Long-term disability in neuromyelitis optica spectrum disorder with a history of myelitis is associated with age at onset, delay in diagnosis/preventive treatment, MRI lesion length and presence of symptomatic brain lesions

Mealy, Maureen A.; Mossburg, Sarah E.; Kim, Su Hyun; Messina, Silvia; Borisow, Nadja; López-González, Reydmar; Ospina, Juan Pablo; Scheel, Michael; Yeshokumar, Anusha K.; Awad, Amine; Leite, Maria Isabel; Arango, Jorge Andrés Jiménez; Paul, Friedemann; Palace, Jacqueline; Kim, Ho Jin; Lévy, Michaël

doi:10.1016/j.msard.2018.12.011

Cited by 52 publications

(43 citation statements)

References 33 publications

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“…However, it is unclear if the NMOSD disease course also leads to covert or diffuse and clinically relevant central nervous system damage, which can be systematically assessed by imaging biomarkers, for example, in the grey matter ( Pache et al , 2016 ) or the retina ( Oertel et al , 2018 ). Normal MRI volumetric deep grey matter (DGM) measures have been reported by some ( Finke et al , 2016 ), and it has been difficult to attribute clinical disability in NMOSD to systematic measures ( Mealy et al , 2019 ). Others reported cortical grey matter atrophy ( Kim et al , 2016 ) or DGM affection with clinical relevance, i.e.…”

Section: Introductionmentioning

confidence: 99%

Imaging markers of disability in aquaporin-4 immunoglobulin G seropositive neuromyelitis optica: a graph theory study

Chien

Oertel

Siebert

et al. 2019

Brain Communications

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Neuromyelitis optica spectrum disorders lack imaging biomarkers associated with disease course and supporting prognosis. This complex and heterogeneous set of disorders affects many regions of the central nervous system, including the spinal cord and visual pathway. Here, we use graph theory-based multimodal network analysis to investigate hypothesis-free mixed networks and associations between clinical disease with neuroimaging markers in 40 aquaporin-4-immunoglobulin G antibody seropositive patients (age = 48.16 ± 14.3 years, female:male = 36:4) and 31 healthy controls (age = 45.92 ± 13.3 years, female:male = 24:7). Magnetic resonance imaging measures included total brain and deep grey matter volumes, cortical thickness and spinal cord atrophy. Optical coherence tomography measures of the retina and clinical measures comprised of clinical attack types and expanded disability status scale were also utilized. For multimodal network analysis, all measures were introduced as nodes and tested for directed connectivity from clinical attack types and disease duration to systematic imaging and clinical disability measures. Analysis of variance, with group interactions, gave weights and significance for each nodal association (hyperedges). Connectivity matrices from 80% and 95% F-distribution networks were analyzed and revealed the number of combined attack types and disease duration as the most connected nodes, directly affecting changes in several regions of the central nervous system. Subsequent multivariable regression models, including interaction effects with clinical parameters, identified associations between decreased nucleus accumbens (β = −0.85, P = 0.021) and caudate nucleus (β = −0.61, P = 0.011) volumes with higher combined attack type count and longer disease duration, respectively. We also confirmed previously reported associations between spinal cord atrophy with increased number of clinical myelitis attacks. Age was the most important factor associated with normalized brain volume, pallidum volume, cortical thickness and the expanded disability status scale score. The identified imaging biomarker candidates warrant further investigation in larger-scale studies. Graph theory-based multimodal networks allow for connectivity and interaction analysis, where this method may be applied in other complex heterogeneous disease investigations with different outcome measures.

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Section: Introductionmentioning

confidence: 99%

Imaging markers of disability in aquaporin-4 immunoglobulin G seropositive neuromyelitis optica: a graph theory study

Chien

Oertel

Siebert

et al. 2019

Brain Communications

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“…Older age at onset was reported as a risk predictor of visual and motor disability in NMOSD (27). The late-onset course was associated with rapid disease progression and long-term disability (28)(29)(30), which might be explained by malfunctions in self-repair and blunted long-lived memory responses in aging individuals (31). Regarding responses to steroid treatment, conflicting results were reported.…”

Section: Discussionmentioning

confidence: 99%

Predictive Factors of Resistance to High-Dose Steroids Therapy in Acute Attacks of Neuromyelitis Optica Spectrum Disorder

et al. 2020

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High-dose steroids, the first-line therapy for acute attacks in neuromyelitis optica spectrum disorder (NMOSD), were ineffective in a proportion of NMOSD attacks. This study aimed to explore possible predictors of high-dose steroid resistance. Demographics and disease characteristics of acute attacks were compared between those who responded to high-dose intravenous methylprednisolone (IVMP) and those resistant to IVMP. In total, 197 attacks in 160 patients were identified in our NMOSD registry. Compared with responders, attacks resistant to high-dose steroids tended to have a higher proportion of previous history of immunosuppressive use (25.5 vs. 15.5%, p = 0.080). Significantly higher levels of proteins in the cerebrospinal fluid (CSF) were found in non-responders than in responders [485.5 (388–656) vs. 387 (291.5–532) mg/L, p = 0.006]. More active lesions were found in the brain stem of non-responders (8 attacks in 55, 14.5%), especially in the pons (7.3%) and medulla (14.5%), as opposed to responders (7 patients in 142, 4.9%). Multivariable logistic regression showed that resistance to high-dose steroid treatment was associated with previous immunosuppressant use [odds ratio (OR), 2.31; 95% confidence interval (CI) 1.002–5.34, p = 0.049], CSF protein level above 450 mg/L (OR 3.42, 95% CI 1.72–6.82, p < 0.001), and active lesions in the brainstem (OR 3.80, 95% CI 1.17–12.32, p = 0.026). In conclusion, NMOSD patients with previous use of immunosuppressants, higher levels of CSF protein, and active lesions in the brainstem are more likely to respond poorly to high-dose IVMP alone during an acute attack.

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“…NMOSD is a relapsing, inflammatory, autoimmune disorder ( Papp et al., 2018 ) characterized in large part by attacks of optic neuritis (ON) and transverse myelitis (TM) causing blindness and paresis in many patients ( Mealy et al., 2019 , Wingerchuk et al., 1999 , Wingerchuk et al., 2007 ). Attacks are unpredictable and tend to be severe (a ‘neuro-immunological stroke’) and recurrent ( Kitley et al., 2012 , Wingerchuk et al., 1999 ).…”

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confidence: 99%

“…Attacks are unpredictable and tend to be severe (a ‘neuro-immunological stroke’) and recurrent ( Kitley et al., 2012 , Wingerchuk et al., 1999 ). The initial presentation is 50% with TM, 35% with ON, and ON & TM in 10% patients, and 4% of patients with other syndromes ( Mealy et al., 2019 , Wingerchuk et al., 2007 , Hinson et al., 2016 ). The seropositive patients are overwhelmingly female ( Jarius et al., 2012 ).…”

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confidence: 99%

“…Therefore, complement fixation by NMO-IgG is unopposed once initiated. Anti-AQP4 antibodies fix compliment and begin a cascade of events to give rise to formation of the membrane attack complex (MAC) resulting in disruption of the astrocyte cell membranes ( Mealy et al., 2019 , Wingerchuk and Weinshenker, 2017 ). This damage can occur quite rapidly, perhaps within hours ( Herwerth et al., 2016 ).…”

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confidence: 99%

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Review of approved NMO therapies based on mechanism of action, efficacy and long-term effects

Brod

2020

Multiple Sclerosis and Related Disorders

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Highlights Neuromyelitis optica (NMO - including NMO spectrum disorders [NMOSD]) is a devastating disease. Up until recently, there was no proven agent to treat to prevent relapses. We now have three agents indicated for the treatment of NMO. We might suggest the following sequence – 1st line using eculizumab for rapid efficacy and stabilization without effect on the acquired immune system followed by satrilizumab (long term immunomodulation). Reserve inebilizumab (immunosuppressant) for breakthrough disease and salvage the severe with AHSCBMT. In NMO, control the complement, transition to modulation, and reserve suppression – and salvage the severe with AHSCBMT.

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Long-term disability in neuromyelitis optica spectrum disorder with a history of myelitis is associated with age at onset, delay in diagnosis/preventive treatment, MRI lesion length and presence of symptomatic brain lesions

Cited by 52 publications

References 33 publications

Imaging markers of disability in aquaporin-4 immunoglobulin G seropositive neuromyelitis optica: a graph theory study

Imaging markers of disability in aquaporin-4 immunoglobulin G seropositive neuromyelitis optica: a graph theory study

Predictive Factors of Resistance to High-Dose Steroids Therapy in Acute Attacks of Neuromyelitis Optica Spectrum Disorder

Review of approved NMO therapies based on mechanism of action, efficacy and long-term effects

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