Multiple sclerosis: disease markers accelerate progress 2003 round-up

2reported that antibodies against myelin oligodendrocyte glycoprotein and myelin basic protein predicted disease course in 103 patients with clinically isolated syndromes suggestive of MS. 81 patients (79%) had antibodies against either myelin oligodendrocyte glycoprotein or myelin basic protein, whereas 22 patients (21%) had antibodies to neither. Over an average of 4 years follow-up, 65 (80%) of the antibody-positive patients, but only 5 (23%) of the antibody-negative patients, had a relapse. Among those who relapsed, time to relapse was three to six times longer in antibody-negative patients. The number of brain lesions or presence of contrast enhancing lesions had minimal effect on time to relapse in this study. The results suggest that autoantibodies may be useful as a prognostic marker early in the course of MS or to select patients for more aggressive therapy. Results are also consistent with a pathogenetic role for autoantibodies in MS. This hypothesis could be tested in randomised controlled clinical trials directed at the humoral immune response. Changes seen on brain imaging relate more closely to MS pathology than do clinical manifestations, but it has been difficult to develop pathologically specific MRI markers. In particular, specific markers for remyelination are lacking. Barkhof and colleagues 3 reported MRI pathology for 149 lesions visible on post-mortem T2-weighted imaging of 36 brains of patients with MS. 3 Remyelination was present in 42% of the lesions. Hypointensity on T1-weighted imaging was more common in fully or partially demyelinated lesions than in fully remyelinated lesions. Also, magnetisation transfer ratio was reduced in demyelinated lesions compared with fully remyelinated lesions. The results suggest that hypointensity on T1-weighted imaging and magnetisation transfer ratio may distinguish lesions with remyelination from those without. Newer MRI approaches, such as functional neuroimaging, may provide better insights into the pathological process. Rocca and colleagues 4 reported a functional MRI study in 14 patients 6–29 months after partial cervical transverse myelitis. The patients had minimal brain disease. A simple repetitive motor task for an arm without previous motor involvement was used to stimulate the cerebral cortex. Compared with healthy control individuals, patients had substantial functional reorganisation of the cerebral cortex, with increased recruitment of the ipsilateral primary sensorimotor cortex, supplementary motor area, and middle frontal gyrus. The degree of cervical cord tissue injury measured by magnetisation transfer ratio was strongly related to the amount of functional reorganisation. This study also showed significant functional reorganisation after a single inflammatory event quite distal to the cortex. The study suggests that cortical reorganisation may be an important adaptive mechanism underlying clinical improvement after inflammatory injury and that secondary progressive MS may develop when multifocal tissue injury outstrips compensatory adaptation, such as cortical reorganisation. A potentially important new approach to MS therapy was reported by Miller and colleagues. 5 Natalizumab, a monoclonal antibody to 41 integrin (VLA4), was used in a placebo-controlled clinical trial in 213 patients with relapsing remitting MS. VLA4 is a mediator of transendothelial leucocyte migration, and its expression is necessary for activated lymphocyte infiltration into the CNS. Patients were randomly assigned to 6 monthly infusions of placebo or natalizumab. Patients randomised to natalizumab had a 90% reduction in contrast enhancing lesions and a 50% reduction in relapses. The study is the first successful MS clinical trial specifically targeting immune cell trafficking. Two larger definitive clinical trials are underway.