient underwent corticosteroid therapy, plasmapheresis, and IVIG, followed by a comprehensive, individualized rehabilitation program. This included balance and stability training, Redcord-based neuromuscular activation, electrostimulation, and pelvic floor therapy. Although no causal link between HPV vaccination and ATM has been established, this case emphasizes the importance of considering post-vaccinal autoimmune phenomena. More importantly, it illustrates the critical role of early, targeted rehabilitation—particularly pelvic floor re-education and neuromodulation—in improving outcomes in patients with significant motor and autonomic deficits. Full article

Transverse myelitis is a rare spinal cord condition that can cause severe motor, sensory, and autonomic dysfunction. This case report describes a 16-year-old male with incomplete paraplegia due to idiopathic transverse myelitis who underwent robotic-assisted gait training (RAGT) using the EKSO exoskeleton, integrated into an intensive rehabilitation programme. After one month, he showed significant improvements in gait speed, dynamic balance, effort tolerance, and trunk mobility. RAGT promoted better weight distribution and reduced compensatory patterns during ambulation. The intervention proved safe and clinically beneficial, highlighting the potential of robotic technologies as effective adjuncts in paediatric spinal cord injury rehabilitation. Full article

Encephalitis is a potentially life-threatening condition with long-term neurological sequelae. However, data on early clinical, demographic, and diagnostic predictors of functional outcomes remain limited. We performed a retrospective monocentric study including 98 patients diagnosed with infectious encephalitis of various etiologies treated in the University Hospital Ulm between January 2014 and December 2024. Ordinal logistic regression models were applied to evaluate associations between admission characteristics and functional outcome at discharge, as measured by the modified Rankin Scale. Three multivariate models incorporating clinical, demographic, and MRI/EEG variables explained up to 53% of the variance in mRS at discharge (p < 0.001), outperforming models based solely on CSF parameters. Key predictors of poor functional outcome included ‘altered consciousness’ (OR 7.08, p < 0.001), higher ‘mRS at admission’ (OR 0.03–0.07 across categories, p < 0.001), ‘focal/generalized EEG slowing’ (OR 9.97, p < 0.001), ‘epileptiform EEG activity’ (OR 17.49, p < 0.001), ‘MRI: myelitis’ (OR 16.44, p = 0.004), and ‘intrathecal IgM synthesis’ (OR 8.93, p = 0.018). Conversely, ‘longer hospitalization’ (OR 0.13–0.17 for different intervals, p < 0.006) and ‘intrathecal IgG synthesis’ (OR 0.05, p = 0.03) were associated with more favorable outcomes. Despite the single-center and retrospective aspects of this study, our findings underscore a multifactorial pattern of outcome determinants in infectious encephalitis, highlighting the prognostic relevance of initial neurological status, electrophysiological abnormalities, and neuroimaging features. Full article

Introduction: Downbeat nystagmus (DBN) is an ocular motor disorder characterized by persistent to-and-fro eye movements with a slow phase directed upwards and a corrective fast phase downwards. DBN in the context of myelin oligodendrocyte glycoprotein-associated disorder (MOGAD) represents a rare clinical presentation. Case Presentation: A 24-year-old male with MOGAD presented with DBN, status epilepticus, and longitudinally extensive transverse myelitis (LETM). Intervention: The clinical course, diagnostic findings, and management approach are described in detail within the full report. Outcomes: The patient at follow-up was able to ambulate independently, and his nystagmus had improved. He continued to demonstrate transient DBN on supine positioning and head-shaking test. Conclusions: This case report contributes to the understanding of DBN as a manifestation of MOGAD. The accompanying literature review examines the neuroanatomy, pathophysiology, and emerging therapeutic approaches for DBN, providing context for this unusual presentation. Full article

While viral pathogens are often subdivided into neurotropic and non-neurotropic categories, systemic inflammation caused by non-neurotropic viruses still possesses the ability to alter the central nervous system (CNS). Studies of CNS disease induced by viral infection, whether neurotropic or not, are presented with a unique set of challenges. First, because brain biopsies are rarely necessary to diagnose viral-associated neurological disorders, antemortem tissue samples are not readily available for study and human pathological studies must rely on end-stage, postmortem evaluations. Second, in vitro models fail to fully capture the nuances of an intact immune system, necessitating the use of animal models to fully characterize pathogenesis and identify potential therapeutic approaches. Non-human primates (NHP) represent a particularly attractive animal model in that they overcome many of the limits posed by more distant species and most closely mirror human disease pathogenesis and susceptibility. Here, we review NHP infection models of viruses known to infect and/or replicate within cells of the CNS, including West Nile virus, the equine encephalitis viruses, Zika virus, and herpesviruses, as well as those known to alter the immune status of the brain in the absence of significant CNS penetrance, including human immunodeficiency virus (HIV) in the current era of combination antiretroviral therapy (cART) and the coronavirus of severe acute respiratory syndrome (SARS)-CoV−2. This review focuses on viruses with an established role in causing CNS disease, including encephalitis, meningitis, and myelitis and NHP models of viral infection that are directly translatable to the human condition through relevant routes of infection, comparable disease pathogenesis, and responses to therapeutic intervention. Full article

Background and Clinical Significance: Neuromyelitis optica (NMO) is a chronic demyelinating inflammatory disease of the central nervous system (CNS), mediated by autoantibodies against aquaporin-4 (AQ4) receptors. In the spectrum of NMO, other autoimmune diseases also coexist, though their association with systemic lupus erythematosus (SLE) is rare. Case Presentation: We present two cases of patients in their 70s who were diagnosed with NMO in the context of SLE. The first case concerns a 78-year-old woman with drug-induced SLE and thoracic myelitis who developed T4-level incomplete paraplegia over three weeks. The second case involves a 71-year-old woman with a history of SLE and myasthenia gravis, presenting with cervical myelitis with progressive worsening of walking and C4-level paraparesis over two months. In both cases, elevated serum anti-AQ4 titers were detected, establishing the diagnosis of NMO and differentiation from an atypical manifestation of SLE-related myelitis. High doses of intravenous corticosteroids with gradual tapering, along with cyclophosphamide, followed by rituximab, were administered in both patients. The first patient showed a poor response, while the second showed improvement. Conclusions: The coexistence of NMO with SLE is rare, but the occurrence of myelitis in patients with connective tissue diseases should raise the suspicion of NMO, especially in elderly women and several years after the diagnosis of SLE. Time to treatment is critical, as delays in treating NMO can result in cumulative and disabling damage. Full article

Background: Enteroviruses, members of the Picornaviridae family, typically cause asymptomatic or mild infections. However, they can also result in central nervous system (CNS) involvement, with transverse myelitis (TM) occurring only on rare occasions. TM is a syndrome characterized by acute or subacute spinal cord dysfunction, leading to neurological deficits below the level of the lesion. Case report: We report a case series of eight pediatric patients admitted over a three-month period, June to August 2024. All patients presented with ataxia and/or other neurological symptoms, alongside abnormal cerebrospinal fluid (CSF) findings. Although ataxia is commonly associated with cerebellitis, magnetic resonance imaging (MRI) in this cohort revealed findings consistent with TM. Notably, all patients demonstrated similar MRI abnormalities. The onset of symptoms occurred over a short time during an enterovirus epidemic. Enteroviral RNA was detected, or the virus was isolated in seven patients, while one patient had a close epidemiological link to the virus. All patients achieved full recovery following immunomodulatory therapy. Conclusions: This case series underscores that ataxia may be an atypical symptom associated with TM. Furthermore, there was a notable distinction between the clinical presentation and neuroradiological findings. Immunomodulatory therapy with immunoglobulins and corticosteroids has been shown to be effective and safe, supporting the hypothesis of an immune-mediated pathogenesis in these patients. Full article

Objectives: Neurosarcoidosis (NS) is a severe and infrequent complication of sarcoidosis. Available data on NS are variable. We aimed to characterize NS epidemiology, clinical and therapeutic characteristics in a well-defined cohort of NS patients. Methods: Observational population-based cohort study of 342 patients diagnosed with sarcoidosis in Northern Spain, between 1999 and 2019. Among them, those patients who fulfilled the Consortium Consensus Group diagnosis criteria for NS were included. The annual incidence between 1999 and 2019 was estimated by gender, age, and year of diagnosis. Additionally, a literature review was performed. Therapeutic efficacy was evaluated using the neurological-related extra-pulmonary physician organ severity tool (ePOST). Results: NS was diagnosed in 29 out of 342 patients with sarcoidosis (8.5%; 18 women/11 men) with a mean age of 42.3 ± 15.1 years. Most NS patients have associated systemic sarcoidosis (93.4%) mainly consisting of lung (n = 22; 75.9%), articular (n = 15; 51.7%) and/or ocular (n = 12; 40%) involvement. The annual incidence of NS during the study period was 1.1 per 1,000,000 people. There is a linear relationship with a weak decrease in age at diagnosis over time. NS was subdivided into chronic headache (n = 11; 36.7%), cranial neuropathy (n = 7; 24.1%), myelitis (n = 4; 13.8%), peripheral neuropathy (n = 3; 10.3%), cranial neuropathy with chronic headache (n = 3; 10.3%) and aseptic meningitis (n = 2; 6.9%). Twenty-five patients (86.2%) received oral glucocorticoids (mean ± SD maximum prednisone dose 49.6 ± 19.4 mg/day). In addition, conventional immunosuppressive drugs were administered to 17 (58.6%) patients and biological therapy to 12 (41.4%) patients. After 12 months of initiating biological therapy, 14 out of 17 patients (82.4%) achieved complete remission, defined as an ePOST score of 0. Severe allergic reaction was observed in only one patient who had received treatment with both Infliximab and Adalimumab. Conclusions: The epidemiological, clinical and treatment characteristics of NS in Northern Spain are similar to that of other countries. Full article

Enterovirus D68 (EV-D68) caused large biennial cyclical outbreaks of respiratory disease and cases of acute flaccid myelitis from 2014 to 2018 in the USA. An anticipated outbreak did not occur in 2020, likely due to non-pharmaceutical interventions targeting the COVID-19 pandemic. A large respiratory disease outbreak occurred again in 2022, but uncertainty remained regarding if circulation of EV-D68 would return to the pre-pandemic patterns. We conducted prospective active surveillance of clinical respiratory specimens from Colorado children for EV-D68 in 2023 and 2024. A subset of residual specimens positive for rhinovirus/enterovirus (RV/EV) were tested for EV-D68 via a validated in-house EV-D68 reverse transcription–PCR assay. During epi weeks 18–44 in 2023, 525 residual specimens positive for RV/EV all tested negative for EV-D68. In 2024, during epi weeks 18–44, 10 (1.8%) of the 546 RV/EV-positive specimens were EV-D68-positive. The EV-D68-positive cases were predominantly young children (median age 4.8 years) receiving treatment with asthma medications. Following the 2022 EV-D68 outbreak, an anticipated outbreak did not occur in 2023. While EV-D68 was detected in 2024, the number of cases was not as significant as in prior outbreak years. Continued surveillance for EV-D68 will be important to understand the future dynamics of EV-D68 circulation and prepare for future outbreaks. Full article

Background/Objectives: Post-market surveillance of COVID-19 vaccines is vital. This study analyzed EudraVigilance data (Jan 2021–Dec 2023) to detect potential safety signals linking COVID-19 vaccines and specific neurological adverse events (aseptic meningitis, Guillain–Barré syndrome, polyradiculoneuropathies, multiple sclerosis, transverse myelitis, neuromyelitis optica). It also explored the impact of non-healthcare professional reports on disproportionality analysis. Methods: EudraVigilance reports were analyzed to quantify neurological events for 5 COVID-19 vaccines and 47 comparators. Disproportionality was assessed using the Proportional Reporting Ratio (PRR). Spearman’s correlation (SCC) was used to examine the impact of non-healthcare professional reports on PRR. Results: An analysis of 4,159,820 COVID-19 vaccine and 114,025 comparator reports showed a reporting decline over time. A higher proportion of adverse drug event reports were submitted by non-healthcare professionals for COVID-19 vaccines compared to control vaccines, a trend observed consistently across 2021 (57.3% vs. 33%, p < 0.001), 2022 (59.4% vs. 36.5%, p = 0.001), and 2023 (42% vs. 24.36%, p = 0.006). In 2023, significant signals (PRR ≥ 2) were found between Jcovden© and polyradiculoneuropathy (PRR 5.4, IC 95% 3.98–7.32), multiple sclerosis (PRR 2.72, IC 95% (1.08–6.87), transverse myelitis (PRR 4.68, IC 95% 1.02–21.35) and neuromyelitis optica (PRR 7.79, IC 95% 3.5–17.37). In addition, both Spikevax© and Comirnaty© showed significant signals with multiple sclerosis (PRR 2.50, IC 95% 1.70–3.68, and PRR 2.33, IC 95% 1.68–3.24) and transverse myelitis (PRR 3.50, IC 95% 1.66–7.50 and PRR 3.58, IC 95% 1.85–6.93). A significant negative correlation between the proportion of reports from non-healthcare professionals and the case/no-case ratio was found (SCC = −0.4683, p = 0.009). Conclusions: While some significant signals emerged in 2023, the combined three-year data showed no vaccine exceeding the PRR threshold of 2. High-quality data and bias mitigation strategies are crucial for accurate PRR estimation in pharmacovigilance and public health. Full article

MOGAD is a demyelinating syndrome with the presence of antibodies against myelin oligodendrocyte glycoprotein, which is, next to multiple sclerosis and the neuromyelitis optica spectrum, one of the manifestations of the demyelinating process, more common in the pediatric population. MOGAD can take a variety of clinical forms: acute disseminated encephalomyelitis (ADEM), retrobulbar optic neuritis, often binocular (ON), transverse myelitis (TM), or NMOSD-like course (neuromyelitis optica spectrum disorders), less often encephalopathy. The course may be monophasic (40–50%) or polyphasic (50–60%), especially with persistently positive anti-MOG antibodies. Very rarely, the first manifestation of the disease, preceding the typical symptoms of MOGAD by 8 to 48 months, is focal seizures with secondary generalization, without typical demyelinating changes on MRI of the head. The paper presents a case of a 17-year-old patient whose first symptoms of MOGAD were focal epileptic seizures in the form of turning the head to the right with the elevation of the left upper limb and salivation. Seizures occurred after surgical excision of a tumor of the right adrenal gland (ganglioneuroblastoma). Then, despite a normal MRI of the head and the exclusion of onconeural antibodies in the serum and cerebrospinal fluid after intravenous treatment, a paraneoplastic syndrome was suspected. After intravenous steroid treatment and immunoglobulins, eight plasmapheresis treatments, and the initiation of antiepileptic treatment, the seizures disappeared, and no other neurological symptoms occurred for nine months. Only subsequent relapses of the disease with typical radiological and clinical picture (ADEM, MDEM, recurrent ON) allowed for proper diagnosis and treatment of the patient both during relapses and by initiating supportive treatment. The patient’s case allows us to analyze the multi-phase, clinically diverse course of MOGAD and, above all, indicates the need to expand the diagnosis of epilepsy towards demyelinating diseases: determination of anti-MOG and anti-AQP4 antibodies. Full article

Enterovirus 68 (EV-D68) is a non-enveloped virus with a positive-sense single-stranded RNA genome that causes respiratory diseases and acute flaccid myelitis, posing significant threats to human health. However, an effective vaccine remains undeveloped. SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent enzyme, plays a key role in cellular metabolism, but its interaction with NAD+ during viral infections is not well understood. In this study, through a metabolomics analysis, we demonstrate that EV-D68 infection influences cellular metabolism. Additionally, we show that NAD+ inhibits EV-D68 infection both in vivo and in vitro. EV-D68 reduces cellular NAD+ levels by regulating the expression of enzymes involved in NAD+ consumption and synthesis. Moreover, the infection increases the expression of sirtuin 1 (SIRT1), which inhibits EV-D68 replication in turn. Mechanistically, SIRT1 suppresses EV-D68 5′UTR-mediated translation, and the antiviral effect of SIRT1 on EV-D68 replication is enhanced by NAD+. Collectively, our findings highlight the critical role of NAD+ metabolism in EV-D68 infection and reveal the antiviral potential of SIRT1, providing valuable insights for the development of antiviral strategies. Full article

Background/Objectives: Chronic neuropathic pain (CNP) stands as one of the most debilitating complications in patients with myelitis owing to its challenging management. Bright spotty lesions (BSLs) are frequently observed in neuromyelitis optica spectrum disorder (NMOSD), but few reports have discussed CNP in myelitis. We aim to demonstrate that BSLs could be one of the potential prognostic factors for CNP development in myelitis. Methods: We examined 63 patients diagnosed with myelitis. Patients were categorized into CNP and non-CNP groups. We assessed the severity of clinical symptoms and the oral steroid dose administered after pulse therapy. Spine magnetic resonance imaging (MRI) of each patient was reviewed to analyze the characteristics of myelitis. Serological and cerebrospinal fluid (CSF) findings were also examined to confirm the etiology. Results: CNP was observed in 27 patients (42.9%). The mean onset age of patients with CNP was 45.26 ± 14.16 years. The MRI lesions exhibited more enhanced features and bright spotty lesions (BSLs) in the CNP group (χ² test, p < 0.05). Patients with CNP received a lower oral steroid dose during the first month after symptom onset (χ² test, p < 0.05). Multivariate logistic regression analysis revealed that patients with CNP exhibited significant BSLs in their myelitis lesions on spine MRI (OR 4.965; 95% CI, 1.282 to 19.235, p = 0.02). Conclusions: Although the exact mechanism remains unknown, the presence of BSLs on spine MRI could serve as an independent prognostic factor for CNP development. Additionally, our study suggests that lower oral steroid doses administered immediately after symptom onset are associated with CNP development. Further investigation with a larger cohort is warranted to validate our findings. Full article

Background/Objectives: Transverse myelitis (TM) is a rare, acute inflammatory disorder affecting the spinal cord, with severe potential consequences, particularly in pediatric patients. Therapeutic plasma exchange (TPE) has emerged as a possible intervention for children unresponsive to high-dose corticosteroids. This study explores the efficacy of early TPE in pediatric TM through a case report and scoping review aiming to clarify the therapeutic benefits of TPE when used in conjunction with corticosteroids in children. Methods: We present a scoping review of existing literature on the early administration of TPE in pediatric patients with TM, supplemented by a case report of a 5-year-old boy with Longitudinally Extensive Transverse Myelitis (LETM), who received early TPE and corticosteroid therapy. Clinical progression, response to TPE, and functional outcomes were documented over a 9-month follow-up period. Results: Among the reviewed cases, early TPE demonstrated potential to expedite neurological recovery and improve functional outcomes. In our case report, the patient showed rapid recovery, achieving unassisted ambulation by day four of TPE. No adverse effects were observed. MRI findings revealed substantial resolution of spinal cord lesions by three months, with near-complete symptom resolution at nine months. Conclusions: Early initiation of TPE, in conjunction with corticosteroids, may offer significant therapeutic benefit in pediatric TM, potentially accelerating recovery and improving outcomes. This case highlights the need for further controlled studies to establish evidence-based guidelines for TPE use in pediatric TM. Full article