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April 2016

In Memoriam: John F. Kurtzke, MD (1926-2015)A Founding Father of Neuroepidemiology and Pioneer of Modern Clinical Trial Design

Author Affiliations
  • 1Department of Ophthalmology, University of Texas Southwestern School of Medicine, Dallas
  • 2Department of Neurology and Neurotherapeutics, University of Texas Southwestern School of Medicine, Dallas
  • 3Department of Bioengineering and Computer Science, University of Texas, Dallas
  • 4Department of Behavioral and Brain Sciences, University of Texas, Dallas
  • 5Department of Neurology, Wayne State School of Medicine, Detroit, Michigan
  • 6Department of Immunology and Microbiology, Wayne State School of Medicine, Detroit, Michigan

Copyright 2016 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

JAMA Neurol. 2016;73(4):482-483. doi:10.1001/jamaneurol.2016.0030

On December 1, 2015, we lost one of the most influential contributors to the field of medical epidemiology, and in particular the man who is credited for performing the most systematic exploration of the geographic distribution patterns for the most common disabling neurologic disorder of young people, multiple sclerosis (MS). John F. Kurtzke, MD, graduated from the Cornell Medical College in 1952, and by 1956 he had ascended to the position of chief of neurology for the Veterans Administration in Coatesville, Pennsylvania. He would later serve as professor of neurology at Georgetown University from 1963 to 1995, during which time he conducted some of the most seminal investigations that collectively helped to establish the field of neuroepidemiology.

John F. Kurtzke, MD

The role of one or more environmental factors, including infections, as a critical factor in the pathogenesis of MS is now widely recognized. It was Kurtzke’s pioneering work that brought forth some of the most persuasive evidence to date supporting a putative role for an infectious agent as a contributing factor in MS.

When the presence of the disorder was nearly unheard of on the remote Faeroe Islands and in Iceland, the recording of many cases of MS following the occupation of these territories by the British troops during World War II fostered Kurtzke’s exploration into the infectious etiologic hypothesis as a contributing factor in the development of MS.18

The contemporary framework for the pathobiological underpinnings of MS is now most consistent with that of an epigenetic disorder predicated on genetic, environmental, nutritional, and behavioral factors, in conjunction with a factor acting as a trigger or “ignition switch.” Kurtzke’s observations and interpretive conclusions resonate with contemporary thinking, particularly given his hypothesis that a modifying etiological factor for developing MS appeared to be influenced by the location, with respect to equatorial latitude, of early life development, with mounting evidence that corroborates the postulated role of vitamin D as a critical mitigating influence potentially linked to its relationship to immune regulatory networks and the derivative achievement of self-tolerance.

Kurtzke’s second major accomplishment was the development of the disability status scale score, which catapulted the clinical assessment within clinical trials from the reporting of the assessor’s subjective impressions to the establishment of an objective, reproducible, and stereotyped gold-standard neurological examination and status ascertainment.9,10 This formidable contribution to the field of medical therapeutics resulted in the transformation of clinical trial design for MS in particular and set forth objective standards for the characterization of clinical outcomes to be emulated for disabling neurologic disorders in general.

Originally proposed in 1955 and 1961, Kurtzke formulated an ordinal scale for the application in MS drug trials (initially for the assessment of isoniazid as a treatment for MS) as a means to objectify the effects of putative therapies on the clinical disposition of neurologic disability in MS.9

Initially conceived as a scale from 0 (no evidence of signs, symptoms, or report of disabling changes in neurologic functioning or status) to 10 (death due to MS or its complications), the scale was later transformed into 0.5-point steps (the Expanded Disability Status Scale score) to account for the functional integrity of each of the functional system scales such as abnormalities affiliated with each of the components of the neurological examination: vision, brainstem functions, pyramidal functions (strength, reflexes, tone), cerebellar functions, sensory functions, bowel-bladder-sexual functions, cerebral functions (depression, euphoria, reduced mentation), and ambulation.10

The scale is an ordinal scale, heavily weighted on the impact and deterioration in walking, other motor functions, and, to a degree, sensory and visual functions. Notwithstanding the ordinal nature of the scale, the heavy bias on ambulation, and the subordination of critical functional deficits such as cognition and fatigue that contribute to disability and severity and are often major factors in the loss of gainful employment for patients with MS, the scale has remained the iconic gold standard for the assessment of disability, against which every attempted new iteration and new scale is compared.

For his monumental contributions to the field, Kurtzke was awarded the 1997 John Dystel Prize for MS Research by the American Academy of Neurology and the National Multiple Sclerosis Society, and in 1999 he received the highly coveted Charcot Award. In his honor, the Consortium of Multiple Sclerosis Centers, the Foundation of the CMSC, the American Academy of Neurology, and the American Brain Foundation created the John F. Kurtzke Clinician-Scientist Development Award, a 3-year training grant to promote and foster the next generation of MS physician investigators.

John F. Kurtzke was a gentleman of the “old school,” a devoted family man, and an active member of the MS community until his death. He could always be seen at the American Academy of Neurology meetings and at MS specialty meetings at platform and poster sessions, interacting with colleagues of long standing and in particular with junior colleagues including residents, fellows, and students. The use of the term giant has been used perhaps too readily but not here. Kurtzke was indeed a giant and a legend in the field of neurology.

Our sympathies go out to his wife Peggy and his family.

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Article Information

Corresponding Author: Elliot M. Frohman, MD, PhD, Department of Neurology and Neurotherapeutics, University of Texas Southwestern School of Medicine, 5323 Harry Hines Blvd, Dallas, TX 75390 (

Conflict of Interest Disclosures: None reported.

Kurtzke  JF, Hyllested  K.  Multiple sclerosis in the Faroes, 1: clinical and epidemiologic features. Trans Am Neurol Assoc. 1978;103:201-205.
Kurtzke  JF, Hyllested  K.  Multiple sclerosis in the Faroe Islands, I: clinical and epidemiological features. Ann Neurol. 1979;5(1):6-21.
Kurtzke  JF, Hyllested  K.  Multiple sclerosis in the Faroe Islands, II: clinical update, transmission, and the nature of MS. Neurology. 1986;36(3):307-328.
Kurtzke  JF, Hyllested  K.  Multiple sclerosis in the Faroe Islands, III: an alternative assessment of the three epidemics. Acta Neurol Scand. 1987;76(5):317-339.
Kurtzke  JF, Hyllested  K.  Validity of the epidemics of multiple sclerosis in the Faroe Islands. Neuroepidemiology. 1988;7(4):190-227.
Kurtzke  JF, Hyllested  K, Arbuckle  JD,  et al.  Multiple sclerosis in the Faroe Islands, IV: the lack of a relationship between canine distemper and the epidemics of MS. Acta Neurol Scand. 1988;78(6):484-500.
Kurtzke  JF, Hyllested  K, Heltberg  A, Olsen  A.  Multiple sclerosis in the Faroe Islands, 5: the occurrence of the fourth epidemic as validation of transmission. Acta Neurol Scand. 1993;88(3):161-173.
Jersild  C, Kurtzke  JF, Riisom  K, Heltberg  A, Arbuckle  J, Hyllested  K.  Multiple sclerosis in the Faroe Islands, VI: studies of HLA markers. Tissue Antigens. 1993;42(2):105-110.
Kurtzke  JF.  A new scale for evaluating disability in multiple sclerosis. Neurology. 1955;5(8):580-583.
Kurtzke  JF.  Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11):1444-1452.