Central Pontine Myelinolysis in a Patient with Alcohol Use Disorder without Hyponatremia: A Case Report

Introduction

Central pontine myelinolysis (CPM) is a rare neurological disorder. It is most commonly observed in patients with chronic hyponatremia who undergo rapid correction of serum sodium levels [1]. Hyponatremia induces adaptive mechanisms in the brain that protect it from life-threatening edema in the event of a decrease in serum tonicity. Rapid correction of serum sodium levels disrupts these adaptations and leads to myelin damage [1,2]. Demyelinating lesions are commonly found in the pons due to the high density of oligodendrocytes [3].

The clinical symptoms of CPM are often delayed, and brain MRI can remain negative for up to 4 weeks after symptom onset [4]. Symptoms include movement disorders, behavioral disturbances, paraparesis or quadriparesis, speech abnormalities, dysphagia, increased muscle tone, and tremor. Prognosis varies depending on the severity of CPM. Indeed, some patients achieve near-complete recovery, while others develop permanent sequelae. In the most severe cases, CPM can result in locked-in syndrome or death [5].

Evidence for CPM is mostly provided by case reports and case series [5]. Risk factors for CPM include malnutrition with refeeding syndrome (RS), hypokalemia, advanced liver disease, hyperemesis gravidarum, and alcohol use disorder (AUD) [1]. Interestingly, several case reports have documented CPM occurring in normonatremic patients [6–8]. In these cases, CPM was also associated with the previously-mentioned risk factors. Recently, the causal relationship between rapid sodium correction and CPM was challenged by the authors of a multicenter cohort study involving more than 20 000 patients with hyponatremia [9]. Although rapid sodium correction occurred in more than 17% of the participants, CMP was present in only 0.05%. In line with previous observations, in this cohort, hypokalemia and detectable blood alcohol levels were observed among patients who developed CPM.

In this case report, we discuss an unusual presentation of CPM in a normonatremic patient with AUD. The patient provided written consent for the publication of this case report.

Case Report

A 30-year-old man was admitted to the Emergency Department for alcohol detoxification. The patient had AUD with heavy chronic alcohol consumption (up to 300 g of ethanol per day). He presented with symptoms of alcohol withdrawal and distal lower-limb pain accompanied by bilateral edema. His medical history was otherwise unremarkable, and he was not taking any medication. Testing of a blood sample taken at admission showed significant abnormalities in his liver function test (aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transferase levels exceeding 10 times the upper limit of normal) but the serum electrolyte balance was normal.

The patient wished to undergo alcohol detoxification. He was therefore admitted to a short-term emergency hospitalization unit for 9 days. He received diazepam to aid with alcohol withdrawal and IV thiamine to prevent Wernicke encephalopathy. His withdrawal symptoms were progressively controlled. On the third day of hospitalization, he developed hypokalemia, which was managed by IV and oral potassium supplementation. There were no significant fluctuations in other serum electrolytes, and no urine electrolyte analysis was performed. The lower-limb pain with edema was not attributed to hypoalbuminemia as albumin levels remained normal, nor to venous or arterial damage as arterial and venous Doppler ultrasonography ruled out such causes. At this stage, electromyography was scheduled to investigate the possibility of alcoholic polyneuropathy as an underlying cause of the pain.

He was repeatedly evaluated by the addiction medicine team, and, after potassium correction, he was transferred to the Addiction Medicine Department. At this point, he was considered to have passed the onset of alcohol withdrawal. It was therefore unusual to observe an asymmetrical rapid postural hand tremor associated with dystonia in the left hand, mild extrapyramidal rigidity in the left wrist, hypokinesia in the left arm, and cerebellar syndrome manifesting as gait abnormality with an enlarged gait, and dysarthria. Lower-limb pain and edema persisted at this point. Upon admission to the Addiction Medicine Department 10 days after symptom onset, a brain CT scan was performed, providing no explanation for these symptoms. The diagnostic work-up was completed with a 1.5T brain MRI 10 days later, which revealed an isolated central lesion of the pons, appearing as hypointense signal on T1-weighted sequence and hyperintense signal on T2-fluid-attenuated (FLAIR) sequence, suggestive of central pontine myelinolysis (Figure 1). No enhancement was noted after gadolinium administration. There was no extension of the lesion to the basal ganglia or to the substantia nigra, which therefore did not suggest associated extrapontine myelinolysis.

The clinical symptoms and liver function test results improved over the course of a 14-day stay in the Addiction Medicine Department. Given the improvement, ultrasound exploration of liver parenchyma was not planned. A neurological exam 1 month after symptom onset showed a favorable outcome, but with persistent extrapyramidal left-wrist rigidity without dystonia or cerebellar syndrome. Electromyography also confirmed the presence of alcoholic polyneuropathy.

Discussion

While CPM has classically been described in association with the rapid correction of hyponatremia in patients with AUD, limited information exists on the pathophysiology, prevalence, and prevention of CPM in patients without hyponatremia. In cases of AUD, the proposed mechanisms could involve the depletion of osmotic molecules due to malnutrition, the direct toxicity of alcohol on glial cells, or neuroinflammation related to alcohol consumption. Potassium levels may play a role given the involvement of potassium channels in apoptosis and oligodendrocyte homeostasis [5]. Current recommendations for the management and prevention of CPM focus primarily on hyponatremia correction rates, although recent articles highlight the importance of carefully monitoring biological and clinical parameters in at-risk patients, even in the absence of hyponatremia [5,9]. At-risk patients include those with AUD, particularly in the context of malnutrition.

In our case, undetected hyponatremia cannot be excluded because blood samples were drawn every 2 to 3 days rather than daily, and urine electrolytes were not monitored. However, this hypothesis is not consistent with the pathophysiology of CPM, which requires several consecutive days of hyponatremia to trigger the brain’s adaptive response. Alternatively, the patient may have had hyponatremia for several days before presenting to the Emergency Department. Severe AUD is frequently associated with digestive symptoms, and transient hyponatremia secondary to inappropriate antidiuretic hormone secretion triggered by severe nausea and vomiting can resolve spontaneously. Since neurological symptoms often appear after an episode of hyponatremia, this hypothesis remains plausible.

Factors other than hyponatremia may also contribute to CPM. In our case, there was an accumulation of previously described risk factors for CPM, including heavy alcohol consumption leading to malnutrition and potential RS, which would explain hypokalemia and lower-limb edema. This could have resulted in CPM even in the absence of hyponatremia. Interestingly, the patient presented symptoms suggestive of basal ganglia involvement, despite the absence of extrapontine myelinolysis on MRI. However, extrapontine lesions can develop later than CPM lesions or remain undetectable on 1.5T MRI.

This case highlights a need for heightened awareness of RS risk in AUD patients during hospitalization. Individuals with severe chronic alcohol consumption often cease eating, as alcohol provides sufficient caloric intake, suppressing hunger. Upon hospitalization, resumption of food intake may occur without adequate attention to RS risk, resulting in an abrupt shift from catabolism to anabolism, leading to electrolyte imbalances and thiamine deficiency [10]. Clinicians managing alcohol detoxification should thus routinely assess RS risk. Given its potential for life-threatening complications, including severe electrolyte imbalance or neurological damage such as CPM, the prevention of RS should be as systematic as thiamine supplementation for Wernicke encephalopathy. The American Society for Parenteral and Enteral Nutrition (ASPEN) provides guidelines for a cautious caloric intake initiation under careful clinical and biological monitoring to prevent and manage RS in at-risk populations [10].

Another critical issue raised here is that alcohol consumption can cause a wide range of neurological symptoms, complicating the distinction between substance-related and organic disorders. Additionally, patients with AUD often face significant stigma, increasing the risk of misattributing neurological abnormalities to functional disturbances rather than organic causes, leading to misdiagnosis and delayed treatment. Patients with substance use disorders should receive the same level of care as those with chronic diseases, and meticulous neurological examinations should guide clinical decision-making.

Conclusions

This case report underscores the importance of a thorough neurological examination in patients with AUD to ensure that neurological symptoms are not misattributed to alcohol intoxication. Clinicians should be aware of the risk of CPM in these patients, even in the absence of hyponatremia, as other metabolic disturbances can contribute to its pathogenesis.