Brain Vol. 128 No. 1 © Guarantors of Brain 2005; all rights reserved
Editorial
Last year, William Feindel and Valerie Grosvenor Myer reviewed medical and social attitudes to the physical basis and nature of the soul; and Ray Tallis tackled the thorny issue of consciousness. But if these arguments were eventually settled in favour of an anatomical locus of mind, how then does the brain work? Leonardo da Vinci first moved neurological attention from functions dependent on the contents of the ventricles to the brain substance itself. But in 1543, Andreas Vesalius doubted whether anatomy would ever explain function and, as late as 1633, Kenelme Digby was still advancing Platonic ideas on the function of the nervous system. In ‘Impulses, good and bad’, Ian McDonald tells the story of how various candidates for the vital force were considered prior to the work of Luigi Galvani (1737–1798) that identified electricity as the stuff that provides function in the nervous system. A history of nerve functions from animal spirits to molecular mechanisms by Sidney Ochs mainly tells the story of knowledge concerning the PNS. Many important lessons were learned from such studies, given the relative ease of access to tissue, but Ian McDonald paints on a broader neuroscience canvas. Modestly, his own seminal contributions as a student with Archie McIntyre in New Zealand, and with Derek Denny Brown in Boston, leading to the characterization of electrical conductance and function in the context of demyelination and remyelination—published in Brain—and work with Tom Sears from the 1960s, are underplayed. Rather, he traces the debates on how one form or another of nervous fluid or humours, vibration, tugging and particulate nudging in peripheral nerves anteceded the elucidation of electrical conduction in the CNS. In turn, the knowledge of normal function informed our understanding of how symptoms are produced, especially in the context of spinal cord compression and multiple sclerosis.Point mutations conferring pathological mutations in mitochondrial DNA were described in the late 1980s. A few small series of cases had earlier been reported suggesting that, in a minority of such patients, clinical features in Leber's hereditary optic neuropathy extend outside the anterior visual pathway (Wilson. Brain 1963; 86: 347–362; Lees et al. J Neurol Neurosurg Psychiatry 1962; 27: 415–421). This story came together in 1992 (Harding et al. Brain 1992; 115: 979–989), since which time the real but rare occurrence of a multiple sclerosis-like illness in individuals with Leber's disease—usually but not invariably females and often without a family history—has been accepted, even if the nature of that relationship remains to be resolved. In this issue, Herbert Budka and colleagues from Hungary, Austria and Germany (page 35) describe, for the first time, the neuropathology in a single case of Harding's disease—white matter involvement and clinical features consistent with multiple sclerosis in the context of Leber's hereditary optic neuropathy. A female with the T14484C point mutation died from complications of progressive immobility 19 years after presentation with relapsing visual failure followed by symptoms attributable to spinal cord, brainstem and cerebral involvement. Post-mortem examination revealed multifocal destructive lesions affecting the optic nerves, frontal lobes and other parts of the cerebrum partially involving U fibres. Histological examination showed loss of oligodendrocytes and axons with astrocyte reactivity. This is an inflammatory disorder with infiltration of CD8-positive lymphocytes, activated macrophages/microglia showing immunoreactivity for inducible nitric oxide synthase (iNOS), and conspicuous upregulation of the mitochondrial manganese superoxide dismutase (MnSOD)—features indicating tissue damage predominantly mediated by T cells and activated microglia.
In the post-human genome world, it is possible to advance rapidly from pedigree .. to chromosomal region of interest .. to positional candidate .. to gene. The dividend for explaining disease mechanisms from identification of the causative mutation may extend beyond these rare families. Alexander Lossos and colleagues from Israel (page 42) move their description of 16 affected individuals in eight families originating within a highly inbred Arab community from the clinical features of ‘chronic progressive external ophthalmoplegia plus’ to the demonstration of type 1 fibre predominance and core-like inclusions, and implication of a nuclear locus narrowed to a 12 cM interval at 17p13.1–p12 encoding several sarcomeric myosin heavy chain genes. MYH2 is excluded, but others remain to be assessed as the explanation for this autosomal recessive Mendelian disorder.
Collectors tend, often rather unconvincingly, to rationalize their habit around the excuse ‘I have an incurable disease’ thereby hoping to justify the activity and disarm their (usually domestic) critics and any bemused on-lookers. It seems that their intuitions were correct. Steven Anderson, Hanna Damasio and Antonio Damasio (page 201) test the hypothesis that ‘normal’ collecting behaviour may be a localized function and ‘pathological’ acquisition associated with brain lesions. ‘Collections of art objects, antiques, books, and coins can be found in homes throughout the world, no category of objects being without its ardent collectors, and there are conferences and organizations for collectors of items ranging from postage stamps to farm tractors’. They identify 87 individuals with heterogenous lesions at sites where a priori abnormal accumulation of objects might be expected. They show that 13 (15%) did indeed forage and store—in their cases—useless objects. The subjects were resistant to advice or change and tolerated the negative consequences of their activities. The trouble lies in the right polar sector of the mesial frontal lobe and the anterior cingulate gyrus. Loss of inhibition has evidently released the innate tendency to acquire and retain objects. Before they protest too much, collectors should acknowledge that, for them also, it is often the gathering that is more rewarding than the possession and use of the books, coins, postage stamps, beer-mats and tractors that litter the offices and hideaways of seemingly normal members of society, from bag ladies to .. editors of Brain. Steven Anderson and colleagues describe a behaviour; but they touch on the issue of whether this can be reduced to an impulsive motoric trait—in its simplest form no more than the uncontrolled grasping of objects in individuals with frontal lesions described by S. A. Kinnier Wilson and F. M. R. Walshe (Brain 1914; 37: 199–246) and W. J. Adie and Macdonald Critchley (Brain 1927; 50: 1423–170), and elaborated by Francois Lhermitte as the inclination to use objects in a stimulus-bound manner, so-called ‘utilization behaviour’. They reject this simple formulation, citing Lhermitte's series of 75 cases showing an extension of bilateral manual grasping (magnetic apraxia) in individuals with frontal lesions who relentlessly grasped and manipulated utilitarian objects (Lhermitte et al. Ann Neurol 1986; 19: 326–334). ‘Utilization behaviour’ was first described by Lhermitte in Brain. We review his 1983 paper in From the archives.
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