Objective: To evaluate the relation between lesions of various brain structures and the development of eating disorders and thus inform the neurobiological research on the aetiology of these mental illnesses.
Method: We systematically reviewed 54 previously published case reports of eating disorders with brain damage. Lesion location, presence of typical psychopathology, and evidence suggestive of causal association were recorded.
Results: Although simple changes in appetite and eating behaviour occur with hypothalamic and brain stem lesions, more complex syndromes, including characteristic psychopathology of eating disorders, are associated with right frontal and temporal lobe damage.
Conclusions: These findings challenge the traditional view that eating disorders are linked to hypothalamic disturbance and suggest a major role of frontotemporal circuits with right hemispheric predominance in the pathogenesis.
- anorexia nervosa
- brain lesions
- bulimia nervosa
- eating disorders
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Eating disorders, including anorexia and bulimia nervosa, are characterised by abnormal eating behaviour and typical psychopathological features, including fear of fatness, drive for thinness, and body image disturbance. In most patients, there is no detectable focal brain abnormality. Nonetheless, associations of anorexia and bulimia nervosa with history of perinatal complications1,2 and head injuries3 suggest a role of cerebral pathology in some cases. A number of case studies describe eating disorders with intracranial tumours, injuries, or epileptogenic foci. However, many clinical descriptions are limited to changes in appetite and lack psychopathological features characteristic of eating disorders. A previous review of 21 anorexia cases associated with brain tumours found that only three of them fulfilled formal diagnostic criteria.4 In the present paper, we provide a systematic review of published case reports and highlight those relatively rare cases where typical eating disorders appear to be causally associated with localised brain damage.
The Web of Knowledge and Medline were searched for articles published up to April 2004 with any combination of keywords: “eating disorders”, “anorexia nervosa”, “bulimia”, “binge eating”, and “compulsive eating” with “brain damage”, “brain lesion”, “tumor”, “injury”, and “epilepsy”. We perused reference lists and performed citation searches for the identified articles. Cases in children under 7 years were excluded. We found 54 case reports of eating disorders related to brain damage. Cases of obesity with brain lesions have been reviewed elsewhere5 and are not included unless there is prominent behavioural disturbance or psychopathology.
As most papers did not use formal diagnostic criteria, we extracted the following symptoms from the case descriptions: underweight (less than 75% of body weight expected for the height and age), vomiting (not self induced), binge eating (eating unusually large amounts of food in a discrete time period), purging (self induced vomiting, laxative, or diuretic abuse for the purpose of weight control), preoccupations and rituals concerning food (calorie counting, specific eating rules, and unusual eating habits), preoccupations and rituals concerning body weight and shape (intention to lose weight, undue fear of fatness, body checking), hyperactivity (over exercising). Based on these symptoms, cases were classified into four categories: “anorexia nervosa” (underweight and either food or body related preoccupations or rituals, purging, or hyperactivity), “atypical anorexia” (underweight without food or body weight related preoccupations, rituals, or purging), “bulimia nervosa” (binge eating and/or purging and either food or body weight related preoccupations or rituals without underweight), and “atypical bulimia” (hyperphagia or binge eating but no food or body weight related preoccupations or rituals). In general, we refer as “typical” to cases for which there is a record of food or body related preoccupations or rituals or when purging behaviour, food restriction, or hyperactivity are intended to cause weight loss or prevent weight gain in the absence of objective overweight.
Evidence suggestive of causal association was noted if one of the following criteria were fulfilled: 1) the onset of eating disorder coincided with the occurrence of brain damage; 2) treatment directed at the lesion (surgical, antiepileptic) resulted in remission of the eating disorder; 3) brain injury coincided with remission of an eating disorder in a patient with previously established brain damage.
There were 23 cases with brain lesions localised in the area of the hypothalamus and the third ventricle (Table 1: cases 1–23).6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24 With one exception these were primary tumours. In addition to abnormal eating behaviour, symptoms commonly included diabetes insipidus, visual impairment, and unprovoked vomiting.
Three female cases were of apparently typical anorexia nervosa of the purging type (Table 1: cases 1–3). Case 1 appeared as typical in the initial phases with fear of fatness and self induced vomiting; later it progressed into an atypical scenario with spontaneous vomiting and good insight; remission occurred after surgical removal of the tumour. Case 2 seems fairly characteristic with onset in adolescence, concern over becoming fat and cheating about eating; however, there was excessive sleepiness and it is unclear whether vomiting was self induced or spontaneous. In case 3, anorexia developed on the background of severe personality disorder with borderline, compulsive, and perfectionist features; after tumour removal, eating urges subsided but the personality pathology persisted. It is notable that the onset of eating disturbance preceded neurological symptoms by a longer interval (2 and 5 years in the two cases where age of onset is reported) than in the atypical anorexia cases.
Twelve cases (4–15) were classified as atypical anorexia with unintentional weight loss and, in seven, unprovoked vomiting. Although typical psychopathology was not reported, lack of concern over emaciation was noted in three, depressed mood in five, and obsessive compulsive symptomatology in one case (8). In three (4, 5, and 6) there was suggestive evidence of causal association in that anorexia remitted after surgical or radiation treatment. None of these cases would fulfil formal diagnostic criteria for anorexia nervosa; their presentation was atypical in terms of sex distribution, age of onset, and associated neurological symptoms.
The eight cases of atypical bulimia (16–23) presented with voracious appetite and emotional lability. Aggressive and antisocial behaviours were manifested mainly when access to food was denied.
In conclusion, lesions in the hypothalamic area can lead to eating disturbance with either loss or increase of appetite. There is little evidence of hypothalamic tumours causing typical eating disorders. Of the three reported cases with eating disorder specific psychopathology, one can be attributed to premorbid personality disorder and the other two developed relatively long time before the neurological symptoms.
Brain stem lesions
Of the seven anorexia cases associated with primary tumours in the area of brain stem and the fourth ventricle (Table 1: cases 24–30),12,25–30 two (24 and 25) presented as typical restrictive anorexia nervosa with fear of fatness; surgical removal of the tumours led to remission and sustained weight gain in both cases.
The other five cases were clearly atypical with weight loss in the absence of weight concerns or body image disturbance. In case 26, atypical anorexia fully remitted after radiation treatment. Other symptoms included unprovoked vomiting, difficulty swallowing, hiccup, coughing, and nystagmus.
In summary, brain stem lesions are associated with loss of appetite and effortless vomiting. The suggestive association with typical cases of restrictive anorexia nervosa relies on two case reports and needs to be substantiated by further evidence.
Thirteen cases of eating disorders associated with lesions in the cerebral hemispheres were identified (Table 1: 31–43).31–38 The damage was predominantly localised in the frontal and temporal lobes (six frontal, four temporal, three frontotemporal) of the right hemisphere (nine right, three left, one bilateral). In eight cases, there was evidence suggestive of causal association between the lesion and eating disorder. Epilepsy was present in all but one. Additional symptoms included depression, mania, psychotic features, substance abuse, obsessions, compulsions, and hyper-religiousness.
Seven cases presented as “typical” anorexia nervosa with weight and shape preoccupations. In three of them there was a suggestive causal association between brain damage and anorexia nervosa. In case 31, the symptoms started after frontal lobe injury in a previously healthy male adolescent. In case 32, a frontotemporal injury led to remission of restrictive anorexia in an adult woman with a history of epilepsy. In case 33, restrictive anorexia nervosa remitted with a successful treatment of epilepsy by anticonvulsive medication in a young man.
There are three cases of atypical anorexia with right frontal epileptic focus. In cases 38 and 39, obsessive compulsive symptomatology was prominent and both anorexia and epilepsy remitted after embolisation of a vascular malformation or surgical tumour removal.
Two cases of typical bulimia nervosa with binging and purging symptomatology resolved with successful management of epilepsy by temporal lobotomy (41) or antiepileptic medication (42). In case 43, atypical bulimia with severe behavioural disturbance resolved with surgical removal of an astrocytoma in the right anterior cingulate cortex.
In summary, there is compelling evidence of hemispheric damage being causally associated with typical eating disorders. This is supported by a large proportion of cases with typical psychopathology, remission of eating disorders after brain lesion removal, and consistent localisation of lesions in the right frontal and temporal lobes.
In case 44, lesion in the right putamen was associated with obsessive compulsive disorder with food-related preoccupations and compulsive exercising.39 Case 45 is of atypical bulimia with growth hormone producing adenoma of the pituitary.38 In case 46, a boy developed typical anorexia nervosa at age 12 followed by a psychotic episode 2 years later; magnetic resonance imaging revealed parietal arachnoidal cyst and frontal lobe atrophy.40
Cases 47–50 had disseminated tumours affecting more than one brain structure.38,41–43 Two of these were classified as atypical anorexia and two as typical anorexia nervosa. In case 49, surgery combined with radiotherapy for a disseminated ependimoma lead to remission of atypical anorexia.
Case 51 is of typical bulimia nervosa with diffuse paroxysmal abnormality on electroencephalogram, which improved with a combination of carbamazepine and lithium.35 In cases 52–54, disordered eating was associated with hydrocephalus.44–46 In two, anorexia (53) or bulimia (54) remitted upon placement of a ventriculo-peritoneal shunt.
These cases with diffuse or disseminated brain damage further support the association between eating disorders and brain pathology; however, they are less informative as to the location of dysfunctional circuits underlying eating disorders.
This review of published case reports challenges the traditional view that hypothalamic disturbance underlies eating disorders. Although hypothalamic lesions are the most commonly reported neural causes of anorexia-like syndrome, most of them lack the typical psychopathology. Of the eight cases with characteristic psychopathological presentation and suggestive evidence for a causal association, four had frontal and temporal cortical lesions, two brain stem tumours, one hypothalamic tumour, and one hydrocephalus. Implication of frontotemporal circuits is consistent with functional neuroimaging research in eating disorders47,48 and with benign changes in eating, such as the gourmand syndrome.49 Therefore, we conclude that evidence favours cortical mechanisms in the genesis of eating disorders over hypothalamic ones.
An association of disordered eating with epilepsy was reported in 12 cases. In six of these, remission after a surgical removal of an epileptogenic focus or anticonvulsant treatment suggests that eating disorder may be actively maintained by an epileptogenic focus rather than being a deficit syndrome due to missing normal brain tissue.31,33–35,37
In five of the reviewed cases, disturbed eating occurred alongside obsessive compulsive psychopathology.8,9,34,37,39 This finding parallels the comorbidity and familial co-occurrence of eating disorders and obsessive compulsive disorder50,51 and suggests a common or overlapping neural substrate of the two.
This review relies on case reports, which represent a highly selected material prone to reporting and publication bias. Notably, sixteen of the 23 hypothalamic lesions associated with disordered eating were published before 1990 compared with only one cortical lesion. This publication trend reflects a shift of emphasis in the eating disorders research from the study of endocrine and autonomic correlates to psychologically informed explanations.
Although resolution of a disorder after removal of a cerebral lesion is highly suggestive of a causal relation, this is not a proof of causality. For example, in a case of anorexia nervosa remitting after surgical removal of a spinal meningioma, it is uncertain whether the mechanism of apparent causality relates to the removal of a tumor mass, decompression of the cerebrospinal fluid spaces, or other unspecific factors.52
The information provided in the case reports is of variable extent and quality. This may have affected the classification of individual cases as typical or atypical. If information on psychopathology was missing, the case was by default regarded as atypical.
Neurological symptoms of hypothalamic (changes in appetite, excessive thirst and drinking) or brain stem (effortless vomiting, difficulty swallowing) lesions resemble symptoms of eating disorders but may be distinguished on clinical grounds because specific psychopathology is usually not present. Onset of disturbed eating in an unusual age or gender, history of head injury, or epilepsy should prompt neurological examination, including a magnetic resonance imaging of the brain. Finally, in a patient with epilepsy or suspected brain damage, the development of disordered eating behaviour is a localising symptom suggestive of a right anterior focus.
We thank Dr Marin Trummer for kindly providing additional information. Rudolf Uher is supported by Nina Jackson Fellowship from the Psychiatry Research Trust, UK.
Competing interests: none declared