Author Of 3 Presentations
P0691 - Autologous Hematopoietic Stem Cell Transplantation in Neuromyelitis Optica – Year 5 Update (ID 1042)
Abstract
Background
Neuromyelitis Optica Spectrum Disorder (NMO/NMOSD) is an immune astrocytopathy characterized by disabling attacks of optic nerves, spine, the area postrema, hypothalamus and other CNS regions. Although new, targeted therapies have recently been approved, they require indefinite use, with data limited essentially to positive aquaporin-4 (AQP4) patients. As well, many patients may not have access to such agents and still rely on older, harsher immunosuppressants. The immunological features of NMO/NMOSD, coupled with its severity, make it an ideal candidate for trials of autologous hematopoietic stem cell transplantation (AHSCT), with the goal of disease remission and freedom from long-term treatment. Several small studies, with a variety of transplant regimens, have been presented thus far, with mixed results.
Objectives
To determine if NMO/NMOSD patients who have failed standard immune maintenance therapy, experience a reduction in relapse and disability without need for immune therapy after AHSCT.
Methods
Starting in 2010, patients were eligible and enrolled if they met Wingerchuk 2006 criteria for NMO, aged 18-65, with => 1 relapse in 12 months or => 2 in 24 months despite immunotherapy and EDSS < 6.5. Patients underwent non-ablative stem cell mobilization and infusion using cyclophosphamide (200mg/kg - divided as 50mg/kg/day over days -5 to -2), ATG and rituximab. The primary endpoint was a 50% reduction in relapse rate at year 3 (secondary at year 5). Additional outcomes included annualized relapse rate (ARR), EDSS, MRI, AQP4 serostatus, and optical coherence tomography over 5 years. Ten subjects were to be enrolled to provide 80% power.
Results
Between 2010-2015, 3 patients were enrolled and underwent AHSCT. A 28F, AQP4-, was transplanted in 2011. Her ARR dropped from 5 to 0 at both year 3 and 5, with her EDSS dropping from 4.0 to 2.0. A 36F, AQP4+, transplanted in 2012, had a reduction in her ARR from 4 to 0.67 at year 3, and 0.5 at year 5, with her EDSS dropping from 4.5 to 3.0 throughout the trial. She was treated with MMF after her two mild post-transplant relapses. The final patient, a 39M, AQP4+ was transplanted in 2014. He had a precipitous decline with an ARR increasing from 1.3 to 2 at year 3 and 5, and an EDSS increasing from 3.5 to 7.5 at year 3, with death from NMO at year 3.5. As well, both seropositive patients remained seropositive after transplant. The trial was closed in 2016 due to challenges in recruitment.
Conclusions
While the small cohort size limits interpretation, two of three patients had a marked improvement in their NMO activity and disability after AHSCT. Regimen selection and patient features may speak to the success and failures in this trial and other published studies, but it appears that AHSCT in NMO/NMOSD is a viable option worthy of further study and refinement.
P0726 - Longitudinally extensive transverse myelitis and NMOSD associated with dengue infection: a case report and systematic review of cases (ID 1155)
Abstract
Background
Neuromyelitis optica spectrum disorder (NMOSD) has been linked to para-and post-infectious triggers. Dengue virus (DENV) is one of the most common arbovirus infections in the world, with a wide spectrum of neurological clinical manifestations, including longitudinally extensive transverse myelitis (LETM), albeit rarely. It is unclear if the association is coincidental, permissive, or causal.
Objectives
We present a case of DENV-associated aquaporin-4 positive (AQP4) NMOSD with LETM with a systematic review of cases reported in the literature.
Methods
In addition to our case report, for the systematic review, we searched Medline/PubMed through April 2020, without language or design restrictions, for case reports, series and observational studies that described patients with DENV-associated LETM and/or NMOSD. We also hand-searched references and relevant conference abstracts.
Results
Case report: An adolescent girl who recently had immigrated from the Philippines presented with a 2-day history of paraparesis and urinary incontinence. Magnetic resonance imaging revealed spinal hyperintensity with patchy enhancement from T4-T7. AQP4 antibodies were positive on cell-based assay testing (Mayo Clinic Laboratories) with a titer of 1:10,000. She was diagnosed with AQP+ NMOSD. Infectious workup revealed serum +IgM and IgG antibodies against DENV, consistent with an acute dengue infection. She responded to high-dose steroids and subsequently started on rituximab maintenance. Literature review: Of 59 unique articles, 15 publications describing 18 patients met inclusion criteria. Age ranged from 8 months to 71-years (mean: 37.3) with no sex predominance. Imaging and CSF findings were heterogeneous. Four cases met 2015 criteria for NMOSD: two had LETM and optic neuritis, two had recurrent myelitis and area postrema syndrome, and one had LETM with AQP4 antibodies. The mainstay of treatment was IV methylprednisolone, although some also had IVIG and/or plasmapheresis. Prognosis varied, but few had long-term follow-up to assess for ongoing NMOSD activity.
Conclusions
DENV-associated LETM is rare, typically monophasic, and presents with severe disability, typically flaccid paraparesis. Immunotherapy should be instituted rapidly, particularly because the presentation could represent NMOSD. Decisions regarding longterm immunotherapy may depend on index of suspicion of true NMOSD, and this is where AQP4 status might be helpful. It is unknown whether there is an epidemiological or pathophysiological association between DENV infection and AQP4+ NMOSD.
P0765 - CRION versus Atypical MOG in a 61 Year-Old Woman (ID 1035)
Abstract
Background
Chronic relapsing inflammatory optic neuropathy (CRION) is defined as recurrent optic neuritis (ON) with relatively good response to steroids. Typical cases show optic nerve enhancement on MRI, and negative aquaporin-4 (AQP4) serology is a suggested criterion. Thus CRION phenotypes not uncommonly overlap with myelin oligodendrocyte glycoprotein (MOG) and MOG-associated disease (MOGAD). Several studies have shown a relatively high rate of positive MOG antibodies in CRION patients, begging the question of how to best investigate and treat CRION patients in the age of MOGAD.
Objectives
We present an atypical case of a 61 year-old woman with CRION to illustrate the behaviour, investigations, and treatment issues in distinguishing between CRION and MOGAD.
Methods
A full outline and timeline of the patient’s history, exam features, investigations and treatment response are presented, as well as data supporting the potential link between CRION and MOGAD.
Results
A 61 year-old woman presented in fall 2019 with a second R ON, her first episode having occurred 18 years prior with full spontaneous recovery. This was followed by another ON in the same eye one month later, and two severe bilateral ON attacks in a matter of a few months, resulting in light perception acuity only, and highly suggestive of MOGAD. Between 2019 and the present, her MRI has shown unchanging right optic nerve T2 hyperintense signal and gadolinium enhancement, with no other demyelinating features. Extensive immune investigations, including screening for SLE and Sjogren’s with an ENA panel, paraneoplastic antibody testing, and both local and Mayo Clinical Laboratories testing for AQP4 and MOG were unremarkable or negative, as was screening for malignancy and sarcoidosis. After her first bilateral ON episode, she had no meaningful response to high-dose steroid therapy with a prolonged taper, but had her subsequent, severe bilateral ON attack to OU LS occurred as she weaned off steroids, and required both high dose corticosteroids and plasma exchange to achieve OD HM and OS 20/60. Maintenance steroids and the initiation of a steroid-sparing agent have prevented further ON relapses thus far.
Conclusions
This case illustrates the similarities between CRION, MOGAD, but with several atypical features. Being aware of the possibility of MOGAD in addition to other entities, and ensuring a thorough workup with consideration of preventative immune therapy in steroid-responsive patients is essential.
Presenter Of 2 Presentations
P0691 - Autologous Hematopoietic Stem Cell Transplantation in Neuromyelitis Optica – Year 5 Update (ID 1042)
Abstract
Background
Neuromyelitis Optica Spectrum Disorder (NMO/NMOSD) is an immune astrocytopathy characterized by disabling attacks of optic nerves, spine, the area postrema, hypothalamus and other CNS regions. Although new, targeted therapies have recently been approved, they require indefinite use, with data limited essentially to positive aquaporin-4 (AQP4) patients. As well, many patients may not have access to such agents and still rely on older, harsher immunosuppressants. The immunological features of NMO/NMOSD, coupled with its severity, make it an ideal candidate for trials of autologous hematopoietic stem cell transplantation (AHSCT), with the goal of disease remission and freedom from long-term treatment. Several small studies, with a variety of transplant regimens, have been presented thus far, with mixed results.
Objectives
To determine if NMO/NMOSD patients who have failed standard immune maintenance therapy, experience a reduction in relapse and disability without need for immune therapy after AHSCT.
Methods
Starting in 2010, patients were eligible and enrolled if they met Wingerchuk 2006 criteria for NMO, aged 18-65, with => 1 relapse in 12 months or => 2 in 24 months despite immunotherapy and EDSS < 6.5. Patients underwent non-ablative stem cell mobilization and infusion using cyclophosphamide (200mg/kg - divided as 50mg/kg/day over days -5 to -2), ATG and rituximab. The primary endpoint was a 50% reduction in relapse rate at year 3 (secondary at year 5). Additional outcomes included annualized relapse rate (ARR), EDSS, MRI, AQP4 serostatus, and optical coherence tomography over 5 years. Ten subjects were to be enrolled to provide 80% power.
Results
Between 2010-2015, 3 patients were enrolled and underwent AHSCT. A 28F, AQP4-, was transplanted in 2011. Her ARR dropped from 5 to 0 at both year 3 and 5, with her EDSS dropping from 4.0 to 2.0. A 36F, AQP4+, transplanted in 2012, had a reduction in her ARR from 4 to 0.67 at year 3, and 0.5 at year 5, with her EDSS dropping from 4.5 to 3.0 throughout the trial. She was treated with MMF after her two mild post-transplant relapses. The final patient, a 39M, AQP4+ was transplanted in 2014. He had a precipitous decline with an ARR increasing from 1.3 to 2 at year 3 and 5, and an EDSS increasing from 3.5 to 7.5 at year 3, with death from NMO at year 3.5. As well, both seropositive patients remained seropositive after transplant. The trial was closed in 2016 due to challenges in recruitment.
Conclusions
While the small cohort size limits interpretation, two of three patients had a marked improvement in their NMO activity and disability after AHSCT. Regimen selection and patient features may speak to the success and failures in this trial and other published studies, but it appears that AHSCT in NMO/NMOSD is a viable option worthy of further study and refinement.
P0765 - CRION versus Atypical MOG in a 61 Year-Old Woman (ID 1035)
Abstract
Background
Chronic relapsing inflammatory optic neuropathy (CRION) is defined as recurrent optic neuritis (ON) with relatively good response to steroids. Typical cases show optic nerve enhancement on MRI, and negative aquaporin-4 (AQP4) serology is a suggested criterion. Thus CRION phenotypes not uncommonly overlap with myelin oligodendrocyte glycoprotein (MOG) and MOG-associated disease (MOGAD). Several studies have shown a relatively high rate of positive MOG antibodies in CRION patients, begging the question of how to best investigate and treat CRION patients in the age of MOGAD.
Objectives
We present an atypical case of a 61 year-old woman with CRION to illustrate the behaviour, investigations, and treatment issues in distinguishing between CRION and MOGAD.
Methods
A full outline and timeline of the patient’s history, exam features, investigations and treatment response are presented, as well as data supporting the potential link between CRION and MOGAD.
Results
A 61 year-old woman presented in fall 2019 with a second R ON, her first episode having occurred 18 years prior with full spontaneous recovery. This was followed by another ON in the same eye one month later, and two severe bilateral ON attacks in a matter of a few months, resulting in light perception acuity only, and highly suggestive of MOGAD. Between 2019 and the present, her MRI has shown unchanging right optic nerve T2 hyperintense signal and gadolinium enhancement, with no other demyelinating features. Extensive immune investigations, including screening for SLE and Sjogren’s with an ENA panel, paraneoplastic antibody testing, and both local and Mayo Clinical Laboratories testing for AQP4 and MOG were unremarkable or negative, as was screening for malignancy and sarcoidosis. After her first bilateral ON episode, she had no meaningful response to high-dose steroid therapy with a prolonged taper, but had her subsequent, severe bilateral ON attack to OU LS occurred as she weaned off steroids, and required both high dose corticosteroids and plasma exchange to achieve OD HM and OS 20/60. Maintenance steroids and the initiation of a steroid-sparing agent have prevented further ON relapses thus far.
Conclusions
This case illustrates the similarities between CRION, MOGAD, but with several atypical features. Being aware of the possibility of MOGAD in addition to other entities, and ensuring a thorough workup with consideration of preventative immune therapy in steroid-responsive patients is essential.