Interferon ß-1b and glatiramer acetate effects on permanent black hole evolution.

OBJECTIVE: To compare interferon ß-1b (IFNß-1b) and glatiramer acetate (GA) on new lesion (NL) (gadolinium-enhancing, new T2) evolution into permanent black holes (PBH)--a marker of irreversible tissue damage--in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: BEYOND was a large, phase III, clinical trial comparing IFNß-1b 250 µg, IFNß-1b 500 µg, and GA (2:2:1). Patient scans were reexamined post hoc for PBH in a rater-blinded manner. Two predefined coprimary endpoints compared IFNß-1b 250 µg with GA: first, number of PBH per patient at year 2 evolving from year 1 NL, then proportion of year 1 NL evolving into PBH at year 2. IFNß-1b 500 µg and GA were compared in an exploratory fashion. RESULTS: Approximately 90% (1,957/2,244) of patients had NL at year 1 with follow-up at year 2. Mean numbers of PBH per patient at year 2 evolving from year 1 NL were lower for IFNß-1b 250 µg than GA (0.30 vs 0.43; p = 0.0451). The proportion of NL evolving into PBH was similar (IFNß-1b 250 µg vs GA: 21.6% vs 23.5%; p > 0.20). For IFNß-1b 500 µg, both the mean PBH number per patient at year 2 evolving from year 1 NL (0.26 vs 0.43; p = 0.0037) and proportion of NL evolving into PBH (16.3% vs 23.5%; p = 0.0409) were lower relative to GA. CONCLUSION: IFNß-1b affected PBH development to a similar or better extent than GA. IFNß-1b favorably influences an MRI outcome indicative of permanent tissue destruction in the brains of patients with multiple sclerosis. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that IFNß-1b is associated with a reduction in MRI PBH formation and evolution compared with GA between years 1 and 2 of treatment.

Minor salivary gland inflammation in Devic's disease and longitudinally extensive myelitis.

Devic's disease is often considered as a variant of multiple sclerosis (MS). However, evidence suggests that Devic's disease may be distinct from MS. Devic's disease can coexist with connective tissue diseases, particularly Sjögren's disease, but this association is rare with MS. Diagnosis of Sjögren's disease in patients with neurological symptoms is often difficult. During early stages of Sjögren's disease, patients may not fulfill all criteria for Sjögren's disease. A high percentage of patients with Sjögren's disease have inflammatory infiltrates in minor salivary glands, and this may be a reliable indicator of early or subclinical disease. We show high prevalence (80%) of salivary gland inflammation in Devic's disease and longitudinally extensive transverse myelitis (LETM). We diagnosed 16 patients with Devic's disease, and 2 of these satisfied criteria for Sjögren's disease as did 2 of 9 patients with LETM. Anti-SSA/B titers were infrequently elevated. Although most did not satisfy criteria for Sjögren's disease. 9 of 12 Devic's disease patients and 7 of 8 LETM patients had severe salivary gland inflammation. Thus: (1) patients with Devic's disease or with LETM who have positive labial biopsies but do not satisfy criteria for Sjögren's disease could have subclinical Sjögren's diseases. Alternatively, (2) as patients with Devic's disease have elevated titers of several autoantibodies, so there may exist a set of antibodies that react with antigens in minor salivary glands and cause inflammation. Minor salivary gland biopsy is more sensitive than anti-SSA/B serology in providing histological evidence for possible Sjögren's disease with CNS lesions.