Contributions
Abstract: 194
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - Repairing mechanisms
Demyelination and oligodendroglial damage are hallmarks of multiple sclerosis (MS) lesions. Remyelination may occur as an important mechanism of regeneration. Children with MS often show a better and faster recovery from relapses than adult patients, which may be attributable to more efficient repair processes.
The present study aims to compare the extent of oligodendroglial damage and the frequency of remyelination in early MS lesions in children and adults.
We analysed brain biopsy samples from 26 patients under the age of 18 years who were diagnosed with an inflammatory demyelinating disease consistent with MS. Lesions were classified with respect to demyelinating activity and presence of remyelination. We counted the numbers of oligodendrocytes (ODs, Nogo-A) and oligodendrocyte precursor cells (OPCs, double staining Nogo-A and Olig2), and evaluated the presence of remyelination using immunohistochemistry for different myelin proteins. Results were compared with data from adult MS patients.
Among the paediatric patients, 36 lesional areas were present, the majority classified as early active demyelinating (EA, n=17, 47%). The number of ODs was significantly reduced in EA lesions compared to the periplaque white matter (PPWM) in children (EA 354 ± 49 ODs/mm², PPWM 493 ± 46 ODs/mm², p=0.04) and adults (EA 454 ± 77 ODs/mm², PPWM 721 ± 73 ODs/mm², p=0.03), with a lower percent reduction of ODs in EA lesions in children (28%) compared to adults (37%). In children, numbers of ODs in late active (LA, 467 ± 49 ODs/mm²) and inactive lesions (IA, 481 ± 55 ODs/mm²) were similar to those of the PPWM (p>0.05). Numbers of OPCs were lowest in EA lesions (70 ± 27 OPCs/mm²) and increased in LA (88 ± 28 OPCs/mm²) and IA lesions from children (85 ± 35 OPCs/mm²) (p>0.05). The percent reduction of OPCs in EA lesions compared to the PPWM was lower in children (reduction 34%, PPWM 106 ± 23 OPCs/mm², p>0.05) than in adults (reduction 69%, EA 42 ± 10 OPCs/mm², PPWM 136 ± 20 OPCs/mm², p< 0.006). In children, signs of remyelination were detectable in 21 (58%) of 36 lesions including all stages of demyelinating activity and in seven (41%) of 17 EA lesions. In adults, 36% of all lesions and 23% of EA lesions were classified as early remyelinating.
In conclusion, our study showed that oligodendroglial cell damage is less, and remyelination more frequent in paediatric compared to adult MS patients. These findings are consistent with the better clinical recovery observed in children.
Disclosure:
S Pfeifenbring has received honoraria for lectures by Bayer Vital.
RF Bunyan has nothing to disclose.
I Metz reports grants from German Ministry for Education and Research (BMBF, ""German Competence Network Multiple Sclerosis"" (KKNMS), Pattern MS/NMO), grants from BiogenIdec as well as personal fees from BiogenIdec, Bayer Healthcare, TEVA, Serono and Novartis outside the submitted work.
P Huppke has received honoraria and consultancy fees from Bayer Vital, Biogen and Novartis and has received research grant support from Biogen.
J Gärtner has received honoraria and consultancy fees from Bayer Vital, Biogen, Teva, and Novartis and has received research grant support from Biogen and Novartis.
CF Lucchinetti has received grant support from Biogen, Sanofi, Novartis, and the National Multiple Sclerosis Society.
W Brück has received honoraria for lectures by Bayer Vital, Biogen, Merck Serono, Teva Pharma, Genzyme, Sanofi-Aventis and Novartis and is a member of scientific advisory boards for Teva Pharma, Biogen, Novartis and Genzyme. He received funding for research projects by Teva Pharma, Biogen, Novartis and Genzyme. Dr Brück serves on the editorial boards of Neuropathology and Applied Neurobiology, Multiple Sclerosis International and Therapeutic Advances in Neurological Disorders.
Abstract: 194
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - Repairing mechanisms
Demyelination and oligodendroglial damage are hallmarks of multiple sclerosis (MS) lesions. Remyelination may occur as an important mechanism of regeneration. Children with MS often show a better and faster recovery from relapses than adult patients, which may be attributable to more efficient repair processes.
The present study aims to compare the extent of oligodendroglial damage and the frequency of remyelination in early MS lesions in children and adults.
We analysed brain biopsy samples from 26 patients under the age of 18 years who were diagnosed with an inflammatory demyelinating disease consistent with MS. Lesions were classified with respect to demyelinating activity and presence of remyelination. We counted the numbers of oligodendrocytes (ODs, Nogo-A) and oligodendrocyte precursor cells (OPCs, double staining Nogo-A and Olig2), and evaluated the presence of remyelination using immunohistochemistry for different myelin proteins. Results were compared with data from adult MS patients.
Among the paediatric patients, 36 lesional areas were present, the majority classified as early active demyelinating (EA, n=17, 47%). The number of ODs was significantly reduced in EA lesions compared to the periplaque white matter (PPWM) in children (EA 354 ± 49 ODs/mm², PPWM 493 ± 46 ODs/mm², p=0.04) and adults (EA 454 ± 77 ODs/mm², PPWM 721 ± 73 ODs/mm², p=0.03), with a lower percent reduction of ODs in EA lesions in children (28%) compared to adults (37%). In children, numbers of ODs in late active (LA, 467 ± 49 ODs/mm²) and inactive lesions (IA, 481 ± 55 ODs/mm²) were similar to those of the PPWM (p>0.05). Numbers of OPCs were lowest in EA lesions (70 ± 27 OPCs/mm²) and increased in LA (88 ± 28 OPCs/mm²) and IA lesions from children (85 ± 35 OPCs/mm²) (p>0.05). The percent reduction of OPCs in EA lesions compared to the PPWM was lower in children (reduction 34%, PPWM 106 ± 23 OPCs/mm², p>0.05) than in adults (reduction 69%, EA 42 ± 10 OPCs/mm², PPWM 136 ± 20 OPCs/mm², p< 0.006). In children, signs of remyelination were detectable in 21 (58%) of 36 lesions including all stages of demyelinating activity and in seven (41%) of 17 EA lesions. In adults, 36% of all lesions and 23% of EA lesions were classified as early remyelinating.
In conclusion, our study showed that oligodendroglial cell damage is less, and remyelination more frequent in paediatric compared to adult MS patients. These findings are consistent with the better clinical recovery observed in children.
Disclosure:
S Pfeifenbring has received honoraria for lectures by Bayer Vital.
RF Bunyan has nothing to disclose.
I Metz reports grants from German Ministry for Education and Research (BMBF, ""German Competence Network Multiple Sclerosis"" (KKNMS), Pattern MS/NMO), grants from BiogenIdec as well as personal fees from BiogenIdec, Bayer Healthcare, TEVA, Serono and Novartis outside the submitted work.
P Huppke has received honoraria and consultancy fees from Bayer Vital, Biogen and Novartis and has received research grant support from Biogen.
J Gärtner has received honoraria and consultancy fees from Bayer Vital, Biogen, Teva, and Novartis and has received research grant support from Biogen and Novartis.
CF Lucchinetti has received grant support from Biogen, Sanofi, Novartis, and the National Multiple Sclerosis Society.
W Brück has received honoraria for lectures by Bayer Vital, Biogen, Merck Serono, Teva Pharma, Genzyme, Sanofi-Aventis and Novartis and is a member of scientific advisory boards for Teva Pharma, Biogen, Novartis and Genzyme. He received funding for research projects by Teva Pharma, Biogen, Novartis and Genzyme. Dr Brück serves on the editorial boards of Neuropathology and Applied Neurobiology, Multiple Sclerosis International and Therapeutic Advances in Neurological Disorders.