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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 -
Neurological Sciences : Official... Sep 2022Prospective studies regarding tuberculous myelitis are lacking. We aimed to prospectively evaluate patients with tuberculous myelitis to identify the features that...
BACKGROUND
Prospective studies regarding tuberculous myelitis are lacking. We aimed to prospectively evaluate patients with tuberculous myelitis to identify the features that distinguish tuberculous myelitis from other myelitis.
METHODS
This was a prospective study. Patients presenting with paraparesis/quadriparesis, and MRI showing myelitis were included. All patients were subjected to clinical, neuroimaging, and laboratory evaluation. Diagnosis of definite tuberculous myelitis was made if GeneXpert test in CSF was positive. Probable tuberculous myelitis was diagnosed if there was evidence of tuberculosis elsewhere in the body. Patients were treated with methylprednisolone and antituberculosis treatment. Patients were followed for 6 months. We compared the clinical, laboratory, and neuroimaging parameters and response to treatment of tuberculous myelitis with other myelitis. P values were adjusted using the Benjamini-Hochberg (BH) procedure to control false discovery rate.
RESULTS
We enrolled 52 patients. Eighteen (34.6%) patients had tuberculous myelitis. Headache (P = 0.018) was significantly more common in tuberculous myelitis. The CSF protein (P < 0.001), and CSF cell count (P < 0.001) were significantly higher in tuberculous myelitis. On neuroimaging, a LETM was common in tuberculous myelitis. Spinal meningeal enhancement (14; 77.8%), extra-axial collection, and CSF loculation (6; 33.4%), arachnoiditis (3;16.7%), and concomitant spinal tuberculoma (2;11.1%) were other common imaging features of tuberculous myelitis. Tuberculous myelitis patients showed a better response (P = 0.025) to treatment.
CONCLUSION
Tuberculous myelitis was seen in approximately 35% of all myelitis cases, in a high tuberculosis endemic zone. Headache, markedly elevated CSF protein and spinal meningeal enhancement were distinguishing features. Tuberculous myelitis patients responded well to corticosteroids.
Topics: Follow-Up Studies; Headache; Humans; Magnetic Resonance Imaging; Myelitis; Prospective Studies; Tuberculosis, Meningeal
PubMed: 35739331
DOI: 10.1007/s10072-022-06221-6 -
Pathology Dec 2023Enterovirus D68 (EV-D68) is one of hundreds of non-polio enteroviruses that typically cause cold-like respiratory illness. The first EV-D68 outbreak in the United States... (Review)
Review
Enterovirus D68 (EV-D68) is one of hundreds of non-polio enteroviruses that typically cause cold-like respiratory illness. The first EV-D68 outbreak in the United States in 2014 aroused widespread concern among the public and health authorities. The infection was found to be associated with increased surveillance of acute flaccid myelitis, a neurological condition that causes limb paralysis in conjunction with spinal cord inflammation. In vitro studies utilising two-dimensional (2D) and three-dimensional (3D) culture systems have been employed to elucidate the pathogenic mechanism of EV-D68. Various animal models have also been developed to investigate viral tropism and distribution, pathogenesis, and immune responses during EV-D68 infection. EV-D68 infections have primarily been investigated in respiratory, intestinal and neural cell lines/tissues, as well as in small-size immunocompetent rodent models that were limited to a young age. Some studies have implemented strategies to overcome the barriers by using immunodeficient mice or virus adaptation. Although the existing models may not fully recapitulate both respiratory and neurological disease observed in human EV-D68 infection, they have been valuable for studying pathogenesis and evaluating potential vaccine or therapeutic candidates. In this review, we summarise the methodologies and findings from each experimental model and discuss their applications and limitations.
Topics: Humans; Animals; United States; Mice; Enterovirus D, Human; Neuromuscular Diseases; Myelitis; Paralysis; Enterovirus Infections
PubMed: 37852802
DOI: 10.1016/j.pathol.2023.08.007 -
Reumatologia Clinica 2017Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple systems. Myelopathy is one of 19 neuropsychiatric syndromes related to SLE... (Review)
Review
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple systems. Myelopathy is one of 19 neuropsychiatric syndromes related to SLE defined by the American College of Rheumatology. Although infrequent, it is a severe manifestation, leading to motor and sensory deficits, and sphincter dysfunction. The pathogenesis is not clearly known, but may be related to arterial thrombosis and vasculitis. Diagnosis is based on clinical findings, laboratory tests and the use of gadolinium-enhanced magnetic resonance imaging. The standard therapy is the combination of intravenous cyclophosphamide and glucocorticoids. In refractory disease, other treatments such as plasmapheresis or rituximab have been used.
Topics: Combined Modality Therapy; Cyclophosphamide; Diagnosis, Differential; Female; Glucocorticoids; Gray Matter; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Myelitis; Neuromyelitis Optica; Plasmapheresis; Practice Guidelines as Topic; Prognosis; Rituximab; White Matter
PubMed: 27567298
DOI: 10.1016/j.reuma.2016.06.004 -
Pediatric Annals Dec 2022
Topics: Humans; Enterovirus D, Human; Enterovirus; Myelitis; Neuromuscular Diseases
PubMed: 36476202
DOI: 10.3928/19382359-20221107-01 -
The Lancet. Infectious Diseases Aug 2018Increased circulation of enterovirus D68 in 2014 and 2016 temporally and geographically coincided with increases in cases of acute flaccid myelitis, an uncommon... (Review)
Review
Increased circulation of enterovirus D68 in 2014 and 2016 temporally and geographically coincided with increases in cases of acute flaccid myelitis, an uncommon condition of paralysis due to lesions in the anterior horn of the spinal cord. The identification of enterovirus D68 in respiratory specimens from cases of acute flaccid myelitis worldwide further supports an association, yet the absence of direct virus isolation from affected tissues, infrequent detection in cerebrospinal fluid, and the absence, until recently, of an animal model has left the causal nature of the relationship unproven. In this Personal View we evaluate epidemiological and biological evidence linking enterovirus D68 and acute flaccid myelitis. We applied the Bradford Hill criteria to investigate the evidence for a causal relationship and highlight the importance of comprehensive surveillance and research to further characterise the role of enterovirus D68 in acute flaccid myelitis and pursue effective therapies and prevention strategies.
Topics: Central Nervous System Viral Diseases; Disease Outbreaks; Enterovirus D, Human; Enterovirus Infections; Humans; Myelitis; Neuromuscular Diseases; Paralysis
PubMed: 29482893
DOI: 10.1016/S1473-3099(18)30094-X -
BMJ Case Reports Mar 2023Transverse myelitis is an extremely rare neuroinflammatory disorder. About half of the affected patients develop paraplegia associated with urinary and bowel...
Transverse myelitis is an extremely rare neuroinflammatory disorder. About half of the affected patients develop paraplegia associated with urinary and bowel dysfunction. The bowel dysfunction is thought to be benign and is usually managed with dietary management and laxatives. We report a case of a man in his 60s presenting with transverse myelitis and the acute disease course complicated with treatment refractory intestinal dysfunction resulting in intestinal perforation, eventually leading to his death. Thus, this case helps us weigh the fact that intestinal dysfunction in the case of transverse myelitis is not always benign but can lead to deadly outcomes as well.
Topics: Male; Humans; Myelitis, Transverse; Constipation; Laxatives; Disease Progression; Intestinal Perforation
PubMed: 36878618
DOI: 10.1136/bcr-2022-254409 -
Neurologic Clinics Aug 2008Meningitis and myelitis represent common and very infrequent viral infections of the central nervous system, respectively. The number of cases of viral meningitis that... (Review)
Review
Meningitis and myelitis represent common and very infrequent viral infections of the central nervous system, respectively. The number of cases of viral meningitis that occurs annually exceeds the total number of meningitis cases caused by all other etiologies combined. Focal central nervous system infections, such as occur in the spinal cord with viral myelitis, are much less common and may be confused with noninfectious disorders that cause acute flaccid paralysis. This article reviews some of the important clinical features, epidemiology, diagnostic approaches, and management strategies for patients with aseptic meningitis and viral myelitis. Particular focus is placed on the diseases caused by enteroviruses, which as a group account for most aseptic meningitis cases and many focal infections of the spinal cord.
Topics: Diagnosis, Differential; Herpesviridae Infections; Humans; Immunoglobulins, Intravenous; Incidence; Meningitis, Aseptic; Mumps; Myelitis; Prevalence; RNA, Viral
PubMed: 18657719
DOI: 10.1016/j.ncl.2008.03.003 -
Handbook of Clinical Neurology 2014Inflammatory injury to the spinal cord causes a well-recognized clinical syndrome. Patients typically develop bilateral weakness, usually involving the legs, although... (Review)
Review
Inflammatory injury to the spinal cord causes a well-recognized clinical syndrome. Patients typically develop bilateral weakness, usually involving the legs, although the arms may also become affected, in association with a pattern of sensory changes that suggests a spinal cord dermatomal level. Bowel and bladder impairment is also common in many patients. Recognition of the clinical pattern of spinal cord injury should lead clinicians to perform imaging studies to evaluate for compressive etiologies. MRI of the spine is particularly useful in helping visualize intraparenchymal lesions and when these lesions enhance following contrast administration a diagnosis of myelitis is made. Cerebrospinal fluid analysis can also confirm a diagnosis of myelitis when a leukocytosis is present. There are many causes of non-compressive spinal cord injury including infectious, parainfectious, toxic, nutritional, vascular, systemic as well as idiopathic inflammatory etiologies. This review focuses on inflammatory spinal cord injury and its relationships with multiple sclerosis, neuromyelitis optica, acute disseminated encephalomyelitis and systemic collagen vascular and paraneoplastic diseases.
Topics: Acute Disease; Animals; Diagnosis, Differential; Disease Progression; Humans; Multiple Sclerosis; Myelitis; Secondary Prevention
PubMed: 24507538
DOI: 10.1016/B978-0-444-52001-2.00027-3 -
MBio Apr 2019Since 2014, acute flaccid myelitis (AFM), a long-recognized condition associated with polioviruses, nonpolio enteroviruses, and various other viral and nonviral causes,... (Review)
Review
Since 2014, acute flaccid myelitis (AFM), a long-recognized condition associated with polioviruses, nonpolio enteroviruses, and various other viral and nonviral causes, has been reemerging globally in epidemic form. This unanticipated reemergence is ironic, given that polioviruses, once the major causes of AFM, are now at the very threshold of global eradication and cannot therefore explain any aspect of AFM reemergence. Instead, the new AFM epidemic has been temporally associated with reemergences of nonpolio enteroviruses such as EV-D68, until recently thought to be an obscure virus of extremely low endemicity. This perspective reviews the enigmatic epidemiologic, virologic, and diagnostic aspects of epidemic AFM reemergence; examines current options for clinical management; discusses future research needs; and suggests that the AFM epidemic offers important clues to mechanisms of viral disease emergence.
Topics: Central Nervous System Viral Diseases; Communicable Diseases, Emerging; Disease Management; Global Health; Humans; Myelitis; Neuromuscular Diseases
PubMed: 30940708
DOI: 10.1128/mBio.00521-19