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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 2013Transverse myelitis (TM) includes a pathobiologically heterogeneous syndrome characterized by acute or subacute spinal cord dysfunction resulting in paresis, a sensory... (Review)
Review
Transverse myelitis (TM) includes a pathobiologically heterogeneous syndrome characterized by acute or subacute spinal cord dysfunction resulting in paresis, a sensory level, and autonomic (bladder, bowel, and sexual) impairment below the level of the lesion. Etiologies for TM can be broadly classified as parainfectious, paraneoplastic, drug/toxin-induced, systemic autoimmune disorders, and acquired demyelinating diseases. We discuss the clinical evaluation, workup, and acute and long-term management of patients with TM. Additionally, we briefly discuss various disease entities that may cause TM and their salient distinguishing features, as well as disorders that may mimic TM.
Topics: History, 19th Century; History, 20th Century; History, 21st Century; Humans; Myelitis, Transverse; Spinal Cord
PubMed: 23186897
DOI: 10.1016/j.ncl.2012.09.008 -
Current Opinion in Neurology Jun 2014Varicella zoster virus (VZV) reactivation results in zoster, which may be complicated by postherpetic neuralgia, myelitis, meningoencephalitis, and VZV vasculopathy.... (Review)
Review
PURPOSE OF REVIEW
Varicella zoster virus (VZV) reactivation results in zoster, which may be complicated by postherpetic neuralgia, myelitis, meningoencephalitis, and VZV vasculopathy. This review highlights the clinical features, laboratory abnormalities, imaging changes, and optimal treatment of each of those conditions. Because all of these neurological disorders produced by VZV reactivation can occur in the absence of rash, the virological tests proving that VZV caused disease are discussed.
RECENT FINDINGS
After primary infection, VZV becomes latent in ganglionic neurons along the entire neuraxis. With a decline in VZV-specific cell-mediated immunity, VZV reactivates from ganglia and travels anterograde to the skin to cause zoster, which is often complicated by postherpetic neuralgia. VZV can also travel retrograde to produce meningoencephalitis, myelitis, and stroke. When these complications occur without rash, VZV-induced disease can be diagnosed by detection of VZV DNA or anti-VZV antibody in cerebrospinal fluid and treated with intravenous acyclovir.
SUMMARY
Awareness of the expanding spectrum of neurological complications caused by VZV reactivation with and without rash will improve diagnosis and treatment.
Topics: Acyclovir; Antibodies, Viral; Antiviral Agents; DNA, Viral; Encephalitis, Varicella Zoster; Herpes Zoster; Herpesvirus 3, Human; Humans; Myelitis; Neuralgia, Postherpetic; Vascular Diseases; Virus Latency
PubMed: 24792344
DOI: 10.1097/WCO.0000000000000092 -
Discovery Medicine Oct 2013Myelitis is a rare neurological disorder of the spinal cord that is caused by inflammation and can have devastating neurologic effects with up to two-thirds of patients... (Review)
Review
Myelitis is a rare neurological disorder of the spinal cord that is caused by inflammation and can have devastating neurologic effects with up to two-thirds of patients having a moderate to severe degree of residual disability. Symptoms typically develop over hours or days and then worsen over a matter of days to weeks. Patients can present with sensory alteration, weakness, and autonomic dysfunction including bowel and bladder problems, temperature dysregulation, or even bouts of hypertension. Evaluation for compressive etiologies must be a priority as compressive myelopathy and transverse myelitis are often clinically indistinguishable and emergent surgical intervention is indicated in such cases. However, if neuroimaging and CSF studies indicate inflammation within the central nervous system, then a work-up for myelitis must include autoimmune, inflammatory, and infectious etiologies. Acute management of these patients is dictated by which etiology is suspected and rapid initiation of that treatment portends a more favorable patient outcome. This review will discuss a practical clinical approach to the diagnosis and acute management of patients with myelitis including clinical symptoms, the role of neuroimaging, and the utility of both CSF and serological studies in the management of these patients.
Topics: Acute Disease; Humans; Myelitis, Transverse; Prognosis
PubMed: 24099672
DOI: No ID Found -
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 -
The New England Journal of Medicine Jun 2019Metagenomic next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has the potential to identify a broad range of pathogens in a single test.
BACKGROUND
Metagenomic next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has the potential to identify a broad range of pathogens in a single test.
METHODS
In a 1-year, multicenter, prospective study, we investigated the usefulness of metagenomic NGS of CSF for the diagnosis of infectious meningitis and encephalitis in hospitalized patients. All positive tests for pathogens on metagenomic NGS were confirmed by orthogonal laboratory testing. Physician feedback was elicited by teleconferences with a clinical microbial sequencing board and by surveys. Clinical effect was evaluated by retrospective chart review.
RESULTS
We enrolled 204 pediatric and adult patients at eight hospitals. Patients were severely ill: 48.5% had been admitted to the intensive care unit, and the 30-day mortality among all study patients was 11.3%. A total of 58 infections of the nervous system were diagnosed in 57 patients (27.9%). Among these 58 infections, metagenomic NGS identified 13 (22%) that were not identified by clinical testing at the source hospital. Among the remaining 45 infections (78%), metagenomic NGS made concurrent diagnoses in 19. Of the 26 infections not identified by metagenomic NGS, 11 were diagnosed by serologic testing only, 7 were diagnosed from tissue samples other than CSF, and 8 were negative on metagenomic NGS owing to low titers of pathogens in CSF. A total of 8 of 13 diagnoses made solely by metagenomic NGS had a likely clinical effect, with 7 of 13 guiding treatment.
CONCLUSIONS
Routine microbiologic testing is often insufficient to detect all neuroinvasive pathogens. In this study, metagenomic NGS of CSF obtained from patients with meningitis or encephalitis improved diagnosis of neurologic infections and provided actionable information in some cases. (Funded by the National Institutes of Health and others; PDAID ClinicalTrials.gov number, NCT02910037.).
Topics: Adolescent; Adult; Cerebrospinal Fluid; Child; Child, Preschool; Encephalitis; Female; Genome, Microbial; High-Throughput Nucleotide Sequencing; Humans; Infant; Infections; Length of Stay; Male; Meningitis; Meningoencephalitis; Metagenomics; Middle Aged; Myelitis; Prospective Studies; Sequence Analysis, DNA; Sequence Analysis, RNA; Young Adult
PubMed: 31189036
DOI: 10.1056/NEJMoa1803396 -
Revue Neurologique 2021The past two decades have been marked by three epidemics linked to emerging coronaviruses. The COVID-19 pandemic highlighted the existence of neurological manifestations... (Review)
Review
INTRODUCTION
The past two decades have been marked by three epidemics linked to emerging coronaviruses. The COVID-19 pandemic highlighted the existence of neurological manifestations associated with SARS-CoV-2 infection and raised the question of the neuropathogenicity of coronaviruses. The aim of this review was to summarize the current data about neurological manifestations and diseases linked to human coronaviruses.
MATERIAL AND METHODS
Articles have been identified by searches of PubMed and Google scholar up to September 25, 2020, using a combination of coronavirus and neurology search terms and adding relevant references in the articles.
RESULTS
We found five cohorts providing prevalence data of neurological symptoms among a total of 2533 hospitalized COVID-19 patients, and articles focusing on COVID-19 patients with neurological manifestations including a total of 580 patients. Neurological symptoms involved up to 73% of COVID-19 hospitalized patients, and were mostly headache, myalgias and impaired consciousness. Central nervous system (CNS) manifestations reported in COVID-19 were mostly non-specific encephalopathies that represented between 13% and 40% of all neurological manifestations; post-infectious syndromes including acute demyelinating encephalomyelitis (ADEM, n=13), acute necrotizing encephalopathy (ANE, n=4), Bickerstaff's encephalitis (n=5), generalized myoclonus (n=3) and acute transverse myelitis (n=7); other encephalitis including limbic encephalitis (n=9) and miscellaneous encephalitis with variable radiologic findings (n=26); acute cerebrovascular diseases including ischemic strokes (between 1.3% and 4.7% of COVID-19 patients), hemorrhagic strokes (n=17), cerebral venous thrombosis (n=8) and posterior reversible encephalopathy (n=5). Peripheral nervous system (PNS) manifestations reported in COVID-19 were the following: Guillain-Barré syndrome (n=31) and variants including Miller Fisher syndrome (n=3), polyneuritis cranialis (n=2) and facial diplegia (n=2); isolated oculomotor neuropathy (n=6); critical illness myopathy (n=6). Neuropathological studies in COVID-19 patients demonstrated different patterns of CNS damage, mostly ischemic and hemorrhagic changes with few cases of inflammatory injuries. Only one case suggested SARS-CoV-2 infiltration in endothelial and neural cells. We found 10 case reports or case series describing 22 patients with neurological manifestations associated with other human coronaviruses. Among them we found four MERS patients with ADEM or Bickerstaff's encephalitis, two SARS patients with encephalitis who had a positive SARS-CoV PCR in cerebrospinal fluid, five patients with ischemic strokes associated with SARS, eight MERS patients with critical illness neuromyopathy and one MERS patient with Guillain-Barré Syndrome. An autopsy study on SARS-CoV patients demonstrated the presence of the virus in the brain of eight patients.
CONCLUSION
The wide range of neurological manifestations and diseases associated with SARS-CoV-2 is consistent with multiple pathogenic pathways including post-infectious mechanisms, septic-associated encephalopathies, coagulopathy or endothelitis. There was no definite evidence to support direct neuropathogenicity of SARS-CoV-2.
Topics: Brain Diseases; COVID-19; Coronavirus Infections; Coronavirus OC43, Human; Female; Guillain-Barre Syndrome; Humans; Male; Middle East Respiratory Syndrome Coronavirus; Myelitis; Nervous System Diseases; SARS-CoV-2; Severe Acute Respiratory Syndrome; Stroke
PubMed: 33446327
DOI: 10.1016/j.neurol.2020.10.001 -
Neurology(R) Neuroimmunology &... Nov 2020To test the hypothesis that the intrathecal synthesis of free light chain kappa (FLC-k) can be used as a CSF biomarker to differentiate patients with myelitis due to...
OBJECTIVE
To test the hypothesis that the intrathecal synthesis of free light chain kappa (FLC-k) can be used as a CSF biomarker to differentiate patients with myelitis due to multiple sclerosis (MS), myelitis due to neuromyelitis optica spectrum disease (NMOSD), and noninflammatory myelopathy, we analyzed FLC-k in 26 patients with MS myelitis, 9 patients with NMOSD myelitis, and 14 patients with myelopathy.
METHODS
This is a retrospective monocentric cohort study. FLC-k were analyzed using the nephelometric Siemens FLC-k kit in paired samples of CSF and sera. Intrathecal fraction (IF) of FLC-k was plotted in a FLC-k quotient diagram.
RESULTS
Ninety-six percent of patients with MS myelitis had an intrathecal synthesis of FLC-k in comparison with 55.6% for NMOSD and 14.3% of patients with noninflammatory myelopathy. The locally synthesized absolute amount of FLC-k was significantly higher in patients with myelitis due to MS than in patients with NMOSD ( = 0.038) or noninflammatory myelopathy ( < 0.0001). The sensitivity of FLC-k synthesis to detect inflammation in patients with myelitis is 85.7%. Using a receiver operating characteristic analysis, FLC-k IF >78% can discriminate patients with myelitis due to MS and NMOSD with a sensitivity of 88.5% and a specificity of 88.9% CONCLUSIONS: With the hyperbolic reference range in quotient diagrams for FLC-k, it is possible to distinguish inflammatory myelitis from noninflammatory myelopathies. An FLC-k IF >78% can be a hint to suspect myelitis due to MS rather than NMOSD.
Topics: Adult; Aged; Biomarkers; Demyelinating Autoimmune Diseases, CNS; Female; Humans; Immunoglobulin kappa-Chains; Male; Middle Aged; Myelitis; Retrospective Studies; Spinal Cord Diseases
PubMed: 32948648
DOI: 10.1212/NXI.0000000000000892 -
The Veterinary Clinics of North... Jul 1992Animals with meningomyelitis have clinical neurologic signs that typically range from paraspinal discomfort to tetraplegia; however, most affected animals also show... (Review)
Review
Animals with meningomyelitis have clinical neurologic signs that typically range from paraspinal discomfort to tetraplegia; however, most affected animals also show evidence of multifocal CNS involvement with brain stem and cerebral cortical structures being affected most commonly. The cause, duration, and host response to the disease process will determine the clinical signs in individual animals. Confirmation of a specific causative agent is difficult, but CSF analysis and immunotesting of serum and CSF yield the most rewarding diagnostic results. Successful treatment is based on formulation of an appropriate and aggressive therapeutic regimen. In some diseases, no effective treatment is available, and some animals may develop permanent neurologic disabilities.
Topics: Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Meningitis; Myelitis
PubMed: 1641927
DOI: 10.1016/s0195-5616(92)50086-9 -
Pediatric Annals Dec 2022
Topics: Humans; Enterovirus D, Human; Enterovirus; Myelitis; Neuromuscular Diseases
PubMed: 36476202
DOI: 10.3928/19382359-20221107-01