Lord Brain Research Articles

The neuromythology of Hashimoto encephalopathy

The initial description of Hashimoto encephalopathy (HE) is credited to Lord Brain and his colleague Jellinek,1 who in 1966 reported a patient with an “extraordinary and puzzling neurologic illness which waxed and waned for over a year.” The patient was a 48-year-old man who had been previously diagnosed with Hashimoto thyroiditis. Just over a year later, he developed an episodic neurologic illness characterized by alteration in mood and consciousness and stroke-like episodes variably inducing transient aphasia, right or left hemiparesis, hemi-sensory deficits, hemianopsia, and monocular blindness. These were followed by episodic hallucinations, agitated confusion, and involuntary movements (tremor, athetosis). Multiple CSF examinations were remarkable only for an elevated protein (maximal 240 mg/dL) and at times a paucicellular pleocytosis (never >8 cells/mm3). Carotid angiography was unremarkable. An EEG showed generalized theta and delta slowing. Neuroimaging was not performed. He was treated intermittently with prednisone and an anticoagulant with little consistent response. Changes in serum thyroid antibodies seemed to parallel the clinical course. The illness resolved spontaneously. Lord Brain and Jellinek summarized the case as one of a “stuttering brain disorder of an unusual kind with concurrent rise in the level of thyroid antibodies.”1

2 Movement disorders – the parkinson’s névrose

Born on Merseyside, Andrew Lees qualified in medicine at the Royal London Hospital Medical College in 1970. His neurological training was at University College London Hospitals and the National Hospital for Neurology and Neurosurgery, Queen Square. He also spent time at L’Hopital Salpetriere, Paris. At the age of thirty-two he was appointed to the consultant staff at the National Hospitals, The Middlesex, and Whittington Hospitals and in 1987 was elected a Fellow of the Royal College of Physicians. He was later appointed Professor of Neurology at the National Hospital for Neurology and Neurosurgery, Queen Square and was Director of the Reta Lila Weston Institute for Neurological Studies (1998–2012). He was Clinical Director of the Queen Square Brain Bank for Neurological Disorders (1985–2012) and Director of the Sara Koe PSP Research Centre (2002–2012). He is a Visiting Professor at the University of Liverpool and has close collaborations with a number of Brazilian universities. For his contributions to Brazilian neurology he was elected an overseas member of the Academia Nacional de Medicina and the Academia Brasileira de Neurologica. He was elected as a Council member of the Academy of Medical Sciences 2012- 2015. Appointed as an Expert Adviser for the UK Government National Institute for Health and Care Excellence Centre for Guidelines (2006–2019). Andrew has achieved international recognition for his work on Parkinson’s disease and abnormal movement disorders. He is an original member of the Highly Cited Researchers ISI Database. Founder member of the international Movement Disorder Society, he was elected President (2004–2006) and co-edited the Movement Disorders Journal between 1995 and 2003. In 2006, he was awarded the Movement Disorders Research Award by the American Academy of Neurology. In recent years, he has delivered the Gowers Memorial Lecture at the National Hospital, The Inaugural Lord Brain Memorial Lecture at Barts and the Royal London Hospitals and David Marsden Memorial Lecture at the European Federation of Neurological Societies. He was the recipient of Stanley Fahn Lectureship Award, MDS Dublin 2012, and has been awarded the German Society of Neurology’s 2012 Dingebauer Prize for outstanding scientific attainment in the field of Parkinson’s disease and Neurodegenerative Disorders. In 2014, Andrew received the prestigious Jay Van Andel award for outstanding research in Parkinson’s disease. Based in Grand Rapids Michigan, the Van Andel Institute is an independent research organisation dedicated to preserving, enhancing and expanding the frontiers of medical science. In 2015, he became the recipient of the Association of British Neurologists Medal, awarded annually in recognition of outstanding contributions by British and Irish neurologists to the science and practice of neurology. Jean-Martin described ‘maladie de Parkinson’ as a nevrose, a term introduced into France by Pinel and used to describe any nervous disorder without demonstrable organic pathology. In 1917 Tretiakoff working at L’Hopital Salpetriere demonstrated that a severe loss of pigmented nerve cells in the pars compacta of the substantia nigra was invariably present giving it a ‘solidity’ denied to many other movement disorders such as dystonia and chorea and brought the disease firmly into the fold of neurology. From the earliest clinical descriptions, it has been recognised that anxiety and depression can have a profound effect on the expression and severity of the motor symptoms of Parkinson’s diseasse and that the kinesics of chronic anxiety and psychomotor retardation bear a superficial similarity to the movement disorder that characterises Parkinson’s disease. Slowness of willed movement an invariable feature of Parkinson’s disease can be seen in depression and also in a rare form of obsessional compulsive disorder. The intimate links between motion and emotion in basal ganglia disorders and the notion of Parkinson’s disease as a neuropsychiatric disorder are now widely acknowledged but the idea that severe emotional stress could cause neurodegeneration is more controversial. In a paper published in 2014 Djamshidian and I hypothesised that chronic stress might cause Parkinson’s disease in susceptible individuals and that many of the symptoms reported in the pre-diagnostic phase of the illness are identical to those seen in functional somatic syndromes (Djamshidian A, et al. J Neurol Neurosurg Psychiatry 2014;85:879–882). The clinical clues that stress might be a neglected risk factor for Parkinson’s disease will be discussed in the hope of stimulating further research.

Noshir Hormusjee Wadia

Pioneer in Indian neurology Noshir Hormusjee Wadia, one of the founding fathers of neurology in India, was at the vanguard of the development of neurological sciences in the country. Born...

Lindsay Mary Elliott

After qualifying as one of only three women in the year, Lindsay Mary Elliott was chosen for one of the most sought after house jobs with Sir Russell Brain, followed...

Book Reviews

Notes On Medical Virology by Morag C. Tinbury. Published by E. & S. Livingstone Ltd., E d in burgh 1967.Racial And Geographical Factors In Tumour Incidence (University of Edinburgh Press— Pfizer Medical). Monograph No. 2. Edited by A. A. Shivas. 63s.Psychiatric Disorders Of Obstetrics by A. A. Baker.Blackwell ScientificPublications. 27s 6d.A Synopsis of Children's Diseases (4th Edition) by Rendle- Short & Gray. John Wright & Sons Ltd.. Bristol, 52s 6d.Biochemical Values In Clinical Medicine by RobertEastham. John Wright & Sons Ltd., Bristol. 15s.Roxburgh’s Common Skin Diseases (13th Edition) by Peter Borrie. H. K. Lewis & Co. Ltd. £2 10s.A New Look At Industrial Medicine by R. L. Luffingham. Pitman Medical 12s 6d.Cervical Spondylosis edited by Lord Brain & Marcia Wilkinson. William Heinemann Ltd. 55s.Diseases Of The Nose, Throat And Ear (8th Ed.) by Hall & Coleman. Livingstone 30s.The Vesico-Vaginal Fistula by J. Chassar Moir. Bailliere Tindall & Cassell Ltd. 60s.

Optic Neuritis: Another Dickensian Diagnosis

The clinical diagnosis and natural history of optic neuritis was established in the late 1880s by the ophthalmologists von Graefe and Nettleship. The earlier, accurate and insightful description of transient, bilateral visual loss of Esther, the main character in the Charles Dickens novel Bleak House (1852--1853), suggests optic neuritis as a Dickensian diagnosis. Remarkably, Dickens’ observations, also preceding the earliest clinical description of multiple sclerosis by Charcot in 1868, described many clinical features such as a prodromal phase; a nadir; gradual recovery over weeks; glare disability; reduced contrast sensitivity; possibly Uhthoff’s phenomenon; and visual fading. All this with an accuracy that, to quote Russell Brain, “would credit a trained physician.”

Hashimoto’s Encephalopathy in the Intensive Care Unit

Since the first description of Hashimoto's Encephalitis (HE) in 1966 by Lord Brain, the number of reported cases has continued to increase. In addition, cases of status epilepticus have been reported, suggesting a role for intensive care unit (ICU) practitioners in taking care of patients with HE. A retrospective cohort study in ICU patients with HE was performed at the University Hospital of Tours, France. Eight HE cases were admitted to the ICU between 1/1/2000 and 1/1/2012. Herein, we describe the characteristics of the patients, with an emphasis on ICU disease management and its outcome. ICU practitioners should be aware of this disease, since it can include life-threatening presentations.

Offline: A sharp mind and a strong pen

I owe a debt of thanks to Dr John McLean. In May last year, he wrote with a gift, The Quiet Art: A Doctor's Anthology. This fine volume of quotations was compiled by Liverpool physician, Dr Robert Coope, and published in 1952. The President of the Royal College of Physicians at the time, Russell Brain, asked in his foreword, “Do lawyers in their quieter moments write on the human aspects of torts, or architects turn from calculations of window space and sunlight to compose hymns to Apollo?” His claim was that doctors made a special contribution to literature.

Pseudobulbar Affect in Stroke in Statesmen: The Peculiar Case of Winston Spencer Churchill (P04.003)

Objective: To review the evidence that Winston Spencer Churchill had pseudobulbar affect as a consequence of his stroke in 1953. Background Few statesmen have had as open a review of his medical condition as Winston Spencer Churchill who was Prime Minister of the United Kingdom. He had a possible stroke in 1949. The stroke that was associated with emotional lability occurred in 1953 with clinical details related in 1] W. Russell Brain, Encounters with Winston Churchill, Medical History, vol. 44, 2000, 3-20, 2) Richard Gordon, An Alarming History of Famous and Difficult Patients. New York: St. Martin9s Press, 1997, 3) Richard Lovell, Churchill9s Doctor: A Biography of Lord Moran, New York: Parthenon, 1993 and 4) Lord Moran, Churchill: The Struggle for Survival 1945-60. Design/Methods: Churchill was examined 9 times by Lord Brain following his stroke in 1953. By one month after the stroke his dysarthria and dysphagia had improved but Churchill had loss of emotional control which had worsened as other deficits improved. Churchill noticed that he was always rather blubbery. Multiple sources identified this clinical change and felt that Churchill could not attend upcoming government and political events lest the public learn of his stroke. The only treatment mentioned for this condition and Churchill9s fatigue was repeated doses of benzedrine. Results: Descriptions of emotionality and its potential political consequences were found 9 times in Lord Moran9s accounts and 4 times in Lord Brain9s account. Other sources alluded to these changes but only the neurologist and treating physician accounts gave appropriate descriptive elements to establish the diagnosis based on historical records. Conclusions: Churchill9s stroke related pseudobulbar affect was described in several medical and non-medical sources. It9s late onset post stroke and resolution remains the best studied example of pseudobulbar affect in a public statesman to date. Disclosure: Dr. Brooks has received personal compensation for activities with Avanir Pharmaceuticals, Bayer Healthcare Pharmaceuticals, Biogen Idec, Genentech, Inc., and Teva Neuroscience. Dr. Brooks has received research support from Avanir Pharmaceuticals, Biogen Idec, NINDS, Novartis, and Teva Neuroscience.

Encéphalopathie d’Hashimoto

Hashimoto's encephalopathy was first described by Lord Brain in 1966. Since, other designations have been proposed and the existence of the disease itself has been debated. However, the number of reported cases in the literature is still increasing and physicians are sometimes confronted with patients with neuropsychiatric manifestations and positive thyroid antibodies. This article is an update based upon a search through Medline database that identified 316 references published between 1961 and 2011. Hashimoto's encephalopathy is a rare condition for which there is a need for both diagnostic criteria and therapeutic consensus.

Paraneoplastic syndromes: from remote to clear and present knowledge

The first book on paraneoplastic neurological disorders was published in 1965 as the proceedings of a symposium sponsored by the Division of Neurology, University of Rochester Medical School (30 September–1 October 1964) (Brain and Norris, 1965). Although the term ‘paraneoplastic’ had already been coined, the editors of the book, (Russell) Lord Brain and Forbes H. Norris, used the term ‘The remote effects of cancer on the nervous system’. It was a timely book that captured the growing interest for these disorders, stirred in large part by a series of studies conducted in the 1950s and 60s by a superb group of British neurologists and neuropathologists including among others Brain, Ronald Henson, Henry Urich and (J) Godwin Greenfield. The field of paraneoplastic neurological syndromes was starting to take shape despite some haziness: disorders considered as paraneoplastic were later demonstrated to have other aetiologies (e.g. progressive multifocal leukoencephalopathy, Waldenstrom macroglobulinaemia and porphyria) while syndromes such as limbic encephalitis described 4 years before the symposium, had not yet been recognized as paraneoplastic. Theories on pathogenesis were abundant and highly speculative. The hypothesis of an autoimmune aetiology was viewed with scepticism, yet some interesting theories were advanced: ‘Thus, it seems reasonable to postulate that, if tumour and nervous tissue were to contain common antigens, remote pathologic effects might sometimes occur in the nervous system’ (Richmond T. Prehn, 1964, in Brain and Norris, 1965). A year after the symposium, Marcia Wilkinson and colleagues discovered a neuronal antibody in the serum of four patients with small-cell lung cancer and sensory neuronopathy (Wilkinson and Zeromski, 1965), likely representing the first description of what became known as ‘anti-Hu’. In the early 1980s, few books were more influential for each of us than Henson and Urich's Cancer and the Nervous System: the Neurological Manifestations of Systemic Malignancy (1982). Although …

Over-Diagnosing Dissociative (Conversion) Disorders

Over-Diagnosing Dissociative (Conversion) Disorders

Lockhart Clarke's contribution to the description of amyotrophic lateral sclerosis

The definition of the clinicopathological entity of amyotrophic lateral sclerosis evolved over half a century. Although the definitive term amyotrophic lateral sclerosis that acknowledged both upper and lower motor neuron involvement was attributed to Jean-Martin Charcot in 1874, his initial case was published nearly a decade earlier; and it is accepted that, from at least the 1830s, several others (including Charles Bell, François-Amilcar Aran and Jean Cruveilhier) had already recognized a progressive lower motor neuron-only syndrome within a broader, clinically-defined group of disorders, termed progressive muscular atrophy. Although William Gowers first grouped the three phenotypes of amyotrophic lateral sclerosis, progressive muscular atrophy and progressive bulbar palsy together as part of the same syndrome, the term motor neuron disease, as an over-arching label, was not suggested until nearly a century later by W. Russell Brain. Augustus Jacob Lockhart Clarke (1817-80) is best known for his descriptions of spinal cord anatomy. However, in two detailed case reports from the 1860s, he carried out rigorous post-mortem neuropathological studies of what appear to be classical cases of amyotrophic lateral sclerosis. Furthermore, he recognized the additional involvement of the corticospinal tracts that distinguished this from progressive muscular atrophy. Several aspects of the exquisite clinical histories documented as part of both studies, one by Charles Bland Radcliffe, resonate with contemporary debates concerning the evolution of disease in amyotrophic lateral sclerosis. These 'past masters' still have much to teach us.

The cerebral basis of consciousness. By W. Russell Brain. Brain 1950: 73; 465-479; and The physiological basis of consciousness. A critical review by Russell Brain. Brain 1958: 81; 426-455.

In his presidential address to the Neurological Section of the Royal Society of Medicine, delivered in October 1950, Russell Brain (Fig. 1) aims to ‘make a broad survey of some aspect of neurology … to consider how far the various pieces of the jigsaw are fitting together, and what kind of picture they are making. If the action of the nervous system is integrative, it is doubly desirable that we should try to integrate knowledge of it’. His topic is consciousness. This exists alongside awareness, perception and emotion but is necessarily not independent of these conscious states. What happens in the nervous system when a conscious state is experienced must therefore be the basis for studies of consciousness itself. Although their spatial and temporal patterns of firing may vary, the character of electrical conduction does not differ materially in pathways that transmit the impressions of sensation, sight and hearing or any other afferent impulses. The clue to consciousness lies more in the fact that focal stimulation of the cerebral cortex can only be perceived and localized to a specific part—say, the big toe—by relating that structure to the entire body schema: ‘to perceive a part of the body as pricked is to perceive it in relationship with the whole of the rest of the body, pin-pointed as it were upon the body-image … we can appreciate touch without knowing its whereabouts, but we cannot know a whereabouts that is vacant of any sensory content’. It follows that electrical activity of the sensory cortex must simultaneously cause widespread irradiation of impulses throughout both hemispheres. John Hughlings-Jackson (1835–1911) has already made the point that the ‘… anatomical substrata of subject-consciousness represent … all parts of the body, mainly sensorily, in relation to one another … [they] are centres of universal coordination … …

A textbook for every neurologist

Neurologic paraneoplastic syndromes (NPSs) account for a tiny percentage of the complications seen in cancer patients, but they were the starting point for the interest of neurology in a discipline that would later be dubbed neuro-oncology. The possibility that not all neurologic lesions seen in cancer patients are due to metastases was first considered by Heinrich Oppenheim in 1888. However, the concept of the remote effect of cancer on the nervous system was first articulated by Derek Denny-Brown, when, in 1948, he reported two patients with lung carcinoma and sensory neuronopathy. The pioneers who further developed this field were mainly British neurologists: Peter Croft, Ronald Henson and Marcia Wilkinson. In the early 1960s these authors confirmed the association of cancer with sensory neuronopathy, and described other paraneoplastic diseases such as limbic encephalomyelitis and subacute cerebellar degeneration. Thanks to the interest of Lord Brain, then editor of the journal, most of the seminal papers were published in Brain . In 1965, Lord Brain and Raymond Adams provided the first clinical classification and pathological characterization of NPSs in their concluding chapter to the remarkable and now classic book edited by Lord Brain and Forbes Norris from San Francisco, The remote effect of cancer on the nervous system (1965). But the pathogenesis of these conditions remained mysterious for some time. Jerome Posner and his associates Francesc Grauss, Josep Dalmau and many others have contributed more than anyone else to the understanding of NPSs by identifying specific antibodies directed against onconeural antigens expressed by some tumours and the nervous system. These antibodies are able to slow tumour growth and even eradicate the cancerous lesion, but their role in the pathogenesis of NPSs has not been entirely elucidated. In Lambert–Eaton myasthenic syndrome (LEMS) the circulating antibodies, directed against voltage-gated calcium-channel protein, are clearly …

James Paget’s median nerve compression (Putnam’s acroparaesthesia)

Sir James Paget (1814–1899) (fig 1) was a man of exceptional human and intellectual qualities.1 He is best known for his original accounts2 of On a form of chronic inflammation...

Lord Brain: an Appreciation

Medical EducationVolume 1, Issue 2 p. 78-79 Lord Brain: an Appreciation First published: June 1967 https://doi.org/10.1111/j.1365-2923.1967.tb01672.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume1, Issue2June 1967Pages 78-79 RelatedInformation

Cerebral involvement in head injury. A study based on the examination of two hundred cases. By W. Ritchie Russell, MD. Brain 1932; 55: 549-603

Head injury has always been, and remains, an unpopular subject with British neurologists, presumably because they tend to see it as a surgical rather than a medical disorder. The subject is ignored in the textbooks of (Sir) William Gowers, (Samuel Alexander) Kinnier Wilson and Russell (Lord) Brain, save for a few oblique references in sections on headache or cerebral haemorrhage. It is therefore the more remarkable that, writing in 1932, 29-year-old William Ritchie Russell (1903–1980) has recently submitted an MD thesis on the topic to the University of Edinburgh, where his father was professor of medicine and his mother (nee Ritchie) an early female graduate, also in medicine (see Jellinek EH, The Russells of Edinburgh: a medical dynasty. Proc R Coll Physicians Edinb 2001; 31: 342–51). The article is a condensed version of the thesis, which earned Russell the Gold Medal. Brain damage through head injuries would remain a life-long interest: he came back to it in 1941 in his joint study with Derek Denny-Brown on experimental head injury (see Brain 2007; 130: 2479–81), and again, after retirement, in a monograph on the ‘Traumatic amnesias’ (1971). The 1932 series describes 200 consecutive patients with any degree of initial cerebral damage from head trauma; the only patients he excludes are those who died within 24 h. A mere 39 of them are female—almost invariably knocked down by a motor vehicle in the street. Amongst the 161 men, the most common cause is a motor cycle accident. Russell starts out by classifying this cohort according to the duration of the loss of full consciousness. It is this very aspect that constitutes his lasting contribution to the management of head injuries. He perceptively points out that the victim of an accident may be able to move and even to talk and yet have …

Visual disorientation with special reference to lesions of the right cerebral hemisphere. By W. Russell Brain (From the Neurological Department, London Hospital) Brain 1941: 64; 244 272.

Visual disorientation with special reference to lesions of the right cerebral hemisphere. By W. Russell Brain (From the Neurological Department, London Hospital) Brain 1941: 64; 244 272.

Neurology in the developing world

NEUROLOGICAL PRACTICE: AN INDIAN PERSPECTIVE By Noshir H. Wadia 2005. New Delhi: Elsevier Price £US75.00 ISBN 81-8147-549-6 On November 16, 1959, I landed in Bombay and met a small group of physicians who were to play a major role in developing neurology in India. Noshir Wadia and Anil Desai were neurologists, Darab Dastur a neuropathologist and Jimmy Sidhwa a neuroradiologist. That evening I met with Eddie Bharucha, the first neurologist in Bombay ( see Fig. 1), and his wife, Piloo, a pediatrician who promptly told me that the key to the serious problem of control of overpopulation was rural electrification. A few days later, in New Delhi, I also met Baldev Singh, who had trained in the USA; he was the first to practise and teach neurology in India and was one of the founders of the Neurological Society of India in 1951, along with the renowned neurosurgeons Jacob Chandy and B. Ramamurthi. Fig. 1 Eddie Bharucha. Each had received his neurological education in the United Kingdom except Dastur, who trained with Webb Haymaker at the Armed Forces Institute of Pathology in Washington. Neurology in India, as in most of Latin America at the time, had long been dominated by neurosurgery. Noshir Wadia would soon become one of leaders in the field of tropical neurology and a legend in his own time ( see Fig. 2). After obtaining his medical degree from the Grant Medical College, named after Sir Robert Grant who was governor of Bombay in the early 19th century, and his neurological education at Maida Vale and the London Hospital under Sir Russell Brain ( see Fig. 3), he returned to found and head the department of neurology at Grant. He has received many honours, among which must be mentioned his Fellowship of both the Indian National Science Academy and the Indian Academy …