When we set out to create this issue of Practical Neurology, I somewhat selfishly suggested autoimmune movement disorders because I have wanted to learn more about this rapidly expanding area that has blossomed with our increasing ability to identify antibodies. We didn’t know then that it would be published during a global pandemic, when everyone, from lay person to medical professional, was learning more about immunology than they may ever have wanted. When faced with an uncertain future, it is only natural to draw on past experiences, and many comparisons have been made between COVID-19 and the Spanish flu pandemic a century ago. The pathogens are different, but the all-consuming culture of science vs conspiracy is not, often bringing to mind the paraphrased aphorism, “Those who cannot learn from history are doomed to repeat it.”1

Perhaps one of the most famous autoimmune movement disorders is the result of the Spanish flu pandemic—Von Economo encephalitis, also known as encephalitis lethargica. First described in 1917 by Viennese neuropsychiatrist Dr. Constance Von Economo, who detailed symptoms of excessive somnolence followed by development of slow, rigid, parkinsonian motor symptoms in combination with compulsions and bradyphrenic nonmotor symptoms. The clinical picture was supported by pathologic findings in subcortical and midbrain regions, leading to localization—the foundation that is the crux of clinical correlation. Neurologic pathology is legitimized by our ability to localize a lesion. Von Economo’s astute documentation and persistent curiosity, from which we still benefit today, enriched our understanding of sleep and parkinsonian and psychiatric pathophysiology.

Encephalitis lethargica affected millions in 1917 to 1928, with peaks in 1920 and 1924 overlaying those of the Spanish flu from 1917 to 1920. Both acute and chronic forms were described. The acute phase was compartmentalized into 3 subtypes: somnolent-opthalmoplegic, hyperkinetic, and amyostatic-akinetic, whereas the chronic form, which could occur years later, was mainly parkinsonian. These classifications were helpful but arbitrary, considering almost any neurologic symptom could be among the constellation of features with day-to-day or even hour-by-hour shifts in presentation. These acute, rapid, and shifting symptoms raised the red flag of functional disorders, which until many of the antibodies discussed in this issue were discovered remained high on our list of differentials too.

The field of autoimmune movement disorders is experiencing its own Awakenings (a great movie about l dopa and encephalitis lethargica), which we attempt to cover in this issue. We begin with overviews of Autoimmune Movement Disorders in Adults by Dr. Balint and Autoimmune Movement Disorders in Children by Drs. Dutt, Hallman-Cooper, Bery, Shahnawaz, and Gombolay. Next, Drs. Shah and McKeon give us an extremely practical article on Utility of Autoantibody Profiles. From there, we take you through specific disorders, from the classic to the rare, with AntiNMDA Receptor Encephalitis by Dr. Anadani; Movement Disorders in Antiphospholipid Syndrome and Systemic Lupus Erythematosus by Drs. Shpiner, Dixon, Ortega, and Moore; Immune-Mediated Cerebellar Ataxia by Drs. Toso, Gleizer, and Dutra; and Stiff-Person Syndrome by Drs. Nolan and Nicholas. In this fast-paced field, we would be remiss not to have as our closing, Trending Autoantibodies Causing Movement Disorders by Drs. Benesh and Agnihotri.

We do well to remember that a peak of encephalitis lethargica occurred nearly 4 years after the peak of the Spanish flu. As we now experience and research the neurologic effects of COVID-19 in real time, we are called upon to be persistent investigators like those who have lived this before. There are many movements afoot in medicine, and nothing occurs in isolation. Current case reports and research often expose endemic issues of bias and racism in the culture of medicine. It is not an uncommon occurrence that medical breakthroughs and enhanced understanding that guide future research and clinical practice starts in tragedy or, in other cases, unethical beginnings. This is a fact of the history of medicine, and we must bear witness to the context of the culture in which all our lessons are realized, for again, those who do not learn from history. . .

1. Moreno, Daniel. Santayana the Philosopher: Philosophy as a Form of Life. Bucknell University Press, 2015. Translated by Charles Padron

2. Lutters B, Foley P, Koehler PJ. The centennial lesson of encephalitis lethargica. Neurology. 2018;90(12):563-567.

3. Hoffman LA, Vilensky JA. Encephalitis lethargica: 100 years after the epidemic. Brain. 2017;140(8):2246-2251.