In the period from 1917 to 1926, a condition called encephalitis lethargica was rampant throughout the world (nearly five million people were affected, a third of whom died). The first acute phase symptoms of encephalitis lethargica were: double vision (diplopia), deep drowsiness, and sometimes mild fever. Around one third of encephalitis lethargica sufferers died during this acute phase, usually of respiratory failure. Autopsies discovered that patients suffered from an inflammation confined to a small region at the base of the brain. For those who survived the first phase, the second phase was characterized by a loss of concentration and loss of interest in life, in a manner which resembled chronic fatigue syndrome. Many encephalitis lethargica patients presented with sore throats, and suffered from sleep inversion (circadian rhythm disruption where the patient is active at night and sleep during the day), similar to the circadian rhythm disruption found in ME/CFS. But during this second period, a process of neurodegeneration would take place (which could occur within days, or take up to 30 years), which led to post-encephalitic parkinsonism. Ref: 1 No recurrence of this epidemic has appeared, though isolated sporadic cases of encephalitis lethargica do occur. The cause of encephalitis lethargica is still uncertain, though there was some speculation that the 1918 influenzavirus pandemic was the culprit (but in fact the encephalitis lethargica outbreak began two years before the 1918 influenzavirus pandemic,1 and furthermore, new research shows no evidence of influenza RNA in the archived brain material of the original encephalitis lethargica patients). But recently, a 2012 study suggested that enterovirus (in particular coxsackievirus B) might in fact be the causal agent of encephalitis lethargica: Evidence for an enterovirus as the cause of encephalitis lethargica And one case of a patient with fatal coxsackievirus B4 meningoencephalitis resulted in symptoms suggestive of encephalitis lethargica. Coxsackievirus B is of course a virus associated with ME/CFS, a disease which shows some similarity to encephalitis lethargica.