Dysautonomia in Guillain-Barré Syndrome: Prevalence, Clinical Spectrum, and Outcomes.

BACKGROUND: Guillain-Barré syndrome (GBS), when severe, involves the autonomic nervous system; our objective was to assess the spectrum and predictors of dysautonomia, and how it may impact functional outcomes. METHODS: A retrospective review of patients admitted to the Mayo Clinic in Rochester, MN between January 1, 2000, and December 31, 2017, with GBS and dysautonomia was performed. Demographics, comorbidities, parameters of dysautonomia, clinical course, GBS disability score, and Erasmus GBS Outcome Score (EGOS) at discharge were recorded. RESULTS: One hundred eighty seven patients were included with 71 (38%) noted to have at least one manifestation of dysautonomia. There are 72% of patients with a demyelinating form of GBS and 36% of patients with demyelination had dysautonomia. Ileus (42%), hypertension (39%), hypotension (37%), fever (29%), tachycardia or bradycardia (27%), and urinary retention (24%) were the most common features. Quadriparesis, bulbar and neck flexor weakness, and mechanical ventilation were associated with autonomic dysfunction. Patients with dysautonomia more commonly had cardiogenic complications, syndrome of inappropriate antidiuretic hormone, posterior reversible encephalopathy syndrome, and higher GBS disability score and EGOS. Mortality was 6% in patients with dysautonomia versus 2% in the entire cohort (P = 0.02). CONCLUSIONS: Dysautonomia in GBS is a manifestation of more severe involvement of the peripheral nervous system. Accordingly, mortality and functional outcomes are worse. There is a need to investigate if more aggressive treatment is warranted in this category of GBS.

Hyponatraemia: the importance of obtaining a detailed history and corroborating point-of-care analysis with laboratory testing.

We describe a 67-year-old man admitted from a mental health unit with an incidental finding of hyponatraemia on routine blood tests. Laboratory investigations were in keeping with syndrome of inappropriate antidiuretic hormone secretion (SIADH). He had been recently commenced on mirtazapine. During his inpatient stay, he became increasingly confused. Review of a previous admission with hyponatraemia raised the possibility of voltage-gated potassium channel antibody-associated limbic encephalitis, although subsequent investigations deemed this unlikely as a cause of hyponatraemia. Although his sodium levels improved with fluid restriction, serial point-of-care testing proved misleading in monitoring the efficacy of treatment as inconsistencies were seen in comparison with laboratory testing. The cause of hyponatraemia may have been medication-induced SIADH and/or polydipsia. This case highlights the importance of collating detailed histories and laboratory blood testing to guide management in cases of hyponatraemia of unknown aetiology.

[Nephrogenic syndrome of inappropriate antidiuresis]. / Syndrome d'antidiurèse inappropriée néphrogénique.

Disorders of water balance are a disease commonly encountered in our clinical practice. Analysis of vasopressin receptor type II (V2R) is essential to understand the physiology of water balance and it is used as a biological prototype of G protein-coupled receptors (GPCRs). Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a syndrome of inappropriate antidiuretic hormone secretion (SIADH) with low plasmatic vasopressin. The evidence on the role of V2 receptor and of aquaporin (AQP) in the mechanism of action for antidiuretic hormone (ADH) was based on the identification of protein gene mutations in patients with nephrogenic diabetes insipidus and NSIAD syndrome. V2R activating mutations were found in patients with NSIAD, contrasting with the numerous V2R inactivating mutations related to X-linked mutations described in patients with nephrogenic diabetes insipidus.

A quantitative approach to intravenous fluid therapy in the syndrome of inappropriate antidiuretic hormone secretion.

BACKGROUND: A wide range of interesting mathematical models has been derived to predict the effect of intravenous fluid therapy on the serum sodium concentration (most notably the Adrogué-Madias equation), but unfortunately, these models cannot be applied to patients with disorders characterized by aberrant antidiuretic hormone (ADH) release, such as the syndrome of inappropriate ADH secretion (SIADH). The use of intravenous fluids in these patients should prompt caution, as the inability of the kidneys to properly dilute the urine can easily result in deterioration of hyponatremia. METHODS: In this report, a transparent and clinically applicable equation is derived that can be used to calculate the estimated effect of different types and volumes of crystalloid infusate on the serum sodium concentration in SIADH patients. As a "proof of concept", we discuss five SIADH patient cases from our clinic. Alternatively, our mathematical model can be used to determine the infusate volume that is required to produce a certain desired change in the serum sodium concentration in SIADH patients. CONCLUSION: The presented model facilitates rational intravenous fluid therapy in SIADH patients, and provides a valuable addition to existing prediction models.

Diabetes Insipidus and Syndrome of Inappropriate Antidiuretic Hormone in Critically Ill Patients.

Diabetes insipidus and the syndrome of inappropriate antidiuretic hormone secretion lie at opposite ends of the spectrum of disordered renal handling of water. Whereas renal retention of water insidiously causes hypotonic hyponatremia in syndrome of inappropriate antidiuretic hormone secretion, diabetes insipidus may lead to free water loss, hypernatremia, and volume depletion. Hypernatremia and hyponatremia are associated with worse outcomes and longer intensive care stays. Moreover, pathologies causing polyuria and hyponatremia in patients in intensive care may be multiple, making diagnosis challenging. We provide an approach to the diagnosis and management of these conditions in intensive care patients.

Efficiency of Single Dose of Tolvaptan Treatment During the Triphasic Episode After Surgery for Craniopharyngioma

Inappropriate antidiuretic hormone syndrome (SIADH) may develop after intracranial surgery. SIADH in the pediatric age group is usually encountered in patients with an intracranial mass both before and after surgery. Fluid restriction is the standard therapy in SIADH. However, a resistant, hyponatremic pattern may be encountered in some cases. Vaptans have been recently introduced for treatment of hyponatremia due to SIADH. There is inadequate data concerning tolvaptan treatment in pediatric patients. We present a 13 year-old female with SIADH of triphasic episode who was transferred to our clinic after surgery for craniopharyngioma. Resistant hyponatremia did not resolve despite fluid restriction and hypertonic saline support. The patient responded rapidly to a single dose of tolvaptan, with no adverse effect, which resulted in successful control of her SIADH.

Possible anti-VGKC autoimmune limbic encephalitis associated with SIADH.

An 80-year-old woman presented with a 5-week history of increasing confusion. Examination was remarkable only for deficits in short-term memory and paranoid thoughts. Blood tests revealed hyponatraemia, and further biochemical testing was consistent with syndrome of inappropriate antidiuretic hormone (SIADH). After an exhaustive diagnostic workup for causes of SIADH, the only abnormal finding was a mildly raised antivoltage-gated potassium channel (VGKC) titre of 185 pmol/L (0-69) consistent with possible anti-VGKC autoimmune limbic encephalitis. However, other diagnostic features were absent. She is currently undergoing outpatient investigation for other causes of memory loss.

Hyponatremia and SIADH: A Case Study for Nursing Consideration.

The leading cause of hyponatremia in patients with cancer is syndrome of inappropriate antidiuretic hormone secretion (SIADH); this oncologic emergency requires immediate intervention. Left untreated, it can result in increased mortality and morbidity. A sodium level less than 135 meq/L is an electrolyte irregularity and defined as hyponatremia. It is extremely critical that oncology nurses are knowledgeable and able to evaluate and determine when patients are in fluid and electrolyte crisis. Nurses should be aware of the specific cancers and treatments that put patients at risk for developing hyponatremia. This article presents a case study for nursing consideration.

The Extracranial Consequences of Subarachnoid Hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) is managed across the full spectrum of healthcare, from clinical diagnosis to management of the hemorrhage and associated complications. Knowledge of the pathogenesis and pathophysiology of SAH is widely known; however, a full understanding of the underlying molecular, cellular, and circulatory dynamics has still to be achieved. Intracranial complications including delayed ischemic neurologic deficit (vasospasm), rebleed, and hydrocephalus form the targets for initial management. However, the extracranial consequences including hypertension, hyponatremia, and cardiopulmonary abnormalities can frequently arise during the management phase and have shown to directly affect clinical outcome. This review will provide an update on the pathophysiology of SAH, including the intra- and extracranial consequences, with a particular focus on the extracranial consequences of SAH. METHODS: We review the literature and provide a comprehensive update on the extracranial consequences of SAH that we hope will help the management of these cohort of patients. RESULTS: In addition to the pathophysiology of SAH, the following complications were examined and discussed: vasospasm, seizures, rebleed, hydrocephalus, fever, anemia, hypertension, hypotension, hyperglycemia, hyponatremia, hypernatremia, cardiac abnormalities, pulmonary edema, venous thromboembolism, gastric ulceration, nosocomial infection, bloodstream infection/sepsis, and iatrogenic complications. CONCLUSIONS: Although the intracranial complications of SAH can take priority in the initial management, the extracranial complications should be monitored for and recognized as early as possible because these complications can develop at varying times throughout the course of the condition. Therefore, a variety of investigations, as described by this article, should be undertaken on admission to maximize early recognition of any of the extracranial consequences. Furthermore, because the extracranial complications have a direct effect on clinical outcome and can lead to and exacerbate the intracranial complications, monitoring, recognizing, and managing these complications in parallel with the intracranial complications is important and would allow optimization of the patient's management and thus help improve their overall outcome.

The screening and management of pituitary dysfunction following traumatic brain injury in adults: British Neurotrauma Group guidance.

Pituitary dysfunction is a recognised, but potentially underdiagnosed complication of traumatic brain injury (TBI). Post-traumatic hypopituitarism (PTHP) can have major consequences for patients physically, psychologically, emotionally and socially, leading to reduced quality of life, depression and poor rehabilitation outcome. However, studies on the incidence of PTHP have yielded highly variable findings. The risk factors and pathophysiology of this condition are also not yet fully understood. There is currently no national consensus for the screening and detection of PTHP in patients with TBI, with practice likely varying significantly between centres. In view of this, a guidance development group consisting of expert clinicians involved in the care of patients with TBI, including neurosurgeons, neurologists, neurointensivists and endocrinologists, was convened to formulate national guidance with the aim of facilitating consistency and uniformity in the care of patients with TBI, and ensuring timely detection or exclusion of PTHP where appropriate. This article summarises the current literature on PTHP, and sets out guidance for the screening and management of pituitary dysfunction in adult patients with TBI. It is hoped that future research will lead to more definitive recommendations in the form of guidelines.

The suspect - SIADH.

BACKGROUND: Hyponatraemia is one of the most commonly encountered electrolyte abnormalities in general practice. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is an important but under-recognised cause. OBJECTIVE: This article explores the presentation, investigation, diagnosis and management of SIADH. DISCUSSION: SIADH can occur secondary to medications, malignancy, pulmonary disease, or any disorder involving the central nervous system. Diagnosis is made on the basis of clinical euvolaemic state with low serum sodium and osmolality, raised urine sodium and osmolality, and exclusion of pseudohyponatraemia and diuretic use. Fluid restriction of 800-1200 mL/24 hours is the mainstay of treatment. Patients with severe hyponatraemia and symptoms of altered mental state or seizures should be admitted to hospital for monitoring of fluid restriction and consideration of hypertonic saline. A rapid increase in sodium levels can precipitate osmotic demyelination and, as such, the increase in serum sodium should not exceed 10 mmol/L in 24 hours or 18 mmol/L in 48 hours.

Exophytic bulbar pilocytic astrocytoma and post-operative cerebral salt wasting syndrome.

Cerebral salt wasting syndrome (CSWS) is a well-described consequence of several neurological disorders. Although the exact etiology of CSWS is still not completely elucidated, it is believed that the hypothalamus plays a pivotal role in the genesis of this disorder. We report for the first time 3 cases of CSWS occurring during the post-operative course following surgical resection of exophytic bulbar pilocytic astrocytomas in children. Since these 3 cases shared in common a medial implication of the medulla, we suggest that specific interconnectivity between the dorso-medial portion of the medulla oblongata and the hypothalamus might thus represent an anatomical pathway of interest in the pathogenesis of CSWS. Our findings suggest that the resection of medially located exophytic bulbar tumors might constitutes a risk factor in the development of CSWS. Particular care should thus be carried towards the prompt detection and treatment of CSWS in the post-operative courses of exophytic bulbar tumors.

Predictors of failure to respond to fluid restriction in SIAD in clinical practice; time to re-evaluate clinical guidelines?

BACKGROUND: Fluid restriction is recommended as first line therapy for Syndrome of Inappropriate Antidiuresis (SIAD), despite of lack of good evidence base to support its use, and poor efficacy in clinical practice and in the literature. AIM: We set out to determine how many patients with well-defined SIAD had pre-treatment criteria which would predict failure to fluid restriction. DESIGN AND METHODS: This was a consecutive, prospective evaluation of 183 patients with a diagnosis of SIAD in two different hospitals. Full ascertainment of the diagnostic criteria for SIAD was obtained in all patients. RESULTS: About 47% of patients had a urine volume <1500 ml in 24 h, 41% had initial urine osmolality > 500 mOsm/kg, 26% a Furst-equation ratio > 1. About 59% had one criterion predicting failure to respond to fluid restriction, 37% two criteria, and 3% three criteria. CONCLUSIONS: Our data suggest that up to 60% of patients with SIAD had criteria which recent clinical guidelines suggest would predict nonresponse to fluid restriction. This may explain why the recommended first line therapy for SIAD has been shown to be ineffective.

Cerebral Salt Wasting Is the Most Common Cause of Hyponatremia in Stroke.

OBJECTIVE: The study aimed to evaluate the frequency, severity, and causes of hyponatremia in stroke and its influence on outcome. MATERIALS AND METHODS: Consecutive computed tomography- or magnetic resonance imaging-proven stroke patients within 7 days of stroke were included. Severity of stroke was assessed using the National Institute of Health Stroke Scale and consciousness using the Glasgow Coma Scale. Hyponatremia was defined if 2 consecutive serum sodium levels were <135 mEq/L and hypernatremia if >145 mEq/L. Causes of hyponatremia, such as cerebral salt wasting (CSW) and syndrome of inappropriate secretion of antidiuretic hormone (SIADH), were based on predefined criteria. Patients with CSW were managed by salt supplementation and normal saline, and fludrocortisone was used in refractory cases. In SIADH, fluid was restricted. Outcome on discharge was defined using the modified Rankin Scale (mRS). RESULTS: One hundred patients with stroke were included: 47% had ischemic stroke and 53% had intracerebral hemorrhage. Forty-three percent of the patients had hyponatremia, 6% had hypernatremia, and 4% had both. Hyponatremia was due to CSW in 19 (44.2%), SIADH in 3 (7%), miscellaneous causes in 14 (32.6%), and indeterminate in 7 (16.3%) patients. Duration of hospitalization was the independent predictor of hyponatremia and CSW. Fourteen patients died, whereas 15 had good outcome (mRS score of ≤2) and 71 had poor outcome (mRS score of 3-5). Hypernatremia was associated with high mortality compared with eunatremia and hyponatremia. CONCLUSION: Hyponatremia occurred in 43% of stroke patients. CSW was the most common cause of hyponatremia. Hyponatremia, however, was not related to death or disability.

Prospective study of hypothalamo-hypophyseal dysfunction in children and adolescents following traumatic brain injury.

BACKGROUND AND AIMS: Retrospective studies of TBI have found a neuroendocrine dysfunction following traumatic brain injury in 23 to 60% of adults and 15 to 21% of children. Our aims were to determine the prevalence of hypothalamo-hypophyseal dysfunction in children following brain injury, assess its relationship to the type of injury and the course of the acute post-traumatic phase. PATIENTS AND METHODS: Body development (growth, pubertal development, and skeletal maturity) were evaluated in 58 patients (21 girls) after a brain injury rated 3 to 12 on the Glasgow Coma Scale (GCS). The patients underwent standard endocrine tests - TSH, fT4, IGF-1, PRL, morning cortisol, FSH, LH, and testosterone in boys and estradiol in girls - in the early post-traumatic period (2 to 14 days; T0) and at 3, 6, and 12 months after the injury (T3, T6, and T12). Dynamic tests were carried out in patients with abnormalities in their clinical examination and/or laboratory results. An MRI was performed on all patients at T12. RESULTS: The median age at the time of injury was 11.3 (0.5 to 18.7) years. Of the 58 patients, 23 had GCS < 8, corresponding to severe brain injury. At T0, diabetes insipidus (DI) was diagnosed in 12 patients, and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was found in 4 patients. Frequent hormonal changes simulated central hypothyroidism (in 45% of patients) and hypogonadotropic hypogonadism (in 25% of adolescents who were already pubertal at the time of injury > Tanner II). Examination at T3 (n = 58) confirmed a combined pituitary hormone deficiency in two boys and DI in another one. At T6 (n = 49), hormonal dysfunctions were diagnosed in two boys (precocious puberty and growth hormone deficiency). At T12 (n = 39), a new endocrine dysfunction was diagnosed in five patients (growth hormone deficiency in two, hypogonadotropic hypogonadism in two, and in one patient, already diagnosed with a growth hormone deficiency, central hypothyroidism, as well). Brain MRI revealed an empty sella in two patients with growth hormone deficiency. Patients with GCS < 8 had more symptoms of SIADH or DI in the early post-traumatic period 11/23 vs. patients with GCS of 8 to 13 (4/35), and more frequent hormonal disorder (6/23) than individuals with moderate trauma (3/35), P = 0.0135. The incidence of endocrine dysfunction at T0 significantly correlated with the severity of injury (P = 0.05), but it was not an indicator for the development of a late hormonal disorder. CONCLUSION: Within a year after injury, a hormonal disorder was found in 17.6% of the patients. Neuroendocrine dysfunction as a late consequence of craniocerebral trauma in children and adolescents was less frequent than in adults. Risk factors for its development are the gravity of the injury, brain scan pathology, and possibly the development of DI, SIADH, or CSWS in the acute post-traumatic phase.