Journal Publications
I have published over 250 articles since 1962 on epilepsy, neurology, neuropsychiatry, metabolic diseases (mainly folate and vitamin B12) and the history of medicine, neurology, psychiatry, epilepsy and the NHS.
| Authors | Title | Year | Source | Vol; pp | Abstract | DOI |
|---|---|---|---|---|---|---|
| Edward H Reynolds | The origins and early development of the ILAE/IBE/WHO global campaign against epilepsy: Out of the shadows. | 2023 | Epilepsia Open | epi4.12850 | The International League Against Epilepsy (ILAE)/International Bureau for Epilepsy (IBE)/World Health Organization (WHO) Global Campaign Against Epilepsy was launched in Geneva and Dublin in the summer of 1997. The second phase of the Campaign was launched by a major event in Geneva, led by WHO Director General Dr. Gro Harlem Brundtland in February 2001. Since then, the Campaign has been gathering momentum around the world culminating in the WHO General Assembly Resolution (WHA 68.20) on Epilepsy in May 2015 supported by 194 countries. Recently, the World Federation of Neurology and other neurological non-governmental organizations (NGOs) have joined forces with the Epilepsy Campaign, leading to the WHO General Assembly Resolution (WHA 73.10) in May 2022 promoting a 10-year Intersectoral Global Action Plan (IGAP) for Epilepsy and Other Neurological Disorders. I was privileged to serve as the first Chairperson of the Global Campaign Against Epilepsy and this year all my documents and correspondence relating to the Campaign have been delivered to the Wellcome Collection in London. These are the basis for this detailed account of the origins and early development of the Campaign. I describe the events leading to the birth of the concept, planning for the Campaign, the launch, development, and the achievements of phase one. This first phase focused on awareness raising, education, and involvement, especially within WHO, ILAE, and IBE, including a series of five Regional Public Health meetings and Declarations on Epilepsy. In 1999, the WHO raised the status of the Campaign to the highest level, the first ever for a Non-Communicable Disease, resulting in the high profile launch of phase two in 2001, paving the way to the continuing global momentum and achievements, including the 2015 and 2022 WHO Resolutions. | https://doi.org/10.1002/epi4.12850 |
| E.H.Reynolds | John Hughlings Jackson and Thomas Laycock: Brain and Mind. | 2023 | World Neurology Bullitin of the World Federation of Neurology August-September | 4-5 | https://worldneurologyonline.com/article/john-hughlings-jackson-and-thomas-laycock-brain-and-mind/ | |
| E.H.Reynolds | John Hughlings Jackson and Thomas Laycock: Brain and Mind: Laycock's Influence on British Neuropsychiatry | 2023 | Newsletter of the History of Psychiatry Section of the Royal College of Psychiatrists November | 18-22 | https://www.rcpsych.ac.uk/docs/default-source/members/sigs/hopsig/newsletters/hopsig-newsletter---news-and-notes-autumn-2023.pdf | |
| Edward H Reynolds | Health effects of poor housing : Medical profession has a role | 2023 | British Medical Journal | 381;p1043 | https://doi.org/10.1136/bmj.p1043 | |
| Edward H Reynolds | How to avoid harmful national quarantines: primary care led local public health: a historical perspective. | 2022 | Journal of the Royal Society of Medicine | 115;12-15 | https://doi.org/10.1177/01410768211046839 | |
| Reynolds E.H. , Broussolle E. | Anglo-French neurological interactions in the 19th and early 20th centuries: Societies and Journals. | 2022 | Revue Neurologique (Paris) | 178;291-297 | We have reviewed seminal interactions between British and French physicians prior to and following the establishment of the Paris and London Schools of Neurology from the mid-19th to the early 20th centuries. Our first article focused on British and French physicians, places and events. In this second part of our review we have examined the interactions between British and French Neurological Societies and Journals, including: (1) The Neuro-logical Society of London founded in 1886, which became the Section of Neurology of the Royal Society of Medicine; (2) The Société de Neurologie de Paris founded in 1899, later renamed as The Société Francaise de Neurologie; (3) The journal Brain and its precursors and successors; (4) The journal Revue Neurologique and its precursors. We illustrate the constructive influence of Anglo-French interactions on the early development of neurology by the distinguished physicians who were corresponding members respectively of the British and French Neurological Societies and the scientific articles published by French authors in Brain and by British scientists in Nouvelle Iconographie de la Salpêtriére, Archives de Neurologie and Revue Neurologique. | https://doi.org/10.1016/j.neurol.2021.09.010 |
| Edward H Reynolds | How to avoid harmful national quarantines: primary care led local public health: a historical perspective. | 2021 | Journal of the Royal Society of Medicine | 115;12-15 | https://doi.org/10.1177/01410768211046839 | |
| E Broussolle, E H Reynolds | Anglo-French neurological interactions in the 19th and early 20th centuries: Physicians, places and events. | 2021 | Revue neurologique | 177;8:859-870 | The development of neurology as an independent discipline in the mid-19th century was considerably influenced by the almost simultaneous foundation of the Charcot School at the Salpêtrière Hospital in Paris and the National Hospital for the Paralysed and Epileptic and it's School at Queen Square in London in the 1860's. We have reviewed the early interactions between Charcot's school and the leading neurologists at the National Hospital and also discussed their neurological antecedents and subsequent links up to the outbreak of World War 1 in 1914. Earlier interactions involved Trousseau and Duchenne in France and Graves, Todd, Laycock and Allbutt in Britain. The French Brown-Séquard was one of the first two physicians appointed to the National Hospital. Charcot was a frequent visitor to Britain culminating in his influential role in the 1881 International Medical Congress in London. He first suggested the terms "Parkinson's Disease" and "Jacksonian Epilepsy". He attracted numerous British visitors to Paris and his studies of hysteria were influenced by Laycock, Todd and Russell Reynolds. Hughlings Jackson drew upon the anatomical studies of Gratiolet in his interactions with Broca and Charcot which influenced French views on aphasia, epilepsy and cortical localisation. Ball, an Englishman, was the first Professor of mental and brain diseases in Paris in 1877. Bruce in Edinburgh and Kinnier Wilson in London both maintained frequent contacts with Paris, where the latter first presented his studies of hepatolenticular degeneration in 1912. The Entente Cordiale of 1904 led to further interactions with the leading role of the French and British physicians Raymond and Duckworth. Two outstanding British women, Elizabeth Garrett and Blanche Edwards, qualified in Medicine in Paris with neurological interests. Our review emphasises the constructive influence of the French and British Schools on each other and thus on the development of neurology. The French influence was primarily the establishment of the anatomo-clinical method and the use of photographic illustrations in publications. The British School influence was its Clinical Assessment Skills and scientific studies of newly recognised diseases and concepts and its early development of neurosurgery. | https://doi.org/10.1016/j.neurol.2020.10.013 |
| Edward H Reynolds | John Hughlings Jackson and Thomas Laycock: brain and mind. | 2020 | Brain : a journal of neurology | 143;2:711-714 | https://doi.org/10.1093/brain/awz385 | |
| Edward H Reynolds | Antiepileptic drugs, folate and one carbon metabolism revisited. | 2020 | Epilepsy & behavior : E&B | 112;:107336- | https://doi.org/10.1016/j.yebeh.2020.107336 | |
| Edward H Reynolds, Ralph Green | Valproate and folate: Congenital and developmental risks. | 2020 | Epilepsy & behavior : E&B | 108;:107068- | Increasing awareness of the congenital and developmental risks associated with the use of sodium valproate (VPA) has led to recent European guidelines designed to avoid the use of this drug in pregnancy if effective alternative treatments are available. In the general population, it is well established that periconceptual folic acid reduces the risk of neural tube defects (NTDs) and possibly other congenital abnormalities. We here review the evidence 1) that VPA interferes with one-carbon metabolism, including the transport of methylfolate into the brain and the placenta by targeting folate receptors; 2) that VPA effects on the folate metabolic system contribute to congenital and developmental problems associated with VPA exposure; and 3) that genetic factors, notably polymorphisms related to one-carbon metabolism, contribute to the vulnerability to these VPA-induced risks. Based on these facts, we propose that the standard periconceptual use of 400 μg of folic acid may not adequately protect against VPA or other antiepileptic drug (AED)-induced congenital or developmental risks. Pending definitive studies to determine appropriate dose, we recommend up to 5 mg of folic acid periconceptually in at-risk women with the caveat that the addition of supplementary vitamin B12 may also be prudent because vitamin B12 deficiency is common in pregnancy in some countries and is an additional risk factor for developmental abnormalities. | https://doi.org/10.1016/j.yebeh.2020.107068 |
| Edward H Reynolds, Charles E Pippenger | The earliest experimental convulsions by Joseph Priestley in 1766 friendship with Benjamin Franklin. | 2020 | Epilepsy & behavior : E&B | 102;:106555- | In 1766, Joseph Priestley (1733-1804) was the first to systematically demonstrate the universal convulsive effect of an electrical discharge applied to the head of all the several species studied. We here republish his overlooked experiments, which often resulted in death, and which ante date the scientific studies of the electrical functions of the brain, the role of "discharges" in seizures, and experimental epilepsy by about a century. Priestley's studies of electricity were influenced by those of Benjamin Franklin (1706-1790), who became a good friend during Franklin's prolonged period in London between 1757 and 1775. Both were elected Fellows of the Royal Society and both were awarded the Copley Medal of that Society. Priestley's experiments are relevant to the history of epilepsy and neuropsychiatry, and to the modern study of sudden unexplained death in epilepsy (SUDEP). | https://doi.org/10.1016/j.yebeh.2019.106555 |
| Edward Henry Reynolds | Epilepsy and Neuroscience: Evolution and Interaction. | 2020 | Frontiers in neuroanatomy | 14;:25- | Neuroscience is a relatively new and fashionable word that emerged in the 1950s in several countries, including the UK, to describe a multidisciplinary clinical and laboratory approach to the study of the brain, mind, and neuropsychiatric disorders. However collaborative study of neurological and psychiatric disorders can be traced to the 17th century with roots in antiquity. I describe the evolution of our understanding of epilepsy beginning with the first detailed clinical descriptions, associated with supernatural theories, in Babylonian medicine in the second millennium BC. Interest in natural causation arose in the Greco-Roman period when it was first suggested that "the sacred disease" was a disorder of the brain. However, this theory did not take root until the 17th and 18th centuries AD when epilepsy began to be separated from other "convulsive" diseases, including hysteria. In the 19th century developments in neuropathology and our understanding of cortical localization led to the much-debated separation of idiopathic from symptomatic epilepsy which continues to influence international classifications of seizures and epilepsies. Also in the 19th century, the concept of seizures as electrical discharges in the brain evolved, reinforced in the 20th century by the discovery of the electroencephalogram. For many reasons, people with epilepsy have experienced a high incidence of cognitive and psychosocial disorders. Epilepsy, which is a global problem, has, therefore, remained a bridge between neurology and psychiatry. Furthermore, the study of epilepsy continues to shed light on brain function and other neuropsychiatric disorders. | https://doi.org/10.3389/fnana.2020.00025 |
| Edward H Reynolds | The prevention of the importation of infectious diseases in England in 1877. | 2020 | Journal of the Royal Society of Medicine | 113;12:478- | https://doi.org/10.1177/0141076820961978 | |
| Edward H Reynolds | Neurometabolic approach to treatment-resistant depression. | 2019 | The British journal of psychiatry : the journal of mental science | 215;3:568- | https://doi.org/10.1192/bjp.2019.170 | |
| James L Mills, Anne M Molloy, Edward H Reynolds | Do the benefits of folic acid fortification outweigh the risk of masking vitamin B12 deficiency? | 2018 | BMJ (Clinical research ed.) | 360;:- | https://doi.org/10.1136/bmj.k724 | |
| Henry R Rollin, Edward H Reynolds | Yorkshire's influence on the understanding and treatment of mental diseases in Victorian Britain: The golden triad of York, Wakefield, and Leeds. | 2018 | Journal of the history of the neurosciences | 27;1:72-84 | In the late-eighteenth and nineteenth centuries, a more humane approach to the care of the insane in Britain was catalyzed in part by the illness of King George III. The Reform Movement envisaged "moral" treatment in asylums in pleasant rural environments, but these aspirations were overwhelmed by industrialization, urbanization, and the scale of the need, such that most asylums became gigantic institutions for chronic insanity. Three institutions in Yorkshire remained beacons of enlightenment in the general gloom of Victorian alienism: the Retreat in York founded and developed by the Quaker Tuke family; the West Riding Lunatic Asylum in Wakefield led by Sir James Crichton-Browne, which initiated research into brain and mental diseases; and the Leeds Medical School and Wakefield axis associated with Sir Thomas Clifford Allbutt, which pioneered teaching of mental diseases and, later, the first Chair of Psychiatry. Three other Yorkshiremen who greatly influenced nineteenth-century "neuropsychiatry" in Britain and abroad were Thomas Laycock in York and Edinburgh, and Henry Maudsley and John Hughlings Jackson in London. | https://doi.org/10.1080/0964704X.2017.1370801 |
| Edward H Reynolds | Hysteria in ancient civilisations: A neurological review: Possible significance for the modern disorder. | 2018 | Journal of the neurological sciences | 388;:208-213 | The word hysteria originated in the Corpus Hippocraticum (c420 BCE) as a natural explanation for a variety of diseases in women linked in the Greco-Roman mind to an animate or inanimate womb, but which in the last five centuries has evolved to describe an elusive disorder of brain ± mind in men and women, currently referred to by neurologists as "functional neurological disorder". The Babylonians, Assyrians and Egyptians had no knowledge of brain or psychological function. Babylonian and Assyrian descriptions of disease and behaviour include only rare examples suggestive of modern hysteria. An earlier suggestion that the Greek concept of hysteria was transmitted from Egypt is not supported by recent evidence. The Greco-Roman civilisations had some knowledge of neuroanatomy, but little of nervous system function, conceived in terms of humors. The examples cited here suggestive of modern hysteria are relatively infrequent and fragmentary. The most plausible are attempts to separate the "sacred disease" from other causes of loss of consciousness. The great achievement of Greco-Roman medicine was in introducing natural causation, including causation linked to the womb, rather than gods or evil spirits. Nevertheless medicine, magic and religion have remained intertwined to varying degrees in all cultures up to the present time, despite the growth of modern scientific medicine. The study of hysteria in ancient civilisations adds interesting insight into the evolution of thinking about brain, psyche, mind and self. Babylonian and Egyptian medical and behavioural descriptions are based on observation. Greek and Roman accounts include some subjective aspects, probably linked to early attempts to understand identity, the psyche, intellectual and emotional functions. The great philosophical debate whether the latter resided in the head/brain (Plato) or the heart (Aristotle) has only been settled in the last few centuries, during which hysteria also became linked to brain ± mind. Our more recent increasing knowledge of brain function has also been accompanied by increasing interest in subjective feelings, thoughts, the inner life and subconscious mechanisms, suggesting we may have become more self-aware than in earlier civilisations, which in turn may perhaps influence the clinical presentation of hysteria. The study of hysteria may be one of the keys to a greater understanding of the relationship between brain and mind. | https://doi.org/10.1016/j.jns.2018.02.024 |
| Edward H Reynolds | A better future for the NHS: a historical perspective from the frontline. | 2018 | Journal of the Royal Society of Medicine | 111;10:374-376 | https://doi.org/10.1177/0141076818790844 | |
| E H Reynolds, E Broussolle | Allbutt of Leeds and Duchenne de Boulogne: Newly discovered insights on Duchenne by a British neuropsychiatrist. | 2018 | Revue neurologique | 174;5:308-312 | It is well-established that Guillaume-Benjamin-Amand Duchenne de Boulogne (1806-1875), and Jean-Martin Charcot (1825-1893) were the founding fathers of Parisian and French neurology during the second half of the 19th century, although much more is known about Charcot than about his "master" Duchenne. In Britain, Thomas Clifford Allbutt (1836-1925) was Leeds' most distinguished physician of the 19th century, eventually becoming Regius Professor of Physic at Cambridge. Allbutt's 1860-1861 year of postgraduate study in Paris and his friendship with Duchenne profoundly influenced his own contributions to nervous system and mental diseases, partly in collaboration with his colleague James Crichton-Browne (1840-1938) at the nearby West Riding Lunatic Asylum in Wakefield, Yorkshire. The present report briefly recalls the careers of Duchenne and Allbutt, and also presents a unique account by Allbutt of Duchenne in action at the height of his powers, investigating and defining the previously uncharted field of neuromuscular diseases with the aid of his localized electrization techniques. This account is discussed in relation to: Duchenne's personality and pioneering neurological achievements; the origins of French neurology; and the development of Anglo-French neurological relationships during the 19th century. Interestingly, both Duchenne and Crichton-Browne separately made important and much-appreciated contributions to the third major book by Charles Darwin (1809-1882), The Expression of the Emotions in Man and Animals, published in 1872. | https://doi.org/10.1016/j.neurol.2017.07.012 |
| Edward H Reynolds | The risks of folic acid to the nervous system in vitamin B12 deficiency: rediscovered in the era of folic acid fortification policies. | 2017 | Journal of neurology, neurosurgery, and psychiatry | 88;12:1097-1098 | https://doi.org/10.1136/jnnp-2017-316296 | |
| Edward H Reynolds | The London Contribution to Neurology and Psychiatry: The second British Symposium on the History of Neurology and Psychiatry. | 2017 | Journal of neurology, neurosurgery, and psychiatry | 88;7:608-611 | https://doi.org/10.1136/jnnp-2016-315514 | |
| Devin K Binder, Edward H Reynolds | Robert Bentley Todd's contributions to the structure and function of nerve tissue. | 2017 | Journal of the history of the neurosciences | 26;3:336-337 | https://doi.org/10.1080/0964704X.2017.1315263 | |
| Edward H Reynolds, James V Kinnier Wilson | The earliest observations on facial palsy. | 2017 | Journal of the history of the neurosciences | 26;1:109-110 | https://doi.org/10.1080/0964704X.2016.1211803 | |
| Edward H Reynolds | The quality of information. | 2017 | Journal of the Royal Society of Medicine | 110;10:388- | https://doi.org/10.1177/0141076817731219 | |
| Edward H Reynolds | The origins of the British Neuroscience Association. | 2017 | Neuroscience | 367;:10-14 | I describe the origins of the British Neuroscience Association (BNA) based on new documents which I have discovered. The foundation of the Brain Research Association (BRA) on February 23rd 1968 was influenced by IBRO, notably its two UK Council members, and by many UK neuroscientists, especially the London-based Black Horse Group. The BRA changed its name to the BNA in 1996. The documents are in the Wellcome Trust Archives. | https://doi.org/10.1016/j.neuroscience.2017.09.057 |
| Edward H Reynolds | A bridge between neurology and psychiatry. | 2016 | Epilepsy & behavior : E&B | 65;:56-59 | https://doi.org/10.1016/j.yebeh.2016.08.017 | |
| E H Reynolds | What is the safe upper intake level of folic acid for the nervous system? Implications for folic acid fortification policies. | 2016 | European journal of clinical nutrition | 70;5:537-540 | Between 1945 and 1959 it was convincingly documented that folic acid can precipitate or aggravate the neurological and haematological consequences of vitamin B12 deficiency by increasing the demand for vitamin B12. Since then there has been much misunderstanding of the issues, mainly by advocates of folic acid fortification who have been inclined to minimise or even dismiss the risks by misinterpreting the evidence as only a 'masking' of the anaemia of pernicious anaemia. Recent studies in the era of fortification are rediscovering the risks to the nervous system, especially cognitive function, of excess folate in the presence of vitamin B12 deficiency. I have reviewed the Reports of four Expert Advisory Committees in Europe and the USA, which suggest that the safe upper tolerable limit (UL) for folic acid is 1 mg in adults. These reports are unsound and there is already evidence of neurological harm from long-term exposure to doses of folic acid between 0.5 and 1 mg in the presence of vitamin B12 deficiency. There is an urgent need to review the safe UL for folic acid and to consider the addition of vitamin B12 to folic acid fortification policies. | https://doi.org/10.1038/ejcn.2015.231 |
| M Trimble, E H Reynolds | A brief history of hysteria: From the ancient to the modern. | 2016 | Handbook of clinical neurology | 139;:3-10 | In this paper we discuss the history of hysteria from the Babylonian and Assyrian texts through to the situation as it appears to us at the end of the 19th century. We note the shifting emphasis on causation, earlier ideas being linked to uterine theories, later speculations moving to the brain, and then the mind. We note the persistence of the condition referred to as hysteria over the millennia and the fascination that the condition has held for physicians, neurologists, and psychiatrists since the origins of known medical texts. | https://doi.org/10.1016/B978-0-12-801772-2.00001-1 |
| E H Reynolds | Kinnier Wilson's French connections. | 2015 | Revue neurologique | 171;1:81-83 | https://doi.org/10.1016/j.neurol.2014.03.011 | |
| Edward H Reynolds, James V Kinnier Wilson | Neurology and psychiatry in Babylon. | 2014 | Brain : a journal of neurology | 137;:2611-2619 | We here review Babylonian descriptions of neurological and psychiatric disorders, including epilepsy, stroke, psychoses, obsessive compulsive disorder, phobias, psychopathic behaviour, depression and anxiety. Most of these accounts date from the first Babylonian dynasty of the first half of the second millennium BC, within a millennium and a half of the origin of writing. The Babylonians were remarkably acute and objective observers of medical disorders and human behaviour. Their detailed descriptions are surprisingly similar to modern 19th and 20th century AD textbook accounts, with the exception of subjective thoughts and feelings which are more modern fields of enquiry. They had no knowledge of brain or psychological function. Some neuropsychiatric disorders, e.g. stroke or facial palsy, had a physical basis requiring the attention of a physician or asû, using a plant and mineral based pharmacology; some disorders such as epilepsy, psychoses, depression and anxiety were regarded as supernatural due to evil demons or spirits, or the anger of personal gods, and thus required the intervention of the priest or ašipu; other disorders such as obsessive compulsive disorder and psychopathic behaviour were regarded as a mystery. The Babylonians were the first to describe the clinical foundations of neurology and psychiatry. We discuss these accounts in relation to subsequent and more modern clinical descriptions. | https://doi.org/10.1093/brain/awu192 |
| Emilio Perucca, Edward H Reynolds | In memoriam: Harry Meinardi (February 20, 1932-December 20, 2013). | 2014 | Epilepsia | 55;4:621-622 | https://doi.org/10.1111/epi.12578 | |
| E H Reynolds | The neurology of folic acid deficiency. | 2014 | Handbook of clinical neurology | 120;:927-943 | The metabolism of folic acid and the metabolism of vitamin B12 are intimately linked such that deficiency of either vitamin leads to an identical megaloblastic anemia. The neurologic manifestations of folate deficiency overlap with those of vitamin B12 deficiency and include cognitive impairment, dementia, depression, and, less commonly, peripheral neuropathy and subacute combined degeneration of the spinal cord. In both deficiency states there is often dissociation between the neuropsychiatric and the hematologic complications. There is a similar overlap and dissociation between neurologic and hematologic manifestations of inborn errors of folate and vitamin B12 metabolism. Low folate and raised homocysteine levels are risk factors for dementia, including Alzheimer's disease, and depression. Even when folate deficiency is secondary to psychiatric illness due to apathy or poor diet it may eventually aggravate the underlying disorder in a vicious circle effect. Clinical responses to treatment with folates are usually slow over weeks and months, probably due to the efficient blood-brain barrier mechanism for the vitamin, perhaps in turn related to the experimentally demonstrated excitatory properties of folate derivatives. The inappropriate administration of folic acid in the presence of vitamin B12 deficiency may lead to both neurologic and, later, hematologic relapse. Impaired maternal folate intake and status increases the risk of neural tube defects. Periconceptual prophylactic administration of the vitamin reduces, but does not eliminate the risk of neural tube defects even in the absence of folate deficiency. Folates and vitamin B12 have fundamental roles in central nervous system function at all ages, especially in purine, thymidine, neucleotide, and DNA synthesis, genomic and nongenomic methylation and, therefore, in tissue growth, differentiation and repair. There is interest in the potential role of both vitamins in the prevention of disorders of central nervous system development, mood, dementia, including Alzheimer's disease, and aging. | https://doi.org/10.1016/B978-0-7020-4087-0.00061-9 |
| Robert Balazs, Edward H Reynolds | Letter to the editor and authors' response: reaction to Abi-Rached JM (2012): from brain to neuro: the brain research association and the making of British neuroscience, 1965-1996. Journal of the History of the Neurosciences 21:189-213). | 2013 | Journal of the history of the neurosciences | 22;2:199-207 | https://doi.org/10.1080/0964704X.2012.750700 | |
| Edward H Reynolds | Personalised medicine and National Health Service culture. | 2013 | Journal of the Royal Society of Medicine | 106;5:167-168 | https://doi.org/10.1177/0141076813485934 | |
| Edward H Reynolds, James V Kinnier Wilson | Depression and anxiety in Babylon. | 2013 | Journal of the Royal Society of Medicine | 106;12:478-481 | https://doi.org/10.1177/0141076813486262 | |
| Edward H Reynolds | Methylfolate as adjunctive treatment in major depression. | 2013 | The American journal of psychiatry | 170;5:560- | https://doi.org/10.1176/appi.ajp.2013.13010084 | |
| Edward H Reynolds | Kinnier Wilson on hysteria: a missing chapter? | 2012 | Journal of neurology, neurosurgery, and psychiatry | 83;4:464-465 | https://doi.org/10.1136/jnnp-2011-301382 | |
| Edward H Reynolds, James V Kinnier Wilson | Obsessive compulsive disorder and psychopathic behaviour in Babylon. | 2012 | Journal of neurology, neurosurgery, and psychiatry | 83;2:199-201 | The history of obsessive compulsive, phobic and psychopathic behaviour can be traced to the 17th century AD. We draw attention to these behaviours in a Babylonian cuneiform medical text known as Shurpu. These three categories were united in the Babylonian mind around the concept of the māmīt 'oath' idea, the behaviour habits being so unbreakable it appeared that the subject had sworn an oath to do or not to do the action involved. The behavioural accounts were entirely objective, including what we would call immature, antisocial and criminal behaviour, and obsessional categories of contamination, aggression, orderliness of objects, sex and religion. They do not include subjective descriptions of obsessional thoughts, ruminations or the subject's attitude to their own behaviour, which are more modern fields of enquiry. The Babylonians had no understanding of brain or psychological function but they were remarkable describers of medical disease and behaviour. Although they had both physical and supernatural theories of many medical disorders and behaviours, they had an open mind on these particular behaviours which they regarded as a 'mystery' yet to be 'resolved'. We are not aware of comparable accounts of these behaviours in ancient Egyptian or classical medicine. These Babylonian descriptions extend the history of these disorders to the first half of the second millennium BC. | https://doi.org/10.1136/jnnp-2011-300455 |
| Edward H Reynolds | Hysteria, conversion and functional disorders: a neurological contribution to classification issues. | 2012 | The British journal of psychiatry : the journal of mental science | 201;4:253-254 | Proposals by psychiatrists to reclassify conversion disorder in DSM-5 and ICD-11 are proving difficult and controversial. Patients with conversion disorder usually present initially to neurologists, who often use different concepts and terminology. History and clinical practice suggest that the way forward is to seek agreed principles and a common understanding between the two disciplines, preferably in a single universal classification. | https://doi.org/10.1192/bjp.bp.111.107219 |
| Peter Wolf, Susanne Lund, Carlos Acevedo, Frederick Andermann, Giuliano Avanzini, Philip Lee, Edward H Reynolds | A century of achievements. | 2011 | Epilepsia | 52;5:1025-1030 | https://doi.org/10.1111/j.1528-1167.2011.03062.x | |
| Devin K Binder, Kiran F Rajneesh, Darrin J Lee, Edward H Reynolds | Robert Bentley Todd's contribution to cell theory and the neuron doctrine. | 2011 | Journal of the history of the neurosciences | 20;2:123-134 | Robert Bentley Todd, who is best remembered for "Todd's paralysis," made many more important contributions to neurology and neuroscience, including the concept of brain electricity and electrical discharges in epilepsy. He was also a pioneering microscopist and we here review his neurohistological studies and his contributions to the application of Schwann's (1839) cell theory to the nervous system and the later neuron doctrine, as described in his textbook The Descriptive and Physiological Anatomy of the Brain, Spinal Cord and Ganglions (Todd, 1845), his Cyclopaedia of Anatomy and Physiology (1847) and his joint textbook with William Bowman The Physiological Anatomy and Physiology of Man (1845). Writing in the mid-1840s, Todd acknowledged that the "vesicles" he observed corresponded to the earlier descriptions of "globules" or "kugeln" by Valentin and which Schwann first interpreted as cell bodies. Todd was among the first to recognize that nerve cell bodies were in continuity with axons ("axis cylinders"), sometimes associated with "the white substance of Schwann" ("tubular" fibers), or sometimes without ("gelatinous" fibers). He also described continuous nerve cell branching processes, later called dendrites. He was the first to recognize the insulating properties of Schwann's "white substance" (myelin) to facilitate conduction. Influenced by his contemporary, Faraday, Todd was also the first to develop the functional concept of dynamic polarization ("nervous polarity") to explain nerve cell conduction. | https://doi.org/10.1080/0964704X.2010.496611 |
| E H Reynolds, D G Healy, A J Lees | A film of patients with movement disorders made in Queen Square, London in the Mid-1920s by Samuel Alexander Kinnier Wilson. | 2011 | Movement disorders : official journal of the Movement Disorder Society | 26;14:2453-2459 | Through Edward Reynolds' collaboration with Samuel Alexander Kinnier Wilson's (SAKW) son, James, on Babylonian neurology and psychiatry, and his contact with James' nephew, Jim, grandson of SAKW, a remarkable film of patients with movement disorders, made by SAKW in the mid-1920s, has come to light. The 20-min silent film with captions by SAKW includes patients with senile tremor, Parkinson's disease and postencephalitic parkinsonism, hemiballismus, Huntington's chorea, Sydenham's chorea, hysterical palsy and tremor, multiple sclerosis, and progressive lenticular degeneration. Most of the patients are filmed in the square outside the National Hospital. The British Film Institute dates the film to 1924 and the captions to 1925. The case records of 6 of the 14 patients, who were admitted to the National Hospital, Queen Square, under the care of Dr. SAKW have been identified and summarized. SAKW may have been stimulated and facilitated to make this film through his personal contact with Charlie Chaplin with whom he stayed at his Californian estate, probably in the summer of 1924. The first films of neurological patients were made in Europe and USA at the beginning of the 20th century, although most have perished. This may be one of the oldest examples from UK. It is also notable for the inclusion of Wilson's disease and a brief shot of SAKW himself. | https://doi.org/10.1002/mds.23536 |
| Edward H Reynolds, Michael R Trimble | Epilepsy, psychiatry, and neurology. | 2009 | Epilepsia | 50;:50-55 | This article reviews the relationship between the psychiatry and neurology of epilepsy, especially in the last 100 years. Throughout most of its recorded history of 3 to 4 millennia epilepsy has been viewed as a supernatural or mental disorder. Although first suggested by Hippocrates in the 5th century B.C., the concept of epilepsy as a brain disorder only began to take root in the 17th and 18th centuries. The discipline of neurology emerged from "nervous disorders" or neuropsychiatry in the late 19th century, when vascular theories of epilepsy predominated. By the turn of the 19th century psychiatry and neurology were diverging and epilepsy remained to some extent in both disciplines. It was only in the middle of the 20th century with the development of electromagnetic theories of epilepsy that the concept of epilepsy per se as a neurological disorder was finally adopted in international classifications of disease. This was associated with a refined definition of the ictal, pre-, post-, and interictal psychological disorders of epilepsy, which have contributed to a renaissance of neuropsychiatry. At the beginning of the 21st century and the centenary of the ILAE psychiatry and neurology have been converging again, led in some respects by epilepsy, which has provided several useful models of mental illness and a bridge between the two disciplines. | https://doi.org/10.1111/j.1528-1167.2009.02039.x |
| Edward H Reynolds, Ernst Rodin | The clinical concept of epilepsy. | 2009 | Epilepsia | 50;:2-7 | This article reviews the history of clinical concepts of epilepsy and its classification, especially in the last 100 years. Throughout its recorded history of 3 to 4 millennia, epilepsy has always been defined by its most dramatic symptoms, for example, falling, motor activity or loss of consciousness, but separation from other causes of the same paroxysmal symptoms has always proved challenging. For over a century there has been some semantic confusion whether to call the various paroxysms fits, convulsions, seizures, or epilepsies. Since the middle of the 19th century a great unresolved debate has continued about whether recurrent seizures or epilepsy should be viewed as a separable symptom of underlying brain disease or as one or more idiopathic diseases or syndromes, with an inherent age-related natural history; or indeed viewed as both a symptom and a disease. A major advance in the 20th century is that vascular theories of epilepsy, which reached their peak with Turner in 1907, have been replaced by electromagnetic discharges, based especially on the work of Todd, Jackson, Berger, Lennox, and the Gibbs, culminating eventually in new ILAE classifications of seizures (1981) and epilepsy syndromes (1989). However 21st century uncertainties about symptomatic versus idiopathic or cross-sectional (seizures) versus longitudinal (epilepsy) approaches to the problem very much reflect similar divergences of view a century ago. More attention is now being directed at interseizure events and processes which may lead either to remission or intractability with associated cognitive and psychosocial consequences. The search for the elusive essence, diathesis or predisposition to epilepsy, including seizure threshold, continues. | https://doi.org/10.1111/j.1528-1167.2009.02034.x |
| Edward H Reynolds | Milestones in epilepsy*. | 2009 | Epilepsia | 50;3:338-342 | https://doi.org/10.1111/j.1528-1167.2009.02050.x | |
| Edward H Reynolds, James V Kinnier Wilson | Psychoses of epilepsy in Babylon: the oldest account of the disorder. | 2008 | Epilepsia | 49;9:1488-1490 | We have previously published translations of Babylonian texts on epilepsy and stroke, which we believe to be the oldest detailed accounts of these neurological disorders from the second millennium BC. We now present a short Babylonian text, which clearly describes what are today known as interictal or schizophrenia-like psychoses of epilepsy. The text includes many of the classical symptoms of the syndrome, for example, paranoid delusions, hallucinations and mood disorders, as well as religiosity and hyposexuality, which have only been crystallized in the twentieth century. The Babylonians were remarkably good observers of human disease and behavior but had little or no understanding of pathology or brain function. Although they recognized many natural causes of disease, epilepsy and behavior disorders were attributed to supernatural, usually evil forces, the forerunner of the Greek concept of the Sacred Disease. | https://doi.org/10.1111/j.1528-1167.2008.01614.x |
| E H Reynolds | Kinnier Wilson and Sherrington. | 2008 | Journal of neurology, neurosurgery, and psychiatry | 79;4:478-479 | https://doi.org/10.1136/jnnp.2007.133298 | |
| Edward H Reynolds | Jackson, Todd, and the concept of "discharge" in epilepsy. | 2007 | Epilepsia | 48;11:2016-2022 | To explore the historical origins of the modern concept of electrical discharges in the brain in epilepsy. I have examined the writings of Hughlings Jackson (1835-1911) and Robert Bentley Todd (1809-1860), especially their Lumleian Lectures on convulsive disorders to the Royal College of Physicians of 1890 and 1849, respectively; and also the influence of Herbert Spencer (1820-1903) on the former and Michael Faraday (1791-1867) on the latter. Contrary to the widely taught view that Jackson was the first to propose electrical discharges in epilepsy it is clear that the discharges suggested by Jackson, influenced by the evolutionary philosopher, Herbert Spencer, were chemical, based on katabolism and anabolism. Jackson had no understanding or proposal based on physics or electricity. On the other hand, Todd had earlier proposed and described electrical concepts of discharges in epilepsy, influenced by his contemporary and colleague in London, Michael Faraday, who at the time was laying the foundations of our modern understanding of electricity and magnetism. Todd and Faraday saw "nervous polarity" as another polar force interchangeable with the polar forces of electricity and magnetism. | https://doi.org/10.1111/j.1528-1167.2007.01162.x |
| E H Reynolds, M Andrew | Hughlings Jackson's early education. | 2007 | Journal of neurology, neurosurgery, and psychiatry | 78;1:92- | https://doi.org/10.1136/jnnp.2006.105437 | |
| Edward H Reynolds | Phenobarbital for epilepsy: much is still to be learnt. | 2005 | BMJ (Clinical research ed.) | 330;7495:846- | https://doi.org/10.1136/bmj.330.7495.846 | |
| Edward H Reynolds | Robert Bentley Todd's electrical theory of epilepsy. | 2005 | Epilepsia | 46;7:991-994 | https://doi.org/10.1111/j.1528-1167.2005.11205.x | |
| E H Reynolds | Vis attractiva and vis nervosa. | 2005 | Journal of neurology, neurosurgery, and psychiatry | 76;12:1711-1712 | https://doi.org/10.1136/jnnp.2005.073858 | |
| E H Reynolds | The John Hughlings Jackson 1935 Centenary Congress Medal. | 2005 | Journal of neurology, neurosurgery, and psychiatry | 76;6:858-859 | https://doi.org/10.1136/jnnp.2004.056184 | |
| Edward H Reynolds, James V Kinnier Wilson | Stroke in Babylonia. | 2004 | Archives of neurology | 61;4:597-601 | https://doi.org/10.1001/archneur.61.4.597 | |
| Edward H Reynolds | Todd, Faraday, and the electrical basis of epilepsy. | 2004 | Epilepsia | 45;8:985-992 | To consider the origins of our understanding of the electrical basis of epilepsy in the light of the Lumleian lectures to the Royal College of Physicians in London for 1849, "On the pathology and treatment of convulsive diseases," by Robert Bentley Todd (1809-1860). I have reviewed Todd's neglected Lumleian lectures and his observations and concepts of the electrical basis of epilepsy in relation to the influence of Michael Faraday (1791-1867), his contemporary in London, and in relation to later nineteenth century writings on the subject by Jackson, Ferrier, and Hitzig, all of whom overlooked Todd's lectures. Todd was a clinical scientist as well as Professor of Physiology and Morbid Anatomy, with a special interest in the nervous system, at King's College, where he came into contact with Michael Faraday, the greatest electrical scientist of all time, at the nearby Royal Institution. On the basis of his own clinical and experimental studies and his cutting-edge knowledge of neuroanatomy, neurophysiology, neuropathology, and electrical science, Todd brilliantly developed his concepts of the electrical basis of brain activity and of epilepsy in particular. With his microscope, he perceived each nerve vesicle and its related fibres (neurone in later terminology) as distinct entities for the generation of nervous polarity (force) and its transmission in the white nerve fibres throughout the nervous system by unknown molecular mechanisms. In epilepsy, an increase in electrical tension, especially in the grey matter of the hemispheres, led to periodic, sudden explosive discharges, based on Faraday's concept of disruptive discharges. Todd was the United Kingdom's first outstanding neurologist and neuroscientist before these disciplines existed. Influenced by Faraday, he proposed and confirmed the electrical basis of nervous discharges in epilepsy more than 20 years ahead of Jackson, Ferrier, and Hitzig, who did not refer to his priority, although Ferrier also worked at King's College, and Jackson also gave his own famous Lumleian lectures on the same subject in 1890. Todd deserves the credit for laying the foundations of our modern understanding of epilepsy. | https://doi.org/10.1111/j.0013-9580.2004.12004.x |
| Edward H Reynolds | Todd, Faraday, and the electrical basis of brain activity. | 2004 | The Lancet. Neurology | 3;9:557-563 | Robert Bentley Todd (1809-60) was the UK's first eminent neurologist and neuroscientist. An anatomist, physiologist, and clinical scientist with an interest in the nervous system, he was the first to confirm the electrical basis of brain activity in the 1840s. He was influenced by his contemporary, Michael Faraday at the Royal Institution, and by two colleagues at King's College, John Daniell and Charles Wheatstone, who were also working at the cutting edge of electrical science. Todd conceived of nervous polarity (force) generated in nervous centres and compared this with the polar force of voltaic electricity developed in the galvanic battery. He brilliantly foresaw each nerve vesicle (cell) and its related fibres (ie, neuron) as a distinct apparatus for the development and transmission of nervous polarity. Epilepsy was the result of periodic unnatural development of nervous force leading to the "disruptive discharge" described by Faraday. Faraday, who studied animal electricity in the Gymnotus (electric eel), and Todd saw nervous polarity as a higher form of interchangeable energy. | https://doi.org/10.1016/S1474-4422(04)00842-7 |
| E H Reynolds | Brain and mind: a challenge for WHO. | 2003 | Lancet (London, England) | 361;9373:1924-1925 | https://doi.org/10.1016/s0140-6736(03)13600-8 | |
| E H Reynolds | Folic acid, ageing, depression, and dementia. | 2002 | BMJ (Clinical research ed.) | 324;7352:1512-1515 | https://doi.org/10.1136/bmj.324.7352.1512 | |
| E H Reynolds | Prevention of refractory epilepsy. | 2002 | Epilepsia | 43;10:1271- | https://doi.org/10.1046/j.1528-1157.2002.10102_3.x | |
| E H Reynolds | The ILAE/IBE/WHO epilepsy global campaign history. International League Against Epilepsy. International Bureau for Epilepsy. | 2002 | Epilepsia | 43;:9-11 | https://doi.org/10.1046/j.1528-1157.43.s.6.5.x | |
| Edward H Reynolds | Introduction: epilepsy in the world. | 2002 | Epilepsia | 43;:1-3 | https://doi.org/10.1046/j.1528-1157.43.s.6.1.x | |
| E H Reynolds | Benefits and risks of folic acid to the nervous system. | 2002 | Journal of neurology, neurosurgery, and psychiatry | 72;5:567-571 | During three decades of neurological practice I have witnessed a remarkable change in attitudes to the benefits and risks of folic acid therapy in nervous system disorders. In the 1960s all that was known and taught was that folic acid was harmful to the nervous system, especially in precipitating or exacerbating the neurological complications of vitamin B12 deficiency. So deeply held was this view that the possibility of neuropsychological benefits from this vitamin was initially viewed with considerable scepticism. | https://doi.org/10.1136/jnnp.72.5.567 |
| E H Reynolds | ILAE/IBE/WHO Global Campaign "out of the shadows": global and regional developments. | 2001 | Epilepsia | 42;8:1094-1100 | https://doi.org/10.1046/j.1528-1157.2001.0420081094.x | |
| E H Reynolds | The impact of epilepsy on Graham Greene. | 2001 | Epilepsia | 42;8:1091-1093 | As a young man, Graham Greene (1904-1991) experienced several episodes of loss of consciousness, which were confidently diagnosed as epilepsy by a Harley Street specialist who saw him on two occasions during the 1920s. The diagnosis was initially concealed from him by his family and the specialist, but when it was revealed, it had a profound effect such that he contemplated suicide. He was particularly concerned about his impending marriage and the risk of having children. His anxiety was not relieved by being told that the famous author, Dostoevsky, had epilepsy. Graham Greene is the only public figure in the United Kingdom, of whom I am aware, who has admitted and discussed the impact of epilepsy, even though this was more than 40 years later when there was some doubt about the diagnosis. | https://doi.org/10.1046/j.1528-1157.2001.0420081091.x |
| E H Reynolds | Mental and physical illness. | 2001 | The British journal of psychiatry : the journal of mental science | 179;:461-462 | https://doi.org/10.1192/bjp.179.5.461-a | |
| Edward H. Reynolds | The ILAE/IBE/WHO Global Campaign against Epilepsy: Bringing Epilepsy "Out of the Shadows" | 2000 | Epilepsy & behavior : E&B | 1;4:- | Epilepsy affects at least 100 million people worldwide at some time in their lives, especially in childhood and adolescence. It is a universal problem involving all ages, races, social classes, and nations. Nevertheless, it has been misunderstood, feared, and stigmatized for more than 3000 years. The psychosocial and economic consequences of epilepsy are considerable in developed nations but are even greater in developing nations, where the treatment gap may vary from 60 to 98%. To address the long-standing worldwide neglect of this disease, a campaign titled Epilepsy: Out of the Shadows has been launched by an alliance of three global organizations: the International League against Epilepsy (ILAE), the International Bureau for Epilepsy (IBE), and the World Health Organization (WHO). Global, regional, and national initiatives are currently underway. | https://doi.org/10.1006/ebeh.2000.0104 |
| T Bottiglieri, E H Reynolds, M Laundy | Folate in CSF and age. | 2000 | Journal of neurology, neurosurgery, and psychiatry | 69;4:562- | https://doi.org/10.1136/jnnp.69.4.562a | |
| T Bottiglieri, M Laundy, R Crellin, B K Toone, M W Carney, E H Reynolds | Homocysteine, folate, methylation, and monoamine metabolism in depression. | 2000 | Journal of neurology, neurosurgery, and psychiatry | 69;2:228-232 | Previous studies suggest that folate deficiency may occur in up to one third of patients with severe depression, and that treatment with the vitamin may enhance recovery of the mental state. There are, however, difficulties in interpreting serum and red cell folate assays in some patients, and it has been suggested that total plasma homocysteine is a more sensitive measure of functional folate (and vitamin B12) deficiency. Other studies suggest a link between folate deficiency and impaired metabolism of serotonin, dopamine, and noradrenaline (norepinephrine), which have been implicated in mood disorders. A study of homocysteine, folate, and monoamine metabolism has, therefore, been undertaken in patients with severe depression. In 46 inpatients with severe DSM III depression, blood counts, serum and red cell folate, serum vitamin B12, total plasma homocysteine, and, in 28 patients, CSF folate, S-adenosylmethionine, and the monoamine neurotransmitter metabolites 5HIAA, HVA, and MHPG were examined. Two control groups comprised 18 healthy volunteers and 20 patients with neurological disorders, the second group undergoing CSF examination for diagnostic purposes. Twenty four depressed patients (52%) had raised total plasma homocysteine. Depressed patients with raised total plasma homocysteine had significant lowering of serum, red cell, and CSF folate, CSF S-adenosylmethionine and all three CSF monoamine metabolites. Total plasma homocysteine was significantly negatively correlated with red cell folate in depressed patients, but not controls. Utilising total plasma homocysteine as a sensitive measure of functional folate deficiency, a biological subgroup of depression with folate deficiency, impaired methylation, and monoamine neurotransmitter metabolism has been identified. Detection of this subgroup, which will not be achieved by routine blood counts, is important in view of the potential benefit of vitamin replacement. | https://doi.org/10.1136/jnnp.69.2.228 |
| E H Reynolds | Doctors in the NHS. National Health Service. | 2000 | Lancet (London, England) | 356;9232:859- | https://doi.org/10.1016/s0140-6736(05)73444-9 | |
| N Adachi, M Koutroumanidis, R D Elwes, C E Polkey, C D Binnie, E H Reynolds, S F Barrington, M N Maisey, C P Panayiotopoulos | Interictal 18FDG PET findings in temporal lobe epilepsy with déjà vu. | 1999 | The Journal of neuropsychiatry and clinical neurosciences | 11;3:380-386 | The authors studied the functional anatomy of the déjà vu (DV) experience in nonlesional temporal lobe epilepsy (TLE), using interictal fluorine-18 fluorodeoxyglucose PET in 14 patients with and 17 patients without DV. Several clinical conditions, such as age at PET study, side of ictal onset zone, and dominance for language, were no different between the two groups. The patients with DV showed significant relative reductions in glucose metabolism in the mesial temporal structures and the parietal cortex. The findings demonstrate that ictal DV is of no lateralizing value. They further suggest that temporal lobe dysfunction is necessary but not sufficient for the generation of DV. Extensive association cortical areas may be involved as part of the network that integrates this distinct experience. | https://doi.org/10.1176/jnp.11.3.380 |
| N Adachi, G Alarcon, C D Binnie, R D Elwes, C E Polkey, E H Reynolds | Predictive value of interictal epileptiform discharges during non-REM sleep on scalp EEG recordings for the lateralization of epileptogenesis. | 1998 | Epilepsia | 39;6:628-632 | EEG recording during sleep is widely used in the assessment of epilepsy, particularly in candidates for surgery, yet the diagnostic value of this procedure is not well established. We evaluated the predictive reliability of interictal epileptiform discharges (IEDs) for localization in presurgical patients with temporal lobe epilepsy (TLE) during non-REM sleep. Preoperative scalp EEG recordings with waking and sleep states were assessed in 83 patients with TLE in whom localization of the epileptogenic zone was subsequently confirmed by successful surgical treatment (patient seizure-free >1 year). The accuracy of EEG recordings for prediction of lateralization significantly changed from 51.8% during waking to 78.3% during sleep. After exclusion of patients who showed no discharges, the predictive value changed from 74.1 to 86.7%. However, in patients in whom the waking scalp EEG lateralized incorrectly, no improvement in reliability was achieved by sleep recording. Our results suggest that IEDs occurring in non-REM sleep provide more accurate information for lateralization of epileptogenesis than do those occurring during waking. This gain of diagnostic information was obtained in patients who showed either bilateral or no discharges in waking records, because unilateral discharges arising de novo in sleep were always correctly lateralizing. On the other hand, in patients who showed unilateral discharges in the awake state, whether ipsilateral or contralateral to the epileptogenic zone, the findings were generally unchanged during sleep. | https://doi.org/10.1111/j.1528-1157.1998.tb01431.x |
| D Chadwick, E H Reynolds | Services for epilepsy in the United Kingdom. | 1997 | Neurology | 48;6:- | https://doi.org/10.1212/wnl.48.6_suppl_8.s3 | |
| M de Silva, B MacArdle, M McGowan, E Hughes, J Stewart, B G Neville, A L Johnson, E H Reynolds | Randomised comparative monotherapy trial of phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed childhood epilepsy. | 1996 | Lancet (London, England) | 347;9003:709-713 | The medical treatment of childhood epilepsy is largely influenced by clinical trials in adult patients. We know of only one randomised comparative trial (of two drugs) in newly diagnosed childhood epilepsy. We have undertaken a long-term, prospective, randomised, unmasked, pragmatic trial of the comparative efficacy and toxicity of four standard antiepileptic drugs used as monotherapy in children with newly diagnosed epilepsy. Between 1981 and 1987, 167 children aged 3-16 years, who had had at least two previously untreated tonic-clonic or partial seizures, with or without secondary generalisation, were randomly allocated treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform to standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to achieving 1-year remission. The overall outcome with all four drugs was good. 20% of children remained free of seizures and 73% had achieved 1-year remission by 3 years of follow-up. We found no significant differences between the drugs for either measure of efficacy at 1, 2, or 3 years of follow-up. The overall frequency of unacceptable side-effects necessitating withdrawal of the randomised drug was 9%. This total included six of the first ten children assigned phenobarbitone; no further children were allocated this drug. Of the other three drugs, phenytoin (9%) was more likely to be withdrawn than carbamazepine (4%) or sodium valproate (4%). INTERPRETATION Our data will inform choice of drug and outcome with four of the standard drugs available for newly diagnosed tonic-clonic or partial seizures with or without secondary generalisation in children. | https://doi.org/10.1016/s0140-6736(96)90074-4 |
| E H Reynolds | Folic acid and the prevention of neural tube defects. Folate has potential to cause harm. | 1995 | BMJ (Clinical research ed.) | 311;6999:257- | https://doi.org/10.1136/bmj.311.6999.257 | |
| E H Reynolds | Do anticonvulsants alter the natural course of epilepsy? Treatment should be started as early as possible. | 1995 | BMJ (Clinical research ed.) | 310;6973:176-177 | https://doi.org/10.1136/bmj.310.6973.176 | |
| E H Reynolds | The Institute of Epileptology of King's College, University of London. | 1995 | Epilepsia | 36;:- | The Institute of Epileptology of King's College, London has arisen from need and from opportunity. The need is due to the relative neglect nationally and internationally of the most common serious brain disorder with important physical, psychological, and social complications. The relative neglect is reflected in services, research, charitable donations, public profile, and stigma and in a serious lack of professional education. The opportunity arose because of the existence in several medical institutions at Denmark Hill, London, of a group of medical and related colleagues with a special interest covering almost every aspect of this multidisciplinary disorder who agreed to combine their expertise in this initiative. The idea was born and developed in 1991-1992 and was supported by all the parent institutions: The Maudsley and King's College Hospitals, St. Piers Lingfield, The Institute of Psychiatry, King's College School of Medicine and Dentistry, and the School of Life, Basic Medical and Health Sciences, all under the umbrella of King's College, University of London. Further stimulus and help came from a group of dedicated supporters in private and public life. There are three strands to this initiative: (a) a charity, The Fund for Epilepsy; (b) the clinical Centre for Epilepsy, which was formally opened at the Maudsley Hospital in July 1994; and (c) the academic Institute of Epileptology for research and teaching, which was launched on November 15, 1994. | https://doi.org/10.1111/j.1528-1157.1995.tb01644.x |
| A J Heller, P Chesterman, R D Elwes, P Crawford, D Chadwick, A L Johnson, E H Reynolds | Phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed adult epilepsy: a randomised comparative monotherapy trial. | 1995 | Journal of neurology, neurosurgery, and psychiatry | 58;1:44-50 | Recent studies have shown that most newly diagnosed epileptic patients can be satisfactorily treated with a single antiepileptic drug. We therefore undertook a prospective randomised pragmatic trial of the comparative efficacy and toxicity of four major antiepileptic drugs, utilised as monotherapy in newly diagnosed epileptic patients. Between 1981 and 1987 243 adult patients aged 16 years or over, newly referred to two district general hospitals with a minimum of two previously untreated tonic-clonic or partial with or without secondary generalised seizures were randomly allocated to treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform with standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to enter one year remission. The overall outcome with all of the four drugs was good with 27% remaining seizure free and 75% entering one year of remission by three years of follow up. No significant differences between the four drugs were found for either measure of efficacy at one, two, or three years of follow up. The overall incidence of unacceptable side effects, necessitating withdrawal of the randomised drug, was 10%. For the individual drugs phenobarbitone (22%) was more likely to be withdrawn than phenytoin (3%), carbamazepine (11%), and sodium valproate (5%). In patients with newly diagnosed tonic-clonic or partial with or without secondary generalised seizures, the choice of drug will be more influenced by considerations of toxicity and costs. | https://doi.org/10.1136/jnnp.58.1.44 |
| E H Reynolds | Lamotrigine versus carbamazepine in epilepsy. | 1995 | Lancet (London, England) | 345;8960:1300- | https://doi.org/ | |
| T Bottiglieri, K Hyland, E H Reynolds | The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. | 1994 | Drugs | 48;2:137-152 | This review focuses on the biochemical and clinical aspects of methylation in neuropsychiatric disorders and the clinical potential of their treatment with ademetionine (S-adenosylmethionine; SAMe). SAMe is required in numerous transmethylation reactions involving nucleic acids, proteins, phospholipids, amines and other neurotransmitters. The synthesis of SAMe is intimately linked with folate and vitamin B12 (cyanocobalamin) metabolism, and deficiencies of both these vitamins have been found to reduce CNS SAMe concentrations. Both folate and vitamin B12 deficiency may cause similar neurological and psychiatric disturbances including depression, dementia, myelopathy and peripheral neuropathy. SAMe has a variety of pharmacological effects in the CNS, especially on monoamine neurotransmitter metabolism and receptor systems. SAMe has antidepressant properties, and preliminary studies indicate that it may improve cognitive function in patients with dementia. Treatment with methyl donors (betaine, methionine and SAMe) is associated with remyelination in patients with inborn errors of folate and C-1 (one-carbon) metabolism. These studies support a current theory that impaired methylation may occur by different mechanisms in several neurological and psychiatric disorders. | https://doi.org/10.2165/00003495-199448020-00002 |
| E H Reynolds, T Bottiglieri, M Laundy, J Stern, J Payan, J Linnell, J Faludy | Subacute combined degeneration with high serum vitamin B12 level and abnormal vitamin B12 binding protein. New cause of an old syndrome. | 1993 | Archives of neurology | 50;7:739-742 | Subacute combined degeneration of the spinal cord due to vitamin B12 deficiency invariably has been associated with a low serum vitamin B12 level. We describe a young man who presented with a unique syndrome of subacute combined degeneration associated with high serum vitamin B12 level, low red blood cell vitamin B12 level, and an abnormal plasma vitamin B12-binding protein. Uptake of cobalamin by his leukocytes in vitro was inhibited by his own but not by normal control plasma. Intensive hydroxocobalamin (vitamin B12) treatment was associated with clinical and electrophysiologic recovery accompanied by normalization of mean corpuscular volume, red blood cell vitamin B12 level, plasma homocysteine, and urinary methylmalonic acid. The subacute combined degeneration was probably precipitated by treatment with folic acid as the significance of his high serum vitamin B12 level was not apparent when he first presented with megaloblastic anemia 3 years earlier. To our knowledge, this is the first example of neurologic disease associated with high serum vitamin B12 level and provides further evidence that sometimes a serum vitamin B12 level may not be a reliable guide to vitamin B12 deficiency. | https://doi.org/10.1001/archneur.1993.00540070055015 |
| R Crellin, T Bottiglieri, E H Reynolds | Folates and psychiatric disorders. Clinical potential. | 1993 | Drugs | 45;5:623-636 | https://doi.org/10.2165/00003495-199345050-00001 | |
| H A Ring, R Crellin, S Kirker, E H Reynolds | Vigabatrin and depression. | 1993 | Journal of neurology, neurosurgery, and psychiatry | 56;8:925-928 | Ten patients who developed a major depressive episode in association with vigabatrin treatment for intractable epilepsy are reported. The depression usually occurred early in the course of treatment, but when delayed followed a recent increase in dose. Depressive symptoms occurred at doses varying between 1.5 g and 4 g a day, often but not always when patients were experiencing a decrease in their seizure frequency. Most patients had a history of affective disturbance, sometimes in association with other GABAergic drugs. The observations support a possible role for GABAergic mechanisms in the biology of mood disorders. | https://doi.org/10.1136/jnnp.56.8.925 |
| E H Reynolds, A J Heller, D Chadwick | Valproate versus carbamazepine for seizures. | 1993 | The New England journal of medicine | 328;3:207-208 | https://doi.org/10.1056/NEJM199301213280310 | |
| E H Reynolds, T Bottiglieri, M Laundy, R F Crellin, S G Kirker | Vitamin B12 metabolism in multiple sclerosis. | 1992 | Archives of neurology | 49;6:649-652 | We have previously described 10 patients with multiple sclerosis (MS) and unusual vitamin B12 deficiency. We have therefore studied vitamin B12 metabolism in 29 consecutive cases of MS, 17 neurological controls, and 31 normal subjects. Patients with MS had significantly lower serum vitamin B12 levels and significantly higher unsaturated R-binder capacities than neurological and normal controls, and they were significantly macrocytic compared with normal controls. Nine patients with MS had serum vitamin B12 levels less than 147 pmol/L and, in the absence of anemia, this subgroup was significantly macrocytic and had significantly lower red blood cell folate levels than neurological and normal controls. Nine patients with MS had raised plasma unsaturated R-binder capacities, including three patients with very high values. There is a significant association between MS and disturbed vitamin B12 metabolism. Vitamin B12 deficiency should always be looked for in patients with MS. The cause of the vitamin B12 disorder and the nature of the overlap with MS deserve further investigation. Coexisting vitamin B12 deficiency might aggravate MS or impair recovery from MS. | https://doi.org/10.1001/archneur.1992.00530300089014 |
| E H Reynolds | Gamma-vinyl GABA (vigabatrin): clinical experience in adult and adolescent patients with intractable epilepsy. | 1992 | Epilepsia | 33;:- | Clinical experience with gamma-vinyl GABA (GVG, vigabatrin) has accumulated mainly in Europe, where the drug has been licensed in several countries since 1989. Short-term efficacy studies in adolescent and adult patients with intractable drug-resistant epilepsy have shown that approximately 50% exhibit a reduction in seizure frequency of one-half or more but rarely complete seizure control. The best results are in patients with partial seizures with or without secondarily generalization. GVG responders have been followed for periods of up to 5 years, and overall 10-20% may exhibit subsequent seizure breakthrough, as probably occurs with any drug in such chronic patients. The most common side effect is drowsiness. Reversible behavior disorders, psychoses, and depression rarely occur in predisposed individuals. No new long-term side effects have been reported but vigilance is necessary. Studies of GVG as a first-line drug in newly diagnosed epileptic patients are proceeding. | https://doi.org/ |
| E H Reynolds | Multiple sclerosis and vitamin B12 metabolism. | 1992 | Journal of neuroimmunology | 40;2:225-230 | Multiple sclerosis (MS) is occasionally associated with vitamin B12 deficiency. Recent studies have shown an increased risk of macrocytosis, low serum and/or CSF vitamin B12 levels, raised plasma homocysteine and raised unsaturated R-binder capacity in MS. The aetiology of the vitamin B12 deficiency in MS is often uncertain and a disorder of vitamin B12 binding or transport is suspected. The nature of the association of vitamin B12 deficiency and MS is unclear but is likely to be more than coincidental. There is a remarkable similarity in the epidemiology of MS and pernicious anaemia. Vitamin B12 deficiency should always be looked for in MS. The deficiency may aggravate MS or impair recovery. There is evidence that vitamin B12 is important for myelin synthesis and integrity but further basic studies are required. | https://doi.org/10.1016/0165-5728(92)90137-a |
| E H Reynolds | Multiple sclerosis and vitamin B12 metabolism. | 1992 | Journal of neurology, neurosurgery, and psychiatry | 55;5:339-340 | https://doi.org/10.1136/jnnp.55.5.339 | |
| J Stewart, E Hughes, E H Reynolds | Lamotrigine for generalised epilepsies. | 1992 | Lancet (London, England) | 340;8829:1223- | https://doi.org/10.1016/0140-6736(92)92922-3 | |
| T Bottiglieri, K Hyland, M Laundy, P Godfrey, M W Carney, B K Toone, E H Reynolds | Folate deficiency, biopterin and monoamine metabolism in depression. | 1992 | Psychological medicine | 22;4:871-876 | Seven (21%) of 34 patients with a severe DSM-III diagnosis of major depression had red-cell folate levels below 150 ng/ml. This subgroup with folate deficiency had significantly lower CSF 5-hydroxyindoleacetic acid (5HIAA) compared to neurological controls. For all depressed patients red-cell folate was significantly correlated with CSF 5HIAA and homovanillic acid (HVA). CSF tetrahydrobiopterin (BH4) was significantly correlated with CSF 5HIAA and HVA and red-cell folate. Our observations provide further evidence of the links between folate, biopterin and monoamine metabolism in depression. | https://doi.org/10.1017/s0033291700038447 |
| P Godfrey, R Crellin, B K Toone, T G Flynn, M W Carney, M Laundy, I Chanarin, T Bottiglieri, E H Reynolds | Enhancement of recovery from psychiatric illness by methylfolate. | 1992 | The British journal of psychiatry : the journal of mental science | 161;:126-127 | https://doi.org/10.1192/bjp.161.1.126 | |
| E H Reynolds | Interictal psychiatric disorders. Neurochemical aspects. | 1991 | Advances in neurology | 55;:47-58 | https://doi.org/ | |
| E H Reynolds, J C Linnell, J E Faludy | Multiple sclerosis associated with vitamin B12 deficiency. | 1991 | Archives of neurology | 48;8:808-811 | We describe 10 patients with a previously unreported, to our knowledge, association of multiple sclerosis and unusual vitamin B12 deficiency. The clinical features and the age at presentation were typical of multiple sclerosis, with eight cases occurring before age 40 years, which is a rare age for vitamin B12 deficiency. Nine patients had hematologic abnormalities, but only two were anemic. All six patients examined had low erythrocyte cobalamin levels. Only two patients had pernicious anemia; in the remaining patients the vitamin B12 deficiency was unexplained. A vitamin B12 binding and/or transport is suspected. The nature of the association of multiple sclerosis and vitamin B12 deficiency is unclear but is likely to be more than coincidental. Further studies of vitamin B12 metabolism, binding, and transport in multiple sclerosis are indicated, as these cases may offer a clue to the understanding of a still mysterious neurologic disorder. | https://doi.org/10.1001/archneur.1991.00530200044017 |
| E H Reynolds, H A Ring, I N Farr, A J Heller, R D Elwes | Open, double-blind and long-term study of vigabatrin in chronic epilepsy. | 1991 | Epilepsia | 32;4:530-538 | We performed an open, double-blind, and long-term study of vigabatrin (gamma-vinyl-GABA, GVG) in patients with treatment-resistant epilepsy who were receiving only one or at most two standard antiepileptic drugs (AEDs). The novel design included a parallel, double-blind, placebo-controlled phase that minimized the number of patients receiving placebo and allowed determination of the optimum dose of GVG for each patient before initiation of the double-blind phase. The study was divided into four phases. The first phase was a 6-week period of baseline observation. In the second phase, GVG was added openly to previous AEDs for 8 weeks. During the first 2 weeks of this phase, the dose of GVG was increased weekly and then, in the absence of adverse effects, was held constant for the next 6 weeks. At the end of this open phase, seizure frequency during the 6 weeks of constant treatment was compared with the baseline seizure frequency for each patient. Patients who experienced reduction greater than 50% in the frequency of any seizure type during the open phase were defined as responders. These responders were then entered into the third and double-blind phase, in which they were randomly allocated wither to continue active GVG treatment or placebo for 8 weeks. Thirty-three patients entered the study; 31 of 33 patients completed the initial open phase. Twenty patients achieved a reduction greater than or equal to 50% in the frequency of one or more seizure types and were eligible for the double-blind phase; 10 were randomized to continue GVG and 10 were randomized to placebo.(ABSTRACT TRUNCATED AT 250 WORDS) | https://doi.org/10.1111/j.1528-1157.1991.tb04688.x |
| H A Ring, A J Heller, W J Marshall, A L Johnson, E H Reynolds | Plasma uric acid in patients receiving anticonvulsant monotherapy. | 1991 | Epilepsy research | 8;3:241-244 | In newly diagnosed adult patients with epilepsy followed prospectively on monotherapy, carbamazepine and phenytoin were associated with a fall in plasma uric acid, but sodium valproate and phenobarbitone were associated with a rise in plasma uric acid. The mechanisms and significance of these findings are discussed. | https://doi.org/10.1016/0920-1211(91)90070-v |
| E H Reynolds | The influence of antiepileptic drugs on the natural history of epilepsy. | 1991 | Epilepsy research. Supplement | 3;:15-20 | https://doi.org/ | |
| T Bottiglieri, E H Reynolds, B K Toone, M W Carney | CSF S-adenosylmethionine in neuropsychiatric disorders. | 1991 | Lancet (London, England) | 338;8759:121- | https://doi.org/10.1016/0140-6736(91)90114-5 | |
| R F Crellin, T Bottiglieri, E H Reynolds | Multiple sclerosis and macrocytosis. | 1990 | Acta neurologica Scandinavica | 81;5:388-391 | Twenty-seven patients with multiple sclerosis had mild but significant macrocytosis when compared with an individually matched neurological control group and the normal laboratory reference range. The cause of the macrocytosis is unknown, but our recent clinical observations implicate a possible disturbance in vitamin B12 metabolism, binding or transport. | https://doi.org/10.1111/j.1600-0404.1990.tb00981.x |
| E H Reynolds | Changing view of prognosis of epilepsy. | 1990 | BMJ (Clinical research ed.) | 301;6761:1112-1114 | https://doi.org/10.1136/bmj.301.6761.1112 | |
| E H Reynolds | Vigabatrin. | 1990 | BMJ (Clinical research ed.) | 300;6720:277-278 | https://doi.org/10.1136/bmj.300.6720.277 | |
| M W Carney, T K Chary, M Laundy, T Bottiglieri, I Chanarin, E H Reynolds, B Toone | Red cell folate concentrations in psychiatric patients. | 1990 | Journal of affective disorders | 19;3:207-213 | Red cell folate and vitamin B12 estimations were performed on 243 successively admitted in-patients at a District General Hospital Psychiatric Unit and 42 out-patients (29 attending a lithium clinic). Patients were classified into five diagnostic groups. The mean ages of the manic and schizophrenic patients were lower than of the depressed or euthymic patients but age was not correlated with red cell folate or serum B12 levels in any group. There were 89 (31%) patients with red cell folate below 200 ng/ml and 35 (12%) with concentrations below 150 ng/ml. Significantly more of these low-folate patients were in-patients than out-patients. The mean red cell folate in the depressed patients was significantly lower than in the euthymic, manic and schizophrenic groups. Alcoholics had a similar mean red cell folate to depressed patients which was not quite significantly lower than the other groups. The mean serum B12 level in the alcoholics was, however, significantly raised. There were no significant differences in red cell folate or serum B12 between lithium-treated and untreated euthymic patients. The highest proportions of values below 200 ng/ml and 150 ng/ml were found in depressed and alcoholic patients. Endogenous depressives had the highest percentage of values below 150 ng/ml (folate-deficient) of all psychiatric groups and alcoholic patients. The significance of these findings is discussed. | https://doi.org/10.1016/0165-0327(90)90093-n |
| T Bottiglieri, P Godfrey, T Flynn, M W Carney, B K Toone, E H Reynolds | Cerebrospinal fluid S-adenosylmethionine in depression and dementia: effects of treatment with parenteral and oral S-adenosylmethionine. | 1990 | Journal of neurology, neurosurgery, and psychiatry | 53;12:1096-1098 | Cerebrospinal fluid (CSF) S-adenosylmethionine (SAM) levels were significantly lower in severely depressed patients than in a neurological control group. The administration of SAM either intravenously or orally is associated with a significant rise of CSF SAM, indicating that it crosses the blood-brain barrier in humans. These observations provide a rational basis for the antidepressant effect of SAM, which has been confirmed in several countries. CSF SAM levels were low in a group of patients with Alzheimer's dementia suggesting a possible disturbance of methylation in such patients and the need for trials of SAM treatment. | https://doi.org/10.1136/jnnp.53.12.1096 |
| H A Ring, A J Heller, I N Farr, E H Reynolds | Vigabatrin: rational treatment for chronic epilepsy. | 1990 | Journal of neurology, neurosurgery, and psychiatry | 53;12:1051-1055 | Vigabatrin is a selective, irreversible suicide inhibitor of GABA transaminase and thus increases brain and CSF GABA. In 33 adult patients with long standing refractory epilepsy on treatment with one or two standard anti-convulsant drugs, the addition of vigabatrin up to 3g daily for eight weeks was associated with a 48.2% reduction in seizure frequency. Twenty patients who had exhibited a 50% or more reduction in frequency of one or more seizure types entered an eight week double-blind placebo controlled phase. Patients on vigabatrin maintained a 54.7% reduction of seizure frequency, whereas those on placebo showed an 18.6% increase in seizure frequency, a highly significant difference between the two groups. In the open phase, seven patients were withdrawn due to unacceptable and reversible adverse events. The commonest side effects were drowsiness, depression and mood instability, and headaches. Vigabatrin is a potentially valuable new treatment for chronic epilepsy, especially partial seizures with or without secondary generalisation. | https://doi.org/10.1136/jnnp.53.12.1051 |
| T Bottiglieri, K Hyland, M Laundy, P Godfrey, M W Carney, B K Toone, E H Reynolds | Enhancement of recovery from psychiatric illness by methylfolate. | 1990 | Lancet (London, England) | 336;8730:1579-1580 | https://doi.org/10.1016/0140-6736(90)93355-s | |
| P S Godfrey, B K Toone, M W Carney, T G Flynn, T Bottiglieri, M Laundy, I Chanarin, E H Reynolds | Enhancement of recovery from psychiatric illness by methylfolate. | 1990 | Lancet (London, England) | 336;8712:392-395 | 41 (33%) of 123 patients with acute psychiatric disorders (DSM III diagnosis of major depression or schizophrenia) had borderline or definite folate deficiency (red-cell folate below 200 micrograms/l) and took part in a double-blind, placebo-controlled trial of methylfolate, 15 mg daily, for 6 months in addition to standard psychotropic treatment. Among both depressed and schizophrenic patients methylfolate significantly improved clinical and social recovery. The differences in outcome scores between methylfolate and placebo groups became greater with time. These findings add to the evidence implicating disturbances of methylation in the nervous system in the biology of some forms of mental illness. | https://doi.org/10.1016/0140-6736(90)91942-4 |
| H A Ring, E H Reynolds | Vigabatrin and behaviour disturbance. | 1990 | Lancet (London, England) | 335;8695:970- | https://doi.org/10.1016/0140-6736(90)91030-e | |
| J V Wilson, E H Reynolds | Texts and documents. Translation and analysis of a cuneiform text forming part of a Babylonian treatise on epilepsy. | 1990 | Medical history | 34;2:185-198 | https://doi.org/10.1017/s0025727300050651 | |
| E H Reynolds | Structure and function in neurology and psychiatry. | 1990 | The British journal of psychiatry : the journal of mental science | 157;:481-490 | In the 19th century the triumphs of neuropathology and the clinico-anatomical method led to the evolution of neurology as a separate 'organically' based discipline associated with the concept of functional localisation. At the same time the growth of psychodynamic psychiatry contributed to the progressive separation of the two disciplines, with neuropsychiatry sitting uneasily in the middle. Psychiatrists are now showing increasing interest in the structure and function of the nervous system, but are having difficulty in integrating their findings into 'functional' diseases. This may be because disorder of function in the nervous system is much more complex than previously envisaged. The function of the nervous system is profoundly affected by psychological and social factors. The view that neurology is wholly 'organic' and synonymous with structural disease of the nervous system is fallacious. Neurological patients have complex dynamic disorders of function in the nervous system whether or not structural disease is present. | https://doi.org/10.1192/bjp.157.4.481 |
| E H Reynolds | Internuclear ophthalmoplegia in pernicious anemia. | 1989 | BMJ (Clinical research ed.) | 298;6671:460-461 | https://doi.org/10.1136/bmj.298.6671.460-e | |
| R F Crellin, T Bottiglieri, E H Reynolds | Multiple sclerosis and macrocytosis. | 1989 | Lancet (London, England) | 2;8672:1157- | https://doi.org/10.1016/s0140-6736(89)91521-3 | |
| R D Elwes, M de Silva, E H Reynolds | Surgery for temporal lobe epilepsy. | 1989 | Lancet (London, England) | 1;8644:959- | https://doi.org/10.1016/s0140-6736(89)92537-3 | |
| M W Carney, T K Chary, T Bottiglieri, E H Reynolds | The switch mechanism and the bipolar/unipolar dichotomy. | 1989 | The British journal of psychiatry : the journal of mental science | 154;:48-51 | During open trials of intravenous and oral S-adenosyl methionine (SAM) and a placebo-controlled trial of intravenous SAM in 29 patients, 25 patients had SAM and four had placebo (27 courses of SAM, two of the patients receiving two trials a piece). Nine of 11 bipolar patients (all SAM-treated) switched into elevated mood state (hypomania, mania and euphoria) and two did not respond. Six endogenous unipolar patients improved and five did not. No non-endogenous patient or placebo patient responded for more than 14 days. No unipolar patient switched into elated mood. In eleven (38%) trials and nine (33%) patients there was a switch from depression to elation. Biochemical data from the cerebrospinal fluid of eight patients suggested that the role of the dopaminergic system should be further explored. | https://doi.org/10.1192/bjp.154.1.48 |
| E H Reynolds | Hughlings Jackson. A Yorkshireman's contribution to epilepsy. | 1988 | Archives of neurology | 45;6:675-678 | Hughlings Jackson (1835-1911), who was born in Yorkshire (England), was the most famous graduate of the York Medical School, which closed in 1862. In York, he received his earliest neurological influences under Laycock. Jackson's most outstanding contributions were in the field of epilepsy. His were the definitive studies of unilateral convulsions that led Charcot to introduce the term Jacksonian epilepsy. His radically new view of epilepsy in terms of discharging lesions was the first neuronal theory and the foundation stone of our modern understanding of the disorder. His theories were based on detailed clinical observation and were later confirmed by the experimental studies of Fritsch and Hitzig, and by his colleague David Ferrier. He was more concerned with the nature than with the classification of epilepsy, and he linked his concepts of the disease to his hierarchical views of nervous system function. His writings on epilepsy over 40 years are on a par with the Hippocratic writings on the Sacred Disease. | https://doi.org/10.1001/archneur.1988.00520300095027 |
| R D Elwes, E H Reynolds | Should people be treated after a first seizure? | 1988 | Archives of neurology | 45;5:490-491 | https://doi.org/10.1001/archneur.1988.00520290016003 | |
| E H Reynolds | A single seizure. | 1988 | BMJ (Clinical research ed.) | 297;6661:1422-1423 | https://doi.org/10.1136/bmj.297.6661.1422 | |
| R D Elwes, A L Johnson, E H Reynolds | The course of untreated epilepsy. | 1988 | BMJ (Clinical research ed.) | 297;6654:948-950 | As little is known about the course of untreated epilepsy the time intervals between untreated tonic clonic seizures were examined retrospectively in a series of 183 patients presenting to a neurological department having had two to five seizures. After the first seizure a second attack had occurred within one month in 56 patients, within three months in 93, and within one year in 159. The median interval between the first two seizures was 12 weeks (95% confidence interval 10 to 18 weeks), between the second and third eight weeks (four to 12 weeks), between the third and fourth four weeks (two to 20 weeks), and between the fourth and fifth three weeks (one to four weeks). When patients who had had three, four, or five untreated seizures were considered separately a similar pattern of decreasing intervals was seen. Successive intervals between seizures could be compared in 82 patients. In 48 the interval decreased, in 16 it did not change, and in 18 it increased. These results suggest that in many patients there is an accelerating disease process in the early stages of epilepsy. | https://doi.org/10.1136/bmj.297.6654.948 |
| E H Reynolds, H Ring, A Heller | A controlled trial of gamma-vinyl-GABA (vigabatrin) in drug-resistant epilepsy. | 1988 | British journal of clinical practice. Supplement | 61;:33- | https://doi.org/ | |
| E H Reynolds | The prevention of chronic epilepsy. | 1988 | Epilepsia | 29;:- | Recent epidemiological and hospital-based studies of newly diagnosed epileptic patients suggest that the prognosis for epilepsy is much more favourable than had previously been reported and believed. Approximately three-quarters of such patients may expect to go into prolonged remission with currently available drugs, utilised as monotherapy. For chronic epileptic patients, however, the outlook for seizure control is poor. Factors that contribute to the development of chronic epilepsy are partial or multiple seizure types, brain pathology, neuropsychiatric or social handicaps, poor compliance, and the early response to treatment. Evidence is presented that epilepsy should be viewed as a process in which early effective treatment may be important to prevent the evolution of chronic epilepsy, which is so difficult to control. | https://doi.org/10.1111/j.1528-1157.1988.tb05788.x |
| A J Heller, H A Ring, E H Reynolds | Factors relating to dramatic response to clobazam therapy in refractory epilepsy. | 1988 | Epilepsy research | 2;4:276-280 | Twenty-five out of 41 (61%) patients with drug-resistant complex partial seizures showed an initial dramatic response to clobazam. Sixteen of these responders developed tolerance to the effects of clobazam so that only 9 (22%) maintained a dramatic response for 1 year. Factors which appeared important in predicting a dramatic response to treatment were a known aetiology for the epilepsy, the occurrence of complex partial seizures alone (i.e., without secondary generalisation) and the absence of mental retardation. | https://doi.org/10.1016/0920-1211(88)90020-4 |
| E H Reynolds, A J Heller, H A Ring | Clobazam for epilepsy. | 1988 | Lancet (London, England) | 2;8610:565- | https://doi.org/10.1016/s0140-6736(88)92680-3 | |
| M W Carney, T K Chary, T Bottiglieri, E H Reynolds | Switch and S-adenosylmethionine. | 1988 | The Alabama journal of medical sciences | 25;3:316-319 | https://doi.org/ | |
| T Bottiglieri, T K Chary, M Laundy, M W Carney, P Godfrey, B K Toone, E H Reynolds | Transmethylation in depression. | 1988 | The Alabama journal of medical sciences | 25;3:296-301 | https://doi.org/ | |
| E H Reynolds | The early treatment and prognosis of epilepsy. | 1988 | The Japanese journal of psychiatry and neurology | 42;3:429-435 | In the last decade community and hospital-based studies of epilepsy from the onset of the disorder have revealed a much more favorable prognosis for seizure control than previously reported. Approximately three-quarters of newly diagnosed patients can enter a prolonged remission on currently available medication. The natural history of untreated epilepsy is unknown but there is some evidence of an escalating process in the early stages in patients with tonic-clonic seizures. The first two years of treatment seem to be important in determining the subsequent course of epilepsy. The longer seizures continue, the less likely they are to be controlled. Early effective treatment may be important in preventing the evolution of chronic epilepsy. These observations have implications for the management of patients with single seizures. | https://doi.org/10.1111/j.1440-1819.1988.tb01333.x |
| A J Heller, H A Ring, E H Reynolds | Clobazam for refractory epilepsy. | 1987 | Archives of neurology | 44;6:578- | https://doi.org/10.1001/archneur.1987.00520180004002 | |
| A Clow, V Glover, M Sandler, R Elwes, E H Reynolds | Tribulin output in neurological disorders. | 1987 | British journal of clinical pharmacology | 24;3:403-404 | https://doi.org/10.1111/j.1365-2125.1987.tb03190.x | |
| E H Reynolds | Early treatment and prognosis of epilepsy. | 1987 | Epilepsia | 28;2:97-106 | Community-based studies and our own prospective hospital-based studies suggest that the prognosis for control of epilepsy is more favorable than previously reported. Approximately three quarters of newly diagnosed patients can enter prolonged remission on currently available medication. The first 2 years of treatment are crucial in determining the subsequent course of epilepsy. The longer seizures continue, the less likely they are to be controlled. Factors that contribute to the evolution of chronic epilepsy are the presence of brain lesions, neuropsychiatric handicaps, and poor compliance. Early effective treatment may also be important in preventing the evolution of chronic epilepsy. Recent studies have not revealed any significant differences in efficacy between the major antiepileptic drugs, and the choice of drug will therefore be influenced by costs and side effects, especially cognitive and behavioral effects. The majority of patients with a single unprovoked tonic-clonic seizure go on to develop epilepsy. Studies are required to evaluate the need for and outcome of therapy in such patients. Information about the natural history of untreated epilepsy, and also the possible influence of drug therapy on the prospects for spontaneous remission, is lacking. | https://doi.org/10.1111/j.1528-1157.1987.tb03633.x |
| E H Reynolds | Polytherapy, monotherapy, and carbamazepine. | 1987 | Epilepsia | 28;:- | Despite the widespread and traditional use of polytherapy in the treatment of epilepsy, there is little evidence of its advantages over monotherapy. Among other undesirable effects, it can produce subtle cognitive and behavioral changes and sometimes even exacerbate the epilepsy. Recent studies provide evidence that in many patients seizures can be controlled by carefully monitored monotherapy: Approximately 75% of newly diagnosed, previously untreated epileptic patients will enter a 2-year remission with this form of treatment. The theory has even been advanced that early control of seizures may help prevent the evolution of drug-resistant, chronic epilepsy. In some patients with chronic epilepsy, multiple-drug therapy can be reduced to single-drug treatment, usually with an improvement in cognitive function and without increase in seizures. Trials conducted to date have shown no evidence of superiority of any one major antiepileptic drug over another in control of a particular seizure type. The choice of antiepileptic drug for monotherapy may therefore be influenced by differences in toxic effects associated with individual agents. On the basis of clinical and psychometric evidence, carbamazepine has been shown to cause fewer adverse effects than other antiepileptic drugs on cognitive function, mood, and behavior. | https://doi.org/10.1111/j.1528-1157.1987.tb05782.x |
| C S Thomas, T Bottiglieri, J Edeh, M W Carney, E H Reynolds, B K Toone | The influence of S-adenosylmethionine (SAM) on prolactin in depressed patients. | 1987 | International clinical psychopharmacology | 2;2:97-102 | Twenty subjects entered a double-blind placebo-controlled trial of SAM in depression. Prolactin concentrations were measured before and after 14 days' treatment. There was a highly significant fall in prolactin concentrations in the SAM-treated group. | https://doi.org/10.1097/00004850-198704000-00001 |
| E H Reynolds, J C Linnell | Vitamin B12 deficiency, demyelination, and multiple sclerosis. | 1987 | Lancet (London, England) | 2;8564:920- | https://doi.org/10.1016/s0140-6736(87)91411-5 | |
| M W Carney, B K Toone, E H Reynolds | S-adenosylmethionine and affective disorder. | 1987 | The American journal of medicine | 83;5:104-106 | Several open and double-blind studies suggest that SAMe may have an anti-depressant effect, and further studies are indicated. SAMe may exert a beneficial effect selectively on endogenous rather than neurotic depression. SAMe crosses the blood-brain barrier. SAMe is involved in several central enzyme pathways relating to transmethylation and folate and monoamine metabolism as well as in membrane function and neuro-transmission. The neuropharmacology of SAMe's effect on mood and the switch mechanism has yet to be fully explored. The actions of SAMe on the dopaminergic system are as yet unclear. SAMe is a physiologic substance that is non-toxic and relatively free of severe side effects (with the exception of mania, which may be a manifestation of the basic mood disorder. | https://doi.org/10.1016/0002-9343(87)90861-8 |
| M W Carney, T K Chary, T Bottiglieri, E H Reynolds, B K Toone | Switch mechanism in affective illness and oral S-adenosylmethionine (SAM) | 1987 | The British journal of psychiatry : the journal of mental science | 150;:724-725 | https://doi.org/10.1192/bjp.150.5.724 | |
| M W Carney, E H Reynolds, B F Sheffield | Prediction of outcome in depressive illness by the Newcastle Diagnosis Scale. Its relationship with the unipolar/bipolar and DSM-III systems. | 1987 | The British journal of psychiatry : the journal of mental science | 150;:43-48 | The Newcastle scores of a group of 64 and subsample of 52 severely depressed inpatients were not normally distributed. Evidence for discontinuity in these distributions was adduced from the contrast in outcome between the endogenous and neurotic patients thus defined, the endogenous consistently doing better than the neurotic group. The unipolar/bipolar system failed to predict different results for endogenous and neurotic patients unless unipolar was subdivided into endogenous and neurotic subgroups. The DSM-III criteria for major depression and melancholia failed to identify subgroups of differing prognoses. | https://doi.org/10.1192/bjp.150.1.43 |
| E H Reynolds | The early treatment and prognosis of epilepsy. | 1987 | The Yale journal of biology and medicine | 60;2:79-83 | Recent community- and hospital-based studies of epilepsy from its onset suggest a much better prognosis than previously recognized, with about three-quarters of patients entering long-term remission on current medication. The first two years of medication are crucial in determining longer-term prognosis. Early effective therapy may be important in preventing the evolution of chronic epilepsy. Adverse prognostic factors include brain lesions, neuropsychiatric handicaps, and poor compliance. | https://doi.org/ |
| D G Andrewes, J G Bullen, L Tomlinson, R D Elwes, E H Reynolds | A comparative study of the cognitive effects of phenytoin and carbamazepine in new referrals with epilepsy. | 1986 | Epilepsia | 27;2:128-134 | This study compares cognitive function in new referrals with epilepsy well-controlled on single drug therapy with either phenytoin or carbamazepine with that in an untreated control group. Patients receiving phenytoin performed consistently less well on memory tasks than did those untreated or receiving carbamazepine. Although patients on phenytoin overall showed a trend towards poorer performance on a tracking task, higher blood levels of this drug were correlated with better tracking performance. The correlation between blood levels of carbamazepine and tracking performance was the opposite from that of phenytoin. Blood levels of carbamazepine were negatively correlated with measures of anxiety, depression, and fatigue. These findings have implications for the choice of drug in the management of epilepsy and also for the reported claims of a psychotropic effect of carbamazepine. | https://doi.org/10.1111/j.1528-1157.1986.tb03515.x |
| E G Lever, R D Elwes, A Williams, E H Reynolds | Subacute combined degeneration of the cord due to folate deficiency: response to methyl folate treatment. | 1986 | Journal of neurology, neurosurgery, and psychiatry | 49;10:1203-1207 | Subacute combined degeneration of the cord is a rare complication of folate deficiency. Disturbance of methylation reactions in nervous tissue probably underlie subacute combined degeneration of the cord arising from folate as well as vitamin B12 deficiency. Methyl tetrahydrofolate is the form in which folic acid is transported into the CNS. Therefore methyl tetrahydrofolate treatment of the neurological and psychiatric manifestations of folate deficiency would seem to be theoretically advantageous. A case of subacute combined degeneration of the cord due to dietary folate deficiency and associated with an organic brain syndrome is reported. There was striking haematological, neurological and psychiatric response to methyl folate treatment. | https://doi.org/10.1136/jnnp.49.10.1203 |
| E H Reynolds | Valproate or infective hepatitis? | 1986 | Lancet (London, England) | 2;8515:1102- | https://doi.org/10.1016/s0140-6736(86)90503-9 | |
| S W Brown, M E McGowan, E H Reynolds | The influence of seizure type and medication on psychiatric symptoms in epileptic patients. | 1986 | The British journal of psychiatry : the journal of mental science | 148;:300-304 | The influence of type of seizure and medication on psychological disability was assessed using the Standard Psychiatric Interview in matched epileptic patients. In comparison to patients with idiopathic tonic-clonic seizures, those with temporal lobe epilepsy complained of more irritability and impaired concentration, and were rated as more depressed and slowed up. Compared to patients on phenytoin, those on carbamazepine complained of more sleep disturbance and were more likely to be taking an hypnotic. | https://doi.org/10.1192/bjp.148.3.300 |
| D Chadwick, E H Reynolds | When do epileptic patients need treatment? Starting and stopping medication. | 1985 | British medical journal (Clinical research ed.) | 290;6485:1885-1888 | Decisions about when to start and stop antiepileptic treatment have important implications for patients with epilepsy. Clinical practice varies and is determined more by dogmatic teaching than by knowledge of either the clinical course of epilepsy or the influence of the drugs. A review of the available evidence shows the need for further studies on the effects of starting and withdrawing treatment on the clinical course and prognosis of epilepsy. | https://doi.org/10.1136/bmj.290.6485.1885 |
| R D Elwes, C Dellaportas, E H Reynolds, W Robinson, W R Butt, D R London | Prolactin and growth hormone dynamics in epileptic patients receiving phenytoin. | 1985 | Clinical endocrinology | 23;3:263-270 | Resting growth hormone and prolactin levels and dynamic responses to bromocriptine and metoclopramide have been measured in epileptic patients before treatment, and compared with a matched group taking phenytoin alone. Mean resting levels of prolactin were higher in patients taking phenytoin (untreated patients 204 mU/l, phenytoin treated patients 302 mU/l), but dynamic responses to metoclopramide and bromocriptine were unaffected. Mean resting levels of growth hormone were also higher in patients taking phenytoin (untreated patients 1.4 mU/l, phenytoin treated patients 6.0 mU/l) and paradoxical suppression was seen following bromocriptine. Phenytoin is unlikely to have any major action on the D2 receptor present on the lactotroph. The abnormalities in growth hormone may explain the well recognized effects of phenytoin on connective tissue. | https://doi.org/10.1111/j.1365-2265.1985.tb00222.x |
| E H Reynolds, M R Trimble | Adverse neuropsychiatric effects of anticonvulsant drugs. | 1985 | Drugs | 29;6:570-581 | Clinical and electrical evidence of peripheral neuropathy may result from long term treatment with phenytoin or barbiturates, especially in combination, or after repeated exposure to toxic blood concentrations of either drug. Prolonged acute toxicity with phenytoin may rarely lead to permanent residual ataxia. Reversible dystonia may occasionally be precipitated by phenytoin or carbamazepine; asterixis by phenytoin, barbiturates or carbamazepine; and, more commonly, tremor by valproate. All the major anticonvulsant drugs, especially in combination, can produce occasional subacute cognitive or behavioural syndromes. In varying degrees, the drugs also impair attention, concentration, memory, mental speed or processing, or motor speed. Possible mechanisms of impaired mental function include neuronal damage, or disturbance of folic acid, monoamine or hormonal metabolism. The relative influence on neurological or psychological function is an important factor in the choice of anticonvulsant drug for the treatment of epilepsy. | https://doi.org/10.2165/00003495-198529060-00004 |
| R Alloway, E H Reynolds, E Spargo, G F Russell | Neuropathy and myopathy in two patients with anorexia and bulimia nervosa. | 1985 | Journal of neurology, neurosurgery, and psychiatry | 48;10:1015-1020 | Two adolescent patients with eating disorders and severe weight loss presented with neuromyopathy. The first was female and had a twenty months' history of bulimia nervosa with weight loss and episodic gorging and vomiting. The second was male with a two-year history of anorexia nervosa characterised by vegetarianism and increasing food restriction. Both had severe wasting and asymmetrical weakness of proximal limb muscles. The first patient deteriorated on refeeding and became temporarily paralysed. Both had a purpuric rash and haematological abnormalities. They made a complete recovery on a mixed diet: vitamin supplements were given to the first but not to the second patient. | https://doi.org/10.1136/jnnp.48.10.1015 |
| R D Elwes, P Chesterman, E H Reynolds | Prognosis after a first untreated tonic-clonic seizure. | 1985 | Lancet (London, England) | 2;8458:752-753 | The prognosis for seizure recurrence was assessed in 133 patients who presented at a median of 1 day after a first-ever tonic-clonic seizure. The cumulative probability of recurrence was 20% by 1 month, 28% by 2 months, 32% by 3 months, 46% by 6 months, 62% by 1 year, and 71% by 3 and 4 years. After a first seizure epilepsy is likely to develop in the majority of patients. | https://doi.org/10.1016/s0140-6736(85)90631-2 |
| J Tikerpae, D Samson, C K Lim, T J Peters, E H Reynolds | The effects of ethanol and anticonvulsants on erythroid delta-aminolaevulinic acid synthase. | 1985 | Scandinavian journal of haematology | 34;3:223-227 | The activity of delta-aminolaevulinic acid (ALA) synthase was measured in bone marrow from 13 control subjects, 12 chronic alcoholic patients and 9 patients on long term anticonvulsant therapy. The majority of patients in both groups had macrocytic red cells in the absence of megaloblastic changes in the marrow. There was a significant increase in ALA synthase activity in the alcoholic patients but no significant increase in enzyme activity in the patients on anticonvulsants and overall there was no correlation of activity with MCV. The macrocytosis associated with these drugs does not therefore appear to result from accelerated erythroid haem synthesis. | https://doi.org/10.1111/j.1600-0609.1985.tb02781.x |
| D G Andrewes, L Tomlinson, R D Elwes, E H Reynolds | The influence of carbamazepine and phenytoin on memory and other aspects of cognitive function in new referrals with epilepsy. | 1984 | Acta neurologica Scandinavica. Supplementum | 99;:23-30 | https://doi.org/10.1111/j.1600-0404.1984.tb05665.x | |
| J A Pratt, P Jenner, A L Johnson, S D Shorvon, E H Reynolds | Anticonvulsant drugs alter plasma tryptophan concentrations in epileptic patients: implications for antiepileptic action and mental function. | 1984 | Journal of neurology, neurosurgery, and psychiatry | 47;10:1131-1133 | In epileptic patients carbamazepine and diphenylhydantoin have opposite effects on whole and free plasma tryptophan concentrations, the former elevating and the latter depressing them. It is unlikely that these observations relate to the similar anti-epileptic properties of these two drugs but they may relate to their different effects on mental function and mood. | https://doi.org/10.1136/jnnp.47.10.1131 |
| T Bottiglieri, M Laundy, R Martin, M W Carney, H Nissenbaum, B K Toone, A L Johnson, E H Reynolds | S-adenosylmethionine influences monoamine metabolism. | 1984 | Lancet (London, England) | 2;8396:224- | https://doi.org/10.1016/s0140-6736(84)90507-5 | |
| E H Reynolds, M W Carney, B K Toone | Methylation and mood. | 1984 | Lancet (London, England) | 2;8396:196-198 | S-adenosylmethionine (SAM) has antidepressant properties. The commonest neuropsychiatric complication of severe folate deficiency is depression. These independent observations suggest that methylation in the nervous system may underlie the expression of mood and related processes and may be implicated in some affective disorders; suggest new biological approaches to the understanding and treatment of some affective disorders; and may explain why methionine sometimes aggravates schizophrenia. | https://doi.org/10.1016/s0140-6736(84)90482-3 |
| R D Elwes, S D Shorvon, E H Reynolds | Epileptics refractory to anticonvulsants. | 1984 | Neurology | 34;2:263-264 | https://doi.org/10.1212/wnl.34.2.263 | |
| R D Elwes, A L Johnson, S D Shorvon, E H Reynolds | The prognosis for seizure control in newly diagnosed epilepsy. | 1984 | The New England journal of medicine | 311;15:944-947 | We assessed the prognosis for seizure control in 106 patients who were referred to an adult neurology clinic with previously untreated tonic-clonic, partial, or mixed seizures and were followed prospectively for a median of 66 months (range, 6 to 96). Twenty-six patients remained completely free of seizures for as long as they were followed. Actuarial analysis showed that 35 per cent of patients could be expected to enter a seizure-free period of at least two years at the start of treatment, 73 per cent would have had a two-year seizure-free period at the end of four years, and 82 per cent would have had a two-year seizure-free period at the end of eight years. Of 79 patients whose seizures were completely controlled for at least two years, 51 subsequently remained seizure-free. If seizures continued for up to two years after the start of treatment, the probability of subsequent seizure control fell by half. The presence of partial seizures; a high frequency of tonic-clonic seizures before treatment; a neurologic, social, or psychiatric handicap; and a family history of epilepsy each indicated a worse prognosis. We conclude that the long-term pattern of seizure control is largely established during the first two years of treatment. | https://doi.org/10.1056/NEJM198410113111503 |
| E H Reynolds, S D Shorvon, G Bauer | [Mono- or polytherapy of epilepsy?]. | 1984 | Wiener klinische Wochenschrift | 96;15:566-568 | Although anticonvulsant polytherapy has been widely and traditionally used in the treatment of epilepsy, there is little evidence of its advantages over monotherapy. It does, however, lead to problems of chronic toxicity, drug interactions, failure to evaluate individual drugs, and sometimes exacerbation of seizures. There are many complications of polytherapy which could be avoided by more careful monitoring and supervision of therapy. Studies in new, previously untreated referrals suggest that there is considerable potential for monotherapy. In the event of failure of optimum monotherapy, the value of polytherapy is not yet clear. In chronic patients on polytherapy there may be scope for careful rationalization to two or sometimes one drug, with reduction in chronic toxicity and sometimes improved seizure control. Reduction of therapy, however, may be impossible or hazardous due to withdrawal seizures. Even after successful reduction, seizure control is much less satisfactory than in new referrals. It is easier to avoid polytherapy than to reduce it. There is a need to define carefully the limits of effective anticonvulsant therapy. | https://doi.org/ |
| B Lewis, W D Mitchell, C B Marenah, C Cortese, E H Reynolds, R Shakir | Cerebrotendinous xanthomatosis: biochemical response to inhibition of cholesterol synthesis. | 1983 | British medical journal (Clinical research ed.) | 287;6384:21-22 | https://doi.org/10.1136/bmj.287.6384.21-a | |
| E H Reynolds | Interictal behaviour in temporal lobe epilepsy. | 1983 | British medical journal (Clinical research ed.) | 286;6369:918-919 | https://doi.org/10.1136/bmj.286.6369.918 | |
| E H Reynolds | Mental effects of antiepileptic medication: a review. | 1983 | Epilepsia | 24;:- | https://doi.org/10.1111/j.1528-1157.1983.tb04651.x | |
| E H Reynolds, R D Elwes, S D Shorvon | Why does epilepsy become intractable? Prevention of chronic epilepsy. | 1983 | Lancet (London, England) | 2;8356:952-954 | Community-based and our own hospital-based studies suggest that the prognosis for seizure control is very good in most patients with epilepsy. However, chronic epilepsy develops in about 25%. The pattern of chronicity is established early in the course of treatment. Factors associated with a high risk of chronicity include additional neurological, psychological, and social handicaps and also partial seizures. In addition a process of evolution of chronic epilepsy may occur by a mechanism proposed by Gowers a century ago. Chronic epilepsy is very difficult to control and may best be prevented by more effective treatment at the onset of the disorder. | https://doi.org/10.1016/s0140-6736(83)90462-2 |
| M W Carney, R Martin, T Bottiglieri, E H Reynolds, H Nissenbaum, B K Toone, B N Sheffield | Switch mechanism in affective illness and S-adenosylmethionine. | 1983 | Lancet (London, England) | 1;8328:820-821 | https://doi.org/10.1016/s0140-6736(83)91876-7 | |
| E H Reynolds, S D Shorvon | [Mono- or polytherapy in the treatment of epileptic patients]. | 1983 | Minerva medica | 74;1:51-57 | https://doi.org/ | |
| E H Reynolds, G Stramentinoli | Folic acid, S-adenosylmethionine and affective disorder. | 1983 | Psychological medicine | 13;4:705-710 | https://doi.org/10.1017/s0033291700051394 | |
| S D Shorvon, E H Reynolds | Early prognosis of epilepsy. | 1982 | British medical journal (Clinical research ed.) | 285;6356:1699-1701 | In 94 previously untreated new referrals to a neurological clinic with tonic-clonic or partial seizures or both the failure rate for optimum single-drug treatment with phenytoin or carbamazepine after a median of 32 months was 17%. Failure of single-drug treatment was associated especially with the presence of additional neuropsychiatric handicaps but also with partial or mixed seizures, symptomatic epilepsy, and a higher number and frequency of tonic-clonic or partial seizures before treatment. Analysis of the recurrence of seizures suggested that the first year of treatment may be crucial in determining the long-term prognosis. These findings are in keeping with the concept that seizures may predispose to further seizures, and imply that early, effective treatment may be important to prevent evolution into chronic and more intractable epilepsy. | https://doi.org/10.1136/bmj.285.6356.1699 |
| D I Dellaportas, S D Shorvon, A W Galbraith, M Laundy, E H Reynolds, W J Marshall, I Chanarin | Chronic toxicity in epileptic patients receiving single-drug treatment. | 1982 | British medical journal (Clinical research ed.) | 285;6339:409-410 | https://doi.org/10.1136/bmj.285.6339.409 | |
| S D Shorvon, E H Reynolds | Anticonvulsant peripheral neuropathy: a clinical and electrophysiological study of patients on single drug treatment with phenytoin, carbamazepine or barbiturates. | 1982 | Journal of neurology, neurosurgery, and psychiatry | 45;7:620-626 | Previous studies of phenytoin neuropathy in selected groups of chronic epileptic patients on polytherapy have indicated a widely varying incidence of clinical or electrophysiological abnormalities. In 51 previously untreated epileptic patients followed prospectively on phenytoin or carbamazepine monotherapy, assisted by blood level monitoring, for 1-5 years we found no clinical evidence of neuropathy. Eighteen per cent of the phenytoin group and none of the carbamazepine group had mild electrophysiological changes (abnormalities of sensory action potentials or sensory conduction). In the former group the occurrence of the electrophysiological abnormalities was possibly related to previous exposure to high phenytoin or low folate levels or both. In 10 chronic epileptic patients we demonstrated reversible slowing of sensory nerve conduction during phenytoin intoxication. In six selected epileptic patients on chronic barbiturate monotherapy we found clinical evidence of neuropathy in two and electrophysiological abnormalities in five, including reversible slowing of sensory conduction during intoxication in one. This suggests that barbiturate drugs may, like phenytoin, also contribute to anticonvulsant neuropathy. Careful monitoring of single drug therapy with avoidance of acute toxicity may reduce the risk of chronic anticonvulsant neuropathy. | https://doi.org/10.1136/jnnp.45.7.620 |
| E H Reynolds | The pharmacological management of epilepsy associated with psychological disorders. | 1982 | The British journal of psychiatry : the journal of mental science | 141;:549-557 | The anticonvulsant treatment of epilepsy associated with psychological disorders is reviewed in the light of modern knowledge of the clinical pharmacology and adverse mental effects of the drugs. Careful monitoring of individual drug therapy from the onset of treatment improves compliance and seizure control and avoids unnecessary and harmful polypharmacy, and some of the neurological and psychosocial problems of chronic epilepsy. In chronic patients on polypharmacy cautious rationalization may improve mental function but can be hazardous due to withdrawal seizures. A clearer perception of the limits of anticonvulsant therapy will allow more attention to appropriate psychosocial measures. | https://doi.org/10.1192/bjp.141.6.549 |
| E H Reynolds, S D Shorvon, E B Andersen | [Monotherapy or polytherapy in the treatment of epilepsy]. | 1982 | Ugeskrift for laeger | 144;51:3815-3818 | https://doi.org/ | |
| L Tomlinson, N Stirling, E Merrifield, E H Reynolds | Recognition memory in treated epileptic patients. | 1981 | Acta neurologica Scandinavica. Supplementum | 89;:43-50 | In this study there was no qualitative difference in the performance of a heterogeneous group of epileptic patients and normal subjects on a recognition task for visually presented verbal material. There was, however, a significant overall difference in the number of words recognised. After a statistical correction for V.I.Q. was made this difference disappeared. The small sample size and statistical corrections made on the data make it difficult to draw firm conclusions. The data is part of a pilot study investigating the parameters of the test procedure itself. This test will be used in a carefully controlled, prospective study of the cognitive effects of anticonvulsant drugs. | https://doi.org/10.1111/j.1600-0404.1981.tb02361.x |
| E H Reynolds, S D Shorvon | Single drug or combination therapy for epilepsy? | 1981 | Drugs | 21;5:374-382 | https://doi.org/10.2165/00003495-198121050-00005 | |
| E H Reynolds, S D Shorvon, A W Galbraith, D Chadwick, C I Dellaportas, L Vydelingum | Phenytoin monotherapy for epilepsy: a long-term prospective study, assisted by serum level monitoring, in previously untreated patients. | 1981 | Epilepsia | 22;4:475-488 | Of 31 previously untreated patients with grand mal and/or partial seizures referred to a neurological clinic and treated with phenytoin monotherapy, assisted by serum level monitoring, 26 have been followed up for a mean of 42 months. Seizures were completely controlled in 80%. Failure of optimum phenytoin monotherapy occurred in 12%. The degree of seizure control was significantly related to phenytoin serum levels. The success of monotherapy was probably related to availability of serum level monitoring and to the study of a previously untreated population with a relatively short history of epilepsy. The main reasons for failure of monotherapy were poor compliance and the presence of additional neuropsychiatric handicaps, which commonly occur together. The place for polytherapy in the event of failure of monotherapy has still to be defined. | https://doi.org/10.1111/j.1528-1157.1981.tb06158.x |
| E H Reynolds, S D Shorvon | Monotherapy or polytherapy for epilepsy? | 1981 | Epilepsia | 22;1:1-10 | Although anticonvulsant polytherapy has been widely and traditionally used in the treatment of epilepsy, there is little evidence of its advantages over monotherapy. It does, however, lead to problems of chronic toxicity, drug interactions, failure to evaluate individual drugs, and sometimes exacerbation of seizures. There are many causes of polytherapy which could be avoided by more careful monitoring and supervision of therapy. Studies in new, previously untreated referrals suggest there is considerable potential for monotherapy. In the event of failure of optimum monotherapy, the value of polytherapy is not yet clear. In chronic patients on polytherapy there may be scope for careful rationalization to two or sometimes one drug, with reduction in chronic toxicity and sometimes improved seizure control. Reduction of therapy, however, may be impossible or hazardous due to withdrawal seizures. Even after successful reduction, seizure control is much less satisfactory than in new referrals. It is easier to avoid polytherapy than to reduce it. There is a need to define more carefully the limits of effective anticonvulsant therapy. | https://doi.org/10.1111/j.1528-1157.1981.tb04327.x |
| E H Reynolds, S D Shorvon | [Medical treatment of epilepsy : monotherapy versus polytherapy (author's transl)]. | 1981 | La Nouvelle presse medicale | 10;45:3717-3719 | Although anticonvulsant polytherapy has traditionally been used on a large scale in epilepsy, there is little evidence that it has advantages over monotherapy. Furthermore, it leads to problems of chronic toxicity, drug interactions, failure to evaluate individual drugs, and sometimes exacerbation of seizures. In many cases polytherapy could be avoided by more careful monitoring and supervision of patient's compliance. Studies in new, previously untreated patients suggest that there is considerable potential for monotherapy. In chronic patients on polytherapy, there may be opportunities for careful rationalization to two or even one drug, with subsequent reduction of chronic toxicity and sometimes improvement in seizure control. Reduction of the number of drugs, however, may be impossible or hazardous owing to withdrawal seizures. It is easier to avoid polytherapy than to reduce it. | https://doi.org/ |
| E H Reynolds, S D Shorvon | Single drug or multiple drug therapy for epilepsy? | 1981 | Lancet (London, England) | 1;8218:507- | https://doi.org/10.1016/s0140-6736(81)91899-7 | |
| E H Reynolds, S D Shorvon, J M Martínez-Lage | [Monotherapy or polytherapy in epilepsy?]. | 1981 | Revista de medicina de la Universidad de Navarra | 25;2:33-37 | https://doi.org/ | |
| E H Reynolds | Anticonvulsants and mental symptoms. | 1980 | Acta neurologica Scandinavica. Supplementum | 80;:46-52 | https://doi.org/10.1111/j.1600-0404.1980.tb02349.x | |
| S D Shorvon, M W Carney, I Chanarin, E H Reynolds | The neuropsychiatry of megaloblastic anaemia. | 1980 | British medical journal | 281;6247:1036-1038 | The neuropsychiatric states of 50 patients with vitamin B12 deficiency and 34 patients with folate deficiency presenting with megaloblastosis in a general hospital were examined and compared. Abnormalities of the nervous system were found in two-thirds of both groups. Peripheral neuropathy was the most common condition associated with vitamin B12 deficiency and affective disorder with folate deficiency. The proportions of patients with organic mental change were similar in the two groups. Subacute combined degeneration of the cord was an uncommon complication and occurred only in the patients with vitamin B12 deficiency. There was no relation between haematological and neuropsychiatric abnormalities. The neuropsychiatry of megaloblastic anaemia seen in this study of patients presenting to haematologists or general physicians contrasts with that reported previously, before haematological techniques for separating the two deficiencies were introduced. | https://doi.org/10.1136/bmj.281.6247.1036 |
| S Shorvon, A W Galbraith, E H Reynolds | Compliance and epilepsy. | 1980 | British medical journal | 280;6225:1228- | https://doi.org/10.1136/bmj.280.6225.1228-a | |
| S D Shorvon, A W Galbraith, E H Reynolds | Compliance or unnecessary prescribing? | 1980 | British medical journal | 280;6212:484- | https://doi.org/10.1136/bmj.280.6212.484-a | |
| E H Reynolds | Serum levels of anticonvulsant drugs. Interpretation and clinical value. | 1980 | Pharmacology & therapeutics | 8;2:217-235 | https://doi.org/10.1016/0163-7258(80)90047-9 | |
| A W Galbraith, E H Reynolds, S D Shorvon | One drug for epilepsy [proceedings]. | 1979 | British journal of clinical pharmacology | 7;4:413- | https://doi.org/10.1111/j.1365-2125.1979.tb00958.x | |
| P Jenner, C D Marsden, J Pratt, E H Reynolds | Modulation of picrotoxin-induced forepaw myoclonus in the rat by benzodiazepines [proceedings]. | 1979 | British journal of pharmacology | 67;3:440- | https://doi.org/ | |
| S D Shorvon, E H Reynolds | Reduction in polypharmacy for epilepsy. | 1979 | British medical journal | 2;6197:1023-1025 | A two-year prospective study of 40 adult outpatients with chronic epilepsy was carried out in which blood drug concentrations were monitored, and anticonvulsant polypharmacy was reduced to treatment with a single drug in 29 patients (72%). In the year after the reduction of treatment the control of seizures was improved in 16 patients (55%), unchanged in eight(28%), and worse in five (17%). Mental function was improved in 16 (55%). The main reason for failure to reduce to or maintain treatment with a single drug was exacerbation of seizures during the difficult withdrawal period, especially in patients with frequent seizures, taking several drugs, or with additional neuropsychological handicaps. It is more difficult to reduce polypharmacy than to avoid it in the first place. Polypharmacy may sometimes aggravate control of seizures. | https://doi.org/10.1136/bmj.2.6197.1023 |
| E H Reynolds | Clinical application of the monitoring of anticonvulsant drug levels. | 1979 | Ciba Foundation symposium | ;74:199-214 | The drug treatment of epilepsy poses considerable problems, including the high prevalence and early age of onset of seizures, the relatively poor prognosis in many patients, prolonged polypharmacy, chronic toxicity, and uncertainty of the relative efficacy of individual drugs. The application of recent knowledge of the clinical pharmacology of the major anticonvulsants offers a partial solution to several of these problems. Although there is no therapeutic range for any drug applicable to all patients, a more simple rational and effective approach to treatment is possible with the guidance of serum level monitoring. In new referrals, there is considerable potential for monotherapy, and the avoidance of polypharmacy and chronic toxicity. Reduction in polypharmacy in chronic patients is more difficult, but in many can be achieved with reduction in toxicity, and sometimes improved seizure control. Further studies will provide a clearer picture of the limits to modern anticonvulsant therapy, the relative efficacy of individual drugs, and the potential for improved long-term prognosis. | https://doi.org/10.1002/9780470720578.ch12 |
| E H Reynolds | Stress, distress, and psychotropic drugs. | 1979 | Lancet (London, England) | 1;8113:445- | https://doi.org/10.1016/s0140-6736(79)90927-9 | |
| J Pratt, P Jenner, E H Reynolds, C D Marsden | Clonazepam induces decreased serotoninergic activity in the mouse brain. | 1979 | Neuropharmacology | 18;10:791-799 | https://doi.org/10.1016/0028-3908(79)90024-8 | |
| E H Reynolds | How do anticonvulsants work? | 1978 | British journal of hospital medicine | 19;5:505-512 | https://doi.org/ | |
| P Jenner, C D Marsden, J Pratt, E H Reynolds | Altered serotoninergic activity in mouse brain induced by clonazepam [proceedings]. | 1978 | British journal of pharmacology | 64;3:432- | https://doi.org/ | |
| D Chadwick, J W Gorrod, P Jenner, C D Marsden, E H Reynolds | Functional changes in cerebral 5-hydroxytryptamine metabolism in the mouse induced by anticonvulsant drugs. | 1978 | British journal of pharmacology | 62;1:115-124 | 1 Acute administration of clonazepam, diazepam, and diphenylhydantoin to mice elevated cerebral 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA); chronic administration had less effect. 2 Acute administration of clonazepam and diazepam but not diphenylhydantoin raised cerebral trytophan levels; chronic administration of clonazepam caused a smaller elevation of cerebral tryptophan but chronic administration of diazepam still caused a large rise in cerebral tryptophan. 3 Neither clonazepam nor diazepam caused induction of drug metabolizing enzymes on chronic administration but diphenylhydantoin had a marked effect. 4 These data suggest that the altered 5-HT metabolism caused by these compounds is unrelated to a common action on tryptophan levels, and that the reduced effect of clonazepam and diazepam on chronic administration cannot be attributed to increased metabolism of these compounds. 5 Clonazepam induced abnormal head movements in mice in a dose-dependent manner. Pretreatment of animals with tranylcypromine increased the intensity of movement, although pargyline was without effect. Similar effects were observed with diazepam and diphenylhydantoin, suggesting that the increase in cerebral 5-HT caused by these compounds is of functional significance in stimulating 5-HT receptors. | https://doi.org/10.1111/j.1476-5381.1978.tb07013.x |
| S D Shorvon, D Chadwick, A W Galbraith, E H Reynolds | One drug for epilepsy. | 1978 | British medical journal | 1;6111:474-476 | We performed prospective trials of phenytoin and carbamazepine, assisted by blood level monitoring, in untreated patients newly referred with grand mal or partial seizures, or both, to a neurological clinic. At the time of follow-up (mean 28.5 months for phenytoin; 12 months for carbamazepine) 76-88% of patients were completely controlled. Twelve per cent of the patients on each drug had further seizures, despite an optimum blood level. When the blood drug concentration was in the optimum range there was a 98% reduction in grand mal attack rate and 92-93% reduction in partial seizure rate. These results suggest that polypharmacy is largely, and possibly totally, unnecessary in newly diagnosed adult epileptics. | https://doi.org/10.1136/bmj.1.6111.474 |
| D Chadwick, M Trimble, P Jenner, M V Driver, E H Reynolds | Manipulation of cerebral monoamines in the treatment of human epilepsy: a pilot study. | 1978 | Epilepsia | 19;1:3-10 | The effects of L-DOPA, L-tryptophan, monoamine oxidase inhibitor (MAOI), and MAOI plus L-tryptophan, each for 3 months, have been assessed in 10 severe, adult epileptics with placebo control. There was no overall reduction in seizure frequency, but 2 patients with minor partial seizures improved, 1 with L-DOPA, MAOI, and MAOI plus L-tryptophan, and the other with L-tryptophan and MAOI plus L-tryptophan. We have not been able to demonstrate an increased turnover of cerebral serotonin (5-HT), as measured by cerebrospinal fluid 5-hydroxyindoleacetic acid, after treatment with L-tryptophan for 3 months. This observation casts doubt on the ability of L-tryptophan to alter the long-term metabolism and functional activity of brain 5-HT. The importance of further exploration of manipulation of cerebral monoamines as a possible approach to the treatment of epilepsy is emphasized. | https://doi.org/10.1111/j.1528-1157.1978.tb05007.x |
| E H Reynolds | Drug treatment of epilepsy. | 1978 | Lancet (London, England) | 2;8092:721-725 | The difficulties of the drug treatment of epilepsy include the high prevalence of the disorder, poor prognosis, prolonged multidrug treatment, chronic toxicity, and uncertainty of the relative efficacy and toxicity of individual anticonvulsants. These problems are reviewed in relation to recent knowledge of the clinical pharmacology of the drugs, the application of which offers the possibility of a more simple, rational, and effective approach to therapy. There is considerable potential for monotherapy assisted by drug-level monitoring. | https://doi.org/10.1016/s0140-6736(78)92713-7 |
| E H Reynolds, M Laundy | Haematological effects of anticonvulsant treatment. | 1978 | Lancet (London, England) | 2;8091:682- | https://doi.org/10.1016/s0140-6736(78)92796-4 | |
| E H Reynolds | Epilepsy symposium. Basic concepts and diagnosis. | 1978 | Nursing mirror | 147;4:14-16 | https://doi.org/ | |
| D Chadwick, P Jenner, E H Reynolds | Serotonin metabolism in human epilepsy: the influence of anticonvulsant drugs. | 1977 | Annals of neurology | 1;3:218-224 | https://doi.org/10.1002/ana.410010304 | |
| D Chadwick, M Hallett, R Harris, P Jenner, E H Reynolds, C D Marsden | Clinical, biochemical, and physiological features distinguishing myoclonus responsive to 5-hydroxytryptophan, tryptophan with a monoamine oxidase inhibitor, and clonazepam. | 1977 | Brain : a journal of neurology | 100;3:455-487 | Fifteen patients with a variety of myoclonic syndromes were studied clinically, pharmacologically, and physiologically. CSF tryptophan, 5HIAA, and HVA were also measured. Of these patients, 8 were improved to varying degrees by therapy with 5HTP, tryptophan in combination with MAOI (but not tryptophan alone), and clonazepam. This group included 6 cases of post-anoxic myoclonus, one case of post-traumatic myoclonus and one undiagnosed case of non-progressive focal myoclonus and epilepsy. In this group low levels of CSF 5HIAA were found compared to non-responsive cases and controls. Two cases of dysynergia cerebellaris myoclonica, 2 cases of undiagnosed aetiology, 2 cases of essential myoclonus, and one case of palatal myoclonus failed to respond to drug therapy. However, even amongst the responsive group the improvement varied. The most dramatic responses were seen in those patients in whom physiological study suggested that myoclonus was mediated by brain-stem structures. Less dramatic responses were seen in patients in whom the myoclonus appeared to originate from cortical structures. The neurochemical basis of myoclonus responding to 5HT precursors and clonazepam is discussed. It is suggested that such myoclonus arises from a relative hypoactivity of the 5HT neuronal system which results in a release of abnormal responses to sensory stimuli which characterize this type of myoclonus. | https://doi.org/10.1093/brain/100.3.455 |
| H Taguchi, M Laundy, C Reid, E H Reynolds, I Chanarin | The effect of anticonvulsant drugs on thymidine and deoxyribosenucleic acid synthesis by human marrow cells. | 1977 | British journal of haematology | 36;2:181-187 | An abnormal deoxyuridine suppression test was found in treated epileptic patients that did not correlate with other evidence of abnormal folate metabolism. Diphenylhydantoin at a level of 100 microgram/ml interfered with the incorporation of [3H]thymidine into DNA. It is suggested that anticonvulsants may exert their effect at a stage of DNA synthesis beyond that at which folate coenzymes operate. Folate deficiency may then arise as a result of death of cells in vivo causing an increased folate requirement. | https://doi.org/10.1111/j.1365-2141.1977.tb00638.x |
| S D Shorvon, E H Reynolds | Unnecessary polypharmacy for epilepsy. | 1977 | British medical journal | 1;6077:1635-1637 | A retrospective survey of 50 adult epileptic outpatients who were taking two anticonvulsants drugs showed that seizure control had improved in the six months after the introduction of the second drug in only 36%. When blood concentrations of the two anticonvulsants were subsequently measured improvement in seizure control was found to be significantly related to the presence of optimum blood concentrations of at least one drug. Much unnecessary polypharmacy in the treatment of epilepsy could be avoided by ensuring an optimum blood concentration of one drug before considering the addition of a second. | https://doi.org/10.1136/bmj.1.6077.1635 |
| W P Stephens, M L Espir, R B Tattersall, N P Quinn, S R Gladwell, A W Galbraith, E H Reynolds | Water intoxication due to carbamazepine. | 1977 | British medical journal | 1;6063:754-755 | https://doi.org/10.1136/bmj.1.6063.754 | |
| H Taguchi, Z Abdul-Cader, J Perry, E H Reynolds, I Chanarin | Effect of anticonvulsants on the uptake of 5-methyltetrahydrofolic acid by the choroid plexus in rabbits. | 1977 | Clinical science and molecular medicine | 53;1:75-80 | 1. The isolated choroid plexus of the rabbit takes up 5-methyltetrahydrofolate from the incubation medium. 2. Other folate analogues (pteroylglutamic acid, methotrexate, 5-formyltetrahydrofolate = folinic acid) inhibited the uptake of 5-methyltetrahydrofolate. 3. The uptake of 5-methyltetrahydrofolate was inhibited by low temperature, anaerobic conditions and dinitrophenol. 4. The anticonvulsant drugs, diphenylhydantoin and phenobarbital, had no effect on 5-methyltetrahydrofolate uptake. 5. The inhibitory effect of pteroylglutamic acid on the uptake of 5-methyltetrahydrofolate by the choroid plexus may explain the effect of long-term folic acid therapy in aggravating vitamin B12 neuropathy in pernicious anaemia. | https://doi.org/10.1042/cs0530075 |
| J Perry, M Lumb, M Laundy, E H Reynolds, I Chanarin | Role of vitamin B12 in folate coenzyme synthesis. | 1976 | British journal of haematology | 32;2:243-248 | Normal red cells in man were found to contain predominantly folate pentaglutamates with smaller amounts of tetra- and hexapolyglutamates. There was no change in the type of polyglutamate present in red cells from patients with vitamin B12 deficiency and primary folate deficiency. In contrast to the fall in red cell polyglutamate concentration in vitamin B12 deficiency, there was a marked fall in short-chain folates in early folate deficiency (treated non-anaemic epileptics) and a fall in both short chain and long chain polyglutamates in patients with severe folate deficiency and megaloblastic anaemia. These differences in folate distribution within cells exclude a primary failure to transport methylfolate into cells as the lesion in vitamin B12 deficiency. The failure of folate polyglutamate synthesis in ivtamin B12 deficiency arises either from a failure to provide the proper substrate for polyglutamate synthesis or to a direct requirement for vitamin B12 for polyglutamate synthesis. | https://doi.org/10.1111/j.1365-2141.1976.tb00927.x |
| E H Reynolds | Letter: Folate-responsive neuropathy. | 1976 | British medical journal | 2;6026:42- | https://doi.org/10.1136/bmj.2.6026.42-d | |
| E H Reynolds | Neurological aspects of folate and vitamin B12 metabolism. | 1976 | Clinics in haematology | 5;3:661-696 | https://doi.org/ | |
| E H Reynolds | Unsatisfactory aspects of the drug treatment of epilepsy. | 1976 | Epilepsia | 17;3:- | https://doi.org/ | |
| D Chadwick, E H Reynolds, C D Marsden | Anticonvulsant-induced dyskinesias: a comparison with dyskinesias induced by neuroleptics. | 1976 | Journal of neurology, neurosurgery, and psychiatry | 39;12:1210-1218 | Anticonvulsants cause dyskinesias more commonly than has been appreciated. Diphenylhydantoin (DPH), carbamazepine, primidone, and phenobarbitone may cause asterixis. DPH, but not other anticonvulsants, may cause orofacial dyskinesias, limb chorea, and dystonia in intoxicated patients. These dyskinesias are similar to those caused by neuroleptic drugs and may be related to dopamine antagonistic properties possessed by DPH. | https://doi.org/10.1136/jnnp.39.12.1210 |
| E H Reynolds | The neurology of vitamin B12 deficiency. Metabolic mechanisms. | 1976 | Lancet (London, England) | 2;7990:832-833 | The widely held view that the neurological and haematological complications of vitamin-B12 deficiency have different metabolic mechanisms appears unsound. It is suggested that the metabolic mechanisms involved are similar and that the neurological manifestations are the result of a secondary disturbance in folate metabolism as has already been postulated for the megaloblastosis. | https://doi.org/10.1016/s0140-6736(76)91213-7 |
| E H Reynolds, D Chadwick, A W Galbraith | One drug (phenytoin) in the treatment of epilepsy. | 1976 | Lancet (London, England) | 1;7966:923-926 | Thirty-one, previously untreated, adult outpatients with idiopathic or focal grand-mal and/or focal minor seizures were treated initially with phenytoin. Serum-phenytoin concentrations were monitored to achieve an optimum range of 10-20 mug/ml if necessary. With a mean duration of follow-up of 14-7 months, only three (10%) patients have required the addition of a second drug, although without the guidance of serum concentrations sixteen (54%) might have been treated with a further drug. In the optimum serum-phenytoin range only 1 grand-mal attack occurred in this series, compared with a mean pre-treatment grand-mal seizure-rate of 1-1/month. Serum phenytoin declined slowly in fourteen (45%) patients. These observations suggest that many epileptic patients could be satisfactorily treated with one drug instead of the polypharmacy which they usually receive. | https://doi.org/10.1016/s0140-6736(76)92709-4 |
| M R Trimble, E H Reynolds | Anticonvulsant drugs and mental symptoms: a review. | 1976 | Psychological medicine | 6;2:169-178 | https://doi.org/10.1017/s0033291700013726 | |
| B D Ridge, E Fairhurst, D Chadwick, E H Reynolds | Ascorbic acid concentrations in human plasma and cerebrospinal fluid [proceedings]. | 1976 | The Proceedings of the Nutrition Society | 35;2:57- | https://doi.org/ | |
| E H Reynolds | Neurotoxicity of carbamazepine. | 1975 | Advances in neurology | 11;:345-353 | https://doi.org/ | |
| E H Reynolds, G Fenton, P Fenwick, A L Johnson, M Laundy | Interaction of phenytoin and primidone. | 1975 | British medical journal | 2;5971:594-595 | The ratio of derived phenobarbitone to unmetabolized primidone in the serum was significantly higher in 50 epileptic patients on a combination of primidone and phenytoin than in 12 patients on primidone alone, though the dose and serum levels of primidone were similar in the two groups. Out of 253 patients attending a seizure clinic 47% were taking a combination of these two anticonvulsants. The effect of phenytoin on the metabolism of primidone may have clinical implications in view of the frequency of their combined use. | https://doi.org/10.1136/bmj.2.5971.594 |
| E H Reynolds | Letter: Plasma levels of antidepressants and anticonvulsants. | 1975 | British medical journal | 1;5956:511- | https://doi.org/10.1136/bmj.1.5956.511-b | |
| E H Reynolds | Chronic antiepileptic toxicity: a review. | 1975 | Epilepsia | 16;2:319-352 | https://doi.org/10.1111/j.1528-1157.1975.tb06062.x | |
| E H Reynolds, D Chadwick, P Jenner, I Chanarin | Folate and monoamine metabolism in epilepsy. | 1975 | Journal of the neurological sciences | 26;4:605-615 | In 27 drug-treated epileptics there was a significant fall in serum, red cell and CSF folate levels compared with 15 untreated epileptics and 22 neurological controls. The 3 folate parameters were positively correlated with each other and negatively correlated with serum phenobarbitone, diphenylhydantoin and primidone. There was also a significant elevation of CSF 5-hydroxyindoleacetic acid (5HIAA) in the drug-treated epileptics; but this was not seen until "therapeutic" serum levels of phenobarbitone and diphenylhydantoin had been achieved and was most marked in clinically intoxicated patients. Similar trends were observed in CSF homovanillic acid (HVA). CSF 5HIAA and HVA were positively correlated with each other, especially in the drug-treated patients, in whom both amine metabolites were also negatively correlated with CSF folate. A possible relationship between folate and monoamine metabolism is discussed with particular reference to the antiepileptic and toxic effects of phenobarbitone, diphenylhydantoin and primidone. | https://doi.org/10.1016/0022-510x(75)90063-5 |
| D Chadwick, P Jenner, R Harris, E H Reynolds, C D Marsden | Manipulation of brain serotonin in the treatment of myoclonus. | 1975 | Lancet (London, England) | 2;7932:434-435 | The response of myoclonus to oral and intravenous L-5-hydroxytryptophan (5-H.T.P.) in combination with a peripheral decarboxylase inhibitor (carbidopa) and to clonazepam has been examined in 9 patients. Moderate improvement or complete cessation of myoclonus followed treatment with one or both of these regimens in 5 patients, 1 of whom also responded to the concurrent administration of L-tryptophan and a monoamineoxidase inhibitor. The remaining 4 patients were at best only slightly improved by either 5-H.T.P. or clonazepam. The responsive group consisted of 3 patients with a history of anoxia, 1 patient with non-history of severe head injury, and 1 patient with non-progressive focal myoclonus and epilepsy. This group had low levels of 5-hydroxyindole acetic acid in the lumbar cerebrospinal fluid. It is suggested that 5-H.T.P. plus carbidopa, L-tryptophan plus a monoamine-oxidase inhibitor, and clonazepam may all act by elevating brain levels of serotonin (5-H.T.) and that some human myoclonic syndromes may be specifically related to a cerebral deficiency of 5-H.T. | https://doi.org/10.1016/s0140-6736(75)90846-6 |
| E H Reynolds | Letter: Folate-responsive schizophrenia. | 1975 | Lancet (London, England) | 2;7926:189-190 | https://doi.org/10.1016/s0140-6736(75)90106-3 | |
| D Chadwick, P Jenner, E H Reynolds | Letter: Amines, anticonvulsants, and epilepsy. | 1975 | Lancet (London, England) | 1;7922:1425-1426 | https://doi.org/10.1016/s0140-6736(75)92639-2 | |
| M Trimble, D Chadwick, E H Reynolds, C D Marsden | Letter: L 5-Hydroxytryptophan and mood. | 1975 | Lancet (London, England) | 1;7906:583- | https://doi.org/10.1016/s0140-6736(75)91612-8 | |
| D Chadwick, P Jenner, E H Reynolds | Amines, anticonvulsants, and epilepsy. | 1975 | Lancet (London, England) | 1;7905:473-476 | Concentrations of 5-hydroxyindoleacetic acid (5-H.I.A.T.) in cerebrospinal fluid (C.S.F.) were significantly raised in twenty-seven anticonvulsant-treated epileptic patients compared with fifteen untreated epileptics and twenty-two neurological controls. This rise was not seen until therapeutic blood-levels of phenobarbitone and diphenylhydantoin had been achieved, and was most striking in clinically intoxicated patients. Similar trends were seen in C.S.F. homovanillic acid (H.V.A). There was a close correlation between C.S.F. 5-H.I.A.A. and H.V.A., especially in the treated epileptics. These findings have implications for the antiepileptic and toxic effects of anticonvulsant drugs. | https://doi.org/10.1016/s0140-6736(75)92827-5 |
| E H Reynolds | The value of serum diphenylhydantoin (phenytoin) levels in the management of epilepsy. | 1975 | Proceedings of the Royal Society of Medicine | 68;2:102-104 | https://doi.org/ | |
| P Jenner, D Chadwick, E H Reynolds, C D Marsden | Proceedings: Clonazepam-induced changes in 5-hydroxytryptamine (5-HT) metabolism in aminals and man. | 1975 | The Journal of pharmacy and pharmacology | 27;:38- | https://doi.org/ | |
| P Jenner, D Chadwick, E H Reynolds, C D Marsden | Altered 5-HT metabolism with clonazepam, diazepam and diphenylhydantoin. | 1975 | The Journal of pharmacy and pharmacology | 27;9:707-710 | https://doi.org/10.1111/j.2042-7158.1975.tb09539.x | |
| I Chanarin, J Perry, E H Reynolds | Transport of 5-methyltetrahydrofolic acid into the cerebrospinal fluid in man. | 1974 | Clinical science and molecular medicine | 46;3:369-373 | https://doi.org/10.1042/cs0460369 | |
| B N Slavin, G M Fenton, M Laundy, E H Reynolds | Serum immunoglobulins in epilepsy. | 1974 | Journal of the neurological sciences | 23;3:353-357 | https://doi.org/10.1016/0022-510x(74)90153-1 | |
| D Chadwick, E H Reynolds, C D Marsden | Letter: Relief of action myoclonus by 5-hydroxytryptophan. | 1974 | Lancet (London, England) | 2;7872:111-112 | https://doi.org/10.1016/s0140-6736(74)91683-3 | |
| E H Reynolds | Folate metabolism and anticonvulsant therapy. | 1974 | Proceedings of the Royal Society of Medicine | 67;1:68- | https://doi.org/ | |
| E H Reynolds, R D Travers | Serum anticonvulsant concentrations in epileptic patients with mental symptoms. A preliminary report. | 1974 | The British journal of psychiatry : the journal of mental science | 124;:440-445 | https://doi.org/10.1192/bjp.124.5.440 | |
| E H Reynolds | Iatrogenic nutritional effects of anticonvulsants. | 1974 | The Proceedings of the Nutrition Society | 33;3:225-229 | https://doi.org/10.1079/pns19740043 | |
| P Sneath, I Chanarin, H M Hodkinson, C K McPherson, E H Reynolds | Folate status in a geriatric population and its relation to dementia. | 1973 | Age and ageing | 2;3:177-182 | https://doi.org/10.1093/ageing/2.3.177 | |
| R H Mattson, B B Gallagher, E H Reynolds, D Glass | Folate therapy in epilepsy. A controlled study. | 1973 | Archives of neurology | 29;2:78-81 | https://doi.org/10.1001/archneur.1973.00490260022002 | |
| C D Marsden, E H Reynolds, V Parsons, R Harris, L Duchen | Myopathy associated with anticonvulsant osteomalacia. | 1973 | British medical journal | 4;5891:526-527 | https://doi.org/10.1136/bmj.4.5891.526 | |
| E H Reynolds, P Rothfeld, J H Pincus | Neurological disease associated with folate deficiency. | 1973 | British medical journal | 2;5863:398-400 | In a general medical hospital population the neurological status of 24 patients with severe folate deficiency was compared with that of a control group of 21 patients with normal serum folate. A significant increase of organic brain syndrome and pyramidal tract damage was found in the folate-deficient group. These findings were independent of the degree of anaemia or the presence of alcoholism. These data are consistent with the view that severe folate deficiency may cause neurological deficits. | https://doi.org/10.1136/bmj.2.5863.398 |
| E H Reynolds | Anticonvulsants, folic acid, and epilepsy. | 1973 | Lancet (London, England) | 1;7816:1376-1378 | https://doi.org/10.1016/s0140-6736(73)91690-5 | |
| R D Travers, E H Reynolds, B B Gallagher | Variation in response to anticonvulsants in a group of epileptic patients. | 1972 | Archives of neurology | 27;1:29-33 | https://doi.org/10.1001/archneur.1972.00490130031004 | |
| E H Reynolds | Anticonvulsant drugs, folate deficiency, and metabolic bone disease. | 1972 | British medical journal | 2;5814:656-657 | https://doi.org/10.1136/bmj.2.5814.656-a | |
| J H Pincus, E H Reynolds, G H Glaser | Subacute combined system degeneration with folate deficiency. | 1972 | JAMA | 221;5:496-497 | https://doi.org/ | |
| M B Bowers, E H Reynolds | Cerebrospinal-fluid folate and acid monoamine metabolites. | 1972 | Lancet (London, England) | 2;7791:1376- | https://doi.org/10.1016/s0140-6736(72)92831-0 | |
| E H Reynolds, B B Gallagher, R H Mattson, M Bowers, A L Johnson | Relationship between serum and cerebrospinal fluid folate. | 1972 | Nature | 240;5377:155-157 | https://doi.org/10.1038/240155a0 | |
| E H Reynolds, R H Mattson, B B Gallagher | Relationships between serum and cerebrospinal fluid anticonvulsant drug and folic acid concentrations in epileptic patients. | 1972 | Neurology | 22;8:841-844 | https://doi.org/10.1212/wnl.22.8.841 | |
| J Preece, E H Reynolds, A L Johnson | Relation of serum to red cell folate concentrations in drug-treated epileptic patients. | 1971 | Epilepsia | 12;4:335-340 | https://doi.org/10.1111/j.1528-1157.1971.tb04381.x | |
| E H Reynolds, R J Wrighton, A L Johnson, J Preece, I Chanarin | Inter-relations of folic acid and vitamin B 12 in drug-treated epileptic patients. | 1971 | Epilepsia | 12;2:165-171 | https://doi.org/10.1111/j.1528-1157.1971.tb03929.x | |
| E H Reynolds, J Preece, A L Johnson | Folate metabolism in epileptic and psychiatric patients. | 1971 | Journal of neurology, neurosurgery, and psychiatry | 34;6:726-732 | Serum and red cell folate levels and serum vitamin B(12) levels have been estimated in 33 normal controls; 34 epileptic outpatients, 19 of whom also suffered from psychiatric illness; 33 epileptic inpatients with psychiatric illness; and 30 non-epileptic inpatients with psychiatric illness. Significant lowering of serum folate and red cell folate levels was observed in epileptic patients with psychiatric illness, and a less significant fall in red cell folate levels was found in non-epileptic psychiatric patients. Serum folate levels less than 2·5 ng/ml. were found in two controls, seven outpatient epileptics, 29 inpatients, and 10 non-epileptic patients. Red cell folate levels less than 100 ng/ml. were found in two controls, nine outpatient epileptics, 23 inpatient epileptics, and seven non-epileptic patients. A significant correlation was found between serum and red cell folate values in control, epileptic, and non-epileptic patients. In the epileptic patients there was a significant association between low serum and red cell folate levels and the presence of psychiatric illness. The origin and possible significance of these findings are discussed. | https://doi.org/10.1136/jnnp.34.6.726 |
| E H Reynolds | Anticonvulsant drugs, folic acid metabolism, fit frequency and psychiatric illness. | 1971 | Psychiatria, neurologia, neurochirurgia | 74;2:167-174 | https://doi.org/ | |
| E H Reynolds, R J Wrighton, J M Preece, A L Johnson | Folate and vitamin B12 in epilepsy. | 1970 | British medical journal | 4;5729:246-247 | https://doi.org/10.1136/bmj.4.5729.246-c | |
| P T Lascelles, R S Kocen, E H Reynolds | The distribution of plasma phenytoin levels in epileptic patients. | 1970 | Journal of neurology, neurosurgery, and psychiatry | 33;4:501-505 | Plasma phenytoin levels were estimated in 111 adult epileptic patients. A wide scatter of values was found, with over half outside the therapeutic limits of 10 to 20 μg/ml. Phenytoin tolerance tests carried out in five patients revealed a possible failure to metabolize the drug adequately in three of them. Factors affecting the plasma phenytoin level are discussed. The importance of this assay is seen in view of the number of patients potentially at risk from toxic blood levels in the absence of accepted clinical manifestations of acute or subacute intoxication. | https://doi.org/10.1136/jnnp.33.4.501 |
| E H Reynolds | Water, electrolytes and epilepsy. | 1970 | Journal of the neurological sciences | 11;4:327-358 | https://doi.org/10.1016/0022-510x(70)90081-x | |
| E H Reynolds | Iatrogenic disorders in epilepsy. | 1970 | Modern trends in neurology | 5;:271-286 | https://doi.org/ | |
| E H Reynolds, J M Preece, J Bailey, A Coppen | Folate deficiency in depressive illness. | 1970 | The British journal of psychiatry : the journal of mental science | 117;538:287-292 | https://doi.org/ | |
| E H Reynolds, J Preece, I Chanarin | Folic acid and anticonvulsants. | 1969 | Lancet (London, England) | 1;7608:1264-1265 | https://doi.org/10.1016/s0140-6736(69)92144-8 | |
| E H Reynolds | Mental effects of anticonvulsants, and folic acid metabolism. | 1968 | Brain : a journal of neurology | 91;2:197-214 | https://doi.org/10.1093/brain/91.2.197 | |
| E H Reynolds | Epilepsy and schizophrenia: relationship and biochemistry. | 1968 | Lancet (London, England) | 1;7539:398-401 | https://doi.org/10.1016/s0140-6736(68)91359-7 | |
| E H Reynolds, I Chanarin, D M Matthews | Neuropsychiatric aspects of anticonvulsant megaloblastic anaemia. | 1968 | Lancet (London, England) | 1;7539:394-397 | https://doi.org/10.1016/s0140-6736(68)91358-5 | |
| E H Reynolds | Effects of folic acid on the mental state and fit-frequency of drug-treated epileptic patients. | 1967 | Lancet (London, England) | 1;7499:1086-1088 | https://doi.org/10.1016/s0140-6736(67)92654-2 | |
| E H Reynolds | Schizophrenia-like psychoses of epilepsy and disturbances of folate and vitamin B12 metabolism induced by anticonvulsant drugs. | 1967 | The British journal of psychiatry : the journal of mental science | 113;501:911-919 | https://doi.org/10.1192/bjp.113.501.911 | |
| E H Reynolds | Vitamin B12 and folate deficiencies. | 1967 | The British journal of psychiatry : the journal of mental science | 113;499:681-683 | https://doi.org/10.1192/bjp.113.499.681 | |
| J B Morley, E H Reynolds | Papilloedema and the Landry-Guillain-Barré syndrome. Case reports and a review. | 1966 | Brain : a journal of neurology | 89;2:205-222 | https://doi.org/10.1093/brain/89.2.205 | |
| E H Reynolds, I Chanarin, G Milner, D M Matthews | Anticonvulsant therapy, folic acid and vitamin B12 metabolism and mental symptoms. | 1966 | Epilepsia | 7;4:261-270 | https://doi.org/10.1111/j.1528-1157.1966.tb03806.x | |
| D M Matthews, E H Reynolds | Gastrointestinal function in anticonvulsant megaloblastic anaemia. | 1966 | Lancet (London, England) | 1;7430:210-211 | https://doi.org/10.1016/s0140-6736(66)90747-1 | |
| E H Reynolds, J F Hallpike, B M Phillips, D M Matthews | Reversible absorptive defects in anticonvulsant megaloblastic anaemia. | 1965 | Journal of clinical pathology | 18;5:593-598 | Two cases of anticonvulsant megaloblastic anaemia are described, showing features of unusual interest. Though both cases were apparently deficient in folic acid, the Figlu tests were negative. One patient had an extremely low serum B(12) concentration apparently associated with defective B(12) absorption due to deficiency of intrinsic factor, and both showed impaired intestinal absorption of D-xylose. There was, however, no evidence of permanent gastro-intestinal dysfunction, and the absorptive defects disappeared completely after treatment with folic acid. Possible reasons for the findings are discussed. It is suggested that absorptive defects produced by the drugs may play some part in initiating anticonvulsant megaloblastic anaemia, and that once deficiencies of haemopoietic factors are established, a vicious circle may be set up owing to the effects of these deficiencies on the gastro-intestinal tract. | https://doi.org/10.1136/jcp.18.5.593 |
| J MARSHALL, E H REYNOLDS | WITHDRAWAL OF ANTICOAGULANTS FROM PATIENTS WITH TRANSIENT ISCHAEMIC CEREBROVASCULAR ATTACKS. | 1965 | Lancet (London, England) | 1;7375:5-6 | https://doi.org/10.1016/s0140-6736(65)90919-0 | |
| J RHODES, E H REYNOLDS, J D FITZGERALD, P FOURMAN | EXAGGERATED RESPONSE TO PARATHYROID EXTRACT IN SARCOIDOSIS. | 1963 | Lancet (London, England) | 2;7308:598-601 | https://doi.org/10.1016/s0140-6736(63)90394-5 | |
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| https://doi.org/10.1016/s0140-6736(63)90394-5 |
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