Correction Of Hyponatremia Research Articles

Utility of Tolvaptan in the Perioperative Management of Severe Hyponatremia During Liver Transplantation: A Case Report

Severe hyponatremia can complicate the pretransplantation management of patients with decompensated cirrhosis while they await liver transplantation. Before the liver transplant, it is critical to correct severe hyponatremia to an appropriate level to reduce the risks of perioperative complications such as central pontine myelinolysis, cerebral edema, and seizures. Vasopressin receptor antagonists, and in particular tolvaptan, offer a therapeutic modality that can correct severe refractory hyponatremia in a timely and predictable manner before liver transplantation. In this case report, we describe a patient with decompensated cirrhosis and severe hyponatremia in whom administration of tolvaptan led to an optimal correction of preoperative severe hyponatremia and allowed for successful liver transplantation with no associated postoperative complications. In light of the increasing pretransplantation disease severity and higher risk of severe hyponatremia, the use of tolvaptan in the pretransplant period may gain increasing importance as a therapeutic intervention for maintaining peritransplant sodium homeostasis.

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.

Regional oligodendrocytopathy and astrocytopathy precede myelin loss and blood-brain barrier disruption in a murine model of osmotic demyelination syndrome.

The osmotic demyelination syndrome (ODS) is a non-primary inflammatory disorder of the central nervous system myelin that is often associated with a precipitous rise of serum sodium concentration. To investigate the physiopathology of ODS in vivo, we generated a novel murine model based on the abrupt correction of chronic hyponatremia. Accordingly, ODS mice developed impairments in brainstem auditory evoked potentials and in grip strength. At 24hr post-correction, oligodendrocyte markers (APC and Cx47) were downregulated, prior to any detectable demyelination. Oligodendrocytopathy was temporally and spatially correlated with the loss of astrocyte markers (ALDH1L1 and Cx43), and both with the brain areas that will develop demyelination. Oligodendrocytopathy and astrocytopathy were confirmed at the ultrastructural level and culminated with necroptotic cell death, as demonstrated by pMLKL immunoreactivity. At 48hr post-correction, ODS brains contained pathognomonic demyelinating lesions in the pons, mesencephalon, thalamus and cortical regions. These damages were accompanied by blood-brain barrier (BBB) leakages. Expression levels of IL-1β, FasL, TNFRSF6 and LIF factors were significantly upregulated in the ODS lesions. Quiescent microglial cells type A acquired an activated type B morphology within 24hr post-correction, and reached type D at 48hr. In conclusion, this murine model of ODS reproduces the CNS demyelination observed in human pathology and indicates ambiguous causes that is regional vulnerability of oligodendrocytes and astrocytes, while it discards BBB disruption as a primary cause of demyelination. This study also raises new queries about the glial heterogeneity in susceptible brain regions as well as about the early microglial activation associated with ODS.

Treatment of Hyponatremic Encephalopathy in the Critically Ill

Hyponatremic encephalopathy, symptomatic cerebral edema due to a low osmolar state, is a medical emergency and often encountered in the ICU setting. This article provides a critical appraisal and review of the literature on identification of high-risk patients and the treatment of this life-threatening disorder. Online search of the PubMed database and manual review of articles involving risk factors for hyponatremic encephalopathy and treatment of hyponatremic encephalopathy in critical illness. Hyponatremic encephalopathy is a frequently encountered problem in the ICU. Prompt recognition of hyponatremic encephalopathy and early treatment with hypertonic saline are critical for successful outcomes. Manifestations are varied, depending on the extent of CNS's adaptation to the hypoosmolar state. The absolute change in serum sodium alone is a poor predictor of clinical symptoms. However, certain patient specific risks factors are predictive of a poor outcome and are important to identify. Gender (premenopausal and postmenopausal females), age (prepubertal children), and the presence of hypoxia are the three main clinical risk factors and are more predictive of poor outcomes than the rate of development of hyponatremia or the absolute decrease in the serum sodium. In patients with hyponatremic encephalopathy exhibiting neurologic manifestations, a bolus of 100 mL of 3% saline, given over 10 minutes, should be promptly administered. The goal of this initial bolus is to quickly treat cerebral edema. If signs persist, the bolus should be repeated in order to achieve clinical remission. However, the total change in serum sodium should not exceed 5 mEq/L in the initial 1-2 hours and 15-20 mEq/L in the first 48 hours of treatment. It has recently been demonstrated in a prospective fashion that 500 mL of 3% saline at an infusion rate of 100 mL per hour can be given safely. It is critical to recognize the early signs of cerebral edema (nausea, vomiting, and headache) and intervene with IV 3% sodium chloride as this is the time to intervene rather than waiting until more severe symptoms develop. Cerebral demyelination is a rare complication of overly rapid correction of hyponatremia. The principal risk factors for cerebral demyelination are correction of the serum sodium more than 25 mEq/L in the first 48 hours of therapy, correction past the point of 140 mEq/L, chronic liver disease, and hypoxic/anoxic episode.

Thyroid emergencies : Thyroid storm and myxedema coma

Thyroid emergencies are rare life-threatening endocrine conditions resulting from either decompensated thyrotoxicosis (thyroid storm) or severe thyroid hormone deficiency (myxedema coma). Both conditions develop out of along-standing undiagnosed or untreated hyper- or hypothyroidism, respectively, precipitated by an acute stress-associated event, such as infection, trauma, or surgery. Cardinal features of thyroid storm are myasthenia, cardiovascular symptoms, in particular tachycardia, as well as hyperthermia and central nervous system dysfunction. The diagnosis is made based on clinical criteria only as thyroid hormone measurements do not differentiate between thyroid storm and uncomplicated hyperthyroidism. In addition to critical care measures therapy focusses on inhibition of thyroid hormone synthesis and secretion (antithyroid drugs, perchlorate, Lugol's solution, cholestyramine, thyroidectomy) as well as inhibition of thyroid hormone effects in the periphery (β-blocker, glucocorticoids).Cardinal symptoms of myxedema coma are hypothermia, decreased mental status, and hypoventilation with risk of pneumonia and hyponatremia. The diagnosis is also purely based on clinical criteria as measurements of thyroid hormone levels do not differ between uncomplicated severe hypothyroidism and myxedema coma. In addition to substitution of thyroid hormones and glucocorticoids, therapy focusses on critical care measures to treat hypoventilation and hypercapnia, correction of hyponatremia and hypothermia.Survival of both thyroid emergencies can only be optimized by early diagnosis based on clinical criteria and prompt initiation of multimodal therapy including supportive measures and treatment of the precipitating event.

Hyponatremia in Traumatic Brain Injury: A Practical Management Protocol.

Hyponatremia (defined as serum sodium <135 mEq/L) is the most common electrolyte abnormality in traumatic brain injury (TBI) and is also an independent predictor of poor neurologic outcome. The reported incidence of hyponatremia varies widely in literature reports, and there is continuing difficulty in clearly differentiating between the 2 common causes of hyponatremia with natriuresis: the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral salt wasting (CSW). We encounter hyponatremia frequently in our practice, and we therefore decided to review data from our center to estimate the incidence of hyponatremia and the results of our management strategies, and attempt to formulate simple guidelines for the correction of hyponatremia in TBI. A retrospective analysis of 1500 consecutively admitted patients with TBI was performed by the use of electronic records and radiographic review. Hyponatremia was defined as serum sodium <135 mEq/L, and natriuresis as a urine spot sodium of more than >40 mEq/L. The incidence of TBI, its management, and the effect of fludrocortisone were evaluated. The incidence of hyponatremia was 13.2%. Early therapy with fludrocortisone significantly reduced the duration of hospital stay (P < 0.05). Traumatic subarachnoid hemorrhage was the most common abnormality on the admission computed tomographic scan in patients who experienced hyponatremia. Early initiation of fludrocortisone in the setting of hyponatremia with natriuresis decreases the hospital stay. This protocol is probably safer in a tropical country where fluid restriction might be harmful. It also eliminates the need to differentiate between SIADH and CSW.

Atypical presentation of central pontine myelinolysis in hyperglycemia.

Central pontine myelinolysis (CPM) usually occurs with rapid correction of severe chronic hyponatremia. Despite the pronounced fluctuations in serum osmolality, CPM is rarely seen in diabetics. This is a case report of CPM associated with hyperglycemia. A 45-year-old non-smoking and non-alcoholic African American male with past medical history of type 2 diabetes, hypertension, stage V chronic kidney disease and hypothyroidism presented with a two-week history of intermittent episodes of gait imbalance, slurred speech and inappropriate laughter. Physical examination including complete neurological assessment and fundoscopic examination were unremarkable. Laboratory evaluation was significant for serum sodium: 140 mmol/L, potassium: 3.9 mmol/L, serum glucose: 178 mg/dL and serum osmolality: 317 mosmol/kg. His ambulatory blood sugars fluctuated between 100 and 600 mg/dL in the six weeks prior to presentation, without any significant or rapid changes in his corrected serum sodium or other electrolyte levels. MRI brain demonstrated a symmetric lesion in the central pons with increased signal intensity on T2- and diffusion-weighted images. After neurological consultation and MRI confirmation, the patient was diagnosed with CPM secondary to hyperosmolar hyperglycemia. Eight-week follow-up with neurology was notable for near-complete resolution of symptoms. This case report highlights the importance of adequate blood glucose control in diabetics. Physicians should be aware of complications like CPM, which can present atypically in diabetics and is only diagnosed in the presence of a high index of clinical suspicion.Learning points:Despite the pronounced fluctuations in serum osmolality, central pontine myelinolysis (CPM) is rarely seen in diabetics. This case report of CPM associated with hyperglycemia highlights the importance of adequate blood glucose control in diabetics.Physicians should be aware of complications like CPM in diabetics.CPM can present atypically in diabetics and is only diagnosed in the presence of a high index of clinical suspicion.

Prevalence of hyponatremia in inpatients with incurable and life-limiting diseases and its association with physical symptoms-a retrospective descriptive study.

Hyponatremia is a common electrolyte abnormality seen in hospitalized patients. It may cause a variety of symptoms and is associated with longer hospitalizations and higher mortality. However, to date, only little is known about the extent of hyponatremia in patients with incurable diseases and whether it is associated with physical symptoms in this patient group. This study aims to describe the prevalence of hyponatremia, associated symptoms, and symptom intensity in inpatients with hyponatremia receiving specialist palliative care (SPC). This is a retrospective study. Demographic and clinical data as well as symptoms, scored symptom intensity, and laboratory values were collected. All inpatients of a large German University Hospital receiving SPC in 2013 with documented sodium values were included. In 2013, 789 inpatients received SPC of which 710 had documented sodium values. The prevalence of hyponatremia was 38.7% (275/710). A mild degree showed 220 (31,0%), 44 (6.2%) had a moderate, and 11 (1.6%) a severe form. Hyponatremia patients experienced significantly more symptoms than normonatremic patients (mean=7.71 vs 6.63; p<0.001). Breathlessness, depressiveness, nausea, vomiting, poor appetite, constipation, and weakness were significantly more frequent in patients with hyponatremia. Furthermore, hyponatremia severity was associated with higher symptom intensity (mean=13.29 vs 11.28; p<0.001). More than one third of all SPC patients showed a hyponatremia, and the hyponatremia grade was associated with symptom burden and symptom intensity. A prospective analysis is needed to further examine this association and the possible influence of hyponatremia correction on symptom burden reduction.

P266 Periodics lateralized épileptiform discharges recorded in a centro-pontic myelinolysis, A case report

Objectives For some authors, the PLEDs are the EEG expression of a dynamic physiopathological state in which an unstable neurobiological process creates a critical-intercritical continum in relation to the nature of the underlying neuro-neuronal damage, Pre-existing ability of the patient to develop epileptic seizures and the coexistence of metabolic disorder [1,2]. We report the case of a young patient with centro-pontic myelinolysis in whom PLEDS were recorded. Materials and methods Observation: a 25-year-old patient with no medical history, hospitalized in the internal medicine department for management of acute renal failure (ARI), cytolysis, severe hyponatremia, over 18 weeks pregnancy Of amenorrhea, poisoning with thistle algae was strongly suspected. During the hospitalization, the patient had convulsive seizures and then a status epilepticus. Results The first EEG (April 2010): awake, slowly waves, frequency at 06 C/S, presence of rapid rhythms in bi-anterior, a sign in favor of cerebral suffering. MRI (magnetic resonance imaging, March 2010): Aspect in favor of centro-pontic myelinolysis. The 2nd EEG (December 2010): absence of the background rhythm. Acute triphasic activity of continuous 2 C/S is observed, its amplitude is from 50 to 70 μ V predominant on the right diffusing towards the left hemisphere, reactive at the opening of the eyes, giving an appearance of PLEDs and bi PLEDS, Which is probably in favor of metabolic encephalopathy. The 3rd EEG (June 2011): normal EEG. Discussion Centro-pontic myelinolysis is the demyelination of the brainstem in this patient following a rapid correction of hyponatremia. PLEDs relate to acute non-specific dysfunction of cortical and/ or subcortical structures, described in rapidly evolving brain tumors, hematomas, strokes (Cerebral Vascular Accidents), encephalopathies, and are described in demyelinating pathologies and Anoxia. Neufeld et al. and Chu et al. Emphasizes the presence of underlying cerebral lesion associated with a metabolic disturbance in the production of PLEDs. Being a transient phenomenon the PLEDs disappeared during the 3rd EEG. Conclusion Our observation emphasizes the EEG expression of some demyelinating lesion in PLEDs, hence the value of performing an EEG to better understand their pathophysiology.

Risk of Serum Sodium Overcorrection with V2 Antagonists in SIADH and Other High Risk Patients

Hyponatremia is a complex process caused by dysregulation of total body sodium and total body water that can be seen in hypovolemic, euvolemic, and hypervolemic states. Rapid correction of hyponatremia can also lead to serious complications. The development of V2 antagonists, such as tolvaptan, has changed and simplified the management of dilutional hyponatremia by allowing the targeting of antidiuretic hormone (ADH) action and blocking its effect on the V2 receptor. This will decrease the synthesis and relocation of aquaporin 2 to the cortical collecting duct apical membrane. Tolvaptan is approved to be used in euvolemic and hypervolemic hyponatremia, specifically in the syndrome of inappropriate antidiuretic hormone secretion and heart failure. The SALT-1 and SALT-2 studies suggested a starting dose of 15 mg of tolvaptan based on pharmacokinetic data, and while this is an effective dose, multiple studies have shown that patients can overcorrect with this starting dose. At least 1 case of osmotic demyelination – the dreaded complication of overly rapid hyponatremia correction – has been observed with tolvaptan use. While strategies for rapid attenuation of this overcorrection exist, and are discussed, starting tolvaptan at a lower dose of 7.5 mg initially and up-titrating even within the first day is another strategy that can avoid overcorrection. This was noted to be especially important in cases of hyponatremia due to the syndrome of inappropriate ADH secretion. We note that this approach can more slowly correct the hyponatremia with less attendant neurological risks than the currently recommended minimum starting dose of tolvaptan.

Prevention of the Osmotic Demyelination Syndrome After Liver Transplantation: A Multidisciplinary Perspective.

The osmotic demyelination syndrome (ODS) is a serious neurologic condition that occurs in the setting of rapid correction of hyponatremia. It presents with protean manifestations, from encephalopathy to the "locked-in" syndrome. ODS can complicate liver transplantation (LT), and its incidence may increase with the inclusion of serum sodium as a factor in the Mayo End-Stage Liver Disease score. A comprehensive understanding of risk factors for the development of ODS in the setting of LT, along with recommendations to mitigate the risk of ODS, are necessary. The literature to date on ODS in the setting of LT was reviewed. Major risk factors for the development of ODS include severe pretransplant hyponatremia (serum sodium [SNa] < 125 mEq/L), the magnitude of change in SNa pre- versus posttransplant, higher positive intraoperative fluid balance, and the presence of postoperative hemorrhagic complications. Strategies to reduce the risk of ODS include correcting hyponatremia pretransplant via fluid restriction and/or ensuring an appropriate rate of increase from the preoperative SNa via close attention to fluid and electrolyte management both during and after surgery. Multidisciplinary management involving transplant hepatology, nephrology, neurology, surgery, and anesthesiology/critical care is key to performing LT safely in patients with hyponatremia.

Secondary parkinsonism in a patient of psychogenic polydipsia

A 44-year-old man presented with history of slurring of speech, slowness in activities, abnormal posturing of the upper limbs and drooling of saliva from the mouth. He had a 5-yearlong...

Thiazide-Associated Hyponatremia, Report of the Hyponatremia Registry: An Observational Multicenter International Study

Background: Hyponatremia is a frequent and potentially life-threatening adverse side effect of thiazide diuretics. This sub-analysis of the Hyponatremia Registry database focuses on current management practices of thiazide-associated hyponatremia (TAH) and compares differences between TAH and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Methods: We analyzed 477 patients from 225 US and EU sites with euvolemic hyponatremia ([Na⁺] ≤130 mEq/L) who were receiving a thiazide diuretic. Of these, 118 met criteria for true thiazide-induced hyponatremia (TIH). Results: Thiazide was withdrawn immediately after hyponatremia was diagnosed only in 57% of TAH; in these patients, the median rate of [Na⁺] change (Δ_daily[Na⁺]) was significantly higher than those with continued thiazide treatment (3.8 [interquartile range: 4.0] vs. 1.7 [3.8] mEq/L/day). The most frequently employed therapies were isotonic saline (29.6%), fluid restriction (19.9%), the combination of these two (8.2%), and hypertonic saline (5.2%). Hypertonic saline produced the greatest Δ_daily[Na⁺] (8.0[6.4] mEq/L/day) followed by a combination of fluid restriction and normal saline (4.5 [3.8] mEq/L/day) and normal saline alone (3.6 [3.5] mEq/L/day). Fluid restriction was markedly less effective (2.7 [2.7] mEq/L/day). Overly rapid correction of hyponatremia occurred in 3.1% overall, but in up to 21.4% given hypertonic saline. Although there are highly significant differences in the biochemical profiles between TIH and SIADH, no predictive diagnostic test could be derived. Conclusions: Despite its high incidence and potential risks, the management of TAH is often poor. Immediate withdrawal of the thiazide is crucial for treatment success. Hypertonic saline is most effective in correcting hyponatremia but associated with a high rate of overly rapid correction. We could not establish a diagnostic laboratory-based test to differentiate TIH from SIADH.

Effectiveness and Tolerability of Conivaptan and Tolvaptan for the Treatment of Hyponatremia in Neurocritically Ill Patients.

To describe the effectiveness and tolerability of conivaptan and tolvaptan for the correction of hyponatremia in neurocritically ill patients. Retrospective cohort study. Neurointensive care units at two academic medical centers. Thirty-six adults admitted to the neurocritical care unit who received at least one dose of conivaptan (5 patients) or tolvaptan (31 patients) between June 2012 and May 2013. A single oral dose or intravenous bolus was administered to 23 (74%) patients who received tolvaptan and 2 (40%) patients who received conivaptan, respectively. The mean maximal increase in serum sodium level at 24 hours following the last dose compared with baseline was 5.2 mEq/L for conivaptan (p=0.05) and 7.9 mEq/L for tolvaptan (p<0.001). The mean ± SD maximal increases in serum sodium level at 48, 72, and 96 hours following the last dose of vaptan therapy compared with baseline were 5.5 ± 2.2 mEq/L (p=0.01), 5.6 ± 2.0 mEq/L (p=0.005), and 4.8 ± 2.2 mEq/L (p=0.03), respectively. Sodium overcorrection occurred in six patients (19%) receiving tolvaptan and none of the patients receiving conivaptan. Hypotension occurred in 20% of patients receiving conivaptan and 52% of patients receiving tolvaptan, whereas hypokalemia was observed in 40% of patients receiving conivaptan. Use of vaptans in neurocritically ill patients led to a significant increase in serum sodium level at 24 hours after the last dose, which was sustained for 96 hours, with the majority of patients receiving a single dose. Risk of sodium overcorrection was high and necessitates appropriate patient selection and frequent monitoring.

Treatment of Cirrhosis-Associated Hyponatremia with Midodrine and Octreotide.

Hyponatremia in the setting of cirrhosis is a common electrolyte disorder with few therapeutic options. The free water retention is due to non-osmotic vasopressin secretion resulting from the cirrhosis-associated splanchnic vasodilatation. Therefore, vasoconstrictive therapy may correct this electrolyte abnormality. The aim of this study was to assess the efficacy of midodrine and octreotide as a therapeutic approach to increasing urinary electrolyte-free water clearance (EFWC) in the correction of cirrhosis-associated hyponatremia. This observational study consisted of 10 patients with cirrhosis-associated hyponatremia. Hypovolemia was ruled out as the cause of the hyponatremia with a 48-h albumin challenge (25 g IV q6 h). Patients whose hyponatremia failed to improve with albumin challenge were started on midodrine and octreotide at 10 mg po tid and 100 μg sq tid, respectively, with rapid up-titration as tolerated to respective maximal doses of 15 mg tid and 200 μg tid within the first 24 h. We assessed urinary EFWC and serum sodium concentration before and 72 h after treatment. Pretreatment serum sodium levels ranged from 119 to 133 mmol/L. The mean pretreatment serum sodium concentration ± SEM was 124 mmol/L ± 1.6 vs 130 mmol/L ± 1.5 posttreatment (p = 0.00001). The mean pretreatment urinary EFWC ± SEM was 0.33 L ± 0.07 vs 0.82 L ± 0.11 posttreatment (p = 0.0003). Our data show a statistically significant increase in serum sodium concentration and urinary EFWC with the use of midodrine and octreotide in the treatment of cirrhosis-associated hyponatremia.

Euvolemic hyponatremia in cancer patients. Report of the Hyponatremia Registry: an observational multicenter international study

PurposeHyponatremia secondary to SIADH is frequent in cancer patients and potentially deleterious. The aim of this sub-analysis of the Hyponatremia Registry database is to analyze current diagnostic and therapeutic management practices in cancer patients with SIADH.MethodsWe analyzed 358 cancer patients who had serum sodium concentration ([Na+]) ≤ 130 mEq/L and a clinical diagnosis of SIADH from 225 sites in the USA and EU.ResultsPrecise diagnostic testing was performed in only 46%. Almost 12% of all patients did not receive any hyponatremia treatment. The most frequent therapies were fluid restriction (20%), isotonic saline (14%), fluid restriction/isotonic saline (7%), tolvaptan (8%), and salt tablets (7%). Hypertonic saline was used in less than 3%. Tolvaptan produced the greatest median rate of [Na+] change (IQR) (3.0 (4.7) mEq/L/day), followed by hypertonic saline (2.0(7.0) mEq/L/day), and fluid restriction/isotonic saline (1.9(3.2) mEq/L/day). Both fluid restriction and isotonic saline monotherapies were significantly less effective (0.8(2.0) mEq/L/day and 1.3(3.0) mEq/L/day, respectively) and were associated with clinically relevant rates of treatment failure. Only 46% of patients were discharged with [Na+] ≥ 130 mEq/L. Overly rapid correction of hyponatremia occurred in 11.7%.ConclusionsAlthough essential for successful hyponatremia management, appropriate diagnostic testing is not routinely performed in current practice. The most frequently employed monotherapies were often ineffective and sometimes even aggravated hyponatremia. Tolvaptan was used less often but showed significantly greater effectiveness. Despite clear evidence that hyponatremia is associated with poor outcome in oncology patients, most patients were discharged still hyponatremic. Further studies are needed to assess the beneficial impact of hyponatremia correction with effective therapies.

Craniopharyngioma presenting with severe hyponatremia, hyponatremia-induced myopathy, and panhypopituitarism: a case report

BackgroundCraniopharyngiomas are rare intracranial tumors commonly presenting with neurological symptoms. Reports of severe hyponatremia as a presenting manifestation of a craniopharyngioma and hyponatremia-induced myopathy are rare. We report the case of a patient with craniopharyngioma presenting with severe hyponatremia, panhypopituitarism, and hyponatremia-induced myopathy.Case presentationA 52-year-old Sri Lankan man presented with anorexia, nausea, fatigue, generalized muscle weakness, and cramps for 1 week. The onset of his illness had been preceded by vomiting and diarrhea for 1 day which he attributed to food poisoning. On examination, he had an apathetic disposition with a generalized “sallow complexion.” He was not dehydrated. Apart from reduced muscle power (4/5) and hyporeflexia, the neurological examination was normal. His serum sodium was 102 mmol/l; potassium 4.1 mmol/l; chloride 63 mmol/l; plasma osmolality 272 mosm/KgH2O; urine osmolality 642 mosm/KgH2O; and urine sodium 79 mmol/l. His creatine phosphokinase was 12,400 U/l, lactate dehydrogenase 628 U/l, aspartate aminotransferase 360 U/l, and alanine aminotransferase 64 U/l. His hormone profile revealed panhypopituitarism. An electromyogram showed nonspecific abnormalities while a muscle biopsy did not show any pathology. Magnetic resonance imaging of his brain demonstrated a well-defined craniopharyngioma with suprasellar extension. His pituitary gland was compressed and the pituitary stalk was displaced by the tumor. He had marked improvement in muscle power and rapid reduction of serum creatine phosphokinase levels paralleling the correction of severe hyponatremia, even before the initiation of hormone replacement.ConclusionsThis case illustrates the rare presentation of severe hyponatremia and hyponatremia-induced myopathy in patients with craniopharyngioma, awareness of which would facilitate early appropriate investigations and treatment.

Achados de fala, deglutição e qualidade de vida na mielinólise extrapontina: relato de caso de uma adolescente com germinoma do sistema nervoso central

RESUMO O presente trabalho é um relato de caso que descreve os achados fonoaudiológicos e de qualidade de vida apresentados por uma adolescente com um tumor do sistema nervoso central acometida pela mielinólise extrapontina. A mielinólise extrapontina é uma doença desmielinizante aguda que pode ser causada por variações abruptas na osmolaridade sérica, como o que ocorre na rápida correção da hiponatremia. Os dados foram obtidos a partir da avaliação clínica fonoaudiológica, de questionários pediátricos sobre a qualidade de vida e dados contidos no prontuário médico. A paciente apresentou mutismo, disartria e disfagia decorrentes da mielinólise extrapontina, com impactos significativos na sua comunicação verbal, alimentação e qualidade de vida. Os escores de qualidade de vida após a mielinólise extrapontina apresentaram piora quando comparados aos do período anterior à doença. Recebeu atendimento fonoaudiológico hospitalar e ambulatorial. Foram observadas evoluções nos padrões de fala, deglutição e mobilidade das estruturas orofaciais, com reversão parcial dos déficits neurológicos. A atuação fonoaudiológica, como parte de uma equipe multiprofissional de saúde, é de grande importância na reabilitação funcional dos pacientes acometidos por esta doença.

Osmotic Stress-Induced Defective Glial Proteostasis Contributes to Brain Demyelination after Hyponatremia Treatment.

Adequate protein folding is necessary for normal cell function and a tightly regulated process that requires proper intracellular ionic strength. In many cell types, imbalance between protein synthesis and degradation can induce endoplasmic reticulum (ER) stress, which if sustained, can in turn lead to cell death. In nematodes, osmotic stress induces massive protein aggregation coupled with unfolded protein response and ER stress. In clinical practice, patients sustaining rapid correction of chronic hyponatremia are at risk of osmotic demyelination syndrome. The intense osmotic stress sustained by brain cells is believed to be the major risk factor for demyelination resulting from astrocyte death, which leads to microglial activation, blood-brain barrier opening, and later, myelin damage. Here, using a rat model of osmotic demyelination, we showed that rapid correction of chronic hyponatremia induces severe alterations in proteostasis characterized by diffuse protein aggregation and ubiquitination. Abrupt correction of hyponatremia resulted in vigorous activation of both the unfolded protein response and ER stress accompanied by increased autophagic activity and apoptosis. Immunofluorescence revealed that most of these processes occurred in astrocytes within regions previously shown to be demyelinated in later stages of this syndrome. These results identify osmotic stress as a potent protein aggregation stimuli in mammalian brain and further suggest that osmotic demyelination might be a consequence of proteostasis failure on severe osmotic stress.

Temporal evolution of the trident and piglet signs of osmotic demyelination syndrome

Central pontine myelinolysis (CPM) is a potentially-devastating complication of rapid osmolar shifts, classically attributed to overlyaggressive correction of chronic hyponatremia. Magnetic resonance imaging (MRI) allowed earlier diagnosis of CPM, but most importantly, it has revealed that the odds of good functional recovery are surprisingly high. A trident shaped pontine lesion is a typical finding in CPM (the trident sign). The “piglet sign” is a much less well-known radiologic finding in CPM. Due to the rarity of CPM, very little has been published on the evolution of these MRI findings. We present a case of CPM in an alcoholic young man, and describe the temporal evolution of both the trident and piglet signs on MRI in CPM.