Clinical characterization of long-term multiple sclerosis (COLuMbus) patients in Argentina: A cross-sectional non-interventional study.

BACKGROUND: Most Multiple Sclerosis (MS) clinical trials fail to assess the long-term effects of disease-modifying therapies (DMT) or disability. METHODS: COLuMbus was a single-visit, cross-sectional study in Argentina in adult patients with ≥10 years of MS since first diagnosis. The primary endpoint was to determine patient disability using the Expanded Disability Status Scale (EDSS). The secondary endpoints were to evaluate the distribution of diagnoses between relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS), patient demographics, disease history, and the risk of disability progression. The relationship between baseline characteristics and the current disability state and the risk of disability progression was assessed. RESULTS: Out of the 210 patients included, 76.7 % had a diagnosis of RRMS and 23.3 % had been diagnosed with SPMS, with a mean disease duration of 17.9 years and 20.5 years, respectively. The mean delay in the initial MS diagnosis was 2.6 years for the RRMS subgroup and 2.8 years for the SPMS subgroups. At the time of cut-off (28May2020), 90.1 % (RRMS) and 75.5 % (SPMS) of patients were receiving a DMT, with a mean of 1.5 and 2.0 prior DMTs, respectively. The median EDSS scores were 2.5 (RRMS) and 6.5 (SPMS). In the RRMS and SPMS subgroups, 23 % and 95.9 % of patients were at high risk of disability, respectively; the time since first diagnosis showed a significant correlation with the degree of disability. CONCLUSIONS: This is the first local real-world study in patients with long-term MS that highlights the importance of recognizing early disease progression to treat the disease on time and delay disability.

Tolerability of subcutaneous ofatumumab with long-term exposure in relapsing multiple sclerosis.

Background: Ofatumumab is approved for treating relapsing multiple sclerosis (RMS). Examining tolerability will enable understanding of its risk-benefit profile. Objective: Report the tolerability profile of ofatumumab in RMS during treatment of up to 4 years and the effect of pre-medication. Methods: Cumulative data from the overall safety population included patients taking continuous ofatumumab or being newly switched from teriflunomide. Injection-related reactions (IRRs) by incidence and severity, and post-marketing surveillance data, with an exposure of 18,530 patient-years, were analyzed. Results: Systemic IRRs affected 24.7% of patients (487/1969) in the overall safety population; most (99.2% [483/487]) were mild (333/487) to moderate (150/487) in Common Terminology Criteria for Adverse Events severity; most systemic IRRs occurred after first injection. Local-site IRRs affected 11.8% (233/1969) and most (99.6% [232/233]) were mild/moderate. Incidence and severity of systemic and localized IRRs were similar between continuous and newly switched patients across repeated injections. Systemic IRR incidence and severity were not substantially affected by steroidal or non-steroidal pre-medication. Post-marketing surveillance identified no new tolerability issues. Conclusion: Ofatumumab is well tolerated, displays a consistent safety profile during continuous use or after switching from teriflunomide and does not require pre-medication. This enables home management of RMS with a high-efficacy treatment.

Influence of physicians' risk perception on switching treatments between high- efficacy and non-high-efficacy disease­modifying therapies in multiple sclerosis.

BACKGROUND: The decision of initiating treatment for multiple sclerosis (MS) with a high-efficacy DMT (HE DMT) or non-high-efficacy DMT (non-HE DMT) is influenced by several factors, including risk perception of patients and physicians. OBJECTIVE: Investigate the influence of physicians' risk perception on decision-making when switching treatments for MS and the reasons for switching. METHODS: Data were drawn from the Adelphi Real-World MS Disease-Specific Program (a retrospective survey) and analysis included people with RMS identified between 2017- 2021. RESULTS: Of 4129 patients with reasons for switch available, 3538 switched from non-HE DMT and 591 from HE DMT. Overall, 4.7% of patients were switched treatment by their physicians due to the risk of malignancies and infections including PML risk. The proportion of switches that were made due to the risk of PML were 23.9% in the HE DMT and 0.5% in the non-HE DMT groups. The top reasons for switching were relapse frequency (non-HE DMT vs HE-DMT: 26.8% vs 15.2%), lack of efficacy (20.9 vs 11.7) and increased number of MRI lesions (20.3% vs 12.4%). CONCLUSIONS: Physicians' risk perception of malignancies and infection excluding PML was not a leading factor when switching treatment. The risk of PML was a key factor, especially for switching patients from HE DMTs. In both groups, lack of efficacy was the key contributing factor for switching. Initiating the treatment with HE DMTs may potentially reduce the number of switches due to sub-optimal efficacy. These findings might help physicians to engage more in discussions with patients about the benefit/risk profile of DMTs.

Optical coherence tomography in multiple sclerosis: A 3-year prospective multicenter study.

OBJECTIVE: To evaluate changes over 3 years in the thickness of inner retinal layers including the peripapillary retinal nerve fiber layer (pRNFL), and combined macular ganglion cell and inner plexiform layers (mGCIPL), in individuals with relapsing-remitting multiple sclerosis (RRMS) versus healthy controls; to determine whether optical coherence tomography (OCT) is sufficiently sensitive and reproducible to detect small degrees of neuroaxonal loss over time that correlate with changes in brain volume and disability progression as measured by the Expanded Disability Status Scale (EDSS). METHODS: Individuals with RRMS from 28 centers (n = 333) were matched with 64 healthy participants. OCT scans were performed on Heidelberg Spectralis machines (at baseline; 1 month; 6 months; 6-monthly thereafter). RESULTS: OCT measurements were highly reproducible between baseline and 1 month (intraclass correlation coefficient >0.98). Significant inner retinal layer thinning was observed in individuals with multiple sclerosis (MS) compared with controls regardless of previous MS-associated optic neuritis--group differences (95% CI) over 3 years: pRNFL: -1.86 (-2.54, -1.17) µm; mGCIPL: -2.03 (-2.78, -1.28) µm (both p < 0.0001; effect sizes 0.39 and 0.34). Greater inner retinal layer atrophy was observed in individuals diagnosed with RRMS <3 years versus >5 years (pRNFL: p < 0.05; mGCIPL: p < 0.01). Brain volume decreased by 1.3% in individuals with MS over 3 years compared to 0.5% in control subjects (effect size 0.76). mGCIPL atrophy correlated with brain atrophy (p < 0.0001). There was no correlation of OCT data with disability progression. INTERPRETATION: OCT has potential to estimate rates of neurodegeneration in the retina and brain. The effect size for OCT, smaller than for magnetic resonance imaging based on Heidelberg Spectralis data acquired in this study, was increased in early disease.

ENCOMS: Argentinian survey in cost of illness and unmet needs in multiple sclerosis.

UNLABELLED: The objective of the study was to assess the cost of multiple sclerosis (MS) patients in Argentina categorized by disease severity using a societal perspective. METHOD: Cross-sectional study including MS patients from 21 MS centers in 12 cities of Argentina. Patients were stratified by disease severity using the expanded disability status scale (EDSS) (group 1 with EDSS score between 0 and 3; group 2 with EDSS >3 and <7; group 3 with EDSS ≥7). Direct and indirect costs were analyzed for the second quarter of 2012 from public sources and converted to US Dollars. RESULTS: 266 patients were included. Mean annual cost per MS patient was USD 36,025 (95%CI 31,985-38,068) for patients with an EDSS between 0-3; USD 40,705 (95%CI 37,199-46,300) for patients with EDSS >3 and <7, and USD 50,712 (95%CI 47,825-62,104) for patients with EDSS ≥7. CONCLUSIONS: This is the first Argentine study evaluating the costs of MS considering disease severity.

ENCOMS: Argentinian survey in cost of illness and unmet needs in multiple sclerosis / ENCOMS: encuesta argentina sobre costos de la enfermedad y necesidades no cubiertas en pacientes con esclerosis múltiple

The objective of the study was to assess the cost of multiple sclerosis (MS) patients in Argentina categorized by disease severity using a societal perspective. Method: Cross-sectional study including MS patients from 21 MS centers in 12 cities of Argentina. Patients were stratified by disease severity using the expanded disability status scale (EDSS) (group 1 with EDSS score between 0 and 3; group 2 with EDSS >3 and <7; group 3 with EDSS ≥7). Direct and indirect costs were analyzed for the second quarter of 2012 from public sources and converted to US Dollars. Results: 266 patients were included. Mean annual cost per MS patient was USD 36,025 (95%CI 31,985-38,068) for patients with an EDSS between 0-3; USD 40,705 (95%CI 37,199-46,300) for patients with EDSS >3 and <7, and USD 50,712 (95%CI 47,825-62,104) for patients with EDSS ≥7. Conclusions: This is the first Argentine study evaluating the costs of MS considering disease severity. .

El objetivo del estudio fue evaluar el costo de los pacientes con esclerosis múltiple (EM) en Argentina categorizados por severidad de la enfermedad. Método: Estudio de corte transversal que incluyó pacientes con EM en 12 ciudades de Argentina. Los pacientes se estratificaron según expanded disability status scale (EDSS) (grupo 1 EDSS entre 0 y 3; grupo 2 EDDS >3 y <7; grupo 3 EDSS ≥7). Los costos directos e indirectos fueron analizados para el segundo trimestre de 2012 y convertidos a dólares estadounidenses. Resultados: 266 pacientes fueron incluidos. El coste medio anual por paciente con EM fue de USD 36,025 (31,985-38,068 IC95%) para los pacientes con un EDSS entre 0-3; USD 40,705 (37,199-46,300 IC95%) para los pacientes con EDSS >3 y <7 y USD 50,712 (47,825-62,104 IC95%) para los pacientes con EDSS ≥7. Conclusiones: Primer estudio argentino evaluar los costes de la EM considerado la gravedad de la enfermedad. .

Rapid and efficient localization of depth electrodes and cortical labeling using free and open source medical software in epilepsy surgery candidates.

Depth intracranial electrodes (IEs) placement is one of the most used procedures to identify the epileptogenic zone (EZ) in surgical treatment of drug resistant epilepsy patients, about 20-30% of this population. IEs localization is therefore a critical issue defining the EZ and its relation with eloquent functional areas. That information is then used to target the resective surgery and has great potential to affect outcome. We designed a methodological procedure intended to avoid the need for highly specialized medical resources and reduce time to identify the anatomical location of IEs, during the first instances of intracranial EEG recordings. This workflow is based on established open source software; 3D Slicer and Freesurfer that uses MRI and Post-implant CT fusion for the localization of IEs and its relation with automatic labeled surrounding cortex. To test this hypothesis we assessed the time elapsed between the surgical implantation process and the final anatomical localization of IEs by means of our proposed method compared against traditional visual analysis of raw post-implant imaging in two groups of patients. All IEs were identified in the first 24 H (6-24 H) of implantation using our method in 4 patients of the first group. For the control group; all IEs were identified by experts with an overall time range of 36 h to 3 days using traditional visual analysis. It included (7 patients), 3 patients implanted with IEs and the same 4 patients from the first group. Time to localization was restrained in this group by the specialized personnel and the image quality available. To validate our method; we trained two inexperienced operators to assess the position of IEs contacts on four patients (5 IEs) using the proposed method. We quantified the discrepancies between operators and we also assessed the efficiency of our method to define the EZ comparing the findings against the results of traditional analysis.

Noninvasive approach to focal cortical dysplasias: clinical, EEG, and neuroimaging features.

Purpose. The main purpose is to define more accurately the epileptogenic zone (EZ) with noninvasive methods in those patients with MRI diagnosis of focal cortical dysplasia (FCD) and epilepsy who are candidates of epilepsy surgery. Methods. Twenty patients were evaluated prospectively between 2007 and 2010 with comprehensive clinical evaluation, video-electroencephalography, diffusion tensor imaging (DTI), and high-resolution EEG to localize the equivalent current dipole (ECD). Key Findings. In 11 cases with white matter asymmetries in DTI the ECDs were located next to lesion on MRI with mean distance of 14.63 millimeters with topographical correlation with the EZ. Significance. We could establish a hypothesis of EZ based on Video-EEG, high-resolution EEG, ECD method, MRI, and DTI. These results are consistent with the hypothesis that the EZ in the FCD is complex and is often larger than visible lesion in MRI.

Association between equivalent current dipole source localization and focal cortical dysplasia in epilepsy patients.

We analysed the association between focal cortical dysplasia (FCD) visible in MRI and the location of equivalent current dipole (ECD) of single interictal scalp EEG spikes (IIS) in 11 epilepsy patients. We calculated several indicators of distance of ECDs to the FCD border. The results confirm some previous studies suggesting that the epileptogenic zone associated to the location of ECDs extends beyond the FCD visible in MRI. The analysis suggests the ECDs to be in a shell parallel to part of the FCD surface.