Risk factors for idiopathic myelitis at admission and predictors for late diagnostic change.

Immune-mediated myelopathy (IMM) diagnosis is challenging, and its etiology may remain unclear despite extensive investigation. We evaluated diagnostic changes in IMM patients during follow-up. We included 80 patients, 61.3% female, with median follow-up time 62.5 months. Diagnoses at discharge were: 48.8% Multiple Sclerosis-IMM (MS-IMM), 32.5% I-IMM, 11.3% Neuromyelitis Optica Spectrum Disorders-IMM (NMOSD-IMM), 1.3% MOG encephalomyelitis (MOGAD), and 6.2% Others IMM (O-IMM). Twenty-two  patients (27.5%) changed diagnosis (median 15.5  months): 68.8% MS-IMM, 12.5%  NMOSD-IMM, 3.8% MOGAD, 10.0% I-IMM, and 5.0% O-IMM. Most patients that changed diagnosis were I-IMM. Predictive factors for diagnostic change in I-IMM were: autonomous gait (p = 0.029), lesions suggestive of MS (p = 0.039), higher number of lesions (p = 0.043), lesions length < 3 vertebral bodies (p = 0.033), cervical involvement (p = 0.038), and lower EDSS at admission (p = 0.013). Etiologic reclassifications in IMM are common, therefore patients require an appropriate follow-up time to increase diagnostic accuracy.

A nation-wide survey of Japanese pediatric MOG antibody-associated diseases.

OBJECTIVE: To elucidate the clinical characteristics of Japanese pediatric patients with acquired demyelinating diseases (ADS), positive for myelin oligodendrocyte glycoprotein antibody (MOG-IgG), we conducted a nation-wide survey. METHODS: Information about pediatric patients under 18 years old with ADS was solicited with surveys sent to 323 facilities. In an initial survey, we asked whether the center had any patients with ADS, and the MOG-IgG serostatus of the patients. In a follow-up survey, we requested more precise information on patients with ADS. RESULTS: Initial survey: 263 replies providing information on 175 patients were received. MOG-IgG were examined in 78 patients and 54 of those (69%) were positive for MOG-IgG. Follow-up survey: The characteristic involvement was optic neuritis, with visual disturbance and optic pain as characteristic symptoms. The relapse rate was 44% in patients positive for MOG-IgG, which was higher than that in seronegative patients (38%). For acute phase treatments, corticosteroid (CS), plasma exchange, and intravenous immunoglobulin (IVIG) were useful. To prevent relapse, CS, intermittent IVIG, immunosuppressants, and monoclonal antibodies were useful, but the efficacies of disease modifying drugs were uncertain. Sequelae such as visual disturbance, cognitive impairment, motor dysfunction, and epilepsy were observed in 11% of patients with MOG-IgG. CONCLUSIONS: MOG antibody-associated diseases were found to be common among pediatric ADS patients. Since a variety of sequelae were observed in these patients, it is important to identify the appropriate treatment to ensure the best outcome. The presence of the MOG autoantibody should be taken into consideration as part of the diagnostic criteria for pediatric ADS.

Clinical analysis of a patient simultaneously positive for antibodies of myelin oligodendrocyte glycoprotein and anti-N-methyl-D-aspartate receptor: A case report.

RATIONALE: Myelin oligodendrocyte glycoprotein (MOG) antibody (MOG-Ab) disease (MOG-AD) is a type of demyelinating disease of the central nervous system characterized by a high frequency of optic neuritis (ON) attacks. anti-Nmethyl-D-aspartate receptor (NMDAR) encephalitis (anti-NMDARe) is an autoimmune disorder characterized by memory deficits, conscious disturbance, and seizures. Cases of simultaneous occurrence of MOG-Ab and anti-NMDARe antibody (anti-NMDARe-Ab) are rarely reported and could be mistaken for overlapping MOG-antibody disease (MOG-AD) and NMDARe. The diagnosis of such patients is challenging. PATIENT CONCERNS: We report the case of a 37-year-old man who presented with recurrent headaches for 3 months and worsening symptoms over 2 weeks. He had a history of ON. He had a generalized seizure after 7 days in the hospital. DIAGNOSIS: Brain magnetic resonance imaging (MRI) and cerebrospinal fluid tests showed no apparent abnormalities. Repeat MRI showed slight lesions 7 days later, and cerebrospinal fluid tests showed the simultaneous occurrence of MOG-Ab and anti-NMDARe-Ab. INTERVENTIONS: He completely recovered after treatment with low doses of oral corticosteroids. OUTCOMES: Two months and 2 years follow-up showed that his condition was stable. LESSONS: The co-occurrence of MOG-Ab and anti-NMDAR-Ab does not indicate the co-occurrence of MOG-AD and anti-NMDARe. Laboratory findings should be combined with the clinical features to achieve an accurate and suitable diagnosis.

Overlapping central and peripheral nervous system syndromes in MOG antibody-associated disorders.

OBJECTIVE: Antibodies to myelin oligodendrocyte glycoprotein (MOG) are associated with CNS demyelination inclusive of optic neuritis (ON) and transverse myelitis (TM). To examine whether peripheral nervous system (PNS) involvement is associated with MOG antibody-associated disorders (MOGAD), we performed detailed characterization of an Australasian MOGAD cohort. METHODS: Using a live cell-based assay, we diagnosed 271 adults with MOGAD (2013-2018) and performed detailed clinical and immunologic characterization on those with likely PNS involvement. RESULTS: We identified 19 adults with MOGAD and PNS involvement without prior TM. All patients had CNS involvement including ON (bilateral [n = 3], unilateral [n = 3], and recurrent [n = 7]), a cortical lesion (n = 1), meningoencephalitis (n = 1), and subsequent TM (n = 4). Clinical phenotyping and neurophysiology were consistent with acute inflammatory demyelinating polyneuropathy (n = 1), myeloradiculitis (n = 3), multifocal motor neuropathy (n = 1), brachial neuritis (n = 2), migrant sensory neuritis (n = 3), and paresthesia and/or radicular limb pain (n = 10). Onset MRI spine was consistent with myeloradiculitis with nerve root enhancement in 3/19 and normal in 16/19. Immunotherapy resulted in partial/complete PNS symptom resolution in 12/15 (80%) (steroids and/or IV immunoglobulin n = 9, rituximab n = 2, and plasmapheresis n = 1). We identified serum antibodies targeting neurofascin 155, contactin-associated protein 2, or GM1 in 4/16 patients with MOGAD PNS compared with 0/30 controls (p = 0.01). There was no binding to novel cell surface antigens using an in vitro myelinating sensory neuronal coculture model. CONCLUSIONS: Myeloradiculitis, combined central and peripheral demyelination syndromes, and inflammatory neuropathies may be associated with MOGAD and may be immunotherapy responsive. We identified a subgroup who may have pathology mediated by coexistent autoantibodies.

E.U. paediatric MOG consortium consensus: Part 4 - Outcome of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders.

There is increasing knowledge on the role of antibodies against myelin oligodendrocyte glycoprotein (MOG-abs) in acquired demyelinating syndromes and autoimmune encephalitis in children. Better understanding and prediction of outcome is essential to guide treatment protocol decisions. Therefore, this part of the Paediatric European Collaborative Consensus provides an oversight of existing knowledge of clinical outcome assessment in paediatric MOG-ab-associated disorders (MOGAD). The large heterogeneity in disease phenotype, disease course, treatment and follow-up protocols is a major obstacle for reliable prediction of outcome. However, the clinical phenotype of MOGAD appears to be the main determinant of outcome. Patients with a transverse myelitis phenotype in particular are at high risk of accruing neurological disability (motor and autonomic), which is frequently severe. In contrast, having a single episode of optic neuritis any time during disease course is broadly associated with a lower risk of persistent disability. Furthermore, MOG-ab-associated optic neuritis often results in good functional visual recovery, although retinal axonal loss may be severe. The field of cognitive and behavioural outcome and epilepsy following demyelinating episodes has not been extensively explored, but in recent studies acute disseminated encephalomyelitis (-like) phenotype in the young children was associated with cognitive problems and epilepsy in long-term follow-up. In conclusion, main domains of importance in determining clinical outcome in paediatric MOGAD are visual, motor, autonomic and cognitive function. A standardised evaluation of these outcome domains in all children is of importance to allow adequate rehabilitation and follow-up.

Free light chains kappa can differentiate between myelitis and noninflammatory myelopathy.

OBJECTIVE: To test the hypothesis that the intrathecal synthesis of free light chain kappa (FLC-k) can be used as a CSF biomarker to differentiate patients with myelitis due to multiple sclerosis (MS), myelitis due to neuromyelitis optica spectrum disease (NMOSD), and noninflammatory myelopathy, we analyzed FLC-k in 26 patients with MS myelitis, 9 patients with NMOSD myelitis, and 14 patients with myelopathy. METHODS: This is a retrospective monocentric cohort study. FLC-k were analyzed using the nephelometric Siemens FLC-k kit in paired samples of CSF and sera. Intrathecal fraction (IF) of FLC-k was plotted in a FLC-k quotient diagram. RESULTS: Ninety-six percent of patients with MS myelitis had an intrathecal synthesis of FLC-k in comparison with 55.6% for NMOSD and 14.3% of patients with noninflammatory myelopathy. The locally synthesized absolute amount of FLC-k was significantly higher in patients with myelitis due to MS than in patients with NMOSD (p = 0.038) or noninflammatory myelopathy (p < 0.0001). The sensitivity of FLC-k synthesis to detect inflammation in patients with myelitis is 85.7%. Using a receiver operating characteristic analysis, FLC-k IF >78% can discriminate patients with myelitis due to MS and NMOSD with a sensitivity of 88.5% and a specificity of 88.9% CONCLUSIONS: With the hyperbolic reference range in quotient diagrams for FLC-k, it is possible to distinguish inflammatory myelitis from noninflammatory myelopathies. An FLC-k IF >78% can be a hint to suspect myelitis due to MS rather than NMOSD.

Psychosocial impact of paediatric demyelinating disorders: a scoping review.

AIM: To: (1) provide greater insight into the psychological and social impact of a range of demyelinating disorders, (2) explore differences between disorders, and (3) provide direction for future research. METHOD: Studies were identified by searching online databases. Studies that explored the psychological, emotional, or social impact of a range of demyelinating disorders in childhood, including acute disseminated encephalomyelitis (ADEM), optic neuritis, transverse myelitis, and multiple sclerosis, were included and screened independently by three authors. Data on the design, sample characteristics, psychosocial measures, key findings, and methodological strengths and limitations were extracted. Twenty-five studies were included in the narrative synthesis. RESULTS: Demyelinating disorders are associated with lower quality of life, affecting young people's emotional, social, school, and behavioural functioning. There is a high prevalence of psychiatric disorders and fatigue, particularly in multiple sclerosis. Subtle differences exist in the psychological presentation between different demyelinating disorders, with clear gaps in the research for the long-term psychosocial impact of monophasic conditions. INTERPRETATION: The difference between the impact of monophasic and relapsing demyelinating disorders on psychosocial functioning is unclear. Future research should aim to identify the psychosocial impact across disorders and over time, ensure that services are capturing those patients who may benefit from tailored interventions. WHAT THIS PAPER ADDS: Prevalence of psychiatric diagnoses in paediatric demyelinating disorders is higher than controls. Depression and emotional concerns are elevated in paediatric demyelinating disorders. Demyelinating disorders impact children's quality of life across school, social, and physical functioning.

Inflammatory Demyelinating Pseudotumor With Liver Dysfunction: IgG4 Related Disease With Primary Biliary Cholangitis.

Immunoglobulin G4 related disease (IgG4-RD) is a recently recognized immune-mediated disease which is far from understanding. A case of inflammatory demyelinating pseudotumor had been confirmed as IgG4-RD according to pathology features and clinical context. Combined with liver dysfunction, IgG4 related sclerotic cholangitis was suspected. However, primary biliary cholangitis was finally diagnosed by immune marks and histopathological findings. This is the first report in which mass lesions in the brain parenchyma were caused by IgG4-RD while liver dysfunction was due to primary biliary cholangitis. The clinical features of IgG4-RD are miscellaneous, and the accumulation of case reports might enrich clinicians experience and broaden their horizons about this condition.

MOG antibody disease manifesting as progressive cognitive deterioration and behavioral changes with primary central nervous system vasculitis.

We report a 60-year-old male with anti-myelin oligodendrocyte glycoprotein (MOG) antibody who developed progressive cognitive deterioration and behavioral changes, with no other focal signs, over 9 months. MRI showed numerous T2-hyperintense lesions with partial contrast enhancement in white and grey matter of cerebrum, cerebellum and spinal cord. A brain biopsy revealed perivascular inflammatory cell infiltration, disturbed vascular continuity and no demyelination, indicative of a lymphocytic pattern of primary CNS vasculitis (PCNSV). Contrast enhancement disappeared after immunotherapy; however, cognitive impairment was not improved. Neurologists should note that MOG antibody disease can present as immunotherapy-resistant progressive cognitive impairment with PCNSV-like histopathology.

Occipital neuralgia associates with high cervical spinal cord lesions in idiopathic inflammatory demyelinating disease.

BACKGROUND: The association of trigeminal neuralgia with pontine lesions has been well documented in multiple sclerosis, and we tested the hypothesis that occipital neuralgia in multiple sclerosis is associated with high cervical spinal cord lesions. METHODS: We retrospectively reviewed the records of 29 patients diagnosed with both occipital neuralgia and demyelinating disease by a neurologist from January 2001 to December 2014. We collected data on demographics, clinical findings, presence of C2-3 demyelinating lesions, and treatment responses. RESULTS: The patients with both occipital neuralgia and multiple sclerosis were typically female (76%) and had a later onset (age > 40) of occipital neuralgia (72%). Eighteen patients (64%) had the presence of C2-3 lesions and the majority had unilateral symptoms (83%) or episodic pain (78%). All patients with documented sensory loss (3/3) had C2-3 lesions. Most patients with progressive multiple sclerosis (6/8) had C2-3 lesions. Of the eight patients with C2-3 lesions and imaging at onset of occipital neuralgia, five (62.5%) had evidence of active demyelination. None of the patients with progressive multiple sclerosis (3/3) responded to occipital nerve blocks or high dose intravenous steroids, whereas all of the other phenotypes with long term follow-up (eight patients) had good responses. CONCLUSIONS: A cervical spine MRI should be considered in all patients presenting with occipital neuralgia. In patients with multiple sclerosis, clinical features in occipital neuralgia that were predictive of the presence of a C2-3 lesion were unilateral episodic symptoms, sensory loss, later onset of occipital neuralgia, and progressive multiple sclerosis phenotype. Clinical phenotype predicted response to treatment.

Ocular flutter as presenting manifestation of pediatric MOG antibody-associated demyelination: A case report.

A 13-year-old girl presented with a 5-day history of oscillopsia. On examination, ocular flutter and mild cerebellar signs were found. Brain magnetic resonance imaging (MRI) revealed four periventricular and subcortical non-enhancing lesions. Cerebrospinal fluid (CSF) oligoclonal bands were negative. Neuroblastoma or other malignancies were not found. She responded well to a corticosteroid-intravenous immunoglobulin (IVIG) combination and remained symptom-free for 3 years until presenting again with isolated ocular flutter. Brain MRI at this time remained atypical for classic multiple sclerosis (MS) with a predominance of juxtacortical demyelinating lesions. CSF was positive for oligoclonal bands. Serum myelin oligodendrocyte glycoprotein (MOG) antibodies were present. Ocular flutter can be the presenting feature of MOG antibody-associated pediatric demyelination.

Tocilizumab in MOG-antibody spectrum disorder: a case report.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-related spectrum disorders (MOG-SD) are a heterogeneous group of inflammatory demyelinating diseases of the central nervous system, usually responsive to conventional immunosuppressive therapies. However, knowledge about treatment of non-responder patients is scarce. METHODS: We report on a 20-year-old MOG-SD patient who experienced clinical deterioration despite rituximab-induced B-cell depletion. RESULTS: Rescue therapy with tocilizumab (TCZ) prevented further relapses, with reduction of spinal-cord load on MRI, and a remarkable reduction of disability at the two-year follow-up. CONCLUSION: Our observations suggest that TCZ could induce clinico-radiologic improvements, which make it as an option for the treatment of MOG-SD.

Progressive solitary sclerosis presented with diplopia: A case report.

OBJECTIVE: To report a patient presented with diplopia followed by progressive quadriparesis in the setting of a solitary pontomedullary lesion. CASE PRESENTATION: We report a 24-year-old woman presented with an attack of diplopia with full recovery, followed by progressive quadriparesis. The patient had a single pontomedullary lesion. Extensive diagnostic work up was negative. After follow up for 6 years, despite of clinical deterioration, the patient had the same pontomedullary lesion consistent with progressive solitary sclerosis. Corticosteroid pulse therapy and rituximab, didn't yield significant improvement, and the course was progressive, but after adding cyclophosphamide, partial improvement was seen. CONCLUSION: Progressive solitary sclerosis can cause progressive quadriparesis after an attack of diplopia without evidence of dissemination in time and space even after a prolonged period. This rare entity should be included in differential diagnosis of demyelinating lesions.

An unusual case of anti-MOG CNS demyelination with concomitant mild anti-NMDAR encephalitis.

We report the case of a patient who presented with progressive unsteadiness and narcoleptic attacks followed by behavioral change and psychosis, without visual disturbances or seizures. MRI revealed multiple areas of fluid attenuation inversion recovery (FLAIR) high-intensity lesions involving the cerebellum, brainstem, thalamus and third ventricular peri-ependymal region consistent with demyelination. Both the serum myelin oligodendrocyte glycoprotein-antibodies (MOG-Abs) and cerebral spinal fluid (CSF) anti-N-methyl-d-as-partate receptor (NMDAR) antibodies were positive using transfected cell based assays. The patient presented simultaneously with symptoms of MOG antibody disease and anti-NMDAR encephalitis, an unusual clinical scenario, indicating the co-existence of the two disorders.