Osmotic Demyelination Syndrome Revisited: Review With Neuroimaging.

Osmotic demyelination syndrome (ODS) is a general term that has become commonplace in the practice of medicine, encompassing both central pontine myelinolysis and extrapontine myelinolysis. Historically ODS arises as a serious complication of rapid correction of hyponatremia, yet its manifestations seem to be influenced by a multifactorial process. Further understanding of this rare demyelinating disease has elucidated the significant role of other electrolyte disturbances and the presence of chronic comorbidities as disease risk factors. This review discusses the current research regarding the pathophysiology, clinical manifestations, neuroimaging features, patient management, and prognosis of osmotic demyelination syndrome. We hope that this review will further endorse and aid in the proper diagnosis of ODS and its suitable management through the understanding of clinical and imaging correlations and outcomes, and the comorbid factors that may predispose the development of ODS in certain patient populations.

Central pontine and extrapontine myelinolysis: a systematic review.

The purpose was to perform a systematic review of studies on central pontine and extrapontine myelinolysis [forms of osmotic demyelination syndrome (ODS)] and define the spectrum of causes, risk factors, clinical and radiological presentations, and functional outcomes of this disorder. A thorough search of the literature was conducted using multiple databases (PubMed, Ovid Medline and Google) and bibliographies of key articles to identify all case series of adult patients with ODS published from 1959 to January 2013. Only series with five or more cases published in English were considered. Of the 2602 articles identified, 38 case series were included comprising a total of 541 patients who fulfilled our inclusion criteria. The most common predisposing factor was hyponatremia (78%) and the most common presentation was encephalopathy (39%). Favorable recovery occurred in 51.9% of patients and death in 24.8%. Liver transplant patients with ODS had a combined rate of death and disability of 77.4%, compared with 44.7% in those without liver transplantation (P < 0.001). ODS is found to have a good recovery in more than half of cases and its mortality has decreased with each passing decade. Favorable prognosis is possible in patients of ODS, even with severe neurological presentation. Further research is required to confirm the differences found in liver transplant recipients.

Identifying risk factors for central pontine and extrapontine myelinolysis after liver transplantation: a case-control study.

BACKGROUND: Central pontine and extrapontine myelinolysis (CPEPM) is a rare but potentially fatal complication after orthotopic liver transplantation (OLT). The aim of this study was to identify risk factors for development of CPEPM after OLT and to assess patient outcome. METHODS: We reviewed the clinical data of 1,378 patients who underwent OLT between 1987 and 2009 in Geneva, Switzerland and Edmonton, Canada. Nineteen patients (1.4 %) developed CPEPM. We compared their characteristics with control patients, matched by age, gender, date of OLT, and MELD score. RESULTS: The 19 patients with CPEPM (7F, mean age 52.1 ± 2 years) had a mean MELD score of 26 ± 2.2. Before OLT, patients who develop CPEPM presented more frequently low (<130 mmol/l; p < 0.04) and very low (<125 mmol/l; p < 0.009) sodium than controls. In patients developing CPEPM, the number of platelet units and fresh frozen plasma transfused during surgery was higher (p = 0.05 and 0.047), hemorrhagic complications were more frequent after OLT (p = 0.049), and variations of sodium before and after OLT were higher (p = 0.023). The association of >2 of these conditions were strongly associated with CPEPM (p = 0.00015). Mortality at 1 year of patients developing CPEPM was higher (63 vs. 13 %, p < 0.0001). CONCLUSIONS: High MELD score patients undergoing OLT, receiving massive perfusions of Na-rich products, experiencing surgery-related hemorrhagic complication and important fluctuations of Na are at risk of developing CPEPM. Therefore careful monitoring of natremia in the perioperative period and use of water-free perfusion in case of massive blood-products transfusion are critical points of this patient management.

Central pontine and extrapontine myelinolysis: a rare and fatal complication after liver transplantation.

Central pontine myelinolysis (CPM) may be more prevalent after liver transplantation (OLT). Central pontine and extrapontine myelinolysis (CPEM) is rare. The occurence of CPM may be associated with hyponatremia, a rapid rise in serum sodium concentrations, postoperatively increased plasma osmolality, and the duration of the operation. Only 1 patient had abnormal sodium levels before LT. No abnormalities were detected in immunosuppressive drug blood levels. The aim of this paper was to report our experience with CPEM among LT patients.

Seasonal postpartum hypernatremic encephalopathy with osmotic extrapontine myelinolysis and rhabdomyolysis.

BACKGROUND: Neurological manifestations secondary to extrapontine myelinolysis and rhabdomyolysis caused by hypernatremia are infrequently reported. Occurrence of neurological manifestations due to spontaneous hypernatremia during postpartum period producing rhabdomyolysis and cerebral parenchymal MRI changes has not been previously reported. OBJECTIVE: Evaluation of clinical and radiological profile of postpartum hypernatremia. METHODS: Clinical, laboratory and radiological data of eleven women in postpartum period presenting with hypernatremic encephalopathy with or without muscle weakness were reviewed. RESULTS: Eleven puerperal women presented with encephalopathy due to hypernatremia from 2007 to 2009. Consciousness was altered in all the patients ranging from confusion to deep coma. Nine patients had quadriparesis, eight had corticospinal and corticobulbar dysfunction, six had ataxia, and seizures occurred in four patients. The patients had hypernatremia ranging from 158 to 199mEq/l with hyperchloremia, markedly elevated serum CK levels (2572 to 61,107U) and azotemia. Ten patients underwent MRI which revealed hyperintensity of corpus callosum in all the patients in T2, FLAIR and diffusion weighted sequences. Symmetrical hyperintensities were seen also in internal capsule, corona radiata, cerebellar peduncles and hippocampus in various combinations. Seven patients improved neurologically with reduction of serum sodium and CK levels while four patients died. CONCLUSION: Hypernatremia is a potentially lethal condition which can produce encephalopathy, osmotic demyelination and rhabdomyolysis. Prompt identification and appropriate management can improve the outcome in these patients.

Reporte de un caso de Mielinolisis Central Pontina / Report one case of Central Pontine Myelinolysis

La Mielinolisis Central Pontina es una enfermedad desmielinizante no inflamatoria infrecuente que se ha asociado a reposición de sodio en hiponatremias severas y sintomáticas. No obstante existen otros factores que pueden alterar la homeostasis y así favorecer la mielinolisis; tales factores deben ser tomados en cuenta ante el manejo de una hiponatremia. Se plantean las diferentes causas que pueden contribuir a producir una mielinolisis pontina y se discute el caso de un paciente quien posterior a politrauma presenta múltiples complicaciones médicas incluyendo hiponatremia que asociado a otros factores generan una mielinolisis pontina demostrada. Palabras claves: Mielinolisis central pontina, hiponatremia, desnutrición.

Possible causes of central pontine myelinolysis after liver transplantation.

AIM: To sum up the clinical characteristics of patients with central pontine myelinolysis (CPM) after orthotopic liver transplantation (OLT) and to document the possible causes of CPM. METHODS: Data of 142 patients undergoing OLT between January 1999 to May 2003 were analyzed retrospectively. Following risk factors during perioperation were analyzed in patients with and without CPM: primary liver disease, preoperative serum sodium level, magnesium level and plasma osmolality, fluctuation degree of serum sodium concentration, and immunosuppressive drug level, etc. RESULTS: A total of 13 (9.2%) neurologic symptoms appeared in 142 patients post-operation including 5 cases (3.5%) with CPM and 8 cases (5.6%) with cerebral hemorrhage or infarct. Two patients developing CPM after OLT had a hyponatremia history before operation (serum sodium<130 mmol/L), their mean serum sodium level was 130.6 +/- 5.54 mmol/L. The serum sodium level was significantly lower in CPM patients than in patients without neurologic complications or with cerebral hemorrhage/infarct (P<0.05). The increase in serum sodiumduring perioperative 48 h after OLT in patients with CPM was significantly greater than that in patients with cerebral hemorrhage/infarct but without neurologic complications (19.5 +/- 6.54 mmol/L, 10.1 +/- 6.43 mmol/L, 4.5 +/- 4.34 mmol/L, respectively, P<0.05). Plasma osmolality was greatly increased postoperation in patients with CPM. Hypomagnesemia was noted in all patients perioperation, but there were no significant differences between groups. The duration of operation on patients with CPM was longer than that on others (492 +/- 190.05 min, P<0.05). Cyclosporin A (CsA) levels were normal in all patients, but there were significant differences between patients with or without neurologic complications (P<0.05). CONCLUSION: CPM may be more prevalent following liver transplantation. Although the diagnosis of CPM after OLT can be made by overall neurologic evaluations including magnetic resonance imaging (MRI) of the head, the mortality is still very high. The occurance of CPM may be associated with such factors as hyponatremia, rapid rise of serum sodium concentration, plasma osmolality increase postoperation, the duration of operation, and high CsA levels.

Central pontine myelinolysis at autopsy; a twelve year retrospective analysis.

Central pontine myelinolysis (CPM) was first described in 1959 and only later was associated with a rapid, sustained rise in serum sodium from a hyponatremic baseline. This discovery in 1981 led to modifications in recommendations for clinical treatment of hyponatremia. Our interest has been in tracking the incidence of CPM found at autopsy by year to see whether changes in medical treatment in hyponatremia have resulted in a decrease in CPM over time. Clinically asymptomatic CPM found at autopsy has always been at least as frequent as cases diagnosed premortem and serves as a reasonable indicator for the incidence of the disease. In over 3,000 autopsies, on most of which the brain was examined macroscopically and microscopically by the same neuropathologist, we have discovered 15 cases of asymptomatic, small pontine CPM. Of these 15, 6 were active lesions and 9 were remote; in the active group, 5 of the 6 cases were associated with a rapid, sustained rise in serum sodium during the appropriate time period. The incidence of asymptomatic CPM has remained steady over the 13-year time period. In contrast, we have encountered no cases of CPM diagnosed premortem that have come to autopsy in the same time period. These cases emphasize that CPM still occurs, but most often as an asymptomatic disorder with small, midline pontine lesions. When small active CPM is found, it still is associated with a rapid sustained rise in serum sodium.

Neuropathology of liver transplantation.

We reviewed retrospectively the clinical records, autopsy protocols and central nervous system tissue sections of 50 patients who underwent orthotopic liver transplantation for end-stage liver disease between 12/83 and 8/93. The postoperative survival period ranged from hours (6), weeks (17), months (17), to years (10). All patients received immunosuppressive drugs from the immediate postoperative period to the time of their death (cyclosporine, steroids; occasionally azathioprine, OKT3, FK506). Nineteen patients had neurological manifestations (hepatic encephalopathy) prior to surgery. Post-transplant neurologic signs and symptoms included: hepatic encephalopathy/altered mental status (11), focal or generalized seizures (9) and stroke (2). In the majority of cases (37) the cause of death was septicemia and/or bleeding diathesis. The neuropathologic findings present in 36 patients could be classified into 3 distinct categories: metabolic disorders: hepatic/anoxic encephalopathy, central pontine myelinolysis (15); cerebrovascular disease: subarachnoid and/or intracerebral hemorrhage, bland or hemorrhagic infarction (23); and infection: bacterial meningitis/cerebritis, multifocal fungal microabscesses, presumptive viral meningitis/encephalomyelitis (10). In conclusion, 72% of 50 patients who came to autopsy after liver transplantation were found to have neuropathologic abnormalities; these abnormalities were predominantly infections and vascular diseases.