A case of acute pulmonary complication due to botulinum toxin: Patient with central pontine myelinolysis developed acute respiratory distress syndrome after botulinum neurotoxin type A injection into spastic lower extremity muscles.

Chemodenervation with botulinum neurotoxin type A (BoNTA) is the preferred method for focal spasticity management among various treatment options. While BoNTA injection is considered safe, its widespread use and increasing evidence raise safety concerns. In this paper, we present a patient with central pontine myelinolysis, a rare disease, who developed acute respiratory distress syndrome on the third day after BoNTA application to the spastic gastrocnemius muscle group and required intubation in the intensive care unit due to this complication. To our knowledge, this is the first case reported in the literature to develop an acute pulmonary complication after BoNTA injection into spastic lower extremity muscles.

Central pontine myelinolysis and locked-IN syndrome associated with tacrolimus after pediatric heart transplantation.

BACKGROUND: Locked-in syndrome represents the most severe form of central pontine myelinolysis and varies in presentation from asymptomatic to fully developed locked-in-syndrome characterized by the combination of quadriplegia, loss of the ability to communicate except through the use of the eyes, and an inability to follow commands. METHODS: We report a 10-year-old boy who developed a severe case of locked-in syndrome after heart transplantation. RESULTS: Patient had a spontaneous recovery, treated with supportive treatment and the improvement was detected with cessation of calcineurin inhibitor therapy by substituting with an mTOR inhibitor (sirolimus). No cases of locked-in syndrome post-heart transplant in pediatrics cases have been documented in the literature. CONCLUSION: Physicians should recognize a rapid progression of central pontine myelinolysis and locked-in syndrome in the context of heart transplant and although several factors likely contributed to this outcome, adjustment of immunosuppression including by substituting tacrolimus with sirolimus could be effective.

A rare presentation of central pontine myelinolysis secondary to hyperglycaemia.

BACKGROUND: Central pontine myelinolysis (CPM) is a rare demyelinating disorder caused by the loss of myelin in the center of the basis pontis. CPM typically occurs with rapid correction of severe chronic hyponatremia and subsequent disturbances in serum osmolality. Although hyperglycaemia is recognized as a pathogenetic factor in serum osmolality fluctuations, CPM is rarely seen in the context of diabetes. CASE PRESENTATION: A 66-year-old Chinese male presented with a history of gait imbalance, mild slurred speech and dysphagia for two weeks. MRI showed the mass lesions in the brainstem, and laboratory examinations showed high blood glucose and HbA1c, as well as increased serum osmolality. The patient was diagnosed with CPM secondary to hyperosmolar hyperglyceamia and received insulin treatment as well as supportive therapy. After six weeks of followup, the patient had fully recovered to a normal state. CONCLUSION: CPM is a potentially fatal neurological condition and can occur in uncontrolled diabetes mellitus. Early diagnosis and timely treatment are crucial for improving the prognosis.

Osmotic demyelination syndrome: novel risk factors and proposed pathophysiology.

BACKGROUND: Osmotic demyelination syndrome (ODS) is non-inflammatory demyelination in response to an osmotic challenge. It can be pontine or extrapontine in presentation. AIMS: To retrospectively review cases involving ODS and define the spectrum of causes, risk factors, clinical and radiological presentations, and functional outcomes. RESULTS: The study utilised data from 15 patients with a mean age of 53.6 years. Malnutrition (9; 60%) and chronic alcoholism (10; 66.7%) were the most common associated disorders. Two (13.3%) patients had severe hyponatraemia (<120 mmol/L). The average highest single-day change was 5.1 mmol/L. Radiologically, 14 (93.3%) had pontine and 6 (40%) had extra-pontine lesions. Hypokalaemia (14; 93.3%) and hypophosphataemia (9; 60%) were commonly associated. Common clinical manifestations include altered consciousness/encephalopathy (9; 60%), dysphagia (4; 26.7%) and limb weakness (4; 26.7%). At 3 months, two (14.3%) had died and six (40%) were functionally independent (modified Rankin scale 0-2). CONCLUSION: We found that ODS occurred despite appropriate correction rates of hyponatraemia. Factors such as malnutrition, chronic alcoholism, hypokalaemia and hypophosphataemia are thought to play a role in its pathogenesis. Approximately half of the patients survived and became functionally independent.

Osmotic demyelination syndrome in patients with non-Hodgkin lymphoma: a case report and literature review.

INTRODUCTION: Osmotic demyelination syndrome (ODS) is a non-inflammatory process of the central nervous system caused by extracellular osmotic changes, which leads to oligodendrocyte apoptosis and disruption of myelin sheaths, usually affecting patients with underlying systemic conditions that impose susceptibility to osmotic stress. Description of ODS in patients with non-Hodgkin lymphoma (NHL) is limited to a few case reports. METHODS: Here, we report a 44-year-old man with NHL that had an incidental diagnosis of ODS. We conducted a literature review of the published cases of ODS in NHL patients from 1959 to 2020, aiming to describe the characteristics of these patients. RESULTS: A total of seven patients were summarized (four men and three women), including our case and six patients from published reports. Risk factors such as weight loss and alcoholism were reported in five (71.4%) patients. Hyponatremia was found in six (85.7%) of the cases, and none of them had overly rapid sodium correction. Four cases were asymptomatic, and diffuse large B-cell lymphoma was the most common subtype of NHL (85.7%). The outcome was favorable in most cases; only two deaths not directly related to ODS were reported. CONCLUSION: We wish to suggest that systemic and metabolic stress induced by NHL may be associated with the development of central osmotic demyelination, and therefore, NHL may be a novel risk factor for ODS. Clinicians should be aware of ODS in patients with hematological malignancies, even in the absence of traditional risk factors.

Central Pontine Myelinolysis: A Case Report.

Central pontine myelinolysis (CPM) classically occurs due to rapid rise in serum osmolarity. Most cases have been associated with a history of chronic alcohol abuse, malnutrition, diuretic abuse, and hyponatremia. The pathological process of CPM starts in the central pons near median raphe and spreads out "like a brush Fire" into the surrounding basis pontis. Extrapontine sites such as internal capsule, basal ganglia, cerebellum, and cerebrum can also be affected. We report a case of 60-year-old male with history of chronic alcoholism who presented to us with severe neurological deficits 10 days after his episode of severe hyponatremia. How to cite this article: Tiwari R, Kumari A. Central Pontine Myelinolysis: A Case Report. Indian J Crit Care Med 2022;26(9):1049-1051.

Central pontine myelinolysis secondary to rapid correction of hyponatremia historical perspective with Doctor Robert Laureno.

OBJECTIVES: Central pontine myelinolysis (CPM) is a neurological disorder characterized by damage to the myelin and oligodendrocytes in the pons. This review focuses on the history of CPM and the discovery of its association with the treatment of hyponatremia. METHODS: The author reviewed original publications regarding CPM, hyponatremia, and the treatment of hyponatremia. The author interviewed Dr. Robert Laureno who was a pioneer in CPM research with his animal work in dogs. RESULTS: Animal models demonstrated the role of the rapid correction of hyponatremia as causative of pontine and extrapontine myelinolytic lesions. Nevertheless, the importance of the speed of correction was widely denied. There were years of debates and only slow changes in expert guidelines. CONCLUSION: CPM occurs as a consequence of a rapid rise in serum sodium in individuals with chronic hyponatremia. It is recommended to increase plasma sodium concentration by no more than 8 to 10 mmol/L per 24 h in chronic hyponatremia.

MGMT-Methylation in Non-Neoplastic Diseases of the Central Nervous System.

Quantifying O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation plays an essential role in assessing the potential efficacy of alkylating agents in the chemotherapy of malignant gliomas. MGMT promoter methylation is considered to be a characteristic of subgroups of certain malignancies but has also been described in various peripheral inflammatory diseases. However, MGMT promoter methylation levels have not yet been investigated in non-neoplastic brain diseases. This study demonstrates for the first time that one can indeed detect slightly enhanced MGMT promoter methylation in individual cases of inflammatory demyelinating CNS diseases such as multiple sclerosis and progressive multifocal leucencephalopathy (PML), as well as in other demyelinating diseases such as central pontine and exptrapontine myelinolysis, and diseases with myelin damage such as Wallerian degeneration. In this context, we identified a reduction in the expression of the demethylase TET1 as a possible cause for the enhanced MGMT promoter methylation. Hence, we show for the first time that MGMT hypermethylation occurs in chronic diseases that are not strictly associated to distinct pathogens, oncogenic viruses or neoplasms but that lead to damage of the myelin sheath in various ways. While this gives new insights into epigenetic and pathophysiological processes involved in de- and remyelination, which might offer new therapeutic opportunities for demyelinating diseases in the future, it also reduces the specificity of MGMT hypermethylation as a tumor biomarker.

Incidence of osmotic demyelination syndrome in Sweden: A nationwide study.

OBJECTIVE: To report the incidence rate of osmotic demyelination syndrome (ODS), associated risk factors, treatment, and long-term outcomes in a nationwide cohort. METHODS: We conducted a retrospective study of individuals diagnosed with central pontine myelinolysis (ICD-10 code G37.2) in the Swedish National Patient Register during 1997-2011. RESULTS: During the study period, we identified 83 individuals with ODS, 47 women and 36 men. Median age at diagnosis was 55 years. The incidence rate of ODS for the entire study period was 0.611 (95% CI: 0.490-0.754) per million person-years and increased during the study period from 0.271 (95% CI: 0.147-0.460) in 1997-2001 to 0.945 (95% CI: 0.677-1.234) individuals per million person-years in 2007-2011. Most cases (86.7%) were hyponatremic with a median sodium level at admission of 104 mmol/L. All hyponatremic cases were chronic. The cause of hyponatremia was multifactorial, including drugs (56.9%), polydipsia (31.9%), and vomiting or diarrhea (41.7%). A majority of patients (69.9%) were alcoholics. Hyponatremic patients were predominantly treated with isotonic saline (93.1%) and only 4.2% with hypotonic fluids. The median correction rate was 0.72 mmol/L/h. Only six patients were corrected in accordance with national guidelines (≤8 mmol/L/24/h). At three months, 7.2% had died and 60.2% were functionally independent (modified Rankin Scale 0-2). INTERPRETATION: We found an increasing incidence during the study period, which could partly be explained by increased access to magnetic resonance imaging. ODS occurs predominantly in patients with extreme chronic hyponatremia which is corrected too fast with isotonic saline. Most patients survived and became functionally independent.

Occult central pontine myelinolysis post liver transplant: A consequence of pre-transplant hyponatremia.

Rapid overcorrection of chronic hyponatremia can lead to osmotic demyelination syndrome or central pontine myelinolysis (CPM), a diagnosis often triggered by observing the characteristics of neurological abnormalities developed as a result of CPM. However, anyone with chronic hyponatremia and overcorrection of serum sodium is at risk of physiological CPM despite the lack of clinical symptoms. We report an adult patient who presented as post-op delirium, had incidental finding of CPM by magnetic resonance imaging (MRI) of the head after a liver transplant. Despite his non-typical presentation, the patient had the typical risk factors of CPM such as chronic hyponatremia, rapid overcorrection of serum sodium and cirrhosis undergoing a transplant. As hyponatremia and neurological disorder such encephalopathy simultaneously affect patients with cirrhosis, CPM may be more common than once thought in the chronic liver disease population and inappropriate hyponatremia management has important medical consequences that can go unnoticed.

The effect of white matter integrity on functional outcome in central pontine demyelination.

[Purpose] Central pontine demyelination is a common osmotic demyelination syndrome. Typically, central pontine demyelination shows high signal intensity with demyelination in the mid-pons. Despite severe imaging findings, patients usually recover. This study investigated the integrity of the corticospinal tract (CST) and corticoreticular pathway (CRP) in patients at 12 months after the onset of central pontine demyelination. [Participants and Methods] This retrospective cross-sectional observational study assessed two patients with central pontine demyelination, who were ultimately able to walk without using an aid or orthosis and to use both hands but with mild residual symptoms. All participants underwent diffusion tensor imaging (DTI) at 12 months after onset. [Results] Both patients had mild ataxia at 12 months after onset. The integrity of the CST was restored in both cases, while the integrity of the CRP recovered partially. [Conclusion] The integrity of the CST and CRP at 12 months after the onset of central pontine demyelination was similar in both cases as well as the recovery status of the hand function and ambulation. These results may be useful in planning therapy for patients with central pontine demyelination.

Osmotic Demyelination Unrelated to Hyponatremia.

Osmotic demyelination unrelated to hyponatremia is rarely reported. We present a case of osmotic demyelination in a patient with hypernatremia in the absence of preceding hyponatremia and review previously reported cases of osmotic demyelination in nonhyponatremic patients. We conclude that a rapid increase in serum sodium concentration and plasma tonicity even in the absence of preceding hyponatremia may surpass the brain's capacity for adaptation to hypertonicity and lead to osmotic demyelination in predisposed individuals. Risk factors for osmotic demyelination in patients with chronic hyponatremia and without hyponatremia are probably similar and are usually associated with states of limited brain osmolyte response, such as alcoholism, liver disease (including those undergoing orthotopic liver transplantation), malnutrition, malignancy, pregnancy/postpartum state, severe illness/sepsis, adrenal insufficiency, and metabolic derangements. Clinicians should be vigilant in identifying individuals who may, even in the absence of hyponatremia, have increased susceptibility to osmotic demyelination and avoid rapid fluctuations in serum sodium concentrations in such patients.

A case of chronic asymptomatic central pontine myelinolysis with histological evidence of remyelination.

Central pontine myelinolysis (CPM) is a neurological demyelinating disease of the pons. Although usually associated with rapid correction of hyponatremia, CPM may occur despite normonatremia, is often associated with chronic alcoholism and may be asymptomatic. Histological confirmation of asymptomatic CPM is rare. We describe an unusual post-mortem case of extensive but asymptomatic CPM in a chronic alcoholic patient with normonatremia. The affected part of the pons contained thinly myelinated axons with appearances supporting remyelination. We suggest that remyelination may account for the subclinical nature of this patient's CPM.

Central pontine myelinolysis during pregnancy: Pathogenesis, diagnosis and management.

Central pontine myelinolysis (CPM) is a rare condition usually caused by rapid sodium correction in hyponatraemia after a severe neurological syndrome. Only few cases have been reported during pregnancy, most of which were reported in patients with hyperemesis. We describe the successful management of the first case of twin pregnancy in a patient who presented with CPM after treatment for premature labour and then review the literature on CPM in pregnancy (aetiology, diagnosis and management). Our patient required emergency delivery to achieve electrolyte and fluid balance. At six months, the twins remained asymptomatic and the mother had minor sequelae. The aetiology is not clear, and there is no evidence regarding the optimal treatment or prognosis of CPM. In our patient, desmopressin-contaminated atosiban showed a certain probability in the Karch-Lasagne algorithm of a causality relationship between hyponatraemia and the drug. To our knowledge, this is the first case of myelinolysis reported in a twin pregnancy possibly related to desmopressin-contaminated atosiban.

Extrapontine myelinolysis associated with severe hypernatremia in infancy.

Extrapontine myelinolysis (EPM) is an uncommon disorder in children, with few pediatric cases reported to date. We report the first case of an infant with EPM without central pontine myelinolysis (CPM) presenting with severe hypernatremia. On admission, the infant had impaired consciousness, mild dehydration, and severe hypernatremia (190 mmol/L). The following day, the patient developed abnormal involuntary movements. Brain magnetic resonance imaging (MRI) confirmed EPM without CPM. He recovered without sequelae, and clinical examinations were within normal limits approximately 6 months after discharge. Brain MRI at 1 year after onset showed complete disappearance of the previous EPM regions. To the best of our knowledge, this represents the youngest patient with EPM without CPM presenting with severe hypernatremia. Given that treatment for osmotic demyelination syndrome (ODS) is yet to be established, preventing the development of ODS is crucial.

Central pontine myelinolysis secondary to hyperglycaemia.

Central pontine myelinolysis is characterised by focal osmotic demyelination within the pons. Its clinical presentation varies, but may include acute paralysis, dysarthria and dysphagia. The cause is traditionally associated with overzealous correction of hyponatraemia in patients who are malnourished, alcoholic or chronically ill. However, it may develop in the context of normal serum sodium, since rapid gradient shifts in brainstem osmolalities can occur in other ways. We present an unusual example of central pontine myelinolysis caused by osmotic shifts secondary to hyperglycaemia in a person with type 1 diabetes mellitus and with consistently normal serum sodium concentrations.

Urinary incontinence a first presentation of central pontine myelinolysis: a case report.

An 84-year-old lady was treated for hyperosmolar hyperglycaemia with IV insulin, fluids and catheterisation for fluid balance monitoring. Trial without catheter failed as the patient complained of new-onset urinary incontinence and lack of awareness of bladder filling. In light of her breast cancer history, we excluded cauda equina. Ultrasound KUB showed an enlarged bladder. Whole-body MRI revealed a lesion in the pons which was highly suggestive of central pontine myelinolysis (CPM). Her electrolytes were normal throughout her admission; thus, the rapid fluctuation in osmolality, secondary to her hyperglycaemic state, was the likely cause of CPM. CPM has been reported secondary to hyperglycaemia; however, this is the first reported case of CPM presenting as urinary incontinence and loss of bladder sensation.

Serum sodium shift in hyponatremic patients undergoing liver transplantation: a retrospective cohort study.

INTRODUCTION: We aimed to describe the pre-operative incidence of hyponatremia in patients undergoing liver transplantation (LTx), as well as the rate and consequences of rapid peri-operative sodium rises in these patients. METHODS: This was a retrospective before and after observational study performed at a University-affiliated LTx center between January 2007 and June 2013. The primary exposure was pre-operative hyponatremia, defined as a serum sodium (SNa) <133 mmol/L. The primary outcome was occurrence of a rapid SNa shift, defined as ≥10 mmol/L in the first 24 h following LTx. The rates of rapid peri-operative SNa shift were compared before and after a focused quality assurance (QA) initiative performed in July 2009. RESULTS: Of 366 LTx, 69 (18.9%) had pre-operative hyponatremia, 6 (8.7%) of whom had a rapid rise in serum sodium (SNa). Rapid rise was associated with a greater intra-operative positive fluid balance (p < 0.001) and use of intra-operative continuous renal replacement therapy (CRRT) (p = 0.017). A rapid rise in SNa was associated with more neurological investigations in the post-transplant period (brain computed tomography, electroencephalogram, swallow studies), increased neurological deficits (p = 0.006), more abnormal swallowing assessments (p = 0.003), a tendency for more neurology consultations (p = 0.058), increased discharge to a rehabilitation or long-term care facility (p < 0.001), and increased 6-month mortality (p < 0.001). Following a QA initiative, rapid peri-operative rises in SNa among hyponatremic patients was significantly reduced (20% vs. 0%, p < 0.003). CONCLUSION: Pre-operative hyponatremia and rapid peri-operative SNa shifts are associated with a more complicated post-operative course and worse outcomes following LTx. Increased education and awareness, along with process changes, such as standardizing CRRT prescription, can reduce iatrogenic rapid peri-operative shifts in SNa.

Chronic Severe Hyponatremia and Cardiopulmonary Bypass: Avoiding Osmotic Demyelination Syndrome.

Serum sodium concentration affects every cell in the body with respect to cellular tonicity. Hyponatremia is the most frequent electrolyte abnormality encountered, occurring at clinical admission in 22% of elderly patients. Any rapid correction of chronic severe hyponatremia can result in rapid cellular shrinking due to loss of intracellular free water. This is commonly associated with paralysis and severe brain damage due to osmotic demyelination syndrome (ODS). ODS occurs because the body has the ability to compensate for cellular fluid shifts due to chronic hyponatremia (by a decrease in brain concentration of several ions, amino acids, and organic osmolytes). Thus, the neurons are often at a functional state of fluid balance despite the sodium imbalance. The initiation of cardiopulmonary bypass (CPB) can introduce between 1 and 2 L of priming solution containing a normal sodium concentration creating a rapid rise in sodium concentration within the extracellular fluid. This abrupt change establishes a situation where intracellular free water can be lost resulting in cellular shrinking and ODS. In presenting this case study, we hope to add to the current literature with a specific isotonic approach to treating the chronically severe hyponatremic patient pre-CPB, during CPB, and post-CPB.

Desmopressin acetate (DDAVP)-associated hyponatremia and brain damage: a case series.

BACKGROUND: Desmopressin (DDAVP) is typically prescribed for central diabetes insipidus, von Willebrands disease and for enuresis. DDAVP-associated hyponatremia is a known complication of DDAVP therapy. The currently recommended treatment for this condition calls for discontinuing DDAVP as part of the initial therapy. This recommendation could lead to a water diuresis and potentially over-correction of the serum sodium. METHODS: The 15 patients in this case series developed symptomatic DDAVP-associated hyponatremia and were admitted to acute care hospitals. Thirty-eight percent presented with symptomatic hyponatremia and 62% developed symptomatic hyponatremia due to concomitant DDAVP and hypotonic intravenous fluid administration during a hospital stay. Group 1 patients (n = 13) were treated by withholding DDAVP and providing intravenous saline. Group 2 patients (n = 2) were treated by continuing DDAVP and providing DDAVP and intravenous hypertonic saline. RESULTS: Among Group 1 patients, in whom DDAVP was withheld as initial management of DDAVP-associated hyponatremia (n = 13), the mean change in serum sodium in the first 2 days of treatment was 37.1 ± 8.1 mEq/L. The ultimate outcome in this group was death in 23%, severe brain damage in 69% and moderate brain damage in 8%. In Group 2 patients, in whom DDAVP was continued (n = 2) as part of the initial management strategy, the mean change in serum sodium was 11.0 ± 0 mEq/L in the first 2 days. The ultimate outcome was survival without neurological sequelae in both cases. CONCLUSIONS: Discontinuing DDAVP in a patient with symptomatic DDAVP-associated hyponatremia can lead to rapid correction of the serum sodium and resultant severe neurological injury. In contrast, continuing the medication while correcting DDAVP-associated hyponatremia may lead to better outcomes by avoiding over-correction of the serum sodium. Thus, an alternative approach that we propose is to continue DDAVP as part of the initial management of this disorder.