Showing papers on "Myelitis published in 2015"

Short Myelitis Lesions in Aquaporin-4-IgG–Positive Neuromyelitis Optica Spectrum Disorders

Abstract: Importance Short transverse myelitis (STM; Objectives To determine the frequency of short lesions at the initial myelitis manifestation of NMOSD and to compare the demographic, clinical, and radiological characteristics of aquaporin-4-IgG (AQP4-IgG) seropositive and seronegative STM. Design, Setting, and Participants We reviewed the records and images of patients at the Mayo Clinic who were identified as AQP4-IgG positive from 1996 to 2014. Inclusion criteria were first STM episode, magnetic resonance imaging performed 90 days or less from symptom onset, spinal cord T2-hyperintense lesion less than 3 vertebral segments, AQP4-IgG seropositivity, and a final diagnosis of NMO or NMOSD. Patients with an initial longitudinally extensive transverse myelitis were excluded (n = 151). Patients with STM who were seronegative for AQP4-IgG among an Olmsted County population–based cohort of inflammatory demyelinating disorders of the central nervous system were used as a control group. Main Outcomes and Measures Delay to diagnosis in months, clinical and radiological characteristics, and disability measured by ambulatory status. Results Twenty-five patients who were AQP4-IgG seropositive with an initial STM represented 14% of initial myelitis episodes among patients with NMOSD. The STM episode was defined as the first manifestation of NMOSD in 10 patients (40%) preceded by optic neuritis in 13 patients (52%) and preceded by a nausea and vomiting episode in 2 patients (8%). In comparison with the excluded patients with NMOSD who had an initial longitudinally extensive transverse myelitis, delay to diagnosis/treatment was greater when initial lesions were short ( P = .02). In AQP4-IgG–positive STM cases, subsequent myelitis episodes were longitudinally extensive in 92%. Attributes more common in patients with AQP4-IgG–positive STM than in 27 population-based patients with AQP4-IgG–negative STM included the following: nonwhite race/ethnicity; tonic spasms; coexisting autoimmunity; magnetic resonance imaging (central cord lesions, T1 hypointensity, and a brain inconsistent with multiple sclerosis); and cerebrospinal fluid (oligoclonal bands lacking). Conclusions and Relevance Short transverse myelitis is not uncommon in NMOSD and, when it is present, delays diagnosis and treatment. Clinical and radiological characteristics identified in this study may help select patients with STM who are at the highest risk for an NMOSD. Short transverse myelitis does not exclude consideration of AQP4-IgG testing or NMOSD diagnosis.

Acute Flaccid Myelitis of Unknown Etiology in California, 2012-2015

Abstract: Importance There has been limited surveillance for acute flaccid paralysis in North America since the regional eradication of poliovirus. In 2012, the California Department of Public Health received several reports of acute flaccid paralysis cases of unknown etiology. Objective To quantify disease incidence and identify potential etiologies of acute flaccid paralysis cases with evidence of spinal motor neuron injury. Design, Setting, and Participants Case series of acute flaccid paralysis in patients with radiological or neurophysiological findings suggestive of spinal motor neuron involvement reported to the California Department of Public Health with symptom onset between June 2012 and July 2015. Patients meeting diagnostic criteria for other acute flaccid paralysis etiologies were excluded. Cerebrospinal fluid, serum samples, nasopharyngeal swab specimens, and stool specimens were submitted to the state laboratory for infectious agent testing. Main Outcomes and Measures Case incidence and infectious agent association. Results Fifty-nine cases were identified. Median age was 9 years (interquartile range [IQR], 4-14 years; 50 of the cases were younger than 21 years). Symptoms that preceded or were concurrent included respiratory or gastrointestinal illness (n = 54), fever (n = 47), and limb myalgia (n = 41). Fifty-six patients had T2 hyperintensity of spinal gray matter on magnetic resonance imaging and 43 patients had cerebrospinal fluid pleocytosis. During the course of the initial hospitalization, 42 patients received intravenous steroids; 43, intravenous immunoglobulin; and 13, plasma exchange; or a combination of these treatments. Among 45 patients with follow-up data, 38 had persistent weakness at a median follow-up of 9 months (IQR, 3-12 months). Two patients, both immunocompromised adults, died within 60 days of symptom onset. Enteroviruses were the most frequently detected pathogen in either nasopharynx swab specimens, stool specimens, serum samples (15 of 45 patients tested). No pathogens were isolated from the cerebrospinal fluid. The incidence of reported cases was significantly higher during a national enterovirus D68 outbreak occurring from August 2014 through January 2015 (0.16 cases per 100 000 person-years) compared with other monitoring periods (0.028 cases per 100 000 person-years;P Conclusions and Relevance In this series of patients identified in California from June 2012 through July 2015, clinical manifestations indicated a rare but distinct syndrome of acute flaccid paralysis with evidence of spinal motor neuron involvement. The etiology remains undetermined, most patients were children and young adults, and motor weakness was prolonged.

Anti-MOG antibodies are frequently associated with steroid-sensitive recurrent optic neuritis

Abstract: Optic neuritis (ON) is an inflammatory disease of the optic nerve characterized by pain and visual loss and often associated with multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMOSD). Recent evidence suggests that certain forms of ON are associated with anti–myelin oligodendrocyte glycoprotein (MOG) antibodies.1,–4 A distinct clinical subset of ON is characterized by multiple episodes that involve one or both optic nerves, occur within months or weeks, and do not involve any other associated clinical or radiologic findings. This entity, defined as either recurrent optic neuritis (rON) or chronic relapsing inflammatory optic neuritis (CRION),5 is typically corticosteroid-responsive and corticosteroid-dependent, often requiring immunosuppressive therapy for corticosteroid-sparing effect. Our aim was to determine whether aquaporin-4 (AQP4)-negative patients with ON harbor antibodies to MOG and whether anti-MOG antibodies are clinically relevant. Methods. We examined sera from 111 patients initially referred to our diagnostic service for AQP4 testing. These patients had at least one episode of unilateral or bilateral ON, as reported by their referring physicians. All 111 patients were APQ4-negative. Twelve patients with primary progressive MS and 30 patients with relapsing-remitting MS (RRMS) were used as disease controls. The Ethics Committee of the University of Athens granted ethical approval. Anti-MOG screening was performed using a cell-based-assay (CBA). Patient sera (1:60 dilution) were applied on live human embryonic kidney 293T cells and transiently transfected with full-length MOG enhanced green fluorescent protein followed by a goat anti-human secondary antibody (Alexa Fluor 568). Positive samples were retested and titrated in a blinded fashion by M.R. To investigate optic nerve specificity, anti-MOG–positive sera were applied onto 10 μm nonfixed or 2% paraformaldehyde-fixed sections of fresh frozen human optic nerves (Netherlands Brain Bank, Amsterdam). A commercial monoclonal anti-MOG antibody was used as a positive control (Millipore, Billerica, MA; clone 8–18C5). Results. Anti-MOG antibodies were detected by CBA in 8/111 AQP4-seronegative patients and in 0/42 MS disease controls (figure 1, B–D). All 8 MOG-positive patients had at least one episode of ON, and 5 of them fulfilled the criteria for rON/CRION (defined as ≥3 episodes of ON within a period of a few months to a year). Fifteen of 30 patients with RRMS had at least one episode of ON, and 10 of the 15 had a relapsing ON course. Figure 1 Clinical characteristics and antibody profile of patients The 5 patients with rON/CRION (followed by M.C.D. for 2–11 years) had recurrent disease confined to optic nerves, often associated with or preceded by pain. Brain/orbital MRI or CSF analyses were normal except for optic nerve enhancement in 2 patients. Spinal MRI depicted one small subclinical chronic lesion in the cervical spine in one of the patients who never developed any clinical symptoms of myelitis. Antibody titers did not correlate with disease severity or number of relapses (figure 1A). All received IV steroids during the early attacks, but they were subsequently maintained on a low-dose oral regimen. In 2 patients, the attacks occurred very frequently when the oral corticosteroid dose was lowered below 15–20 mg every other day, necessitating the concurrent administration of an immunosuppressant such as mycophenolate mofetil. One patient with multiple episodes over many years who eventually developed optic atrophy in one eye also received rituximab without success; relative stability (only 1 or 2 episodes yearly) was induced by bimonthly plasmapheresis (figure e-1 at Neurology.org/nn). As human MOG antibodies do not recognize paraffin-fixed denaturated epitopes,6 we used fresh-frozen, nonfixed, or lightly fixed human optic nerve tissue as substrate. No specific binding of the patients' sera or IgG was observed (figure e-2A). Discussion. We have characterized and longitudinally followed up 5/8 patients with anti-MOG–positive rON/CRION without spinal cord or brain symptomatology These patients do not fall within the rubric of NMOSD, and our follow-up revealed that relapses were confined to the optic nerves and were highly sensitive to even low doses of oral corticosteroids. Our results confirm recent observations3,4 that anti-MOG antibodies are frequently associated with recurrent forms of ON. Anti-MOG antibodies have also been associated with pediatric inflammatory demyelinating diseases, including acute disseminated encephalomyelitis.7 A comparative epitope mapping of MOG antibodies from different syndromes identified a dominant MOG epitope but failed to elucidate a causative relationship or define distinct clinical phenotypes.6 No binding of patients' sera was observed in our optic nerve preparations, in which native epitopes are preserved. Whether the rON-associated anti-MOG antibodies are pathogenic, causing conduction block in the optic nerve, demyelination, or edema, remains unclear. Our observations suggest that anti-MOG antibodies are frequently associated with the rON/CRION phenotype, which is a highly steroid-responsive disorder. Although the rON series is small, the finding is supported by the observation that all of the RRMS control patients with ON were MOG-seronegative.

Two cases of acute severe flaccid myelitis associated with enterovirus D68 infection in children, Norway, autumn 2014

Abstract: Enterovirus D68 (EV-D68), phylogenetic clade B was identified in nasopharyngeal specimens of two cases of severe acute flaccid myelitis. The cases were six and five years-old and occurred in September and November 2014. EV-D68 is increasingly associated with acute flaccid myelitis in children, most cases being reported in the United States. Awareness of this possible neurological complication of enterovirus D68 infection is needed.

Inflammation in the Pathogenesis of Lyme Neuroborreliosis

Abstract: Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, affects both peripheral and central nervous systems. We assessed a causal role for inflammation in Lyme neuroborreliosis pathogenesis by evaluating the induced inflammatory changes in the central nervous system, spinal nerves, and dorsal root ganglia (DRG) of rhesus macaques that were inoculated intrathecally with live B. burgdorferi and either treated with dexamethasone or meloxicam (anti-inflammatory drugs) or left untreated. ELISA of cerebrospinal fluid showed significantly elevated levels of IL-6, IL-8, chemokine ligand 2, and CXCL13 and pleocytosis in all infected animals, except dexamethasone-treated animals. Cerebrospinal fluid and central nervous system tissues of infected animals were culture positive for B. burgdorferi regardless of treatment. B. burgdorferi antigen was detected in the DRG and dorsal roots by immunofluorescence staining and confocal microscopy. Histopathology revealed leptomeningitis, vasculitis, and focal inflammation in the central nervous system; necrotizing focal myelitis in the cervical spinal cord; radiculitis; neuritis and demyelination in the spinal roots; and inflammation with neurodegeneration in the DRG that was concomitant with significant neuronal and satellite glial cell apoptosis. These changes were absent in the dexamethasone-treated animals. Electromyography revealed persistent abnormalities in F-wave chronodispersion in nerve roots of a few infected animals; which were absent in dexamethasone-treated animals. These results suggest that inflammation has a causal role in the pathogenesis of acute Lyme neuroborreliosis.

Systemic lupus erythematosus-associated acute transverse myelitis: manifestations, treatments, outcomes, and prognostic factors in 20 patients

Abstract: Background: Transverse myelitis is a rare complication of systemic lupus erythematosus (SLE). This retrospective multicentre study identifies the prognostic factors in a relatively large patient series. Patients and methods: Twenty patients fulfilled the SLE criteria of the ACR classification and the Transverse Myelitis Consortium Working Group. A severe neurological flare was defined as muscle strength grade <3/5 in more than half the muscle groups at the motor neurological level. Inability to run or another significant ambulation-unrelated disability was considered as ‘unfavourable neurological outcome’. Results: Myelitis was the first SLE symptom in 12 patients; in the eight others, it occurred 8.6 years (median delay) after SLE onset. Eleven patients presented severe neurological impairments. The treatment included corticosteroids in all patients associated with intravenous cyclophosphamide in 11 and/or hydroxychloroquine in 14. Unfavourable outcomes were observed in 53% of the patients at six months and in 28% at end of follow-up (median: 5.9 years). An initial severe neurological impairment and no cyclophosphamide use were associated with unfavourable neurological outcomes at six months and at end of follow-up, respectively. Conclusion: Transverse myelitis may reveal SLE or occur more than 10 years after SLE diagnosis. The initial severity of the neurological flare (with paraplegia) is the main prognostic marker. The study provides arguments for cyclophosphamide use. Lupus (2015) 24, 74–81.

Frequent involvement of central nervous system in primary Sjögren syndrome

Abstract: Primary Sjogren syndrome (pSS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the salivary and tear glands, and autoantibody secretion, in the absence of other systemic autoimmune disorder. Among autoimmune diseases, it is a relatively common disease, but the burden of central nervous system (CNS) involvement is controversial. This retrospective study evaluates the prevalence, clinical patterns and outcomes of CNS involvement in a cohort of patients with primary Sjogren syndrome. We evaluated 93 patients with pSS diagnosed according to American-European Consensus Group criteria. Fourteen patients (15.1 %) had CNS involvement. All were women with an average age of onset of the disease of 42.1 ± 14.7 years (average ± SD) and an average age of onset of neurological involvement of 47.29 ± 16 years. Three had parkinsonian syndrome, two epilepsy, two motor and sensory deficits, two headache with brain magnetic resonance abnormalities, two neuromyelitis optica, two chronic progressive myelitis and one aseptic meningitis. Neurological involvement preceded Sjogren syndrome diagnosis in nine of the patients (64 %), and neurological outcome was good in 11 patients (78.6 %). Central nervous involvement was not as rare as expected, and the frequency was similar to the frequency of peripheral nervous system involvement. In half of the patients, this was the first symptom of the disease, emphasizing the importance of considering this diagnosis, especially in young female with neurological symptoms without other evident cause.

Spinal cord involvement in tuberculous meningitis.

Abstract: To summarize the incidence and spectrum of spinal cord-related complications in patients of tuberculous meningitis. Reports from multiple countries were included. An extensive review of the literature, published in English, was carried out using Scopus, PubMed and Google Scholar databases. Tuberculous meningitis frequently affects the spinal cord and nerve roots. Initial evidence of spinal cord involvement came from post-mortem examination. Subsequent advancement in neuroimaging like conventional lumbar myelography, computed tomographic myelography and gadolinium-enhanced magnetic resonance-myelography have contributed immensely. Spinal involvement manifests in several forms, like tuberculous radiculomyelitis, spinal tuberculoma, myelitis, syringomyelia, vertebral tuberculosis and very rarely spinal tuberculous abscess. Frequently, tuberculous spinal arachnoiditis develops paradoxically. Infrequently, spinal cord involvement may even be asymptomatic. Spinal cord and spinal nerve involvement is demonstrated by diffuse enhancement of cord parenchyma, nerve roots and meninges on contrast-enhanced magnetic resonance imaging. High cerebrospinal fluid protein content is often a risk factor for arachnoiditis. The most important differential diagnosis of tuberculous arachnoiditis is meningeal carcinomatosis. Anti-tuberculosis therapy is the main stay of treatment for tuberculous meningitis. Higher doses of corticosteroids have been found effective. Surgery should be considered only when pathological confirmation is needed or there is significant spinal cord compression. The outcome in these patients has been unpredictable. Some reports observed excellent recovery and some reported unfavorable outcomes after surgical decompression and debridement. Tuberculous meningitis is frequently associated with disabling spinal cord and radicular complications. Available treatment options are far from satisfactory.

Acute idiopathic transverse myelitis in children: early predictors of relapse and disability

Abstract: Objective: To identify early prognostic factors of relapse and disability in children presenting with an acute idiopathic transverse myelitis (TM). Methods: Ninety-five children with acute idiopathic TM from 2 national European cohorts (France and United Kingdom) of CNS demyelinating diseases in children were identified and studied for early factors that predict relapse and disability using logistic regression models. Results: Sixteen (17%) relapsed, with a diagnosis of multiple sclerosis in 13 (14%) and neuromyelitis optica in 3 (3%). Logistic regression revealed 2 main criteria as risk factors for relapse: female sex (odds ratio [OR] 3.21, 95% confidence interval [CI] 0.88–11.78) and presence of associated brain lesions (OR 14.0, 95% CI 2.8–69.3). Twenty-eight (30%) children had a poor outcome defined by a Kurtzke Expanded Disability Status Scale score ≥4 or an American Spinal Injury Association impairment (ASIA) scale Conclusions Early predictors of relapse and disability identified in this large childhood study of acute idiopathic TM have important utility for clinical management. Larger prospective collaborative studies are required to validate these findings, which may improve the design of clinical trials.

Very late-onset neuromyelitis optica spectrum disorder beyond the age of 75

Abstract: Aquaporin-4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorder (NMOSD) is a rare but often severe autoimmune disease with median onset around 40 years of age. We report characteristics of three very-late-onset NMOSD (including complete NMO) patients >75 years of age, in whom this diagnosis initially seemed unlikely because of their age and age-associated concomitant diseases, and briefly review the literature. All three patients, aged 79, 82 and 88 years, presented with a spinal cord syndrome as the first clinical manifestation of AQP4-Ab-positive NMOSD. They all had severe relapses unless immunosuppressive therapy was initiated, and one untreated patient died of a fatal NMOSD course. Two patients developed side effects of immunosuppression. We conclude that a first manifestation of NMOSD should be considered even in patients beyond the age of 75 years with a compatible syndrome, especially longitudinally extensive myelitis. Early diagnosis and treatment are feasible and highly relevant. Special attention is warranted in the elderly to recognize adverse effects of immunosuppressive therapies as early as possible.

Rationale for the Evaluation of Fluoxetine in the Treatment of Enterovirus D68-Associated Acute Flaccid Myelitis

Abstract: Enterovirus D68 (EV-D68) has emerged worldwide as an important cause of respiratory disease. Between midAugust 2014 and January 15, 2015, the Centers for Disease Control and Prevention confirmed 1153 cases of EVD68–associated respiratory illness originating from 49 states. With this outbreak, there have been at least 107 cases of children presenting with acute flaccid myelitis associated with lesions identified on magnetic resonance imaging that were largely restricted to the spinal gray matter.1-4 Children with this syndrome typically present with an acute febrile respiratory syndrome followed within 2 weeks by the development of acute flaccid myelitis, characterized by motor weakness, decreased tone and reflexes, and relatively preserved sensation. Weakness is of acute onset, preferentially affects upper limbs, and is often asymmetric. Cranial nerve involvement, including facial weakness, dysarthria, or dysphagia, may occur. Findings from the electrodiagnostic and magnetic resonance imaging studies are consistent with involvement of spinal cord motor neurons. Most patients have an associated cerebrospinal fluid pleocytosis. Paralysis has typically been prolonged and recovery incomplete. The exact role of EV-D68 in this syndrome has not been conclusively established, but approximately 50% of affected children have polymerase chain reaction–amplifiable EVD68 RNA in nasopharyngeal or other upper respiratory tract secretions but not, to date, in cerebrospinal fluid.1,2,4 The occurrence of EV-D68–associated cases of poliomyelitis-like illness and the prior emergence of enterovirus 71 as the cause of severe and sometimes fatal central nervous system infection have refocused attention on the urgent need to develop effective antienteroviral drugs. Three antiviral drugs that are in clinical trials for enteroviral infections—pleconaril, pocapavir, and vapendavir—do not show activity against EV-D68 in vitro,2 increasing the urgency to identify novel drugs that could treat EV-D68. If a current Food and Drug Administration–approved drug were found to have antiviral efficacy against EV-D68, this discovery would have several advantages, including the availability of known adverse event and pharmacokinetic profiles. Zuo and colleagues5 screened more than 1100 compounds in the Prestwick Chemical Library to identify potentially novel compounds with antiviral efficacy against enteroviruses. They found that fluoxetine hydrochloride and its metabolite norfluoxetine inhibited the replication of coxsackievirus B3 in HeLa cells with a 50% effective concentration of 2.3μM, a concentration more than 10-fold less than its cytotoxic concentration. Ulferts and colleagues6 subsequently screened the National Institutes of Health Clinical Collections 2 library of 281 compounds for their antiviral efficacy against enteroviruses. They again found that fluoxetine inhibited replication of a variety of enteroviruses, and more specifically, that it inhibited replication of EV-D68 in HeLa cells with a 50% effective concentration of 1.35μM, a concentration more than 20-fold lower than its cytotoxic concentration. The antiviral mechanism of fluoxetine and norfluoxetine remains uncertain. The antiviral activity of fluoxetine has nothing to do with its action as a selective serotonin reuptake inhibitor, as other selective serotonin reuptake inhibitors do not have antiviral effects.6 Fluoxetine’s antiviral effects appear to be caused by a direct interaction with the highly conserved enteroviral 2C protein. Fluoxetine has structural similarity to a thiazolobenzimidazole compound with anti-enteroviral activity, TBZE-029, that is known to target this protein.7 The antiviral effects of both fluoxetine and TBZE-029 are abrogated in enteroviruses containing mutations within amino acid region 224-229 of the 329–amino acid long 2C protein. The mechanism by which an interaction with 2C interferes with viral replication remains unknown; although this protein is essential for viral replication, its essential function is unclear. Protein 2C may play a role in the assembly of viral proteins and RNA into virion particles (encapsidation) and interact with the enteroviral 3C protease that cleaves the translated enteroviral polyprotein into smaller structural and nonstructural proteins. Neither fluoxetine nor TBZE-029 interfere with enteroviral binding, entry into target cells, or viral polyprotein processing.6,7 However, treatment of infected cells with these drugs reduces both the amount of viral RNA and protein accumulating. It is therefore likely that the mechanism of action of fluoxetine involves a direct interaction with the viral 2C protein that results in an inhibition of viral RNA synthesis. Is the fluoxetine concentration achievable using standard dosing regimens likely to be in the antiviral range? One study of fluoxetine pharmacokinetics in 10 children aged 6 to 12 years and 11 adolescents aged 13 to 18 years found fluoxetine plasma concentrations of 127 ng/mL (to convert to micromoles per liter, multiply by 0.00323),8 which is likely below the desired target of a 50% effective concentration. However, fluoxetine and norfluoxetine concentrations in the central nervous system are up to 20-fold higher than those in serum.9 A study using fluorine-19 magnetic resonance spectroscopy in 22 adult psychiatric patients receiving fluoxetine, 20 to 40 mg/d, found mean (SD) brain concentrations of fluoxetine and norfluoxetine of 4.24 (2.83) μg/mL (approximately 14μM), although the exact concentration was dependent on both the dose and duraVIEWPOINT

Notes from the field: acute flaccid myelitis among persons aged ≤21 years - United States, August 1-November 13, 2014.

Abstract: Division of Viral Diseases, National Centers for Immunization and Respiratory Diseases, CDC; Division of Vector-Borne Diseases, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, CDC; Children’s Hospital Colorado; Council of State and Territorial Epidemiologists In August 2014, physicians at Children’s Hospital Colorado in Aurora, Colorado, noted a cluster of cases of acute limb weakness among children (1). Most patients were found to have distinctive abnormalities of the central spinal cord (i.e., gray matter) on magnetic resonance imaging, and most reported a respiratory or febrile illness preceding the onset of neurologic symptoms. On September 12, the Colorado Department of Public Health and Environment alerted CDC about this cluster. These cases coincided with a national outbreak of severe respiratory disease among children caused by enterovirus D68 (EV-D68) (2). On September 26, CDC issued a health advisory requesting state and local health departments to report cases and send specimens to CDC for testing (3). A case was defined as acute onset of focal limb weakness occurring on or after August 1, 2014, and a magnetic resonance image showing a spinal cord lesion largely restricted to gray matter in a patient aged ≤21 years. As of November 13, CDC had verified reports of 88 cases in 32 states (Figure). The median age of patients was 7.6 years (range = 5 months–20 years), and 54 (61%) were males. Limb weakness was asymmetrical in most patients. Cranial nerve motor dysfunction was reported in 30 (34%) cases. Six (7%) patients had altered mental status, and three (3%) had seizures. Most patients reported a respiratory illness (81%), a febrile illness (68%), or both, occurring before neurologic symptom onset; 8% had neither condition. Among 86 patients for whom past medical history was reported, 65 (76%) were previously healthy, and 21 (24%) had underlying illnesses, most commonly asthma (nine [10%]). All but one patient was hospitalized because of neurologic illness, and 17 (19%) required ventilator support. Among 80 patients from whom cerebrospinal fluid was obtained, 68 (85%) showed a moderate pleocytosis and normal or mildly elevated protein. Information regarding current clinical status was reported for 77 patients (median follow-up = 19 days). Of those, 49 (64%) reported some symptom improvement, and 28 (36%) showed no improvement; none were fully recovered. No deaths were reported. Among 71 patients with cerebrospinal fluid testing performed by their health care providers, state and local public health departments, or CDC, no enteroviruses or other pathogens have been confirmed to date. Among 41 patients whose upper respiratory tract samples were available for enterovirus/ rhinovirus testing at CDC, 17 (41%) tested positive: eight (20%) for EV-D68 and nine (22%) for eight other enterovirus/ rhinovirus types. Of the 19 patients whose upper respiratory tract samples were obtained <14 days from respiratory illness onset, 10 (53%) were positive: seven (37%) for EV-D68 and three (16%) for rhinoviruses. Laboratory testing for other pathogens is ongoing. On November 7, CDC published interim clinical management considerations, summarizing expert opinion based on current evidence on management and care of children with acute flaccid myelitis (4). CDC continues to collaborate with partners nationally to investigate reported cases, risk factors, and possible etiologies of this condition. Although the specific causes of this illness are still under investigation, and causal relationship to EV-D68 has not yet been substantiated, being up to date on all recommended vaccinations is essential to prevent a number of severe diseases. Vaccine-preventable diseases include poliomyelitis, which is caused by poliovirus; infection with this enterovirus can present with acute flaccid paralysis. There are also numerous other vaccine-preventable diseases that can result in severe illness. Prevention of viral infections includes general hygienic measures, such as frequent hand washing with soap and water, avoiding close contact with sick persons, and disinfecting frequently touched surfaces. Additional information is available at http://www.cdc.gov/flu/ protect/habits/index.htm. If a child appears to have a sudden onset of weakness in arms or legs, caregivers should contact a health care provider to have the child assessed for possible neurologic illness. Health care providers are encouraged to report patients meeting the case definition to their state or local health department. Health departments should report patients with illness meeting the case definition to CDC using a brief patient summary form* and may contact CDC by e-mail to arrange further laboratory testing (limbweakness@cdc.gov). Additional information is available at http://www.cdc.gov/ ncird/investigation/viral/sep2014.html.

Anti-MOG antibodies with longitudinally extensive transverse myelitis preceded by CLIPPERS

Abstract: Symmonds et al.1 reported a case presenting an initial brainstem attack sharing chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) features. After steroid weaning, MOG-seropositive longitudinally extensive transverse myelitis (LETM) involving the conus appeared, but in absence of brainstem lesions.1 A diagnosis of CLIPPERS is difficult in this clinical picture. Brainstem punctate and curvilinear enhancements, a characteristic radiologic finding of CLIPPERS, may conceal several diseases such as glioma, primary CNS lymphoma, lymphomatoid …

Bright spotty lesions on the spinal cord: an additional MRI indicator of neuromyelitis optica spectrum disorder?

Abstract: Neuromyelitis optica spectrum disorder (NMOSD) is a devastating inflammatory disease of the central nervous system (CNS), thus, an early and accurate diagnosis is important.1 The aquaporin-4 (AQP4) antibody is a specific marker of NMOSD that has generally modest sensitivity but is not always available in time. The radiological characteristics, such as longitudinally extensive transverse myelitis (LETM), are helpful in the diagnosis, but LETM is not a pathognomonic feature of NMOSD. Therefore, it would be good to identify the other specific features associated with NMOSD. Bright spotty lesions (BSLs) on spinal MRIs have recently been identified as a discriminative feature that distinguishes NMOSD from multiple sclerosis (MS).2 However, previous study was conducted with a small number of patients and the timing of the MRIs was not controlled. Furthermore, it has not been investigated whether BSLs may help to discriminate NMOSD from other entities, such as idiopathic transverse myelitis (ITM), which share many similar features with NMOSD. Thus, the present study investigated whether BSLs can be utilised as a discriminative feature of NMOSD to distinguish it from MS and ITM in a large cohort of patients with myelitis, particularly during the acute phases. A total of 114 patients, who presented with acute myelitis and underwent spinal MRIs (≤3 weeks since the latest clinical attack), were enrolled from the National Cancer Centre registry of CNS idiopathic inflammatory diseases between 2005 and 2014. Of 114 patients, 59 patients with NMOSD were positive for AQP4 antibody, 31 patients met the McDonald criteria for MS and 24 patients fulfilled the criteria for ITM.3 All patients with MS and ITM were negative for AQP4 antibody following repeated assays of three different methods.4 Myelin-oligodendroglycoprotein (MOG) antibodies were also tested using a cell-based assay at Tohoku University and all patients were negative for MOG antibodies.4 …

Double Inversion Recovery Sequence of the Cervical Spinal Cord in Multiple Sclerosis and Related Inflammatory Diseases

Abstract: BACKGROUND AND PURPOSE: MR imaging plays an important role in diagnosing MS and other related inflammatory diseases; however, imaging of the spinal cord is still challenging We hypothesized that a 3D double inversion recovery sequence for cervical spinal cord imaging would be more sensitive in detecting inflammatory lesions than a conventional 2D T2-weighted TSE sequence at 3T MATERIALS AND METHODS: On a 3T MR imaging scanner, we examined 30 patients with suspected or established MS (MS, n = 16; clinically isolated syndrome, n = 12; isolated myelitis, n = 2) and 10 healthy controls Newly developed 3D double inversion recovery and conventional 2D axial and sagittal T2-weighted TSE images of the cervical spinal cord were acquired Two blinded neuroradiologists independently assessed the scans in pseudorandomized order for lesion numbers and rated lesion visibility and overall image quality on 5-point scales A subsequent consensus reading delivered definite lesion counts Standardized contrast-to-noise ratios were calculated in representative lesions of each patient RESULTS: Overall, 28% more lesions could be detected with 3D double inversion recovery than with conventional T2WI (119 versus 93, P P P CONCLUSIONS: The novel 3D double inversion recovery sequence allowed better detection of lesions in MS and related inflammatory diseases of the cervical spinal cord, compared with conventional 2D T2WI

Update on Neurological Manifestations of HTLV-1 Infection

Abstract: The human T cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects 10–20 million persons around the world. Initially associated with the hematological malignancy adult T cell leukemia/lymphoma (ATLL), HTLV-1 is also the cause of a chronic progressive myelopathy named “HTLV-1-associated myelopathy/tropical spastic paraparesis” (HAM/TSP). HAM/TSP arises as the tip of the iceberg of an assortment of neurological syndromes triggered by the virus such as inflammatory myopathies, polyneuropathies, amyotrophic lateral sclerosis (ALS)-like syndromes, dysautonomia, and cognitive impairment. HAM/TSP typifies a chronic progressive spastic paraparesis with neurogenic bladder and minimal sensory signs. The neuropathology of HAM/TSP is concentrated in the thoracic spinal cord and is typically biphasic. Initially, there is a perivascular lymphocytic cuffing and mild parenchymal mononuclear infiltrates. Subsequently, this is replaced by gliosis and scarring. The neuropathogenesis of HTLV-1 is still partially understood. At present, the therapy of HAM/TSP remains basically symptomatic.

Recurrent longitudinal extensive transverse myelitis in a neuro-Behçet syndrome treated with infliximab.

Abstract: BackgroundSpinal cord involvement is not common, but can be seen in neuro-Behcet's syndrome (NBS). The major site of involvement is the cervical spinal cord with the myelitis-like inflammatory lesions continuing more than two segments, and extending to the brainstem.CaseA 30-year-old male patient who has been followed with a diagnosis of Behcet's syndrome admitted to our neurology department clinically and radiologically suggestive of recurrent and extensive longitudinal myelitis. His anti-aquaporine antibody was negative. Because of insufficient effect of azathioprine, cyclophosphamide, and corticosteroids, infliximab was started. His clinical and radiological status is stationary for 3 years under infliximab treatment.DiscussionMyelitis such as that occurring in our patient may have a similar presentation like neuromyelitis optica (NMO), which should therefore be included in differential diagnosis. Myelitis observed in both NMO and NBS shows spinal cord lesions longer than three or more vertebra...

Bladder and bowel dysfunction affect quality of life. A cross sectional study of 60 patients with aquaporin-4 antibody positive Neuromyelitis Optica spectrum disorder

Abstract: Background Transverse myelitis (TM) associated with Neuromyelitis Optica (NMO) can be severe and is well known to reduce mobility early in the disease. However the burden of bladder and bowel dysfunction is unknown and overlooked. We studied the frequency of bladder and bowel dysfunction and their impact on quality of life. Methods A cross-sectional study of 60 patients who had AQP4-IgG positive NMO associated TM was performed using the Bladder Control Scale, Lower Urinary Tract Quality of Life, Bowel Control Scale and Neurogenic Bowel Score, Short-Form-36 Health Survey and EDSS. The relationships between the variables were analysed with multiple linear regression. Results Fifty women and 10 men participated. 78% (47/60) patients reported bladder symptoms and a similar number reported bowel problems. 87% (52/60) patients reported either bladder or bowel dysfunction. 65% (39/60) developed residual symptoms after the first episode of myelitis and the remaining by the second episode. Both bladder and bowel dysfunction reduced quality of life and required modification of lifestyle in 83% (39/47) and 70% (33/47) respectively. Conclusion Bladder and bowel dysfunction is very common in NMO associated myelitis developing early in the disease and significantly affects quality of life.

Asymptomatic myelitis in neuromyelitis optica and autoimmune aquaporin-4 channelopathy

Abstract: Neuromyelitis optica (NMO) is an autoimmune inflammatory CNS disease associated with pathogenic aquaporin-4 autoantibodies (AQP4-IgG); optic neuritis (ON) and myelitis are required to fulfill diagnostic criteria.1 NMO spectrum disorders (NMOSDs) are defined as one or more typical NMO syndromes accompanied by AQP4-IgG seropositivity but not yet fulfilling NMO diagnostic criteria (e.g., AQP4-IgG–seropositive recurrent ON). Non-Caucasian ethnicity and coexisting autoimmunity are common in NMO/NMOSD.2 Transverse myelitis episodes in patients with NMO/NMOSD are characteristically longitudinally extensive (extending ≥3 vertebral segments on MRI), and the resulting clinical phenotype is typically severe, with paraplegia and wheelchair dependence at nadir a frequent finding.2 In contrast, multiple sclerosis (MS) myelitis episodes are typically mild and often asymptomatic.3 Herein we report 3 AQP4-IgG–seropositive4 women with asymptomatic myelitis in the setting of NMO/NMOSD.

Protocol for a multicentre randomiSed controlled TRial of IntraVEnous immunoglobulin versus standard therapy for the treatment of transverse myelitis in adults and children (STRIVE)

Abstract: Introduction Transverse myelitis (TM) is an immune-mediated disorder of the spinal cord which causes motor and sensory disturbance and limited recovery in 50% of patients. Standard treatment is steroids, and patients with more severe disease appear to respond to plasma exchange (PLEX). Intravenous immunoglobulin (IVIG) has also been used as an adjunct to steroids, but evidence is lacking. We propose the first randomised control trial in adults and children, to determine the benefit of additional treatment with IVIG. Methods and analysis 170 adults and children aged over 1 year with acute first episode TM or neuromyelitis optica (with myelitis) will be recruited over a 2.5-year period and followed up for 12 months. Participants randomised to the control arm will receive standard therapy of intravenous methylprednisolone (IVMP). The intervention arm will receive the above standard therapy, plus additional IVIG. Primary outcome will be a 2-point improvement on the American Spinal Injury Association (ASIA) Impairment scale at 6 months postrandomisation by blinded assessors. Additional secondary and tertiary outcome measures will be collected: ASIA motor and sensory scales, Kurtzke expanded disability status scale, International Spinal Cord Injury (SCI) Bladder/Bowel Data Set, Client Services Receipt Index, Pediatric Quality of Life Inventory, EQ-5D, SCI Pain and SCI Quality of Life Data Sets. Biological samples will be biobanked for future studies. After 6-months' follow-up of the first 52 recruited patients futility analysis will be carried out. Health economics analysis will be performed to calculate cost-effectiveness. After 6 months’ recruitment futility analysis will be performed.

Spinal cord toxoplasmosis in human immunodeficiency virus infection/acquired immunodeficiency syndrome

Abstract: Neurological complications in patients with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) are still common, even in the era of highly active antiretroviral therapy. Opportunistic infections, immune reconstitution, the virus itself, antiretroviral drugs and neurocognitive disorders have to be considered when establishing the differential diagnosis. Toxoplasmic encephalitis remains the major cause of space-occupying lesions in the brain of patients with HIV/AIDS; however, spinal cord involvement has been reported infrequently. Here, we review spinal cord toxoplasmosis in HIV infection and illustrate the condition with a recent case from our hospital. We suggest that most patients with HIV/AIDS and myelitis with enhanced spine lesions, multiple brain lesions and positive serology for Toxoplasma gondii should receive immediate empirical treatment for toxoplasmosis, and a biopsy should be performed in those cases without clinical improvement or with deterioration.

Immunoadsorption therapy for neuromyelitis optica spectrum disorders long after the acute phase.

Abstract: Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease with exacerbations involving recurrent or bilateral optic neuritis and longitudinally extensive transverse myelitis. Pulse steroid therapy is recommended as the initial, acute-phase treatment for NMO. If ineffective, treatment with plasma exchange (PE) should commence. However, no evidence exists to support the effectiveness of PE long after the acute phase. Immunoadsorption therapy (IA) eliminates pathogenic antibodies while sparing other plasma proteins. With IA, side effects of PE resulting from protein substitution can be avoided. However, whether IA is effective for NMO remains unclear. We describe a patient with anti-aquaporin-4-positive myelitis who responded to IA using a tryptophan polyvinyl alcohol gel column that was begun 52 days after disease onset following the acute phase. Even long after the acute phase when symptoms appear to be stable, IA may be effective and should not be excluded as a treatment choice.

The first reported case of West Nile encephalitis in Korea.

Abstract: West Nile encephalitis was first identified in 1937, but until now, it was never diagnosed in Korea. A 58-yr-old Korean man was admitted with headache and cognitive dysfunction. The patient had been on a business trip in Guinea. Cerebrospinal fluid (CSF) showed pleocytosis. The patient complained of both leg weakness,and arachnoiditis and myelitis were observed on lumbar magnetic resonance imaging (MRI). A specific neutralizing antibody for West Nile virus was positive in serum. After a treatment with interferon-α 3mu, follow up CSF findings recovered completely after 3 months later. The first case of West Nile encephalitis in Korea was imported from Guinea, and was cured successfully.

Arbovirus infections of the nervous system: Current trends and future threats

Abstract: Systemic viral infections are common. Symptomatic involvement of the nervous system in viral infections is uncommon.1 Encephalitis is the most worrying manifestation of nervous system involvement by viruses. Arthropod-borne viruses (arboviruses) are among the most serious international infectious threats to the human nervous system.2 The neurologic diseases that may be transmitted by arthropods to humans include meningitis, encephalitis, myelitis, encephalomyelitis, neuritis (including anterior horn cells and dorsal root ganglia), and myositis.2 The authors thank Dr. Talha Vaqar and Musa Khan for help in obtaining cited articles.

Cytomegalovirus-associated transverse myelitis: a review of nine well-documented cases.

Abstract: Cytomegalovirus-associated transverse myelitis is a rare disease. We found 12 cases in the medical literature, 8 of which met our criteria for being well documented. Our aim was to review this clinical entity using information from our own clinical experience as well as published cases.