Contributions
Abstract: EP1521
Type: ePoster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Rebound of disease activity after fingolimod (FTY) discontinuation has been recently described in MS patients as an unfrequent but potentially severe event. Tumefactive demyelination has been described as the most frequent radiological pattern observed in these cases. The mechanisms leading to a rebound of disease activity after FTY discontinuation are not fully understood and no descriptions of autoptic cases are available.
We present a case of fatal rebound of disease activity after FTY discontinuation in a young MS patient (27 years old). The patient, affected by relapsing-remitting MS with a disease duration of 11 years, had been treated for 3 years with natalizumab and then switched to FTY because of JCV antibodies positivity. After 3 years of FTY treatment, the patient interrupted treatment because of pregnancy. Disease course had been stable during natalizumab and later FTY treatment. After 4 months from FTY discontinuation, the patient began to experience severe relapses poorly reponsive to corticosteroids, with rapid progression of disability. MRI showed several large new demyelinating lesions with ring gadolinium enhancement and peripheral oedema, suggestive of tumefactive lesions. Immunosuppressive treatment with cyclophosphamide was initiated, but the patient continued to worsen and died after 8 months from FTY discontinuation.
The neuropathological examination showed several large confluent active demyelinating lesions with a preponderance of large hypertrophic reactive astrocytes with multiple nuclei and fragmented nuclear inclusion (Creuztfeldt-Peters cells) intermingled with foamy macrophages. Such pattern has been previously described as typical of tumefactive demyelinating lesions. Little lymphocyte infiltration was observed in active demyelinating lesions, possibly due to the recent exposure to immunosuppresive therapy. Frequent cortical lesions were observed, mainly as leukocortical lesions extending from the subcortical white matter into the cortex. Strong S1P1 receptor immunoreactivity was observed on the hypertrophic reactive astrocytes in active demyelinating lesions.
Tumefactive demyelination is uncommon in MS but appears to be a frequent pattern in cases of rebound of MS after FTY withdrawal. A rebound of increased expression of the S1P1 receptor on astrocytes after withdrawal of FTY might represent a possible contributing mechanism and might explain the unusual neuropathological features observed in this case.
Disclosure:
Dr. Vercellino has received travel grants for scientific congresses from Biogen, Genzyme, Merck Serono, Novartis, Teva.
Dr. Cavalla has received travel grants for scientific congresses and speaking honoraria from Almirall, Biogen, Genzyme, Merck Serono, Novartis, Teva.
Dr. Capello has received travel grants for scientific congresses from Biogen.
Dr. Bandini has received speaking honoraria from Novartis.
Prof. Uccelli has received consulting honoraria and/or speaker fees and a basic science study grant from Biogen; consulting honoraria and/or speaker fees from Genentech, Roche, Allergan, Sanofi-Aventis, Biogen-Dompé, and Novartis; consulting honoraria and/or speaker fees and a basic science study grant from Merck-Serono.
Prof. Giordana has nothing to disclose.
Prof. Mancardi has received honoraria, travel expenses, and financial support for research from Bayer Schering, Biogen, Sanofi Aventis, Teva, Merck Serono and Novartis.
Abstract: EP1521
Type: ePoster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Rebound of disease activity after fingolimod (FTY) discontinuation has been recently described in MS patients as an unfrequent but potentially severe event. Tumefactive demyelination has been described as the most frequent radiological pattern observed in these cases. The mechanisms leading to a rebound of disease activity after FTY discontinuation are not fully understood and no descriptions of autoptic cases are available.
We present a case of fatal rebound of disease activity after FTY discontinuation in a young MS patient (27 years old). The patient, affected by relapsing-remitting MS with a disease duration of 11 years, had been treated for 3 years with natalizumab and then switched to FTY because of JCV antibodies positivity. After 3 years of FTY treatment, the patient interrupted treatment because of pregnancy. Disease course had been stable during natalizumab and later FTY treatment. After 4 months from FTY discontinuation, the patient began to experience severe relapses poorly reponsive to corticosteroids, with rapid progression of disability. MRI showed several large new demyelinating lesions with ring gadolinium enhancement and peripheral oedema, suggestive of tumefactive lesions. Immunosuppressive treatment with cyclophosphamide was initiated, but the patient continued to worsen and died after 8 months from FTY discontinuation.
The neuropathological examination showed several large confluent active demyelinating lesions with a preponderance of large hypertrophic reactive astrocytes with multiple nuclei and fragmented nuclear inclusion (Creuztfeldt-Peters cells) intermingled with foamy macrophages. Such pattern has been previously described as typical of tumefactive demyelinating lesions. Little lymphocyte infiltration was observed in active demyelinating lesions, possibly due to the recent exposure to immunosuppresive therapy. Frequent cortical lesions were observed, mainly as leukocortical lesions extending from the subcortical white matter into the cortex. Strong S1P1 receptor immunoreactivity was observed on the hypertrophic reactive astrocytes in active demyelinating lesions.
Tumefactive demyelination is uncommon in MS but appears to be a frequent pattern in cases of rebound of MS after FTY withdrawal. A rebound of increased expression of the S1P1 receptor on astrocytes after withdrawal of FTY might represent a possible contributing mechanism and might explain the unusual neuropathological features observed in this case.
Disclosure:
Dr. Vercellino has received travel grants for scientific congresses from Biogen, Genzyme, Merck Serono, Novartis, Teva.
Dr. Cavalla has received travel grants for scientific congresses and speaking honoraria from Almirall, Biogen, Genzyme, Merck Serono, Novartis, Teva.
Dr. Capello has received travel grants for scientific congresses from Biogen.
Dr. Bandini has received speaking honoraria from Novartis.
Prof. Uccelli has received consulting honoraria and/or speaker fees and a basic science study grant from Biogen; consulting honoraria and/or speaker fees from Genentech, Roche, Allergan, Sanofi-Aventis, Biogen-Dompé, and Novartis; consulting honoraria and/or speaker fees and a basic science study grant from Merck-Serono.
Prof. Giordana has nothing to disclose.
Prof. Mancardi has received honoraria, travel expenses, and financial support for research from Bayer Schering, Biogen, Sanofi Aventis, Teva, Merck Serono and Novartis.