Multiple Sclerosis That Is Progressive From the Time of Onset

Abstract

The clinical characteristics and disability progression of these MS subtypes were indistinguishable, with the exception of 1 or 2 relapses in patients with PRMS that occurred 8 months to 9 years after the onset of symptoms. We see little reason to consider PPMS and PRMS separate clinical entities; however, whether they can be better distinguished by radiological, histopathological, or immunological markers of disease activity remains unknown.

Association of Inflammation and Disability Accrual in Patients With Progressive-Onset Multiple Sclerosis

“…To date and to our knowledge, there are limited epidemiologic data describing the characteristics of progressive-onset MS with superimposed relapse vs without. The ratio of men to women in our study (1:1.19 in PRMS and 1:1.20 in PPMS) was consistent with previous studies describing the clinical characteristics of PPMS and those comparing PRMS with PPMS . Where previous research has identified no difference in age at onset between patients with vs without relapse, we demonstrated that patients with PRMS were younger at disease onset compared with those with PPMS .…”

“…Our median annualized relapse rate of 0.15 (quartiles 0.08 to 0.26) is likely a conservative estimate, as it includes time from symptom onset prior to inclusion date. Consistent with previous findings, the domain most commonly affected by relapses was the motor system …”

“…Several recent studies have identified superimposed relapse as an independent determinant of disability accrual . Conversely, other studies have identified no influence of superimposed relapse on the accumulation of disability in progressive-onset MS phenotypes . Our study established a negative association between superimposed relapses in progressive-onset MS and the likelihood of confirmed disability progression, which can be attributed to an association of treatment in the PRMS but not the PPMS group.…”

Association of Inflammation and Disability Accrual in Patients With Progressive-Onset Multiple Sclerosis

“…To date and to our knowledge, there are limited epidemiologic data describing the characteristics of progressive-onset MS with superimposed relapse vs without. The ratio of men to women in our study (1:1.19 in PRMS and 1:1.20 in PPMS) was consistent with previous studies describing the clinical characteristics of PPMS and those comparing PRMS with PPMS . Where previous research has identified no difference in age at onset between patients with vs without relapse, we demonstrated that patients with PRMS were younger at disease onset compared with those with PPMS .…”

“…Our median annualized relapse rate of 0.15 (quartiles 0.08 to 0.26) is likely a conservative estimate, as it includes time from symptom onset prior to inclusion date. Consistent with previous findings, the domain most commonly affected by relapses was the motor system …”

“…Several recent studies have identified superimposed relapse as an independent determinant of disability accrual . Conversely, other studies have identified no influence of superimposed relapse on the accumulation of disability in progressive-onset MS phenotypes . Our study established a negative association between superimposed relapses in progressive-onset MS and the likelihood of confirmed disability progression, which can be attributed to an association of treatment in the PRMS but not the PPMS group.…”

Genome sequencing uncovers phenocopies in primary progressive multiple sclerosis

“…Understanding the role of phenocopies in PPMS has important clinical implications. The finding that PPMS patients are enriched for HSP‐related mutations that cause progressive axonal injury is consistent with the observation that the most common clinical presentation in PPMS is a progressive spastic paraparesis and might help explain why these patients respond poorly to immunomodulatory therapies. Moreover, carrying a pathogenic mutation for a MS phenocopy disorder does not cause MS, but rather modulates the disease course through mechanisms independent of immune‐mediated pathways implicated by reported MS susceptibility loci.…”

From wearable sensor data to digital biomarker development: ten lessons learned and a framework proposal

“…At baseline, most participants were female, had a median age of 46, had MS for a median of 11 years and were either working part-time or were unemployed. These characteristics align with the typical demographics observed in MS populations with a more progressed disease state 29 – 31 . A follow-up study 23 involving participants with different characteristics and chronic illnesses, such as cardiovascular diseases, revealed conclusions consistent with the main BarKA-MS analyses, suggesting that the findings discussed in this lessons learned paper may be applicable to other chronic disease populations.…”

Association of Inflammation and Disability Accrual in Patients With Progressive-Onset Multiple Sclerosis

“…To date and to our knowledge, there are limited epidemiologic data describing the characteristics of progressive-onset MS with superimposed relapse vs without. The ratio of men to women in our study (1:1.19 in PRMS and 1:1.20 in PPMS) was consistent with previous studies describing the clinical characteristics of PPMS and those comparing PRMS with PPMS . Where previous research has identified no difference in age at onset between patients with vs without relapse, we demonstrated that patients with PRMS were younger at disease onset compared with those with PPMS .…”

“…Our median annualized relapse rate of 0.15 (quartiles 0.08 to 0.26) is likely a conservative estimate, as it includes time from symptom onset prior to inclusion date. Consistent with previous findings, the domain most commonly affected by relapses was the motor system …”

“…Several recent studies have identified superimposed relapse as an independent determinant of disability accrual . Conversely, other studies have identified no influence of superimposed relapse on the accumulation of disability in progressive-onset MS phenotypes . Our study established a negative association between superimposed relapses in progressive-onset MS and the likelihood of confirmed disability progression, which can be attributed to an association of treatment in the PRMS but not the PPMS group.…”

Genome sequencing uncovers phenocopies in primary progressive multiple sclerosis

“…Understanding the role of phenocopies in PPMS has important clinical implications. The finding that PPMS patients are enriched for HSP‐related mutations that cause progressive axonal injury is consistent with the observation that the most common clinical presentation in PPMS is a progressive spastic paraparesis and might help explain why these patients respond poorly to immunomodulatory therapies. Moreover, carrying a pathogenic mutation for a MS phenocopy disorder does not cause MS, but rather modulates the disease course through mechanisms independent of immune‐mediated pathways implicated by reported MS susceptibility loci.…”

From wearable sensor data to digital biomarker development: ten lessons learned and a framework proposal

“…At baseline, most participants were female, had a median age of 46, had MS for a median of 11 years and were either working part-time or were unemployed. These characteristics align with the typical demographics observed in MS populations with a more progressed disease state 29 – 31 . A follow-up study 23 involving participants with different characteristics and chronic illnesses, such as cardiovascular diseases, revealed conclusions consistent with the main BarKA-MS analyses, suggesting that the findings discussed in this lessons learned paper may be applicable to other chronic disease populations.…”

Association of Inflammation and Disability Accrual in Patients With Progressive-Onset Multiple Sclerosis

“…To date and to our knowledge, there are limited epidemiologic data describing the characteristics of progressive-onset MS with superimposed relapse vs without. The ratio of men to women in our study (1:1.19 in PRMS and 1:1.20 in PPMS) was consistent with previous studies describing the clinical characteristics of PPMS and those comparing PRMS with PPMS . Where previous research has identified no difference in age at onset between patients with vs without relapse, we demonstrated that patients with PRMS were younger at disease onset compared with those with PPMS .…”

“…Our median annualized relapse rate of 0.15 (quartiles 0.08 to 0.26) is likely a conservative estimate, as it includes time from symptom onset prior to inclusion date. Consistent with previous findings, the domain most commonly affected by relapses was the motor system …”

“…Several recent studies have identified superimposed relapse as an independent determinant of disability accrual . Conversely, other studies have identified no influence of superimposed relapse on the accumulation of disability in progressive-onset MS phenotypes . Our study established a negative association between superimposed relapses in progressive-onset MS and the likelihood of confirmed disability progression, which can be attributed to an association of treatment in the PRMS but not the PPMS group.…”

Genome sequencing uncovers phenocopies in primary progressive multiple sclerosis

“…Understanding the role of phenocopies in PPMS has important clinical implications. The finding that PPMS patients are enriched for HSP‐related mutations that cause progressive axonal injury is consistent with the observation that the most common clinical presentation in PPMS is a progressive spastic paraparesis and might help explain why these patients respond poorly to immunomodulatory therapies. Moreover, carrying a pathogenic mutation for a MS phenocopy disorder does not cause MS, but rather modulates the disease course through mechanisms independent of immune‐mediated pathways implicated by reported MS susceptibility loci.…”

From wearable sensor data to digital biomarker development: ten lessons learned and a framework proposal

“…At baseline, most participants were female, had a median age of 46, had MS for a median of 11 years and were either working part-time or were unemployed. These characteristics align with the typical demographics observed in MS populations with a more progressed disease state 29 – 31 . A follow-up study 23 involving participants with different characteristics and chronic illnesses, such as cardiovascular diseases, revealed conclusions consistent with the main BarKA-MS analyses, suggesting that the findings discussed in this lessons learned paper may be applicable to other chronic disease populations.…”