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.

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.

Osmotic Demyelination Syndrome in Children.

Osmotic demyelination syndrome is an acute demyelination process that usually occurs several days following an osmotic stress. This syndrome is rare in adults (0.4% to 0.56%) and even more uncommon in children. We performed a review of all reported pediatric osmotic demyelination syndrome patients from 1960 to 2018. Among all 106 cases, 49 presented with isolated central pontine myelinolysis, 30 with isolated extrapontine myelinolysis, and 27 with combined central pontine myelinolysis and extrapontine myelinolysis. There was no gender preponderance, and the highest prevalence was noted between the ages one and five years. Magnetic resonance imaging remains the diagnostic modality of choice, and diffusion tensor imaging is now increasingly used for prognostication in osmotic demyelination syndrome. Sixty percent of the children had a complete neurological recovery. Current management of osmotic demyelination syndrome in children consists of supportive medical care, steroids, and intravenous immunoglobulin. Our review of the literature supports the hypothesis that steroids and immunoglobulins are potentially helpful, although additional controlled studies are needed.

Comprehensive risk assessment for early neurologic complications after liver transplantation.

AIM: To determine risk factors for early neurologic complications (NCs) after liver transplantation from perspective of recipient, donor, and surgeon. METHODS: In all, 295 adult recipients were enrolled consecutively between August 2001 and February 2014 from a single medical center in Taiwan. Any NC in the first 30 d post-liver transplantation, and perioperative variables from multiple perspectives were collected and analyzed. The main outcome was a 30-d NC. Generalized additive models were used to detect the non-linear effect of continuous variables on outcome, and to determine cut-off values for categorizing risk. Risk factors were identified using multiple logistic regression analysis. RESULTS: In all, 288 recipients were included, of whom 142 (49.3%) experienced at least one NC, with encephalopathy being the most common 106 (73%). NCs prolonged hospital stay (35.15 ± 43.80 d vs 20.88 ± 13.58 d, P < 0.001). Liver recipients' age < 29 or ≥ 60 years, body mass index < 21.6 or > 27.6 kg/m(2), Child-Pugh class C, history of preoperative hepatoencephalopathy or mental disorders, day 7 tacrolimus level > 8.9 ng/mL, and postoperative intra-abdominal infection were more likely associated with NCs. Novel risk factors for NCs were donor age < 22 or ≥ 40 years, male-to-male gender matching, graft-recipient weight ratio 0.9%-1.9%, and sequence of transplantation between 31 and 174. CONCLUSION: NCs post- liver transplantation occurs because of factors related to recipient, donor, and surgeon. Our results provide a basis of risk stratification for surgeon to minimize neurotoxic factors during transplantation.

Movement disorders and the osmotic demyelination syndrome.

With the advent of MRI, osmotic demyelination syndromes (ODS) are increasingly recognised to affect varied sites in the brain in addition to the classical central pontine lesion. Striatal involvement is seen in a large proportion of cases and results in a wide variety of movement disorders. Movement disorders and cognitive problems resulting from ODS affecting the basal ganglia may occur early in the course of the illness, or may present as delayed manifestations after the patient survives the acute phase. Such delayed symptoms may evolve over time, and may even progress despite treatment. Improved survival of patients in the last few decades due to better intensive care has led to an increase in the incidence of such delayed manifestations of ODS. While the outcome of ODS is not as dismal as hitherto believed - with the acute akinetic-rigid syndrome associated with striatal myelinolysis often responding to dopaminergic therapy - the delayed symptoms often prove refractory to medical therapy. This article presents a review of the epidemiology, pathophysiology, clinical features, imaging, and therapy of movement disorders associated with involvement of the basal ganglia in ODS. A comprehensive review of 54 previously published cases of movement disorders due to ODS, and a video recording depicting the spectrum of delayed movement disorders seen after recovery from ODS are also presented.

Clinical and radiologic correlations of central pontine myelinolysis syndrome.

OBJECTIVE: To characterize clinical and radiologic features of patients with central pontine myelinolysis (CPM) and identify variables that predict outcome. PATIENTS AND METHODS: We retrospectively studied patients diagnosed as having CPM identified by a search of Mayo Clinic medical records from January 1, 1999, through December 31, 2010. Diagnosis was made by clinical and radiologic features. Favorable outcome was defined by a modified Rankin Scale score of 2 or lower. Volume of signal abnormality on brain magnetic resonance imaging (MRI) was quantified by a neuroradiologist blinded to outcomes. Wilcoxon rank sum tests were used to assess association between volume of signal abnormality and outcomes at discharge and last follow-up. RESULTS: Of 24 patients, 14 (58%) had only CPM, and 10 (42%) had extrapontine involvement. Hyponatremia was documented in 18 patients (75%), with median sodium nadir of 114 mmol/L. Eighteen patients (75%) had alcoholism, and malnutrition was documented in 12 (50%). Presenting symptoms included encephalopathy (n=18 [75%]), ataxia (n=11 [46%]), dysarthria (n=7 [29%]), eye movement abnormalities (n=6 [25%]), and seizures (n=5 [21%]). Favorable outcome was seen in 15 patients (63%) at last follow-up. Findings on initial brain MRI were normal in 5 patients, but all MRI scans were abnormal with serial imaging. The volume of radiologic signal abnormality was not associated with outcome at discharge or last follow-up (P=.67 and P=.37, respectively). CONCLUSION: Clinical outcome in patients with CPM is not predicted by the volume of radiologic T2 signal abnormality on MRI or the severity of hyponatremia. Serial brain imaging is of value because a substantial proportion of patients have normal findings on initial MRI.

Impact of pretransplant hyponatremia on outcome following liver transplantation.

UNLABELLED: Hyponatremia is associated with reduced survival in patients with cirrhosis awaiting orthotopic liver transplantation (OLT). However, data are sparse regarding the impact of hyponatremia on outcome following OLT. We investigated the effect of hyponatremia at the time of OLT on mortality and morbidity following the procedure. The study included 2,175 primary OLT recipients between 1990 and 2000. Serum sodium concentrations obtained immediately prior to OLT were correlated with subsequent survival using proportional hazards analysis. Morbidity associated with hyponatremia was assessed, including length of hospitalization, length of intensive care unit (ICU) admission, and occurrence of central pontine myelinolysis (CPM). Out of 2,175 subjects, 1,495 (68.7%) had normal serum sodium (>135 mEq/L) at OLT, whereas mild hyponatremia (125-134 mEq/L) was present in 615 (28.3%) and severe hyponatremia (<125 mEq/L) in 65 (3.0%). Serum sodium had no impact on survival up to 90 days after OLT (multivariate hazard ratio = 1.00, P = 0.99). Patients with severe hyponatremia tended to have a longer stay in the ICU (median = 4.5 days) and hospital (17.0 days) compared to normonatremic recipients (median ICU stay = 3.0 days, hospital stay = 14.0 days; P = 0.02 and 0.08, respectively). There were 10 subjects that developed CPM, with an overall incidence of 0.5%. Although infrequent, the incidence of CPM did correlate with serum sodium levels (P < 0.01). CONCLUSION: Pre-OLT serum sodium does not have a statistically significant impact on survival following OLT. The incidence of CPM correlates with hyponatremia, although its overall incidence is low. Incorporation of serum sodium in organ allocation may not adversely affect the overall post-OLT outcome.

Central pontine lesions observed with MRI in four diabetic patients.

We report four diabetic patients with a central pontine lesion on magnetic resonance imaging (MRI). All patients also had hypertension, diabetic neuropathy and nephropathy, and three had chronic hepatitis C. Their neurological symptoms were disproportionately mild compared with the MRI features, which were of high intensity on T2-weighted images, but were less prominent on T1- and diffusion-weighted images. A subclinical pontine lesion was found in two patients who had undergone MRI previously. We consider that diabetes mellitus is an important factor for developing a pontine lesion with or without symptoms, probably in association with hepato-renal problems and hypertension.

Amelioration of extrapontine myelinolysis and reversible parkinsonism in a patient with asymptomatic hypopituitarism.

A 37-year-old woman with a history of transphenoidal surgery and gamma knife treatment for prolactinoma was admitted because of pneumoniae with hyponatremia (Na 109 mmol/l). After the careful correction of the serum sodium level within 15 mmol/l/day, the patient developed parkinsonism. MRI of the brain disclosed a signal increase in the bilateral basal ganglias on T2-weighted images, a finding consistent with extrapontine myelinolysis (EPM). Interestingly, the parkinsonism fully disappeared after the replacement therapy of hydrocortisone for adrenal insufficiency due to hypopituitarism, and MRI 5 months later showed complete disappearance of the lesions, indicating the patient had ameliorated from the EPM.

Myelinolysis after correction of hyponatremia.

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.

High incidence of neurologic complications following rapid correction of severe hyponatremia in polydipsic patients.

BACKGROUND: Patients with self-induced water intoxication usually tolerate a large, rapid increase in plasma sodium without developing osmotically induced central pontine myelinolysis. However, we have previously reported a case of clinically suspected pontine myelinolysis in a patient with self-induced water intoxication. The purpose of our study was to investigate if a subgroup of these patients may also be vulnerable to neurologic complications of hyponatremia therapy. METHOD: Over a 10-year period, we identified retrospectively 12 polydipsic patients having a total of 24 episodes of symptomatic hyponatremia with plasma sodium < or = 115 mmol/L. The mode of treatment, the kinetics of correction, and the neurologic outcome were recorded. The presence of alcoholism was noted. RESULTS: Seven patients recovered uneventfully from 19 episodes of symptomatic hyponatremia. Five patients had delayed neurologic complications. Late therapy and/or respiratory arrest might have been associated with the complications for 2 patients. The other 3 patients experienced clinical features of central pontine myelinolysis leading to death in 1. Patients with neurologic complications had a higher maximal 24-hour increase in plasma sodium concentration (21.8 +/- 3.9 vs. 15.5 +/- 5.1 mmol/L, p < .02), and a higher incidence of both overcorrection to hypernatremia and chronic alcoholism, often associated with poor nutrition. All 5 patients became water intoxicated at home, and 2 patients with pontine dysfunction had subacute rather than acute hyponatremia. CONCLUSION: A large rapid increase in plasma sodium may also be detrimental in patients with self-induced water intoxication when they are alcoholic, malnourished, and have nonacute hyponatremia.

Mielinolisis póntica central con síndrome de enclaustramiento

Tha case of a 55 year old man who presented with severe global headache 8 hours after having been drinking heavily, and who over a two hour period developed deep coma and flaccid paralysis of all four extremities is reported. A CT scan of the brain was normal; however, on Magnetic Resonance Imaging (MRI) extensive hyperintense areas in the brain stem, mainly in the pons, were easily identified. Based upon the clinical and MRI findings a diagnosis of Central Pontine Myelinolysis was made. Following several months of supportive therapy the patient partially recovered and was able to leave the hospital.