LAUSR

Dear Sirs, The study of the causes of bewitchment throughout history has captured the imagination of both modern historians and scientists. In an article in Science in 1976, Caporael proposed convulsive ergotism, from the rye fungus, Claviceps purpurea, as a biomedical explanation for the events at the Salem witch trials of 1692 [1]. The article generated a significant amount of debate on the subject [2] and interest in modern interpretation of historical epidemics of witchcraft. Encephalitis lethargica (EL) was suggested as another possible cause in Salem by Carlson [3]. More recently, historian Uszkalo compared symptomatology of the bewitched of early modern England to that of anti-Nmethyl-D-aspartate (NMDA) receptor encephalitis [4]. Considering recent findings in anti-NMDA receptor encephalitis, it is possible that Uszkalo’s proposition may also apply to the famous episode in Salem. Anti-NMDA receptor encephalitis is a disease first described in 2007, characterised by a flu-like prodrome, followed by a variable set of neuropsychiatric symptoms such as behavioural changes, psychosis, visual and auditory hallucinations, seizures, as well as dystonic and rhythmic movements and autonomic dysfunction [5]. The disease occurs more frequently in young women, with one case series identifying the median age to be 23 years (range 5–76) [6]. The disease has been shown to undergo spontaneous remission and relapses [7, 8]. Case reports of NMDA receptor encephalitis often make comparisons to ‘‘demonic possession’’, especially in paediatric cases [9]. These features bear striking resemblance to the seventeenth century descriptions of Abigail Williams and Betty Parris, two cousins who were the first afflicted at Salem. Table 1 shows an interpretation of descriptions from seventeenth century Salem sources and a comparison to the clinical features of anti-NMDA receptor encephalitis. During the Salem witch trials a total of 20 people, accused by dozens of victims of witchcraft, were tried and executed. Previous theories on a medical explanation of witchcraft have attempted to account for the epidemic phenomenon amongst the townsfolk of Salem. Caporael suggested ergot poisoning from a common contaminated food source [1]. Carlson’s EL theory is based on epidemics of the disease that occurred between 1917 and 1940. In recent studies, anti-NMDA receptor autoantibodies have been found in patients previously diagnosed with hyperkinetic EL [13], suggesting an overlap in the pathogenesis of anti-NMDA receptor encephalitis and EL. Additionally, there are numerous reports which suggested that the EL epidemics were provoked by a post-influenza autoimmune response, especially in children [14]. However, there is no direct evidence to prove this theory, which remains speculative. With indirect evidence alone we can only speculate about the epidemic potential of autoimmune encephalitis. In the context of the Salem witch trials it is unlikely that all those involved had encephalitis. The socio-political and religious factors probably played bigger roles in fuelling symptoms or invoking bewitchment on a mass scale. & Johnny Tam [email protected]