Osmotic Demyelination Syndrome in a High-Risk Patient Despite Cautious Correction of Hyponatremia.

The treatment of hyponatremia is controversial: some authorities have cautioned that rapid correction causes central pontine myelinolysis, and others warn that severe hyponatremia has a high mortality rate unless it is corrected rapidly. Eight patients treated over a five-year period at our two institutions had a neurologic syndrome with clinical or pathological findings typical of central pontine myelinolysis, which developed after the patients presented with severe hyponatremia. Each patient's condition worsened after relatively rapid correction of hyponatremia (greater than 12 mmol of sodium per liter per day)--a phenomenon that we have called the osmotic demyelination syndrome. Five of the patients were treated at one hospital, and accounted for all the neurologic complications recorded among 60 patients with serum sodium concentrations below 116 mmol per liter; no patient in whom the sodium level was raised by less than 12 mmol per liter per day had any neurologic sequelae. Reviewing published reports on patients with very severe hyponatremia (serum sodium less than 106 mmol per liter) revealed that neurologic sequelae were associated with correction of hyponatremia by more than 12 mmol per liter per day; when correction proceeded more slowly, patients had uneventful recoveries. We suggest that the osmotic demyelination syndrome is a preventable complication of overly rapid correction of chronic hyponatremia.

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

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.

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.

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.

Rapid correction of hyponatremia can result in osmotic demyelination syndrome (ODS). Sheehan's syndrome, a rare pituitary disorder caused by severe postpartum hemorrhage, is a potential cause of chronic hyponatremia. This case report describes a rare progression of extrapontine myelinolysis to central pontine myelinolysis, ultimately leading to ODS, following the correction of chronic hyponatremia associated with Sheehan's syndrome. Notably, this event occurred a decade after the initial postpartum hemorrhage due to placenta previa. A 40-year-old woman from rural West Bengal, India, presented in a comatose state after five years of progressively worsening symptoms, including fatigue, gastrointestinal disturbances, cold intolerance, hair loss, and severe apathy, which had been misdiagnosed as psychogenic and treated with selective serotonin reuptake inhibitors. Two days before her admission to our hospital, she was diagnosed with a lower respiratory tract infection, dehydration, and severe hyponatremia (118 mEq/L) at a local private healthcare facility. Despite treatment with 3% sodium chloride and intravenous antibiotics, her condition deteriorated, prompting her transfer. At the time of hospitalization, the patient was diagnosed with chronic hyponatremia and hypopituitarism consistent with Sheehan's syndrome. This condition was attributed to a severe postpartum hemorrhage that occurred a decade prior, resulting from placenta previa. Initial MRI revealed extrapontine myelinolysis, and the correction of her "compensated" hyponatremia was identified as the cause of her neurological decline. Follow-up MRIs at 7 and 14 weeks confirmed the development of cavitating ODS. This case highlights several key points: First, even a relatively gradual correction of hyponatremia can precipitate ODS, especially in patients with chronic conditions like Sheehan's syndrome. Second, it underscores the importance of meticulous management of chronic hyponatremia to prevent severe neurological outcomes. Third, it illustrates the diagnostic challenges of differentiating Sheehan's syndrome from primary psychiatric disorders, particularly in low-resource settings where the syndrome remains prevalent. The case also emphasizes the need for awareness among healthcare providers about the potential for severe complications arising from even minor corrections in serum sodium levels in such patients.

Centro and extrapontine myelinolysis (MCP-MEP) or osmotic demyelination syndrome, is a demyelination of the central part of the protuberance and other extraprotuberance territories, the main predisposing factor being too rapid correction of severe hyponatremia. We report a case of osmotic demyelination syndrome in a 37-year-old patient, followed for acute adrenal insufficiency, complicated by three cardiorespiratory arrests, with recoveries after resuscitation measures, the evolution was marked by a neurological aggravation with confusion and generalised hypotonia and myoclonic seizures. The diagnosis of centropontine and extrapontine myelinolysis was confirmed by brain magnetic resonance imaging performed seven days after an initial scan, which showed no specific abnormalities. Rapid correction of hyponatremia was the main cause of this syndrome. The course of centropontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) is variable. Treatment is mainly preventive, based on careful correction of severe hyponatremia and the factors contributing to it.

Rapid correction of chronic hyponatremia can lead to osmotic demyelination syndrome (ODS), a severe demyelination disease. The microglia that accumulate in the demyelinative lesions may play a detrimental role in the pathogenesis of ODS by producing proinflammatory cytokines, suggesting that they may be a target for therapeutic intervention. Here, we investigated whether minocycline, a selective and potent inhibitor of microglial activation, could protect against ODS in rats. We induced hyponatremia by liquid diet feeding and dDAVP infusion. Rapid correction of the hyponatremia 7 days later resulted in neurologic impairment with severe demyelinative lesions. Activated microglia accumulated at the site of demyelination. Treatment with minocycline within 24 hours of rapid correction, however, was protective: rats exhibited minimal neurologic impairment, and survival improved. Histologic analysis showed that minocycline inhibited demyelination and suppressed the accumulation of microglia at the site of demyelination. Real-time RT-PCR and immunohistochemical analyses showed that minocycline inhibited the activity of microglia and the expression of inflammatory cytokines (e.g. IL-1β, inducible nitric-oxide synthase, and TNF-α), monocyte chemoattractant protein-1, and matrix metalloproteinase-12 in microglia. These results demonstrate that minocycline can protect against ODS by inhibiting the activation and accumulation of microglia at the site of demyelinative lesions, suggesting its possible use in clinical practice.

Rapid correction of chronic hyponatremia can lead to osmotic demyelination syndrome (ODS), a severe demyelination disease. The microglia that accumulate in the demyelinative lesions may play a detrimental role in...

Myelinolysis is a neurologic disorder that can occur after rapid correction of hyponatremia. Initially named "central pontine myelinolysis," this disease is now known to also affect extrapontine brain areas. Manifestations of myelinolysis usually evolve several days after correction of hyponatremia. Typical features are disorders of upper motor neurons, spastic quadriparesis and pseudobulbar palsy, and mental disorders ranging from mild confusion to coma. Death may occur. The motor and localizing signs of myelinolysis differ from the generalized encephalopathy that is caused by untreated hyponatremia. Experiments have duplicated the clinical and pathologic features of myelinolysis by rapidly reversing hyponatremia in animals. Myelinolysis is more likely to occur after the treatment of chronic rather than acute hyponatremia and is more likely to occur with a rapid rate of correction. The exact pathogenesis of myelinolysis has not been determined. Optimal management of hyponatremic patients involves weighing the risk for illness and death from untreated hyponatremia against the risk for myelinolysis due to correction of hyponatremia. Experiments in animals and clinical experience suggest that correction of chronic hyponatremia should be kept at a rate less than 10 mmol/L in any 24-hour period.

BackgroundOsmotic Demyelination Syndrome (ODS) encompasses Central Pontine Myelinolysis and Extrapontine Myelinolysis, both of which are serious neurological conditions linked to the overly rapid correction of hyponatremia. Despite growing evidence, the exact etiology of ODS remains incompletely understood. The present paper describes two case studies, aiming to provide a comprehensive overview of the pathological findings and clinical outcomes associated with ODS.Case presentationCase #1. A 74-year-old woman was admitted to the emergency department following a head trauma caused by a loss of consciousness. Initial laboratory tests revealed severe hyponatremia (sodium level of 101 mmol/L) and hypokalemia (potassium level of 2.9 mmol/L). The patient underwent corrective therapy with saline and potassium chloride. Despite the correction of electrolyte imbalances, the patient developed a hyperintense lesion in the median portion of the pons on T2-fluid-attenuated inversion recovery (FLAIR) MRI sequence 14 days post-treatment, consistent with ODS. The patient’s condition deteriorated, leading to irreversible coma and status epilepticus, culminating in death 32 days after admission. Case #2. An 81-year-old woman with a medical history of hypothyroidism, hypertension, major depression, and stage 3 chronic kidney disease presented with mild gait disturbances. Subsequent testing revealed severe hyponatremia (sodium level of 100 mmol/L). Following an initial clinical improvement due to sodium correction, the patient’s condition worsened, with symptoms progressing to confusion, lethargy, and eventually, ODS. Dermatological manifestations, including blistering lesions and facial edema, appeared as the condition advanced. The patient succumbed to irreversible coma 47 days after admission.ConclusionODS traditionally carried a poor prognosis, with high mortality rates and diagnoses often made postmortem. However, recent advances in understanding the pathophysiology, along with improvements in diagnostic techniques such as MRI and intensive care treatments, have led to earlier identification, treatment, and recognition of milder forms of the syndrome. Despite these advancements, ODS remains a critical condition with significant risks, particularly following the rapid correction of severe hyponatremia.

ImportanceHyponatremia is the most common electrolyte disorder and it affects approximately 5% of adults and 35% of hospitalized patients. Hyponatremia is defined by a serum sodium level of less than 135 mEq/L and most commonly results from water retention. Even mild hyponatremia is associated with increased hospital stay and mortality.ObservationsSymptoms and signs of hyponatremia range from mild and nonspecific (such as weakness or nausea) to severe and life-threatening (such as seizures or coma). Symptom severity depends on the rapidity of development, duration, and severity of hyponatremia. Mild chronic hyponatremia is associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures. In a prospective study, patients with hyponatremia more frequently reported a history of falling compared with people with normal serum sodium levels (23.8% vs 16.4%, respectively; P < .01) and had a higher rate of new fractures over a mean follow-up of 7.4 years (23.3% vs 17.3%; P < .004). Hyponatremia is a secondary cause of osteoporosis. When evaluating patients, clinicians should categorize them according to their fluid volume status (hypovolemic hyponatremia, euvolemic hyponatremia, or hypervolemic hyponatremia). For most patients, the approach to managing hyponatremia should consist of treating the underlying cause. Urea and vaptans can be effective treatments for the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure, but have adverse effects (eg, poor palatability and gastric intolerance with urea; and overly rapid correction of hyponatremia and increased thirst with vaptans). Severely symptomatic hyponatremia (with signs of somnolence, obtundation, coma, seizures, or cardiorespiratory distress) is a medical emergency. US and European guidelines recommend treating severely symptomatic hyponatremia with bolus hypertonic saline to reverse hyponatremic encephalopathy by increasing the serum sodium level by 4 mEq/L to 6 mEq/L within 1 to 2 hours but by no more than 10 mEq/L (correction limit) within the first 24 hours. This treatment approach exceeds the correction limit in about 4.5% to 28% of people. Overly rapid correction of chronic hyponatremia may cause osmotic demyelination, a rare but severe neurological condition, which can result in parkinsonism, quadriparesis, or even death.Conclusions and RelevanceHyponatremia affects approximately 5% of adults and 35% of patients who are hospitalized. Most patients should be managed by treating their underlying disease and according to whether they have hypovolemic, euvolemic, or hypervolemic hyponatremia. Urea and vaptans can be effective in managing the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure; hypertonic saline is reserved for patients with severely symptomatic hyponatremia.

Osmotic demyelination syndrome (ODS) is a clinic-pathologic entity characterized by edema and demyelination of pons and extra pontine area. It frequently occurs as a result of rapid correction of chronic hyponatremia. It is characterized by altered sensorium and neurological deficits. Diagnosis of ODS is often difficult. MRI brain remains the gold standard for diagnosis. Here, we reported a case of osmotic demyelination syndrome resulting from rapid correction of hyponatremia. Through this case, we would like to illustrate the classical MRI brain findings of ODS.