Mayo Clinic

Author Of 4 Presentations

Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0693 - Brainstem and cerebellar involvement in MOG-IgG Associated Disorder versus Aquaporin-4-IgG and Multiple Sclerosis (ID 1244)

Speakers
Presentation Number
P0693
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Brainstem and cerebellar involvement are recognized to occur in myelin-oligodendrocyte-glycoprotein-antibody-associated-disorder (MOGAD) and the clinical syndrome can be severe. However, data on brainstem and cerebellar involvement in MOGAD is limited.

Objectives

To determine the frequency and characteristics of brainstem/cerebellar involvement in MOGAD versus aquaporin-4-IgG-seropositive-neuromyelitis-spectrum-disorder (AQP4-IgG-NMOSD) and multiple sclerosis (MS).

Methods

In this observational study, we retrospectively identified 185 Mayo Clinic MOGAD patients and included those with: 1) characteristic MOGAD phenotype; 2) MOG-IgG seropositivity by live-cell-based-assay; 3) brainstem/cerebellar MRI lesion(s). We compared clinical, MRI and cerebrospinal fluid (CSF) characteristics of symptomatic brainstem/cerebellar attacks in MOGAD to AQP4-IgG-NMOSD (n=30) and MS (n=30).

Results

Brainstem/cerebellum involvement occurred in 62/185 (34%) MOGAD patients of which 39/62 (63%) had accompanying brainstem/cerebellum symptoms/signs. Ataxia (45%) and diplopia (26%) were common manifestations. The median age in years (range) in MOGAD of 24 (2–65) was younger than MS at 36 (19–65) and AQP4-IgG-NMOSD at 45 (6–72)(P<.05). Isolated brainstem/cerebellar attacks in MOGAD (9/39[23%]) were less frequent than MS (22/30[73%]; p<0.05) but not significantly different from AQP4-IgG-NMOSD (14/30[47%]; p=0.07). Diffuse middle cerebellar peduncle MRI-lesions favored MOGAD (17/37[46%]) over MS (3/30[10%]; P<0.05) and AQP4-IgG-NMOSD (3/30[10%]; p<0.05), while diffuse medulla, pons or midbrain MRI-lesions occasionally occurred in MOGAD and AQP4-IgG-NMOSD but never in MS. CSF oligoclonal bands were similarly rare in MOGAD (2/30[7%]) and AQP4-IgG-NMOSD (1/22[5%]; p>0.99) but common in MS (17/22[77%]; p<0.05). Expanded-disability-status-scale-score (EDSS) and brainstem/cerebellar functional-system-scores (FSS) at nadir and recovery did not significantly differ between the groups.

Conclusions

Brainstem/cerebellar involvement is common in MOGAD but usually occurs as a component of a multifocal CNS attack rather than in isolation. We identified clinical, CSF, and MRI attributes that can help discriminate MOGAD from AQP4-IgG-NMOSD and MS.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0696 - Characteristics of Myelin Oligodendrocyte Glycoprotein Antibody Positive Children with Demyelinating Disorders (ID 1565)

Speakers
Presentation Number
P0696
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Myelin oligodendrocyte glycoprotein (MOG) antibodies (ab) are detected in approximately 1/3 of children with demyelinating disease at onset; presentations commonly overlap with optic neuritis, neuromyelitis optica spectrum disorder (NMOSD) or acute disseminated encephalomyelitis. Serum MOG-ab titers have unclear relevance to disease course, and optimal treatment strategy is unknown.

Objectives

We aimed to characterize children with CNS demyelinating disorders who tested positive for MOG-ab. We also aimed to evaluate the relevance of serum MOG-ab titers for diagnosis, risk and severity of subsequent demyelinating events. Finally, we aimed to evaluate treatment strategies for MOG-ab positive children.

Methods

This retrospective study evaluated children with demyelinating disorders with onset before 18 years of age seen at the University of California, San Francisco who tested positive for MOG-ab (tested by live cell-based fluorescent activated cell sorting assay at Mayo Clinic) between October 2006-June 2020. Demographic information, clinical presentation at onset, MRI, CSF, brain biopsy, and treatment data were collected by chart review.

Results

Sixty children were included (mean onset age 8.2 years; 53% female; 72% white; 40% Hispanic or Latino). The most common clinical localization at onset included optic nerve (ON) (53%) and/or brainstem/cerebellum (42%). 83% of initial events were severe. Median EDSS assessed within 6 months of onset was 1.5 (range 0-4). 81% of initial brain MRIs had T2 bright lesions and 61% had gadolinium-enhancing lesions; T2 bright lesions were most commonly seen in subcortical areas (50%) and/or brainstem/cerebellum (33%). Oligoclonal bands were positive in 17% of initial CSF. 57% had initial serum MOG-ab titers ≥1:100 (median time from onset to first titer 15.4 months). Titers ≥1:320 were only observed within 2 months of an event (disease onset or relapse). While 38% had no relapses (mean follow-up 1.42 years), those who did had a median of 2 relapses (mean follow-up 3.83 years). The most commonly used treatments were interferon beta (28%) and rituximab (27%). Brain biopsy was performed in 2 patients and showed overt demyelination and prominent infiltration of monocyte lineage and polymorphonuclear cells.

Conclusions

The most common clinical onset localizations in MOG-ab positive children were ON and brainstem/cerebellum. Higher MOG-ab titers were only observed close to a clinical event.

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Neuromyelitis Optica and Anti-MOG Disease Poster Presentation

P0730 - More rapid recovery and improved outcome with early steroid therapy in MOG-IgG associated  optic neuritis (ID 1109)

Speakers
Presentation Number
P0730
Presentation Topic
Neuromyelitis Optica and Anti-MOG Disease

Abstract

Background

Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) are a biomarker of MOG-IgG associated disorder (MOGAD), a CNS demyelinating disease that disproportionately affects the optic nerves as optic neuritis (ON). MOG-IgG ON is usually associated with pain and is often steroid responsive, but details of this in a large cohort are lacking.

Objectives

To investigate whether timing of steroid treatment affects the rate and extent of visual recovery in a large cohort of MOGAD patients and examine the temporal relation of eye pain to visual loss.

Methods

We included consecutive patients evaluated by the neuro-ophthalmology departments at 5 centers from January 2017 to April 2020. Patients fulfilling the following criteria were included: (1) clinically documented history of ON; (2) serum positivity for MOG-IgG by live cell-based-assay. The details of each ON attack was recorded, including presence of eye pain, days of eye pain prior to the onset of vision loss, nadir of visual acuity loss, type of acute treatment, time to treatment, time to recovery, and final visual acuity after each attack.

Results

A total of 221 ON attacks in 115 patients with one or more episodes of MOG-IgG ON were included. The average age at the initial ON onset was 36.8 (SD 19.3); 71 (62%) were female. Eye pain was present in 171/193 (89%) of attacks with data collected on eye pain. Among 98 attacks with available temporal data, the pain began a mean of 4.2 (SD 4.2) days prior to the vision loss. Early steroid therapy administered to 9 patients (6 with MRI optic nerve enhancement; 3 had clinical ON but no MRI) with eye pain but lacking vision loss had resolution of eye pain and never developed vision loss.

Among 37 ON attacks treated with intravenous methylprednisolone (IVMP) within 2 days of onset of vision loss, the average time to recovery was 1.9 days (SD 3.1) compared to 12.1 days (SD 12.1) in 84 ON attacks treated later than 2 days (p<0.001). Those treated within 2 days had less severe visual acuity (VA) loss at time of treatment (mean LogMAR VA 0.62, SD .77) compared to those treated later than 2 days (mean LogMAR VA 1.6, SD 0.9), p<0.001, and also had a better final VA after IVMP (mean LogMAR VA 0.05, SD 0.11) compared to those treated later than 2 days (LogMAR VA 0.26, SD 0.57), p=0.034.

Conclusions

The observational findings that early IVMP leads to faster recovery and better outcomes and that pain precedes vision loss in the majority of MOG-IgG ON attacks suggests there may be a therapeutic window for steroid treatment that reduces the risk of permanent deficits.

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Invited Presentations Invited Abstracts

TC11.01 - Presentation 01 (ID 620)

Speakers
Authors
Presentation Number
TC11.01
Presentation Topic
Invited Presentations

Abstract

Abstract

Determining the cause of myelitis and distinguishing inflammatory from non-inflammatory etiologies is crucial as without early disease specific-treatment, morbidity can develop quickly and be irreversible. Recent studies have shown that large proportions of patients referred with idiopathic transverse myelitis actually have a specific cause identified for their myelopathy. Thus, idiopathic transverse myelitis is a diagnosis of exclusion and requires a comprehensive evaluation for alternative etiologies prior to assigning this diagnosis. The increasing number of specific causes of myelopathy/myelitis identified over the last two decades has made evaluation of such patients more challenging. This course will focus on demographic, clinical, serologic, and radiologic pearls that can help determine the cause of myelitis. We will also briefly review acute treatment. Determining the speed of onset and time to nadir is very helpful in narrowing the differential diagnosis of myelopathies. Improved recognition of the MRI features of myelopathies, particularly the gadolinium enhancement patterns, can give a clue to the diagnosis. The identification of diagnostic autoantibody biomarkers of myelitis (e.g., Aquaporin-4-IgG and Myelin Oligodendrocyte Glycoprotein-IgG IgG) has led to major improvements in our understanding of its underlying mechanisms and allowed their distinction from MS and other etiologies. Moreover, they have provided insight into the risk of recurrence, likelihood of treatment response and long-term outcome. Ancillary investigations including brain MRI are useful and may help determine the underlying cause (e.g., identification of typical multiple sclerosis lesions). The frequency of infectious myelitis varies by location and outbreaks of acute flaccid myelitis associated with enterovirus D69 are recognized to occur in children and should be specifically considered in endemic regions. The acute treatment of transverse myelitis associated with central nervous system inflammatory demyelinating diseases typically includes high-dose intravenous steroids with the addition of plasmapheresis in those with residual deficits. In conclusion, myelitis has a broad differential diagnosis and using the demographic, clinical, radiologic and serologic features can help determine the diagnosis and guide treatment.

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Presenter Of 1 Presentation

Invited Presentations Invited Abstracts

TC11.01 - Presentation 01 (ID 620)

Speakers
Authors
Presentation Number
TC11.01
Presentation Topic
Invited Presentations

Abstract

Abstract

Determining the cause of myelitis and distinguishing inflammatory from non-inflammatory etiologies is crucial as without early disease specific-treatment, morbidity can develop quickly and be irreversible. Recent studies have shown that large proportions of patients referred with idiopathic transverse myelitis actually have a specific cause identified for their myelopathy. Thus, idiopathic transverse myelitis is a diagnosis of exclusion and requires a comprehensive evaluation for alternative etiologies prior to assigning this diagnosis. The increasing number of specific causes of myelopathy/myelitis identified over the last two decades has made evaluation of such patients more challenging. This course will focus on demographic, clinical, serologic, and radiologic pearls that can help determine the cause of myelitis. We will also briefly review acute treatment. Determining the speed of onset and time to nadir is very helpful in narrowing the differential diagnosis of myelopathies. Improved recognition of the MRI features of myelopathies, particularly the gadolinium enhancement patterns, can give a clue to the diagnosis. The identification of diagnostic autoantibody biomarkers of myelitis (e.g., Aquaporin-4-IgG and Myelin Oligodendrocyte Glycoprotein-IgG IgG) has led to major improvements in our understanding of its underlying mechanisms and allowed their distinction from MS and other etiologies. Moreover, they have provided insight into the risk of recurrence, likelihood of treatment response and long-term outcome. Ancillary investigations including brain MRI are useful and may help determine the underlying cause (e.g., identification of typical multiple sclerosis lesions). The frequency of infectious myelitis varies by location and outbreaks of acute flaccid myelitis associated with enterovirus D69 are recognized to occur in children and should be specifically considered in endemic regions. The acute treatment of transverse myelitis associated with central nervous system inflammatory demyelinating diseases typically includes high-dose intravenous steroids with the addition of plasmapheresis in those with residual deficits. In conclusion, myelitis has a broad differential diagnosis and using the demographic, clinical, radiologic and serologic features can help determine the diagnosis and guide treatment.

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Moderator Of 1 Session

Teaching Course Fri, Sep 11, 2020

Invited Speaker Of 1 Presentation

Invited Presentations Invited Abstracts

TC11.01 - Presentation 01 (ID 620)

Speakers
Authors
Presentation Number
TC11.01
Presentation Topic
Invited Presentations

Abstract

Abstract

Determining the cause of myelitis and distinguishing inflammatory from non-inflammatory etiologies is crucial as without early disease specific-treatment, morbidity can develop quickly and be irreversible. Recent studies have shown that large proportions of patients referred with idiopathic transverse myelitis actually have a specific cause identified for their myelopathy. Thus, idiopathic transverse myelitis is a diagnosis of exclusion and requires a comprehensive evaluation for alternative etiologies prior to assigning this diagnosis. The increasing number of specific causes of myelopathy/myelitis identified over the last two decades has made evaluation of such patients more challenging. This course will focus on demographic, clinical, serologic, and radiologic pearls that can help determine the cause of myelitis. We will also briefly review acute treatment. Determining the speed of onset and time to nadir is very helpful in narrowing the differential diagnosis of myelopathies. Improved recognition of the MRI features of myelopathies, particularly the gadolinium enhancement patterns, can give a clue to the diagnosis. The identification of diagnostic autoantibody biomarkers of myelitis (e.g., Aquaporin-4-IgG and Myelin Oligodendrocyte Glycoprotein-IgG IgG) has led to major improvements in our understanding of its underlying mechanisms and allowed their distinction from MS and other etiologies. Moreover, they have provided insight into the risk of recurrence, likelihood of treatment response and long-term outcome. Ancillary investigations including brain MRI are useful and may help determine the underlying cause (e.g., identification of typical multiple sclerosis lesions). The frequency of infectious myelitis varies by location and outbreaks of acute flaccid myelitis associated with enterovirus D69 are recognized to occur in children and should be specifically considered in endemic regions. The acute treatment of transverse myelitis associated with central nervous system inflammatory demyelinating diseases typically includes high-dose intravenous steroids with the addition of plasmapheresis in those with residual deficits. In conclusion, myelitis has a broad differential diagnosis and using the demographic, clinical, radiologic and serologic features can help determine the diagnosis and guide treatment.

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