Central pontine myelinolysis caused by hyperglycemia: A case report and mechanistic review

Abstract

This report highlights a rare case of a man in his 50s with central pontine myelinolysis who initially presented with dysphagia and dysarthria. The patient also exhibited unsteady gait, dizziness, and weakness in all extremities. Imaging studies revealed a typical “bat-wing” lesion at the base of the pons. The patient was diagnosed with central pontine myelinolysis secondary to a diabetic hyperglycemic hyperosmolar state complicated with hypernatremia. Following insulin therapy and rehydration, his symptoms were resolved within 1 week, while the imaging-detected lesions persisted. In most cases, central pontine myelinolysis develops due to the rapid correction of chronic hyponatremia; central pontine myelinolysis resulting from a hyperglycemic hyperosmolar state combined with hypernatremia is extremely rare. This case suggests that the coexistence of a hyperglycemic hyperosmolar state and hypernatremia can lead to central pontine myelinolysis, with a synergistic interaction between their pathogenic mechanisms. It emphasizes that in diabetic patients with poor glycemic control presenting with neurological symptoms, the possibility of central pontine myelinolysis should be vigilantly considered. Furthermore, this case supplements the understanding of the etiology and pathogenesis of central pontine myelinolysis, reminding clinicians to pay attention to central pontine myelinolysis caused by nontraditional factors.

Introduction

Central pontine myelinolysis (CPM) is a rare neurological disorder characterized by symmetric demyelination at the base of the pons, classically associated with rapid correction of hyponatremia. Cranial magnetic resonance imaging (MRI) typically reveals a “bat-wing” lesion, while axonal preservation distinguishes it pathologically. ¹ Here, we report an uncommon case of CPM triggered by a diabetic hyperglycemic hyperosmolar state (HHS) (blood glucose level, 35.43 mmol/L; plasma osmolality, 346.6 mOsm/L) complicated with hypernatremia (152 mmol/L) and hyperchloremia, highlighting a nontraditional pathogenic mechanism.

Case description

The patient was admitted to the People’s Hospital of Anyuan County in April 2025. We have de-identified all patient details. The reporting of this study conforms to the Case Report (CARE) guidelines. ²

Clinical presentation

The patient was a man in his 50s who had presented with dry mouth, polydipsia, polyuria, and polyphagia 3 months ago. Over the past 15 days, he had developed dysphagia and experienced choking while drinking water, unsteady gait, dizziness, and weakness in all limbs. Upon admission, he presented with somnolence and a blood pressure (BP) level of 135/80 mmHg. Neurological examination revealed dysphagia, dysarthria, choking while drinking water, positive pharyngeal reflex, limb weakness, grade 3/5 muscle strength in both lower limbs, hypotonia, tendon reflex (+), negative pathological signs, and ataxia (abnormal finger-to-nose test and heel–knee–shin test). The patient had a 2-year history of type 2 diabetes mellitus but no relevant personal or family medical history of surgery.

Key laboratory findings

The laboratory findings were as follows: serum glucose, 35.43 (reference range: 3.9–6.1) mmol/L; glycated hemoglobin, 15% (reference range: 4%–6%); serum sodium, 152 (reference range: 135–145) mmol/L; serum chloride, 111 (reference range: 98–106) mmol/L; plasma osmolality, 346.6 (reference range: 280–310) mOsm/L; blood urea nitrogen, 7.17 (reference range: 3.2–7.1) mmol/L; urine glucose, 4+ (reference range: negative); and urine protein, 3+ (reference range: negative).

Imaging findings

MRI showed a characteristic “bat-wing” lesion at the base of the pons (Figures 1(a) to (e) and 2(a) to (d)), with normal susceptibility weighted imaging, magnetic resonance angiography, and magnetic resonance venography.

Figure 1.

Pretreatment axial diffusion weighted imaging (DWI) (a–d) showed symmetric pontine diffusion restriction. Sagittal T2WI (e) revealed central hyperintensity. Posttreatment DWI (f–l) revealed persistent restriction; T2WI (m) showed stable hyperintensity without progression. T2WI: T2-weighted imaging.

Figure 2.

Pretreatment (a, b) axial T2WI at the pontine arms level showed symmetric long T2 hyperintensity in the center of the pons and pontine arms. (c, d) Axial T2 fluid-attenuation inversion recovery (FLAIR) images showed long T2 hyperintensity in the center of the pons and pontine arms. Posttreatment (e, f) axial T2WI at the pontine arms level revealed persistent symmetric long T2 hyperintensity in the center of the pons and pontine arms, with no significant change in the lesion extent compared with that before the treatment. (g, h) Axial T2 FLAIR images showed persistent symmetric hyperintensity in the center of pons and pontine arms, with no significant change in the lesion extent compared with that before the treatment.

Diagnosis and differential diagnosis

CPM should be differentiated from reversible posterior leukoencephalopathy syndrome (RPLS). First, the etiologies of RPLS mainly include hypertensive encephalopathy, eclampsia, renal insufficiency, and the use of drugs such as immunosuppressants. However, in this case, the patient had normal BP and renal function, with no history of taking immunosuppressive drugs. Second, the pathogenesis of RPLS involves vasogenic edema, with MRI and diffusion weighted imaging (DWI) showing isointense or slightly hyperintense signals and apparent diffusion coefficient (ADC) maps showing hyperintense signals. However, our patient mainly had demyelination and cellular edema, with MRI and DWI showing hyperintense signals and ADC maps showing hypointense signals, which do not support the diagnosis of RPLS. We excluded other toxic diseases from the differential diagnosis because the patient had no history of exposure to toxic substances.

Integrating the patient’s clinical manifestations, various examination findings, and differential diagnosis from other diseases helps confirm the diagnosis of CPM caused by diabetic HHS complicated with hypernatremia.

Treatment and outcome

At admission, the patient had a blood glucose level of 35.43 mmol/L. Intravenous insulin infusion was initiated at a rate of 4 units per hour, with blood glucose monitored hourly and the infusion rate adjusted accordingly based on the measured values. Aggressive fluid replacement was administered, and warm water was provided via nasogastric tube feeding. On the following day, the fasting capillary blood glucose level was 11 mmol/L, prompting a switch to subcutaneous insulin therapy with 18 units of insulin glargine once daily at night and 6 units of insulin aspart subcutaneously 5 min before each meal. After 5 days of treatment, the indwelling gastric tube was removed, and the patient resumed oral intake independently. Due to suboptimal glycemic control, acarbose and pioglitazone tablets were added to the regimen. The patient’s symptoms alleviated within 1 week; however, the lesions detected on MRI persisted (Figures 1(f) to (m) and 2(e) to (h)). The patient was discharged on day 10. At discharge, his fasting blood glucose level was 6.3 mmol/L, and his postprandial blood glucose level ranged between 7 and 8 mmol/L, indicating optimal glycemic control. The discharge medication regimen included subcutaneous injection of 12 units of insulin glargine and 5 units of insulin aspart before each meal, supplemented with oral acarbose (50 mg thrice daily) and pioglitazone tablets (15 mg once daily). Two months later, the patient returned to the hospital for a repeat head MRI. Compared with the findings before discharge, the slightly hyperintense DWI signals in the pons and bilateral pontine arms were weaker, while the signals of the remaining lesions were similar. At that time, the patient was conscious and walked into the consulting room unaided, with clear speech and normal muscle strength and tone of the limbs. Currently, the patient only takes oral hypoglycemic drugs and has resumed normal life.

Discussion

Pathological characteristics of osmotic demyelination syndrome (ODS) and CPM

ODS is a rare central nervous system demyelinating disorder, classified into CPM and extrapontine myelinolysis syndrome based on lesion location. First reported by Adams in 1959, CPM is characterized pathologically by symmetric demyelination at the pontine base, preserving neurons and axons without inflammation or vascular lesions. ¹ Cranial MRI shows a characteristic “bat-wing” lesion with symmetric long T1 and T2 signals, no mass effect, and no enhancement. ³

Traditional etiologies of CPM and the uniqueness of this case

The most common cause of CPM is rapid correction of hyponatremia, followed by chronic alcoholism, post-liver transplantation, and renal failure. CPM induced by hyperglycemia, hyperchloremia, and hypernatremia is clinically rare.^1,4,5 It is generally believed that the pathophysiology of CPM is related to osmotic pressure imbalance in the brain. If chronic hyponatremia is corrected quickly, potassium, sodium, and organic solutes cannot enter the brain cells immediately, which may cause acute dehydration of brain cells, leading to myelin sheath and oligodendrocyte detachment; the basal part of the pontine bridge may be an area particularly vulnerable to metabolic disorders. ⁵

The patient presented with pseudobulbar palsy symptoms, including dysphagia, spastic dysarthria, choking while drinking water, and increased jaw jerk, alongside preserved pharyngeal reflexes, which indicate damage to the corticobulbar tracts. The presence of quadriparesis (muscle strength grade 3), hypotonia, tendon reflexes (+++), and bilateral pathological signs reflects involvement of the corticospinal tracts. The somnolent state is associated with impairment of the ascending reticular activating system, which is crucial for maintaining a conscious state; its functional suppression can lead to a decline in the level of consciousness. Additionally, the presence of ataxia (abnormal finger-to-nose test and heel–knee–shin test) suggests the involvement of the pontine tegmentum and cerebellar connecting fibers. The co-occurrence of these multisystem symptoms indicates that the lesion is located near the midline of the basilar pons, consistent with the characteristic “bat-wing” lesion observed on imaging. This region is densely populated with important structures such as the corticospinal tracts, corticobulbar tracts, ascending reticular activating system, and cerebellar connecting fibers, which are highly consistent with the clinical localization of symptoms.

This case stands out due to the following reasons:

No clear history of sodium supplementation or rapid electrolyte correction: The hyperosmolar state was driven by chronic elevation of both blood glucose and sodium levels.

Atypical clinical manifestations, predominantly including pseudobulbar palsy (dysphagia, dysarthria, and positive pharyngeal reflex) and ataxia rather than the typical locked-in syndrome, suggesting early involvement of the pontine arms and cerebellar connecting fibers.

Clinical imaging dissociation, characterized by significant improvement in symptoms after treatment, with persistent MRI lesions, consistent with CPM’s characteristic finding of “neurological function recovery preceding imaging resolution.”

Literature summary and comparison

Our PubMed literature review revealed that hyperglycemia-associated CPM accounts for only 5%–8% of all CPM cases, predominantly linked to diabetic ketoacidosis or HHS.^3,6–18 Concomitant hypernatremia is exceedingly rare.^6,8

Kusumoto et al. ⁶ reported a case of HHS complicated with CPM. The patient developed hyperglycemia induced by pneumonia, which progressed to HHS. Upon admission, the patient’s blood glucose level reached 55.5 mmol/L, and the serum sodium level was 179 mmol/L. After treatment, when the blood glucose and serum sodium levels returned to normal, a follow-up MRI examination performed 30 days later revealed symmetric demyelinating lesions in the pontine base, leading to the confirmation of CPM diagnosis. This study indicated that rapid osmotic fluctuations during the correction of hyperosmolality, malnutrition, and metabolic disorders were the key pathogenic factors.

A summary of the reported cases reveals that pontine myelinolysis in such patients is consistently associated with hyperosmolar stress driven by severe hyperglycemia, with hypernatremia superimposed in some cases. The clinical manifestations are heterogeneous, including altered consciousness, bulbar palsy, limb weakness, ataxia, and gait instability. All patients exhibit symmetric pontine demyelination on imaging. This finding suggests that rapid osmotic fluctuations constitute the core pathogenic mechanism.^6,7,9

Synergistic pathogenic mechanism of hyperglycemia and hypernatremia

Hyperglycemia and hypernatremia synergistically induce CPM through the following three core pathways: osmotic imbalance, metabolic injury, and inflammatory cascade. The specific mechanisms are described below.

Dual hyperosmotic stress and neuronal dehydration

Hyperglycemia (blood glucose level >33.3 mmol/L) induces osmotic diuresis, leading to significant fluid loss. This process reduces the glomerular filtration rate and enhances sodium reabsorption, thereby increasing the serum sodium level. ¹⁹ If there is concurrent impairment of thirst sensation or insufficient fluid replacement, hypernatremia is further exacerbated, forming a vicious cycle of “hyperglycemia–hyperosmolality–hypernatremia.” Together, these two factors elevate plasma osmolarity, which exceeds the compensatory capacity of the blood–brain barrier (BBB), ²⁰ resulting in dehydration of pontine neurons and myelin damage.^8,21

Metabolic disturbance and oxidative stress

Hyperglycemia activates the polyol pathway, which consumes antioxidant factors and accumulates sorbitol, thereby triggering oxidative stress and cellular swelling. ²² In contrast, hypernatremia inhibits insulin receptor signaling, interferes with Na⁺/K⁺-adenosine triphosphatase (ATPase) activity, and leads to ATP depletion and ionic homeostasis imbalance, ultimately forming a “glucose–sodium toxicity” cycle. ²³

BBB disruption and inflammatory cascade

The core characteristic of the BBB lies in the tight endothelial junctions within cerebral capillaries; these junctions permit the passage of water while restricting the transport of sodium, glucose, and other solutes. ²⁴ Consequently, hyperglycemia and hypernatremia generate an “effective osmotic pressure,” which drives water efflux from the neurons and leads to demyelination in the pontine base. ²³ More importantly, sustained hyperosmolality further impairs the structural integrity of the BBB: it induces the contraction of vascular endothelial cells, increases BBB permeability, and allows high concentrations of glucose and sodium ions to enter the brain parenchyma. These substances then activate microglia, which release inflammatory factors (e.g. tumor necrosis factor-alpha and interleukin-1 beta) that exacerbate myelin damage.^20,25 This entire process constitutes the core link in CPM pathogenesis^7,12 (Figure 3).

Figure 3.

Diagram of the synergistic pathogenic mechanism of hyperglycemia and hypernatremia.

Prognostic characteristics

The prognosis of ODS is usually poor because it may lead to permanent neurologic sequelae or death.^4,8 Due to the scarcity of reported cases, there are no available data on the morbidity and mortality of ODS associated with hyperglycemia and hypernatremia. We searched the PubMed database for information on cases of hyperglycemia-induced central myelinolysis of the pons. Analysis of 14 reported cases of hyperglycemia-induced CPM revealed a 92.9% improvement rate after symptomatic treatment such as glycemic control, which was significantly better than the usual prognosis of hyponatremia-related CPM. ¹⁴ Summarizing the cases of hypernatremia-induced central myelinolysis of the pons,^26,27 it was found that the neurological function of these patients improved significantly after electrolyte correction. This case aligns with the literature, indicating that the prognosis of hyperglycemia–hypernatremia-induced CPM varies widely. Early recognition of osmolar fluctuations and gradual correction of metabolic disorders are critical. Existing cases suggest that most patients have good outcomes with potential for full recovery, while a few patients experience disability, with severe cases linked to high mortality rates.^6,8

Conclusion

This case demonstrates that elevated plasma osmolality can induce CPM even without a history of sodium supplementation. Hyperglycemia and hypernatremia synergistically drive CPM through a pathological network of “osmotic imbalance–metabolic damage–inflammatory” cascade. Clinicians should suspect CPM in diabetic patients with poor glycemic control and neurological symptoms (e.g. altered consciousness and quadriplegia) and promptly perform cranial MRI to address the underlying cause. Early imaging evaluation and etiological intervention can significantly improve outcomes and prevent severe sequelae.