Author Of 5 Presentations
P0153 - Serum neurofilament light chain and retinal layer thickness measurements are complementary predictors of disease activity in early multiple sclerosis. (ID 1808)
Abstract
Background
Serum neurofilament light chain (sNfL) and retinal optical coherence tomography (OCT) measurements have individually been shown to be promising biomarkers for future disease activity in multiple sclerosis (MS).
Objectives
To investigate the complementary value of sNfL and retinal OCT measurements for predicting disease activity in patients with early MS at a stable disease state.
Methods
We retrospectively screened patients with early MS or clinically isolated syndrome (CIS) from a prospective cohort study (Berlin CIS cohort). The baseline sNfL (single-molecule array (SimoaTM) assay) were determined between 12 and 24 months after initial disease onset. Inclusion criteria were the availability of baseline sNfL, OCT measurements, clinical and MRI follow-up data (new relapses, expanded disability status scale (EDSS), new T2 lesions, composing the no evidence of disease activity (NEDA-3) criteria) over a period of at least 365 days. Exclusion criteria were concomitant eye diseases interfering with OCT and a relapse within 120 days before baseline visit. For Cox regression hazard models, patients were grouped with regards to their sNfL level (abnormal/normal: ≥/< 95th percentile of age-matched reference value) and their peripapillary retinal nerve fiber layer (pRNFL: >/≤ 100 µm) and ganglion cell and inner plexiform layer (GCIP: >/≤ 1.99 mm3) in non-optic neuritis eyes. Analysis was censored after 760 days.
Results
We included 78 patients (50 females, age: 36.4 ± 7.6 years) with a median follow-up of 728 days (range: 709 – 751 days). Patients with abnormal sNfL at baseline showed a significantly higher risk for developing a new relapse (Hazard Ratio (HR): 3.33, 95% confidence interval (CI): 1.43 – 7.71, p = 0.003), a new lesion (HR: 2.64, CI: 1.35 – 5.18, p = 0.003) and violating NEDA-3 (HR: 3.22, CI: 1.73 – 6.01. p < 0.001). Patients with both thinner pRNFL and abnormal sNfL value had a greater risk for developing a new relapse (HR: 8.12, CI: 2.17 – 30.46, p = 0.002) and violating NEDA-3 criteria (HR: 4.28, CI: 1.81 – 10.14, p < 0.001) than patients with only one of the risk factors. Meanwhile, patients with thinner GCIP and abnormal sNfL not only yielded greater risk for new relapse (HR: 6.51, CI 2.06 – 20.63, p = 0.001) and NEDA-3 violation (HR: 4.48, CI: 2.11 – 9.50, p < 0.001), but also for new lesion (HR: 3.11, CI: 1.42 – 6.80, p = 0.004).
Conclusions
In patients with early MS, presence of both abnormal sNfL and OCT measurements may be a stronger risk factor for future disease activity than presence of each risk factor alone.
P0509 - Utility of NEDA-3 status as a predictor of future disease activity (ID 1643)
Abstract
Background
No evidence of disease activity (NEDA) is viewed as an important goal in relapsing multiple sclerosis (MS) and has been advocated as a benchmark for treatment decisions. However, NEDA status is maintained only by a minority of MS patients over prolonged periods, regardless of disease-modifying treatment. The predictive value and utility of NEDA in guiding individual therapy remains unclear.
Objectives
To investigate the association of NEDA-3 status and criteria subitems in a one-year reference period with subsequent disease activity.
Methods
We included 113 patients (age 35 ± 10 years, 67 (59.3%) female) with relapsing remitting MS who had annual clinical and MRI follow-up visits. There were no restrictions on disease-modifying therapy. The first year of follow-up was considered the reference period. Patients had a median of 2.8 years follow-up time (interquartile range 1.1 - 4.0 years) after the reference period. NEDA-3 status was established based on relapse assessment, 1-point increase in the expanded disability status scale (EDSS, unrelated to relapse activity) and the appearance of new T2-weighted or contrast-enhancing lesions.
Results
Patients who failed NEDA-3 criteria during the reference period had an increased rate of subsequent NEDA-3 failure (Hazard ratio (HR) 1.84, 95% confidence interval (CI) 1.12-3.02, p=0.0165). Attacks and new lesions during the reference period were associated with a new relapse (HR 2.872, CI 1.31-6.30, p=0.00843) or a new lesion (HR 2.57, CI 1.49-4.43, p=0.000691) during subsequent follow-up, respectively. An EDSS increase in the reference period was not predictive of a future failure of NEDA-3.
Conclusions
Relapses and new lesions increase the risk of future disease activity in relapsing-remitting MS, irrespective of disease-modifying therapy. Relapse-independent disability progression appears to be less useful in predicting future disease activity.
P0741 - Pain, depression and quality of life in adults with MOG-antibody associated disease (ID 1622)
Abstract
Background
Myelin oligodendrocyte glycoprotein-antibody (MOG-ab) associated disease (MOGAD) is an inflammatory autoimmune condition of the CNS, clinically resembling seropositive neuromyelitis spectrum disorder (NMOSD). Despite severe pain is one of the most frequent and disabling symptoms in NMOSD, data on pain in MOGAD are scarce and clinical case reports and series often ignore it as a severe symptom.
Objectives
To assess features of chronic pain, depression, and their impact on health-related quality of life (hr-QoL) in MOG-antibody associated disease (MOGAD).
Methods
Patients with MOGAD were identified in the Neuromyelitis Optica Study Group (NEMOS) registry. Data were acquired by a questionnaire, including clinical, demographic, pain (PainDetect, Brief Pain Inventory - short form, McGill Pain Questionnaire - short form), depression (Beck Depression Inventory-II), and hr-QoL (Short Form-36 Health Survey) items.
Results
Forty-three patients (29 female, 14 male) were included. Twenty-two patients suffered from disease-related pain (11 nociceptive, 8 definite neuropathic, 3 possible neuropathic pain). Patients with neuropathic pain reported higher pain intensity compared to those with nociceptive (pain severity index (PSI)±SD: 5.7±2.0 vs. 2.8±1.3, p=0.003) and more profound impairment of activity of daily living (ADL). Fifteen patients reported spasticity-associated pain, including four with short lasting painful tonic spasms. Twelve patients received pain medication, still suffering from moderate pain (PSI±SD: 4.6±2.3). Only four out of 10 patients with moderate to severe depression took antidepressants. Physical QoL was more affected in pain-sufferers (p<0.001) than in patients without pain, being most severely reduced in patients with neuropathic pain (p=0.016) compared to other pain-sufferers. Pain severity (B=-5.455, SE=0.810, p<0.001), visual impairment (B=-8.163, SE=1.742, p<0.001), and gait impairment (B=-5.756, SE=1.875, p=0.005) were independent predictors of low physical QoL. Depressive state (B=-15.484, SE=2.896, p<0.001) was the only predictor for reduced mental QoL.
Conclusions
Being highly prevalent, pain and depression strongly reduce QoL and ADL in MOGAD. Although treatable, both conditions remain insufficiently controlled in real-life clinical practice
P0742 - Pain, depression and quality of life in NMOSD: a cross-sectional study of 166 AQP4-antibody seropositive patients in Europe (ID 1645)
Abstract
Background
“Spinal pain”, girdle-like dysesthesia, and painful spasms were noted already in earliest disease descriptions in the 18th century. Nowadays it has become clear that pain is a frequent and one of the most disabling symptoms in these patients. Due to the rarity of NMOSD most previous studies of pain and depression were relatively small or included a mixed population AQP4-IgG-seropositive and seronegative patients, while recent clinical trials clearly indicate that pathogenetic mechanisms are different in these forms.
Objectives
To evaluate prevalence, clinical characteristics and predictive factors of pain, depression and their impact on the quality of life (QoL) in a large European seropositive neuromyelitis optica spectrum disease (NMOSD) cohort.
Methods
We included 166 patients with aquaporin-4-seropositive NMOSD from 13 tertiary referral centers of Neuromyelitis Optica Study Group (NEMOS). Clinical data, including expanded disability status scale and localization of spinal lesions on MRI, were retrieved from the NEMOS database or local electronic patient records. Data on pain, depression and quality of life were captured by self-reporting questionnaires.
Results
125 (75.3%) patients suffered from chronic NMOSD-associated pain. Of these, 65.9% had neuropathic pain, 68.8% reported spasticity-associated pain and 26.4% painful tonic spasms. Number of previous myelitis attacks (OR 1.27, p=0.018) and involved upper thoracic segments (OR 1.31, p=0.018) were the only predictive factors for chronic pain. Interestingly, the latter was specifically associated with spasticity-associated (OR 1.36, p=0.002), but not with a neuropathic pain. 39.8% suffered from depression (moderate to severe in 51.5%). Pain severity (OR 1.81, p<0.001) and especially neuropathic character (OR 3.44, P<0.001) were strongly associated with depression. 70.6% of patients with moderate or severe depression and 42.5% of those with neuropathic pain had no specific medications. 64.2% of those under symptomatic treatment still reported moderate to severe pain. Retrospectively, 39.5% of pain-sufferers reported improvement of pain after start of immunotherapy: 37.3% under rituximab, 40.0% under azathioprine, 33.3% under mycophenolate mofetil and 66.7% under tocilizumab. However, there was no difference in terms of pain prevalence or intensity in patients with different immunotherapies. Pain intensity, walking impairment and depression could explain 56% of the physical QoL variability, while depression was the only factor, explaining 46% of the mental QoL variability.
Conclusions
Myelitis episodes involving upper thoracic segments are main drivers of pain in NMOSD. Although pain intensity was lower than in previous studies, pain and depression remain undertreated and strongly affect QoL. Interventional studies on targeted treatment strategies for pain are urgently needed in NMOSD.
P0945 - Brain choroid plexus volume in Multiple Sclerosis versus Neuromyelitis Optica Spectrum Disease (ID 1476)
Abstract
Background
Neuromyelitis optica spectrum disease (NMOSD) and multiple sclerosis (MS) have a different pathophysiology. Accumulating evidence suggests that the choroid plexus plays a pivotal role in the pathogenesis of MS. However, MRI data comparing the choroid plexus volume between MS and NMOSD are scarce.
Objectives
To compare the choroid plexus volume in MS vs. NMOSD in vivo using high-resolution 3D MRI data. Migraine patients and healthy individuals served as control groups.
Methods
We included 95 MS patients [45% secondary progressive (SP); mean age 51.0±11.5 years; disease duration 20.8±10.4 years, 62% female; median Expanded Disability Status Scale (EDSS) 4.0], 43 NMOSD patients [28/43 anti-aquaporin 4 antibody positive; 11/43 anti-myelin oligodendrocyte glycoprotein antibody positive; 87% female; mean age 50.0±13.8 years; disease duration 6.8±7.3 years, median EDSS 3.0], 38 migraine patients [mean age 39±13 years, 79% female; 15/38 migraine with aura] and 65 healthy individuals [HCs, mean age 41±17 years, 48% female]. The choroid plexus of the lateral ventricles and T2-weighted (T2w) white matter lesions (WMLs) were segmented fully automated on T1-weighted (T1w) magnetization-prepared rapid gradient echo (MPRAGE) images and fluid attenuated inversion recovery sequences (FLAIR, voxel size of both sequences 1x1x1 mm3), respectively, using a supervised deep learning algorithm (multi-dimensional gated recurrent units). Total intracranial volume (TIV) and lateral ventricle volumes were assessed fully automated using Freesurfer. All outputs were reviewed and manually corrected (if necessary) using 3D-Slicer by trained raters who were blinded to the clinical information. Group differences were analyzed using multivariable generalized linear models (GLMs) adjusted for age, gender, TIV and lateral ventricle volume. Cohens’ d was used to calculate the standardized difference between the respective groups. Given p-values are adjusted for multiple comparisons (Bonferroni).
Results
Mean choroid plexus was larger in MS compared to NMOSD (1907±455 vs. 1467±408 µl; p<0.001, d=0.86), HCs (1663±424 µl; p=0.007, d=1.17) and migraine (1527±366 µl; p=0.02, d=0.72). There was no statistical difference in the choroid plexus volume between NMOSD, migraine and HCs. The choroid plexus was marginally larger in RRMS than SPMS (1959±482 vs. 1875±476 µl; p=0.28; d=0.17) and in untreated MS patients compared to MS patients on disease modifying therapy (2111±382 vs. 1876±459 µl; p=0.36). However, these differences did not reach statistical significance after correction for multiple comparisons. There was no association between the choroid plexus volume and total T2w WML volume in MS.
Conclusions
Patients with MS have larger choroid plexus than HCs, migraine and NMOSD patients. Further studies are warranted to investigate the respective roles of the choroid plexus in the pathogenesis of MS and NMOSD.