Patients more susceptible to CPM include those with a history of malnutrition, alcohol use disorder, chronic liver disease, and hyperemesis gravidarum. Patients most commonly have a history of rapid sodium correction, greater than 0.5-1.0 mEq/L per hour. The most susceptible patients are those with chronic hyponatremia (>48 hours) or those with severe hyponatremia (Na <120 mEq/L). 

The onset of symptoms is usually seen 1 to 14 days after electrolyte correction. Clinical features of central pontine myelinolysis reflect damage to upper motor neurons and generally present in a biphasic course. Initially, patients present with acute encephalopathy and seizures that typically resolve as normal sodium levels are restored. This is later followed by clinical deterioration 3-5 days later. Signs and symptoms include dysphagia, dysarthria, spastic quadriparesis, pseudobulbar paralysis, ataxia, lethargy, tremors, dizziness, catatonia, and in the most severe cases, locked-in-syndrome and coma. [11][12]

Clinical assessment, review of labs with particular attention to the rate of sodium correction is essential in the evaluation and diagnosis of CPM. Imaging is not required but can be used to confirm the diagnosis, especially if the diagnosis is uncertain. Characteristic findings on magnetic resonance imaging are seen on diffusion-weighted imaging (DWI), showing diffusion restriction of the central pons with sparing of the periphery. These findings are usually seen within 24 hours of the onset of signs or symptoms. T2 and T2-flair images signal in a “bat-wing” shaped central pontine distribution and are generally seen later in presentation [13] Imaging findings can be delayed for up to 2 weeks, thus if imaging is negative, the diagnosis of CPM is not excluded. If clinical suspicion for CPM remains high, MRI should be repeated within two weeks. [14]

Prevention

The treatment of central pontine myelinolysis is primarily aimed at prevention. Various studies have been conducted to determine the rate at which sodium should be corrected. The current recommendations are to correct the sodium not more than 8-12 mEq/L per 24 hours. However, in patients with hyponatremia lasting 48 hours or of unknown duration, the rate of serum sodium correction should not exceed 6-8 mEq/L per 24 hours. 

In cases of severe hyponatremia (sodium <120 mEq/L) with neurologic symptoms, a hypertonic solution of 3% saline should be administered. If neurologic symptoms are not present, the primary focus should be on a slow rate of sodium correction with intravenous fluids to achieve a rate that does not exceed 8-12 mEq/L per 24 hours. During the infusion of fluids, it is essential to monitor serum sodium levels every 4-6 hours. If there are severe derangements in sodium, sodium levels can be monitored hourly.

Retrospective studies have shown that desmopressin has been safe and effective in preventing and reversing the overcorrection of hyponatremia. These studies also assessed the introduction of desmopressin as either proactive therapy, reactive therapy, or rescue therapy. They concluded that a proactive strategy of desmopressin administration with hypertonic saline was associated with a lower incidence of sodium overcorrection. Typically, desmopressin 1 to 2 mcg is administered intravenously or subcutaneously, every 6-8 hours for 24 hours. Patients are simultaneously given intravenous hypertonic saline at 15 to 30 ml/hr. [15][16]

Reintroduction of Hyponatremia 

5% dextrose in water (D5W) and desmopressin can be utilized with the goal of reintroducing hyponatremia to ensure that the rate of correction will be 8-12 mEq/L when the rate of sodium correction has been too rapidly corrected. Desmopressin binds to V2 receptors of the renal collecting duct, which translocates aquaporin channels to the apical lumen of the collecting duct and increases water reabsorption. It can be given at a dose of 2 to 4 mcg intravenously or subcutaneously. D5W at 6 mL/kg of lean body weight can be infused over 1 to 2 hours and should decrease serum sodium by 2 mEq/L. Infusion of D5W is continued until goal serum sodium is reached. [17]

Supportive care

Supportive care measures include ventilator support, intense physiotherapy and rehabilitation, and anti-parkinsonism drugs.

Experimental Strategies

There have been no randomized control studies conducted to confirm the efficacy of these treatment modalities. However, they have been used in a small number of cases and have been shown to have positive outcomes.

Plasmapheresis has also been studied to improve neurologic sequelae of CPM. In a small number of case studies in patients with severe hyponatremia, plasmapheresis was seen to improve neurologic manifestations from 10 days to 1-year post-therapy. Although patients improved clinically, MRI findings remained unchanged after plasmapheresis. These studies lead investigators to believe that therapeutic plasmapheresis could possibly reduce high-molecular myelinotoxic substances that are released during osmotic stress. [18][19]

The use of glucocorticoids, such as dexamethasone, has also been studied as glucocorticoids are known to impact the permeability of the blood-brain barrier. Studies done in rat models showed minimal neurologic impairment in rats that were treated with dexamethasone 2mg/kg at 0 and 6 hours after hypertonic 3% saline was administered. The rats that were treated with dexamethasone also exhibited rare lesions on brain imaging in comparison to the untreated group, which exhibited numerous brain lesions. There have been few cases where dexamethasone was used in humans. However, this is not well studied, and further investigation is warranted. [20]

Differential diagnoses for central pontine myelinolysis include hypertensive encephalopathy, multiple sclerosis, brainstem infarct, pontine neoplasms such as astrocytomas, CNS lymphoma, brainstem metastasis, progressive multifocal leukoencephalopathy, acute autoimmune or infectious encephalitis, mitochondrial encephalopathies, and CNS vasculitis

Central pontine myelinolysis was once thought to be fatal, with a mortality of 90% to 100%. This is likely because it was initially diagnosed at autopsy. The mortality rate has significantly decreased, with recent retrospective studies showing 94% survival. These studies cite that about 25%-40% make a complete recovery without deficits, and 25%-30% remain incapacitated. [21][22][23]

Patients with risk factors for poor prognostic outcomes are those with serum sodium of <120 mEq/L, hypokalemia, and low Glasgow coma scale (GCS) during hospitalization. Autologous liver transplant patients who develop central pontine myelinolysis or osmotic demyelination syndrome were also reported to have worse outcomes, with a mortality of 63% at one year. [24] [23]

Clinical and radiological features were not found to be of prognostic significance. Improving prognostic outcomes focuses on early recognition of those patients that are at higher risk of developing CPM, avoiding rapid overcorrection of sodium, and making a prompt diagnosis of the condition. Favorable prognostic outcomes also include the avoidance of secondary complications of the condition such as aspiration pneumonia, urinary tract infection, or deep venous thrombosis. [21]

Complications of CPM can vary on a case by case basis. Central pontine myelinolysis can have neurologic manifestations such as locked-in syndrome, coma, and death. 

Secondary complications include venous thromboembolism, aspiration pneumonia, ventilator dependence, muscle atrophy, urinary tract infections, and decubitus ulcers. 

Given the possible deleterious complications of CPM, patients should be educated on the disease process, treatment options, and prognosis. Patients should also be involved in regular interval follow-up once they are discharged from the hospital in order to better evaluate their clinical improvement. 

The management of central pontine myelinolysis is challenging and requires the coordination of physicians and ancillary staff to have positive outcomes. The critical component is the prevention of the condition, which is structured around close monitoring of serum sodium levels. Patients being monitored should be under close surveillance in the appropriate setting, such as the intensive care unit. Serum sodium levels should be monitored every 4-6 hours, or hourly if there are severe derangements. Current recommendations for the rate of sodium correction are 8 to 12 mEq/L per 24 hours. However, in patients with hyponatremia lasting 48 hours or of unknown duration, the rate of serum sodium correction should not exceed 6 to 8 mEq/L per 24 hours. [Level 1]

The interprofessional team may include intensivists, neurologists, nurse practitioners, critical care nurses, and pharmacists. Providers should be aware of this devastating complication. Nurses must monitor sodium levels and patient condition, reporting back to managing providers. Pharmacists review orders for intravenous fluids and should communicate with ordering clinicians if there is a concern. [Level 5]