Editorial
Writing in The Naval Surgeon (1734), John Atkins (1685–1757) noted that natives in western Africa are prone to a ‘sleeping distemper’, usually fatal, and resulting at best in an irresistible tendency to sleep such that survivors ‘lose the little reason they have and turn idiots’. As Roy Porter explains in The greatest benefit to mankind (1997), HM (Henry) Stanley's success as economic development director to King Leopold II flushed this disease into the central areas, and missionaries conveying the sick to mission stations inadvertently triggered infection of previously uninfected zones such that fatalities soared and the horrors of sleeping sickness seized the public imagination. In Missionary travels and researches in South Africa (1857), David Livingstone gave an account of the tsetse fly and of the disease of livestock resulting from its bite; in line with the ubiquitous approach to most diseases presumed to be infective, he treated ‘nagana’ in horses with arsenic.Colonial officers and others who worked ‘In Darkest Africa’ have not always had a good press. But, in ‘To sleep; to die’ (with apologies to Hamlet), reviewing The fatal sleep: Africa's killer disease that went undiscovered for centuries by Peter Kennedy, professor of neurology in the University of Glasgow, Eldryd Parry makes a plea for clemency on behalf of those who ran the British Empire and ‘were changed, hardened and matured by the cultural front-line from which there was no retreat’ (page 1402). Professor Parry has worked in Africa since 1960, first in Nigeria and then as professor of medicine in Ethiopia and dean of medicine in Nigeria, Ghana and Somaliland. In 1988, he founded the Tropical Health and Education Trust and, in 2007, was awarded the centenary medal by the Royal Society of Tropical Medicine and Hygiene for life-time achievement in tropical medicine. Writing for Brain from rural Ethiopia, Professor Parry brings to our attention the writings of those who studied victims of the climatically fastidious tsetse fly, whose bite is ‘a profound challenge to any African government where the disease is endemic ... a brake on development, a torpedo to the best rehearsed plans to combat poverty, and a clamp on increased livestock breeding’. Drawing on the Sleeping Sickness Commission's 17 reports (1903–1919), he reminds us of the interplay between opportunism on the part of the tsetse fly, corruption in Government and civil unrest in encouraging epidemics of sleeping sickness in Angola, Congo, Sudan and Uganda. Eldryd Parry rehearses the parasitology of the two forms of human African trypanosomiasis: the naming of the East African protozoan after the work of (Sir) David Bruce in Zululand and the no less brilliant contributions of Aldo Castellani in Uganda; identification of the West African trypanosome by Dr Everett Dutton—first announced in a telegram to Ronald Ross (of malaria fame) published in the British Medical Journal (1902); and the more recent scientific and sociological contributions from the Medical Research Council (UK) Laboratories in the Gambia and by Médecins sans Frontières. He reminds us that ‘science is alone if it is not married to political stability, attended by social stability without movement of people, by responsible government and by a strong infrastructure in the health service’—an analysis from which he senses optimism in the catalytic persuasion to act set out in Peter Kennedy's wholly admirable book.
The March cover of Brain reproduced aspects of a study in which patients with disease of the basal ganglia performed badly in a reward-based task. Building on this interest in how the brain deals with choice—a function that requires the interplay of macrocircuits and functional systems in generating goal-directed behaviours that advantage humans and other primates—three papers in the present issue report related aspects of decision-making under risky conditions in the context of focal brain disease. Liane Schmidt and colleagues from Lille and Paris (France) examine responses requiring mechanical force in tests motivated by financial reward in patients with diseases of the basal ganglia (page 1303): they show that dopamine depletion is associated with inability to distinguish monetary incentives indicating that bilateral striatal damage dissociates motor responses from the affective evaluation of fiscal gain. Luke Clark and a team from Cambridge (UK) and Los Angeles and Iowa (USA) make the distinction between the ability to resolve genuinely ambiguous outcomes and those where a calculated but informed risk must be taken (page 1311): they show that patients with ventromedial prefrontal cortical lesions prove irresponsible in placing bets regardless of the odds of winning, whereas those with damage to the insular cortex are more discriminating but fail to register the probability of a poor outcome by moderating their stakes. Elizabeth Wheeler and Lesley Fellows from San Diego and Philadelphia (USA) also consider the role of the ventromedial cortex in adjudicating between the possibility of loss and gain to show that the essential defect of ventromedial prefrontal cortical damage is failure to pick up the negative vibes that ought to be apparent from prior experience (page 1323).
On page 1268, Siobhan Garbutt and investigators from San Francisco (USA) assess whether the presence of abnormal eye movements usefully distinguishes the overlapping phenotypes of the frontotemporal dementias, Alzheimer's disease, corticobasal degeneration and supranuclear palsy: other than in semantic dementia, abnormalities are common but the only specific feature is slowing of saccadic velocity in supranuclear palsy; together, the study of eye movements is no less discriminatory than neuropsychological tests in classifying these neurodegenerative disorders. Ian Mackenzie and colleagues from Vancouver and Ottawa (Canada) describe frontotemporal dementia with ubiquinated inclusions but no accumulation of TDP-43 (page 1282): the cases show early onset with neurobehavioural features but few motor or cognitive abnormalities, and pathological examination also distinguishes this variant of frontotemporal dementia from those with specific proteinopathies. Sean O'Sullivan and colleagues from London (UK) and Melbourne (Australia) carry out a retrospective review of the clinical features and course of pathologically confirmed supranuclear palsy and multiple system atrophy to show that individuals with the Richardson phenotype present later and progress faster than those with the parkinsonian variant of supranuclear palsy or multiple system atrophy; and the prognosis can reliably be predicted in any individual if there is early transition to one of several designated clinical milestones (page 1362).
Helping the nervous system to recover from injury through adaptation and plasticity and maximizing the impact of strategies for structural repair are enshrined in the doctrines of rehabilitation as a biological rather than merely a coping discipline. Cathy Stinear and colleagues from Auckland (New Zealand) use active–passive bilateral therapy to manipulate intracortical inhibition and increase excitability within the ipsilesional motor cortex as assessed by transcortical magnetic stimulation targeted at M1 and studied at 1 month after therapy starting 6 months from onset of acute stroke (page 1381): they show that therapy improves motor function in the upper limb in association with altered regional and transcallosal inhibitory activities attributed to increased plasticity. And Maria Richter, Wolfgang Miltner and Thomas Straube from Jena (Germany) assess right and left hemisphere brain regions in patients with chronic non-fluent aphasia exposed to constraint induced aphasia therapy to show that therapeutic success correlates with a reduction in the abnormal right inferior frontal gyrus and insular cortex activity that they detect prior to therapy (page 1391).
Amongst four papers dealing with nerve and muscle, Arun Krishnan and investigators from Sydney (Australia) show electrophysiological evidence for a reduction in nodal sodium ion conductance at rest followed by axonal hyperpolarization after 1 min of maximal voluntary contraction, reflecting sodium/potassium pump dysfunction that may underlie the weakness and fatigue of diabetic neuropathy (page 1209). Ines Dierick and colleagues from Antwerp, Brussels and Leuven (Belgium), Ferrara (Italy), Belgrade (Serbia), St Gallen (Switzerland), Montpellier (France), Zagreb (Croatia), Prague (Czech Republic), Warsaw (Poland) Graz (Austria) and Leiden and Utrecht (The Netherlands) catalogue mutations of the seven genes already implicated in autosomal dominant distal hereditary motor neuropathies to show, in 112 patients, nine mutations affecting HSPB8, HSPB1, BSCL2 and SETX but none in GARS, DCTN1 and VAPB endorsing the concept of genetic heterogeneity in autosomal dominant distal hereditary motor neuropathies and suggesting a future strategy for screening unclassified cases (page 1217). Insights into the pathogenesis of the Guillain–Barré syndrome are provided by the demonstration of antibodies directed against gangliosides that may show molecular mimicry with epitopes of micro-organisms, such as Campylobacter jejuni. Anti-GQ1b is a reliable biomarker for the Miller Fisher syndrome, binding presynaptic motor nerve terminals at the neuromuscular junction, and with complement activation and formation of membrane attack complexes. But does it actually cause the damage? Susan Halstead and investigators from Glasgow and Cheshire (UK) and Leiden and Rotterdam (The Netherlands) use a murine model of the Miller Fisher syndrome to show that the human monoclonal antibody ecluzimab completely inhibits electrophysiological and structural damage in vitro and in vivo by preventing C5b-9 complex formation from C5a (page 1197). As Helmar Lehmann and Hans-Peter Hartung point out in their commentary (page 1168), the implications for improved management of neurological disorders in which complement activation is implicated are considerable.
The Miller Fisher syndrome has long caused confusion amongst neurologists. First, how should the condition described by Charles Miller Fisher, aka CM Fisher, properly be designated? Miller Fisher syndrome and Fisher syndrome each have their proponents. We understand that the nonagenarian Dr Fisher evidently prefers Miller Fisher syndrome. Secondly, what is the relationship between the Miller Fisher syndrome and the condition described 5 years earlier by Edwin Bickerstaff and since dubbed Bickerstaff's brainstem encephalitis? Each is characterized by the triad of ophthalmoplegia, ataxia and areflexia. In From the Archives, we review two papers that examine this question—Brain stem encephalitis and the syndrome of Miller Fisher. A clinical study by Amir Najim Al-Din, Milne Anderson, Edwin R. Bickerstaff and Ian Harvey (Brain 1982: 105; 481–495) and Bickerstaff's brainstem encephalitis: clinical features of 62 cases and a subgroup associated with Guillain-Barré syndrome by Masaaki Odaka and six colleagues (Brain 2003: 126; 2279–2290).
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