CONSCIOUSNESS REDUX NEUROPATHOLOGY Sleep without End A long-forgotten epidemic teaches us about the science of slumber Unity Kinkaid finds it harder and harder to stay awake. She now sleeps for almost 20 hours a day. She used to dream; to shift in her sleep, muttering and sighing, locked in half-remembered fanta- sies ... Now she lies unmoving, breath shallow and silent, lost to the world. Unity sleeps. —Neil Gaiman, The Sandman: Preludes & Nocturnes, 1991 In the above-cited comic, a necromancer imprisons Morpheus, an immortal who is master of sleep and dreams. Conse- quently, people are unable to stay awake, sleeping the days, months and years away, until Morpheus escapes and restores the natural order. The chilling real-life inspi- ration for this compelling serialized com- ic was an epidemic that swept the world It emerged from the cold, wet plains Constantin von Economo in Vienna, between 1916 and 1926. A hundred years and trenches of northern France and Bel- identified the condition’s principal man- after the first cases of “sleepy sickness” gium, the battlefields of World War I, ifestation—its profound effect on sleep, came to the attention of the medical com- shorn apart and denuded of trees by the that restorative period during which the munity, we still do not know what agents endless barrage of explosions from artil- body is at rest and the brain disconnects were responsible for this disease. lery, mines and machine-gun fire, a from the external environment. It was landscape crowded with millions of the clinical acumen of the aristocratic young men living under atrocious and von Economo, a professor of psychiatry BY CHRISTOF KOCH unsanitary conditions at close quarters. and neurology of Greek origin, whose Indeed, one of the most famous victims masterful monographs on the subject of the disease may have been Adolf Hit- gave us the best description of the dis- OVE Christof Koch is president L and chief scientific officer of ler, who was wounded at the Battle of ease and its underlying pathology of en- AN the Allen institute for Brain the Somme. cephalitis, an inflammation of the brain. L Science in Seattle. He serves on Scientific American Mind ’s Two physicians from opposing sides, Encephalitis lethargica (EL), epidem- board of advisers. Jean-René Cruchet in Paris and Baron ic encephalitis or von Economo disease JEFFREY A 22 SCIENTIFIC AMERICAN MIND MarcH/APRIL 2016 Exploring the riddle of our existence starts with sore throat, nausea, head- ache, joint pain and fever—the general malaise associated with flu. From there the illness progresses to abnormal eye movements (which often cause double vision as the two eyes are no longer coordinated), drooping eyelids, an inability to open the eyes, and an ir- resistible need to sleep, day and night. This lethargy lasts for weeks, even in some cases for a year or more. Eleanore Carey, an eloquent young woman living in New York City, fell into a Sleeping Beauty–like trance in February 1923. Many years later she described these symptoms in a The aristocratic Viennese physician Baron magazine article: Constantin von Economo composed master- ful monographs on a condition that began with a sore throat, progressed to abnormal After two months of illness I was eye movements, and ended with a lethargy in little pain, in fact, I was very that could last for a year or more. comfortable, provided they did not prod me nor stand me on my head, turn me over in bed nor dash my fingers on its sides nor any questions asked. The victims could not cold water on my face to waken places to put my feet, but I must feed or clean themselves. In severe cases, me. It was so heavenly just to be al- climb out of that pit with my bare they were stuporous or even comatose. lowed to sleep, but these people hands!... Perhaps it will give the EL is a protean disease with some vic- around me seemed determined to reader a vague inkling of the tims showing the opposite pattern, suf- prevent my being comfortable! dreadful lethargy which complete- fering from extreme insomnia or from in- When the idea finally crept ly overpowers the victim of this verted sleep—drowsy and lethargic dur- through my sleeping brain that I disease and renders him impotent ing the day but delirious at night. must waken, it seemed to be a to make the effort to help himself. Mortality in this acute phase of the physical impossibility. I wanted to disease ran as high as 30 to 40 percent. be obliging, but I just could not. It These periods experienced by Carey Medical science was powerless to inter- seemed to me to be just as difficult and others came replete with vivid vene and had to let the disease run its to come to consciousness as it dreams, hallucinations and nightmares. natural course. Hand in hand with EL’s would have been had I been buried When patients were woken up by calling impact on sleep were its variegated ef- in a pit as deep as the center of the their name or shaking them, they re- fects on motor behavior, with patients ); ) earth, where the circular walls sponded intelligently before quickly suc- displaying a menagerie of tics, motor about me were of shiny, polished cumbing to somnolence again, often be- and linguistic compulsions, tremors, ri- marble. There were no crevices for fore they could fully provide answers to gidities and unconscious activities title page title von Economo von known as automatisms. RESS ( From Europe the disease spread to the P Americas by way of New York and other AN ELOQUENT YOUNG WOMAN LIVING port cities on the Atlantic coast. Esti- mates for the number of people world- IN NEW YORK CITY IN 1923 IBRARY OF MEDICINE ( wide who contracted EL ranged from L DESCRIBED THE SYMPTOMS OF about 52,000 reported cases upward to one million. The uncertainty derives from ENCEPHALITIS LETHARGICA AS AKIN TO not knowing how many infected people A SLEEPING BEAUTY–LIKE TRANCE. experienced mild and short-lasting symp- COURTESY OF U.S. COURTESY OF OXFORD UNIVERSITY toms of EL that went unreported. MIND.SCIENTIFICAMERICAN.COM SCIENTIFIC AMERICAN MIND 23 CONSCIOUSNESS REDUX Why the epidemic strain of EL disap- Anatomy of a Trance peared 10 years later as abruptly as it did remains unknown. Since then, only a In 1916 neurologist Constantin von Economo encountered his first handful of sporadic cases have been re- patients afflicted with a form of encephalitis in areas of the midbrain ported. Medical sleuthing has revealed that are involved with the regulation of sleep and wakefulness. previous instances of outbreaks of an EL- like disease, in particular in Tübingen, Germany, in 1712 (where it was dubbed die Schlafkrankheit ) and in northern Italy in 1890 ( la nona). It is disconcerting that to this day, the culprit responsible for EL remains un- known and, presumably, at large. As ep- idemic encephalitis partially overlapped with the 1918–1920 epidemic of influen- za—the H1N1 or “Spanish flu” that killed an estimated 50 million people— some consider the former a consequence of the latter. Yet no concrete causal evi- Von Economo’s drawing of the midbrain dence of any such link to influenza has ( right ) and surrounding regions shows a lesion surfaced. Nor did pathologists isolate where the brain stem and forebrain meet from the brains of EL patients any bac- ( diagonal hatching ) that produced prolonged sleep teria or viruses that could be identified in a patient. The lesion in the anterior hypothalamus ( horizontal hatching ) caused extended insomnia. The as the responsible agents. condition came to be known as encephalitis lethargica (EL) A currently popular hypothesis sug- or von Economo disease. More advanced methods have gests that the initial cold or flu virus trig- confirmed that the areas identified by von Economo gered an inappropriate immune re- ( depicted below ) are indeed essential elements of the sleep-wake regulatory system. The vertical red ellipse highlights­­ sponse. If true, EL would join an ever ) a key region involved in wakefulness; the horizontal blue one growing list of autoimmune afflictions. corresponds to a critical area that regulates sleep. bottom This hypothesis, however, fails to ex- plain how the epidemic form of EL could burst onto the world stage, affect tens of thousands and then vanish. Most likely JOURNAL OF OF JOURNAL Thalamus multiple factors were responsible, a set of antecedents that might in time con- ); SCIENCE SOURCE ( verge again under the appropriate con- top ditions to haunt humankind. 1930 ( Unfortunately, worse was in store for H some of the patients who survived the acute phase of EL. They subsequently developed Parkinson’s disease to a vary- IZATION,” ECONOMO, BY C. V. IN L ing degree, including an extreme form of NO. 3; MARC. 71, L OCA L akinesia, in which they remained immo- VO bile for decades, frozen statues locked EM OF away in nursing homes or wards for the L terminally demented. These long-for- ROB P gotten postencephalitic parkinsonian AS A Cerebellum patients were the ones that neurologist P EE Oliver Sacks awakened with l-DOPA L drug therapy in the late 1960s, as fa- mously described in his 1973 master- FROM “S DISEASE, MENTAL AND NERVOUS 24 SCIENTIFIC AMERICAN MIND MarcH/APRIL 2016 CONSCIOUSNESS REDUX piece Awakenings. The book became an existence of a structure in the midbrain within three dozen or more highly het- eponymous movie with Robin Williams that keeps the overlying thalamus and erogeneous nuclei with idiosyncratic cell playing a character based on Sacks and the neocortex in an activated, awakened structures housed within the brain stem an amazing, heart-wrenching perfor- state.