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Continuum (Minneapolis, Minn.) Feb 2021This article provides an update on the clinical diagnosis and management of immune-mediated myelopathies, including the relevance of imaging, ancillary testing with an... (Review)
Review
PURPOSE OF REVIEW
This article provides an update on the clinical diagnosis and management of immune-mediated myelopathies, including the relevance of imaging, ancillary testing with an emphasis on autoantibody biomarkers, recognition of myelitis mimics, and therapeutic approach.
RECENT FINDINGS
The imaging characterization of immune-mediated myelopathies and the discovery of neural autoantibodies have been crucial in improving our ability to accurately diagnose myelitis. The identification of autoantibodies directed against specific central nervous system targets has led to major improvements in our understanding of the mechanisms underlying inflammation in myelitis. It has also allowed distinction of these myelopathy etiologies from noninflammatory etiologies of myelopathy and from multiple sclerosis and provided insight into their risk of recurrence, treatment response, and long-term clinical outcomes. Prompt recognition and appropriate testing in the setting of acute and subacute myelopathies is critical as timely administration of immunotherapy can help improve symptoms and prevent permanent neurologic disability. A patient should not be classified as having "idiopathic transverse myelitis" without a comprehensive evaluation for a more specific etiology. Achieving the correct diagnosis and learning to recognize noninflammatory myelitis mimics is crucial as they have therapeutic and prognostic implications.
SUMMARY
Identifying the clinical and radiographic features of immune-mediated myelitis and recognizing mimics and pitfalls will help clinicians treat confirmed autoimmune myelitis appropriately.
Topics: Autoantibodies; Diagnosis, Differential; Humans; Multiple Sclerosis; Myelitis, Transverse; Spinal Cord Diseases
PubMed: 33522737
DOI: 10.1212/CON.0000000000000900 -
Lancet (London, England) Jan 2021Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and... (Review)
Review
Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for AFM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population.
Topics: Central Nervous System Viral Diseases; Child; Enterovirus Infections; Global Health; Humans; Magnetic Resonance Imaging; Muscle Hypotonia; Muscle Weakness; Myelitis; Neuromuscular Diseases; Patient Outcome Assessment
PubMed: 33357469
DOI: 10.1016/S0140-6736(20)32723-9 -
Neurologic Clinics Feb 2022Myelopathy can present acutely or more insidiously and has a broad differential diagnosis. In addition to the clinical history and neurologic examination, diagnostic... (Review)
Review
Myelopathy can present acutely or more insidiously and has a broad differential diagnosis. In addition to the clinical history and neurologic examination, diagnostic testing, including MRI and cerebrospinal fluid analysis, as well as thorough review of patient comorbidities, risk factors, and potential toxic exposures, can help neurohospitalists distinguish between various causes and potentially start appropriate empiric therapy while awaiting definitive testing. This article focuses on how imaging can help in determining the most likely cause of myelopathy and highlights a range of causes, including compressive, vascular, metabolic and toxic, infectious, autoimmune, neoplastic, and paraneoplastic causes of spinal cord dysfunction.
Topics: Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Myelitis, Transverse; Spinal Cord; Spinal Cord Diseases
PubMed: 34798966
DOI: 10.1016/j.ncl.2021.08.009 -
Handbook of Clinical Neurology 2023Transverse myelitis is a noncompressive myelopathy of inflammatory origin. The causes are broad, ranging from infective or toxic to immuno-mediated etiology. They can be... (Review)
Review
Transverse myelitis is a noncompressive myelopathy of inflammatory origin. The causes are broad, ranging from infective or toxic to immuno-mediated etiology. They can be manifestations of systemic diseases, such as sarcoidosis and systemic lupus erythematous, or phenotypes of neuroinflammation; in a portion of cases, the etiology remains unknown, leading to the designation idiopathic. The clinical presentation of transverse myelitis depends on the level of spinal cord damage and may include sensorimotor deficits and autonomic dysfunction. The age of onset of the disorder can impact the symptoms and outcomes of affected patients, with differences in manifestation and prognosis between children and adults. Spinal cord magnetic resonance imaging and cerebrospinal fluid examination are the main diagnostic tools that can guide clinicians in the diagnostic process, even though the search for antibodies that target the structural components of the neural tissue (anti-aquaporin4 antibodies and anti-myelin-oligodendrocyte antibodies) helps in the distinction among the immune-mediated phenotypes. Management and outcomes depend on the underlying cause, with different probabilities of relapse according to the phenotypes. Hence, immunosuppression is often recommended for the immune-mediated diseases that may have a higher risk of recurrence. Age at onset has implications for the choice of treatment.
Topics: Humans; Child; Myelitis, Transverse; Spinal Cord Diseases; Antibodies; Autonomic Nervous System Diseases
PubMed: 37620065
DOI: 10.1016/B978-0-323-98817-9.00020-X -
Genome Research May 2019Metagenomic next-generation sequencing (mNGS) for pan-pathogen detection has been successfully tested in proof-of-concept case studies in patients with acute illness of...
Metagenomic next-generation sequencing (mNGS) for pan-pathogen detection has been successfully tested in proof-of-concept case studies in patients with acute illness of unknown etiology but to date has been largely confined to research settings. Here, we developed and validated a clinical mNGS assay for diagnosis of infectious causes of meningitis and encephalitis from cerebrospinal fluid (CSF) in a licensed microbiology laboratory. A customized bioinformatics pipeline, SURPI+, was developed to rapidly analyze mNGS data, generate an automated summary of detected pathogens, and provide a graphical user interface for evaluating and interpreting results. We established quality metrics, threshold values, and limits of detection of 0.2-313 genomic copies or colony forming units per milliliter for each representative organism type. Gross hemolysis and excess host nucleic acid reduced assay sensitivity; however, spiked phages used as internal controls were reliable indicators of sensitivity loss. Diagnostic test accuracy was evaluated by blinded mNGS testing of 95 patient samples, revealing 73% sensitivity and 99% specificity compared to original clinical test results, and 81% positive percent agreement and 99% negative percent agreement after discrepancy analysis. Subsequent mNGS challenge testing of 20 positive CSF samples prospectively collected from a cohort of pediatric patients hospitalized with meningitis, encephalitis, and/or myelitis showed 92% sensitivity and 96% specificity relative to conventional microbiological testing of CSF in identifying the causative pathogen. These results demonstrate the analytic performance of a laboratory-validated mNGS assay for pan-pathogen detection, to be used clinically for diagnosis of neurological infections from CSF.
Topics: Child; Computational Biology; Encephalitis; High-Throughput Nucleotide Sequencing; Humans; Meningitis, Aseptic; Metagenomics; Myelitis; Sensitivity and Specificity; Viruses
PubMed: 30992304
DOI: 10.1101/gr.238170.118 -
Virologie (Montrouge, France) Oct 2020Central nervous system (CNS) infections caused by herpes simplex viruses 1 (HSV-1) and 2 (HSV-2) greatly vary in frequency and severity. HSV-1 causes mostly herpes... (Review)
Review
Central nervous system (CNS) infections caused by herpes simplex viruses 1 (HSV-1) and 2 (HSV-2) greatly vary in frequency and severity. HSV-1 causes mostly herpes simplex encephalitis (HSE) which represents 5% to 15% of infectious encephalitis in children and adults. Despite available molecular diagnosis tools and antiviral drugs, the prognosis of HSE remains unacceptably low. In addition to mortality and immediate sequelae, auto-immune encephalitis (AIE) may occur, associated with the development of anti-neuronal antibodies in 1/4 of cases. Replicative relapses have been associated in few cases with genetic defects altering the innate immune response of neuronal cells. Herpetic meningitis is frequent, mostly associated with HSV-2 and genital herpes, sometimes recurrent and, mostly benign, except in immunocompromised individuals. Finally, exceptional cases of myelitis have been reported, due to ascending propagation of HSV-2 in the CNS. This review does not include neonatal infections.
Topics: Adult; Child; Encephalitis, Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Meningitis; Myelitis
PubMed: 33111702
DOI: 10.1684/vir.2020.0862 -
No Shinkei Geka. Neurological Surgery Sep 2022Viral central nervous system(CNS)infections due to direct viral infection in the CNS include encephalitis/myelitis and meningitis. Acute encephalopathy is a CNS disorder...
Viral central nervous system(CNS)infections due to direct viral infection in the CNS include encephalitis/myelitis and meningitis. Acute encephalopathy is a CNS disorder that is mainly associated with viral respiratory infections. This article outlines herpes encephalitis, poliomyelitis, enterovirus A71 brainstem encephalitis/myelitis, and enterovirus D68 paralytic myelitis as acute encephalitis/myelitis, enteroviral meningitis and mumps meningitis as acute viral meningitis, and influenza encephalopathy and HHV-6 encephalopathy as acute encephalopathy.
Topics: Encephalitis; Enterovirus Infections; Humans; Meningitis; Myelitis
PubMed: 36128809
DOI: 10.11477/mf.1436204653 -
Journal of Neuroimmunology Dec 2021The differential diagnosis for immune-mediated myelopathies is broad. Although clinical manifestations overlap, certain presentations are suggestive of a particular... (Review)
Review
The differential diagnosis for immune-mediated myelopathies is broad. Although clinical manifestations overlap, certain presentations are suggestive of a particular myelopathy etiology. Spine MRI lesion characteristics including the length and location, and the pattern of gadolinium enhancement, help narrow the differential diagnosis and exclude an extrinsic compressive cause. The discovery of specific antibodies that serve as biomarkers of myelitis such as aquaporin-4-IgG and myelin-oligodendrocyte -glycoprotein-IgG (MOG-IgG), has improved our understanding of myelitis pathophysiology and facilitated diagnosis. In this review we will focus on the pathophysiology, clinical presentation, imaging findings and treatment and outcomes of uncommon immune-mediated myelopathies.
Topics: Aquaporin 4; Autoantibodies; Biomarkers; Contrast Media; Diagnosis, Differential; Gadolinium; Humans; Magnetic Resonance Imaging; Myelitis; Rare Diseases
PubMed: 34715593
DOI: 10.1016/j.jneuroim.2021.577750 -
Seminars in Neurology Aug 2019Myelitis refers to inflammation of the spinal cord which can result in a spectrum of neurologic impairment. Infectious pathogens are an important etiologic category, and... (Review)
Review
Myelitis refers to inflammation of the spinal cord which can result in a spectrum of neurologic impairment. Infectious pathogens are an important etiologic category, and can result in myelitis through direct pathogenic effect or through immune-mediated parainfection; this review focuses on the former category. The spectrum of clinical manifestations is summarized and a diagnostic workup provided to aid clinicians in developing an approach to patients presenting with symptoms suggestive of infectious myelitis. This is followed by an overview of the important viral, bacterial, parasitic, and fungal causes of infectious myelitis. The typical presentations, diagnostic modalities, and treatment approaches are outlined for key pathogens culprit in infectious myelitis to allow clinicians to promptly recognize and diagnose specific infectious etiologies of myelitis.
Topics: Anti-Retroviral Agents; Central Nervous System Bacterial Infections; Central Nervous System Fungal Infections; HIV Infections; Humans; Myelitis; Spinal Cord
PubMed: 31533188
DOI: 10.1055/s-0039-1688923 -
Revue Neurologique 2019Infectious pathogens can directly affect the spinal cord or trigger autoimmune reactions, which may result in permanent damage to cord structures. The most common... (Review)
Review
Infectious pathogens can directly affect the spinal cord or trigger autoimmune reactions, which may result in permanent damage to cord structures. The most common aetiology comes from virus but depend on age, location of the patient and co-morbidities. Acute Flaccid paralysis and acute transverse myelitis are considered as emergencies. Differential diagnosis is mainly relapses of autoimmune diseases, which can mimic infectious myelopathies.
Topics: Humans; Myelitis
PubMed: 31375285
DOI: 10.1016/j.neurol.2019.07.001