Introduction
Osmotic demyelination syndrome (ODS) is a non-inflammatory demyelinating syndrome that affects the pons and other parts of the central nervous system. Extrapontine myelinolysis and central pontine myelinolysis (CPM) are components of ODS.[1] CPM is the characteristic presentation due to the pons’ increased vulnerability, and damage to brain tissue and pontine white matter tracts is a defining feature.[2]
As a side effect of postoperative serum sodium anomalies and suspected tacrolimus neurotoxicity, CPM is a documented complication of liver transplantation. In some cases, there are no evident precipitating events for CPM.[3]
This report reviews the pathophysiology, assessment, and treatment of CPM and highlights the role of the anesthesiologist in preventing this condition.
Case Report
A 64-year-old male patient with decompensated cirrhosis is undergoing a deceased donor liver transplant (LT). Before the surgery, the patient presented with end-stage liver disease complicated by portal hypertension, esophageal varices, and hepatic encephalopathy.
On the day of the surgery, serum sodium was 125 mmol/L. The initial immunosuppression regimens were intravenous methylprednisolone, tacrolimus, and mycophenolate.
Peripheral venous access and a central venous line were established. An arterial catheter was inserted into the left radial artery. Anesthetic induction was performed with etomidate 20 mg, midazolam 5 mg, sufentanil 50 μg and rocuronium 50 mg, and was maintained with sevoflurane. The Swan-Ganz catheter was inserted into the right internal jugular vein and continuous cardiac output, mixed venous saturation, and vascular resistance were measured. Surgery was performed without any unusual events. The patient received 3000 mL of ringer lactate, 900 mL of red blood cells, and 1800 UI of prothrombin complex. Fluid management was goal-guided through hemodynamic parameters and blood gas analysis. After liver reperfusion, the patient presented with severe acidemia and hemodynamic instability, receiving 250 mL of 8.4% sodium bicarbonate. Vasopressors in bolus (adrenaline) and infusion (vasopressin and noradrenaline) were required to maintain mean arterial pressure above 65 mmHg. He was transferred to the ICU after surgery, still unstable, receiving norepinephrine 0.03 mcg/kg/min and vasopressin 0.06 UI/min. On arrival, the serum sodium was 135 mmol/L.
In the postoperative period, the patient developed acute confusion and memory loss. Abnormal tongue, eye (gaze deviation), and foot movements were detected. The symptoms worsened and he presented with a non-convulsive seizure. An electroencephalogram was performed and a status epilepticus was detected. The patient was intubated and maintained with continuous sedation. Magnetic resonance was performed and showed alterations in the pons, mesencephalon, and thalamus suggestive of ODS [Figure 1]. The patient had no clinical neurological improvement and died after 20 days.
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Figure 1: MRI of the brain shows a hyperintense signal detected in the central pons
Discussion
CPM is a central basis of pontis-specific, frequently symmetric, non-inflammatory demyelination. At least 10% of patients also experience demyelination in extrapontine areas. Histology revealed demyelination and astrocytosis, along with macrophage and lymphocyte infiltration. The incidence of CPM is not well known due to underdiagnosis.[4]
The majority of cases revealed a connection with swift metabolic disruption repair, including hyponatremia. Patients were shown to have higher odds of related neurologic sequelae when their hyponatremia was more chronic and corrected quickly within the first 48 hours. The primary risk factors for myelinolysis include an abrupt rise in serum sodium, even in the absence of underlying hyponatremia, and osmotic imbalances. The danger of developing a demyelinating syndrome exists not just in individuals with pretransplant hyponatremia but also in patients who have preoperative, intraoperative, or postoperative serum osmotic changes.[3]
Patients who underwent an orthotopic LT had a higher incidence of CPM, with the majority of cases occurring within 10 days after the transplant. The rapid sodium correction of more than 0.5 to 1.0 mEq/L per hour is one of the main risk factors. Patients with severe hyponatremia (less than 120 mEq/L) or chronic hyponatremia (>48 hours) are the most vulnerable.[5]
Depending on the level of pontine involvement and the presence of extrapontine lesions, the clinical manifestations may vary. The patient may have no symptoms or develop lethargy, quadriparesis, dysarthria, ophthalmoplegia, and ataxia over time. It may occasionally result in coma or death.[6]
Hyponatremia is characterized by serum sodium levels of less than 135 mEq/L. It is also typical in end-stage liver disease. Osmosis will cause extracellular water to enter cells with higher tonicity to balance the gradient in response to falling serum tonicity, which will resulting in cerebral edema. There are various hypothesized methods by which the brain can adjust to a drop in serum tonicity. As one defense strategy, water is displaced from the cells into the cerebrospinal fluid. Another method to reduce brain swelling and restore normal brain volume involves the elimination of intracellular solutes and water via ion channels. When hyponatremia is rapidly corrected, the brain is unable to replenish lost osmolytes, which causes brain tissue dehydration, white matter tract demyelination, and apoptosis of astrocytes. The condition is known as ODS [Figure 2].[1]
Figure 2: Changes in extracellular osmolarity lead to transient cell swelling, activation of ion channels, and efflux of osmolytes and electrolytes. The rapid correction of hyponatremia leads to rapid water efflux, cell shrinkage, and triggers apoptosis
The blood-brain barrier is damaged and the glial cells are maladapted in patients with advanced liver disease and preexisting hepatic encephalopathy, which leaves their neurons vulnerable to tacrolimus damage. Tacrolimus may promote demyelination by suppressing immunophilins and by having a vasospastic effect from decreased nitric oxide production.[7]
Imaging is used to confirm the diagnosis, especially if the diagnosis is uncertain and may take up to two weeks to become available. A negative imaging result does not rule out a CPM diagnosis. Within two weeks, an MRI should be performed if there is still a high clinical suspicion of CPM.[6]
The avoidance of CPM is the main goal. The rate at which sodium should be adjusted has been the subject of numerous investigations. The recommended correction for sodium is currently 8–12 mEq/L per 24 hours.[8]
In patients undergoing LT, the maintenance of hyponatremia homeostasis is challenging. Stable hemodynamics require enough volume to restore lost fluid, ascites, and blood; therefore, care must be taken to ensure that the rise in serum sodium is less than 12 mEq in 24 hours or that the change in sodium is kept within an acceptable range.[9] It is not well understood how much fluid should be replaced for acute, ongoing, and significant intravascular volume losses in LT without adversely impacting the serum sodium in hyponatremic patients. One of the biggest challenges of LT is to treat the severe acidemia that occurs after the reperfusion of the organ. Frequently, a sodium bicarbonate solution is used, and it may be one of the reasons for rising serum sodium.[10] Unfortunately, post-LT CPM is still being observed as a result of the fast rise in serum sodium caused by overcorrection during LT.[9]
Conclusion
Our patient presented many previously cited risk factors for ODS, such as hyponatremia, previous episodes of encephalopathy, and tacrolimus immunosuppression therapy. Improving prognostic outcomes focuses on early recognition of CPM, avoiding rapid overcorrection of sodium, making a prompt diagnosis of the condition, and performing early treatment.
Financial support and sponsorship
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Conflicts of interest
There are no conflicts of interest.
References
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