Reduced cerebrospinal fluid BACE1 activity in multiple sclerosis.

BACKGROUND: Cell and animal experiments have shown that beta-site APP-cleaving enzyme 1 (BACE1) may be involved in myelination. OBJECTIVE: Here, we assess the association of cerebrospinal fluid (CSF) BACE1 activity with multiple sclerosis (MS). METHODS: BACE1 activity and levels of secreted amyloid precursor protein (APP) and amyloid-beta (Abeta) isoforms were analyzed in CSF from 100 patients with MS and 114 neurologically healthy controls. Patients with systemic lupus erythematosus (SLE), 26 with and 41 without cerebral engagement, were also included to enable comparisons with regards to another autoimmune disease. A subset of patients with MS and controls underwent a second lumbar puncture after 10 years. RESULTS: MS patients had lower CSF BACE1 activity than controls (P = 0.03) and patients with cerebral SLE (P < 0.001). Patients with cerebral SLE had higher BACE1 activity than any other group (P < 0.05 for all comparisons). BACE1 activity correlated with the different amyloid markers in all study groups. BACE1 activity decreased over 10 years in the MS group (P = 0.039) and correlated weakly with clinical disease severity scores in an inverse manner. CONCLUSIONS: These results suggest an involvement of BACE1 in the MS disease process.

Anti-T-lymphocyte globulin treatment in inclusion body myositis: a randomized pilot study.

The authors performed an open, randomized trial in patients with inclusion body myositis comparing 1) 12-month treatment with oral methotrexate 7.5 mg/week alone (MTX group) with 2) 12-month MTX treatment preceded by 7 days of IV anti-T-lymphocyte immunoglobulin treatment (ATG group). Eleven patients were randomized; 10 patients completed 12 months follow-up. Myometry showed that patients in the ATG group (n = 6) increased in mean muscle strength by 1.4% compared with the MTX group (n = 5), whose muscle strength decreased by 11.1% (p = 0.021).

Cerebrospinal fluid neurofilament and glial fibrillary acidic protein in patients with cerebral vasculitis.

Few diseases in clinical medicine cause as much diagnostic consternation as central nervous system (CNS) vasculitis because of its varying modes of presentation and frequently overlapping clinical and pathological features. There are no pathognomonic clinical or laboratory findings. The purpose of the present retrospective study was to validate the use of the light subunit of neurofilament triplet protein (NFL) and glial fibrillary acidic protein (GFAP) as markers of CNS tissue damage for patients with systemic or isolated CNS vasculitis. Levels of cerebrospinal fluid (CSF) NFL and GFAP were measured using ELISAs. Both CSF NFL and CSF GFAP concentrations were significantly higher in a patient group diagnosed with CNS vasculitis (P < 0.01 and P < 0.05, respectively) than in a patient group for whom CNS vasculitis was excluded. In the future, analysis of CSF NFL in particular, but also GFAP, may be a useful complement in the difficult clinical task of diagnosing CNS vasculitis.

Intrathecal cytokines in systemic lupus erythematosus with central nervous system involvement.

Symptoms originating from central nervous system (CNS) are frequently occuring in patients with systemic lupus erythematosus (SLE). Reliable diagnostic markers for this condition are presently lacking. Importantly, CNS involvement in lupus patients is associated with increased morbidity and mortality. The aim of this retrospective evaluate was to study the diagnostic value of cerebrospinal fluid (CSF) cytokine levels in SLE patients with CNS involvement. 34 patients with SLE were hospitalized and investigated for the presence of CNS lupus. These patients were evaluated clinically and with magnetic resonance imaging (MRI) and CSF analyses, as well as with neuropsychiatric tests. 13 patients were found to have CNS lupus whereas another four of the patients fulfilled the criteria for CNS involvement but were excluded from this group due to other causes of CNS involvement. Lastly, in 17 SLE cases, the diagnosis of CNS lupus could not be confirmed. CSF levels of interleukin-6 (IL-6) and IL-8, as well as the CSF/serum IL-6 ratio, were elevated in the CNS lupus group, compared with the 17 SLE patients not fullfilling a diagnosis of cerebral lupus. Interestingly, follow-up of five patients being successfully treated for CNS lupus revealed profound decrease of intrathecal IL-6 levels. These results indicate that analysis of CSF cytokine levels, especially IL-6 and IL-8, may be useful in the diagnostics and possibly follow-up of SLE patients with cerebral lupus.

Autologous stem cell transplantation in a case of treatment resistant central nervous system lupus.

This case report describes a young woman with systemic lupus erythematosus starting at 16 years of age and giving rise to severe neurological complications including bilateral opticus neuritis and transverse myelitis. Despite heavy immunosuppression her condition steadily aggravated. At this point it was decided to perform autologous stem cell transplantation. Haematopoietic stem cells were mobilised with cyclophosphamide and granulocyte colony stimulating factor. Enrichment of CD34(+)cells was followed by depletion of peripheral T and B cells. The post-transplantation course was uneventful, and all the neurological deficits improved promptly during the 15 months of follow up. This is the first description of successful autologous stem cell transplantation in a case of life threatening central nervous system lupus.