Contributions
Abstract: 169
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - Genetics /Epigenetics and Pharmacogenetics
Background: Multiple sclerosis (MS) concordance rates in monozygotic (MZ) twins have been reported to range from 5-25%. Data regarding subclinical disease in clinically non-affected co-twins are scarce.
Goal: Prospective case-control study in MZ twins who were clinically discordant for MS at study entry, and in-depth assessment of subclinical disease in non-affected co-twins.
Methods: Twins were recruited in Germany by launching a nationally televised and internet-based appeal. MZ twin pairs were eligible for the study if they were clinically discordant, and one co-twin was diagnosed with MS according to the McDonald criteria, or with Clinically Isolated Syndrome (CIS). All twin pairs were assessed by an MS experienced neurologist (LAG), including a detailed interview, neurological exam, MRI (3 Tesla, elaborate protocol), optional CSF sampling and follow-ups. In the twin cohort and 100 non-affected singletons, 33 MS susceptibility loci were genotyped and a weighted genetic risk score (wGRS) was calculated. The study was approved by the local ethics committee and all participants gave written informed consent.
Results: Overall, the cohort includes 53 MZ twin pairs (39 female, 14 male) with a mean age of 41.5 years and mean age of 29.0 years at disease onset. Mean time span of discordance for MS is 13.6 years. In total, 17 (32%) pairs reported a positive MS family history. In addition, the MZ twin cohort had a significantly higher wGRS compared to 100 non-affected singletons (4.48±0.77 vs. 3.83±0.72, p=1.24x10-6).
MRI was performed in 44/53 pairs and was unremarkable in 21/44 (48%) of the clinically non affected twins. Radiologically isolated syndrome (RIS) was detected in 15/44 (34%), and unspecific white matter changes in 8/44 (18%). CSF analysis was performed in 12/15 RIS cases and revealed inflammatory changes with positive oligoclonal bands in 8/12 (67%).
Conclusion: This is the first in-depth assessment of subclinical disease in non-affected healthy co-twins from a large cohort of MZ twins who were clinically discordant for MS at study entry. Our data demonstrate a high subclinical concordance rate, with evidence for RIS in 34% of clinically unaffected twins, confirmed by inflammatory CSF findings in the majority of tested RIS cases. In addition, our MZ twin cohort is enriched for MS susceptibility loci. In summary, our data underline the impact of genetic risk factors in MS.
Disclosure: LA Gerdes: nothing to disclose.
NYP Souren: nothing to disclose.
B Ertl-Wagner: nothing to disclose.
J Walter: nothing to disclose.
T Kümpfel: nothing to disclose.
R Hohlfeld: nothing to disclose.
This work was supported by the German Multiple Sclerosis Foundation (national German and regional Bavarian foundation), German Research Council [SFB-TR 128 SyNergy], Klinische Kompetenznetz Multiple Sklerose, Verein zur Therapieforschung für MS Kranke, and the Gemeinnützige Hertie Stiftung.
Abstract: 169
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - Genetics /Epigenetics and Pharmacogenetics
Background: Multiple sclerosis (MS) concordance rates in monozygotic (MZ) twins have been reported to range from 5-25%. Data regarding subclinical disease in clinically non-affected co-twins are scarce.
Goal: Prospective case-control study in MZ twins who were clinically discordant for MS at study entry, and in-depth assessment of subclinical disease in non-affected co-twins.
Methods: Twins were recruited in Germany by launching a nationally televised and internet-based appeal. MZ twin pairs were eligible for the study if they were clinically discordant, and one co-twin was diagnosed with MS according to the McDonald criteria, or with Clinically Isolated Syndrome (CIS). All twin pairs were assessed by an MS experienced neurologist (LAG), including a detailed interview, neurological exam, MRI (3 Tesla, elaborate protocol), optional CSF sampling and follow-ups. In the twin cohort and 100 non-affected singletons, 33 MS susceptibility loci were genotyped and a weighted genetic risk score (wGRS) was calculated. The study was approved by the local ethics committee and all participants gave written informed consent.
Results: Overall, the cohort includes 53 MZ twin pairs (39 female, 14 male) with a mean age of 41.5 years and mean age of 29.0 years at disease onset. Mean time span of discordance for MS is 13.6 years. In total, 17 (32%) pairs reported a positive MS family history. In addition, the MZ twin cohort had a significantly higher wGRS compared to 100 non-affected singletons (4.48±0.77 vs. 3.83±0.72, p=1.24x10-6).
MRI was performed in 44/53 pairs and was unremarkable in 21/44 (48%) of the clinically non affected twins. Radiologically isolated syndrome (RIS) was detected in 15/44 (34%), and unspecific white matter changes in 8/44 (18%). CSF analysis was performed in 12/15 RIS cases and revealed inflammatory changes with positive oligoclonal bands in 8/12 (67%).
Conclusion: This is the first in-depth assessment of subclinical disease in non-affected healthy co-twins from a large cohort of MZ twins who were clinically discordant for MS at study entry. Our data demonstrate a high subclinical concordance rate, with evidence for RIS in 34% of clinically unaffected twins, confirmed by inflammatory CSF findings in the majority of tested RIS cases. In addition, our MZ twin cohort is enriched for MS susceptibility loci. In summary, our data underline the impact of genetic risk factors in MS.
Disclosure: LA Gerdes: nothing to disclose.
NYP Souren: nothing to disclose.
B Ertl-Wagner: nothing to disclose.
J Walter: nothing to disclose.
T Kümpfel: nothing to disclose.
R Hohlfeld: nothing to disclose.
This work was supported by the German Multiple Sclerosis Foundation (national German and regional Bavarian foundation), German Research Council [SFB-TR 128 SyNergy], Klinische Kompetenznetz Multiple Sklerose, Verein zur Therapieforschung für MS Kranke, and the Gemeinnützige Hertie Stiftung.