Background

Ultra-high field MRI highlighted the crucial role of cortical injury in multiple sclerosis (MS). Cortical pathology is frequent in MS, and seems to be more pronounced in progressive stages of the disease. One aspect of cortical pathology is represented by focal cortical lesions (CL).

Pioneering studies demonstrated the high frequency of CL in MS, their independence from white matter injury and their clinical relevance, particularly for cognitive impairment. Nevertheless, very few is known about their presence from the onset of the disease, their dynamics of apparition, neither the differential impact of intracortical (IC) and leukocortical (LC) lesions in early MS.

Objectives

The present study aims to assess the prevalence, the topography and the clinical counterpart of cortical lesions in patients included in the first year of MS.

Methods

16 MS patients in the first year of their disease course and 12 matched controls were included. All subjects underwent a 7T brain MRI scan designed to maximize the accuracy of CL detection (sequences: MP2RAGE, FLAIR, FLAWS with 600μm³ isotropic resolution and T2*/QSM with 600μm² in-plane resolution and thickness of 600μm, total acquisition time 58 min). EDSS and MSFC were performed by rated physicians.

Radiological analysis: a cortical lesion was considered in case of signal change with identifiable boundaries compared to adjacent cortex on MP2RAGE, confirmed by at least one other sequence (FLAIR, FLAWS and T2*/QSM), excluding anatomical structure (eg vessels). CL were divided into two groups according to their location: leukocortical when the lesion extended across both white matter (WM) and grey matter (GM) and intracortical when the lesion is exclusively located within the GM. WM lesions were depicted on MP2RAGE and FLAIR sequences with a 3 mm minimal size.

Statistical analysis: patients and lesions descriptive data were presented with means and standard deviation (SD). Spearman correlations were performed between cortical and WM lesions count and clinical evaluations.

Results

Patients' caracteristics: 13 females, 3 males; mean age = 33 yo (SD = 9); mean disease duration = 6 months (SD = 3); mean EDSS = 0.28 (SD=0.51); mean relapse = 1.68 (SD = 1.01).

399 cortical lesions were detected in 14 patients (mean = 11.68, SD = 12.32). Among them 211 LC lesions were seen in 11 patients and 187 IC lesions in 14 patients. Mean number of WM lesions was 27 (SD = 27.45), mean volume was 2.15 mL (SD = 2.75). LC lesions were significantly correlated with WM lesions (ρ=0.91, p<.001). In opposite, IC lesions were not correlated with WM lesions (ρ=0.49, p=0.05) nor LC lesions (ρ=042, p=0.09). No lesions were seen in controls.

No correlations were found between cortical lesions and EDSS nor MSFC.

Conclusions

We evidenced that the prevalence of cortical lesions is very high at the earliest stage of MS and is not correlated with white matter impairment. This study confirms the accuracy of MP2RAGE to depicit these lesions.

Background

Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-antibody associated disease (MOG-AD) are orphan diseases with high impact on quality of life and to date unknown socio-economic burden.

Objectives

The aim of this study was to evaluate costs and health-related quality of life of NMOSD and MOG-AD from the societal perspective.

Methods

In a multicenter cross-sectional study throughout Germany between 04/2017 and 04/2019, the primary data on retrospective consumption of medical and non-medical resources and work ability related to NMOSD and MOG-AD were assessed via standardized and pre-tested paper-based patient questionnaires. Health-related quality of life was captured by the EuroQoL Group EQ-5D-5L questionnaire. Clinical data were retrieved from the Neuromyelitis Optica Study Group (NEMOS) database. Patient recruitment took place at 17 German NEMOS centers. Costs were analyzed in EUR for 2018.

Results

During the recruitment period, 218 of 275 adult patients were screened for eligibility. 212 patients (80.2% women; mean age 49 ± SD 15 years; mean disease duration 9 ± SD 8.5 years; Expanded Disability Status Scale (EDSS) 3.7 ± SD 2.1) were analyzed. The mean total annual per capita cost of illness accounted for EUR 59 576 and the mean index value of the EQ-5D-5L was 0.693. Given an estimated prevalence of NMOSD in Germany of 1.3/100 000, the annual burden from the societal perspective adds to EUR 64.3 Mio for Germany. The most important cost drivers were informal care costs (27.6% of total costs), indirect costs (23.3%; particularly loss of salary) and drugs, especially immunotherapeutics (16.4%). Costs showed a significant positive correlation with disease severity (p<0.0001); in the EDSS 6.5-8.5 subgroup the annual costs were EUR 129 436. Moreover, the health-related quality of life revealed a negative correlation with disease severity (p<0.0001); in the EDSS 6.5-8.5 subgroup the mean index value was 0.195.

Conclusions

These German data from the era without approved standard medications show enormous effects of the disease on costs and quality of life and might be helpful for estimating the impact and cost-effectiveness of new therapeutic approaches.

Background

“Spinal pain”, girdle-like dysesthesia, and painful spasms were noted already in earliest disease descriptions in the 18^th 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.