Cytotoxic Lesions of the Corpus Callosum Preceding Osmotic Demyelination Syndrome in Hypernatremia and Hyperosmolar Hyperglycemic State: A Case Report

Hyperglycemic Emergencies in Adults

Central pontine myelinolysis (CPM) is a demyelinating disorder, which is associated most commonly with the rapid correction of hyponatraemia and other abrupt changes in physiological osmotic conditions. This includes the treatment of hyperosmolar hyperglycaemia in diabetes mellitus (DM) sufferers. Herein, we report a case of CPM in a 55-y-old patient with new-onset DM who presented with partial focal seizures and a sudden-onset right-sided hemiplegia. Magnetic resonance imaging revealed a lesion in the central pons. The patient responded to glucose control and antiepileptic medication, and achieved a recovery of limb function within 17 d of admission. CPM occurred in this patient before the correction of hyperglycaemic hyperosmolar state, and a disturbance in his initial electrolytes was not found. This report is the first documented case of long-term hyperglycaemic hyperosmolar state leading to CPM, and highlights that CPM can present as an isolated hemiplegia.

Central Pontine Myelinolysis as a Complication of Refeeding Syndrome in a Patient With Anorexia Nervosa

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.

Osmotic demyelination syndrome (ODS) is typically associated with rapid correction of severe hyponatremia but is a rare complication of hyperosmolar hyperglycemic state (HHS). We describe two cases of ODS developing in HHS with contrasting initial sodium levels: one with profound hyponatremia (Na 112 mmol/L, corrected 167 mmol/L) and the other with hypernatremia (Na 149 mmol/L, corrected 177 mmol/L). Both patients exhibited severe hyperglycemia (2,398 and 1,277 mg/dL, respectively) and marked hyperosmolality (387 and 421 mOsm/kg) and were managed with cautious correction rates (1.2 and 1.0 mOsm/kg/hour). Despite this, each patient developed ODS diagnosed by MRI on days three and seven, respectively. Neurological function gradually improved in both, with final modified Rankin Scale scores of 2 and 1, respectively. To our knowledge, this is the first case report to directly compare hyponatremic and hypernatremic ODS in the context of HHS. Severe hyperosmolality can itself trigger ODS, regardless of measured and corrected sodium levels or the rate of correction. Clinicians should maintain a low threshold for timely MRI in HHS patients with persistent or unexplained neurological deficits.

Central pontine myelinolysis (CPM) is an uncommon disorder, characterized by non-inflammatory demyelination, which may be caused by an abrupt change of serum osmolarity, especially of sodium concentration [1]. Although rapid correction of chronic hyponatremia leads to the disruption of the blood–brain-barrier (BBB) [2], CPM associated with intracerebral hemorrhage (ICH) has rarely been reported [3, 4]. Cerebral microbleed (CMB) is a 2–5-mm sized small hypointense lesion that is generally detected by gradient echo (GRE) magnetic resonance imaging (MRI), which is thought to be associated with advanced microangiopathy, focal breakdown of the BBB and risk of bleeding [5]. In view of the possible effects of CPM and CMB on the BBB, we can postulate that the affected region is in a hemorrhagic-prone state. We describe a patient who suffered CPM and subsequent ICH at the site of pontine microbleeds. An 89-year-old female attended the emergency room (ER) with stuporous mentality. In the past, she had suffered from hypertension and chronic kidney disease with antihypertensives and diuretics without dialysis. Seven days before visiting the ER, her general condition had worsened after fall down and oral intake was poor. It had not been possible to wake her for the last 5 h before she appeared in the ER. Neurological examination revealed stupor mentality with decreased corneal, vestibulo-ocular and gag reflexes. Her withdrawal response to painful stimuli on all extremities was reduced especially on her left side. Laboratory findings revealed mild anemia (hemoglobin 9.3 g/dL) and elevated renal function values (blood urea nitrogen 42 mg/dL, creatinine 3.2 mg/dL) and normal range electrolyte values. Total protein (4.9 g/dL) and albumin (2.6 g/dL) levels were low, suggesting malnutrition. Brain fluid attenuated inversion recovery (FLAIR) MRI revealed diffuse high signal areas in the basis pontis (Fig. 1a). In addition, multiple microbleed signals were detected in the whole brain area as well as the lower pons within FLAIR high signal area on GRE imaging (Fig. 1b). Her diagnosis was CPM without any hyponatremia correction and we initiated general and nutritional care. Three days after admission, she became alert and motor power was partially recovered. However, on the 8th day, her mental functioning deteriorated abruptly to stupor. Neurological examination showed pin-pointed pupils with impaired light reflex. Brainstem reflexes were also completely absent. Brain MRI revealed pontine hemorrhage in two different foci that coincided with microbleed sites on the previous MRI (Fig. 1c, d). The patient died from respiratory and renal failure 3 weeks after admission. CPM is an osmotic demyelination syndrome (ODS) which is a well-known disease caused by rapid correction of hyponatremia, alcoholism, liver transplantation and malnutrition [1]. Although the exact mechanism of ODS is not clear, it has been suggested that any rapid change in serum osmolality with resulting changes in brain cell volume may lead to stereotyped injury to myelin sheaths [2]. Therefore, ICH, which is due to rupture of intracerebral arteries, is an unusual complication and has been rarely reported [3, 4]. However, these previous reports differ from Y. S. Kim and J. Lee equally contributed to this work.

Objective: To report a rare association of central pontine myelinolysis (CPM) with hyperosmolar hyperglycaemic state (HHS). Clinical Presentation and Intervention: A diabetic female presented with HHS and prolonged severe hypernatraemia. The metabolic derangement was adequately treated with proper correction of both hyperglycaemia and hypernatraemia. Lack of improvement in the presenting confusional state and the development of a fresh neurological deterioration led to the suspicion of CPM that was confirmed with magnetic resonance imaging. She fully recovered after 4 weeks with no specific medical treatment. Conclusion: This case report showed that osmotic demyelination was linked to hypernatraemia and that CPM could result from severe hypernatraemia of HHS.

Objective: To highlight the occurrence of osmotic demyelination syndrome (ODS) in settings other than the classical ODS induced by rapid correction of hyponatremic states. The background, clinico- radiological features, treatment and outcome of eight ODS patients are discussed here. We encountered eight patients with ODS in Materials and Methods: uncommon clinical settings at the department of neurology, Government Stanley medical college hospital, Chennai between April 2017 to October 2018. Patients were evaluated, investigated, treated and outcome was assessed. Results: Eight patients in the age group 22 to 60 years had ODS. The clinical presentations were diverse. Akinetic mutism was the commonest presenting feature of ODS. Four out of eight patients had hyperglycemia out of which three had diabetic ketoacidosis (DKA) and one was in hyperglycemic hyperosmolar state (HHS). Two patients with chronic kidney disease (CKD) developed myelinolysis following hemodialysis. One patient each in post liver transplant state and following alcohol binge were diagnosed with ODS. Serum sodium levels were in normal range and there was no undue fluctuation in all. Four had central pontine myelinolysis (CPM), three had Extrapontine myelinolysis (EPM) and one had both in Magnetic Resonance Imaging (MRI) of Brain. Background illnesses were addressed. Five patients were independent with mRS of 1 and one patient had mRS of 2 at the end of 3 months and two CKD patients succumbed due to disease per se. ODS commonly occurs in the setting of rapid correction of hyponatremia especially in chronic Conclusion: alcoholics and debilitated individuals. We have described myelinolysis in diabetic ketoacidosis, hyperglycemic hyperosmolar state, Renal failure following dialysis, post liver transplant and alcohol binge drinking where there were no undue fluctuation in sodium levels. The prognosis is variable and also depends on presence of secondary complications like deep venous thrombosis, sepsis and aspiration pneumonitis.

Central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) are rare neurological disorders associated with rapid correction of hyponatremia, particularly in individuals with chronic alcohol use. We present the case of a 52-year-old male with a history of chronic alcoholism who developed CPM and EPM following correction of severe hyponatremia. The patient presented with dysarthria, hemiparesis, and altered mental status, which progressed rapidly to pseudobulbar features and spastic quadriparesis. Neuroimaging revealed characteristic findings of CPM and EPM. Treatment with intravenous dexamethasone, intravenous immunoglobulin (IVIG), and methylprednisolone led to gradual neurological improvement. The patient showed significant recovery after two months, highlighting the importance of early recognition and cautious management of electrolyte disturbances in high-risk individuals to prevent devastating neurological complications.

Osmotic demyelination syndrome (ODS) is a rare and devastating neurological condition linked with the rapid correction of serum hyponatremia. We present a case report of a young female patient who developed ODS following an aggressive correction of low serum sodium levels. ODS is characterized by demyelination in the central and extrapontine regions of the brain, resulting in disastrous outcomes. The pathophysiology involves disruption of the blood-brain barrier (BBB) due to a sudden rise in serum sodium, which leads to astrocyte dysfunction secondary to osmotic shift, leading to inflammation, brain edema, and finally demyelination. A rapid rise in the serum sodium levels can overwhelm the brain’s adaptive capacity, ultimately leading to ODS. Our case emphasizes the importance of careful sodium correction; in our patient, the serum sodium levels were raised precipitously, beyond the recommended 8-10 mmol/L limit within its first 24 hours, leading to calamitous neurological consequences. Despite the management of this disastrous condition with plasmapheresis, the patient succumbed to complications. A review of the literature suggests that no definitive treatment of ODS exists; therefore, cautious monitoring and raising the serum sodium levels to prevent ODS is critical. Our case report also highlights the necessity of heedful management of hyponatremia to prevent permanent neurological injury.

Parkinsonism after correction of hyponatremia with radiological central pontine myelinolysis and changes in the basal ganglia

Pontine myelinolysis was first described in 1959 by Adams, Victor and Mancall and reported in alcoholic patients.[1] It is characterized, above all, by acute non-inflammatory symmetrical lesion of myelin sheath and apoptosis of oligodendrocytes affecting the central part of thebasis pontis.[5] Demyelination may also appear in other parts of central nervous system such as thalamus, basal nuclei and cerebellum. Involvement of the regions beyond pons is called extrapontine myelinolysis. These two manifestations- pontine and extrapontine myelinolysis are combined in one neurological entity- osmotic demyelination syndrome.Pontine and extrapontine myelinolysis are mainly caused by rapid increase in extracellular fluid osmolarity; usually in situation of iatrogenic correction of chronic hyponatremia.[7]The other causes include severe electrolyte disturbances other than hyponatremia (hypokalemia, hypophosphatemia, hypernatremia), anorexia nervosa, AIDS, acute alcoholic hepatitis, liver transplantation, Vernickes syndrome, chemotherapy, chronic renal failure. [11,12] Osmotic demyelination syndrome vary in clinical manifestations. The most common presentations include encephalopathies, pareses, dystonias. The method of choice in diagnostic process is MRI imaging. Treatment of osmotic demyelination syndrome is still in an experimental phase.

Patient: Male, 44-year-oldFinal Diagnosis: Central pontine myelinolysisSymptoms: Bulbar paralysis • locked-in syndrome • tetraplegiaMedication: —Clinical Procedure: Brain MRISpecialty: Neurology • RehabilitationObjective:Unusual clinical courseBackground:Central pontine myelinolysis (CPM) includes symmetric demyelination of the central pons. CPM is a rare neurological disorder that generally develops after rapid correction of hyponatremia in individuals having underlying conditions, such as malnutrition, alcoholism, and severe burns. It can cause severe long-term disabilities. However, there is currently no pharmacotherapy capable of promoting remyelination, a process crucial for recovery from CPM. We present the case of a patient with alcoholism and malnutrition-related CPM, which developed following rapid correction of hyponatremia but then improved remarkably with supportive physical therapy.Case Report:A 44-year-old alcoholic and malnourished man was admitted to an emergency hospital for disorientation due to overdrinking, but later developed bulbar palsy after hyponatremia was unexpectedly, but rapidly, corrected. Axial scans of the diffusion-weighted brain MRI revealed a characteristic lesion known as a piglet sign in the central pons. Based on his underlying conditions, present episode of sodium correction, and MRI finding, the patient was diagnosed as having CPM, which progressively worsened, resulting in locked-in syndrome after 12 days. The patient was then transferred to a long-term care unit and received simple motion exercise daily, but no specific medication. His symptoms gradually improved, achieving discontinuation of tube feeding on day 21, independent walking on day 110, and discharge after 6 months.Conclusions:This report highlights the importance of physical therapy, the potential of which is often underestimated despite its broad benefits for human health, as a readily applicable intervention for patients with CPM. Further understanding of mechanisms underlying exercise-induced myelination should contribute to establishing novel therapies for a wide spectrum of brain disorders.

Osmotic demyelination syndrome (ODS) is a life-threatening demyelinating syndrome. The association of ODS with hyperosmolar hyperglycemic state (HHS) has been seldom reported. The aim of this study was to present and discuss previous cases and the pathophysiological mechanisms involved in ODS secondary to HHS. A 47-year-old man arrived to the emergency room due to generalized tonic-clonic seizures and altered mental status. The patient was lethargic and had a Glasgow coma scale of 11/15, muscle strength was 4/5 in both lower extremities, and deep tendon reflexes were diminished. Glucose was 838 mg/dL; serum sodium and venous blood gas analyses were normal. Urinary and plasma ketones were negative. Brain magnetic resonance revealed increased signal intensity on T2-weighted FLAIR images with restricted diffusion on the medulla and central pons. Supportive therapy was started and during the next 3 weeks the patient progressively regained consciousness and muscle strength and was able to feed himself. At 6-month follow-up, the patient was asymptomatic and MRI showed no residual damage. In conclusion, the association of ODS with HHS is extremely rare. The exact mechanism by which HHS produces ODS still needs to be elucidated, but we favor a rapid hypertonic insult as the most plausible mechanism.

Osmotic demyelination syndrome (ODS) is well known to be associated with the rapid correction of hyponatremia. However, there is limited literature on its link to persistent or corrected hyperglycemic states in diabetic patients. We report two young patients with ODS and hyperglycemia. Neuroimaging and blood tests indicated central pontine and extrapontine myelinolysis with a hyperglycemic hyperosmolar state (HHS). These unusual cases provide insight into the neurologic complications of hyperglycemia.