Editorial
Sir Charles Bell (1774–1842) might be considered the Great Houdini of functional neuroanatomy. Neatly side-stepping the correction to his ‘discovery’ (Idea of a New Anatomy of the Brain, 1811: published privately and not made generally available until 1839) that the anterior nerve roots of the spinal cord are motor and sensory (the ‘way in’) and the posterior roots entirely motor (the ‘way out’) offered by Francois Magendie (1753–1855) in 1822, Bell allowed it be known that this was what he had in fact always said. The story is told in Paul Cranefield's magnificent ‘The way in and the way out’ (1974); but 196 years later, Thomas Dormandy evidently makes the same mistake. In ‘Pain past, present and future: the unhappy paradox of scientific advances and therapeutic standstill’, despite Dr Dormandy's rich historical account of the many attempts to grapple with this story, Geoff Schott reasonably declares lack of confidence in ‘The worst of evils: the fight against pain’ because the author perpetrates the same neuroanatomical howler (page 1704). Better is the less racy but more scholarly historical record of anaesthesia and analgesia told by Stephanie Snow in ‘Operations without pain’. And in surveying where the neuroscience of pain is heading through his reading of the papers in ‘Emerging strategies for the treatment of neuropathic pain’, Dr Schott concludes that the nervous system seems to be extraordinarily resistant to switching it off when the protective properties of pain need to be suppressed. Therapy still has a long way to go.In an ‘occasional paper’, Geoff Schott analyses what can be learned about pathophysiology from the depictions of visual hallucinations experienced by migraineurs, especially those drawn by clinicians and scientists well placed to offer an informed interpretation of their symptoms (page 1690). Uniformity in representations of the expanding scotoma and fortification spectra provides evidence for these being authentic expressions of spreading cortical depression: following Leonardo da Vinci, Dr Schott concludes that ‘what we see emanates from within rather than from without’. His account is richly decorated with anecdotes and illustrations that document the many thick heads suffered down the years since John Fothergill (1712–80) first reported ‘Remarks on that complaint commonly known under the name of the sick head-ache’ to the Select Society of Licentiates on December 14, 1778, and published in his journal (Medical Observations and Inquiries 1777–84: 6; 103–37). A collage of these images appears on the cover of this issue. We hope it does not precipitate an attack in any of our readers. Jaime Parra and colleagues from Heemstede, Amsterdam and Tilburg (The Netherlands) show that coloured stimuli are inferior provocateurs of photoparoxysmal responses in individuals known to have photosensitive epilepsy compared with black and white stroboscopic or patterned triggers. Within the colour spectrum, red–blue sequences are the most epileptogenic; dark glasses are recommended (page 1679). On a somewhat related theme, Vincenzo Donadio and a team from Bologna (Italy) and Göteborg (Sweden) show enhanced and prolonged transient inhibition of muscle sympathetic nerve activity in response to phobic arousal stimuli in individuals who faint at the sight of blood or threats of injury (page 1653). A different type of response to stimulation is studied by Simone Shamay–Tsoory and investigators from Haifa (Israel) who describe the reduced ability of individuals with prefrontal lesions to appreciate the fortune of others in a theory of mind task: sensing envy may localize to the right and gloating (schadenfreude) to the left ventromedial cortex (page 1663).
Six papers in this issue relate to muscle disease. In ‘More surprises in sarcomeric protein diseases’ (page 1453), Nigel Laing comments on three articles that describe distal myopathy or the scapulo-peroneal syndrome in association with mutations in sarcomeric proteins (pages 1465, 1477 and 1485). In August 2006, we published work by Clarke Slater and colleagues describing the clinical features and endplate characteristics of eight patients with ‘limb girdle myasthenia’ (Brain 2006: 129; 2061–76). That work left open the genetic explanation for these cases. On September 29, 2006 (Epublished, August 17), David Beeson on behalf of much the same team and co-authors from Oxford and Newcastle (UK) and Munich (Germany) reported mutations in DOK7 (‘downstream-of-kinase’ 7) as the genetic basis for ‘congenital myasthenia with proximal muscle weakness’ in 21 patients, together with experiments showing that DOK7 mutations affect maturation of the neuromuscular junction post-synaptic structure (Science 2006: 313; 1975–8): six patients came from Newcastle, eight from Oxford and seven from Munich. Now, we publish two further papers on the phenotype of DoK7 congenital myasthenia. Hanns Lochmuller and colleagues from Munich, Neuss, Halle/Saale and Dresden (Germany), Budapest (Hungary), Valencia and Barcelona (Spain), Porto and Lisbon (Portugal), Turku (Finland), Houston (Texas, USA), Quebec (Canada) and Oxford (UK) describe in detail the phenotypes of 14 patients from 12 kinships with DOK7 mutations (page 1497); Jacqueline Palace and investigators from Oxford (UK) and Toyko (Japan) report on 27 patients from 24 kinships with DoK7 neuromuscular junction synaptopathy and describe 15 in detail (page 1507). Readers may reasonably ask whether they have seen these cases before, or detect double vision through reading about the same material in two companion papers. We understand that in the paper by Hanns Lochmuller, six cases are newly identified, seven are listed by Beeson et al. (2006) and one is the sibling of a patient in that paper, not previously reported. Of the 27 listed by Jacqueline Palace, 6 feature in Slater et al. (2006) but only 2 are among the 15 patients now reported in detail; of those, 6 are newly identified and 9 already listed in Beeson et al. (2006). Despite shared authorship, there is no overlap of cases between the papers we now publish. Together, these reveal differences in phenotype of the limb girdle congenital myasthenic disorders—a form due to DOK7 mutations and the previously described ‘limb girdle’ congenital myasthenic syndrome with tubular aggregates—that were not apparent last autumn. Furthermore, amongst the newly reported cases are missense mutations, and the first example of an heteroallelic missense mutation; exon 7, towards the C-terminus of DOK7, is shown to be fundamental in the development of this disorder.
Eight papers deal with aspects of Parkinson's disease, supranuclear palsy or essential tremor. Amongst these, Rolf Fronczek and investigators from Leiden, Amsterdam and Nijmegen (The Netherlands) pursue the issue of sleep disturbance in the context of Parkinson's disease by showing a reduced number of hypocretin positive neurons in the hypothalamus, and lower concentrations of secreted hypocretin in prefrontal cortex and ventricular cerebrospinal fluid in cases compared to controls (page 1577). Thomas Thannickal and colleagues from Los Angeles (USA) add to this evidence and correlate the loss of hypocretin neurons and melanin concentrating hormone cells in the hypothalamus with disease progression and severity, whereas neuromelanin decreases only with disease duration (page 1586). Times have moved on since Russell Brain advocated ‘a ride in a motor car’ as preferred treatment for tremor in Parkinson's disease (Diseases of the nervous system, 1933, p. 456). Jan Herzog and a team from Kiel and Hamburg (Germany) correlate components of the tremor and reaching-to-grasp movements with each contact of the quadripolar electrode in defined anatomical positions in and around the thalamus based on intra-operative micro-recordings in patients with essential tremor or multiple sclerosis undergoing deep brain stimulation (page 1608); the most responsive sites, in all respects, are the posterior zona incerta and prelemniscal radiation where stimulation settles the movement disorder more effectively than stimulating the thalamus itself. Alessando Stefani and colleagues from Rome and L’Aquila (Italy) and Toronto (Canada) compare stimulation of the pedunculopontine and subthalamic nuclei in patients with Parkinson's disease who have not responded to pharmacological treatment. Stimulation of the subthalamic nucleus is marginally more useful than treatment targeted to the pedunculopontine nucleus, although this is particularly useful for gait and posture; both together are more effective than either alone, and the surgical approach may complement the response to medication (page 1596).
The first stereotactic procedures for movement disorders were performed in the 1940s and, over the next 20 years, a range of sites for destruction and stimulation were explored. For a while, the advent of L-dopa derivatives in the 1960s parked surgical treatments for movement disorders. But with the increased awareness and refractory nature of dyskinesias and failed pharmacological management, functional neurosurgery came back into the frame. All of the surgical procedures require accurate placement of probes using topographical references outside the head to target structures of interest deep in the brain and depend on atlases for stereotaxis. The first apparatus that reliably guided the neurosurgeon to defined brain regions was developed at University College, London. In From the Archives, we describe ‘The structure and functions of the cerebellum examined by a new method’, by Sir Victor Horsley and Dr RH Clarke (Brain 1908: 31; 45–124).
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