- Email: [email protected]
History as a medical tool
Perspectives
The art of medicine History as a medical tool The dominant view in medicine until recently was that, although history is interesting, its use is didactic, to remind practitioners of past successes and failures. But a new generation of medical historians, often trained in both medicine and history, has argued that an applied history of medicine can serve as an important tool in medical research. These practitioner-historians often participate as members of collaborative interdisciplinary teams searching for more effective interventions or for clues to the cause of elusive disorders. An examination of two very different elusive syndromes, Tourette’s syndrome and Kawasaki’s disease, illustrates how a medically informed historical perspective can provide a useful tool, opening new directions for identification of aetiological clues. Unlike diseases for which a diagnosis is confirmed or rejected through a laboratory test indicating infection by a pathogen or the presence of a genetic mutation, the cause of a syndrome is unknown. Diagnosis of a syndrome, such as Tourette’s syndrome or Kawasaki’s disease, depends on identification of a list of possible combinations of signs
Portrait of Georges Gilles de la Tourette (1857-1904)
552
and symptoms displayed by a patient within a specified time. The longer a syndrome’s cause remains unidentified, the more disagreements can emerge over which signs and symptoms are necessary to authorise a diagnosis. As a result, the constituents of a syndrome can vary over time and in different places. Tourette’s syndrome is named after French neurologist Georges Gilles de la Tourette who, in 1885, identified a combination of multiple motor tics and involuntary vocalisations as a distinct disorder he called “convulsive tic disease with coprolalia”. According to Gilles de la Tourette, the illness began with childhood motor and vocal tics that over time increased in number and variety with the eventual appearance of coprolalia (convulsive cursing). This disease, he proposed, had a “degenerative” cause in which the afflicted inherited a nervous system weakened by the cumulative effects of the preceding generations’ immoral behaviours. Although the tics might wax and wane, they ultimately resisted all interventions. Because he had identified a set of signs and symptoms, a course of illness, and a predisposing cause, Gilles de la Tourette described a disease. Although what today is called Tourette’s syndrome claims its pedigree from Gilles de la Tourette’s 1885 article, the current designation draws only on Gilles de la Tourette’s description of signs and symptoms, rejecting his attribution of the underlying degenerative causes and progressively deteriorating outcome. Beginning in the 1980s, disputes arose over whether obsessive-compulsive behaviours should be included within the Tourette’s syndrome typology. The current diagnostic criteria laid out in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Revised (DSM-IVR) have been the subject of disagreement ever since they first appeared in 1994. Divisions emerged among those who believe that conduct disorders are part of Tourette’s syndrome and those who resist too wide a spectrum of symptoms. Additionally, experts disagree over the length of time a symptom or sign must be present and whether onset must occur before the age of 18 years. By 1997, a team of experienced Tourette’s researchers at Yale University, New Haven, CT, USA, noted that disagreements over the Tourette’s syndrome phenotype continued to frustrate attempts to locate its cause. Although the DSM is a diagnostic tool, its Tourette’s syndrome typology frames research protocols, restricting data to that which fulfil the criteria. However, a recent comprehensive international study of more than 6800 patients with Tourette’s syndrome found that just 14·2% met the DSM criteria for Tourette’s syndrome only; 85·8% had comorbidities (Eur Child Adolesc Psychiatry 2007; 16 (suppl 1): 15–23). www.thelancet.com Vol 371 February 16, 2008
Perspectives
The DSM excludes infection as a possible feature of Tourette’s syndrome. Yet in early 19th-century clinical literature, those who displayed the signs we now associate with Tourette’s syndrome were often reported to have had a previous episode of rheumatic fever. Gilles de la Tourette’s mentor, Jean Charcot, dismissed this connection, and since then the possible role of infection has been excluded from research on the cause of convulsive tics. However, those with Sydenham’s chorea, a sequel to rheumatic fever, display tics and vocalisations similar, but not identical, to those of Tourette’s syndrome. Although neurological and psychiatric residents are taught to distinguish between Tourette’s syndrome and Sydenham’s chorea on the basis of the differences in presenting signs, there is no compelling reason to exclude common predisposing mechanisms. Thus, Tourette’s syndrome and Sydenham’s chorea could have similar causes but slightly different presentations owing to host differences or to the developmental stage at the time of an insult. Alternatively, what is seen as Tourette’s syndrome might result from various different underlying mechanisms. In the 1990s, clinical teams at Brown University, Providence, RI, USA, and at the US National Institute of Mental Health reported that subsets of patients with Tourette’s syndrome displayed exacerbations of tics and vocalisations after infection by rheumatic streptococcus. They postulated that, as with Sydenham’s chorea, antibodies to the bacterium crossreacted with brain tissue (in the circuitry of the basal ganglia), causing tics and vocalisations. Nevertheless, there has been great resistance to exploring this possible line of research, not least because it seems to challenge the dominant typology of Tourette’s syndrome as a genetic disorder. Reminding researchers that Tourette’s syndrome is a syndrome with a tentative typology is crucial in legitimating new research protocols. Kawasaki’s disease, despite its name, is also a syndrome. An elusive rash and fever illness of early childhood, Kawasaki’s disease was first identified by Tokyo paediatrician Tomisaku Kawasaki in the mid-1960s. Although generally benign and treatable with a timely diagnosis, coronary artery aneurysms (CAA), sometimes fatal, can develop in up to 25% of untreated children. Because the cause and mechanisms of Kawasaki’s disease are unknown, diagnosis, as with Tourette’s syndrome, is made by relying on a list of clinical signs. Despite the case definition’s reliability in identifying children at risk of CAA, researchers have long noted that strict reliance on the classic case definition has led to delay in treatment of children with atypical presentations, who fail to meet the criteria, yet who develop CAA. In fact, a series of recent studies have reported that children with atypical or incomplete clinical signs are at greater risk of developing CAA than those who meet the diagnostic criteria for classic Kawasaki’s disease. A historical investigation into the construction of the clinical diagnostic criteria for Kawasaki’s disease reveals www.thelancet.com Vol 371 February 16, 2008
why this might be so and suggests new avenues for prevention of CAA in children at risk. Kawasaki constructed his case definition in 1967, assuming that the syndrome resolved without intervention and without sequelae. Notwithstanding the emerging epidemiological and pathological evidence, Kawasaki continued, as late as 2003, to express doubts about the extent to which CAA were part of the syndrome’s spectrum. Although Benjamin Landing and Eunice Larson’s 1977 study is regularly cited as proof that Kawasaki’s syndrome runs a spectrum from benign to fatal outcomes, the authors admitted that “none” of 20 fatal patients in their study “totally fulfills the Kawasaki criteria”. Rather, they concluded that the data indicated that children with CAA and those with fatal Kawasaki’s disease were “indistinguishable” (Pediatrics 1977; 59: 651–62). However, Kawasaki had insisted that, by definition, fatal cases were different disorders that sometimes, but not always, shared several presenting clinical signs. Nevertheless, Kawasaki’s clinical case definition, endorsed by the US Centers for Disease Control and Prevention in 1978 and subsequently adopted by the paediatric Redbook and the American Heart Association, became the accepted diagnostic criteria for predicting the risk of acquired CAA. As a result, research on the cause of CAA was restricted to cases that fulfilled Kawasaki’s classic criteria. Atypical cases, which were widely acknowledged to have a higher risk of CAA than those meeting the classic criteria, were thus excluded from research protocols. Ironically, the goal of predicting and preventing CAA was restricted by adherence to a case definition constructed under the presumption that it did not result in CAA. Acknowledging that Kawasaki’s disease is a syndrome would liberate researchers from assuming they are looking at only one scenario leading to CAA. Such a recognition has contributed to the development of revised criteria in the 2003 paediatric Redbook and in the recent American Heart Association criteria that adopted the label “Kawasaki’s syndrome” in place of Kawasaki’s disease. These revisions have in turn alerted treating clinicians to be sensitive to atypical presentations, which often pose a greater risk of CAA than those that fulfil the classic criteria. A combination of clinical anomalies and historical research prompted both the Tourette’s syndrome and Kawasaki’s syndrome investigations. These examples illustrate how historical interrogations of syndrome construction can elicit useful issues for the development of research hypotheses and novel approaches to medical conundrums.
Further reading Gilles de la Tourette GP. Étude sur une affection nerveuse caractérisée par de l’incoordination motrice accompagnée d’écholalie et de coprolalie. Archives de Neurologie 1885; 9: 158-200. Burns JC. Translation of Dr Tomisaku Kawasaki’s original report of fifty patients in 1967. Pediatr Infect Dis 2002; 21: 993–95. Kushner HI. A cursing brain? The histories of Gilles de la Tourette syndrome. Cambridge, MA: Harvard University Press, 1999.
Howard I Kushner
Kushner HI, Bastian JF, Turner CL, Burns JC. Rethinking the boundaries of Kawasaki disease: toward the next case definition. Persp Biol Med 2003; 46: 216–33.
Rollins School of Public Health and the Graduate Institute of Liberal Arts, Emory University, Atlanta, GA 30322, USA. [email protected]
Swedo SE, Grant PJ. PANDAS: a model for human autoimmune disease. J Child Psychol Psychiatry 2005; 46: 227–34.
553
The art of medicine History as a medical tool The dominant view in medicine until recently was that, although history is interesting, its use is didactic, to remind practitioners of past successes and failures. But a new generation of medical historians, often trained in both medicine and history, has argued that an applied history of medicine can serve as an important tool in medical research. These practitioner-historians often participate as members of collaborative interdisciplinary teams searching for more effective interventions or for clues to the cause of elusive disorders. An examination of two very different elusive syndromes, Tourette’s syndrome and Kawasaki’s disease, illustrates how a medically informed historical perspective can provide a useful tool, opening new directions for identification of aetiological clues. Unlike diseases for which a diagnosis is confirmed or rejected through a laboratory test indicating infection by a pathogen or the presence of a genetic mutation, the cause of a syndrome is unknown. Diagnosis of a syndrome, such as Tourette’s syndrome or Kawasaki’s disease, depends on identification of a list of possible combinations of signs
Portrait of Georges Gilles de la Tourette (1857-1904)
552
and symptoms displayed by a patient within a specified time. The longer a syndrome’s cause remains unidentified, the more disagreements can emerge over which signs and symptoms are necessary to authorise a diagnosis. As a result, the constituents of a syndrome can vary over time and in different places. Tourette’s syndrome is named after French neurologist Georges Gilles de la Tourette who, in 1885, identified a combination of multiple motor tics and involuntary vocalisations as a distinct disorder he called “convulsive tic disease with coprolalia”. According to Gilles de la Tourette, the illness began with childhood motor and vocal tics that over time increased in number and variety with the eventual appearance of coprolalia (convulsive cursing). This disease, he proposed, had a “degenerative” cause in which the afflicted inherited a nervous system weakened by the cumulative effects of the preceding generations’ immoral behaviours. Although the tics might wax and wane, they ultimately resisted all interventions. Because he had identified a set of signs and symptoms, a course of illness, and a predisposing cause, Gilles de la Tourette described a disease. Although what today is called Tourette’s syndrome claims its pedigree from Gilles de la Tourette’s 1885 article, the current designation draws only on Gilles de la Tourette’s description of signs and symptoms, rejecting his attribution of the underlying degenerative causes and progressively deteriorating outcome. Beginning in the 1980s, disputes arose over whether obsessive-compulsive behaviours should be included within the Tourette’s syndrome typology. The current diagnostic criteria laid out in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Revised (DSM-IVR) have been the subject of disagreement ever since they first appeared in 1994. Divisions emerged among those who believe that conduct disorders are part of Tourette’s syndrome and those who resist too wide a spectrum of symptoms. Additionally, experts disagree over the length of time a symptom or sign must be present and whether onset must occur before the age of 18 years. By 1997, a team of experienced Tourette’s researchers at Yale University, New Haven, CT, USA, noted that disagreements over the Tourette’s syndrome phenotype continued to frustrate attempts to locate its cause. Although the DSM is a diagnostic tool, its Tourette’s syndrome typology frames research protocols, restricting data to that which fulfil the criteria. However, a recent comprehensive international study of more than 6800 patients with Tourette’s syndrome found that just 14·2% met the DSM criteria for Tourette’s syndrome only; 85·8% had comorbidities (Eur Child Adolesc Psychiatry 2007; 16 (suppl 1): 15–23). www.thelancet.com Vol 371 February 16, 2008
Perspectives
The DSM excludes infection as a possible feature of Tourette’s syndrome. Yet in early 19th-century clinical literature, those who displayed the signs we now associate with Tourette’s syndrome were often reported to have had a previous episode of rheumatic fever. Gilles de la Tourette’s mentor, Jean Charcot, dismissed this connection, and since then the possible role of infection has been excluded from research on the cause of convulsive tics. However, those with Sydenham’s chorea, a sequel to rheumatic fever, display tics and vocalisations similar, but not identical, to those of Tourette’s syndrome. Although neurological and psychiatric residents are taught to distinguish between Tourette’s syndrome and Sydenham’s chorea on the basis of the differences in presenting signs, there is no compelling reason to exclude common predisposing mechanisms. Thus, Tourette’s syndrome and Sydenham’s chorea could have similar causes but slightly different presentations owing to host differences or to the developmental stage at the time of an insult. Alternatively, what is seen as Tourette’s syndrome might result from various different underlying mechanisms. In the 1990s, clinical teams at Brown University, Providence, RI, USA, and at the US National Institute of Mental Health reported that subsets of patients with Tourette’s syndrome displayed exacerbations of tics and vocalisations after infection by rheumatic streptococcus. They postulated that, as with Sydenham’s chorea, antibodies to the bacterium crossreacted with brain tissue (in the circuitry of the basal ganglia), causing tics and vocalisations. Nevertheless, there has been great resistance to exploring this possible line of research, not least because it seems to challenge the dominant typology of Tourette’s syndrome as a genetic disorder. Reminding researchers that Tourette’s syndrome is a syndrome with a tentative typology is crucial in legitimating new research protocols. Kawasaki’s disease, despite its name, is also a syndrome. An elusive rash and fever illness of early childhood, Kawasaki’s disease was first identified by Tokyo paediatrician Tomisaku Kawasaki in the mid-1960s. Although generally benign and treatable with a timely diagnosis, coronary artery aneurysms (CAA), sometimes fatal, can develop in up to 25% of untreated children. Because the cause and mechanisms of Kawasaki’s disease are unknown, diagnosis, as with Tourette’s syndrome, is made by relying on a list of clinical signs. Despite the case definition’s reliability in identifying children at risk of CAA, researchers have long noted that strict reliance on the classic case definition has led to delay in treatment of children with atypical presentations, who fail to meet the criteria, yet who develop CAA. In fact, a series of recent studies have reported that children with atypical or incomplete clinical signs are at greater risk of developing CAA than those who meet the diagnostic criteria for classic Kawasaki’s disease. A historical investigation into the construction of the clinical diagnostic criteria for Kawasaki’s disease reveals www.thelancet.com Vol 371 February 16, 2008
why this might be so and suggests new avenues for prevention of CAA in children at risk. Kawasaki constructed his case definition in 1967, assuming that the syndrome resolved without intervention and without sequelae. Notwithstanding the emerging epidemiological and pathological evidence, Kawasaki continued, as late as 2003, to express doubts about the extent to which CAA were part of the syndrome’s spectrum. Although Benjamin Landing and Eunice Larson’s 1977 study is regularly cited as proof that Kawasaki’s syndrome runs a spectrum from benign to fatal outcomes, the authors admitted that “none” of 20 fatal patients in their study “totally fulfills the Kawasaki criteria”. Rather, they concluded that the data indicated that children with CAA and those with fatal Kawasaki’s disease were “indistinguishable” (Pediatrics 1977; 59: 651–62). However, Kawasaki had insisted that, by definition, fatal cases were different disorders that sometimes, but not always, shared several presenting clinical signs. Nevertheless, Kawasaki’s clinical case definition, endorsed by the US Centers for Disease Control and Prevention in 1978 and subsequently adopted by the paediatric Redbook and the American Heart Association, became the accepted diagnostic criteria for predicting the risk of acquired CAA. As a result, research on the cause of CAA was restricted to cases that fulfilled Kawasaki’s classic criteria. Atypical cases, which were widely acknowledged to have a higher risk of CAA than those meeting the classic criteria, were thus excluded from research protocols. Ironically, the goal of predicting and preventing CAA was restricted by adherence to a case definition constructed under the presumption that it did not result in CAA. Acknowledging that Kawasaki’s disease is a syndrome would liberate researchers from assuming they are looking at only one scenario leading to CAA. Such a recognition has contributed to the development of revised criteria in the 2003 paediatric Redbook and in the recent American Heart Association criteria that adopted the label “Kawasaki’s syndrome” in place of Kawasaki’s disease. These revisions have in turn alerted treating clinicians to be sensitive to atypical presentations, which often pose a greater risk of CAA than those that fulfil the classic criteria. A combination of clinical anomalies and historical research prompted both the Tourette’s syndrome and Kawasaki’s syndrome investigations. These examples illustrate how historical interrogations of syndrome construction can elicit useful issues for the development of research hypotheses and novel approaches to medical conundrums.
Further reading Gilles de la Tourette GP. Étude sur une affection nerveuse caractérisée par de l’incoordination motrice accompagnée d’écholalie et de coprolalie. Archives de Neurologie 1885; 9: 158-200. Burns JC. Translation of Dr Tomisaku Kawasaki’s original report of fifty patients in 1967. Pediatr Infect Dis 2002; 21: 993–95. Kushner HI. A cursing brain? The histories of Gilles de la Tourette syndrome. Cambridge, MA: Harvard University Press, 1999.
Howard I Kushner
Kushner HI, Bastian JF, Turner CL, Burns JC. Rethinking the boundaries of Kawasaki disease: toward the next case definition. Persp Biol Med 2003; 46: 216–33.
Rollins School of Public Health and the Graduate Institute of Liberal Arts, Emory University, Atlanta, GA 30322, USA. [email protected]
Swedo SE, Grant PJ. PANDAS: a model for human autoimmune disease. J Child Psychol Psychiatry 2005; 46: 227–34.
553