Abstract: EP1325
Type: ePoster
Abstract Category: Clinical aspects of MS - 4 Natural course
Objective: To demonstrate how the topographical model of MS can depict early manifestations of progressive disease utilizing a longitudinal clinical cohort.
Background: The topographical model depicts the admixture of relapsing and progressive aspects of MS. Central to this model is the observation that progression recapitulates a patient's prior relapse symptoms and clinically reveals previously silent lesions, incrementally manifesting a patient's underlying “disease topography”. Using this cohort, we have previously demonstrated protracted diagnostic uncertainty during the transition to SPMS. Earlier identification of progressive disease may have implications for patient care and trial design.
Methods: We examined a subgroup of 10 patients from our published longitudinal cohort who transitioned from RRMS to SPMS. Neurologic exams were analyzed from all MS relapses during the RRMS phase, at time of formal SPMS diagnosis, and at most recent clinical visit. Functional Systems (FS) affected, location/laterality, and extent of recovery were recorded. Given its prognostic significance, the pyramidal/motor system served as the target FS for assessment of laterality and severity of symptoms at relapse and SPMS timepoints. Each patient's clinical course was mapped using the topographical model disease simulation software.
Results: Our cohort was 80% female, aged 31.6±8.6 years at diagnosis, followed for an average of 23.8±8.8 years with a mean of 3.1 relapses prior to SPMS classification. Symptoms were categorized by topographical regions of the model (spinal cord/optic nerve, brainstem/cerebellum, cerebral hemispheres). 83.3±0.2% of acute relapse symptoms were present at the transition to SPMS, increasing to 91.0±0.2% at most recent visit. These data demonstrate a correlation between the topographical distribution of relapse symptoms and accumulated deficits from subsequent progression. Mapped in the topographical model, above-threshold progressive disease became apparent an average of 7.3 years (range 5-11) earlier than the diagnosis of SPMS was applied in practice.
Conclusions: We have demonstrated the model's utility in depicting patients' disease topography as the loci of clinical progression. We utilize the recapitulation hypothesis to identify leading indicators of progression in individual patients to allow for precise, early recognition of progressive disease. Future empirical refinement using large clinical cohorts is planned.
Disclosure:
SC. Krieger has received compensation for consulting and advisory board work with Acorda Therapeutics Inc.; Bayer; Biogen; EMD Serono (Merck & Co., Inc.); Genentech; Genzyme; Mallinckrodt; Novartis; and Teva Pharmaceutical Industries Ltd. and has given non-promotional lectures with Biogen.
K. Cook, and M. Fletcher are employees of Harrison and Star, LLC, a healthcare communications company, which provided services for this project on a pro bono basis.
BM. Laitman has nothing to disclose.
Abstract: EP1325
Type: ePoster
Abstract Category: Clinical aspects of MS - 4 Natural course
Objective: To demonstrate how the topographical model of MS can depict early manifestations of progressive disease utilizing a longitudinal clinical cohort.
Background: The topographical model depicts the admixture of relapsing and progressive aspects of MS. Central to this model is the observation that progression recapitulates a patient's prior relapse symptoms and clinically reveals previously silent lesions, incrementally manifesting a patient's underlying “disease topography”. Using this cohort, we have previously demonstrated protracted diagnostic uncertainty during the transition to SPMS. Earlier identification of progressive disease may have implications for patient care and trial design.
Methods: We examined a subgroup of 10 patients from our published longitudinal cohort who transitioned from RRMS to SPMS. Neurologic exams were analyzed from all MS relapses during the RRMS phase, at time of formal SPMS diagnosis, and at most recent clinical visit. Functional Systems (FS) affected, location/laterality, and extent of recovery were recorded. Given its prognostic significance, the pyramidal/motor system served as the target FS for assessment of laterality and severity of symptoms at relapse and SPMS timepoints. Each patient's clinical course was mapped using the topographical model disease simulation software.
Results: Our cohort was 80% female, aged 31.6±8.6 years at diagnosis, followed for an average of 23.8±8.8 years with a mean of 3.1 relapses prior to SPMS classification. Symptoms were categorized by topographical regions of the model (spinal cord/optic nerve, brainstem/cerebellum, cerebral hemispheres). 83.3±0.2% of acute relapse symptoms were present at the transition to SPMS, increasing to 91.0±0.2% at most recent visit. These data demonstrate a correlation between the topographical distribution of relapse symptoms and accumulated deficits from subsequent progression. Mapped in the topographical model, above-threshold progressive disease became apparent an average of 7.3 years (range 5-11) earlier than the diagnosis of SPMS was applied in practice.
Conclusions: We have demonstrated the model's utility in depicting patients' disease topography as the loci of clinical progression. We utilize the recapitulation hypothesis to identify leading indicators of progression in individual patients to allow for precise, early recognition of progressive disease. Future empirical refinement using large clinical cohorts is planned.
Disclosure:
SC. Krieger has received compensation for consulting and advisory board work with Acorda Therapeutics Inc.; Bayer; Biogen; EMD Serono (Merck & Co., Inc.); Genentech; Genzyme; Mallinckrodt; Novartis; and Teva Pharmaceutical Industries Ltd. and has given non-promotional lectures with Biogen.
K. Cook, and M. Fletcher are employees of Harrison and Star, LLC, a healthcare communications company, which provided services for this project on a pro bono basis.
BM. Laitman has nothing to disclose.