Cerebrospinal fluid eosinophils in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND: Eosinophils in cerebrospinal fluid (CSF) are an uncommon finding most often associated with parasitic infections, but have also been described in some neuroinflammatory disorders. Eosinophilic infiltration is not thought to be a typical feature of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). We aim to describe the rate of CSF eosinophil positivity in a cohort of pediatric MOGAD patients. METHODS: Single-center retrospective chart review of pediatric MOGAD patients. Clinical and laboratory data was collected from the electronic medical record and analyzed. RESULTS: Of 46 pediatric patients with positive serum myelin oligodendrocyte glycoprotein antibody (MOG-IgG) identified, 38 patients fulfilling internationally proposed MOGAD diagnostic criteria were included for analysis. 6 patients with MOGAD were excluded as no CSF data was available, and 2 patients with positive MOG-IgG but diagnosis more consistent with MS were excluded. Median age was 7.3 years, and 19/38 (50 %) were female. Acute disseminated encephalomyelitis (ADEM) was the most common presenting phenotype (23/38, 61 %), and other phenotypes included optic neuritis (10/38, 26 %), transverse myelitis (3/38, 8 %), and neuromyelitis optica spectrum disorder (NMOSD) (2/38, 5 %). 12 of 36 (33 %) patients with all lumbar puncture (LP) data available had CSF eosinophils present, with eosinophil mean of 3 % and range from 1 % to 18 % of CSF while blood cells. CONCLUSION: CSF eosinophils were present in one third of pediatric MOGAD patients, which is a higher rate than previously reported in either MOGAD or aquaporin-4 antibody positive NMOSD cohorts. Understanding the CSF composition of pediatric MOGAD patients helps to facilitate more prompt diagnosis and treatment and may shed light onto underlying pathologic mechanisms of disease with the goal to inform future therapeutic targets.

MOG encephalomyelitis: distinct clinical, MRI and CSF features in patients with longitudinal extensive transverse myelitis as first clinical presentation.

BACKGROUND: Based on clinical, immunological and histopathological evidence, MOG-IgG-associated encephalomyelitis (MOG-EM) has emerged as a distinct disease entity different from multiple sclerosis (MS) and aquaporin-4-antibody-positive neuromyelitis optica spectrum disorder (NMOSD). MOG-EM is associated with a broader clinical phenotype including optic neuritis, myelitis, brainstem lesions and acute disseminated encephalomyelitis with a substantial clinical and radiological overlap to other demyelinating CNS disorders. OBJECTIVE: To evaluate common clinical, MRI and CSF findings, as well as therapy responses in patients with longitudinal extensive transverse myelitis (LETM) as initial clinical presentation of MOG-EM. METHODS: After excluding patients with a known diagnosis of MS, we identified 153 patients with myelitis of which 7 fulfilled the inclusion criteria and were investigated for MRI, CSF and clinical parameters. RESULTS: Patients with LETM as first clinical presentation of MOG-EM display similar characteristics, namely a lack of gadolinium-enhancement in spinal cord MRI, marked pleocytosis, negative oligoclonal bands, a previous history of infections/vaccinations and response to antibody-depleting treatments for acute attacks and long-term treatment. CONCLUSIONS: We identify common pathological findings in patients with LETM as first clinical presentation of MOG-EM which distinguishes it from other forms of LETM and should lead to testing for MOG-IgG in these cases.

Neuromyelitis Optica Spectrum Disorder and Other Non-Multiple Sclerosis Central Nervous System Inflammatory Diseases.

PURPOSE OF REVIEW: This article reviews the clinical features, diagnostic approach, treatment, and prognosis of central nervous system inflammatory diseases that mimic multiple sclerosis (MS), including those defined by recently discovered autoantibody biomarkers. RECENT FINDINGS: The discovery of autoantibody biomarkers of inflammatory demyelinating diseases of the central nervous system (aquaporin-4 IgG and myelin oligodendrocyte glycoprotein IgG) and the recognition that, despite some overlap, their clinical phenotypes are distinct from MS have revolutionized this field of neurology. These autoantibody biomarkers assist in diagnosis and have improved our understanding of the underlying disease pathogenesis. This has allowed targeted treatments to be translated into clinical trials, three of which are now under way in aquaporin-4 IgG-seropositive neuromyelitis optica (NMO) spectrum disorder. SUMMARY: Knowledge of the clinical attributes, MRI findings, CSF parameters, and accompanying autoantibody biomarkers can help neurologists distinguish MS from its inflammatory mimics. These antibody biomarkers provide critical diagnostic and prognostic information and guide treatment decisions. Better recognition of the clinical, radiologic, and laboratory features of other inflammatory MS mimics that lack autoantibody biomarkers has allowed us to diagnose these disorders faster and initiate disease-specific treatments more expeditiously.

Bartonella-Associated Transverse Myelitis.

Each year in the United States, 500 patients are hospitalized for cat-scratch disease, caused by Bartonella henselae infection. We report a case of rare but serious neurologic B. henselae infection. When typical features of cat-scratch disease occur with neurologic findings, Bartonella infection should be suspected and diagnostic testing should be performed.

Cytomegalovirus-associated encephalomyelitis in an immunocompetent adult: a two-stage attack of direct viral and delayed immune-mediated invasions. case report.

BACKGROUND: It is clinically rare to find cytomegalovirus (CMV)-associated encephalomyelitis in immunocompetent adults. Here, we present the case of an adult patient who developed acute transverse myelitis that was followed by immune-mediated disseminated encephalomyelitis. CASE PRESENTATION: A 38-year-old man developed acute paraplegia with paresthesia below the level of the T7-8 dermatome. Both brain and spinal cord MRIs performed at admission appeared normal. Corticosteroid therapy was initiated, with the later addition of high-dose intravenous immunoglobulins. After polymerase chain reaction analysis indicated the presence of CMV DNA in his cerebrospinal fluid (CSF), anti-viral therapy was added. Forty days after symptom onset, despite an initial positive response to this therapy, he developed dysarthria and truncal ataxia. Repeated magnetic resonance imaging scans demonstrated progressively expanding lesions involving not only the spinal cord but also the cerebral white matter, suggestive of extensive immune-mediated demyelination involving the central nervous system (CNS), as is observed in acute disseminated encephalomyelitis (ADEM). CONCLUSION: This case report underscores the importance of careful patient observation following the initial diagnosis of a CMV-associated CNS infection, such as transverse myelitis, on the possibility that post-infectious ADEM may appear.

Hypothalamic abnormality in patients with inflammatory demyelinating disorders.

BACKGROUND: Hypothalamic lesions in neuromyelitis optica (NMO) patients might be more specific for NMO than multiple sclerosis (MS). However, this is controversial. OBJECTIVE: To characterize clinical features of patients with inflammatory demyelinating disorders (IDDs) with visible hypothalamic lesions using magnetic resonance imaging (MRI). METHODS: Patients with IDDs (n = 429) were recruited retrospectively. RESULTS: Of 52 patients with hypothalamic images enrolled, 42 were positive for aquaporin-4 (AQP4) antibodies, including 28 patients with NMO, 6 with recurrent transverse myelitis, 3 with recurrent optic neuritis, and 5 with brainstem and brain syndrome. The remaining 10 patients were anti-AQP4-negative, including 3 with MS, 3 with acute disseminated encephalomyelitis, and 4 with other disorders. In the AQP4-positive group, manifestations, including ataxia, intractable hiccup and nausea, syndrome of inappropriate antidiuretic hormone secretion and encephalopathy were more frequent in those with hypothalamic lesions than those without. Cell counts of cerebrospinal fluid in patients with hypothalamic lesions differed from patients without lesions. Brain MRI abnormalities were more frequent in brainstem and hemisphere of the hypothalamic lesion group. CONCLUSIONS: Hypothalamic lesions were observed frequently in patients with AQP4 antibodies. Clinical manifestations and paraclinical features in AQP4-positive patients with hypothalamic lesions differed from those without lesions.

Spinal cord involvement in Behçet's disease.

BACKGROUND: Spinal cord involvement in Behçet's disease is not well studied. OBJECTIVE: To evaluate the clinical, laboratory and magnetic resonance imaging characteristics of spinal cord involvement in Behçet's disease. METHODS: We retrospectively reviewed 10 spinal cord involvements in seven patients with Behçet's disease. RESULTS: The median age of onset for spinal cord involvement was 32 (23-45 years). Two patients showed a secondary progressive course. Cerebrospinal fluid findings revealed mild to moderate pleocytosis and/or elevated protein levels. In eight spinal cord involvements, the lesion was longer than three vertebrae. Serum anti-aquaporin-4 antibody was negative in all four patients tested. CONCLUSIONS: Longitudinally extensive transverse myelitis is a characteristic manifestation of spinal cord involvement in Behçet's disease.

Antibodies to MOG and AQP4 in children with neuromyelitis optica and limited forms of the disease.

OBJECTIVE: To determine the frequency and clinical-radiological associations of antibodies to myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) in children presenting with neuromyelitis optica (NMO) and limited forms. METHODS: Children with a first event of NMO, recurrent (RON), bilateral ON (BON), longitudinally extensive transverse myelitis (LETM) or brainstem syndrome (BS) with a clinical follow-up of more than 12 months were enrolled. Serum samples were tested for MOG- and AQP4-antibodies using live cell-based assays. RESULTS: 45 children with NMO (n=12), LETM (n=14), BON (n=6), RON (n=12) and BS (n=1) were included. 25/45 (56%) children had MOG-antibodies at initial presentation (7 NMO, 4 BON, 8 ON, 6 LETM). 5/45 (11%) children showed AQP4-antibodies (3 NMO, 1 LETM, 1 BS) and 15/45 (33%) were seronegative for both antibodies (2 NMO, 2 BON, 4 RON, 7 LETM). No differences were found in the age at presentation, sex ratio, frequency of oligoclonal bands or median EDSS at last follow-up between the three groups. Children with MOG-antibodies more frequently (1) had a monophasic course (p=0.018) after one year, (2) presented with simultaneous ON and LETM (p=0.004) and (3) were less likely to receive immunosuppressive therapies (p=0.0002). MRI in MOG-antibody positive patients (4) less frequently demonstrated periependymal lesions (p=0.001), (5) more often were unspecific (p=0.004) and (6) resolved more frequently (p=0.016). CONCLUSIONS: 67% of all children presenting with NMO or limited forms tested positive for MOG- or AQP4-antibodies. MOG-antibody positivity was associated with distinct features. We therefore recommend to measure both antibodies in children with demyelinating syndromes.

Cytokines and matrix metalloproteinases in the cerebrospinal fluid of patients with acute transverse myelitis: an outcome analysis.

BACKGROUND: Role of cytokines as well as matrix metalloproteinases (MMPs) is well defined in various central nervous system inflammatory diseases. However, the role of these cytokines and MMPs in acute transverse myelitis is inadequately studied. MATERIALS AND METHODS: Patients with acute transverse myelitis, fulfilling the inclusion and exclusion criteria defined by Transverse Myelitis Consortium Working Group, were enrolled along with age and sex matched controls. A detailed clinical evaluation and magnetic resonance imaging of patients was done. Cerebrospinal fluid (CSF) samples both from patients and controls were collected. CSF samples were analyzed for cytokines [interleukin (IL)-6, IL-8, IL-10 and IL-17)] and matrix metalloproteinases (MMP-2, MMP-9). Patients were followed up for 3 months. Disability was assessed using modified Barthel index (MBI). RESULTS: CSF levels of all cytokines IL-6, IL-8, IL-10, MMP-2 and MMP-9, except IL-17, were significantly higher in patients with acute transverse myelitis (p < 0.001). CSF IL-6 and IL-8 were significantly associated with severity of the disease (MBI ≤ 12). After 3 months, quadriparesis (p = 0.001, odd's ratio 19.5, 95 % CI 2.34-62.39) and long-segment myelitis (p = 0.035, odd's ratio 4.37, 95 % CI 1.17-5.95) were significantly associated with poor outcome. Among cytokines and MMPs, IL-6 levels at baseline correlated significantly with the MBI at 3 months (Spearmen's ρ = -0.335, p = 0.01). CONCLUSION: In conclusion, both anti-inflammatory and pro-inflammatory cytokines, MMP-2, and MMP-9 are elevated in the acute phase of transverse myelitis. Possibly, IL-6 plays a role in determining the disability.

[Demyelinating diseases in children with acute neurological symptoms]. / Demyeliniserende sygdom hos børn med akutte neurologiske symptomer

Demyelinating diseases in children is a broad group of illnesses, which affect the central nervous system. Demyelinating diseases can be monophasic or chronic and comprise acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, multiple sclerosis and neuromyelitis optica. Demyelinating diseases are rare, but it is important for the physician to recognize these diseases, as well as to understand the differential diagnoses. This review summarizes the current knowledge of demyelinating disorders in children, focusing on an approach to diagnosis and management.

Tumefactive demyelination of the spinal cord: a case report.

STUDY DESIGN: Case report. OBJECTIVES: We report on a 52-year-old male patient with tumefactive demyelination of the spinal cord. SETTING: University Hospital and Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia. BACKGROUND: In contrast to relatively frequent tumefactive fulminant lesions in the brain, cases affecting the spinal cord in isolation have been reported less frequently. METHODS: Description of the case report. RESULTS: Clinical, neuroradiological and necropsy findings are described in a 52-year-old man with tumefactive fulminant demyelination of the spinal cord. Progression of the demyelination process produced paraplegia, mild paresis of the right upper limb, neurogenic bladder and sensitive loss over 2 weeks. MRI scans revealed several ovoid lesions in cervical segments and tumefactive T2-hyperintense signals with oedema and post-contrast enhancement located in thoracic segments Th3 to Th6. Cerebrospinal fluid (CSF) examination displayed lymphomonocytic pleocytosis with normal proteinorhachia, positive CSF oligoclonal IgG bands (OCB) and elevated IgG index (1.55). Serum anti-AQP4-Ab was not tested. Stored frozen CSF samples were later repeatedly examined with negative findings of anti-AQP4-Ab. Treatment with high-dose methylprednisolon and plasma exchange had limited effect. Immunosuppressive medication was interrupted because of an acute urinary infection. The patient died suddenly because of pulmonary embolism as a secondary complication. Histopathology of the spinal cord confirmed active demyelination. We considered that tumefactive demyelination could be a variant of neuromyelitis optica. CONCLUSION: Our case could be anti-AQP4-Ab-negative longitudinally extensive transverse myelitis, a variant of neuromyelitis optica.

Idiopathic aquaporin-4 antibody negative longitudinally extensive transverse myelitis.

BACKGROUND: Longitudinally extensive transverse myelitis (LETM) is a characteristic manifestation of neuromyelitis optica (NMO). However, not all patients with LETM are positive for aquaporin-4 (AQP4) antibodies. We evaluated the characteristics of idiopathic isolated LETM negative for AQP4 antibodies. METHODS: From the National Cancer Center registry of inflammatory diseases of the central nervous system, patients with LETM as an initial manifestation and follow-up for at least two years were enrolled. Their medical records and MRIs were reviewed retrospectively. AQP4 antibody was confirmed by three different validated methods at least three times. Cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP) levels were measured to investigate astrocyte damage. RESULTS: Among 108 patients with first-ever LETM, 55 were positive for AQP4 antibodies (P-LETM) and 53 were consistently negative. Of them, seven were later diagnosed with seronegative NMO, and four were positive for MOG antibodies. The remaining 42 patients (N-LETM) showed several features distinct from P-LETM: male predominance, older age of onset, milder clinical presentation, spinal cord confinement and absence of combined autoimmunity. CSF GFAP levels were not increased in N-LETM but were markedly elevated in P-LETM. CONCLUSIONS: Idiopathic isolated N-LETM is not that rare among first-ever LETM, and has many features distinct from P-LETM where astrocytic damage is evident.

Longitudinal extensive transverse myelitis due to tuberculosis: a report of four cases.

Tuberculosis of the central nervous system (CNS) accounts for approximately 1% of all cases of tuberculosis and half of these involve the spine. Intramedullary involvement is rare in tuberculosis and usually present in the form of radiculomyelitis, transverse myelitis, intraspinal granulomas, or thrombosis of anterior spinal artery. Transverse myelitis typically extends two or less spinal segments, whereas longitudinal extensive transverse myelitis (LETM) extends three or more spinal segments in length and may occasionally span all the segments of the spinal cord. LETM is most frequently associated with neuromyelitis optica (NMO). Moreover, associations between NMO and active pulmonary tuberculosis have been suggested by a number of case reports and case series. We present here four cases of spinal tuberculosis that presented with LETM and none of them had a clinical profile fulfilling the diagnostic criteria for NMO.

Clinical manifestations and spinal cord magnetic resonance imaging findings in Chinese neuromyelitis optica patients.

Neuromyelitis optica (NMO) is a disease distinct from multiple sclerosis in terms of clinical and magnetic resonance imaging (MRI) manifestations. Antibody to aquaporin-4 (AQP4) has been identified as a specific biomarker and part of the diagnostic criteria for NMO. Although it is relatively common in Asia, a comprehensive clinical and imaging evaluation of NMO has not been reported in Chinese patients. Here, we reviewed data from 57 Chinese cases. The patients had an obvious female preponderance (female/male = 8.5:1), and transverse myelitis (82.5%) and optic neuritis (56.1%) were the most common manifestations. In MRI, longitudinally extensive transverse myelitis (6.9 ± 2.3 segments) dominated the spinal cord lesions, which were mainly (69.7%) distributed in cervical and thoracic cord. However, the length of the lesions was not correlated with onset age, paralysis severity, relapse rate, or duration. Among 29 patients who underwent AQP4 antibody assay, 17 (58.6%) were positive. There was no difference between seropositive and seronegative patients in terms of female preponderance, onset age, relapse rate, and Expanded Disability Status Scale score. However, seropositive patients had significantly more damaged segments (8.3 ± 3.5) than did seronegative patients (4.5 ± 1.6) (p < 0.001). The data revealed the clinical and MRI characteristics and AQP4 antibody status of NMO in Chinese patients and the correlations between them, which may have important implications for the diagnosis of the disease.

Cerebrospinal fluid interleukin-6 in central nervous system inflammatory diseases.

BACKGROUND: Interleukin (IL)-6 is recognised as an important cytokine involved in inflammatory diseases of the central nervous system (CNS). OBJECTIVE: To perform a large retrospective study designed to test cerebrospinal fluid (CSF) IL-6 levels in the context of neurological diseases, and evaluate its usefulness as a biomarker to help discriminate multiple sclerosis (MS) from other inflammatory neurological diseases (OIND). PATIENTS AND METHODS: We analyzed 374 CSF samples for IL-6 using a quantitative enzyme-linked immunosorbent assay. Groups tested were composed of demyelinating diseases of the CNS (DD, n = 117), including relapsing-remitting MS (RRMS, n = 65), primary progressive MS (PPMS, n = 11), clinically isolated syndrome (CIS, n = 11), optic neuritis (ON, n = 30); idiopathic transverse myelitis (ITM, n = 10); other inflammatory neurological diseases (OIND, n = 35); and non-inflammatory neurological diseases (NIND, n = 212). Differences between groups were analysed using Kruskal-Wallis test and Mann-Whitney U-test. RESULTS: CSF IL-6 levels exceeded the positivity cut-off of 10 pg/ml in 18 (51.4%) of the 35 OIND samples, but in only three (3.9%) of the 76 MS samples collected. CSF IL-6 was negative for all NIND samples tested (0/212). IL-6 cut-off of 10 pg/ml offers 96% sensitivity to exclude MS. CONCLUSION: CSF IL-6 may help to differentiate MS from its major differential diagnosis group, OIND.

[Acute transverse myelitis and Lyme borreliosis: a case report]. / Myélite transverse aiguë et maladie de Lyme: à propos d'un cas.

Lyme disease is an infectious disease caused by a spirochete of the Borrelia sensu lato group. Its incidence has greatly increased in recent years. The main vector is a tick of the Ixodes family. Clinical manifestations are multiple and show the multi-organ character of the disease. In terms of frequency, joint and neurological presentations, respectively more frequent in North America and Europe, are the main manifestations after cutaneous symptoms, of which erythema migrans is the most common, followed by cardiac and ocular signs. Other signs exist but are anecdotal. Neuroborreliosis manifests itself most often with peripheral facial palsy, but there are other clinical forms, which include acute myelitis (4-5% of neuroborreliosis). We present here the case of a 16-year-old teenager with acute myelitis and meningeal involvement due to Lyme disease, who presented with atypical symptoms (massive and rapid weight loss, vomiting). MRI showed localized marrow edema as well as leptomeningeal and root enhancement. Lumbar puncture showed lymphocytic pleocytosis. Lyme serology was positive both in blood and cerebrospinal fluid. Even if acute myelitis remains exceptional among neuroborreliosis manifestations, this diagnosis has to be thought of when a child presents with unexplained neurological symptoms.