Editorial
When his book first appeared in 1933, (Walter) Russell Brain surveyed all that was then known about Diseases of the Nervous System. His position on treatments might now raise an eyebrow. Thus, stroke should be treated with potassium iodide and thyroid extract, arsenic was useful in disseminated sclerosis, and tremor in Parkinson's disease improved with ‘a ride in a motor car’. Diseases of the Nervous System went through many editions and the 7th was under revision when Lord Brain, editor of this journal, died in 1966. Responsibility for Brain, the book, passed to John Walton, who wrote the next two editions without assistance and then secured a team of younger British neurologists to help with the 10th, in 1993, before handing over stewardship of the book that had proved supremely influential throughout the English speaking world for several decades to a new editor in 2001. In this and his many other writings on clinical neurology, Lord Walton of Detchant described the evolution of neurological practice over a period in which therapeutics moved from its origins in folklore to a more mechanistic account, as he and other clinical scientists systematically began to understand the true nature of neurological disease—to the gradual advantage of their patients. Thus, in 1952 Irving Cooper had to ligate the blood supply to the globus pallidus and fortuitously improved the tremor of Parkinson's disease, making redundant an excursion in Dr Brain's Bentley and pioneering the functional neurosurgery that is still much used in Parkinson's disease. In 1967, the year that Professor Walton took on the editorship of Brain's Diseases of the Nervous System, George C Cotzias first used L-dopa to correct the deficiency of dopamine in the striatum of people with Parkinson's disease. And in 1975, Anders Björklund and colleagues provided the experimental evidence suggesting that cells transplanted into the striatum might restore structure and function in Parkinson's disease. In ‘Neurology: the case for treatment’, John Walton charts the progress of therapeutic neurology, as the grip of myth and tradition gradually loosened, and a more scientific rationale for neurological treatments gained its foothold (page 2750). Reviewing ‘From Neuroscience to Neurology: Neuroscience, molecular medicine, and the therapeutic transformation of neurology’ edited by Stephen Waxman, Lord Walton reflects on the primitive attitudes and limited availability of investigations that conditioned neurological practice in the 1940s. He writes with authority and from personal acquaintance on the people and discoveries that changed that situation, and of the promises to come. His account is decorated with anecdotes and wry comments gathered from an experience of clinical neurology covering 60 years, which has left Lord Walton, now the doyen of British and World neurology, ‘almost but not quite wish(ing) that I were starting again’.
Central nervous system manifestations of the Guillain Barré are well recognized but not everyone knows about the characteristic hallucinations and sleep disturbance. On (page 2535), Isabelle Arnulf and colleagues from Paris describe the range of mental status changes observed in 139 cases, mostly but not exclusively managed in an intensive care setting. These are not the result of delirium that occurs in that environment; rather, they are wakeful dreams caused by a rapid eye movement sleep disorder perhaps in association with reduced levels of hypocretin-1. Two papers in the present issue characterize the consequences of impaired preterm development or perinatal brain injury. Stefan Sunaert and a multidisciplinary team from Leuven (page 2562 and see cover) map corticofugal, thalamocortical and association fibre tracts in individuals with cerebral palsy, and correlate reduction in fibre count with lesion sites and their dependent pathways, providing some evidence for reorganization of these compromised sensorimotor tracts. On (page 2588), Marit Martinussen and a group from the United States (Boston and San Diego), Norway and Denmark link abnormalities of cortical thickness and surface area, and impaired cognitive ability, to reduced intrauterine growth in a large cohort of 15-year-old adolescents. Three papers deal with regional brain atrophy in neurodegenerative disorders. Howard Rosen and colleagues from San Francisco (page 2612) show that abnormalities affecting a selection of test conditions correlate with regional voxel-based morphometric changes in 148 patients with dementia, leading to the specific conclusion that the right cerebral hemisphere, especially the medial wall of the frontal lobe, governs social and emotional behaviour. Using a novel imaging protocol, Stefan Teipel and collaborators from Munich and Würzburg (page 2626) suggest that changes within the substantia innominata of the nucleus basalis of Meynert in Alzheimer's disease are signatures of cholinergic neuronal loss with consequential reductions in volume of the prefrontal cortex, inferior parietal lobule and cingulated gyrus. The Morris water maze, which requires rats cast into opaque water to swim until they re-locate a submerged platform on which to rest, is much loved by behavioural scientists (but is understood to have rather a poor reputation amongst rodents): Thomas Brandt and a group from Munich and Bielefeld (Germany), Austria, New Mexico and New Zealand use a variant of this test to show that people with bilateral vestibular loss have mnestic difficulties with navigation, correlating with hippocampal atrophy and thereby indicating that vestibular input informs spatial memory even when individuals are stationary (page 2732). The role of inflammation in tissue injury and repair, and the range of disorders in which this fundamental process is now implicated are much debated. Glenda Halliday and colleagues from Sydney and Aarhus, Denmark (page 2654) stained tissue from patients with idiopathic and genetic causes of Parkinson's disease using a variety of markers as mediators of humoral immunity to show that Lewy bodies and dopamine nigral neurons are each rich in IgG deposits—the amount correlating with activated microglia (expressing Fc
R1 receptors for IgG1) and inversely with neuronal loss. Heinz Wiendl and a group from Tübingen, Dusseldorf, Göttingen and Würzberg in Germany, and Montreal, use expression of HLA-G and its receptor ILT2 in tissue from individuals with multiple sclerosis, and elevated levels of HLA-G in cerebrospinal fluid, to provide evidence for processes that regulate the inflammatory response in plaques, perilesional areas and normal appearing white matter (page 2689).
The recent description of axonal pathology in multiple sclerosis (Trapp et al. 1986 New England Journal of Medicine 338: 278–285) contained illustrations that soon achieved iconic status as contemporary depictions of the disease. But as commentators were quick to point out, neither the description nor the appearances were original and each could be found in the classical literature. Nonetheless, the emphasis on axonal pathology has triggered a useful debate on whether the disease process in multiple sclerosis is primarily inflammatory, from which all others features follow as the cascade of damage unfolds; the result of fully independent inflammatory and degenerative processes such that suppression of the one will not influence the other; or a mixture in which intrinsic axonal vulnerability is exposed by the arrival of an inflammatory process, the interplay eventually allowing each to proceed under its own momentum. On page (2713), Ian Pomeroy and colleagues from Oxford show that, in the marmoset model of experimental autoimmune encephalomyelitis, large subpial lesions account for most demyelination in the cortex despite having the least evidence for inflammatory infiltrates. And on page (2705), Alexandra Kutzelnigg and investigators from Austria, Germany and the United States (Mayo Clinic) show that the progressive forms of multiple sclerosis are characterized by diffuse white matter injury and cortical demyelination: these lesions show axonal injury with microglial activation and global inflammation throughout the whole brain and meninges, and this type of appearance correlates poorly with the number of discrete plaques seen elsewhere. The authors consider that multiple sclerosis starts as a focal inflammatory disorder manifesting as white matter plaques but chronicity is associated with diffuse inflammation and axonal loss. In ‘From the Archives’, we review two papers describing histological features of the lesions in multiple sclerosis published 81 and 69 years ago, respectively (Symonds CP. Brain 1924: 47; 36–56 and Greenfield JG and King LS. Brain 1936: 59; 445–458).
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