Timothy Peters

King George III and porphyria: a clinical re-examination of the historical evidence:

The diagnosis that George III suffered from acute porphyria has gained widespread acceptance, but re-examination of the evidence suggests it is unlikely that he had porphyria.The porphyria diagnosis was advanced by Ida Macalpine and Richard Hunter, whose clinical symptomatology and historical methodology were flawed. They highlighted selected symptoms, while ignoring, dismissing or suppressing counter-evidence. Their claims about peripheral neuropathy, cataracts, vocal hoarseness and abdominal pains are re-evaluated; and it is also demonstrated that evidence of discoloured urine is exceedingly weak. Macalpine and Hunter believed that mental illnesses were primarily caused by physical diseases, and their diagnosis of George III formed part of a wider agenda to promote controversial views about past, contemporary and future methods in psychiatry.

The madness of King George III: a psychiatric re-assessment

This research, based on a study of King George III’s medical records and of contemporary diaries of his courtiers and equerries, further confirms the considerable doubt on the claim of Richard Hunter and Ida Macalpine that the King suffered from recurrent attacks of acute porphyria. The present study examines the above records from a psychiatric viewpoint, together with some additional reports, to re-assess the nature of the King’s maladies. It concludes that he suffered from recurrent mania (four episodes), with chronic mania and possibly a degree of fatuity during the last decade of his life. This is in agreement with previous reports that he suffered from manic-depressive psychosis.

Effect of areca nut on salivary copper concentration in chronic chewers

The chewing of areca nut is associated with the development of oral submucous fibrosis (OSF), a condition predominantly encountered in Asians indulging in the habit. The pathogenesis of this condition is however, unclear, though several mechanisms have been proposed. Copper has previously been implicated as a possible aetiological factor. In this study, total copper concentration was measured via atomic absorption spectrophotometry in whole mouth saliva of 15 volunteers who were regular chewers, before and after their habitual chew. An aliquot of the latter was also analysed for copper. Six non-chewing volunteers acted as controls. Salivary copper concentrations were corrected for protein content. Over 50% of the subjects had basal salivary copper concentration higher than the range seen in normal controls. All but two subjects demonstrated an increase in the salivary [Cu] following their habitual chew. Marked changes were seen in those with low basal salivary concentrations. These data indicate that soluble copper found in areca nut is released into the oral environment of habitual chewers. Its buccal absorption may contribute to the oral fibrosis in Asians who regularly chew this nut.

Attenuated variants of Lesch–Nyhan disease: the case of King James VI/I

Sir, We read with interest the paper by Jinnah et al . (2010) in the March 2010 issue of Brain , describing the clinical characteristics of a large series of patients with an attenuated variant of Lesch–Nyhan disease. All of the patients reported had either a deficiency of hypoxanthine–guanine phosphoribosyltransferase (HPRT) or a mutation in the HPRT gene, and all had evidence of overproduction of uric acid; but neurological involvement was highly variable and none exhibited the self injurious behaviour that is diagnostic of the full-blown condition. The existence of a clinically variable phenotype highlights the importance of considering the condition in the differential diagnosis of atypical neurological presentations in adults as well as children, particularly when they are associated with raised levels of serum and/or urinary uric acid. It also opens new possibilities for retrospective diagnosis of historical figures …

Mental health issues of Maria I of Portugal and her sisters: the contributions of the Willis family to the development of psychiatry:

Contemporary accounts credit Dr Francis Willis (1718–1807) with facilitating the recovery of King George III from his major episode of acute mania in 1788–9. Subsequently Willis was summoned to Lisbon to advise on the mental health problems of Queen Maria I. This article reports the nature of the illnesses of Maria and her two similarly affected sisters, and uses the program OPCRIT to propose diagnoses of major depressive disorders. The high prevalence of consanguinity and insanity among the Portuguese monarchy and their antecedents probably contributed to their mental health problems. The successive contributions of the Willis family from Thomas Willis (1621–75) to his grand-nephew, Francis Willis (1792–1859), are reviewed; the popular image is somewhat inaccurate and does not highlight their part in the development of psychiatry.

The nature of King James VI/I's medical conditions: new approaches to the diagnosis

It has been claimed that King James VI/I, an antecedent of King George III, suffered from acute porphyria, and that the disease was passed on to George III through his grand-daughter Sophie, mother of George I. The life of James is reviewed and previously-proposed diagnoses are considered. James’s medical history is discussed in detail and, where possible, examined with validated symptom scales. Using an online database of neurological diseases, the authors show that James’s symptomatology is compatible with a diagnosis of Attenuated (mild) Lesch-Nyhan disease; no evidence was found to support a diagnosis of acute porphyria. In addition, there is evidence of associated Asperger traits which may explain some of the King’s unusual behavioural and psycho-social features.

FitzPatrick Lecture: King George III and the porphyria myth – causes, consequences and re-evaluation of his mental illness with computer diagnostics

Recent studies have shown that the claim that King George III suffered from acute porphyria is seriously at fault. This article explores some of the causes of this misdiagnosis and the consequences of the misleading claims, also reporting on the nature of the kings recurrent mental illness according to computer diagnostics. In addition, techniques of cognitive archaeology are used to investigate the nature of the kings final decade of mental illness, which resulted in the appointment of the Prince of Wales as Prince Regent. The results of this analysis confirm that the king suffered from bipolar disorder type I, with a final decade of dementia, due, in part, to the neurotoxicity of his recurrent episodes of acute mania.

The acute mania of King George III: A computational linguistic analysis

We used a computational linguistic approach, exploiting machine learning techniques, to examine the letters written by King George III during mentally healthy and apparently mentally ill periods of his life. The aims of the study were: first, to establish the existence of alterations in the King’s written language at the onset of his first manic episode; and secondly to identify salient sources of variation contributing to the changes. Effects on language were sought in two control conditions (politically stressful vs. politically tranquil periods and seasonal variation). We found clear differences in the letter corpus, across a range of different features, in association with the onset of mental derangement, which were driven by a combination of linguistic and information theory features that appeared to be specific to the contrast between acute mania and mental stability. The paucity of existing data relevant to changes in written language in the presence of acute mania suggests that lexical, syntactic and stylometric descriptions of written discourse produced by a cohort of patients with a diagnosis of acute mania will be necessary to support the diagnosis independently and to look for other periods of mental illness of the course of the King’s life, and in other historically significant figures with similarly large archives of handwritten documents.

‘Details on the Establishment of Doctor Willis, for the Cure of Lunatics’ (1796):

The ‘mad-doctor’ Dr Francis Willis achieved national and international celebrity following his successful treatment of King George III’s first major episode of insanity in 1788–9. At the time of his summons to attend the King, Willis was a well-established provincial practitioner and madhouse proprietor. An anonymous French visitor published a description of Willis’s Lincolnshire madhouse and his therapeutic practices in 1796. The translated text of the full article provides a unique insight into the work of a key figure in the historical development of psychological medicine. The accompanying Introduction summarizes Francis Willis’s career as a mad-doctor and uses salient information from the original text to place him and his madhouse practice within a contemporary context.

Re-Evaluation of the Diagnosis of Porphyria Cutanea Tarda in Admiral Sir Francis Beaufort

Objectives Two biographies of Admiral Francis Beaufort (1774–1857) have stated that, aged 20–25 years, he suffered from porphyria cutanea tarda (PCT) that was ‘cured’ following severe blood loss during a naval skirmish. We have examined the evidence concerning the nature of his skin disease. Design Primary records, most notably Beauforts correspondence with his family, his journals and his fathers diaries were sought out and analysed. Setting This case report is discussed in the context of 18th-century naval medicine and concepts and treatment of skin disease. Results The description of his lesions, their age of onset, their progression and response to treatment, particularly topical tar and associated features are quite inconsistent with a diagnosis of PCT. His mother, Mary Waller Beaufort (1739–1821), consulted Dr Robert Darwin in 1803 about a painful skin disease affecting her legs. Detailed description of the lesions and a contemporary diagnosis are not available but possible diagnoses include chronic psoriasis and stasis eczema. Conclusions A more tenable diagnosis is that Francis Beaufort had chronic plaque psoriasis remitted by bed rest and convalescence in the sunny Mediterranean climate with cessation of alcohol consumption and improved nutrition as well as topical and oral medications.