Cross-sectional and Longitudinal MRI Markers of Pathology in Neuromyelitis Optica and Multiple Sclerosis

Neuromyelitis optica (NMO) is a severe neurological condition that damages the myelin insulation that surrounds the nerve fibres in the brain and spinal cord. NMO can cause blindness, paralysis and death. Although there is now an immunological marker for the many NMO cases, we don‘t know enough about how the disease progresses over time. There are also several overlapping features of NMO and multiple sclerosis (MS), which also causes damage to myelin, and it can be difficult to differentiate the two conditions. It is important to make the distinction as the treatment for the two conditions is significantly different.

Using specialised MRI techniques that can detect changes in water molecule motion and chemical constituents within the brain, we aim to find an imaging tool that can identify NMO and distinguish it from MS. This would then allow us to target treatment appropriately. In addition, our high resolution imaging will help to establish how the nerve damage associated with NMO compares with MS (especially as the cause of nerve damage in MS is unknown), and whether there is on-going disease activity even between the relapses. This should be very useful for monitoring treatments in the future.

Background: Neuromyelitis optica (NMO) is a severe demyelinating neurological condition of the brain and spinal cord that often results in blindness, quadriplegia and death. Until recently NMO was considered a sub-type of multiple sclerosis (MS), but it is now thought to be a discrete pathological entity supported by the discovery that 70-90% of patients have serum antibodies to aquaporin-4. In contrast to MS it responds to conventional immunosuppression and seems to follow a relapsing course with little recovery. The clinical phenotype is broadening and, in antibody negative cases, may be difficult to classify. The distinction is imperative due to the treatment implications. There are unanswered questions about the pathophysiology of NMO and whether, like MS, background inflammation and neural damage continues between relapses. Prospective longitudinal studies combining conventional and non-conventional MRI to contrast NMO with MS are lacking.

Aims:
1. To differentiate NMO brain and spinal cord MRI characteristics from MS (including the use of non-conventional and novel techniques i.e. diffusion tensor imaging (DTI), multi-voxel magnetic resonance spectroscopy (MRS), resting state functional networks and myelin water imaging).
2. To use longitudinal measures to establish whether NMO is purely a relapsing condition or whether there is ongoing progressive change during the periods of remission (as in MS).
3. To assess and contrast with MS the anatomical location of the changes, and metabolic and DTI characteristics of lesions

Lessons learnt from contrasting two inflammatory demyelinating CNS conditions, one antibody-mediated, may also benefit MS research.

Study Design: Includes a cross-sectional and a longitudinal component using a 3 Tesla field. Four study groups will be compared: a. NMO patients (n=20-25), b. age/sex matched relapsing remitting MS controls (n=20-25), c. age/sex matched healthy controls (n=20-25) and d. patients with MS who are considered borderline for NMO (n?5). A 7 Tesla MRI scan will be performed on a sub-group to investigate the use of this tool in imaging demyelinating lesions. Correlates of MRI indices with clinical and immunological markers will be sort.

Methodology: The MRI brain and spinal cord protocol will include structural imaging (T1, T2, FLAIR), DTI, MRS and myelin water imaging. MRI data will be analysed for volumetric measures, voxel wise diffusion indices and biochemical content, and resting networks.

Opportunities: This study will investigate the role of MRI in the diagnosis and monitoring of NMO, and inform on the pathological processes in-vivo with particular reference to multiple sclerosis, the aetiology of which remains unknown.