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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 -
CMAJ : Canadian Medical Association... Nov 2022
Topics: Humans; Poliomyelitis; Disease Eradication
PubMed: 36379554
DOI: 10.1503/cmaj.221320 -
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 -
Neurologia Jun 2022Patients presenting sequelae of poliomyelitis may present new symptoms, known as post-polio syndrome (PPS).
INTRODUCTION
Patients presenting sequelae of poliomyelitis may present new symptoms, known as post-polio syndrome (PPS).
OBJECTIVE
To identify the clinical and functional profile and epidemiological characteristics of patients presenting PPS.
PATIENTS AND METHODS
We performed a retrospective study of 400 patients with poliomyelitis attended at the Institut Guttmann outpatient clinic, of whom 310 were diagnosed with PPS. We describe patients' epidemiological, clinical, and electromyographic variables and analyse the relationships between age of poliomyelitis onset and severity of the disease, and between sex, age of PPS onset, and the frequency of symptoms.
RESULTS
PPS was more frequent in women (57.7%). The mean age at symptom onset was 52.4 years, and was earlier in women. Age at primary infection > 2 years was not related to greater poliomyelitis severity. The frequency of symptoms was: pain in 85% of patients, loss of strength in 40%, fatigue in 65.5%, tiredness in 57.8%, cold intolerance in 20.2%, dysphagia in 11.7%, cognitive complaints in 9%, and depressive symptoms in 31.5%. Fatigue, tiredness, depression, and cognitive complaints were significantly more frequent in women. Fifty-nine percent of patients presented electromyographic findings suggestive of PPS.
CONCLUSIONS
While the symptoms observed in our sample are similar to those reported in the literature, the frequencies observed are not. We believe that patients' clinical profile may be very diverse, giving more weight to such objective parameters as worsening of symptoms or appearance of weakness; analysis of biomarkers may bring us closer to an accurate diagnosis.
Topics: Disease Progression; Fatigue; Female; Humans; Poliomyelitis; Postpoliomyelitis Syndrome; Retrospective Studies
PubMed: 35672121
DOI: 10.1016/j.nrleng.2019.03.023 -
Pharmacology & Therapeutics Jul 2019Clioquinol, one of the first mass-produced drugs, was considered safe and efficacious for many years. It was used as an antifungal and an antiprotozoal drug until it was... (Review)
Review
Clioquinol, one of the first mass-produced drugs, was considered safe and efficacious for many years. It was used as an antifungal and an antiprotozoal drug until it was linked to an outbreak of subacute myelo-optic neuropathy (SMON), a debilitating disease almost exclusively confined to Japan. Today, new information regarding clioquinol targets and its mechanism of action, as well as genetic variation (SNPs) in efflux transporters in the Japanese population, provide a unique interpretation of the existing phenomena. Further understanding of clioquinol's role in the inhibition of cAMP efflux and promoting apoptosis might offer promise for the treatment of cancer and/or neurodegenerative diseases. Here, we highlight recent developments in the field and discuss possible connections, hypotheses and perspectives in clioquinol-related research.
Topics: ATP-Binding Cassette Transporters; Animals; Anti-Infective Agents; Asian People; Clioquinol; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Humans; Myelitis; Neoplasms; Neurodegenerative Diseases; Optic Neuritis; Polymorphism, Single Nucleotide; Syndrome
PubMed: 30898518
DOI: 10.1016/j.pharmthera.2019.03.009 -
MMW Fortschritte Der Medizin May 2023
Topics: Humans; Measles; Poliomyelitis; Vaccination
PubMed: 37202671
DOI: 10.1007/s15006-023-2674-9 -
CMAJ : Canadian Medical Association... Feb 2023
Topics: Humans; Poliomyelitis
PubMed: 36781198
DOI: 10.1503/cmaj.221320-f -
Pediatric Annals Dec 2022
Topics: Humans; Enterovirus D, Human; Enterovirus; Myelitis; Neuromuscular Diseases
PubMed: 36476202
DOI: 10.3928/19382359-20221107-01 -
European Journal of Pediatrics Sep 2019Acute flaccid myelitis is characterized by the combination of acute flaccid paralysis and a spinal cord lesion largely restricted to the gray matter on magnetic... (Review)
Review
Acute flaccid myelitis is characterized by the combination of acute flaccid paralysis and a spinal cord lesion largely restricted to the gray matter on magnetic resonance imaging. The term acute flaccid myelitis was introduced in 2014 after the upsurge of pediatric cases in the USA with enterovirus D68 infection. Since then, an increasing number of cases have been reported worldwide. Whereas the terminology is new, the clinical syndrome has been recognized in the past in association with several other neurotropic viruses such as poliovirus.Conclusion: This review presents the current knowledge on acute flaccid myelitis with respect to the clinical presentation and its differential diagnosis with Guillain-Barré syndrome and acute transverse myelitis. We also discuss the association with enterovirus D68 and the presumed pathophysiological mechanism of this infection causing anterior horn cell damage. Sharing clinical knowledge and insights from basic research is needed to make progress in diagnosis, treatment, and prevention of this new polio-like disease. What is Known: • Acute flaccid myelitis (AFM) is a polio-like condition characterized by rapid progressive asymmetric weakness, together with specific findings on MRI • AFM has been related to different viral agents, but recent outbreaks are predominantly associated with enterovirus D68. What is New: • Improving knowledge on AFM must increase early recognition and adequate diagnostic procedures by clinicians. • The increasing incidence of AFM urges cooperation between pediatricians, neurologists, and microbiologists for the development of treatment and preventive options.
Topics: Central Nervous System Viral Diseases; Diagnosis, Differential; Enterovirus D, Human; Enterovirus Infections; Global Health; Guillain-Barre Syndrome; Humans; Myelitis; Myelitis, Transverse; Neuromuscular Diseases; Prognosis
PubMed: 31338675
DOI: 10.1007/s00431-019-03435-3