Stanley Fahn Research Articles

Elucidating Mechanism of Ammonia Toxicity Using Cortical Organoids (P5-7.001)

<h3>Objective:</h3> This study seeks to understand the cell type-specific changes that occur from acute ammonia exposure in the brain. We used cortical organoids derived from human inducible pluripotent stem cells because they reproduce aspects of spatial organization and cellular diversity seen <i>in vivo</i>. Importantly, cortical organoids contain neurons and astrocytes that are structurally juxtaposed, an intercellular interaction that is likely critical in acute ammonia toxicity. <h3>Background:</h3> Hyperammonemia is a common clinical outcome from a variety of pathologies including acute liver failure. At high levels, ammonia can produce cerebral edema and in severe cases result in brain herniation and death. Edema is thought to result from astrocyte swelling, but the precise mechanism of ammonia toxicity remains unknown. A better understanding of the cellular pathways involved will lead to targeted therapies and improved clinical outcomes. <h3>Design/Methods:</h3> Cortical organoids were exposed to supraphysiological levels of ammonia for 24 hours. Following exposure, organoids were dissociated and immunopanned to purify astrocytes and neurons. Gene expression changes between ammonia and unexposed samples were identified in a cell-specific manner. Gene ontology analysis was conducted to detect cellular pathways that are perturbed due to ammonia exposure. <h3>Results:</h3> Organoids exposed to high ammonia retained their structural integrity. Molecularly, we observed changes common to both neurons and astrocytes as well as cell-type specific signatures. Both astrocytes and neurons demonstrated upregulation of genes involved in cholesterol biosynthesis and lipid metabolism though a greater number of genes were upregulated in astrocytes, suggesting a possible link between these pathways in the setting of hyperammonemia. <h3>Conclusions:</h3> These results demonstrate a cell type-specific response following acute ammonia exposure and suggest cholesterol synthesis and lipid metabolism may play a role in ammonia toxicity. In future work, we will study cell type-specific functional consequences and proteomic changes to better understand how astrocytes and neurons responds to high ammonia environments. <b>Disclosure:</b> Dr. Barton has nothing to disclose. Ms. King has nothing to disclose. Mr. Sing has nothing to disclose. The institution of Dr. Sampson has received research support from NIH NIEHS K00. The institution of Dr. Sampson has received research support from Burroughs Wellcome Fund PDEP. The institution of an immediate family member of Dr. Sampson has received research support from Parkinsons Foundation. The institution of an immediate family member of Dr. Sampson has received research support from Parkinsons Foundation Stanley Fahn. The institution of an immediate family member of Dr. Sampson has received research support from ASAP Collab Network. The institution of an immediate family member of Dr. Sampson has received research support from NIEHS. An immediate family member of Dr. Sampson has received intellectual property interests from a discovery or technology relating to health care. Dr. Sloan has nothing to disclose.

Editorial introductions.

Current Opinion in Neurology was launched in 1988. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of neurology is divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Martin J. McKeownMartin J. McKeownDr McKeown is the John Nichol Chair in Parkinson's Research, Director at the Pacific Parkinson's Research Centre (PPRC), Professor in the Department of Medicine, and adjunct professor in the Department of Electrical and Computer Engineering at the University of British Columbia, Canada. The PPRC is deemed an International Centre of Excellence by the (US-based) Parkinson's Foundation. He did his Engineering Physics, Medicine and Neurology training at McMaster, University of Toronto, and University of Western Ontario, Canada respectively. He did a three-year research fellowship at the Computational Neurobiology Laboratory at the Salk Institute for Biological Studies in San Diego before being hired as an Assistant Professor of Medicine and Biomedical Engineering at Duke University, USA. He was recruited to UBC in 2003. He is currently the Medical Advisor to the Parkinson's Society of BC, and Chair, Research and Clinical Advisory committee, Parkinson Canada. His research interests include privacy-compliant video monitoring technologies for Parkinson's disease and non-invasive neuromodulation. Marie VidailhetMarie VidailhetMarie Vidailhet is Professor of Neurology, Head of the Movement Disorders section and of the Dystonia and rare movement disorders National Reference Centre at Salpêtrière Hospital, Sorbonne Université, France; Head of the Research Team (Movement, investigations, and of the Therapeutics MOV’IT research group) at Paris Brain Institute, ICM (co-head Stephane Lehéricy), Paris, France, focused on the pathophysiology of motor and behaviour dysfunctions in movement disorders including dystonia, tremor and Tourette syndrome. She part of the ERN (European Reference Network) and of several international working groups in movement disorders and Parkinson's disease. She held the positions of Head of Neurology Department, Saint-Antoine University Hospital, Pierre et Marie Curie University, from 1997 to 2007, and previously of Assistant Professor, then Associate Professor in Salpêtriere, Paris, France. As a Visiting Research Fellow, Institute of Neurology, Queen Square, London, UK, she worked at the Human Movement Balance Unit research section London, UK with Pr CD Marsden, JC Rothwell and Ph Thompson. She is involved in the Movement Disorders Society including the MDS-ES (European section) and in the European Academy of Neurology (EAN) as board, and in international mentorship and fellowships programs (EAN, MDS). She was Vice-chair du COST action BM1101 European network for dystonia. She co-authored over 400 publications (total H index 85) with her group, with a focus on pathophysiology of dystonia, tremors and Tourette syndrome, deep brain stimulation and non-invasive stimulation both for research and experimental therapeutics. The other focus is multimodal/neuroimaging characterization of Parkinson's disease and isolated REM sleep disorders, current research programs, JP-RD Eurodyscover E-Rare (Europe), Dystonia Coalition (USA) on dystonia and several collaborative programs on Parkinson's disease. She was awarded the MDS Presidential lecture (Stanley Fahn Lecture) and the Prix Memin-Pelletier (Biology) French Academy of Science.

Recent advancements toward non-invasive imaging of retinal amyloid-beta for early detection of Alzheimer's disease.

Recent advancements toward non-invasive imaging of retinal amyloid-beta for early detection of Alzheimer's disease.

A brief history of neurological botulinum toxin therapy in Germany.

Botulinum toxin (BT) has long been infamous in food safety and biological warfare. In the early 1970s, Alan B Scott of San Francisco invented its therapeutic use originally in extraocular eye muscles to treat strabismus using a therapeutic BT type A preparation provided by Edward J Schantz and Eric A Johnson. Subsequently a large number of medical indications based on motor and glandular hyperactivity and-most recently-chronic migraine are now treated by BT therapy. BT's highly specific and elaborate mechanism of action represents a completely novel therapeutic principle which will have consequences far beyond existing indications. BT therapy entered neurology through Stanley Fahn in New York from where C David Marsden brought it to London. From here neurological BT therapy came to Germany through Reiner Benecke and Dirk Dressler. Ophthalmological BT therapy was brought directly to Germany by Peter Roggenkämper, a fellow of Scott. By the early 1990s, several users in Germany had learned about BT therapy and made the country one of the most productive countries in clinical BT science-backed up by a long tradition of solid basic BT research. For several years now, however, BT therapy in Germany has been stagnating due to a lack of reimbursement for the medical treatment and due to off-label use challenges.

2 Movement disorders – the parkinson’s névrose

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

Clinical and scientific perspectives on movement disorders: Stanley Fahn's contributions.

Dr. Stanley Fahn, the H. Houston Merritt Professor of Neurology and Director Emeritus of the Center for Parkinson's Disease and Other Movement Disorders at Columbia University, one of the founders of the field of movement disorders, was the first president of the Movement Disorders Society (subsequently renamed as the International Parkinson and Movement Disorder Society). Together with his friend and colleague, Professor David Marsden, he also served as the first co-editor of the journal Movement Disorders. By emphasizing phenomenology as the key element in differentiating various hypokinetic and hyperkinetic movement disorders, Dr. Fahn drew attention to the clinical history and the power of observation in the diagnosis of movement disorders. Dr. Fahn had major influence on the development of classifications and assessments of various movement disorders and in organizing various research groups such as the Parkinson Study Group. As the founder and president of the World Parkinson Coalition and an organizer of the initial three World Parkinson Congresses, he has demonstrated his long-standing commitment to the cause of including patients as partners. The primary goal and objective of this invited review is to highlight some of Dr. Fahn's most impactful scientific and clinical contributions to the understanding and treatment of Parkinson's disease, dystonia, and other movement disorders.

Psychogenic Movement DisordersPsychogenic Movement Disordersby HallettMarkLangAnthony E.JankovicJosephFahnStanleyHalliganPeterVoonValerieCloningerC. Robert336 pp., Cambridge University Press, 2011, $120

Psychogenic Movement Disorders by Mark Hallett, Anthony E. Lang, Joseph Jankovic, Stanley Fahn, Peter Halligan, Valerie Voon, C. Robert Cloninger 336 pp., Cambridge University Press, 2011, $120 This multi-author (and multi-editor) book is generally well …

Charles David Marsden. 15 April 1938 — 29 September 1998

David Marsden was the most outstanding UK clinical neuroscientist of his generation, making key discoveries in the neurophysiology, neurochemistry and clinical aspects of diseases of the basal ganglia, and their normal function. His legacies are the establishment, with Stanley Fahn in the USA, of movement disorders as a subspecialty within neurology, of the international Movement Disorder Society, and of the journal Movement Disorders ; his ex-students and fellows around the globe; and his research and teaching output embodied in his extraordinarily prolific publication record of more than 1360 papers, books and chapters, culminating in the posthumous completion and publication in December 2011 of Marsden’s book of movement disorders , a project he had started in 1984. All of these were achieved through the combination of his intellect and drive, his communication skills, and his forceful and charismatic personality.

Book Review: PRINCIPLES AND PRACTICE OF MOVEMENT DISORDERS

edited by Stanley Fahn and Joseph Jankovic , 631 pp., Philadelphia, Churchill Livingstone, 2007, $199 Movement disorders is a complex field in neurology and clinical phenomenology is usually the first step in differential diagnosis. Principles and Practice of Movement Disorders, written by Drs. Stanley Fahn and Joseph Jankovic, provides a comprehensive overview of this field, and the complementary DVD with high-quality video clips help readers to recognize the clinical phenomenology. It contains concise clinical information and the scientific basis of all major aspects of movement disorders. This book is very well-written, and in a reader-friendly style. Most importantly, in contrast to most major neurology textbooks, this book is mainly written by only …

Susan Bressman: deciphering dystonia in the Big Apple

Susan Bressman: deciphering dystonia in the Big Apple

MOVEMENT DISORDER EMERGENCIES: DIAGNOSIS AND TREATMENT

MOVEMENT DISORDER EMERGENCIES: DIAGNOSIS AND TREATMENT Steven J. Frucht and Stanley Fahn , 250 pp., Humana Press, 2005, $135.00 Movement disorders are typically recognized for their gradual evolution and progressive insinuation into the life of the patient. On casual consideration, many neurologists are likely disinclined to carry a robust differential diagnosis of emergent movement situations to the emergency department with them. For this reason, …

Stanley Fahn Lecture 2005: The staging procedure for the inclusion body pathology associated with sporadic Parkinson's disease reconsidered

The synucleinopathy known as sporadic Parkinson's disease (PD) is a multisystem disorder that severely damages predisposed nerve cell types in circumscribed regions of the human nervous system. A recent staging procedure for the inclusion body pathology associated with PD proposes that, in the brain, the pathological process (formation of proteinaceous intraneuronal Lewy bodies and Lewy neurites) begins at two sites and continues in a topographically predictable sequence in six stages, during which components of the olfactory, autonomic, limbic, and somatomotor systems become progressively involved. In stages 1 to 2, the Lewy body pathology is confined to the medulla oblongata/pontine tegmentum and anterior olfactory structures. In stages 3 to 4, the substantia nigra and other nuclei of the basal mid- and forebrain become the focus of initially subtle and, then, severe changes. During this phase, the illness probably becomes clinically manifest. In the final stages 5 to 6, the lesions appear in the neocortex. This cross-sectional study originally was performed on 168 autopsy cases using material from 69 incidental cases and 41 clinically diagnosed PD patients as well as 58 age- and gender-matched controls. Here, the staging hypothesis is critically reconsidered and discussed.

Movement disorder emergencies

For the past 4 years, Dr. Stanley Fahn and I have given a course at the American Academy of Neurology annual meeting on the topic of movement disorder emergencies. The purpose of this review article is to summarize the topic and to present it to readers of this journal. The text of this article has appeared in nearly the same form as the Academy syllabus accompanying our course. It is being presented here so that readers of the journal may review the material.

High-Dosage Vitamin E Supplementation and All-Cause Mortality

Letters19 July 2005High-Dosage Vitamin E Supplementation and All-Cause MortalityConnie Marras, MD, Anthony E. Lang, MD, David Oakes, PhD, Michael P. McDermott, PhD, Karl Kieburtz, MD, MPH, Ira Shoulson, MD, Caroline M. Tanner, MD, PhD, and Stanley Fahn, MDConnie Marras, MDFrom the University of Toronto, Toronto, Ontario MST 258, Canada; University of Rochester Medical Center, Rochester, NY 14642; The Parkinson's Institute, Sunnyvale, CA 94809-1605; and Columbia University, New York, NY 10032.Search for more papers by this author, Anthony E. Lang, MDFrom the University of Toronto, Toronto, Ontario MST 258, Canada; University of Rochester Medical Center, Rochester, NY 14642; The Parkinson's Institute, Sunnyvale, CA 94809-1605; and Columbia University, New York, NY 10032.Search for more papers by this author, David Oakes, PhDFrom the University of Toronto, Toronto, Ontario MST 258, Canada; University of Rochester Medical Center, Rochester, NY 14642; The Parkinson's Institute, Sunnyvale, CA 94809-1605; and Columbia University, New York, NY 10032.Search for more papers by this author, Michael P. McDermott, PhDFrom the University of Toronto, Toronto, Ontario MST 258, Canada; University of Rochester Medical Center, Rochester, NY 14642; The Parkinson's Institute, Sunnyvale, CA 94809-1605; and Columbia University, New York, NY 10032.Search for more papers by this author, Karl Kieburtz, MD, MPHFrom the University of Toronto, Toronto, Ontario MST 258, Canada; University of Rochester Medical Center, Rochester, NY 14642; The Parkinson's Institute, Sunnyvale, CA 94809-1605; and Columbia University, New York, NY 10032.Search for more papers by this author, Ira Shoulson, MDFrom the University of Toronto, Toronto, Ontario MST 258, Canada; University of Rochester Medical Center, Rochester, NY 14642; The Parkinson's Institute, Sunnyvale, CA 94809-1605; and Columbia University, New York, NY 10032.Search for more papers by this author, Caroline M. Tanner, MD, PhDFrom the University of Toronto, Toronto, Ontario MST 258, Canada; University of Rochester Medical Center, Rochester, NY 14642; The Parkinson's Institute, Sunnyvale, CA 94809-1605; and Columbia University, New York, NY 10032.Search for more papers by this author, and Stanley Fahn, MDFrom the University of Toronto, Toronto, Ontario MST 258, Canada; University of Rochester Medical Center, Rochester, NY 14642; The Parkinson's Institute, Sunnyvale, CA 94809-1605; and Columbia University, New York, NY 10032.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-143-2-200507190-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In a meta-analysis of selected randomized trials, Miller and colleagues (1) found an increase in all-cause mortality associated with high-dosage vitamin E supplementation for at least 1 year (1). Their analysis included the DATATOP study, a randomized, placebo-controlled trial of selegiline and vitamin E in 800 patients with early Parkinson disease (2). In the DATATOP trial, 399 of 800 participants were randomly assigned to receive 2000 IU of vitamin E per day, the highest dosage studied in Miller and colleagues' meta-analysis. Median duration of vitamin E exposure during the randomized phase was 2.6 years. We have now ...

Mental and Behavioral Dysfunction in Movement Disorders

Mental and Behavioral Dysfunction in Movement Disorders

Dystonia. Volume 94, Advances in Neurology. 2004. Edited by Stanley Fahn, Mark Hallett, Mahlon R. DeLong. Published by Lippincott Williams and Wilkins, Philadelphia. 312 pages. C$220 approx.

Dystonia. Volume 94, Advances in Neurology. 2004. Edited by Stanley Fahn, Mark Hallett, Mahlon R. DeLong. Published by Lippincott Williams and Wilkins, Philadelphia. 312 pages. C$220 approx. - Volume 31 Issue 3

ADVANCES IN NEUROLOGY, VOL. 89: MYOCLONUS AND PAROXYSMAL DYSKINESIAS

ADVANCES IN NEUROLOGY, VOL. 89: MYOCLONUS AND PAROXYSMAL DYSKINESIAS Edited by Stanley Fahn, Steven J. Frucht, Mark Hallett and Daniel D. Truong 2002. Lippincott Williams & Wilkins Price £130. pp. 528. ISBN 0781737591 This book is the product of a symposium held in Atlanta in October 2000. The symposium was planned as tribute to the late C. David Marsden and the book is dedicated to his memory. It comprises 43 chapters with contributions from almost 100 authors and represents a comprehensive review of the subject and recent developments. Myoclonus, defined as sudden, brief, shock‐like involuntary movement caused by muscular contraction or inhibition, can arise from any level of the nervous system (cerebral cortex, brainstem, spinal cord and peripherally) and is caused by a wide variety of neurological and systemic disorders. Detailed neurophysiology and advances in molecular biology have lead to a better understanding of the pathophysiology of myoclonus in different disorders, but with only one randomised controlled trial in the treatment of myoclonus, there is only limited evidence on which to base treatment. Valproate and clonazepam, which are frequently used in the treatment of myoclonus, have not been systematically studied. Paroxysmal dyskinesias are …

Placebo surgery for Parkinson's disease: do the benefits outweigh the risks?

In April 1999, Dr. Curt Freed of the University of Colorado in Denver and Dr. Stanley Fahn of Columbia Presbyterian Center in New York presented the results of a four-year, $5.7 million government-financed study using tissue from aborted fetuses to treat Parkinson’s disease at a conference of the American Academy of Neurology. The results of the first government-financed, placebo-controlled clinical study using fetal tissue showed that the symptoms of some Parkinson’s patients had been relieved. This research study involved forty subjects, nineteen women and twenty-one men; all suffered from Parkinson’s disease for an average of 13.5 years. In the study, each subject underwent neurosurgery: “four tiny burr holes, drilled through the wrinkle lines above the eyebrows into the skull, to clear a pathway to the brain. But only half received injections of fetal cells into the putamen, the region of the brain that controls movement; the other half received nothing. One year later, three members of the placebo group said their symptoms had improved.” In two-thirds of the transplant recipients, the fetal tissue took hold and seemed to establish a new network to produce the missing neurochemical dopamine.

Movement disorders 1 and 2 reissue (Blue Books Of Practical Neurology).Editors: C. David Marsden and Stanley Fahn, Oxford, UK, Butterworth-Heinemann, 1995, 379 and 468 pp., ill., $135.00

Movement disorders 1 and 2 reissue (Blue Books Of Practical Neurology).Editors: C. David Marsden and Stanley Fahn, Oxford, UK, Butterworth-Heinemann, 1995, 379 and 468 pp., ill., $135.00

Editorial

Movement DisordersVolume 10, Issue 1 p. 1-1 Editorial Editorial Stanley Fahn, Stanley FahnSearch for more papers by this authorC. David Marsden, C. David MarsdenSearch for more papers by this author Stanley Fahn, Stanley FahnSearch for more papers by this authorC. David Marsden, C. David MarsdenSearch for more papers by this author First published: January 1995 https://doi.org/10.1002/mds.870100102Citations: 4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume10, Issue1January 1995Pages 1-1 RelatedInformation