Neurological rehabilitation: from mechanisms to management.

The main messages contained within this review are firstly that any advance in the management of patients with neurological disability must come from improved understanding of the mechanisms underlying that disability and secondly that the only way to demonstrate real benefit is by a process of evaluation which must incorporate appropriate measuring tools. In other words, to emphasise the crucial role of the basic sciences (be it cellular biology, immunology, physiology, or imaging) in elucidating the mechanisms underlying disability and similarly to underline the importance of the scientific principles which underpin the outcome measures used to evaluate disease management. The three great challenges currently facing the field of neurological rehabilitation are firstly to elucidate these mechanisms, secondly to ensure that this knowledge transfers speedily to the clinical arena, and thirdly to identify scientifically sound outcome measures with which to evaluate clinical intervention. There have been several recent advances in our understanding of the mechanisms underlying disability in neurological disorders, and multiple sclerosis provides an excellent example. This is one of the main causes of neurological disability in young adults and recent work in this area has shown the value of scientific investigation which is driven by addressing important clinical questions. There have also been encouraging advances in measuring outcome in the field of neurological rehabilitation and these will be discussed with particular reference to their application to the evaluation of therapy and rehabilitation. Multiple sclerosis is a complex neurological disorder perhaps best exemplified by its diverse patterns of disease activity, incorporating relapses and progression. The development of MRI has provided an invaluable diagnostic tool which may also be used to monitor and predict disease activity and evaluate therapeutic interventions. However, once the initial flush of enthusiasm passed, it became clear that there was a major discrepancy between the extent of the abnormalities seen on brain MRI and the impact the disease was having on the patient. This was particularly obvious in patients with primary progressive multiple sclerosis—who have the worst clinical prognosis. In the first serial study of this group in the late 1980s it was shown that, despite the fact that patients in this subgroup were getting progressively worse they showed very little new activity on MRI and even less inflammation. This discrepancy encouraged investigators to consider other reasons for their disability and stimulated the development of faster and more accurate imaging of the spinal cord—an area known to be both a common target and a major source of disability in multiple sclerosis. The improved imaging certainly confirmed these views— lesions were seen in most patients but, again, failed to explain their level of disability. These studies did, however, produce one interesting observation which has been subsequently exploited to the full—patients in the progressive phase of the condition were found to have marked tissue loss and the degree of cord atrophy correlated well with disability. Refinement of this measurement technique and relocalisation to a higher and more anatomically consistent level (C2) provided the scientific properties necessary for serial measurement which in turn demonstrated measurable change within as short a period as 1 year. 9 This observation led to studies of atrophy in other areas, led by work from LosseV who developed a technique capable of measuring a defined volume of the brain at the periventricular level. Although this was only a partial measure of brain volume, it focused on the area of greatest potential change and was therefore sensitive to change over time and, perhaps more importantly, demonstrated an encouraging correlation with disability. Subsequently, a range of new techniques have been developed, confirming the initial observations and demonstrating that changes are detectable over a relatively short period of time, may be seen early in the disease course, 12 and have the potential to be useful outcomes in therapeutic trials. What do these observations mean pathologically and clinically? Atrophy could be described as an end stage process which may result from loss of various tissue components including myelin and axons. Clinically it could be the cause of the irreversible deficit seen in multiple sclerosis although that is likely to depend on the severity of the axonal loss and its precise location. There has been renewed interest in axonal loss in multiple sclerosis as a result of recent publications from Ferguson et al and Trapp et al, reminding us of what has This review is the content of the Inaugural Lecture of the Garfield Weston Chair of Clinical Neurology and Neurorehabilitation given by Professor A J Thompson at the Institute of Neurology, UCL, 10 July 1999 J Neurol Neurosurg Psychiatry 2000;69:718–722 718