Pontine Myelinolysis Research Articles

Effects of hypernatremia on the microglia

Signs and symptoms of hypernatremia largely indicate central nervous system dysfunction. Acute hypernatremia can cause demyelinating lesions similar to that observed in osmotic demyelination syndrome (ODS). We have previously demonstrated that microglia accumulate in ODS lesions and minocycline protects against ODS by inhibiting microglial activation. However, the direct effect of rapid rise in the sodium concentrations on microglia is largely unknown. In addition, the effect of chronic hypernatremia on microglia also remains elusive. Here, we investigated the effects of acute (6 or 24 h) and chronic (the extracellular sodium concentration was increased gradually for at least 7 days) high sodium concentrations on microglia using the microglial cell line, BV-2. We found that both acute and chronic high sodium concentrations increase NOS2 expression and nitric oxide (NO) production. We also demonstrated that the expression of nuclear factor of activated T-cells-5 (NFAT5) is increased by high sodium concentrations. Furthermore, NFAT5 knockdown suppressed NOS2 expression and NO production. We also demonstrated that high sodium concentrations decreased intracellular Ca2+ concentration and an inhibitor of Na+/Ca2+ exchanger, NCX, suppressed a decrease in intracellular Ca2+ concentrations and NOS2 expression and NO production induced by high sodium concentrations. Furthermore, minocycline inhibited NOS2 expression and NO production induced by high sodium concentrations. These in vitro data suggest that microglial activity in response to high sodium concentrations is regulated by NFAT5 and Ca2+ efflux through NCX and is suppressed by minocycline.

Case Report: Quantitative Evaluation of Gait Function Following Treatment Progression in a Patient with Central Pontine Myelinolysis

Introduction: Central pontine myelinolysis (CPM) is a rare neurological disorder marked by symmetric nerve fiber damage, commonly following rapid hyponatremia correction, with no established treatment and a poor prognosis. The condition, often linked to alcoholism, malnutrition, and various diseases, lacks comprehensive studies on its impact on gait. This research aims to quantitatively analyze gait changes in CPM patients receiving both traditional Korean and conventional rehabilitation treatments, addressing a gap in current understanding of CPM management.Case presentation: A 56-year-old male diagnosed with CPM following an initial misdiagnosis underwent combined electoracupuncture and rehabilitative treatment at ○○ university Korean medical center, resulting in significant gait improvements. A treadmill gait analysis system was used to measure changes in key gait parameters at 2-week intervals, and the patient’s progress was documented.Conclusions: The quantitative analysis revealed significant gait improvements. Foot rotation decreased from 8.9° to 6.4° (right) and from 11.1° to 7.2° (left); lateral symmetry improved from -7.8 to 0.8; step length increased from 21 cm to 44 cm (right) and from 19 cm to 44 cm (left); and velocity increased from 1.2 m/s to 2.7 m/s. These findings highlight decreased foot rotation and lateral symmetry, along with increased step length and velocity, suggesting a positive outcome of the treatment regimen. Notably, the patient experienced no adverse effects related to the treatments. Despite limitations, including the singe case focus and lack of prior gait-focused CPM research, this case report provides valuable insights into effective CPM management strategies, paving the way for future research in this domain.

Central Pontine Myelinolysis: A Rare and Life-Threatening Adverse Effect of Clobazam and Quetiapine

Central Pontine Myelinolysis: A Rare and Life-Threatening Adverse Effect of Clobazam and Quetiapine

Is It Structural or Metabolic? A Diagnostic Dilemma

Is It Structural or Metabolic? A Diagnostic Dilemma

Prediction quality of patients’ composited outcomes of interest and how much variations on the outcomes explained by the patients’ sodium levels

Background: Hypernatremia can be caused by medications, glucose/urea-related hyperosmolarity, overdiuresis, compartmental fluid distribution imbalances, iatrogenic hypertonic saline excess, renal concentrating performance defects, overdiuresis, and hypermetabolic states. Patients who are in critical condition, encompassing ailments of the heart, liver, lungs, brain, and kidneys, frequently manifest hyponatremia (sodium < 135 mEq/L). Similar to hypernatremia, hyponatremia signifies the severity of the illness and a bleak prognosis. Hyponatremia is less lethal than central pontine myelinolysis, which overcorrects sodium concentrations urgently. Aim: The objective of this research endeavour was to investigate the strength of correlations, the extent to which the independent variables account for the overall variability in the dependent variable, and the accuracy of the dependent variable's predictions. In addition, the purpose of this test was to extract the coefficients required to present the Binary Logistic Regression models that were investigated. Methods: Between May 2018 and May 2021, this study examined two Na-based prognosticators for overall mortality in critically ill patients admitted to the King Hussein Medical Centre. An investigation was conducted on 2155 cases utilising Receiver Operating Characteristic (ROC) and Sensitivity Indices Test analyses to ascertain the most effective cut-off points, specificities, sensitivity, predictive values, likelihood ratios, Youden and accuracy indices, and mortality rates. The research discovered that serial termination points with lower values suggested more robust evidence for a positive actual state, whereas higher values suggested less robust evidence for a negative actual state. A Binary Logistic Regression (BLgR) test was performed to examine correlations, the extent of total variations in the dependent variable, and the accuracy of the prediction for each Na-related mortality prognosticator in relation to overall mortality. The analysis was conducted utilising version 25 of SPSS for Windows. Results: The research revealed that the AUROC for cNa was considerably greater in magnitude compared to its prognosticator that is genealogically related to Na. 129.35 mEq/l and 131.05 mEq/l were the optimal cut-off points, TPRs, TNRs, PPVs, NLRs, YIs, and AIs for the two comparative Na investigated statutes. The BLgR models were developed in order to simulate the relationship between the corrected and measured Na levels of patients and their overall mortality rate. For critically ill patients, the probabilities of overall mortality at the optimal cutoff operating Na levels were 79.59 and 81.62 percent, respectively.

Analysis of central pontine myelinolysis in HIV-infected patients

Aim: to conduct a clinical and epidemiological analysis of cases of central pontine myelinolysis (CPM) in HIV-infected patients. Materials and methods. Four patients hospitalized in the infectious diseases department of No. 1 Clinic of the South Ural State Medical University were under dynamic observation. Results and its discussion. Four patients hospitalized in the infectious diseases department of Clinic No. 1 of the South Ural State Medical University were under dynamic observation. Patient management was carried out in accordance with current clinical recommendations for the provision of medical care to patients with HIV infection with a set of clinical and laboratory methods, including examination of lumbar puncture, its cytological and biochemical composition, determination of DNA of cytomegalovirus (CMV) and Epstein-Barr viruses (EBV) herpes simplex types 1 and 2, T. gondii, Cr. Neoformans, M. Tuberculosis, Cryptococcus neoformans, the presence of pathogens of bacterial infections. All patients underwent magnetic resonance imaging (MRI) of the brain. Conclusion. The process of demyelination of the central nervous system develops regardless of the level of CD4 lymphocytes and HIV viral load. The main method for verifying the diagnosis is MRI of the brain

Recurrent demyelination attacks after BNT162b2 vaccination: Two case reports and literature review

We describe two cases with recurrent demyelinating attacks following BioNTech BNT162b2 immunization. No reports of any recurring demyelinating attack cases connected to COVID-19 immunization. Case-1: A 37-year-old male patient was admitted due to diplopia and ptosis. Neurological examination showed isolated oculomotor cranial paralysis on the right side. The second dose of BNT162b2 was given 10 days ago. On T2- and fluid-attenuated inversion recovery (FLAIR)-weighted magnetic resonance imaging (MRI), hyperintense lesions were seen in the pons on T1, with no evidence of contrast enhancement. We diagnosed the patient with central pontine myelinolysis associated with BNT162b2. Six months later after the first attack, a new lesion appeared in the same region. Case-2: He applied to the hospital at the age of 57 years, complaining of numbness in his hands and feet, confusion, and cooperation disorder. During the neurological assessment, apathy, cooperation, and orienting disorders were found. Hyperintense lesions were seen in both hemispheres, with cortico-subcortical localization on MRI. The patient received the BNT162b2 two weeks ago. After the initial attack six months ago, new clinical signs and an increase in demyelinating lesions were found. Despite early corticosteroid treatment, BNT162b2 immunization may be associated with repeated demyelination attacks. In patients with diffusion restriction on MRI, we might suggest using corticosteroid therapy for approximately one year, a lot longer than the literatures suggested.

From wernicke-korsakoff to central pontine myelinolysis: the potentially irreversible risks of alcohol use

Introduction Sustained alcohol intake, when combined with incomplete treatment, can result in chronic structural changes in the Central Nervous System, including generalized cortical and cerebellar atrophy, amnesic syndromes like Korsakoff’s syndrome, and white matter disorders such as Central Pontine Myelinolysis and Marchiafava-Bignami syndrome. It is crucial to prevent these complications due to their potential for irreversible and debilitating consequences. For Wernicke-Korsakoff syndrome, early recognition and thiamine administration for prevention are paramount, as it arises from thiamine deficiency due to malnutrition caused by persistent alcohol use. In the case of Central Pontine Myelinolysis, which is caused by abrupt fluctuations in serum osmolality, controlled sodium correction is essential.ObjectivesThrough a clinical case and a review of published literature, this study aims to reflect on the importance of preventing neurological injuries associated with chronic alcohol consumption, specifically Wernicke-Korsakoff Syndrome and Central Pontine Myelinolysis.Methods A literature review was conducted by searching for articles on PubMed using the terms “Alcohol Use Disorder,” “Wernicke-Korsakoff syndrome,” and “Central pontine myelinolysis.” A clinical case is presented, featuring a 50-year-old patient with alcohol use disorder who developed Wernicke-Korsakoff syndrome and Central Pontine Myelinolysis. Considering this case, we reflect on the primary approaches that could have been beneficial in preventing these complications and propose a straightforward method for doing so.Results A 50-year-old patient presented with poor general condition, characterized by low weight, significant loss of strength in the limbs and arms, and incoherent speech with anterograde amnesia and confabulation. This condition had progressed to a point where the patient could no longer walk, perform basic self-care tasks such as bathing, dressing, and eating independently, underscoring the severity of his condition. The diagnoses of Wernicke-Korsakoff syndrome and Central Pontine Myelinolysis were established based on clinical manifestations and the presence of hyperintense lesions observed in the central pons on T2/FLAIR axial MRI scans. This clinical case highlights the importance of proper and precocious prevention of complications in patients with alcohol use disorder. The foremost step in preventing these complications is to treat alcohol dependence effectively, even when faced with patient resistance. It’s vital to remain vigilant about potential complications and implement suitable prophylactic measures.ConclusionsThe devastating effects of complications arising from Alcohol Use Disorder, such as Wernicke-Korsakoff syndrome and Central Pontine Myelinolysis, underscore the importance of enhanced attention that clinicians should provide when approaching these patients at all clinical interactions.Disclosure of InterestNone Declared

Osmotic demyelination syndrome (ODS), and psychiatric manifestations

IntroductionHyponatriemia can be potentially fatal if it is not corrected immediately. The rapid correction of chronic hyponatriemia can cause demyelinating brain lesions.ObjectivesA fifty-six year old female was brought to the emergency department of the psychiatric clinic by her daughter, with incomprehensible speech and psycomotor agitation. She was diagnosed several years ago with bipolar disorder, with valproic acid and quetiapine being her current medication. She has been living alone, in a small suburban city. Approximately twenty four hours before her admission to the hospital she visited her daughter, which aligns with the onset of symptoms.MethodsAfter both the brain CT scan and the lab results came back normal, the patient was admitted to the psychiatric clinic of the General Hospital of Corfu. On the fourth day of the patient’s hospitalization - when both her speech and the psycomotor agitation showed signs of improvement- we were informed that three days before her admission to the clinic she visited the emergency department of another hospital where she was treated for hyponatriemia. The patient’s hyponatriemia was corrected over the span of twelve hours by 35 mEq.ResultsAfter receiving this information, we ordered a brain MRI scan which revealed a central pontine myelinolysis. The result can explain the clinical symptoms that our patient showcased before her admission and could have been caused by the rapid correction of hyponatriemia.ConclusionsThe patient’s speech was fully restored after four weeks and there were no symptoms consistent with any psycho emotional disorder.Disclosure of InterestNone Declared

Safety and efficacy of proactive versus reactive administration of desmopressin in severe symptomatic hyponatremia: a randomized controlled trial

This randomized controlled trial aimed to evaluate the safety and efficacy of proactive versus reactive desmopressin (DDAVP) strategies in treating severe symptomatic hyponatremia. Conducted from June 20, 2022, to February 20, 2023, it involved 49 patients with serum sodium levels below 125 mmol/L. Patients were assigned to either the proactive group, receiving DDAVP immediately upon diagnosis, or the reactive group, receiving DDAVP only if the serum sodium level tended to be overcorrected. The primary outcome was the incidence of overcorrection. The study revealed no significant difference in the overcorrection incidence between the proactive (16.7%) and reactive (28%) groups (p = 0.54). The change in serum sodium levels at 1, 6, 12, and 24 h were not different, however, at 48 h, the proactive group exhibited a higher but still safe change in serum sodium levels compared to the reactive group (10.3 ± 3.6 mmol/L vs. 7.7 ± 3.6 mmol/L, p = 0.013). Other parameters including time to symptom improvement, total intravenous fluid administered, DDAVP dose, urine volume, hospital stay duration, osmotic demyelination syndrome incidence, and 28-day mortality did not significantly differ between the groups. In conclusion, our findings suggest that there was no significant disparity in overcorrection rates between proactive and reactive DDAVP strategies for treating severe symptomatic hyponatremia. However, further large-scale studies are warranted to validate these results.

Retracted: Osmotic Demyelination Syndrome: Clinical, Neuroimaging Characteristics, and Outcomes in a Series of 18 Cases.

[This retracts the article DOI: 10.1155/2021/9944632.].

Study of Clinicoetiological profile of hyponatremia patients admitted in Medical wards

Hyponatraemia is the most common electrolyte disorder in hospitalized patients. Its epidemiology depends on the serum sodium used to define hyponatraemia, which varies from study to study. It can be an early or even first sign of important underlying disease. It can be complicated by two types of neurological disorders cerebral oedema and osmotic demyelination syndrome. It is associated with increased morbidity and mortality rates in hospitalized patients, although it remains unclear whether these associations are mainly due to the underlying disease, direct effects of hyponatraemia, or a combination of both. Aims and Objectives - to study clinical profile of hyponatremia in hospitalized subjects. To study the aetiology of hyponatremia in hospitalized subjects. To assess morbidity and mortality due to hyponatremia. Materials and Methods - 100 patients with hyponatremia were studied. Most common symptoms were Lethargy and tremors, followed by headache, nausea, altered sensorium, convulsion and coma, in order. Hypervolemic hyponatremia is most common followed by euvolemic hyponatremia and hypovolemic hyponatremia. Euvolemic subjects had propensity to develop more severe and symptomatic hyponatremia. Dilutional hyponatremia is the most prevalent underlying pathophysiology of hyponatremia followed by diuretic use, SIADH, GI loss, Hypothyroidism, extra renal/GI loss and Cerebral salt wasting in order. Congestive cardiac failure was the most common cause of hypervolemic hyponatremia, followed by cirrhosis of liver and renal failure. Acute gastroenteritis was most common cause of hypovolemic hyponatremia. SIADH was the most common cause of euvolemic hyponatremia, followed by thiazide diuretics and hypothyroidism, in order.

Assessment of 2% vs 3% Peripheral Hypertonic Sodium Chloride Administration and Its Impact on Safe and Timely Treatment

Abstract Objectives Evaluate if peripheral administration of 3% hypertonic saline (HTS) provides timely treatment with a rate of infusion-related adverse events at or below what is reported in the literature. Methods This was a single-center, retrospective study conducted in a large academic medical center in New York City. Eligible patients were inpatients receiving either 2% or 3% HTS for severe hyponatremia, elevated intracranial pressure, or cerebral edema. The primary outcome was incidence of infusion-related adverse events. Secondary endpoints included achievement of appropriate sodium correction, incidence of over-correction, length of time from ordering to medication administration, and incidence of osmotic demyelination syndrome (ODS). Main Results A total of 199 patients were included in analysis (85 in the 3% HTS group and 114 in the 2% HTS group). No difference was found between groups for rate of infusion related adverse events or incidence of sodium overcorrection groups (0 vs 1 [0.9%]; p = 0.39). Significantly more patients in the 3% HTS group received intermittent administration (p < 0.001), whereas more patients in the 2% HTS group received a continuous infusion (p < 0.001). There were no reports of ODS in either group. No difference in length of time to administration was found between groups. Conclusion Our study, one of the largest to evaluate peripheral administration of 3% HTS, found that it is not associated with an increase in infusion related adverse events or sodium overcorrection versus 2% HTS. Peripheral administration should be recommended to provide timely treatment for patients requiring HTS.

The Response of Osmotic Demyelination Syndrome to Plasmapheresis in a Patient Presenting with Catatonia after Correction of Hyponatraemia in Hyperemesis Gravidarum.

Osmotic demyelination syndrome (ODS) is a rare but potentially devastating neurological complication, such as catatonia, resulting from the correction of hyponatraemia.Pregnancies complicated by hyperemesis gravidarum tend to exhibit hyponatraemia and hypokalaemia, which serve as contributing risk factors for ODS.Plasmapheresis is considered as an option in the treatment of ODS for the removal of inflammatory substances.

Hand knob sign in osmotic demyelinating syndrome

BackgroundOsmotic demyelinating syndrome, commonly recognized as a consequence of the rapid correction of hyponatremia, has been known to cause motor, neuropsychiatric, or extrapyramidal symptoms. We reported a patient with an unusual presentation involving bilateral hand weakness, and pseudobulbar affect. The imaging was compatible with osmotic demyelinating syndrome with bilateral hand knob lesions, despite no history of overcorrection of hyponatremia.Case presentationA 44-year-old female presented with three weeks of emotional lability, spastic dysarthria, and bilateral hand weakness following ankle surgery and a mild head injury. Physical examination revealed weakness in the intrinsic hand muscles, leading to a claw-like deformity of the hands, although sensation remained unimpaired. Magnetic resonance imaging (MRI) of the brain revealed several hyperintensities on fluid-attenuated inversion recovery imaging involving various areas, including the hand knob area of the bilateral precentral gyri, caudate, lentiform nuclei, and pons, suggestive of osmotic demyelinating syndrome. Clinical improvement was observed following a trial of intravenous pulse methylprednisolone and plasmapheresis.ConclusionsBilateral hand weakness is an unusual manifestation of osmotic demyelinating syndrome. The precentral gyrus, specifically in the hand knob area, is the vulnerable region that can result from osmotic demyelinating syndrome.

Psychosis Due to Osmotic (Pontine) Myelinolysis in Non-Hodgkin’s Lymphoma: Case Report

Introduction: central pontine myelinolysis (CPM) is rare neurological condition. The severe symptoms of neurologic and psychiatric disorders accompanying this condition are not sufficiently disclosed in the literature. Most often CPM develops on infusion therapy and forced correction of hyponatremia. The complexity of diagnosis and the lack of certain algorithms for the management of this category of patients cause a high frequency of disability, persistent neurological and psychiatric symptoms, and lethal outcomes.The aim was to present and analyze clinical picture of psychosis in CPM on the example of non-Hodgkin’s lymphoma case report. Patient and method: clinical analysis of disorders in 14-years old patient with diagnosis of non-Hodgkin’s lymphoma.Results: clinical polymorphism of psychotic features, catatonic disorders, neurological symptoms at the end stage and development of psychosis associated with CPM during cytotoxic treatment. A year and a half follow-up of the first generation antipsychotics administration is presented.Conclusion: CPM may occur on cytotoxic infusion therapy in patients with non-Hodgkin’s lymphoma and be accompanied by severe psychotic disorders. Thus, practitioners should be aware of the risks of this condition, its diagnostic and therapeutic options when working with these patients.

Osmotic demyelination as a complication of hyponatremia correction: a systematic review

RESUMO Antecedentes: A correção rápida da hiponatremia, principalmente quando grave e crônica, pode resultar em desmielinização osmótica. A última diretriz para diagnóstico e tratamento da hiponatremia (2014) recomenda um limite de correção de 10 mEq/L/dia. Nosso objetivo foi sumarizar os casos publicados de desmielinização osmótica para avaliar a adequação dessa recomendação. Método: Revisão sistemática de relatos de caso de desmielinização osmótica. Incluímos casos confirmados por imagem ou anatomia patológica, em maiores de 18 anos, publicados entre 1997 e 2019, nas línguas inglesa ou portuguesa. Resultados: Avaliamos 96 casos de desmielinização osmótica, sendo 58,3% do sexo feminino e com média de idade de 48,2 ± 12,9 anos. A mediana de sódio sérico admissional foi 105 mEq/L e > 90% dos pacientes apresentavam hiponatremia grave (<120 mEq/L). Foram comuns os relatos de distúrbios do trato gastrointestinal (38,5%), etilismo (31,3%) e uso de diuréticos (27%). A correção da hiponatremia foi feita principalmente com solução salina isotônica (46,9%) ou hipertônica (33,7%). Correção de hipocalemia associada ocorreu em 18,8%. Em 66,6% dos casos houve correção da natremia acima de 10 mEq/L no primeiro dia de internamento; a velocidade não foi relatada em 22,9% e em apenas 10,4% foi menor que 10 mEq/L/dia. Conclusão: O desenvolvimento da desmielinização osmótica foi predominante em mulheres, abaixo de 50 anos, com hiponatremia grave e correção rápida. Em 10,4% dos casos, houve desmielinização mesmo com correção <10 mEq/L/dia. Esses dados reforçam a necessidade de alvos conservadores para pacientes de alto risco, como 4–6 mEq/L/dia, não ultrapassando o limite de 8 mEq/L/dia.

Hyponatremia in the Context of Liver Disease.

Hyponatremia is common in patients with liver disease and is associated with increased mortality, morbidity, and a reduced quality of life. In liver transplantation, the inclusion of hyponatremia in organ allocation scores has reduced waitlist mortality. Portal hypertension and the resulting lowering of the effective arterial blood volume are important pathogenetic factors, but in most patients with liver disease, hyponatremia is multifactorial. Treatment requires a multifaceted approach that tries to reduce electrolyte-free water intake, restore urinary dilution, and increase nonelectrolyte solute excretion. Albumin therapy for hyponatremia is a peculiarity of advanced liver disease. Its use appears to be increasing, while the vaptans are currently only given in selected cases. Osmotic demyelination is a special concern in patients with liver disease. Serial checks of serum sodium concentrations and urine volume monitoring are mandatory.

Consensus recommendations on the diagnosis and treatment of hyponatremia from the Austrian Society for Nephrology 2024

Hyponatremia is adisorder of water homeostasis. Water balance is maintained by the collaboration of renal function and cerebral structures, which regulate thirst mechanisms and secretion of the antidiuretic hormone. Measurement of serum-osmolality, urine osmolality and urine-sodium concentration help to diagnose the different reasons for hyponatremia. Hyponatremia induces cerebral edema and might lead to severe neurological symptoms, which need acute therapy. Also, mild forms of hyponatremia should be treated causally, or at least symptomatically. An inadequate fast increase of the serum sodium level should be avoided, because it raises the risk of cerebral osmotic demyelination. Basic pathophysiological knowledge is necessary to identify the different reasons for hyponatremia which need different therapeutic procedures.

Osmotic demyelinating syndrome and its manifestations

Osmotic demyelination syndrome (ODS) is a rare and severe dysmetabolic lesion of the central nervous system which is difficult to diagnose. Its prevalence in the general population reaches 0.5 %, and in intensive care nits — 2.5 %. Within the framework of ODS, central pontine myelinolysis with demyelination of the pons and extrapontine myelinolysis with foci of demyelination in the cerebellum and cerebral hemispheres are distinguished. Clinical cases of ODS that developed against the background of dehydration are presented