Clinical manifestations

Presentation and course

Eating disorders involve serious disturbances in eating behavior such as extreme reduction of food intake or severe overeating, as well as feelings of distress or extreme concern about body shape or weight (10; 68; 72; 43). These disorders usually begin with a prepubertal preoccupation with body image and an intense fear of being overweight. This stage is followed by intense dieting during adolescence and during the normal body shape changes that accompany it. As dieting becomes a perceived tool for controlling weight, disordered eating or chronic dieting is a frequent result. Patients often count calories, participate in activities that promote weight loss such as ballet or wrestling, and may have been witnessed vomiting.

Anorexia nervosa. Anorexia nervosa is characterized by an intense fear of weight gain, often associated with a disturbance in body image perception (Table 1) (67; 68; 76; 50). This prompts severe dietary restriction including fasting or other weight loss behaviors like purging or excessive physical activity. Medical complications of anorexia nervosa can affect all systems and are commonly due to malnutrition (17). Anorexia nervosa is further subdivided into the restricting or binge-eating/purging subtypes (05).

Severe emaciation may be accompanied by hypotension, bradycardia, and hypothermia. The skin may be dry and scaly. Hair loss, brittle hair, or fine downy body hair (lanugo) may be present. Dental erosions may be present. Additional features include delayed puberty, amenorrhea, infertility, arrested growth, and osteopenia or osteoporosis. Gastrointestinal manifestations include prolonged gastrointestinal transit and constipation. Neurologic complications in anorexia nervosa are primarily due to malnutrition and deficiency of specific nutrients and are discussed below.

Bulimia nervosa. Bulimia nervosa is characterized by repeated episodes of binge eating with compensatory behaviors to prevent weight gain like self-induced vomiting, fasting, extreme exercise, or inappropriate use of medications like diuretics and laxatives (74; 68) (Table 2). Body shape, weight, and appearance influence negative self-evaluation. Bulimia nervosa can occur at normal or elevated weight.

Physical findings in bulimia nervosa are less severe than those in anorexia nervosa; specific problems related to purging may include cardiac arrhythmias, electrolyte disturbances, metabolic acidosis due to laxative use, alkalosis due to vomiting, esophageal or gastric erosions or perforation, dental erosions, and acute renal injury.

Binge eating disorder. Recurrent episodes of binge eating are the hallmark of binge eating disorder (31; 21; 32; 23; 68) (Table 3). Both bulimia and binge eating disorder can be associated with obesity; compensatory behaviors are less common in binge eating disorder as compared to bulimia nervosa.

Avoidant-restrictive food intake disorder. Avoidant-restrictive food intake disorder is characterized by avoidance or restriction of food intake (15; 68) (Table 4). Milder cases may come across as being picky eaters. Additional symptoms include weight loss, nutritional deficiencies, dependence on enteral feeding or nutritional supplements, and psychosocial impairment. Patients may fear eating due to prior experiences like choking or vomiting, They may demonstrate extreme food selectivity, or have a lack of interest in food and eating.

Pica. Pica is characterized by intake of non-food or non-nutritive substances (20; 68) (Table 5). Boredom, curiosity, psychological stress, or taste of the substance being ingested are the primary triggers.

Rumination disorder. Rumination involves regurgitation of food after eating (68) (Table 6). Nausea or retching are not seen and a medical cause needs to be ruled out.

Psychiatric and neurologic comorbidities are commonly seen in patients with eating disorders and include mood and anxiety disorders, attention deficit hyperactivity disorder, personality disorders, neurodevelopmental disorders including intellectual disability and autism, and substance abuse (52; 61; 59; 69; 68).

Additionally, DSM-5 contains two additional categories: other specified feeding and eating disorders that includes atypical anorexia nervosa, bulimia nervosa or binge-eating disorder of low frequency and/or limited duration, purging disorder, and night eating syndrome. Another category called “others” includes muscle dysmorphia (body dysmorphic disorder) and orthorexia nervosa (obsession with healthy eating that can be associated with restrictive eating behaviors and malnutrition risk).

Table 1. DSM-IV-TR Diagnostic Criteria for Anorexia Nervosa

	(A) Restriction of energy intake relative to requirements, leading to a significantly low body weight in the context of age, sex, developmental trajectory, and physical health. Significantly low weight is defined as a weight that is less than minimally normal or, for children and adolescents, less than that minimally expected.
	(B) Intense fear of gaining weight or of becoming fat, or persistent behavior that interferes with weight gain, even though at a significantly low weight.
	(C) Disturbance in the way in which one’s body weight or shape is experienced, undue influence of body weight or shape on self-evaluation, or persistent lack of recognition of the seriousness of the current low body weight.
Specify whether:
	Restricting type: During the last 3 months, the individual has not engaged in recurrent episodes of binge eating or purging behavior (ie, self-induced vomiting or the misuse of laxatives, diuretics, or enemas). This subtype describes presentations in which weight loss is accomplished primarily through dieting, fasting, and/or excessive exercise.
	Binge-eating/purging type: During the last 3 months, the individual has engaged in recurrent episodes of binge eating or purging behavior (ie, self-induced vomiting or the misuse of laxatives, diuretics, or enemas).
Specify if:
	• In partial remission: After full criteria for anorexia nervosa were previously met, criterion A (low body weight) has not been met for a sustained period, but either criterion B (intense fear of gaining weight or becoming fat or behavior that interferes with weight gain) or criterion C (disturbances in self-perception of weight and shape) is still met.
	• In full remission: After full criteria for anorexia nervosa were previously met, none of the criteria have been met for a sustained period of time.
Specify current severity:
	The minimum level of severity is based, for adults, on current body mass index (BMI) (see below) or, for children and adolescents, on BMI percentile. The ranges below are derived from World Health Organization categories for thinness in adults; for children and adolescents, corresponding BMI percentiles should be used. The level of severity may be increased to reflect clinical symptoms, the degree of functional disability, and the need for supervision. • Mild: BMI ≥ 17 kg/m2 • Moderate: BMI 16 to 16.99 kg/m2 • Severe: BMI 15 to 15.99 kg/m2 • Extreme: BMI < 15 kg/m2

Table 2. DSM-5 Diagnostic Criteria for Bulimia Nervosa

	(A) Recurrent episodes of binge eating. An episode of binge eating is characterized by both of the following:
		1. Eating, in a discrete period of time (eg, within any 2-hour period), an amount of food that is definitely larger than most people would eat during a similar period of time and under similar circumstances. 2. A sense of lack of control over eating during the episode (eg, feeling that one cannot stop eating or control what or how much one is eating).
	(B) Recurrent inappropriate compensatory behaviors in order to prevent weight gain, such as self-induced vomiting; misuse of laxatives, diuretics, or other medications; fasting; or excessive exercise. (C) The binge eating and inappropriate compensatory behaviors both occur, on average, at least once a week for 3 months. (D) Self-evaluation is unduly influenced by body shape and weight. (E) The disturbance does not occur exclusively during episodes of anorexia nervosa.
Specify if:
	• In partial remission: After full criteria for bulimia nervosa were previously met, some, but not all, of the criteria have been met for a sustained period of time. In full remission: After full criteria for bulimia nervosa were previously met, none of the criteria have been met for a sustained period of time.
Specify current severity:
	The minimum level of severity is based on the frequency of inappropriate compensatory behaviors (see below). The level of severity may be increased to reflect other symptoms and the degree of functional disability. • Mild: An average of 1 to 3 episodes of inappropriate compensatory behaviors per week. • Moderate: An average of 4 to 7 episodes of inappropriate compensatory behaviors per week. • Severe: An average of 8 to 13 episodes of inappropriate compensatory behaviors per week. • Extreme: An average of 14 or more episodes of inappropriate compensatory behaviors per week.

Table 3. DSM-5 Diagnostic Criteria for Binge-Eating Disorder

	(A) Recurrent episodes of binge eating. An episode of binge eating is characterized by both of the following:
		1. Eating, in a discrete period of time (eg, within any 2-hour period), an amount of food that is definitely larger than what most people would eat in a similar period of time under similar circumstances.
		2. A sense of lack of control over eating during the episode (eg, a feeling that one cannot stop eating or control what or how much one is eating).
	(B) The binge-eating episodes are associated with 3 (or more) of the following:
		1. Eating much more rapidly than normal.
		2. Eating until feeling uncomfortably full.
		3. Eating large amounts of food when not feeling physically hungry.
		4. Eating alone because of feeling embarrassed by how much one is eating.
		5. Feeling disgusted with oneself, depressed, or very guilty afterward.
	(C) Marked distress regarding binge eating is present.
	(D) The binge eating occurs, on average, at least once a week for 3 months
	(E) The binge eating is not associated with the recurrent use of inappropriate compensatory behavior as in bulimia nervosa and does not occur exclusively during the course of bulimia nervosa or anorexia nervosa.
Specify if:
	• In partial remission: After full criteria for binge-eating disorder were previously met, binge eating occurs at an average frequency of less than 1 episode per week for a sustained period of time.
	• In full remission: After full criteria for binge-eating disorder were previously met, none of the criteria have been met for a sustained period of time.
Specify current severity:
	The minimum level of severity is based on the frequency of episodes of binge eating (see below). The level of severity may be increased to reflect other symptoms and the degree of functional disability. • Mild: 1 to 3 binge-eating episodes per week • Moderate: 4 to 7 binge-eating episodes per week • Severe: 8 to 13 binge-eating episodes per week • Extreme: 14 or more binge-eating episodes per week

Table 4. DSM-5 Diagnostic Criteria for Avoidant-Restrictive Food Intake Disorder

	(A) An eating or feeding disturbance (eg, apparent lack of interest in eating or food, avoidance based on the sensory characteristics of food, concern about aversive consequences of eating) associated with one (or more) of the following:
		1. Significant weight loss (or failure to achieve expected weight gain or faltering growth in children)
		2. Significant nutritional deficiency
		3. Dependence on enteral feeding or oral nutritional supplements
		4. Marked interference with psychosocial functioning
	(B) The disturbance is not better explained by lack of available food or by an associated culturally sanctioned practice.
	(C) The eating disturbance does not occur exclusively during the course of anorexia nervosa or bulimia nervosa, and there is no evidence of a disturbance in the way in which one’s body weight or shape is experienced.
	(D) The eating disturbance is not attributable to a concurrent medical condition or not better explained by another mental disorder. When the eating disturbance occurs in the context of another condition or disorder, the severity of the eating disturbance exceeds that routinely associated with the condition or disorder and warrants additional clinical attention.
Specify if:
	• In remission: After full criteria for avoidant/restrictive food intake disorder were previously met, the criteria have not been met for a sustained period of time.

Table 5. DSM-5 Diagnostic Criteria for Pica

	(A) Persistent eating of nonnutritive, nonfood substances over a period of at least 1 month.
	(B) The eating of nonnutritive, nonfood substances is inappropriate to the developmental level of the individual.
	(C) The eating behavior is not part of a culturally supported or socially normative practice.
	(D) If the eating behavior occurs in the context of another mental disorder (eg, intellectual disability or intellectual developmental disorder, autism spectrum disorder, schizophrenia) or medical condition (including pregnancy), it is sufficiently severe to warrant additional clinical attention.
Specify if:
	• In remission: After full criteria for pica were previously met, the criteria have not been met for a sustained period of time.

Table 6. DSM-5 Diagnostic Criteria for Rumination Disorder

	(A) Repeated regurgitation of food over a period of at least 1 month. Regurgitated food may be re-chewed, re-swallowed, or spit out.
	(B) The repeated regurgitation is not attributable to an associated gastrointestinal or other medical condition (eg, gastroesophageal reflux, pyloric stenosis).
	(C) The eating disturbance does not occur exclusively during the course of anorexia nervosa, bulimia nervosa, binge-eating disorder, or avoidant/restrictive food intake disorder.
	(D) If the symptoms occur in the context of another mental disorder (intellectual disability [intellectual developmental disorder] or another neurodevelopmental disorder), they are sufficiently severe to warrant additional clinical attention.
Specify if:
	• In remission: After full criteria for rumination disorder were previously met, the criteria have not been met for a sustained period of time.

Neurologic complications. Of all the eating disorders, anorexia nervosa and bulimia nervosa in particular can cause significant medical complications (53; 54; 28). Neurologic complications when present are generally the direct result of malnutrition (Table 7) (34).

Table 7. Neurologic Dysfunction in Eating Disorders

Peripheral nervous system and muscle
	• Peripheral neuropathy (including compression neuropathies) • Myopathy
Central nervous system
	• Cerebral or cerebellar atrophy • Limbic system dysfunction • Osmotic demyelination disorder • Neuroendocrine dysregulation • Wernicke-Korsakoff syndrome • Marchiafava-Bignami disease

Peripheral neuropathic and muscle disease. In reviewing records of 100 patients with anorexia nervosa, Patchell and colleagues found that neuromuscular abnormalities were the most common type of neurologic complication, being present in 45% of the patients. Generalized muscle weakness was detected in 43% of the patients and peripheral neuropathies in 13%. Only one patient had symptoms directly attributable to a vitamin B12 deficiency, and in most patients, the neurologic complications were reversed completely after correction of nutritional deficiencies and fluid and electrolyte imbalances (54).

One prospective controlled study of 51 patients with anorexia nervosa found that peripheral neuropathy is a notable complication of anorexia nervosa and is thought to be a product of chronic malnutrition rather than a specific nutrient deficiency (41). Micronutrient status is commonly altered in anorexia nervosa (02). Vitamin B deficiency, in particular vitamin B12, vitamin B1 (thiamine), vitamin B9 (folic acid), and vitamin B6 (pyridoxine) can cause peripheral neuropathy (34). Nutritional causes of neuropathy also include copper and vitamin E deficiency, though copper deficiency typically causes a myeloneuropathy and vitamin E deficiency is associated with a neuronopathy and often has a spinocerebellar presentation (34).

Patients with anorexia nervosa also appeared to be at increased risk for developing localized compression neuropathies secondary to subcutaneous tissue loss (41). Peroneal nerve palsy is the best characterized compression neuropathy and is thought to be due to a loss of tissue around the head of the fibula, which makes the peroneal nerve more susceptible to the direct pressure of crossed legs. This direct pressure can cause both focal demyelination and axonal loss. Given the absence of generalized neuropathy in these cases, concomitant nutrient deficiency is unlikely to have been the primary cause of the peroneal nerve palsy (30; 40). Two case reports by Alloway and colleagues describe neuromyopathy with severe wasting and asymmetrical weakness of proximal limb muscles (04). Both of these patients made complete recoveries on a mixed diet. Structural and functional changes in skeletal muscle in eight patients with anorexia nervosa were recorded by McLoughlin and colleagues (42). They found that protein-energy malnutrition lead to metabolic myopathy that could be successfully treated with an appropriate refeeding program.

Central nervous system disease.

Cerebral atrophy and functional brain changes. Multiple studies have shown that patients with anorexia nervosa have reduced brain mass (75). These include postmortem studies that showed reduced cerebral mass with prominent sulci and small gyri, CT neuroimaging studies that have additionally shown enlarged ventricles, and MRI studies that have shown large CSF volumes in association with deficits in total gray matter and total white matter volumes as well as enlarged ventricles. These abnormalities are less pronounced in individuals with bulimia nervosa.

A study by Wagner and colleagues, which examined 40 patients recovered from anorexia nervosa as well as 10 patients recovered from bulimia nervosa, suggests that these structural brain abnormalities may be reversible after long-term recovery from the eating disorder (75). It is thought that the degree of recovery from an eating disorder may be critical for normalization of brain morphometry. Although emaciation and malnutrition are known to be associated with altered brain morphology abnormalities in anorexia nervosa, the physiology underlying changes in the brain structure remains elusive. Because the abnormalities are reversible, it is thought that they may be related to fluid shifts that are perhaps caused by altered hormonal function. Cortisol levels and triiodothyronine levels have been studied and found to be correlated to CSF volumes and ventricular size, respectively. It is also thought that decreased serum proteins may result in decreased colloidal osmotic pressure and a resultant shift of fluid from the intravascular space into the subarachnoid spaces.

In an attempt to identify brain regions critically involved in the pathophysiology of anorexia nervosa, Muhlau and colleagues applied voxel-based morphometry in recovered anorexia nervosa patients compared to controls (48). They found that gray matter was significantly decreased across the whole brain in the anorexia nervosa group, and only one small cluster of gray matter loss was identified, within the left anterior cingulate cortex. The severity of anorexia nervosa was the only clinical variable that correlated with the gray matter content of the anterior cingulate cortex cluster. The relevance of this is not yet fully understood.

Although neuroanatomical abnormalities often correct in weight-restored anorectic individuals, specific functions in certain cortical areas fail to correct in these patients, suggesting trait-related abnormalities. For example, reduced 5-HT2A receptor binding has been found to remain after long-term weight restoration in patients with anorexia nervosa. In individuals with bulimia nervosa, thalamic and hypothalamic serotonin transporter availability is reduced in relation to the duration of the bulimia nervosa (62). Studies that used single positron emission computed tomography in patients with anorexia nervosa showed hypoperfusion in the medial prefrontal cortex and anterior cingulated cortex even after weight restoration (64). Using functional magnetic resonance imaging, patients with recovered anorexia nervosa compared to controls had increased medial prefrontal and anterior cingulate cortex activation as well as lack of activity in the inferior parietal lobule (71). Chronically ill patients showed increased activation of the right lateral prefrontal, frontopolar, and dorsal anterior cingulated cortices. Additionally, asymmetric functional deficits have been found in women with anorexia nervosa and bulimia nervosa, which supports the hypothesis that anorexia nervosa involves specific left hemisphere dysfunction and bulimia nervosa involves specific right hemispheric dysfunction (16).

Cerebellar atrophy. At least two cases of cerebellar atrophy have been reported in the literature, with one patient displaying marked cerebellar ataxia (03; 45). Although the exact relationships between eating disorders and cerebellar atrophy are not clear, it is possible that the atrophy may be induced by life-threatening undernutrition. The reversibility of the cerebellar atrophy has not been determined.

Limbic system dysfunction. Some functional neuroimaging studies in patients with early-onset (onset in individuals younger than 15 years) anorexia nervosa have shown unilateral reduction of blood flow in the temporal region and impaired visuospatial ability, impaired visual memory, and enhanced speed of information processing (36). The reduced regional cerebral blood flow is noted to persist independently of variables such as previous or current nutritional status as well as eating disorder psychopathology so that the hypoperfusion is thought to be either a primary phenomenon or a result of starvation that is slow to reverse or is irreversible. It is thought that the system most likely to account for the characteristic features of anorexia nervosa as well as reduced blood flow and impaired cognitive functioning is the limbic system. Lask and colleagues hypothesize that limbic system dysfunction in anorexia nervosa might emerge as a final pathway of interactions between predisposing and precipitating factors, though clearly further research is required to test these hypotheses (36).

Osmotic demyelination disorder. Patients with eating disorders may attempt weight loss through vomiting, polydipsia, and laxative and/or diuretic abuse. These behaviors can lead to hyponatremia and/or hypokalemia. Hyponatremia when rapidly corrected can lead to rapid shifts in plasma osmolality with disruption of myelin (osmotic demyelination disorder). Pontine or extrapontine myelinolysis have been described in patients with eating disorders (58). Sites involved on MRI may include the pons, mesencephalon, caudate, putamen, globus pallidus, and centrum semiovale. Symptoms resulting during osmotic demyelination disorder have been reported to include agitation, emotional lability, tremulousness, dystonia, gait ataxia, quadriparesis, locked-in syndrome, encephalopathy, dysarthria, dysphagia, and bradykinesia.

Neuroendocrine dysregulation. It is still not clear what comes first, neuroendocrine alterations that could represent pathogenetic causes of eating disorders or eating disorder psychopathology that results in nutritional impairment and, as a result, neuroendocrine changes (47). Either way, changes are seen in multiple hormones and peptides, including leptin, ghrelin, brain-derived neurotrophic growth factor, and endocannabinoids. These changes likely occur to signal to the brain that a more energy-saving metabolic state and increased caloric ingestion are needed. In addition to modulating food intake, some of these compounds intervene in the regulation of psychological dimensions that are altered in anorexia nervosa and bulimia nervosa. Most of the neuroendocrine changes are state dependent, but some do persist after recovery from the eating disorder, especially if the recovery is not to full body weight. These persistent changes may then make relapse or recurrence more likely to occur (47).

Refeeding syndrome. Studies have shown that over one quarter of adolescents with anorexia nervosa hospitalized for malnutrition experience mild to moderate hypophosphatemia during refeeding. This can lead to muscle weakness, acute areflexic paralysis, paraesthesias, and cranial nerve palsies, all thought to be owing to tissue hypoxia. Hypophosphatemia may also cause seizures, coma, and mental status changes including delirium (22).

Wernicke encephalopathy. Wernicke encephalopathy is an acute neuropsychiatric syndrome due to thiamine deficiency that is characterized by mental status changes, gait ataxia, and ophthalmoplegia (56; 34). As the encephalopathy resolves, an amnestic confabulatory syndrome called Korsakoff psychosis evolves. It has classically been described in the setting of alcoholism but can be seen in many different settings including anorexia-nervosa-related malnutrition (56).

Marchiafava-Bignami disease. Marchiafava-Bignami disease is a rare disorder characterized by demyelination involving the corpus callosum and is typically seen in the setting of chronic alcoholism. It has rarely been described in association with other conditions like malnutrition, including anorexia nervosa-related malnutrition (65).

Prognosis and complications

It is estimated that nearly one half of patients with anorexia nervosa recover, 33% improve somewhat, and 20% remain chronically ill. Similar to anorexia nervosa, approximately 50% of patients with bulimia nervosa recover, 30% improve somewhat, and 20% continue to meet full diagnostic criteria for bulimia nervosa. Long-term follow-up studies suggest that only 10% of bulimic individuals continue to fully meet diagnostic criteria after 10 years of the illness (01).

Mortality rates for anorexia nervosa and bulimia nervosa are the highest in psychiatric conditions and amongst the highest in medical conditions (10). Mortality from anorexia nervosa has been estimated to be 5% per decade which is about 12 times higher than the annual death rate due to all causes of death among females ages 15 to 24 in the general population. The most common causes of death are complications of the disorder, such as cardiac arrest or electrolyte imbalance, and suicide (51).

The prognosis of any neurologic event occurring in the setting of an eating disorder depends on the specific clinical situation and etiology of the process in question. Many symptoms resolve with re-establishment of proper nutrition. Refeeding needs to be done with care and in a controlled setting to avoid the neurologic complications associated with hypophosphatemia.

Biological basis

Etiology and pathogenesis

Biological, social, and psychological factors are implicated in the causes of both anorexia nervosa and bulimia nervosa. Family and twin studies have shown that eating disorders are strongly familial and that the familial association is due primarily to genetic factors. It has been suggested that a trait-related disturbance of serotonergic neuronal modulation predates the onset of anorexia nervosa and contributes to premorbid symptoms of anxiety and inhibition. This disturbance may also mediate the hedonic aspects of feeding, thereby making individuals susceptible to disturbed appetitive behaviors. In these persons, restricting food intake is powerfully reinforcing because it provides temporary respite from dysphoric mood (29). Environment may also play an important role in the expression of underlying genetic predispositions. Enhanced research efforts are required to be able to identify true risk and protective factors for eating disorders (13). There has been considerable recent interest in the importance of hypothalamic adaptive processes to our understanding of the etiology and pathogenesis of eating disorders (66).

The etiologies of the various neurologic complications of eating disorders are diverse and discussed in the paragraphs describing the specific neurologic complications in the “Clinical Manifestations” section.

The pathophysiology of the various neurologic complications of eating disorders are diverse and noted, if known, in the paragraphs that discuss the individual neurologic features in the “Clinical Manifestations” section.

Epidemiology

Adolescents and young adults are particularly at risk for eating disorders. Identified risk factors include abuse, trauma, and childhood obesity; personality and mood disorders are recognized comorbidities (08). Increased vulnerability has also been recognized in sexual minorities (70). It has been suggested that there may be a link between eating disorders and autism spectrum disorder (14). Anorexia nervosa generally starts earlier than bulimia nervosa or binge eating disorder; it is rare for anorexia nervosa to start after 30 years of age (26; 38; 10; 68). Anecdotal reports of anorexia nervosa, however, have noted increasing presentations in prepubertal children as well as new-onset cases in mid-life and late-life (13).The duration of untreated eating disorder before start of treatment appears to be shorter for anorexia nervosa as compared to bulimia nervosa or binge eating disorder. A 2007 study noted lifetime prevalence estimates of DSM-IV anorexia nervosa, bulimia nervosa, and binge-eating disorder to be 0.9%, 1.5%, and 3.5%, respectively among women, and 0.3%, 0.5%, and 2%, respectively among men (25). Over the past decade incidence rates have been stable for anorexia nervosa, stable or declining for bulimia nervosa, and rising for binge eating disorder (44; 60).

The most common late-life eating disorder is binge eating disorder. This is more common in women; comorbid anxiety or depression is common and body image perception is the underlying concern (39). It is important to be aware of these particularly since most eating disorders present in childhood.

Formal incidence and prevalence studies of the neurologic complications of eating disorders have not been performed.

Prevention

Early detection of eating disorders and ways to facilitate that detection are of paramount importance (27). Further identification of risk factors for eating disorders will hopefully lead to the ability to modify these factors in order to prevent or minimize eating disorders. Preliminary evidence supports that the development of eating disorders is related to dieting, media use, body image dissatisfaction, and weight-related teasing. Other potential risk and/or protective factors are thought to include self-esteem, depression, dietary intake patterns, the role of parental encouragement or role modeling of weight-related behaviors, and the role of a home environment that is supportive of healthy eating and physical activity behaviors (19; 33).

The prevention of the neurologic complications of eating disorders involves preventing the malnutrition and electrolyte imbalances associated with eating disorders. Careful correction of the malnutrition and electrolyte imbalances is also imperative to minimize osmotic demyelination disorder and to avoid the hypophosphatemia associated with refeeding.

Differential diagnosis

The differential diagnosis of eating disorder symptoms includes the following:

	• Anorexia nervosa
	• Bulimia nervosa
	• Binge eating disorder
	• Avoidant-restrictive food intake disorder
	• Pica
	• Rumination disorder
	• Medical illnesses causing weight loss, in particular inflammatory bowel disease, thyrotoxicosis, diabetes mellitus, and systemic malignancies
	• A broad range of psychiatric and neurodevelopmental disorders
	• Neurologic disorders like epilepsy, brain tumor, Kluver-Bucy syndrome, Kleine-Levin syndrome
	• Sleep-related eating disorder
	• Body dysmorphic disorder

Diagnostic workup

A broad range of laboratory abnormalities can be seen due to starvation or purging (55; 10; 68). This is particularly so in anorexia nervosa. Laboratory abnormalities could include anemia, leukopenia, thrombocytopenia, hypoglycemia, elevated liver enzymes, hypothyroidism, low levels of estrogen or testosterone, elevated levels of corticotrophin-releasing hormone and growth hormone, and elevated salivary amylase due to vomiting. Purging can result in hypokalemic alkalosis. Laxative use may result in metabolic acidosis. Dehydration can result in acute kidney injury. Electrolyte abnormalities hypokalemia and hypophosphatemia can result in electrocardiographic abnormalities. Hyponatremia may also be seen.

The diagnostic workup for any neurologic complication of an eating disorder depends on the type of neurologic process present and the clinical situation. The goal of each workup is to confirm the presence of the specific problem and to exclude other processes that may be co-occurring with, but are independent from, the eating disorder itself. It is important to remember that neurologic complications related to thiamine deficiency in anorexia nervosa can be present despite normal serum thiamine levels (56; 34).

If peripheral nerve involvement is suspected, EMG and nerve conduction velocity studies can be performed and additional laboratories obtained as would be done for any routine peripheral neuropathy evaluation. It is important to remember the potential for electrolyte abnormalities and nutritional deficits in individuals with eating disorders. If the clinical presentation suggests muscle involvement, EMG and nerve conduction velocity can be obtained. Additional laboratory studies such as muscle enzymes and erythrocyte sedimentation rate can also be useful. Muscle biopsy may be performed but is rarely recommended as myopathy in eating disorders is treated by simply instituting an appropriate refeeding program (42).

MRI of the brain or spinal cord may show specific findings in vitamin B12 or copper deficiency and in Wernicke-Korsakoff syndrome (34). In a patient presenting with a seizure or encephalopathy, a structural lesion should be excluded with appropriate neuroimaging and an electroencephalogram should also be obtained. Metabolic and/or nutritional derangements (especially hypophosphatemia) must be sought with appropriate laboratory testing.

Management

The goals of treating an eating disorder involve restoring the patient to a healthy weight, treating the physical complications, enhancing the patient’s motivation, providing education regarding healthful nutrition, helping patients reassess and change core dysfunctional cognitions and feelings related to the eating disorder, treating associated psychiatric conditions, enlisting family support and providing family counseling, and preventing relapse (06; 07; 73; 24; 49; 12; 37; 46). These goals are often best met with the cooperation of a team of treatment providers, including a psychiatrist, therapist, and dietician. Antidepressants have not been associated with benefit on weight or symptoms; in some cases, the second generation antipsychotic olanzapine has been associated with weight gain in anorexia nervosa (49).