Prisoners of Time
The Misdiagnosis of FDR’s 1921 Illness, and Why it Matters

by Armond S. Goldman, MD
with Daniel A. Goldman, MD, MPH


Table of Contents



List of Portraits

List of Figures

List of Tables

Foreword

Acknowledgments

Most Important People in This Story

Timeline of Main Events in FDR’s Illness

Chapter 1. Prologue

    Re-examination of FDR’s 1921 Illness in 2000
    Publication of the Investigation and Its Impact (2003)
    Reactions to the Publication
    Why This Book Was Written

Chapter 2. Prelude to the Illness

    FDR’s Childhood and Early Adulthood
    FDR’s Political Career Begins (1910)
    Election to New York Senate - “Typhoid Fever”
    Assistant Secretary of the Navy (1913)
    Acute Abdominal Illness (1915)
    United States Enters World War I (1917)
    FDR in Europe during World War I (1918)
    FDR Contracts Influenza (1918)
    Near End of FDR’s Marriage (1918)
    Mission to Europe - Tonsillectomy (1919)
    Vice Presidential Campaign (1920)

Chapter 3. Campobello Island

    Environment of the Island
    Journey to Campobello - Summer of 1921

Chapter 4. Acute Neurological Illness

    Onset (August 10, 1921)
    Dr. Eben Bennet’s Examination and Diagnosis
    Dr. William Keen’s Examination and Diagnosis
    The Illness Worsens
    Fears for the Family
    Dr. Samuel A. Levine’s Role in the Diagnosis of Polio
    Dr. Robert W. Lovett Diagnoses Paralytic Polio
    Further Progression of the Illness
    Regression to an Infantile State
    Dangers of Bladder Catheterizations
    Possible Nutritional Deficiencies
    Eleanor’s Nursing Care
    Fears for the Roosevelt Family during August 1921
    Plans to Transfer FDR to a New York Hospital

Chapter 5. Hospitalization in New York

    Transfer to New York City-Presbyterian Hospital
    Draper’s Assessment Letter to Lovett (September 24)
    Post-Hospitalization – Partial Recovery (10/21 - 1/22)

Chapter 6. Rehabilitation

    Decision to Rehabilitate and Reenter Politics
    Efforts to Rehabilitate (1922)
    Long Stay at Warm Springs (1924)
    Development of Warm Springs Institute (1925)

Chapter 7. Return to Public Life

    Governor of New York (1928)
    Health Assessment before First Presidential Run (1931)
    Elected President Four Times (1932-1945)

Chapter 8. Polio: Mid 19th to Early 20th Century

    Polio Epidemics Emerge In the Nineteenth Century
    Experimental Transmission of Poliomyelitis (1908)
    Simon Flexner Confirms Landsteiner’s Discovery (1908)
    What Happened After Those Discoveries
    Tragic 1916 Epidemic of Paralytic Poliomyelitis
    What Was Known About Poliomyelitis in 1921
    Seasonal Occurrence of Poliomyelitis

Chapter 9. The Diagnosis of Polio Persisted

    Expertise of FDR’s Physicians
    No Neurological Consultation in FDR’s Case
    Fears of Paralytic Poliomyelitis
    Development of Poliovirus Vaccines
        Unsuccessful First Efforts to Develop a Vaccine (1936)
        Discovery of How Poliovirus is Transmitted (1941)
        Polioviruses Cultured In Vitro (1948)
        Salk’s Killed Poliovirus Vaccine (Early 1950s)
        Preparations for Clinical Trials of Salk’s Vaccine
        Field Trials of Salk’s Poliovirus Vaccine (1954)
        Approval and Widespread Use of Salk’s Vaccine (1955)
        Salk Vaccines Contain Live Virus - Remedial Measures
        Success of Revised Killed Poliovirus Vaccine
        First Live Attenuated Poliovirus Vaccine
        Sabin’s Live Attenuated Poliovirus Vaccine
    Public Reminders of FDR’s Poliomyelitis
        Famous People with Poliomyelitis
        Sunrise at Campobello
        “The Waltons - The Easter Story”
        “American Experience - The Polio Crusade”
        The Roosevelts. An Intimate History

Chapter 10. Cause of FDR’s Illness Questioned

    Discovery at Windy Hill
    What to Do With the Discovery
    Plans to Reappraise FDR’s 1921 Neurological Illness

Chapter 11. Diagnostic Methods

    Art and Science of Medical Diagnosis
    Pattern Recognition
    Bayesian Analysis
    Reconstruction of the Pathogenesis

Chapter 12. Unlikely Causes of FDR’s Illness

    Coxsackie infection
    Rabies
    Viral encephalitis
    Botulism
    Tetanus
    Other Toxins
    Other Neurological Diseases
    Poliomyelitis and Guillain-Barré Syndrome Most Likely

Chapter 13. Was It Paralytic Poliomyelitis?

    Prior Exposure to Poliomyelitis
    Vigorous Exercise and Paralytic Poliomyelitis
    Prior Tonsillectomy and Bulbar Poliomyelitis
    Fever and Permanent Paralysis in Paralytic Polio
    Improbability of Paralytic Poliomyelitis

Chapter 14. Was It Guillain-Barré Syndrome?

    Discovery of Guillain-Barré Syndrome
        Octave Landry (1859)
        Louis Duménil (1864)
        Ernst von Leyden (1879)
        Georges Guillain, Jean Alexandre Barré, André Strohl (1916)
    Pattern Recognition Favors Guillain-Barré Syndrome

Chapter 15. Bayesian Analysis of Clinical Data

    Prior Probability of Guillain-Barré Syndrome
    Prior Probability of Paralytic Poliomyelitis
    Bayesian Analysis Greatly Favors GBS

Chapter 16. Pathogenesis of FDR’s Illness

    Poliomyelitis
        Initial Infection and Multiplication
        Systemic Spread of Polioviruses
        Uptake and Transport by Motor Nerve Axons
        Paralytic Poliomyelitis Inconsistent with FDR’s Illness
    Guillain-Barré Syndrome
        Role of Prior Infections in GBS
        Experimental Animal Model of Guillain-Barré Syndrome
        Inadvertent Creation of GBS by Treatment with Gangliosides
        Swine Flu Vaccine Triggers Guillain-Barré Syndrome
        Possible Association of GBS with Zika Virus
        Autoantibodies Interfere with Nerve Function and Repair
        Features of Main Inciting Agent - Campylobacter jejuni
        Epidemics of Guillain-Barré Syndrome in Children
        Principal Immunogens in Pathogenic Campylobacter
        Possible Past Campylobacter jejuni Infections in FDR
    Other Autoimmune Neuropathies
    FDR’s Illness Most Consistent with GBS

Chapter 17. Was FDR Close to Death in 1921?

    Potential Respiratory Failure
    Lack of Artificial Respiratory Assistance
    Lack of Other Supportive Measures
    Other Potential Health Threats
    Eleanor Saved FDR’s Life

Chapter 18. Could FDR’s Outcome Have Been Improved?

    Current Medical Management of GBS
    Immunotherapy of Guillain-Barré Syndrome
    Rehabilitation of Patients with GBS

Chapter 19. Other Famous People with GBS

    Dr. Harvey Williams Cushing
        Military Service in World War I
        Cushing’s Neurological Illness (1918)
        Analysis of Cushing’s Illness
        Attendance at Meeting With George Guillain (11-11-1918)
        What Might Have Been
    Joseph Heller
        Heller’s Neuropathy
        Life in Intensive Care
        Rehabilitation
    Insights from the Cushing and Heller Cases

Chapter 20. Responses to Critics of GBS Diagnosis

    Historian David Oshinksy (2005)
    Historian Susan Richards Shreve (2007)
    Historian Jean Edward Smith (2007)
    Physicians Gareth Parry and Joel Steinberg (2008)
    Physician Zachary Friedenberg (2009)
    Physician Stephen Lomazow (2010)
    Historian James Tobin (2013)
    Physicians Ditunno, Becker, and Herbison (2016)

Chapter 21. Confirmation Bias

    Recognition of Confirmation Bias
    N-Rays
    Confirmation Bias in Medical Practice
    Possible Confirmation Bias in FDR’s Case
    Escalation of Confirmation Bias in FDR’s Case

Chapter 22. Epilogue

    Beliefs Subject to Change
    A Cautionary Tale
    Irony of the Misdiagnosis
    Prisoners of Time
    What If FDR Had Died?
    Why it Matters
    Last Words?

Appendix A. Bayesian Analysis Explained

Appendix B. Overall Bayesian Probabilities

Appendix C. Pathogenesis Example

Appendix D. Letters and Telegrams

Appendix E. Dr. Levine’s "Unpublished Note"

References

Glossary

Index

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