This patient developed EPM unexpectedly after the intravenous use of pituitrin to control hemoptysis. Pituitrin, extracted from the posterior pituitary, consists of oxytocin and vasopressin. The latter can activate type-1A receptors located in vascular smooth muscle cells resulting in vasoconstriction [
5]. Thus, pituitrin has been used in gastrointestinal or pulmonary haemorrhage, and the result is almost as if forceps had been applied directly to the bleeding vessel. In addition, water reabsorption is mediated by vasopressin activation of type-2 receptors in the basolateral membrane of cells in the renal collecting ducts, which causes a decrease in plasma osmolality [
5]. There was no medical history of hyponatremia, absence of adrenal, thyroid, pituitary or renal insufficiency, and no recent use of diuretic agents in this patient; pituitrin was implicated as the very probable contributory factor to the development of severe hyponatremia.
Hyponatremia can be classified into acute (<48 h) and chronic (≥48 h) hyponatremia. When hyponatremia develops, the brain reduces the number of osmotically active particles within its cells (mostly organic solutes) in an attempt to adapt to the osmotic change, which takes 48 h [
6]. CPM and EPM are acquired metabolic disorders of acute central demyelination strongly associated with rapid correction of hyponatremia [
7]. CPM typically involves the central pontine and EPM involves different brain regions, such as the cerebellum, thalamus, basal ganglia or subcortical white matter. Clinical heterogeneity due to CPM/EPM affecting the basal ganglia has been reviewed by de Souza A [
8], such as dystonia, tremor, myoclonus, gait disorders, dysarthria, cognitive impairment, depression and others. Focal oromandibular dystonia and asymmetric myoclonus that developed in a delayed manner in the patient are rare presentations. The possibility that delayed movement disorders may arise in EPM due to ineffective or faulty reorganization in the basal ganglia has been considered in an earlier report [
9]. Sequential observation of symptoms and brain images in the case of CPM and EPM revealed that delayed movement disorders as a result of changes in the signal of the basal ganglia, were explained by the destruction of regional myelin [
10]. Special populations seem vulnerable to the development of osmotic myelinolysis, including not only alcoholics and malnourished patients but also those with liver disease, sepsis, adrenal insufficiency and severe burns [
11]. Previous cases have shown that the chronicity of hyponatremia before correction is a critical risk factor for the development of osmotic myelinolysis [
12],[
13]. In this patient, chronic hyponatremia was documented to exist for at least 48 h, and after a rapid increase of serum sodium from 118 mmol/L to 134 mmol/L in 24 h, there was a delay of one day before progressive neurological decline. Recommendations suggest that ideally hyponatremia should be corrected by limiting the sodium increase to not more than 8–10 mmol/L every 24 h [
2]. We identified three cases, each reporting a single case in which deamino arginine vasopressin, a type of vasopressin analogue, was implicated as a possible contributory factor to the development of severe electrolyte imbalances that triggered osmotic demyelination [
14]-[
16]. Although the true aetiology of CPM/EPM remains unclear, abrupt osmotic shifts have been considered to play a critical role in their pathogenesis. Deamino arginine vasopressin and pituitrin may predispose patients to osmotic demyelination by causing hyponatremia and extreme serum sodium fluctuations rather than by exerting any direct myelinolytic effect. Further studies are needed to clarify whether the use of pituitrin or its analogue is associated with a risk of osmotic demyelination independent of the electrolyte disturbance.
This case and literature review highlight that: 1) Hyponatremia is the most frequent electrolyte disturbance observed in hospitalized patients [
17]. Drugs such as pituitrin can cause profound hyponatremia, which should be considered in the differential diagnosis when approaching a patient with hyponatremia. 2) Osmotic myelinolysis is most frequently associated with rapid correction of hyponatremia [
3]. Prevention of CPM and EPM by exercising caution in the correction of hyponatremia, especially chronic hyponatremia, is more important than early diagnosis.