Cerebral salt wasting syndrome: review

Hyponatremia is the most frequent electrolyte disorder in critically neurological patients. Cerebral salt wasting syndrome (CSW) is defined as a renal loss of sodium during intracranial disease leading to hyponatremia and a decrease in extracellular fluid volume. The pathogenesis of this disorder is still not completely understood. Sympathetic responses as well as some natriuretic factors play a role in this syndrome. Distinction between SIADH and CSW might be difficult. The essential point is the volemic state. It is necessary to rule out other intermediate causes. Treatment requires volume replacement and maintenance of a positive salt balance. Mineral corticoids may be useful in complicated cases.     

Prevalence and clinical demographics of cerebral salt wasting in patients with aneurysmal subarachnoid hemorrhage

Hyponatremia is a frequent complication following subarachnoid hemorrhage (SAH), and is commonly attributed either to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or cerebral salt wasting syndrome (CSW). The object of this study is to elucidate the clinical demographics and sequelae of hyponatremia due to CSW in subjects with aneurysmal SAH. Retrospective chart review of patients >18 years with aneurysmal SAH admitted between January 2004 and July 2007 was performed. Subjects with moderate to severe hyponatremia (serum sodium <130 mmol l⁻¹) were divided into groups consistent with CSW and SIADH based on urine output, fluid balance, natriuresis, and response to saline infusion. Clinical demographics were compared. Of 316 subjects identified, hyponatremia (serum sodium <135 mmol l⁻¹) was detected in 187 (59.2%) subjects and moderate to severe hyponatremia in 48 (15.2%). Of the latter group, 35.4% were categorized with SIADH and 22.9% with CSW. Compared to eunatremic subjects, hyponatremia was associated with significantly longer hospital stay (15.7 ± 1.9 vs. 9.6 ± 1.1 days, p < 0.001). Subjects with CSW had similar mortality and duration of hospital stay vs. those with SIADH. Though less common than SIADH, CSW was detected in approximately 23% of patients with history of aneurysmal SAH and was not clearly associated with enhanced morbidity and mortality compared to subjects with SIADH. Further studies regarding the pathogenesis and management, along with the medical consequences, of CSW are important.     

Chronic hyponatremia in a patient with renal salt wasting and without cerebral disease: relationship between RSW,risk of fractures and cognitive impairment

Renal salt wasting syndrome (RSW) is defined as a renal loss of sodium leading to hyponatremia and a decrease in extracellular fluid volume (ECV). Differentiation of this disorder from the syndrome of inappropriate antidiuretic hormone secretion (SIADH), a common cause of hyponatremia, can be difficult because both can present with hyponatremia and concentrated urine with natriuresis. Our clinical case about a 78-year-old woman with a recent fracture of the right femur not only confirms that this syndrome can occur in patients without intracranial pathologies (CT documented), but depicts how the hyponatremia caused by RSW can show a chronic, oscillating course. This is an interesting point of view because it suggests to us to consider RSW in the differential diagnosis of patients with chronic hyponatremia.     

Cerebral salt wasting syndrome in bacterial meningitis

Subarachnoid hemorrhage is the most common cause of cerebral salt wasting syndrome. There are few reports of this condition in infectious meningitis. We describe a patient with hyponatremia and bacterial meningitis. Hyponatremia rapidly improved after administration of sodium chloride. The purpose of this report is to alert clinicians to the fact that hyponatremic patients with central nervous system disease do not necessarily have a syndrome of inappropriate secretion of antidiuretic hormone (SIADH), but may have cerebral salt wasting syndrome. By contrast with SIADH, the treatment requires saline administration.     

Syndrome of inappropriate antidiuretic hormone secretion: Revisiting a classical endocrine disorder

Hyponatremia occurs in about 30% of hospitalized patients and syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia. SIADH should be differentiated from other causes of hyponatremia like diuretic therapy, hypothyroidism and hypocortisolism. Where possible, all attempts should be made to identify and rectify the cause of SIADH. The main problem in SIADH is fluid excess, and hyponatremia is dilutional in nature. Fluid restriction is the main stay in the treatment of SIADH; however, cerebral salt wasting should be excluded in the clinical setting of brain surgeries, subarachnoid hemorrhage, etc. Fluid restriction in cerebral salt wasting can be hazardous. Sodium correction in chronic hyponatremia (onset >48 hours) should be done slowly to avoid deleterious effects in brain.     

Central salt-wasting diuresis syndrome as a cause of hyponatremia in patients at the internal medicine department

Hyponatremia is a common electrolyte disorder related to central nervous system diseases and is often attributed to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and on the other hand to the cerebral salt wasting syndrome (CSWS). This syndrome is characterized by hyponatremia due to excessive renal sodium excretion resulting from a centrally mediated process. Given the divergent nature of the treatment it is of paramount importance for a clinician to be able to recognize and differentiate between these two entities. Thus the monitoring of renal function tests, which are needed for earlier diagnosis of effective osmolality disorders, is important to do in intensive care units, which are caring for patients with central nervous system lesons. Two patients successfully treated for CSW due to ischemic stroke caused by arterial embolism from heart cavities are described.     

脑耗盐综合征的研究进展

中枢神经系统疾病如动脉瘤引起的蛛网膜下腔出血、头部创伤等常可致低钠血症。除医源性因素外,脑耗盐综合征（CSWS）和抗利尿激素分泌不当综合征是引起上述低钠血症的常见原因。CSWS可引起液体和钠盐的丢失,尿钠排出增多。关于心房利钠肽、脑钠肽在CSWS发病机制中的作用尚存在争议。CSWS患者伴随的低钠血症和血容量不足会加重神经系统症状,故适时的液体和钠盐补充治疗十分重要,必要时可予氟氢考的松以增加肾小管对钠盐的重吸收。     

Hyponatremia in patients with central nervous system disease: SIADH versus CSW.

The syndromes of inappropriate antidiuretic hormone secretion (SIADH) and cerebral salt wasting (CSW) are two potential causes of hyponatremia is patients with disorders of the central nervous system. Distinguishing between these two causes can be challenging because there is considerable overlap in the clinical presentation. The primary distinction lies in the assessment of the effective arterial blood volume (EABV). SIADH is a volume-expanded state because of antidiuretic hormone-mediated renal water retention. CSW is characterized by a contracted EABV resulting from renal salt wasting. Making an accurate diagnosis is important because the treatment of each condition is quite different. Vigorous salt replacement is required in patients with CSW, whereas fluid restriction is the treatment of choice in patients with SIADH. Although most physicians are familiar with SIADH, they are much less familiar with CSW. This review emphasizes the need for CSW to be included in the differential diagnosis of hyponatremia in a patient with central nervous system disease. Distinguishing between these two disorders is of crucial importance because therapy indicated for one disorder but used in the other can result in negative clinical consequences.     

Recurrent hyponatremia after traumatic brain injury

Dysregulation of the neuroendocrine system is a frequent complication after traumatic brain injury (TBI). Symptoms of these hormonal abnormalities might be subtle and thus easily ignored. Hyponatremia usually indicates underlying disorders that disrupt fluid homeostasis. In most patients with TBI, hyponatremia is a feature of the syndrome of inappropriate antidiuretic hormone (SIADH) secretion due to pituitary dysfunction after head injury. Usually TBI-associated hyponatremia is transient and reversible. We report the case of a 48-year-old man with TBI-associated hyponatremia with delayed recovery and recurrent hyponatremia precipitated by subsequent surgery. In this report, we emphasize the importance of identifying patients with slow recovery of the injured brain, which could complicate with SIADH and acute hyponatremia. Differentiating TBI-associated SIADH from other important causes of hyponatremia such as cerebral salt wasting, and hypocortisonism are also reviewed. Prevention of its recurrence by avoiding further risk is mandatory in managing patients with TBI.     

低钠血症诊断思路

低钠血症(血清钠<135 mmol/L)是临床最常见的电解质紊乱之一，临床表现主要包括神经系统和肌肉系统表现两个方面。首先应该查血渗透压水平除外假性低钠血症，尿渗透压检查可以鉴别大量饮用低渗液体或其他肾外失钠的情况，容量判断有助于进一步鉴别低钠血症原因。利尿剂过量、脑耗盐综合征和盐皮质激素减少都能造成低容性低钠血症。而等容或高容性低钠血症则常常因为抗利尿激素不适当分泌综合征、甲状腺激素不足、糖皮质激素缺乏或心、肝、肾功能不全引起。     

中枢性低钠血症的诊治体会

目的探讨中枢性低钠血症的发病机制、诊断及治疗方法。方法对该院21例中枢性低钠血症患者的临床资料进行回顾性分析。结果19例低钠血症恢复正常;2例因合并颅内感染,高热不退,1例死亡,1例经控制感染后,低钠血症恢复正常,但仍昏迷不醒。结论低血钠、高尿钠和意识状态改变是中枢性低钠血症的诊断依据,抗利尿激素分泌不当综合征（SIADH）应限水治疗,脑性盐耗综合征（CSWS）则作水化和补盐治疗。     

Hyponatraemia in acute brain disease.

Hyponatraemia (HN) can result from a wide range of mechanisms, and therapy must be individualized. Two theories of the origin of HN in acute brain disease have prevailed. The first is the cerebral salt wasting syndrome (CSWS), where excessive natriuresis caused by some unknown cerebral natriuretic factor lowers the total sodium pool of the body and hence the plasma concentration. The second theory is the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), where an increase in total body water is caused by unphysiological secretion of ADH, lowering the concentration of sodium in the plasma. A third possibility is 'sodium shift', i.e. a displacement of sodium from the extracellular to the intracellular space with a simultaneous movement of potassium in the opposite direction. The morbidity and mortality associated with HN only arise in cases where the rate of development of HN was 0.5 mmol h-1 or more. Symptoms respond promptly when the HN is quickly corrected with furosemide and 3% sodium chloride.     

低钠血症诊疗中问题和处理经验

低钠血症是临床最常见的电解质紊乱之一,它也是内分泌会诊的常见疾病。血钠水平与低钠血症的症状间关系密切。抗利尿激素分泌失调综合征和脑性失盐综合征常需鉴别,它们都表现为低钠血症,但脑性失盐综合征患者尿量常较大,体液容量不足,抗利尿激素分泌失调综合征患者体液容量通常无明显不足。低钠血症的治疗将血钠纠正至130 mmol/L左右即可,24 h血钠升高不要超过10~12 mmol/L。血钠纠正过快容易引起渗透性脱髓鞘病变。V2受体拮抗剂治疗抗利尿激素分泌失调综合征时应从小量开始,且不能严格限水。     

Very delayed hyponatremia after surgery and radiotherapy for a pituitary macroadenoma

Severe hyponatremia (118 mmol/l) with natriuresis, consistent with cerebral salt wasting syndrome (CSWS), occurred 38 days after transsphenoidal surgery in a 59-year-old woman affected by a pituitary non-functioning macroadenoma. From the 35th day after surgery, she showed progressive polyuria, hypotension and hyponatremia associated with natriuresis, decreased plasma and increased urinary osmolality. The clinical examination revealed signs of dehydration and gradual decline in the level of consciousness. The anterior pituitary function was normal due to appropriate replacement of thyroid and adrenal axis. The patient was treated with saline administration until normal natremia and water balance were restored and neurological symptoms had completely disappeared. This case focuses on the unusually prolonged time of development of post-surgery hyponatremia, despite delayed symptomatic hyponatremia being reported to commonly occur 7 days after transsphenoidal surgery. Therefore, we would advise not to limit the periodic follow-up of the hydroelectrolytic balance to the first two weeks after surgery, but to prolong it until after discharge from hospital. In fact, an early diagnosis is of great importance to prevent permanent neurological damage or death. Since CSWS and syndrome of inappropriate secretion of ADH, the two disorders alternatively imputed to generate post-surgical hyponatremia, are characterized by different pathogenic mechanisms and require opposing therapeutic approaches, the occurrence of extracellular volume dilution or of increased sodium renal loss should be carefully investigated. The evidences in favor of CSWS, the possible mechanisms behind the syndrome and diagnosis and management of patients with post-transsphenoidal surgery CSWS are discussed.     

Behandlung der Hyponatriämie

Hyponatremia is encountered quite frequently in everyday clinical practice. The symptomatology mainly includes neurological manifestations. In addition, it has been noted in recent years that uncertain gait, falls, fractures, and osteoporosis are also associated with hyponatremia. Based on clinical and laboratory analyses, hyponatremia can be classified into three categories: hypovolemic (decreased volume), hypervolemic (with venous edema), and euvolemic. The severity of the neurological symptoms related to hyponatremia should serve to guide the therapeutic approach. Severe cerebral symptoms due to acute cerebral edema require a prompt and closely monitored course of action with administration of hypertonic saline solution. Milder and moderate symptoms as well as the syndrome of inappropriate ADH secretion (SIADH) can now also be managed with controlled use of the ADH antagonist tolvaptan, one of a new class of vaptans. Tolvaptan is a selective antagonist of the antidiuretic effect of vasopressin without primarily affecting blood pressure and depending on the dose leads to increased excretion of free water (aquaresis). Side effects predominantly concern thirst, polyuria, and hypernatremia. Under these conditions, vaptans represent a valuable asset to the therapeutic spectrum in SIADH. Further studies are needed to determine whether falls and fractures can also be beneficially influenced.     

Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH)

The syndrome of inappropriate ADH secretion (SIADH), also recently referred to as the "syndrome of inappropriate antidiuresis", is an often underdiagnosed cause of hypotonic hyponatremia, resulting for instance from ectopic release of ADH in lung cancer or as a side-effect of various drugs. In SIADH, hyponatremia results from a pure disorder of water handling by the kidney, whereas external Na+ balance is usually well regulated. Despite increased total body water, only minor changes of urine output and modest edema are usually seen. Renal function and acid-base balance are often preserved, while neurological impairment may range from subclinical to life-threatening. Hypouricemia is a distinguishing feature. The major causes and clinical variants of SIADH are reviewed, with particular emphasis on iatrogenic complications and hospital-acquired hyponatremia. Effective treatment of SIADH with water restriction, aquaretics, or hypertonic saline + loop diuretics, as opposed to worsening of hyponatremia during parenteral isotonic fluid administration, underscores the importance of an early accurate diagnosis and careful follow-up of these patients.     

Inappropriate ADH secretion-induced hyponatremia and associated with paroxetine use

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRI) are the most common antidepressants prescribed for elderly people. Although they are generally better tolerated than other antidepressant treatment classes, they can be responsible for potentially life-threatening hyponatremia, related to syndrome of inappropriate antidiuretic hormone secretion (SIADH). OBSERVATION: A 64 years-old woman was hospitalized for cognitive function alteration and vomiting after introduction of paroxetine for depressive symptoms. Serum investigations revealed hyponatremia (121 mmol/l) with low plasma osmolarity and normal natriuria consistent with diagnosis of SIADH. Hyponatremia was reversible after paroxetine withdrawal. DISCUSSION: Hyponatremia induced by SIADH is a serious but underestimated complication of SSRI treatment. This complication occurs in the elderly people within the first month of treatment. Monitoring of the serum sodium concentration during the first month of treatment is recommended for older patients.     

Syndrome of inappropriate secretion of antidiuretic hormone associated with localized herpes zoster ophthalmicus

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with localized herpes zoster is rarely reported and may be under-appreciated. We describe two diabetic men with herpes zoster ophthalmicus (HZO) who developed hyponatremia (114 and 116 mmol/L) during acute illness. Both were euvolemic and had elevated urine osmolality (435 and 368 mmol/kg.H₂O) and sodium (Na⁺) concentration (61 and 63 mmol/L) along with normal cardiac, renal, liver, and endocrine function consistent with the diagnosis of SIADH. Thorough investigation for other causes of SIADH, including detailed physical examination, laboratory studies, and computed tomography of the brain, chest, and abdomen, were negative. Despite antiviral therapy (acyclovir) for herpes zoster, ophthalmoplegia, keratitis, and post-herpetic neuralgia (PHN) developed. Even with fluid restriction and high salt diet, SIADH lasted for 3 to 4 months and resolved concomitantly with resolution of PHN, suggesting an association between SIADH and HZO. These two cases raise the potential for herpes zoster infection, especially HZO, to involve the regulatory pathway of ADH secretion, contributing to SIADH. The presence of PHN, which reflects greater neural damage may, at least in part, explain the prolonged ADH secretion and hyponatremia.     

Severe hyponatremia caused by syndrome of inappropriate secretion of antidiuretic hormone developed as initial manifestation of human herpesvirus‐6–associated acute limbic encephalitis after unrelated bone marrow transplantation

Severe hyponatremia is a critical electrolyte abnormality in allogeneic stem cell transplantation (allo‐SCT) recipients and >50% of cases of severe hyponatremia are caused by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Here, we present a patient with rapidly progressive severe hyponatremia as an initial sign and symptom of human herpesvirus‐6–associated post‐transplantation acute limbic encephalitis (HHV‐6 PALE) after allo‐SCT. A 45‐year‐old woman with acute lymphoblastic leukemia received unrelated bone marrow transplantation from a one locus‐mismatched donor at the DR locus. On day 21, she developed a generalized seizure and loss of consciousness with severe hyponatremia, elevated serum antidiuretic hormone (ADH), and decreased serum osmolality. A high titer of HHV‐6 DNA was detected in cerebrospinal fluid. Treatment with foscarnet sodium and hypertonic saline was started with improvement of neurological condition within several days. Although an elevated serum ADH, low serum osmolality, and high urinary osmolality persisted for 2 months, she had no other recurrent symptoms of encephalitis. Our experience suggests that hyponatremia accompanied by SIADH should be recognized as a prodromal or concomitant manifestation of HHV‐6 PALE, and close monitoring of serum sodium levels in high‐risk patients for HHV‐6 PALE is necessary for immediate diagnosis and treatment initiation.