Editorial

‘They order, said I, this matter better in France.’ This opening to A Sentimental Journey through France and Italy (1768), of which Lawrence Sterne (1713–68) only managed to complete the first two of the four intended volumes, refers to prostitution. But it was another profession that concerned neurologists when making their way overland across France to the UK, following the recent meeting of the American Academy of Neurology in Toronto. With the closure of European airspace on 16 April 2010, special arrangements were needed if the unimaginable catastrophe of unrelenting headache, intolerable dizziness and unbridled tingling of the extremities resulting from the enforced absence from their clinics and consulting rooms of approximately 2000 neurologists was to be avoided. The situation called for extraordinary resourcefulness. And while Eurostar inflated prices for tickets that disappeared at the blink of a web site leaving expectant travellers abandoned at the Gard du Nord, and the British Navy gathered off Trafalgar merely to watch the hordes that thronged the quaysides of Spain and France, one community rose to the occasion, put profit aside, asked no questions of prior loyalty, added altruism to responsibility, and acted decisively and effectively. This was the pharmaceutical industry. The first British team home from Toronto was shepherded by Biogen Idec and Novartis. Operations for Biogen Idec were coordinated by Eric Fidelin (Director for France), Gerrit Tent (Director for Benelux) and Terry O’Regan (Director for the UK)—the latter staying at his post in Canada to allow others, including many who were not guests of that company in Canada, seats on the chartered ex-Singapore airlines Boeing 747 that evacuated 400 neurologists to Madrid on the first leg of journeys by land and sea to their respective homes. In marked contrast to the debilitating wall of silence and recorded messages from airlines and official organizations (invariably ending in the eternal silence of piped music or statements that bore no resemblance to reality), the senior employees of these companies provided a human face for this grateful and ever-cheerful ‘confusion of neurologists’. For those caught up in this unexpected situation but accepting each dénouement phlegmatically and with patience, and who emerged at Temple tube station in London after travelling for 72 h, one memory of this fully acceptable face of Big Pharma was ‘Le Picnic’ at Bordeaux Saint Jean railway station, while waiting for a Train à Grande Vitesse (TGV) laid on by the French Ministry of the Intérieur in order to salvage the neurological health of the European Union. The editor of Brain and the Association of British Neurologists are grateful to Biogen Idec and Novartis for their help. Ever since René Descartes depicted the neural circuitry of a young lad abruptly withdrawing his hand from the flames of burning faggots (De Homine, 1662: Figure XLVII, page 108), neuroscience has worked its way up and down the pain pathways of the brain and spinal cord, seeking in vain a comprehensive account of the system that warns when something is wrong and aspires to symptomatic relief from its occasional perturbations. In ‘The lost domain of pain’, Maria Fitzgerald reviews Pain and its Transformations: the Interface of Biology and Culture (2008) edited by Sarah Coakley and Kay Kaufman Shelemay (page 1850). Professor Fitzgerald praises this collection of essays for placing the biology of pain in a cultural context and, in so doing, offering a formulation that goes beyond the explanatory model of the gate-control concept proposed by Ronald Melzack and Patrick Wall—revolutionary in its day and thoroughly exposing ‘the inadequacies of classic sensory physiology’. Legacies of the gate-control theory are the notions of filtration, modulation and selection of crude inputs; but any explanation for regulation of the pain experience by social and cultural conditioning is lacking. For Professor Fitzgerald, the contributions of neuroscientists, theologians, ethnographers, historians, linguists and anthropologists to this book are ‘truly extraordinary’. Pain is needed in order to develop the complex and varied emotional and affective equipment of being human. These correlates develop in parallel and social modulation may even anticipate the final laying down of neural pathways to register the crude physical experience. Pain has a mental and, in all faiths, spiritual currency that questions whether it is better suffered than suppressed. In many species, pain is collective not individual, and therefore a necessary part of social organization and communication between members of a population. That said, the materialist doctrine is supported by evidence that patterns of regional brain activation in response to pain differs in Catholics, depending on whether or not they contemplate a religious image. After training in physiology at Oxford University, Professor Fitzgerald worked with Professor Patrick Wall at University College London where she is now Professor of Developmental Neurobiology. ‘Having worked as a pain neuroscientist for my whole career and prided myself on being open to new ideas, this book really made me question my intellectual direction and reach beyond science into the social, cultural world.’ Among three papers on neurogenetics in the present issue, Jin-Sung Choi and colleagues from New Haven and West Haven (USA), Erlangen (Germany) and Nijmegen (The Netherlands) add Nav1.7-G616R to the list of sodium channel mutations that alter activation of dorsal root ganglion neurons, leaving these hyperexcitable in response to graded stimuli and leading to chronic pain in affected individuals (page 1823). Sarosh Irani and colleagues from Oxford, Cambridge, Southampton and London (UK) and Hamburg and Bonn (Germany) correlate clinical features in patients with complement activating serum and cerebrospinal fluid immunoglobulin G1 antibodies targeting the N-methyl-d-aspartate receptor (page 1655). They show that this recently described condition evolves from neuropsychiatric features and epilepsy at presentation that is responsive to early intervention with immunotherapy, to a movement disorder with autonomic abnormalities and altered consciousness. They propose a model in which initial diffusion of serum antibodies into the cortical grey matter is followed by secondary intrathecal expansion of the immunological repertoire and selective damage to subcortical neurons. Three papers address language and music. Fang Liu and investigators from London (UK) and San Diego (USA) question whether individuals with congenital amusia also have difficulty in their appreciation of speech intonation; they confirm impaired performance on discriminating and imitating statements that require the interpretation of pitch direction of verbal sounds, indicating a shared deficit in mechanisms responsible for appreciating the sounds of language and of music (page 1682). Wei Hu and a team from Jiangsu Province (China), Tubingen (Germany) and Oxford and London (UK) report that, although different brain regions are normally activated when reading English and Chinese scripts (left inferior frontal and posterior superior temporal sulci, respectively), brain activation in those with dyslexia for these languages converges on reduced activation of the left angular gyrus and left middle frontal, posterior temporal and occipitotemporal regions, explaining why the complex cognitive consequences of dyslexia transcend different cultures (page 1694). Nicolaas Bohnen and investigators from Ann Arbor (USA) use [11C]methyl-4-piperidinyl proprionate acetylcholinesterase and [11C]dihydrotetrabenazine vesicular monoamine transporter type 2 positron emission tomography to show that cholinergic denervation of the limbic archicortex is a better signature of altered olfaction in people with Parkinson’s disease than nigrostriatal dopaminergic denervation, and may identify individuals early in the disease course who have an increased risk of subsequent cognitive impairment (page 1747). Several papers in the current issue deal with the eyes and vision. Using changes in muscle tone as indicators of the dream sequence in patients with rapid eye movement sleep behavioural disorder, Laurène Leclair-Visonneau and colleagues from Paris (France) show that affected individuals also move their eyes in order to ‘watch’ these dreams—as probably normal individuals do when dreaming (page 1737 and see cover). Vision is an integral part of social interaction and, hence, its emotional content. Corinna Klinge, Brigitte Röder and Christian Büchel from Hamburg (Germany) report that, in those who are blind from an early age, the amygdala and the occipital cortex have a much enhanced response to auditory signals, indicating that the limbic system adapts to whichever stimulus is most abundant in shaping emotional responses to the social world (page 1729). Alison Lane and colleagues from Durham (UK) show that in people with homonymous hemianopia, rehabilitation based on visual attention does not improve further with eye movement exploration of the hemianopic field, indicating that attention is crucial in adapting successfully to lost function (page 1717). Ari Green and investigators from San Francisco (USA) and Belfast (UK) use a tissue bank of eyes to revisit the issue of inflammation and axonopathy in people with multiple sclerosis (page 1591). They report active inflammation, and neuronal and axonal loss in the retinal nerve fibre, ganglion cell and inner nuclear layers, at all stages of the disease; and show that even late in the clinical course, there is active iritis and retinal periphlebitis. The eye has long served as a window on the brain when providing insights into the pathogenesis of multiple sclerosis. In From the Archives, we review ‘Retinal venous sheathing in optic neuritis: its significance for the pathogenesis of multiple sclerosis’ by Lightman S, McDonald WI, Bird AC, Francis DA, Hoskins A, Batchelor JR and Halliday AM (Brain 1987; 110: 405–414).

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