Showing papers on "Myelitis published in 2016"
TL;DR: The predominantly relapsing and often severe disease course and the short median time to second attack support the use of prophylactic long-term treatments in patients with MOG-IgG-positive ON and/or myelitis; however, treatment failure leading to rapid accumulation of disability was noted in many patients as well as flare-ups after steroid withdrawal.
Abstract: A subset of patients with neuromyelitis optica spectrum disorders (NMOSD) has been shown to be seropositive for myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) To describe the epidemiological, clinical, radiological, cerebrospinal fluid (CSF), and electrophysiological features of a large cohort of MOG-IgG-positive patients with optic neuritis (ON) and/or myelitis (n = 50) as well as attack and long-term treatment outcomes Retrospective multicenter study The sex ratio was 1:28 (m:f) Median age at onset was 31 years (range 6-70) The disease followed a multiphasic course in 80% (median time-to-first-relapse 5 months; annualized relapse rate 092) and resulted in significant disability in 40% (mean follow-up 75 ± 465 months), with severe visual impairment or functional blindness (36%) and markedly impaired ambulation due to paresis or ataxia (25%) as the most common long-term sequelae Functional blindness in one or both eyes was noted during at least one ON attack in around 70% Perioptic enhancement was present in several patients Besides acute tetra-/paraparesis, dysesthesia and pain were common in acute myelitis (70%) Longitudinally extensive spinal cord lesions were frequent, but short lesions occurred at least once in 44% Fourty-one percent had a history of simultaneous ON and myelitis Clinical or radiological involvement of the brain, brainstem, or cerebellum was present in 50%; extra-opticospinal symptoms included intractable nausea and vomiting and respiratory insufficiency (fatal in one) CSF pleocytosis (partly neutrophilic) was present in 70%, oligoclonal bands in only 13%, and blood-CSF-barrier dysfunction in 32% Intravenous methylprednisolone (IVMP) and long-term immunosuppression were often effective; however, treatment failure leading to rapid accumulation of disability was noted in many patients as well as flare-ups after steroid withdrawal Full recovery was achieved by plasma exchange in some cases, including after IVMP failure Breakthrough attacks under azathioprine were linked to the drug-specific latency period and a lack of cotreatment with oral steroids Methotrexate was effective in 5/6 patients Interferon-beta was associated with ongoing or increasing disease activity Rituximab and ofatumumab were effective in some patients However, treatment with rituximab was followed by early relapses in several cases; end-of-dose relapses occurred 9-12 months after the first infusion Coexisting autoimmunity was rare (9%) Wingerchuk’s 2006 and 2015 criteria for NMO(SD) and Barkhof and McDonald criteria for multiple sclerosis (MS) were met by 28%, 32%, 15%, 33%, respectively; MS had been suspected in 36% Disease onset or relapses were preceded by infection, vaccination, or pregnancy/delivery in several cases Our findings from a predominantly Caucasian cohort strongly argue against the concept of MOG-IgG denoting a mild and usually monophasic variant of NMOSD The predominantly relapsing and often severe disease course and the short median time to second attack support the use of prophylactic long-term treatments in patients with MOG-IgG-positive ON and/or myelitis
671 citations
TL;DR: This is the largest cohort studied for IgG to human full-length MOG by means of an up-to-date CBA and finds MOG-IgG is present in a substantial subset of patients with ON and/or myelitis, but not in classical MS.
Abstract: Antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) have been suggested to play a role in a subset of patients with neuromyelitis optica and related disorders To assess (i) the frequency of MOG-IgG in a large and predominantly Caucasian cohort of patients with optic neuritis (ON) and/or myelitis; (ii) the frequency of MOG-IgG among AQP4-IgG-positive patients and vice versa; (iii) the origin and frequency of MOG-IgG in the cerebrospinal fluid (CSF); (iv) the presence of MOG-IgG at disease onset; and (v) the influence of disease activity and treatment status on MOG-IgG titers 614 serum samples from patients with ON and/or myelitis and from controls, including 92 follow-up samples from 55 subjects, and 18 CSF samples were tested for MOG-IgG using a live cell-based assay (CBA) employing full-length human MOG-transfected HEK293A cells MOG-IgG was detected in 95 sera from 50 patients with ON and/or myelitis, including 22/54 (407%) patients with a history of both ON and myelitis, 22/103 (214%) with a history of ON but no myelitis and 6/45 (133%) with a history of longitudinally extensive transverse myelitis but no ON, and in 1 control patient with encephalitis and a connective tissue disorder, all of whom were negative for AQP4-IgG MOG-IgG was absent in 221 further controls, including 83 patients with AQP4-IgG-seropositive neuromyelitis optica spectrum disorders and 85 with multiple sclerosis (MS) MOG-IgG was found in 12/18 (67%) CSF samples from MOG-IgG-seropositive patients; the MOG-IgG-specific antibody index was negative in all cases, indicating a predominantly peripheral origin of CSF MOG-IgG Serum and CSF MOG-IgG belonged to the complement-activating IgG1 subclass MOG-IgG was present already at disease onset The antibodies remained detectable in 40/45 (89%) follow-up samples obtained over a median period of 165 months (range 0–123) Serum titers were higher during attacks than during remission (p < 00001), highest during attacks of simultaneous myelitis and ON, lowest during acute isolated ON, and declined following treatment To date, this is the largest cohort studied for IgG to human full-length MOG by means of an up-to-date CBA MOG-IgG is present in a substantial subset of patients with ON and/or myelitis, but not in classical MS Co-existence of MOG-IgG and AQP4-IgG is highly uncommon CSF MOG-IgG is of extrathecal origin Serum MOG-IgG is present already at disease onset and remains detectable in the long-term course Serum titers depend on disease activity and treatment status
352 citations
Ruhr University Bochum1, Charité2, Ludwig Maximilian University of Munich3, University of Düsseldorf4, Technische Universität München5, University Hospital Regensburg6, University of Hamburg7, Hannover Medical School8, University of Ulm9, Goethe University Frankfurt10, University of Tübingen11, University of Erlangen-Nuremberg12, University of Münster13, Leipzig University14, Bayreuth Medical Center15, University of Rostock16, Heidelberg University17
TL;DR: The frequency, sequence, and efficacy of therapies used for NMO attacks are analyzed and it is shown that certain therapies are more effective than others in cases of severe N MO attacks.
Abstract: ObjectiveNeuromyelitis optica (NMO) attacks often are severe, are difficult to treat, and leave residual deficits. Here, we analyzed the frequency, sequence, and efficacy of therapies used for NMO attacks. MethodsA retrospective review was made of patient records to assess demographic/diagnostic data, attack characteristics, therapies, and the short-term remission status (complete remission [CR], partial remission [PR], no remission [NR]). Inclusion criteria were NMO according to Wingerchuk's 2006 criteria or aquaporin-4 antibody-positive NMO spectrum disorder (NMOSD). Remission status was analyzed with generalized estimating equations (GEEs), a patient-based statistical approach. ResultsA total of 871 attacks in 185 patients (142 NMO/43 NMOSD, 82% female) were analyzed. The 1,153 treatment courses comprised high-dose intravenous steroids (HD-S;n=810), plasma exchange (PE;n=192), immunoadsorption (IA;n=38), other (n=80), and unknown (n=33) therapies. The first treatment course led to CR in 19.1%, PR in 64.5%, and NR in 16.4% of attacks. Second, third, fourth, and fifth treatment courses were given in 28.2%, 7.1%, 1.4%, and 0.5% of attacks, respectively. This escalation of attack therapy significantly improved outcome (p<0.001, Bowker test). Remission rates were higher for isolated optic neuritis versus isolated myelitis (p<0.001), and for unilateral versus bilateral optic neuritis (p=0.020). Isolated myelitis responded better to PE/IA than to HD-S as first treatment course (p=0.037). Predictors of CR in multivariate GEE analysis were age (odds ratio [OR]=0.97, p=0.011), presence of myelitis (OR=0.38, p=0.002), CR from previous attack (OR=6.85, p<0.001), and first-line PE/IA versus HD-S (OR=4.38, p=0.006). InterpretationParticularly myelitis and bilateral optic neuritis have poor remission rates. Escalation of attack therapy improves outcome. PE/IA may increase recovery in isolated myelitis. Ann Neurol 2016;79:206-216
305 citations
TL;DR: The presence of Zika virus in the cerebrospinal fl uid of a 15-year-old girl with acute myelitis suggests that this virus might be neurotropic, and should be considered in patients with acute Myelitis living in or from endemic areas.
300 citations
TL;DR: Brainstem involvement is present in around one third of MOG-IgG-positive patients with ON and/or myelitis, and is associated with a more aggressive general disease course.
Abstract: Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) are present in a subset of aquaporin-4 (AQP4)-IgG-negative patients with optic neuritis (ON) and/or myelitis. Little is known so far about brainstem involvement in MOG-IgG-positive patients. To investigate the frequency, clinical and paraclinical features, course, outcome, and prognostic implications of brainstem involvement in MOG-IgG-positive ON and/or myelitis. Retrospective case study. Among 50 patients with MOG-IgG-positive ON and/or myelitis, 15 (30 %) with a history of brainstem encephalitis were identified. All were negative for AQP4-IgG. Symptoms included respiratory insufficiency, intractable nausea and vomiting (INV), dysarthria, dysphagia, impaired cough reflex, oculomotor nerve palsy and diplopia, nystagmus, internuclear ophthalmoplegia (INO), facial nerve paresis, trigeminal hypesthesia/dysesthesia, vertigo, hearing loss, balance difficulties, and gait and limb ataxia; brainstem involvement was asymptomatic in three cases. Brainstem inflammation was already present at or very shortly after disease onset in 7/15 (47 %) patients. 16/21 (76.2 %) brainstem attacks were accompanied by acute myelitis and/or ON. Lesions were located in the pons (11/13), medulla oblongata (8/14), mesencephalon (cerebral peduncles; 2/14), and cerebellar peduncles (5/14), were adjacent to the fourth ventricle in 2/12, and periaqueductal in 1/12; some had concomitant diencephalic (2/13) or cerebellar lesions (1/14). MRI or laboratory signs of blood-brain barrier damage were present in 5/12. Cerebrospinal fluid pleocytosis was found in 11/14 cases, with neutrophils in 7/11 (3-34 % of all CSF white blood cells), and oligoclonal bands in 4/14. Attacks were preceded by acute infection or vaccination in 5/15 (33.3 %). A history of teratoma was noted in one case. The disease followed a relapsing course in 13/15 (87 %); the brainstem was involved more than once in 6. Immunosuppression was not always effective in preventing relapses. Interferon-beta was followed by new attacks in two patients. While one patient died from central hypoventilation, partial or complete recovery was achieved in the remainder following treatment with high-dose steroids and/or plasma exchange. Brainstem involvement was associated with a more aggressive general disease course (higher relapse rate, more myelitis attacks, more frequently supratentorial brain lesions, worse EDSS at last follow-up). Brainstem involvement is present in around one third of MOG-IgG-positive patients with ON and/or myelitis. Clinical manifestations are diverse and may include symptoms typically seen in AQP4-IgG-positive neuromyelitis optica, such as INV and respiratory insufficiency, or in multiple sclerosis, such as INO. As MOG-IgG-positive brainstem encephalitis may take a serious or even fatal course, particular attention should be paid to signs or symptoms of additional brainstem involvement in patients presenting with MOG-IgG-positive ON and/or myelitis.
204 citations
TL;DR: Empirical data suggest this AFM cluster was likely associated with the large outbreak of EV-D68-associated respiratory illness, although direct laboratory evidence linking AFM with EV- D68 remains inconclusive.
Abstract: Background During late summer/fall 2014, pediatric cases of acute flaccid myelitis (AFM) occurred in the United States, coincident with a national outbreak of enterovirus D68 (EV-D68)-associated severe respiratory illness. Methods Clinicians and health departments reported standardized clinical, epidemiologic, and radiologic information on AFM cases to the Centers for Disease Control and Prevention (CDC), and submitted biological samples for testing. Cases were ≤21 years old, with acute onset of limb weakness 1 August-31 December 2014 and spinal magnetic resonance imaging (MRI) showing lesions predominantly restricted to gray matter. Results From August through December 2014, 120 AFM cases were reported from 34 states. Median age was 7.1 years (interquartile range, 4.8-12.1 years); 59% were male. Most experienced respiratory (81%) or febrile (64%) illness before limb weakness onset. MRI abnormalities were predominantly in the cervical spinal cord (103/118). All but 1 case was hospitalized; none died. Cerebrospinal fluid (CSF) pleocytosis (>5 white blood cells/µL) was common (81%). At CDC, 1 CSF specimen was positive for EV-D68 and Epstein-Barr virus by real-time polymerase chain reaction, although the specimen had >3000 red blood cells/µL. The most common virus detected in upper respiratory tract specimens was EV-D68 (from 20%, and 47% with specimen collected ≤7 days from respiratory illness/fever onset). Continued surveillance in 2015 identified 16 AFM cases reported from 13 states. Conclusions Epidemiologic data suggest this AFM cluster was likely associated with the large outbreak of EV-D68-associated respiratory illness, although direct laboratory evidence linking AFM with EV-D68 remains inconclusive. Continued surveillance will help define the incidence, epidemiology, and etiology of AFM.
179 citations
TL;DR: Clinical features and epidemiological evidence and biological plausibility support an association between enterovirus D68 and the recent increase in acute flaccid myelitis cases in the United States.
Abstract: This review highlights clinical features of the increasing cases of acute flaccid paralysis associated with anterior myelitis noted in the United States from 2012 to 2015. Acute flaccid myelitis refers to acute flaccid limb weakness with spinal cord gray matter lesions on imaging or evidence of spinal cord motor neuron injury on electrodiagnostic testing. Although some individuals demonstrated improvement in motor weakness and functional deficits, most have residual weakness a year or more after onset. Epidemiological evidence and biological plausibility support an association between enterovirus D68 and the recent increase in acute flaccid myelitis cases in the United States. Ann Neurol 2016;80:326-338.
170 citations
TL;DR: To compare longitudinally extensive myelitis in neuromyelitis optica spectrum disorders (NMOSD) and spinal cord sarcoidosis (SCS) with real world examples, a large number of patients with NMOSD and SCS are treated with chemotherapy.
Abstract: Objective
To compare longitudinally extensive myelitis in neuromyelitis optica spectrum disorders (NMOSD) and spinal cord sarcoidosis (SCS).
Methods
We identified adult patients evaluated between 1996 and 2015 with SCS or NMOSD whose first myelitis episode was accompanied by a spinal cord lesion spanning ≥3 vertebral segments. All NMOSD patients were positive for aquaporin-4–immunoglobulin G, and all sarcoidosis cases were pathologically confirmed. Clinical characteristics were evaluated. Spine magnetic resonance imaging was reviewed by 2 neuroradiologists.
Results
We studied 71 patients (NMOSD, 37; SCS, 34). Sixteen (47%) SCS cases were initially diagnosed as NMOSD or idiopathic transverse myelitis. Median delay to diagnosis was longer for SCS than NMOSD (5 vs 1.5 months, p 2 months favored SCS, and ringlike enhancement favored NMOSD (p < 0.05). Maximum disability was similar in both disorders.
Interpretation
SCS is an under-recognized cause of longitudinally extensive myelitis that commonly mimics NMOSD. We identified clinical, laboratory, systemic, and radiologic features that, taken together, help discriminate SCS from NMOSD. ANN NEUROL 2016;79:437–447
138 citations
TL;DR: MOG autoimmunity in adult patients associates with a clinical spectrum wider than the one expected for patients with suspected NMOSD and overall good outcome and Antibodies to rodent MOG epitopes do not associate with any phenotypic variant.
Abstract: The aim of this study was to report the clinical spectrum associated with antibodies to myelin oligodendrocyte glycoprotein (MOG) in adult patients, and to assess whether phenotypic variants are dependent on recognition of rodent MOG epitopes. We retrospectively analyzed the features, course and outcome of 56 patients whose samples were investigated by brain tissue immunohistochemistry and cell-based assays using human and rodent MOG. The median age at symptom onset was 37 years (range 18–70); 35 patients (63 %) were female. After a median follow-up of 43 months (range 4–554), only 14 patients (25 %) developed a neuromyelitis optica spectrum disorder (NMOSD), 27 patients (47 %) retained the initial diagnosis of isolated optic neuritis, 7 (12 %) of longitudinally extensive transverse myelitis, and 2 (4 %) of acute disseminated encephalomyelitis; 6 patients (11 %) developed atypical demyelinating syndromes (4 had relapsing episodes of short myelitis lesions which in one occurred with optic neuritis; 1 had relapsing brainstem symptoms, and 1 relapsing demyelinating encephalomyelitis). The course was frequently associated with relapses (71 %) and good outcome. Twenty-seven patients (49 %) had antibodies that recognized rodent MOG epitopes, and 9 of them (16 %) showed a myelin staining pattern in rodent tissue. Only the myelin staining pattern was linked to NMOSD (p = 0.005). In conclusion, MOG autoimmunity in adult patients associates with a clinical spectrum wider than the one expected for patients with suspected NMOSD and overall good outcome. Antibodies to rodent MOG epitopes do not associate with any phenotypic variant.
114 citations
TL;DR: Odds of this viral infection in the nasopharynx were 10 times greater for children with this condition than for controls.
Abstract: During August 8, 2014-October 14, 2014, a total of 11 children with acute flaccid myelitis and distinctive neuroimaging changes were identified near Denver, Colorado, USA. A respiratory prodrome was experienced by 10, and nasopharyngeal specimens were positive for enterovirus D68 (EV-D68) for 4. To determine whether an association exists between EV-D68 infection and acute flaccid myelitis, we conducted a retrospective case-control study comparing these patients with 2 groups of outpatient control children (1 group tested for acute respiratory illness and 1 for Bordetella pertussis infection). Adjusted analyses indicated that, for children with acute flaccid myelitis, the odds of having EV-D68 infection were 10.3 times greater than for those tested for acute respiratory infection and 4.5 times greater than for those tested for B. pertussis infection. No statistical association was seen between acute flaccid myelitis and non-EV-D68 enterovirus or rhinovirus infection. These findings support an association between EV-D68 infection and acute flaccid myelitis.
102 citations
TL;DR: An overview of current knowledge of clinical features, investigative workup, pathogenesis, and management of acute transverse myelitis is provided and suggests future directions.
Abstract: Pediatric acute transverse myelitis (ATM) is an immune-mediated CNS disorder and contributes to 20% of children experiencing a first acquired demyelinating syndrome (ADS). ATM must be differentiated from other presentations of myelopathy and may be the first presentation of relapsing ADS such as neuromyelitis optica (NMO) or multiple sclerosis (MS). The tenets of the diagnostic criteria for ATM established by the Transverse Myelitis Consortium Working Group can generally be applied in children; however, a clear sensory level may not be evident in some. MRI lesions are often centrally located with high T2 signal intensity involving gray and neighboring white matter. Longitudinally extensive ATM occurs in the majority. Asymptomatic lesions on brain MRI are seen in more than one-third and predict MS or NMO. The role of antibodies such as myelin oligodendrocyte glycoprotein in monophasic and relapsing ATM and their significance in therapeutic approaches remain unclear. ATM is a potentially devastating condition with variable outcome and presents significant cumulative demands on health and social care resources. Children generally have a better outcome than adults, with one-half making a complete recovery by 2 years. There is need for standardization of clinical assessment and investigation protocols to enable international collaborative studies to delineate prognostic factors for disability and relapse. There are no robust controlled trials in children or adults to inform optimal treatment of ATM, with one study currently open to recruitment. This review provides an overview of current knowledge of clinical features, investigative workup, pathogenesis, and management of ATM and suggests future directions.
TL;DR: An enhancement pattern in 9 patients with spinal cord sarcoidosis with subacute onset (<4 weeks) myelitis as the initial manifestation of sarCOidosis is reported, often resembling a trident head on axial sequences.
Abstract: We report an enhancement pattern in 9 patients with spinal cord sarcoidosis (SCS) with subacute onset (<4 weeks) myelitis as the initial manifestation of sarcoidosis. Presenting symptoms included numbness in 9, urinary complaints in 7, and weakness in 6. Examination revealed abnormal proprioception in 8, spastic quadriparesis/paraparesis in 6, and sensory level in 6. MRI showed central canal enhancement alone (11%) or in combination with dorsal-subpial enhancement1 (89%) (figure 1), often resembling a trident head on axial sequences (figure 2). Lung biopsies in 7 patients confirmed sarcoidosis; both patients without biopsies had hilar adenopathy. Central canal enhancement and the trident sign in subacute myelitis should raise suspicion for SCS.
TL;DR: Although cases of encephalopathy and myelitis have also been linked to ZIKV infection, the evidence is scarce and there is a need for virological, epidemiological, and controlled studies to better characterize such relationship.
Abstract: Zika virus (ZIKV) has caused a major infection outbreak in the Americas since 2015. In parallel with the ZIKV epidemic, an increase in cases of neurological disorders which include Guillain–Barre syndrome (GBS), encephalitis, and myelitis have been linked to the infection. We reviewed the evidence suggesting a relationship between ZIKV and neurological disorders in adults. A search of the literature supporting such link included databases such as PubMed and the World Health Organization (WHO) surveillance system. Through June 1, 2016, 761 publications were available on PubMed using the search word “Zika.” Among those publications as well as surveillance reports released by the WHO and other health organizations, 20 articles linked ZIKV with neurological complications other than microcephaly. They corresponded to population and surveillance studies (n = 7), case reports (n = 9), case series (n = 3), and case–control studies (n = 1). Articles were also included if they provided information related to possible mechanisms of ZIKV neuropathogenesis. Evidence based on epidemiological and virological information supports the hypothesis that ZIKV infection is associated with GBS. Although cases of encephalopathy and myelitis have also been linked to ZIKV infection, the evidence is scarce and there is a need for virological, epidemiological, and controlled studies to better characterize such relationship.
TL;DR: Recognition of this disorder enables clinicians to obtain appropriate imaging and laboratory testing, initiate treatment, and provide families with accurate prognostic information.
TL;DR: The IPND criteria well-reflected the broader clinical spectrum of NMOSD and markedly improved the diagnostic yield compared to the previous criteria, even in patients with an unknown AQP4-IgG status.
Abstract: Objective: To evaluate the application of the 2015 International Panel for NMO Diagnosis (IPND) criteria to consecutive cases of neuromyelitis optica spectrum disorder (NMOSD) in a large cohort of individuals with CNS inflammatory diseases. Methods: In total, 594 patients with CNS inflammatory diseases were included. Rigorous confirmation of the patients9 aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) status throughout the disease duration (mean 9.2 ± 5.7 years) using repeated assays, including ELISA and cell-based assay, was performed. Results: A total of 252 patients fulfilled the IPND criteria (AQP4-IgG positive: 226 [90%], AQP4-IgG negative: 26 [10%]). Of these, 136 (54%) patients met the 2006 neuromyelitis optica criteria. When we assumed an unknown AQP4-IgG status in the confirmed NMOSD group with AQP4-IgG, 162 of 226 (72%) patients with AQP4-IgG were classified as having NMOSD by the IPND criteria. The majority of patients were diagnosed with NMOSD within 2 years of onset (73%) or after a second attack (72%). Acute myelitis (83%) and optic neuritis (65%) were the most common clinical features throughout the disease duration. Optic neuritis (42%) was the most common initial manifestation, followed by acute myelitis (38%) and area postrema syndrome (14%). Conclusions: The IPND criteria well-reflected the broader clinical spectrum of NMOSD and markedly improved the diagnostic yield compared to the previous criteria, even in patients with an unknown AQP4-IgG status.
TL;DR: The treatment for ZIKV and CHIKV infections are symptomatic and the management for neurological complications depends on the type of affliction; Intravenous immunoglobulin, plasmapheresis, and corticosteroid pulse therapy are options.
Abstract: The epidemics of Chikungunya virus (CHIKV) and Zika virus (ZIKV) infections have been considered the most important epidemiological occurrences in the Americas. The clinical picture of CHIKV infection is characterized by high fever, exanthema, myalgia, headaches, and arthralgia. Besides the typical clinical picture of CHIKV, atypical manifestations of neurological complications have been reported: meningo-encephalitis, meningoencephalo-myeloradiculitis, myeloradiculitis, myelitis, myeloneuropathy, Guillain-Barre syndrome and others. The diagnosis is based on clinical, epidemiological, and laboratory criteria. The most common symptoms of ZIKV infection are skin rash (mostly maculopapular), fever, arthralgia, myalgia, headache, and conjunctivitis. Some epidemics that have recently occurred in French Polynesia and Brazil, reported the most severe conditions, with involvement of the nervous system (Guillain-Barre syndrome, transverse myelitis, microcephaly and meningitis). The treatment for ZIKV and CHIKV infections are symptomatic and the management for neurological complications depends on the type of affliction. Intravenous immunoglobulin, plasmapheresis, and corticosteroid pulse therapy are options.
TL;DR: Neurotoxocariasis, a completely preventable zoonosis, could lead to severe sequelae failing prompt diagnosis, and a compatible clinical picture, presence of risk factors, blood eosinophilia and high titers of antibodies against Toxocara spp.
Abstract: Toxocariasis is a widespread zoonosis, which may result in central nervous system injury. We conducted a systematic literature review in MEDLINE, SciELO, ScienceDirect and Google Scholar up to April 2015 using a combination of the following search terms: “neurotoxocariasis” or “neurotoxocarosis”, “toxocariasis” or “toxocarosis” and “cerebral” or “neurologic”. One hundred cases of neurotoxocariasis were identified in literature. The majority of patients were male (58 %), with a median age of 42 years. The predominant clinical pictures were myelitis (60 %), encephalitis (47 %) and/or meningitis (29 %). Fever was inconstant (23 %). The suspected mode of transmission, mentioned in only 49 % of cases, was mainly contact with dogs and/or cats (67 %) and ingestion of contaminated food (31 %). Diagnostic imaging examinations found hypodense lesions in cerebral scanner sequences and hyperintense lesions in cerebral MRI T2-weighted sequences in 65 and 57 % of encephalitis cases respectively, and in 92 % of myelitis cases in medullary MRI T2-weighted sequences. The detection of antibodies against Toxocara spp. was almost constant in blood and cerebrospinal fluid (CSF), 99 and 93 %, respectively. The two most commonly used drugs were corticosteroids (72 %) and/or albendazole (68 %) for a period of at least 3 weeks, which often needed to be repeated. Despite a low mortality rate (6 %), complete remission was observed in only 40 % of cases. Neurotoxocariasis, a completely preventable zoonosis, could lead to severe sequelae failing prompt diagnosis. A compatible clinical picture, presence of risk factors, blood eosinophilia and high titers of antibodies against Toxocara spp. in CSF should alert physicians.
TL;DR: In this paper, the mean upper cervical cross-sectional area (MUCCA) in patients with NMOSD without MRI cord lesions or history of myelitis was compared to patients with MR images of the spinal cord.
Abstract: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease that usually presents with optic neuritis or severe myelitis. NMOSD can be diagnosed after only one typical clinical syndrome if immunoglobulin G (IgG) antibodies against the aquaporin-4 receptor (NMO-IgG) are present.1 Patients with NMOSD can develop marked spinal cord atrophy after myelitis,2,3 but it is unknown whether atrophy can occur without a history of myelitis. To address this question, we compared the mean upper cervical cross-sectional area (MUCCA) in patients with NMOSD without MRI cord lesions or history of myelitis, patients with NMOSD with MRI cord lesions or history of myelitis, patients with multiple sclerosis (MS), and neurologically intact controls.
TL;DR: Most patients experienced clinical improvement with corticosteroids and/or immunosuppressive treatment and the long-term functional prognosis was correlated with the initial severity.
Abstract: Sarcoidosis of the spinal cord is a rare disease. The aims of this study are to describe the features of spinal cord sarcoidosis (SCS) and identify prognostic markers. We analyzed 20 patients over a 20-year period in 8 French hospitals. There were 12 men (60 %), mostly Caucasian (75 %). The median ages at diagnosis of sarcoidosis and myelitis were 34.5 and 37 years, respectively. SCS revealed sarcoidosis in 12 patients (60 %). Eleven patients presented with motor deficit (55 %) and 9 had sphincter dysfunction (45 %). The median initial Edmus Grading Scale (EGS) score was 2.5. The cerebrospinal fluid (CSF) showed elevated protein level (median: 1.00 g/L, interquartile range (IQR) 0.72–1.97), low glucose level (median 2.84 mmol/L, IQR 1.42–3.45), and elevated white cell count (median 22/mm3, IQR 6–45). The cervical and thoracic cords were most often affected (90 %). All patients received steroids and an immunosuppressive drug was added in 10 cases (50 %). After a mean follow-up of 52.1 months (range 8–43), 18 patients had partial response (90 %), 7 displayed functional impairment (35 %), and the median final EGS score was 1. Six patients experienced relapse (30 %). There was an association between the initial and the final EGS scores (p = 0.006). High CSF protein level showed a trend toward an association with relapse (p = 0.076). The spinal cord lesion was often the presenting feature of sarcoidosis. Most patients experienced clinical improvement with corticosteroids and/or immunosuppressive treatment. The long-term functional prognosis was correlated with the initial severity.
TL;DR: It is concluded that alemtuzumab failed to prevent disabling relapses and poor outcome in neuromyelitis optica (NMO) spectrum disorders and hypothesise that rituximab is more effective, because it causes much more prolonged B lymphocyte depletion than alem T cell depletion.
Abstract: Alemtuzumab is an anti-CD52 monoclonal antibody recently licensed for use in relapsing-remitting multiple sclerosis. Here, we report our experience of its use in neuromyelitis optica (NMO) spectrum disorders. A retrospective case review of patients treated with alemtuzumab in Cambridge, UK, was conducted to identify those who fulfil the criteria for NMO spectrum disorder. Three cases were identified. Case 1, 9-year-old female, presented with transverse myelitis and bilateral optic neuritis,with one lower medullary and several longitudinally extensive cord lesions. Despite immunosuppression including two courses of alemtuzumab, she continued to relapse, was wheelchair bound and registered blind by age 12, and died at age 18. Case 2, 41-year-old female, presented with bilateral optic neuritis and transverse myelitis with longitudinally extensive cervical cord lesions. Despite three courses of alemtuzumab, she had five relapses with visual impairment and new cord lesions. She later developed tumefactive white matter lesions and died aged 51.Case 3, 31-year-old female, presented with transverse myelitis with longitudinally extensive cervical cord lesions and positive aquaporin-4 antibody. After one course of alemtuzumab, she relapsed with 4 episodes of myelitis with new enhancing lesions and accumulating disability. She became relapse free after rituximab and mycophenolate mofetil. From this case series, we conclude that alemtuzumab failed to prevent disabling relapses and poor outcome in NMO. We hypothesise that rituximab is more effective, as in case 3, because it causes much more prolonged B lymphocyte depletion than alemtuzumab. We therefore caution against the use of alemtuzumab in NMO.
TL;DR: The presence of antibodies directed against aquaporin-4 strongly supports a diagnosis of neuromyelitis optica, and should be assayed in children manifesting with severe optic neuritis, longitudinally extensive myelitis, or brainstem/hypothalamic syndromes.
Abstract: Approximately one-third of children with an acquired demyelinating syndrome (ADS) will be diagnosed with multiple sclerosis (MS), either at onset according to the 2010 McDonald criteria, or on the basis of clinical or MRI evidence of relapsing disease, in the majority of patients within 2-4 years. ADS in adolescents, female patients, and patients with polyfocal deficits is associated with the highest likelihood of MS, while children with acute disseminated encephalomyelitis, those with documented preceding infection, and ADS presentation in young children more commonly portends a monophasic outcome. While pediatric MS associates with similar genetic risk alleles as have been documented in adult-onset MS, such associations are not diagnostically valuable at the individual level. The presence of antibodies directed against aquaporin-4 strongly supports a diagnosis of neuromyelitis optica, and should be assayed in children manifesting with severe optic neuritis, longitudinally extensive myelitis, or brainstem/hypothalamic syndromes. Further research will determine whether other antibody signatures are indicative of relapsing demyelination distinct from MS.
TL;DR: Along with patient demographic characteristics, lesion features on MRI, including lesion location, extension to pial border and presence of 'bright spotty lesion' can help differentiate acute myelitis of NMO from SCI in the acute setting.
Abstract: Background There is substantial overlap between MRI of acute spinal cord lesions from neuromyelitis optica (NMO) and spinal cord infarct (SCI) in clinical practice. However, early differentiation is important since management approaches to minimize morbidity from NMO or SCI differ significantly. Objective To identify MRI features at initial presentation that may help to differentiate NMO acute myelitis from SCI. Methods 2 board-certified neuroradiologists, blinded to final diagnosis, retrospectively characterized MRI features at symptom onset for subjects with serologically-proven NMO (N=13) or SCI (N=11) from a single institution. Univariate and multivariate analyses were used to identify factors associated with NMO or SCI. Results SCI was more common in men and Caucasians, while NMO was more common in non-Caucasian women (P 0.05). Conclusion Along with patient demographic characteristics, lesion features on MRI, including lesion location, extension to pial border and presence of ‘bright spotty lesion’ can help differentiate acute myelitis of NMO from SCI in the acute setting.
TL;DR: This report describes the first evidence to show tocilizumab could be effective for NMO-SD with SS, and suggests it could help patients with relapsing longitudinal extensive transverse myelitis and Sjogren's syndrome.
Abstract: A 38-year-old woman with relapsing longitudinal extensive transverse myelitis and Sjogren's syndrome (SS) was admitted with lower extremity muscle weakness. Studies showed high serum titer of anti-aquaporin4 antibody and gadolinium-enhanced-MRI T1-weighted lesions within thoracic cord. Clinical findings suggested neuromyelitis optica-spectrum disorder (NMO-SD). High-dose corticosteroids, plasma exchange and cyclophosphamide were not effective. After starting tocilizumab, her neurological findings gradually improved. This report describes the first evidence to show tocilizumab could be effective for NMO-SD with SS.
TL;DR: Mice with asthma, atopic dermatitis, or atopic diathesis had widespread and significantly more activated microglia and astroglia in the spinal cord than those without atopy, and displayed tactile allodynia, suggesting a novel mechanism whereby atopy induces glial activation and neuropathic pain via an ET-1/EDNRB pathway.
Abstract: Allergic and atopic disorders have increased over the past few decades and have been associated with neuropsychiatric conditions, such as autism spectrum disorder and asthmatic amyotrophy. Myelitis presenting with neuropathic pain can occur in patients with atopic disorder; however, the relationship between allergic inflammation and neuropathic pain, and the underlying mechanism, remains to be established. We studied whether allergic inflammation affects the spinal nociceptive system. We found that mice with asthma, atopic dermatitis, or atopic diathesis had widespread and significantly more activated microglia and astroglia in the spinal cord than those without atopy, and displayed tactile allodynia. Microarray analysis of isolated microglia revealed a dysregulated phenotype showing upregulation of M1 macrophage markers and downregulation of M2 markers in atopic mice. Among the cell surface protein genes, endothelin receptor type B (EDNRB) was most upregulated. Immunohistochemical analysis revealed that EDNRB expression was enhanced in microglia and astroglia, whereas endothelin-1, an EDNRB ligand, was increased in serum, lungs, and epidermis of atopic mice. No EDNRA expression was found in the spinal cord. Expression of FBJ murine osteosarcoma viral oncogene homolog B was significantly higher in the dorsal horn neurons of asthma mice than nonatopic mice. The EDNRB antagonist BQ788 abolished glial and neural activation and allodynia. We found increased serum endothelin-1 in atopic patients with myelitis and neuropathic pain, and activation of spinal microglia and astroglia with EDNRB upregulation in an autopsied case. These results suggest that allergic inflammation induces diffuse glial activation, influencing the nociceptive system via the EDNRB pathway. SIGNIFICANCE STATEMENT The prevalence of allergic disorders has markedly increased over the past few decades. Allergic disorders are associated with neuropsychiatric conditions; however, the relationship between allergic inflammation and CNS complications is unknown. A peculiar myelitis presenting with persistent neuropathic pain has been reported in patients with allergic disorders. We studied how atopy exerts substantial influence on the nociceptive system. We found that mice with allergic disorders had severe allodynia with activated astroglia and microglia, and showed marked upregulation of endothelin-1 (ET-1) receptor type B (EDNRB) in the spinal cord. A selective EDNRB antagonist prevented allodynia and glial activation. Our findings suggest a novel mechanism whereby atopy induces glial activation and neuropathic pain via an ET-1/EDNRB pathway.
TL;DR: Vision loss in NMOSD is strongly suggestive of a true relapse vs a pseudorelapse, and the only early predictor that reliably differentiated relapse from pseudORElapse among this NMOSd patient population was vision loss.
Abstract: Objective: The purpose of this study was to review cases of neuromyelitis optica spectrum disorder (NMOSD) relapses and pseudorelapses to identify early features that differentiate between them at onset of symptoms. Methods: This was a retrospective analysis of 74 hospitalizations of patients with NMOSD who were admitted to the Johns Hopkins Hospital for workup and treatment of a presumed relapse. Standard workup included MRI and blood and urine testing for metabolic and infectious etiologies. The gold standard for a relapse was defined as new or worsening symptoms and a change in neurologic examination correlating with a new or enhancing MRI lesion. A pseudorelapse was a clinical exacerbation with similar symptoms and signs but the MRI was negative, and workup identified an alternative cause for the symptoms that, when treated, resulted in the improvement of neurologic symptoms. Factors considered to be early predictors of relapses vs pseudorelapses were analyzed using the Fisher test. Results: Among 74 NMOSD hospitalizations for presumed relapse, 57 were confirmed relapses while 17 had a negative MRI and an identifiable cause of pseudorelapse. The most common causes of pseudorelapse were infection, pain, and dysautonomia. The only early predictor that reliably differentiated relapse from pseudorelapse among this NMOSD patient population was vision loss ( p = 0.039). Race, sex, presentations of weakness, numbness, and bowel/bladder dysfunction, white blood cell count, and urinary tract infection were not different among patients with relapses vs pseudorelapses. Conclusions: Vision loss in NMOSD is strongly suggestive of a true relapse vs a pseudorelapse. Pseudorelapses localized to the spinal cord in patients with previous myelitis presented similarly to true relapses and could only be ruled out by a negative MRI.
TL;DR: A 54-year-old female with a relapsing-remitting course of optic neuritis and myelitis for six years, diagnosed initially as MS, had been treated with interferon beta-1b and oral corticosteroid and was recognized to be positive for AQP-4 antibody during fingolimod treatment, and may be contraindicated in patients with NMOSD.
Abstract: Fingolimod (FTY720) is used for reducing the annualized relapse rate and slowing progression of neurological disability in relapsing-remitting forms of multiple sclerosis (MS). However, its safety is not confirmed in patients with neuromyelitis optica spectrum disorder (NMOSD), who characteristically have positive aquaporin-4 (AQP-4) antibody. A 54-year-old female with a relapsing-remitting course of optic neuritis and myelitis for six years, diagnosed initially as MS, had been treated with interferon beta-1b and oral corticosteroid. Magnetic resonance imaging (MRI) consistently revealed lesions on the optic nerve and spinal cord, but never on the brainstem or cerebral white matter during acute exacerbation. After treatment was switched to fingolimod from interferon beta-1b, multiple new lesions appeared at the brainstem and cerebral white matter. Following discontinuation of fingolimod, these lesions completely cleared, concomitantly with clinical improvement. During fingolimod treatment, she was recognized to be positive for AQP-4 antibody. Fingolimod may be contraindicated in patients with NMOSD.
TL;DR: The spectrum of diseases causing LETM is reviewed and interpretation is proposed to guide the radiologist when presented with the MRI finding of LETM.
TL;DR: Using multi-shot DTI spinal tractography acute inflammatory lesions can be differentiated from other tumorous intramedullary lesions.
TL;DR: 3 patients diagnosed with acute flaccid myelitis during a province-wide outbreak of enterovirus D68 with the virus detected in 2 of the patients are described, and prompt identification and notification of public health authorities are warranted.
Abstract: Poliomyelitis is a historically devastating neurological complication of poliovirus infection. Poliovirus vaccines have decreased the incidence of poliomyelitis to 209 global cases in 2014, with new cases of acute flaccid myelitis primarily associated with nonpolio enteroviruses. Recently, during outbreaks of enterovirus D68 throughout North America and Europe, cases of acute flaccid myelitis have been reported, suggesting another nonpolio enterovirus associated with acute flaccid myelitis. The authors describe 3 patients diagnosed with acute flaccid myelitis during a province-wide outbreak of enterovirus D68 with the virus detected in 2 of the patients. Given the significant morbidity associated with acute flaccid myelitis and potential for nonpolio enterovirus to cause outbreaks, prompt identification and notification of public health authorities are warranted.
TL;DR: This chapter reviews current knowledge in clinical and imaging findings in the most common spinal infections divided according to the compartment primarily involved.
Abstract: Predisposing factors for developing spinal infections include: immunodeficiency; drug abuse; the widespread use of broad-spectrum antibiotics, corticosteroids, and immunosuppressive drugs; diabetes mellitus; and spinal surgery. Infections can be bacterial, fungal, parasitic, or viral in origin. This chapter reviews current knowledge in clinical and imaging findings in the most common spinal infections divided according to the compartment primarily involved.