Central pontine myelinolysis in anorexia nervosa: case report of a Chinese adolescent

Abstract

Central pontine myelinolysis (CPM) is a rare neurologic disorder characterized by symmetric demyelination in the central region of pons. Until recently its prognosis was considered poor if not fatal. CPM may manifest as a severe complication of eating disorders, especially anorexia nervosa (AN), primarily due to a rapid correction of hyponatremia. In this report, we presented the case of a 13-year-old girl with a five-month history of AN who exhibited typical CPM brain lesions, confirmed by magnetic resonance imaging (MRI) examination without the context of severe electrolyte imbalances. Surprisingly, despite the patient’s critical clinical manifestations in the initial stages, her prognoses of both AN and CPM were relatively optimistic. We discussed these observations in the light of recent reports on CPM and AN comorbidity. Although the clinical implications of MRI-detected lesions remain uncertain, psychiatrists should be cautious about CPM when refeeding patients with AN. Further studies about the relationship between CPM and AN are imperative.

Introduction

Central pontine myelinolysis (CPM) is a rare neurologic disorder characterized by symmetric demyelination of axons within the central pon [1]. The etiology and pathogenesis of CPM remain elusive, which may be potentially related to neuronal swelling resulting from rapid alterations in osmotic gradients [2]. Consequently, CPM often manifests as a severe complication in eating disorders, particularly anorexia nervosa (AN), primarily attributed to the rapid correction of hyponatremia and hypokalemia [3]. It is noteworthy that the initial symptoms of CPM may be unspecific, potentially leading to a misdiagnosis as functional impairments associated with eating disorders. Herein, we reported the case of a 13-year-old girl with a diagnosis of AN who exhibited CPM without the context of severe hyponatremia and hypokalemia.

Case report

The patient had a five-month history of AN. Due to high academic pressure, she began to control her calorie intake strictly and consume excessive amounts of water (2–4 L per day) since February 2023. This resulted in a significant weight loss of 15.5 kg over two months, from 44 kg to 28.5 kg, with a corresponding drop in BMI from 17.2 kg/m² to 11.1 kg/m² (height: 160 cm). She gradually became irritable and lost her temper very easily. She was first admitted to the pediatric ward of a general hospital due to unconsciousness, disorganized speech and behaviors, in April 2023. Upon initial assessment, her physician noted that she was cachectic and might not have a favorable prognosis. Her neurological examination at admission was unremarkable except for a slight increase in muscle tone.

She underwent a series of laboratory tests and examinations upon initial admission, revealing malnutrition (BMI:11.32 kg/m²) and mild hyponatremia (Na = 133.9mmol/L), both attributed to her AN. The ultrasonic cardiogram indicated the presence of a small amount of pericardial effusion. Brain MRI showed enlarged sulci in both hemispheres and a possible demyelination in the right frontal lobe (Fig. 1a). Despite undergoing lumbar puncture, cerebrospinal fluid tests failed to yield significant abnormalities. To restore normal electrolyte levels and fluid homeostasis, a combination of enteral and parenteral supplementation, along with high doses of B vitamins and antibiotics, were administered. Following six days of nasogastric tube feeding, the patient developed hypophosphatemia with a level of 0.88mmo/L. Throughout her entire hospital stay, she was in a continuous state of delirium, necessitating constant supervision and care from her mother and medical personnel for her daily routines, which consequently restricted her ability to consume water autonomously. All fluid replacements and enteral nutrition were administered following consultations between pediatric specialists and dietitians. During her hospitalization, her fluid intake and output maintained a consistent balance, with daily intake ranging from approximately 1650 ml to 3000 ml and output from approximately 1500 ml to 2800 ml. Table 1 showed the changes of her electrolytes during hospitalization. Her daily medication regimen included sertraline (25 mg qd), olanzapine (2.5 mg qn), lorazepam (0.5 mg tid), and diazepam (10 mg qn). Three weeks later, a repeat MRI revealed an abnormal signal in the pons, indicating a possible diagnosis of CPM (Fig. 1b). Her muscle tone progressively returned to normal, her consciousness began to slowly regain, and her weight increased to 35.7 kg (BMI:13.9 kg/m²).

As her physical and mental conditions showed marked improvements, her parents decided to transfer her to a specialized psychiatric inpatient ward for the treatment of AN. Upon admission, a comprehensive psychiatric assessment revealed her distorted perception of being overweight, excessive focus on weight and body shape, irritability, and suicidal thoughts. Initially, she displayed resistance towards dietary plans, insisted on discharge, and held hostility towards all medical staff. Remarkably, however, her attitude underwent a significant shift within one week. She embraced pharmacological and dietary interventions, engaging in the study of the Motivation and Psycho-Education Self-Help (MOPED) manual under the guidance of her psychiatrist. Over the subsequent month, she underwent an integrated treatment program encompassing medication (sertraline and olanzapine), psychotherapy, and a gradual increase of enteral nutrition, starting from 1725 kcal/day and gradually increasing to 2700 kcal/day (Fig. 2). She actively studied the contents of MOPED manual, completed relevant exercises, and shared her confusions openly with her psychiatrist. Following a 28-day hospital stay, she was discharged weighing 41 kg, which equated to a BMI of 16.01 kg/m² and fell within the normal range for 13-year-old [4]. Recognizing her outstanding progress, she was selected to deliver a speech titled My Journey to Recovery to all patients before her discharge. She clearly described the changes in her mental state and firmly expressed her commitment to persist in her battle against AN.

Table 1 Variations in electrolyte levels during the period of stay in the pediatric ward

Fig. 1

a. Initial MRI (DWI and T2-weighted images) were negative upon admission

b. The second MRI (T1- and T2-weighted images) showing long T1 and T2 signals in central pontine (as indicated by the arrow)

Fig. 2

The patient’s treatment program in the psychiatric inpatient ward

Discussion

Central pontine myelinolysis (CPM), initially documented by Adams and his colleagues in 1959, constitutes a subset of Osmotic Demyelination Syndrome (ODS) [5]. It is characterized by the deterioration of select brain regions, predominantly the pontine white matter tracts. Early cases were reported in individuals with alcohol use disorder or malnutrition. Subsequent reports have documented CPM occurring in a diverse range of conditions, including severe burns, liver transplantation, anorexia nervosa (AN), hyperemesis gravidarum, and hyperglycemic states [6]. Despite the lack of a comprehensive understanding of the etiology, Laureno and colleagues leveraged animal models to suggest that the rate of sodium correction might be a pivotal factor contributing to CPM [7]. Rapid correction of hyponatremia prevents the brain from reabsorbing lost osmolytes, resulting in brain tissue dehydration and white matter demyelination. Patients diagnosed with CPM exhibited histological features including demyelination accompanied by astrocytosis, as well as infiltration of lymphocytes and macrophages into affected tissues [8]. Recent studies showed that myelin loss preceded astrocyte apoptosis, which was observed within 48–72 h following hyponatremia correction [9].

The clinical manifestations of CPM reflect damage to upper motor neurons, commonly exhibiting a distinct two-stage progression [10]. Initially, patients present with acute encephalopathy and seizures, which tend to resolve upon normalization of sodium levels. However, within 3 to 5 days, a clinical deterioration sets in, marked by a range of signs and symptoms including altered consciousness, dysphagia, dysarthria, spastic quadriparesis, pseudobulbar paralysis, ataxia, lethargy, tremors, dizziness, catatonia, and in the most severe cases, locked-in syndrome and coma [11,12,13]. Brain MRI is not required but can be used to confirm the diagnosis, especially when the diagnosis remains uncertain, as exemplified in this case. Characteristic findings on diffusion-weighted imaging (DWI) reveal diffusion restriction centered within the pons while sparing the peripheral regions. T2 and T2-flair images typically exhibit a “bat-wing” shaped distribution within the central pons, which are generally seen later in presentation [5, 14]. It is important to note that imaging findings may be delayed up to two weeks. Thus, a negative MRI image does not exclude the diagnosis of CPM.

The association between CPM and AN remains uncertain due to limited case reports in the literature. Typically, patients with AN exhibit severe malnutrition and abnormal eating behaviors [3]. CPM occurring in people with AN has already been reported as a direct consequence of the abnormal eating behaviors [15,16,17]. However, the progression from AN to CPM seems to be complicated, encompassing water-electrolyte imbalances and refeeding syndrome (RS) [18]. RS has been defined as a severe electrolyte and fluid imbalance associated with metabolic abnormalities in patients with malnutrition undergoing realimentation [19]. The syndrome comprises elevated serum glucose levels, electrolyte disturbances (especially hypophosphatemia and hypomagnesemia), vitamin deficiencies (particularly vitamin B1), fluid imbalance, and salt retention, leading to impaired organ function and cardiac arrhythmias [20]. For the case present, she displayed clinical and typical imaging indicators of CPM alongside mild hyponatremia. She was diagnosed with a hypophosphatemia (0.88mmol/L) in the pediatric ward, which was probably attributed to RS.

In this case, the patient’s clinical presentation is marked by psychiatric manifestations resembling a delirious organic brain syndrome. The progressive transformation of the clinical manifestation and her previous history of AN, along with an initial normal MRI, posed a diagnostic challenge in identifying the coexistence of CPM and AN as a comorbid condition. Despite the severity of her initial clinical manifestations, her prognosis for both AN and CPM appeared relatively favorable. Several case studies have documented instances of benign clinical prognosis of CPM in adolescents [21]. Notably, Lilje CG and colleagues described a comparable case, exhibiting reversible neuroimaging abnormalities and a favorable clinical outcome [22]. Nevertheless, there has been a scarcity of pertinent case reports in past two decades, with virtually no contributions from developing nations. This case highlights not only a complication of eating disorders but also critical aspects deserving further exploration. While electrolyte imbalances might be overemphasized, psychiatrists must proceed with caution when refeeding patients with eating disorders, mindful of potential CPM. Although the clinical implications of lesions detected by MRI are still uncertain, psychiatrists may recommend a brain MRI examination to patients when CPM is suspected. Facilitating seamless interdisciplinary communication in the management of patients with eating disorders is paramount. The patient’s swift recovery in the psychiatric ward suggested that the concurrence of AN and CPM may herald a positive treatment outcome. Further research elucidating the intricate relationship between CPM and AN is imperative.