Elan D Louis, MD, MS

Professor of Neurology and of Epidemiology (Chronic Diseases); Chief, Division of Movement Disorders; Co-director, Center for Neuroepidemiology and Clinical Neurological Research

Research Interests

Central Nervous System Diseases; Environment and Public Health; Humanities; Disorders of Environmental Origin; Nervous System Diseases; Neurologic Manifestations; Neurodegenerative Diseases; Neurotoxicity Syndromes

Public Health Interests

Aging; Biomarkers; Chronic Conditions; Dietary factors; Environmental Health; Genetic epidemiology; History of medicine; History of science; Neuroepidemiology; Risk assessment

Research Organizations

Neurology

School of Public Health: Chronic Disease Epidemiology

Center for Neuroepidemiology and Clinical Neurological Research

Lysosomal Disease & Inherited Metabolic Liver Disease Program

Extensive Research Description

Contributions to Science

Development of Clinical Rating Scales: When I entered the ET field in 1995, there were few ET-specific rating scales. Between 1995 and 2000, I assembled a population-based cohort of ET cases in the Washington Heights-Inwood community in northern Manhattan, NY (NIH K08 NS01863). The cohort was unprecedented in terms of its size and the level of detail we devoted to the clinical evaluation. In studying this cohort, I dedicated a great deal of effort to the development and validation of standardized assessment tools for ET. These included screening questionnaires, clinical rating scales, and functional assessments. These published assessment tools are now widely used in ET research. I also formulated research-grade diagnostic criteria for ET; these criteria are now used by tremor investigators worldwide.

a. Louis ED, Ottman RA, Ford B, Pullman S, Martinez M, Fahn S, Hauser WA. The Washington Heights Essential Tremor Study: Methodologic issues in essential-tremor research. Neuroepidemiology 1997;16:124-133.

b. Louis ED, Wendt KJ, Albert SM, Pullman SL, Yu Q, Andrews H. Validity of a performance-based test of function in essential tremor. Arch Neurol 1999;56:841-846.

Defining the Clinical Features of ET: ET is mis-diagnosed in 30 – 50% of cases, making it the most commonly mis-diagnosed movement disorder. One of the reasons for this is the over-simplified approach to the diagnosis and the relatively small number of papers that have carefully catalogued the clinical features. Over the past two decades, I have written numerous papers that have systematically dissected the clinical features of this disorder as well as attempted to precisely quantify its rate of progression. Among the novel concepts we have put forward and attempted to carefully substantiate over the past 20 years are that ET is a multifaceted neuropsychiatric disorder (with both motor and non-motor features) rather than a monosymptomatic entity. Also, as with Parkinson’s disease and Huntington’s disease, ET likely has a pre-motor stage ET.

a.Louis ED, Agnew A, Gillman A, Gerbin M, Viner AS. Estimating annual rate of decline: Prospective, longitudinal data on arm tremor severity in two groups of essential tremor cases. J Neurology Neurosurg Psychiatry 2011;82:761-765. PMCID: PMC3696191.

b. Thenganatt MA, Louis ED. Personality profile in essential tremor: A case-control study. Parkinsonism Related Disord 2012;18:1042-1044. PMCID: PMC3467349.

Descriptive and Analytic Epidemiology: When I entered the ET field 20 years ago, there was virtually no associated epidemiology. Besides my work on ET in the Washington Heights-Inwood population, in recent years I have had productive mentoring collaborations with investigators in Turkey (Dr. Dogu in Mersin, 2002 - present) and Spain (Dr. Benito-Leon in Madrid, 2004 - present), defining the prevalence, incidence, and clinical features of ET in population samples. I am particularly proud of our prevalence study in Turkey; because of its door-to-door design, it provides the most valid estimate of disease prevalence in the neurological literature. In addition, Dr. Benito-Leon and I have published the only population-based study of disease incidence and disease-associated mortality. Our studies have also shown that ET itself increases the risk for developing other degenerative disorders such as Alzheimer’s disease and Parkinson’s disease, and that ET may be associated with increased risk of mortality.

a. Benito-Leon J, Bermejo-Pareja F, Louis ED. Incidence of essential tremor in three elderly populations of central Spain. Neurology 2005;64:1721-1725.

b. Louis ED, Benito-Leon J, Ottman R, Bermejo-Pareja F. A population-based study of mortality in essential tremor.Neurology 2007;69:1982-1989.

Environmental Epidemiology: In 2000, I hypothesized that environmental toxins would likely be of etiological importance in ET. Previously, it had been assumed that the disease was genetic. Accordingly, I decided to study possible toxic/environmental exposures in ET (NIH 1R01 NS39422, 2000 - 2014). This line of investigation was unique at that time; since then, other investigators have followed suit. Through these studies, we were the first to identify several environmental exposures that are associated with ET, including the beta-carboline alkaloids (harmane) and possibly lead, suggesting that these ubiquitous toxins may play a role in the etiology of ET.

a. Louis ED. Etiology of essential tremor: Should we be searching for environmental causes? Mov Disord

2001;16:822-829.

b. Louis ED, Zheng W, Jurewicz EC, Watner D, Chen J, Factor-Litvak P, Parides M. Elevation of blood β-

carboline alkaloids in essential tremor. Neurology 2002;59:1940-1944.

Pathophysiology: In 2003, I decided to begin a new research effort to study the underlying disease mechanisms (i.e., pathogenesis) of ET. The existing dogma was that there was no identifiable pathology in ET. However, at that time, there were only 15 published postmortem brain examinations, many of which were performed 50 – 100 years ago. Hence, our understanding of the basic structural and neurochemical basis for ET was largely unexplored. In June of 2003, in collaboration with Dr. Jean Paul Vonsattel (Neuropathology), I established the Essential Tremor Centralized Brain Repository, which is an NIH-funded centralized repository for the collection and study of ET brains in the United States (NIH R01 NS42859, 2003 - present). It involves a nation-wide network of more than 400 ET patients who have signed up as brain donors and whom we follow regularly. We now have the largest collection of ET brains in the world, and the research has resulted in more than 40 papers that have identified underlying pathology in ET. Interestingly, our initial studies have revealed that, indeed, there is an identifiable pathology in ET, and that it is likely to be degenerative. Moreover, the pathology seems to be heterogeneous, segregating into two main patterns, suggesting that this disease could be a family of diseases rather than a single entity.

a. Louis ED, Faust PL, Vonsattel JPG, Honig LS, Rajput A, Robinson CA, Rajput A, Pahwa R, Lyons KE, Ross W, Borden S, Moskowitz CB, Lawton A, Hernandez N. Neuropathological changes in essential tremor: 33 cases compared with 21 controls. Brain 2007;130:3297-3307.

b. Babij R, Lee M, Cortés E, Vonsattel JPG, Faust PL, Louis ED. Purkinje cell axonal anatomy: Quantifying morphometric changes in essential tremor vs. control brains. Brain 2013;136:3051-3061. PMCID: PMC3784286.

NIH Funded Projects:

“Patholo-gomics”: Essential Tremor In The Broader Context of Neurodegeneration

NINDS R01 NS088257

Clinical-Pathological Study of Cognitive Impairment in Essential Tremor

NINDS R01 NS046436

In Vivo Quantification of Cerebellar GABA and NAA in Essential Tremor

NINDS R01 NS085136

Environmental Epidemiology of Essential Tremor

NINDS R01 NS39422

Pathogenesis of Essential Tremor: Cerebellar Metabolism

NINDS R01 NS42859

Identification of Susceptibility Genes for Essential Tremor

NINDS R01 NS073872

Selected Publications

Full List of PubMed Publications

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Contact Info

Elan D Louis, MD, MS
Patient Care Locations
Yale NeurologyYale Physicians Building
800 Howard Avenue, Ste Lower Level

New Haven, CT 06519
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260 Long Ridge Road
Stamford, CT 06902
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Yale NeurologyYale New Haven Hospital
20 York Street

New Haven, CT 06510
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Yale NeurologyYale New Haven Hospital Saint Raphael Campus
1450 Chapel Street

New Haven, CT 06511
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Mailing Address
LCI 710
15 York Street, PO Box 208018

New Haven, CT 06520-8018
Research Image 1

Model of essential tremor pathogenesis

Research Image 2

Calbindin immunohistochemistry on 100 µm cerebellar neocortex sections, 100x. (A) Normal control brain with thin visible axonal profiles. (B) Three torpedoes (arrow heads), two of which are on axons with recurrent collaterals (carets). Several thickened axonal profiles are shown (short arrows). (C) Terminal axonal sprouting (thick arrow). (D) Arciform axon profile; profile is also thickened. (E) Torpedoes (arrow heads) with axonal recurrent collaterals (carets) and axonal branching (long arrows and inset). (F) A visible portion of the recurrent collateral plexus at the Purkinje cell layer (boxed). (G) Thickened axonal profiles (short arrows).