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Sample records for neurogenic diabetes insipidus

  1. Diabetes Insipidus

    MedlinePlus

    ... Kidneys & How They Work Kidney Disease A-Z Diabetes Insipidus What is diabetes insipidus? Diabetes insipidus is a rare disorder that ... produce more urine. What are the types of diabetes insipidus? The types of diabetes insipidus include central ...

  2. Diabetes insipidus - nephrogenic

    MedlinePlus

    Nephrogenic diabetes insipidus; Acquired nephrogenic diabetes insipidus; Congenital diabetes insipidus; NDI ... of very dilute urine. NDI is rare. Congenital diabetes insipidus is present at birth. It is a ...

  3. Central neurogenic diabetes insipidus, syndrome of inappropriate secretion of antidiuretic hormone, and cerebral salt-wasting syndrome in traumatic brain injury.

    PubMed

    John, Cynthia A; Day, Michael W

    2012-04-01

    Central neurogenic diabetes insipidus, syndrome of inappropriate secretion of antidiuretic hormone, and cerebral salt-wasting syndrome are secondary events that affect patients with traumatic brain injury. All 3 syndromes affect both sodium and water balance; however, they have differences in pathophysiology, diagnosis, and treatment. Differentiating between hypernatremia (central neurogenic diabetes insipidus) and the 2 hyponatremia syndromes (syndrome of inappropriate secretion of antidiuretic hormone, and cerebral salt-wasting syndrome) is critical for preventing worsening neurological outcomes in patients with head injuries.

  4. Diabetes Insipidus

    MedlinePlus

    Diabetes insipidus (DI) causes frequent urination. You become extremely thirsty, so you drink. Then you urinate. This ... is almost all water. DI is different from diabetes mellitus (DM), which involves insulin problems and high ...

  5. [Diabetes insipidus].

    PubMed

    Krysiak, Robert; Handzlik-Orlik, Gabriela; Okopień, Bogusław

    2014-01-01

    Diabetes insipidus is an uncommon disorder of water-electrolyte balance characterized by the excretion of abnormally large volumes of diluted urine (polyuria) and increased fluid intake (polydipsia). The disease may result from the insufficient production of vasopressin, its increased degradation, an impaired response of kidneys to vasopressin, or may be secondary to excessive water intake. Patients with severe and uncompensated symptoms may develop marked dehydration, neurologic symptoms and encephalopathy, and therefore diabetes insipidus can be a life-threatening condition if not properly diagnosed and managed. Patients with diabetes insipidus require treatment with desmopressin or drugs increasing sensitivity of the distal nephron to vasopressin, but this treatment may be confusing because of the disorder's variable pathophysiology and side-effects of pharmacotherapy. This review summarizes the current knowledge on different aspects of the pathophysiology, classification, clinical presentation, diagnosis, and management of diabetes insipidus. The reader is also provided with some practical recommendations on dealing with patients suffering from this disease.

  6. Diabetes Insipidus.

    PubMed

    Lu, H A Jenny

    2017-01-01

    Disruption of water and electrolyte balance is frequently encountered in clinical medicine. Regulating water metabolism is critically important. Diabetes insipidus (DI) presented with excessive water loss from the kidney is a major disorder of water metabolism. To understand the molecular and cellular mechanisms and pathophysiology of DI and rationales of clinical management of DI is important for both research and clinical practice. This chapter will first review various forms of DI focusing on central diabetes insipidus (CDI) and nephrogenic diabetes insipidus (NDI ) . This is followed by a discussion of regulatory mechanisms underlying CDI and NDI , with a focus on the regulatory axis of vasopressin, vasopressin receptor 2 (V2R ) and the water channel molecule, aquaporin 2 (AQP2 ). The clinical manifestation, diagnosis and management of various forms of DI will also be discussed with highlights of some of the latest therapeutic strategies that are developed from in vitro experiments and animal studies.

  7. Diabetes insipidus.

    PubMed

    Maghnie, Mohamad

    2003-01-01

    Diabetes insipidus is a heterogeneous condition characterized by polyuria and polydipsia caused by a lack of secretion of vasopressin, its physiological suppression following excessive water intake, or kidney resistance to its action. In many patients, it is caused by the destruction or degeneration of the neurons that originate in the supraoptic and paraventricular nuclei of the hypothalamus. Known causes of these lesions include: germinoma or craniopharyngioma; Langerhans cell histiocytosis and sarcoidosis of the central nervous system; local inflammatory, autoimmune or vascular diseases; trauma following surgery or accident; and, rarely, genetic defects in vasopressin biosynthesis inherited as autosomal dominant or X-linked recessive traits. Thirty to fifty percent of cases are considered idiopathic. Magnetic resonance imaging (MRI) allows identification of the posterior pituitary hyperintensity and of hypothalamic-pituitary abnormalities. Thickening of the pituitary stalk is the second most common finding on MRI scans in several local inflammatory pathologies and autoimmune diseases or germinoma, but it is not specific to any single subtype. A progressive increase in the size of the anterior pituitary gland should alert physicians to the possibility that a germinoma is present, whereas a decrease can suggest the presence of an inflammatory or autoimmune process. Most children with acquired central diabetes insipidus and a thickened pituitary stalk have anterior pituitary hormone deficiencies during follow-up. Biopsy of enlarged pituitary stalk should be reserved for patients with a hypothalamic-pituitary mass and progressive thickening of the pituitary stalk, since spontaneous recovery may occur.

  8. [Diabetes insipidus and pregnancy].

    PubMed

    Gutiérrez Cruz, Oswaldo; Careaga Benítez, Ricardo

    2007-04-01

    Diabetes insipidus is an uncommon pathology; its incidence varies from two to six cases in 100,000 pregnancies. It has multiple etiologies and it is classified in central and neurogenic. Patients with diabetes insipidus generally show intense thirst, polyuria, neurologic symptoms and hypernatremia. It does not seem to alter the patient's fertility. Diabetes insipidus is usually associated with pre-eclampsia, HELLP syndrome, and fatty liver disease of pregnancy. This is a report of a case seen at the Hospital General de Cholula, in Puebla, Mexico. A 19 year-old female, with 37.2 weeks of pregnancy, had a history of Langerhans cell histiocytosis since she was four years. Patient was treated with intranasal desmopressin until 2005. She went to an obstetric evaluation; laboratory and cabinet studies were obtained. A healthy 1900 g female was obtained through vaginal delivery, with a 7/9 Apgar score. We should be familiarized with this uncommon pathology because of its association with several obstetric emergencies.

  9. Diabetes insipidus.

    PubMed

    Leroy, Clara; Karrouz, Wassila; Douillard, Claire; Do Cao, Christine; Cortet, Christine; Wémeau, Jean-Louis; Vantyghem, Marie-Christine

    2013-12-01

    Diabetes insipidus (DI) is characterized by hypotonic polyuria greater than 3 liters/24 hours in adults and persisting even during water deprivation. It is mostly due to a defect in arginin-vasopressin (AVP) synthesis (central DI); other causes are: AVP resistance (nephrogenic DI), abnormal thirst regulation (primary polydipsia) or early destruction of AVP by placental enzymes (gestational DI). A thorough medical history is warranted to investigate nocturnal persistence of polyuria (night waking being a good sign of its organic nature) to specify the onset and duration of the trouble, the medication use and the potential hereditary nature of the disorder. The next step is based on weight and blood pressure measurements and especially the quantification of beverages and diuresis over a 24-hour cycle. Assessment of signs of dehydration, bladder distention, pituitary hormone hyper- or hyposecretion, tumor chiasmatic syndrome, granulomatosis and cancer is required. The diagnosis is based on biological assessment, pituitary magnetic resonance imaging (MRI) and results of a desmopressin test. In severe forms of DI, urine osmolality remains below 250 mOsmol/kg and serum sodium greater than 145 mmol/L. In partial forms of DI (urine osmolality between 250 and 750), the water deprivation test demonstrating the incapacity to obtain a maximal urine concentration is valuable, together with vasopressin or copeptin measurement. The pituitary MRI is done to investigate the lack of spontaneous hyperintensity signal in the posterior pituitary, which marks the absence of AVP and supports the diagnosis of central DI rather than primary polydipsia (although not absolute); it can also recognize lesions of the pituitary gland or pituitary stalk. Acquired central DI of sudden onset should suggest a craniopharyngioma or germinoma if it occurs before the age of 30 years, and metastasis after the age of 50 years. Fifteen to 20% of head trauma lead to hypopituitarism, including DI in 2% of

  10. History of Diabetes Insipidus.

    PubMed

    Valenti, Giovanna; Tamma, Grazia

    2016-02-01

    Under physiological conditions, fluid and electrolyte homoeostasis is maintained by the kidney adjusting urine volume and composition according to body needs. Diabetes Insipidus is a complex and heterogeneous clinical syndrome affecting water balance and characterized by constant diuresis, resulting in large volumes of dilute urine. With respect to the similarly named Diabetes Mellitus, a disease already known in ancient Egypt, Greece and Asia, Diabetes Insipidus has been described several thousand years later. In 1670s Thomas Willis, noted the difference in taste of urine from polyuric subjects compared with healthy individuals and started the differentiation of Diabetes Mellitus from the more rare entity of Diabetes Insipidus. In 1794, Johann Peter Frank described polyuric patients excreting nonsaccharine urine and introduced the term of Diabetes Insipidus. An hystorical milestone was the in 1913, when Farini successfully used posterior pituitary extracts to treat Diabetes Insipidus. Until 1920s the available evidence indicated Diabetes Insipidus as a disorder of the pituitary gland. In the early 1928, De Lange first observed that some patients with Diabetes Insipidus did not respond to posterior pituitary extracts and subsequently Forssman and Waring in 1945 established that the kidney had a critical role for these forms of Diabetes Insipidus resistant to this treatment. In 1947 Williams and Henry introduced the term Nephrogenic Diabetes Insipidus for the congenital syndrome characterized by polyuria and renal concentrating defect resistant to vasopressin. In 1955, du Vigneaud received the 1955 Nobel Prize in chemistry for the first synthesis of the hormone vasopressin representing a milestone for the treatment of Central Diabetes Insipidus.

  11. Idiopathic central diabetes Insipidus.

    PubMed

    Grace, Mary; Balachandran, Venu; Menon, Sooraj

    2011-10-01

    Idiopathic central diabetes insipidus (CDI) is a rare disorder characterized clinically by polyuria and polydipsia, and an abnormal urinary concentration without any identified etiology. We report a case of central diabetes insipidus in a 60-year-old lady in the absence of secondary causes like trauma, infection, and infiltrative disorders of brain.

  12. Diabetes insipidus: historical aspects.

    PubMed

    Lindholm, Jörgen

    2004-01-01

    The contributions to our present knowledge and understanding of diabetes insipidus are briefly surveyed. Though a disease presenting with polyuria and thirst had been recognized since Antiquity, it was not until the 17. Century the distinction was made between diabetes insipidus and diabetes mellitus. At the beginning of the 20. Century almost nothing was known about the function of the pituitary. It was generally believed that diabetes insipidus was a renal disease. Two clinical observations in 1912 suggested an association between the hypophysis and diabetes insipidus. This view was supported by the recognition in 1913 that extract of the posterior lobe of the pituitary was effective in diabetes insipidus. Despite much evidence to the contrary, it was assumed that the antidiuretic hormone was produced in the intermediate lobe of the pituitary. Around 1950 it was finally established that 'the posterior lobe hormones' are in fact secreted in the hypothalamus. At the same time the antidiuretic hormone was isolated and synthesized. More recently, progress within genetics has made it possible to characterize in details other rare types of diabetes insipidus.

  13. [Nephrogenic diabetes insipidus].

    PubMed

    Bichet, Daniel Georges

    2006-11-01

    Nephrogenic diabetes insipidus which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine-vasopressine (AVP). Polyuria, with hyposthenuria and polydipsia are the cardinal clinical manifestations of the disease. Hypercalcemia, hypokaliemia, lithium administration and chronic renal failure are the principal causes of acquired nephrogenic diabetes insipidus. About 90 percent of patients with congenital nephrogenic diabetes insipidus are males with X-linked recessive nephrogenic diabetes insipidus who have mutations in the arginine-vasopressin receptor 2 (AVPR2) gene that codes for the vasopressin V2 receptor. The gene is located in chromosome region Xq28. In about 10 percent of the families studied, congenital nephrogenic diabetes insipidus has an autosomal recessive or autosomal dominant mode of inheritance. In these cases, mutations have been identified in the aquaporin-2 gene (AQP2), which is located in chromosome region 12q13 and codes for the vasopressin-sensitive water channel. Other inherited disorders with mild, moderate or severe inability to concentrate urine include Bartter's syndrome and Cystinosis. Identification of the molecular defect underlying congenital nephrogenic diabetes insipidus is of immediate clinical significance because early diagnosis and treatment of affected infants can avert the physical and mental retardation associated with episodes of dehydration.

  14. Diabetes insipidus in children.

    PubMed

    Jain, Vandana; Ravindranath, Aathira

    2016-01-01

    Diabetes insipidus (DI) is one of the common disorders affecting sodium and water homeostasis, and results when ADH is either inadequately produced, or unable to negotiate its actions on the renal collecting tubules through aquaporins. The diagnostic algorithm starts with exclusion of other causes of polyuria and establishing low urine osmolality in the presence of high serum osmolality. In this paper, we have reviewed the diagnosis, etiology and management of DI in children, with special emphasis on recent advances in the field.

  15. Intracranial calcification in central diabetes insipidus.

    PubMed

    Al-Kandari, Salwa Ramadan; Pandey, Tarun; Badawi, Mona H

    2008-01-01

    Intracranial calcification is a known but extremely rare complication of diabetes insipidus. To date, only 16 patients have been reported and all had the peripheral (nephrogenic) type of diabetes insipidus. We report a child with intracranial calcification complicating central diabetes insipidus. We also report a child with nephrogenic diabetes insipidus, and compare the patterns of intracranial calcification.

  16. Gestational diabetes insipidus. Case Report.

    PubMed

    Ejmocka-Ambroziak, Anna; Grzechocińska, Barbara; Jastrzebska, Helena; Kochman, Magdalena; Cyganek, Anna; Wielgoś, Mirosław; Zgliczyński, Wojciech

    2015-01-01

    Gestational diabetes insipidus is a very rare complication. However, undiagnosed and untreated may lead to serious complications in both mother and fetus. In this study, a case of 34-year-old female patient with diabetes insipidus associated with pregnancy was reported. We discussed process of diagnosis and treatment with particular emphasis on the monitoring of water-electrolyte imbalance during labor.

  17. Subclinical diabetes insipidus.

    PubMed

    Bellastella, Antonio; Bizzarro, Antonio; Colella, Caterina; Bellastella, Giuseppe; Sinisi, Antonio A; De Bellis, Annamaria

    2012-08-01

    Subclinical central diabetes insipidus (CDI) can be the outcome of a number of diseases that affect the hypothalamus-infundibulum-post hypophysis axis. One of the most common forms of subclinical CDI is linked to an autoimmune pathogenesis even if other causes may be also responsible. Among these, pregnancy, traumatic and surgical brain injury and some infiltrative, vascular, infectious and neoplastic diseases have been reported with increasing frequency. The natural history of autoimmune CDI seems to evolve through 4 functional stages according to the presence of antibodies to vasopressin-secreting cells (AVPcAb) and the relationship between their behavior overtime, the variations of posterior pituitary function and the characteristics of hypothalamic-hypophyseal region on magnetic resonance imaging. This staging is of crucial importance for the therapeutic strategy, taking into account that some stages could be still reversible. Several medical treatments have been suggested to interrupt the progression toward clinical CDI but the results are still discussed.

  18. Diabetes insipidus and pregnancy.

    PubMed

    Chanson, Philippe; Salenave, Sylvie

    2016-06-01

    Diabetes insipidus (DI) is a rare complication of pregnancy. It is usually transient, being due to increased placental production of vasopressinase that inactivates circulating vasopressin. Gestational, transient DI occurs late in pregnancy and disappears few days after delivery. Acquired central DI can also occur during pregnancy, for example in a patient with hypophysitis or neuroinfundibulitis during late pregnancy or postpartum. Finally, pre-existing central or nephrogenic DI may occasionally be unmasked by pregnancy. Treatment with dDAVP (desmopressin, Minirin(®)) is very effective on transient DI of pregnancy and also on pre-existing or acquired central DI. Contrary to vasopressin, dDAVP is not degraded by vasopressinase. Nephrogenic DI is insensitive to dDAVP and is therefore more difficult to treat during pregnancy if fluid intake needs to be restricted.

  19. Water homeostasis and diabetes insipidus in horses.

    PubMed

    Schott, Harold C

    2011-04-01

    Diabetes insipidus (DI) is a rare disorder of horses characterized by profound polyuria and polydipsia (PU/PD), which can be caused by loss of production of arginine vasopressin (AVP). This condition is termed neurogenic or central DI. DI may also develop with absence or loss of AVP receptors or activity on the basolateral membrane of collecting-duct epithelial cells. This condition is termed nephrogenic DI. Equine clinicians may differentiate true DI from more common causes of PU/PD by a systematic diagnostic approach. DI may not be a correctable disorder, and supportive care of affected horses requires an adequate water source.

  20. Nephrogenic diabetes insipidus.

    PubMed

    Bichet, Daniel G

    2006-04-01

    Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone arginine vasopressin (AVP). Polyuria, with hyposthenuria, and polydipsia are the cardinal clinical manifestations of the disease. About 90% of patients with congenital NDI are males with X-linked recessive NDI (OMIM 304800) who have mutations in the arginine-vasopressin receptor 2 (AVPR2) gene that codes for the vasopressin V2 receptor. In about 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance (OMIM 222000 and 125800). In these families, mutations have been identified in the aquaporin-2 gene (AQP2) (OMIM 107777), which codes for the vasopressin-sensitive water channel. Most missense AVPR2 mutations lead to receptors that are trapped intracellularly; a few mutant receptors reach the cell surface but are unable to bind AVP or to properly trigger an intracellular cyclic adenosine monophosphate signal. Similarly, most AQP2 mutant proteins are also misrouted. Prior knowledge of AVPR2 or AQP2 mutations in NDI families and perinatal mutation testing is of direct clinical value because early diagnosis and treatment can avert the physical and mental retardation associated with repeated episodes of dehydration.

  1. Central diabetes insipidus

    PubMed Central

    Arima, Hiroshi; Azuma, Yoshinori; Morishita, Yoshiaki; Hagiwara, Daisuke

    2016-01-01

    ABSTRACT Central diabetes insipidus (CDI), characterized by polyuria and polydipsia, is caused by deficiency of arginine vasopressin (AVP), an antidiuretic hormone which acts on V2 receptors in kidney to promote reabsorption of free water. CDI is classified into three subtypes; idiopathic, secondary and familial. A previous study suggests that infundibulo-neurohypophysitis might be an underlying cause of idiopathic CDI. Among secondary CDI, the tumors in the central nervous system such as craniopharyngioma and germ cell tumors are the most frequent causes. Familial CDI is inherited mostly in an autosomal dominant mode, and the number of causal mutations in the AVP gene locus reported so far exceeds 80. CDI is treated with desmopressin, an analogue of vasopressin, and the tablet is preferred to the nasal form because it is easier to administer. It is also shown that the oral disintegrating tablet formula increases QOL and decreases the incidence of hyponatremia in CDI patients. In some CDI patients, the osmoreceptors in the hypothalamus do not function and patients do not sense thirst. These adipsic CDI patients are treated with desmopressin and adjusting the amount of daily water intake based on body weight measurement; but controlling the water balance is extremely difficult, and morbidity and mortality are shown to be high in these patients. PMID:28008190

  2. [Congenital nephrogenic diabetes insipidus].

    PubMed

    Morin, D; Delenne, A L; Kervran, A

    2005-01-01

    Nephrogenic diabetes insipidus is a rare hereditary disease, characterized by a resistance of the renal collecting duct to the action of the antidiuretic hormone, arginine vasopressin, responsible for the inability of the kidney to concentrate urine. More than 90% of the patients are males and have the X-linked recessive form of the disease usually presenting with polyuria and polydipsia in infancy. This mode of inheritance is related to mutations in the V(2) receptor gene, located in the Xq28 chromosomal region. Less than 10% of the patients have an autosomal-recessive or an autosomal-dominant mode of inheritance with clinical manifestations occurring in males and females, related to mutations in the aquaporin-2 gene, located in chromosome region 12q13. The aim of the treatment is to avoid chronic and acute dehydration episodes. It remains symptomatic, mainly based on an hypoosmotic diet and the use of hydrochlorothiazide and indomethacin. Recent findings showed that pharmacological chaperones, such as V(2) nonpeptide antagonists, are able to rescue some of the V(2) receptor mutants and could be useful tools for treatment in the future.

  3. Diabetes insipidus: clinical and basic aspects.

    PubMed

    Majzoub, Joseph A; Srivatsa, Abhinash

    2006-12-01

    Water homeostasis in the body is finely balanced by the release of the antidiuretic hormone vasopressin and the stimulation of thirst. Vasopressin acts in the kidneys to concentrate urine and reduce plasma osmolality. Diabetes insipidus is a disorder of water balance characterized by a failure to concentrate urine. There are two types of diabetes insipidus: central and nephrogenic. Central diabetes insipidus is caused by insufficient production of vasopressin, while nephrogenic diabetes insipidus is caused by an impaired response of the kidneys to vasopressin. Patients with central diabetes insipidus respond to treatment with vasopressin or its synthetic analogue, desmopressin; however, caution should be utilized in treating infants with vasopressin or analogues-infants can be treated successfully with fluids alone. Treatment of nephrogenic diabetes insipidus involves removing the underlying cause, if possible, reducing solute load or therapy with a diuretic agent.

  4. Diabetes insipidus in infants and children.

    PubMed

    Dabrowski, Elizabeth; Kadakia, Rachel; Zimmerman, Donald

    2016-03-01

    Diabetes insipidus, the inability to concentrate urine resulting in polyuria and polydipsia, can have different manifestations and management considerations in infants and children compared to adults. Central diabetes insipidus, secondary to lack of vasopressin production, is more common in children than is nephrogenic diabetes insipidus, the inability to respond appropriately to vasopressin. The goal of treatment in both forms of diabetes insipidus is to decrease urine output and thirst while allowing for appropriate fluid balance, normonatremia and ensuring an acceptable quality of life for each patient. An infant's obligate need to consume calories as liquid and the need for readjustment of medication dosing in growing children both present unique challenges for diabetes insipidus management in the pediatric population. Treatment modalities typically include vasopressin or thiazide diuretics. Special consideration must be given when managing diabetes insipidus in the adipsic patient, post-surgical patient, and in those undergoing chemotherapy or receiving medications that alter free water clearance.

  5. Diabetes insipidus: The other diabetes

    PubMed Central

    Kalra, Sanjay; Zargar, Abdul Hamid; Jain, Sunil M.; Sethi, Bipin; Chowdhury, Subhankar; Singh, Awadhesh Kumar; Thomas, Nihal; Unnikrishnan, A. G.; Thakkar, Piya Ballani; Malve, Harshad

    2016-01-01

    Diabetes insipidus (DI) is a hereditary or acquired condition which disrupts normal life of persons with the condition; disruption is due to increased thirst and passing of large volumes of urine, even at night. A systematic search of literature for DI was carried out using the PubMed database for the purpose of this review. Central DI due to impaired secretion of arginine vasopressin (AVP) could result from traumatic brain injury, surgery, or tumors whereas nephrogenic DI due to failure of the kidney to respond to AVP is usually inherited. The earliest treatment was posterior pituitary extracts containing vasopressin and oxytocin. The synthetic analog of vasopressin, desmopressin has several benefits over vasopressin. Desmopressin was initially available as intranasal preparation, but now the oral tablet and melt formulations have gained significance, with benefits such as ease of administration and stability at room temperature. Other molecules used for treatment include chlorpropamide, carbamazepine, thiazide diuretics, indapamide, clofibrate, indomethacin, and amiloride. However, desmopressin remains the most widely used drug for the treatment of DI. This review covers the physiology of water balance, causes of DI and various treatment modalities available, with a special focus on desmopressin. PMID:26904464

  6. Genetics Home Reference: nephrogenic diabetes insipidus

    MedlinePlus

    ... Review. Citation on PubMed Fujiwara TM, Bichet DG. Molecular biology of hereditary diabetes insipidus. J Am Soc Nephrol. 2005 Oct;16(10):2836-46. Epub 2005 Aug 10. Review. Citation on ... NV, Deen PM. Molecular and cellular defects in nephrogenic diabetes insipidus. Pediatr ...

  7. [Gestational diabetes insipidus during a twin pregnancy].

    PubMed

    De Mesmay, M; Rigouzzo, A; Bui, T; Louvet, N; Constant, I

    2013-02-01

    Gestational diabetes insipidus is an uncommon clinical disease whose prevalence is approximately two to three pregnancies per 100,000. It may be isolated or associated with preeclampsia. We report a case of gestational diabetes insipidus in a twin pregnancy, originally isolated during two months, and secondarily complicated by HELLP-syndrome. We recall the specific pathophysiology of polyuric-polydipsic syndrome during pregnancy and summarize its various causes. Finally, we discuss the indications, in case of isolated gestational diabetes insipidus, of treatment by dDAVP.

  8. Diabetes insipidus in a patient with diabetes mellitus.

    PubMed

    Paulose, K P; Padmakumar, N

    2002-09-01

    The association of Diabetes Mellitus (DM) and Diabetes Insipidus (DI) without any congenital defects is very rare and we report here a case of type 2 diabetes mellitus (NIDDM) whose blood sugar was controlled by insulin, developing central diabetes insipidus 2 years later, which could be successively controlled by synthetic vasopressin.

  9. Genetics Home Reference: neurohypophyseal diabetes insipidus

    MedlinePlus

    ... G, Colao A. Central diabetes insipidus and autoimmunity: relationship between the occurrence of antibodies to arginine vasopressin- ... healthcare professional . About Genetics Home Reference Site Map Customer Support Selection Criteria for Links USA.gov Copyright ...

  10. Adipsia in a Diabetes Insipidus Patient.

    PubMed

    Pereira, Maria Conceição; Vieira, Margarida M; Pereira, Joana Simões; Salgado, Duarte

    2015-01-01

    Central diabetes insipidus is a very common disorder after brain surgery or/trauma or even in the presence of brain inflammatory diseases. Polyuria and polydipsia are the clinical markers, but sometimes clinical situations are presenting with no thirst. These are not frequent but are life-treating conditions. Diagnosis is not easy, and for this reason some cases are treated late. We describe here a very infrequent oncological case of dangerous adipsic diabetes insipidus in a young girl who survived.

  11. Diabetes insipidus following resection of pituitary tumors.

    PubMed

    Schreckinger, Matthew; Szerlip, Nicholas; Mittal, Sandeep

    2013-02-01

    Diabetes insipidus (DI) is a common complication following pituitary surgery and can be transient or permanent. Neurogenic DI occurs following injury to the magnocellular neurons in the hypothalamus that produce and transport arginine vasopressin (AVP) and form the hypothalamo-hypophyseal tract. DI is defined by a constellation of signs and symptoms resulting in dilute high-volume urine output and increasing serum osmolality. The body's inability to concentrate urine leaves the patient dehydrated and leads to metabolic abnormalities that can be life threatening if not recognized and treated in a timely manner with an exogenous AVP analog. The reported incidence of postsurgical central DI varies from 1 to 67%. This wide range likely reflects inconsistencies in the working definition of DI across the literature. Factors affecting the rate of DI include pituitary tumor size, adherence to surrounding structures, surgical approach, and histopathology of pituitary lesion. The likelihood of postoperative DI can be reduced by careful preservation of the neurovascular structures of the hypothalamus, infundibulum, and neurohypophysis. Vigilance and meticulous surgical technique are essential to minimize injury to these critical regions that can lead to postsurgical DI.

  12. Post-hemorrhagic hydrocephalus and diabetes insipidus in preterm infants.

    PubMed

    Borenstein-Levin, Liron; Koren, Ilana; Kugelman, Amir; Bader, David; Toropine, Arina; Riskin, Arieh

    2014-11-01

    We present two cases of transient central diabetes insipidus in preterm neonates with post-hemorrhagic hydrocephalus. Although the association between intraventricular hemorrhage and diabetes insipidus has been described in preterm infants, the association between diabetes insipidus and hydrocephalus, and the fact that such central diabetes insipidus could be reversible with the reduction of ventricular size, either because of spontaneous resolution or the placement of ventriculo-peritoneal shunt is first described here in neonates.

  13. V2R mutations and nephrogenic diabetes insipidus.

    PubMed

    Bichet, Daniel G

    2009-01-01

    Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP). Polyuria, with hyposthenuria, and polydipsia are the cardinal clinical manifestations of the disease. Nephrogenic failure to concentrate urine maximally may be due to a defect in vasopressin-induced water permeability of the distal tubules and collecting ducts, to insufficient buildup of the corticopapillary interstitial osmotic gradient, or to a combination of these two factors. Thus, the broadest definition of the term NDI embraces any antidiuretic hormone-resistant urinary-concentrating defect, including medullary disease with low interstitial osmolality, renal failure, and osmotic diuresis. About 90% of patients with congenital NDI are males with X-linked recessive NDI (OMIM 304800)(1) and have mutations in the AVP receptor 2 (AVPR2) gene that codes for the vasopressin V(2) receptor; the gene is located in chromosome region Xq28. In about 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance (OMIM 222000 and 125800)(1). Mutations have been identified in the aquaporin-2 gene (AQP2, OMIM 107777)(1), which is located in chromosome region 12q13 and codes for the vasopressin-sensitive water channel. NDI is clinically distinguishable from neurohypophyseal diabetes insipidus (OMIM 125700(1); also referred to as central or neurogenic diabetes insipidus) by a lack of response to exogenous AVP and by plasma levels of AVP that rise normally with increase in plasma osmolality. Hereditary neurohypophyseal diabetes insipidus is secondary to mutations in the gene encoding AVP (OMIM 192340)(1). Neurohypophyseal diabetes insipidus is also a component of autosomal recessive Wolfram syndrome 1 or DIDMOAD syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) (OMIM

  14. Genetics and diagnosis of central diabetes insipidus.

    PubMed

    Bichet, Daniel G

    2012-04-01

    Most of the central diabetes insipidus cases seen in general practice are acquired but the rare cases of hereditary autosomal dominant or recessive neurohypophyseal diabetes insipidus have provided further cellular understanding of the mechanisms responsible for pre-hormone folding, maturation and release. Autosomal dominant central diabetes insipidus is secondary to the toxic accumulation of vasopressin mutants as fibrillar aggregates in the endoplasmic reticulum of hypothalamic magnocellular neurons producing vasopressin. As well, Trpv1(-/-) and Trpv4(-/-) mice have shed new light on the perception of tonicity through the stretch receptors TRPVs expressed both in central and peripheral neurons. The genomic information provided by sequencing the AVP gene is key to the routine care of these patients and, as in other genetic diseases, reduces health costs and provides psychological benefits to patients and families. In addition, simple, inexpensive blood and urine measurements together with clinical characteristics and brain magnetic resonance imaging (MRI) could distinguish between central, nephrogenic and polydipsic cases.

  15. Pemetrexed-Induced Nephrogenic Diabetes Insipidus.

    PubMed

    Fung, Enrica; Anand, Shuchi; Bhalla, Vivek

    2016-10-01

    Pemetrexed is an approved antimetabolite agent, now widely used for treating locally advanced or metastatic nonsquamous non-small cell lung cancer. Although no electrolyte abnormalities are described in the prescribing information for this drug, several case reports have noted nephrogenic diabetes insipidus with associated acute kidney injury. We present a case of nephrogenic diabetes insipidus without severely reduced kidney function and propose a mechanism for the isolated finding. Severe hypernatremia can lead to encephalopathy and osmotic demyelination, and our report highlights the importance of careful monitoring of electrolytes and kidney function in patients with lung cancer receiving pemetrexed.

  16. [Diabetes insipidus: approaches to desmopressin substitution therapy].

    PubMed

    Thanh, N C; Prokof'ev, A B

    2011-01-01

    There is a worldwide tendency toward the growing prevalence of diabetes insipidus due to the elevated frequency of its central form attributable to the large number of surgical brain interventions and craniocerebral injuries. The overall diabetes insipidus morbidity is estimated at 30%. During the last 100 years, the patients were treated first with pituitary posterior lobe extract then with synthetic arginine-vasopressin. The break-through came in 1974 with the advent of desmopressin, a synthetic analog of natural arginine-vasopressin, that antagonizes V2 receptors, lacks vasoconstrictor activity, and exerts strong long-term antidiuretic action.

  17. Profound hypernatremia due to central diabetes insipidus.

    PubMed

    Vaqar, Abeer; Rafiq, Asim; Javaid, Khalid Hussain; Parveen, Rashida; Sadaf, Rabia

    2012-06-01

    Diabetes insipidus is a rare endocrine disorder in paediatric patients. Polyuria is a cardinal manifestation that is extremely difficult to recognize in diapered infants. Careful urine quantification is the key to diagnosis in appropriate clinical setting. We report a case of a 4 months old infant presenting with an acute life threatening event following an episode of vomiting and decreased oral intake. She had profound hypernatremia which persisted after stabilization. Polyuria unrecognized by the mother was revealed by 24-hour urine output measurement. A diagnosis of diabetes insipidus was made after appropriate laboratory investigations including serum and urine osmolality. The central nature of the disease was confirmed by neuroimaging which showed holoprosencephaly.

  18. [Diabetes insipidus in infancy. II. Study of eleven cases (author's transl)].

    PubMed

    de Yturriaga, R; Barrio, R; Nieto, J A; Rabadán, B; Lledó, G; Gracia, R

    1977-01-01

    Eleven cases of diabetes insipidus are revised and distributed in the following four groups: I. Idiopathic diabetes insipidus, three. II. Secondary diabetes insipidus, four. III. Nephrogenic diabetes insipidus, two. IV. Psychogenic diabetes insipidus, two. In all these cases, clinical parameters, general analysis, hydric metabolism (static and dinamic), are studied. The precocious beginning of psychogenic diabetes insipidus, and some conclusions, on a difficult case of hard diagnosis are emphasized.

  19. A case of Rathke's cleft cyst presenting with diabetes insipidus.

    PubMed

    Erşahin, Y; Ozdamar, N; Demirtaş, E; Mutluer, S

    1995-11-01

    Rathke's cleft cysts (RCCs) are considered to arise from the remnants of Rathke's pouch, an invagination of the stomodeum. They are classically described as benign epithelium lined intrasellar cysts containing mucoid material, and also found in 2-33% of routine autopsy series. The most common presenting symptoms are visual impairment, hypothalamic dysfunction, hypopituitarism and headache. Diabetes insipidus has been described in patients with RCC. Very few cases presented with only diabetes insipidus in adults. To our knowledge, our patient is the first case of RCC presenting with only diabetes insipidus in childhood. A 9-year-old girl presented with diabetes insipidus. The physical, neurological and endocrinological examinations were normal, except for diabetes insipidus. Magnetic resonance imaging scan revealed a hyperintense lesion with supra sellar extension in the posterior pituitary both on T1 and T2 weighted images. Subtotal excision of RCC was performed via transsphenoidal surgery. However, diabetes insipidus persisted after the surgery.

  20. Transient diabetes insipidus in pregnancy

    PubMed Central

    Gunawardana, Kavinga; Grossman, Ashley

    2015-01-01

    Summary Gestational diabetes insipidus (DI) is a rare complication of pregnancy, usually developing in the third trimester and remitting spontaneously 4–6 weeks post-partum. It is mainly caused by excessive vasopressinase activity, an enzyme expressed by placental trophoblasts which metabolises arginine vasopressin (AVP). Its diagnosis is challenging, and the treatment requires desmopressin. A 38-year-old Chinese woman was referred in the 37th week of her first single-gestation due to polyuria, nocturia and polydipsia. She was known to have gestational diabetes mellitus diagnosed in the second trimester, well-controlled with diet. Her medical history was unremarkable. Physical examination demonstrated decreased skin turgor; her blood pressure was 102/63 mmHg, heart rate 78 beats/min and weight 53 kg (BMI 22.6 kg/m2). Laboratory data revealed low urine osmolality 89 mOsmol/kg (350–1000), serum osmolality 293 mOsmol/kg (278–295), serum sodium 144 mmol/l (135–145), potassium 4.1 mmol/l (3.5–5.0), urea 2.2 mmol/l (2.5–6.7), glucose 3.5 mmol/l and HbA1c 5.3%. Bilirubin, alanine transaminase, alkaline phosphatase and full blood count were normal. The patient was started on desmopressin with improvement in her symptoms, and normalisation of serum and urine osmolality (280 and 310 mOsmol/kg respectively). A fetus was delivered at the 39th week without major problems. After delivery, desmopressin was stopped and she had no further evidence of polyuria, polydipsia or nocturia. Her sodium, serum/urine osmolality at 12-weeks post-partum were normal. A pituitary magnetic resonance imaging (MRI) revealed the neurohypophyseal T1-bright spot situated ectopically, with a normal adenohypophysis and infundibulum. She remains clinically well, currently breastfeeding, and off all medication. This case illustrates some challenges in the diagnosis and management of transient gestational DI. Learning points Gestational DI is a rare complication of

  1. Nephrogenic diabetes insipidus in a dog with intestinal leiomyosarcoma.

    PubMed

    Cohen, M; Post, G S

    1999-12-15

    Nephrogenic diabetes insipidus was diagnosed in a dog with an intestinal leiomyosarcoma. The diagnosis of nephrogenic diabetes insipidus was made on the basis of results of serum biochemical tests, urinalyses, and a water-deprivation test, along with a lack of response to exogenous administration of vasopressin following the water-deprivation test. The temporal association between resection of the intestinal mass and resolution of clinical signs of diabetes insipidus (i.e., polyuria and polydipsia) and between recurrence of clinical signs and detection of metastatic disease suggests that there may have been a causal relationship, and nephrogenic diabetes insipidus may have developed as a paraneoplastic syndrome in this dog.

  2. Diabetes Insipidus and Polydipsia in a Patient with Asperger's Disorder and an Empty Sella: A Case Report.

    ERIC Educational Resources Information Center

    Raja, Michele; Azzoni, Antonella; Giammarco, Vincenzo

    1998-01-01

    Describes an Italian patient with Asperger disorders, Neurogenic Diabetes Insipidus, and Primary Empty Sella. His response to vasopressin treatment suggested a concomitant presence of primary polydipsia. Implications of the observed concurrence of these rare disorders are discussed in relation to diagnosis and pathogenesis. (Author/CR)

  3. Sheehan's syndrome with central diabetes insipidus.

    PubMed

    Laway, Bashir Ahmad; Mir, Shahnaz Ahmad; Dar, Mohd Iqbal; Zargar, Abdul Hamid

    2011-03-01

    Sheehan's syndrome refers to the occurrence of hypopituitarism after delivery, usually preceded by postpartum hemorrhage. The condition still continues to be a common cause of hypopituitarism in developing countries like India. The disorder usually presents with anterior pituitary failure with preservation of posterior pituitary functions. Posterior pituitary dysfunction in the form of central diabetes insipidus is rare in patients with Sheehan's syndrome. We describe the clinical course of a young lady who after her sixth childbirth developed severe postpartum hemorrhage followed by development of panhypopituitarism which was confirmed by hormonal investigation and demonstration of empty sella on imaging. In addition, she developed Polyuria. The water deprivation test and response to vasopressin test results indicated central diabetes insipidus. She needed oral desmopressin on a continuous basis to control polyuria.

  4. Molecular biology of hereditary diabetes insipidus.

    PubMed

    Fujiwara, T Mary; Bichet, Daniel G

    2005-10-01

    The identification, characterization, and mutational analysis of three different genes-the arginine vasopressin gene (AVP), the arginine vasopressin receptor 2 gene (AVPR2), and the vasopressin-sensitive water channel gene (aquaporin 2 [AQP2])-provide the basis for understanding of three different hereditary forms of "pure" diabetes insipidus: Neurohypophyseal diabetes insipidus, X-linked nephrogenic diabetes insipidus (NDI), and non-X-linked NDI, respectively. It is clinically useful to distinguish two types of hereditary NDI: A "pure" type characterized by loss of water only and a complex type characterized by loss of water and ions. Patients who have congenital NDI and bear mutations in the AVPR2 or AQP2 genes have a "pure" NDI phenotype with loss of water but normal conservation of sodium, potassium, chloride, and calcium. Patients who bear inactivating mutations in genes (SLC12A1, KCNJ1, CLCNKB, CLCNKA and CLCNKB in combination, or BSND) that encode the membrane proteins of the thick ascending limb of the loop of Henle have a complex polyuro-polydipsic syndrome with loss of water, sodium, chloride, calcium, magnesium, and potassium. These advances provide diagnostic and clinical tools for physicians who care for these patients.

  5. Familial forms of diabetes insipidus: clinical and molecular characteristics.

    PubMed

    Babey, Muriel; Kopp, Peter; Robertson, Gary L

    2011-07-05

    Over the past two decades, the genetic and molecular basis of familial forms of diabetes insipidus has been elucidated. Diabetes insipidus is a clinical syndrome characterized by the excretion of abnormally large volumes of diluted urine (polyuria) and increased fluid intake (polydipsia). The most common type of diabetes insipidus is caused by lack of the antidiuretic hormone arginine vasopressin (vasopressin), which is produced in the hypothalamus and secreted by the neurohypophysis. This type of diabetes insipidus is referred to here as neurohypophyseal diabetes insipidus. The syndrome can also result from resistance to the antidiuretic effects of vasopressin on the kidney, either at the level of the vasopressin 2 receptor or the aquaporin 2 water channel (which mediates the re-absorption of water from urine), and is referred to as renal or nephrogenic diabetes insipidus. Differentiation between these two types of diabetes insipidus and primary polydipsia can be difficult owing to the existence of partial as well as complete forms of vasopressin deficiency or resistance. Seven different familial forms of diabetes insipidus are known to exist. The clinical presentation, genetic basis and cellular mechanisms responsible for them vary considerably. This information has led to improved methods of differential diagnosis and could provide the basis of new forms of therapy.

  6. V2R structure and diabetes insipidus.

    PubMed

    Birnbaumer, Mariel

    2002-01-01

    For most audiences, the term "diabetes" conjures thoughts of high levels of blood glucose and of the symptoms that characterize diabetes mellitus. In the last few years, a spirited campaign spear-headed by the families of affected individuals has made progress in educating nonprofessional and medical communities about diabetes insipidus (DI), the other disease characterized by polyuria (i.e., diabetes). Much work lies ahead to find better treatments for this affliction, but the progress in molecular biology over the last years made possible the identification of the genetic defects underlying the inherited forms of the disease. Numerous cases of adult-onset DI are triggered by toxic damage to the kidneys that impairs the concentrating capacity of the nephrons by a nonspecific mechanism. In these pages I shall deal mostly with the inherited forms of the disease. Diabetes insipidus is characterized by the inability of the kidneys of affected individuals to produce concentrated urine (Morello and Bichet 2001). The elimination of large volumes of diluted urine (polyuria) and excessive thirst (polydipsia) are the chief symptoms of the disease. Although this condition and the hints that it was a hereditary disease were described at the end of the 19th century, it took almost 100 years to gain molecular knowledge about its etiology. A brief review of the important role played by vasopressin in the maintenance of body fluids will help the reader understand the severity of this disease.

  7. Genetic forms of neurohypophyseal diabetes insipidus.

    PubMed

    Rutishauser, Jonas; Spiess, Martin; Kopp, Peter

    2016-03-01

    Neurohypophyseal diabetes insipidus is characterized by polyuria and polydipsia owing to partial or complete deficiency of the antidiuretic hormone, arginine vasopressin (AVP). Although in most patients non-hereditary causes underlie the disorder, genetic forms have long been recognized and studied both in vivo and in vitro. In most affected families, the disease is transmitted in an autosomal dominant manner, whereas autosomal recessive forms are much less frequent. Both phenotypes can be caused by mutations in the vasopressin-neurophysin II (AVP) gene. In transfected cells expressing dominant mutations, the mutated hormone precursor is retained in the endoplasmic reticulum, where it forms fibrillar aggregates. Autopsy studies in humans and a murine knock-in model suggest that the dominant phenotype results from toxicity to vasopressinergic neurons, but the mechanisms leading to cell death remain unclear. Recessive transmission results from AVP with reduced biologic activity or the deletion of the locus. Genetic neurohypophyseal diabetes insipidus occurring in the context of diabetes mellitus, optic atrophy, and deafness is termed DIDMOAD or Wolfram syndrome, a genetically and phenotypically heterogeneous autosomal recessive disorder caused by mutations in the wolframin (WFS 1) gene.

  8. Gestational Diabetes Insipidus Associated with HELLP Syndrome: A Case Report.

    PubMed

    Gambito, Renela; Chan, Michael; Sheta, Mohamed; Ramirez-Arao, Precious; Gurm, Harmeet; Tunkel, Allan; Nivera, Noel

    2012-01-01

    Gestational diabetes insipidus is a rare, but well recognized, complication of pregnancy. It is related to excess vasopressinase enzyme activity which is metabolized in the liver. A high index of suspicion of gestational diabetes insipidus is required in a correct clinical setting especially in the presence of other risk factors such as preeclampsia, HELLP syndrome, and twin pregnancies. We are presenting a case of gestational diabetes insipidus in a patient with HELLP syndrome. The newborn in this case also had hypernatremia thereby raising possibilities of vasopressinase crossing the placenta.

  9. Gestational diabetes insipidus: a morphological study of the placenta.

    PubMed

    Castiglione, F; Buccoliero, A M; Garbini, F; Gheri, C F; Moncini, D; Poggi, G; Saladino, V; Rossi Degl'Innocenti, D; Gheri, R G; Taddei, G L

    2009-12-01

    Gestational diabetes insipidus (GDI) refers to the state of excessive water intake and hypotonic polyuria. Those cases manifesting in pregnancy and referred to as GDI may persist thereafter or may be a transient latent form that resolves after delivery. Microscopic examination of affected subjects has not been previously reported. In the literature, there are various case reports and case series on diabetes insipidus in pregnancy. In this study, we present a case that had transient diabetes insipidus during pregnancy in which the placenta was examined.

  10. [Growth in children with diabetes insipidus].

    PubMed

    Morla Báez, E; Dorantes Alvarez, L M; Chavarría Bonequi, C

    1980-01-01

    Commercial preparations of vasopressin for the treatment of diabetes insipidus are not available in Mexico. Besides, the hormone is useless in the nephrogenic variety. In the department of Endocrinology at the Hospital Infantil de Mexico, a preparation containing hydrochlorothiazide, aminopyrine and potassium chloride, which reduces urinary volumes in about two thirds, is employed in all varieties of the disease. Growth in stature was investigated in 44 patients under treatment, attending the Endocrine Outpatient Clinic since 1967 for a period of 2 to 12 years. Clinical material included 29 males and 15 females. There were 23 idiopathic, 7 histiocytosis, 5 nephrogenic, 4 craniopharyngiomas, 2 psychogenic polydipsia, 2 traumatic and 1, as a sequel of tuberculous meningoencephalitis. Six idiopathic, 2 nephrogenic, 2 traumatic, 1 histiocytosis, and 1 psychogenic proceeded between percentiles 3 and 97, parallel to the nearest line of reference along the whole period of study. Two nephrogenic, 2 histiocytosis, 1 psychogenic, 1 post-meningoencephalitis and 14 idiopathic, grew below the third percentile, but parallel to it. One nephrogenic, 4 histiocytosis, 4 craniopharyngioma and 3 idiopathic progressively departed from the initial centile. Two of the latter had growth hormone deficiency, and 1 had been very irregularly treated. It is concluded that the therapy employed limits stature impairment but does not produce catch-up growth. Accordingly, it is proposed that the treatment of diabetes insipidus should be started as early as possible, and that if progress in stature is appreciably deteriorated, the presence of additional pathology should be suspected.

  11. Diabetes insipidus: a challenging diagnosis with new drug therapies.

    PubMed

    Saifan, Chadi; Nasr, Rabih; Mehta, Suchita; Sharma Acharya, Pranab; Perrera, Isera; Faddoul, Giovanni; Nalluri, Nikhil; Kesavan, Mayurakhan; Azzi, Yorg; El-Sayegh, Suzanne

    2013-01-01

    Diabetes Insipidus (DI) is either due to deficient secretion of arginine vasopressin (central) or to tubular unresponsiveness (nephrogenic). Drug induced DI is a well-known entity with an extensive list of medications. Polyuria is generally defined as urine output exceeding 3 liters per day in adults. It is crucial to identify the cause of diabetes insipidus and to implement therapy as early as possible to prevent the electrolyte disturbances and the associated mortality and morbidity. It is very rare to have an idiosyncratic effect after a short use of a medication, and physicians should be aware of such a complication to avoid volume depletion. The diagnosis of diabetes insipidus is very challenging because it relies on laboratory values, urine output, and the physical examination of the patient. A high clinical suspicion of diabetes insipidus should be enough to initiate treatment. The complications related to DI are mostly related to the electrolyte imbalance that can affect the normal physiology of different organ systems.

  12. Isolated central diabetes insipidus in a newborn with congenital toxoplasmosis.

    PubMed

    Karadag, Ahmet; Erdeve, Omer; Atasay, Begum; Arsan, Saadet; Deda, Gulhis; Ince, Erdal; Ocal, Gonul; Berberoglu, Merih

    2006-02-01

    We present a 5 day-old male newborn with isolated central diabetes insipidus due to congenital toxoplasmosis. This patient was referred to us for hydrocephalus. As we investigated the aetiology of the hydrocephalus, the patient's serum and cerebrospinal fluid tested positive for toxoplasmosis via ELISA and polymerase chain reaction. Computed tomography showed obstructive hydrocephalus and disseminated cranial calcifications. Central diabetes insipidus developed on the 10th day, apparently as a result of the toxoplasmosis infection, and was treated successfully with oral desmopressin.

  13. Central diabetes insipidus in children with acute brain insult.

    PubMed

    Yang, Yun-Hsuan; Lin, Jainn-Jim; Hsia, Shao-Hsuan; Wu, Chang-Teng; Wang, Huei-Shyong; Hung, Po-Cheng; Chou, Min-Liang; Hsieh, Meng-Ying; Lin, Kuang-Lin

    2011-12-01

    Central diabetes insipidus occurs in patients with overwhelming central nervous system injuries, and may be associated with brain death. The clinical picture of children with acquired central diabetes insipidus after acute brain insult is seldom reported. We retrospectively reviewed cases dating from January 2000-February 2008 at a tertiary pediatric intensive care unit. Fifty-four patients (28 girls, 26 boys), aged 3 months to 18 years, were enrolled. Etiologies included severe central nervous system infection (35.2%), hypoxic-ischemic events (31.5%), head injury (18.5%), and vascular lesions (14.8%). In 39 (72.2%) patients, diabetes insipidus was diagnosed during the first 2 days after acute central nervous system injury, and 40 (74.0%) developed maximum serum sodium concentrations of >160 mEq/L. In 16, sequential cerebral salt wasting syndrome developed after their initial diabetes insipidus presentation. Overall mortality at 2 months after admission was 77.8%. Our results demonstrate that patients who develop central diabetes insipidus after acute central nervous system injury manifest high mortality. Development of central diabetes insipidus within the first 2 days and a maximum plasma sodium >160 mEq/L were significant predictors of outcomes.

  14. Physiopathology and diagnosis of nephrogenic diabetes insipidus.

    PubMed

    Devuyst, Olivier

    2012-04-01

    Nephrogenic diabetes insipidus (NDI) is caused by an improper response of the kidney to the antidiuretic hormone arginine vasopressin (AVP), leading to a decreased ability to concentrate urine which results in polyuria and polydipsia. The clinical diagnosis of NDI relies on demonstration of subnormal ability to concentrate urine despite the presence of AVP. NDI is most commonly acquired, secondary to kidney disorders, electrolyte imbalance and various drugs. Congenital forms of NDI are rare, and most commonly inherited in a X-linked manner with mutations of the AVP receptor type 2 (AVPR2). Mutations of the water channel aquaporin-2 (AQP2) can be detected in autosomal recessive or dominant forms of NDI. Management of NDI should focus on free access to drinking water and reduction of polyuria.

  15. Transient Diabetes Insipidus Following Cardiopulmonary Bypass.

    PubMed

    Ekim, Meral; Ekim, Hasan; Yilmaz, Yunus Keser; Bolat, Ali

    2015-04-01

    Diabetes insipidus (DI) results from inadequate output of Antidiuretic Hormone (ADH) from the pituitary gland (central DI) or the inability of the kidney tubules to respond to ADH (nephrogenic DI). ADH is an octapeptide produced in the supraoptic and paraventricular nuclei of the hypothalamus and stored in the posterior lobe of the pituitary gland. Cardiopulmonary Bypass (CPB) has been shown to cause a six-fold increased circulating ADH levels 12 hours after surgery. However, in some cases, ADH release may be transiently suppressed due to cardioplegia (cardiac standstill) or CPB leading to DI. We present the postoperative course of a 60-year-old man who developed transient DI after CPB. He was successfully treated by applying nasal desmopressin therapy. Relevant biochemical parameters should be monitored closely in patients who produce excessive urine after open heart surgery.

  16. A Rare Case of Congenital Diabetes Insipidus.

    PubMed

    Rege, Tanvi; Polsani, Srujana; Jim, Belinda

    2015-01-01

    Congenital nephrogenic diabetes insipidus (NDI) is a conformation disease resulting from protein misfolding. Ninety percent of mutations result from the inactivating mutations of the arginine vasopressin receptor 2 (AVPR2) gene transmitted in an X-linked fashion, blocking the response to vasopressin, resulting in the inability to concentrate urine. Clinical features include polyuria, polydispsia, dehydration, and hypernatremia. They are generally more severely in affected males but present variably in females due to skewed inactivation of the X chromosome. We describe a case of a 40-year-old woman with a history of Type 2 diabetes mellitus, hyperlipidemia, and obesity, who presents with debilitating polyuria since the age of 5 with no clear diagnosis. Interestingly, her son was diagnosed with NDI. Genetic testing revealed that she was heterozygous for the Val88Met mutation in the AVPR2 gene while her son was hemizygous for the same. The patient has since been successfully treated with diuretics and a low solute diet. We highlight that although X-linked NDI patients are mostly males, it should be considered in symptomatic females to prevent delays in the diagnosis. Conformational diseases such as NDI are presently the subject of research using pharmacological chaperones to restore proper receptor membrane localization and function.

  17. [Mutations in the arginine vasopressin neurophysin-II gene in familial neurohypophyseal diabetes insipidus patients].

    PubMed

    Peralta-Leal, Valeria; Durán-González, Jorge; Leal-Ugarte, Evelia

    2008-01-01

    Neurogenic diabetes insipidus (NDI) is a rare condition characterized by polyuria and polydipsia caused by deficient arginine vasopressin hormone production. More than a 50 mutations have been identified for familial autosomic dominant neurogenic diabetes insipidus (FadNDI). These mutations can cause citotoxicity and lead to the degeneration of magnocellular neurons of the hipofisis by aberrant protein accumulation. The NDI diagnosis is based on the water deprivation test, quantification of AVP hormone and Magnetic Resonance Image (MRI), and in families with history of FadNDI has been suggested the molecular analysis of mutation in the arginine vasopressin neurophisin II gene before the signs and symptoms development, with the purpose of offering a suitable diagnosis, clinical follow up and treatment. The treatment with a synthetic analogue of AVP hormone allows the remission of the signs and symptoms in NDI patients and the advances in gene therapy in animal models has been promising, as much for NDI as for other diseases in which the mutant protein production has been involved.

  18. Diabetes insipidus secondary to sarcoidosis presenting with caseating granuloma.

    PubMed

    Alam, Taimour; Thomas, Steven

    2011-03-03

    Diabetes insipidus is a rare complication of sarcoid infiltration of the hypothalamic-pituitary region. Non-caseating granuloma formation is typical of sarcoidosis. Anterior and posterior pituitary function may be affected. MRI coupled with endocrinology assessment is the usual method of investigation. A 25-year-old Caucasian male with no significant medical history presented with polyuria and polydipsia. Water deprivation test confirmed diabetes insipidus. CT scanning of the chest confirmed lymphadenopathy. Lymph node biopsy revealed caseating granuloma. Extensive investigation for tuberculosis was negative. The patient was started on intranasal desmopressin and steroids with marked improvement in symptoms. This is the first reported case of neurosarcoidosis with diabetes insipidus and caseation on histology that we are aware of. Differentiating between caseation due to sarcoidosis and tuberculosis on histology is possible by the use of special stains. Return of normal endocrine function is unusual and the patient is likely to require desmopressin therapy for life.

  19. Diabetes Insipidus after Traumatic Brain Injury

    PubMed Central

    Capatina, Cristina; Paluzzi, Alessandro; Mitchell, Rosalid; Karavitaki, Niki

    2015-01-01

    Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in many age groups. Neuroendocrine dysfunction has been recognized as a consequence of TBI and consists of both anterior and posterior pituitary insufficiency; water and electrolyte abnormalities (diabetes insipidus (DI) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH)) are amongst the most challenging sequelae. The acute head trauma can lead (directly or indirectly) to dysfunction of the hypothalamic neurons secreting antidiuretic hormone (ADH) or of the posterior pituitary gland causing post-traumatic DI (PTDI). PTDI is usually diagnosed in the first days after the trauma presenting with hypotonic polyuria. Frequently, the poor general status of most patients prevents adequate fluid intake to compensate the losses and severe dehydration and hypernatremia occur. Management consists of careful monitoring of fluid balance and hormonal replacement. PTDI is associated with high mortality, particularly when presenting very early following the injury. In many surviving patients, the PTDI is transient, lasting a few days to a few weeks and in a minority of cases, it is permanent requiring management similar to that offered to patients with non-traumatic central DI. PMID:26239685

  20. Diabetes insipidus: Differential diagnosis and management.

    PubMed

    Robertson, Gary L

    2016-03-01

    Diabetes insipidus (DI) is a syndrome characterized by the excretion of abnormally large volumes of dilute urine. It can be caused by any of 4 fundamentally different defects that must be distinguished for safe and effective management. They are: (1) pituitary DI, due to inadequate production and secretion of antidiuretic hormone, arginine-vasopressin (AVP); (2) gestational DI due to degradation of AVP by an enzyme made in placenta; (3) primary polydipsia, due to suppression of AVP secretion by excessive fluid intake; and (4) nephrogenic DI due to renal insensitivity to the antidiuretic effect of AVP. This review describes several methods of differential diagnosis, indicates the advantages and disadvantages of each and presents a new approach that is simpler and less costly but just as reliable as the best of the older methods. The various treatments for the different types of DI and recent findings on the genetic basis of the familial forms of DI are also discussed with emphasis on their contributions to improved diagnosis and management.

  1. Diabetes insipidus--diagnosis and management.

    PubMed

    Di Iorgi, Natascia; Napoli, Flavia; Allegri, Anna Elsa Maria; Olivieri, Irene; Bertelli, Enrica; Gallizia, Annalisa; Rossi, Andrea; Maghnie, Mohamad

    2012-01-01

    Central diabetes insipidus (CDI) is the end result of a number of conditions that affect the hypothalamic-neurohypophyseal system. The known causes include germinoma/craniopharyngioma, Langerhans cell histiocytosis (LCH), local inflammatory, autoimmune or vascular diseases, trauma resulting from surgery or an accident, sarcoidosis, metastases and midline cerebral and cranial malformations. In rare cases, the underlying cause can be genetic defects in vasopressin synthesis that are inherited as autosomal dominant, autosomal recessive or X-linked recessive traits. The diagnosis of the underlying condition is challenging and raises several concerns for patients and parents as it requires long-term follow-up. Proper etiological diagnosis can be achieved via a series of steps that start with clinical observations and then progress to more sophisticated tools. Specifically, MRI identification of pituitary hyperintensity in the posterior part of the sella, now considered a clear marker of neurohypophyseal functional integrity, together with the careful analysis of pituitary stalk shape and size, have provided the most striking findings contributing to the diagnosis and understanding of some forms of 'idiopathic' CDI. MRI STIR (short-inversion-time inversion recovery sequencing) is a promising technology for the early identification of LCH-dependent CDI.

  2. Diabetes mellitus, diabetes insipidus, and optic atrophy. An autosomal recessive syndrome?

    PubMed Central

    Fraser, F C; Gunn, T

    1977-01-01

    Twenty-one families were selected from the published reports in which the propositus had the triad of juvenile diabetes mellitus, diabetes insipidus, and optic atrophy. The data were consistent with the hypothesis of an autosomal gene which, in the homozygote, causes juvenile diabetes mellitus and one or more of diabetes insipidus, optic atrophy, and nerve deafness. Heterozygotes appear to have an increased probability of developing juvenile diabetes mellitus. PMID:881709

  3. Adipsic diabetes insipidus following pituitary surgery for a macroprolactinoma.

    PubMed

    Sherlock, M; Agha, A; Crowley, R; Smith, D; Thompson, C J

    2006-01-01

    Adipsic diabetes insipidus (ADI) is a rare condition in which thirst, an essential clinical feature for the prevention of hypernatraemic dehydration, is absent. We report the first case of adipsic diabetes insipidus to occur following surgery for a pituitary macroprolactinoma, with loss of both osmoregulated and baroregulated vasopressin release. Following extensive surgery for a vision threatening macroprolactinoma a 14-year-old boy developed profound hypernatraemia with absent thirst sensation. Detailed investigation, with hypertonic saline infusion and trimetaphan infusion, revealed absence of both osmoregulatory and baroregulatory release of vasopressin. We discuss the investigation and management of such patients and the physiology of hypothalamic-neurohypophyseal dysfunction in such patients.

  4. Central diabetes insipidus following digestion Solanum indicum L. concentrated solution.

    PubMed

    Huang, Wen-Hung; Hsu, Ching-Wei; Fang, Ji-Tseng

    2008-04-01

    In Taiwan, Solanum indicum L. has been used in folk medicine for the treatment of inflammation, toothache, ascites, edema, and wound infection. The plant is rich in solanine, an alkaloidal glycoside. We report a 43-year-old man who developed polyuria and polydipsia after taking seven doses of concentrated solution of Solanum indicum L. over two weeks. A water deprivation test and a low serum antidiuretic hormone level helped to confirm a diagnosis of central diabetes insipidus. We suggest that excessive doses of Solanum indicum L. may cause central diabetes insipidus.

  5. Lithium-associated primary hyperparathyroidism complicated by nephrogenic diabetes insipidus

    PubMed Central

    Aksakal, Nihat; Erçetin, Candaş; Özçınar, Beyza; Aral, Ferihan; Erbil, Yeşim

    2015-01-01

    Lithium-associated hyperparathyroidism is the leading cause of hypercalcemia in lithium-treated patients. Lithium may lead to exacerbation of pre-existing primary hyperparathyroidism or cause an increased set-point of calcium for parathyroid hormone suppression, leading to parathyroid hyperplasia. Lithium may cause renal tubular concentration defects directly by the development of nephrogenic diabetes insipidus or indirectly by the effects of hypercalcemia. In this study, we present a female patient on long-term lithium treatment who was evaluated for hypercalcemia. Preoperative imaging studies indicated parathyroid adenoma and multinodular goiter. Parathyroidectomy and thyroidectomy were planned. During the postoperative course, prolonged intubation was necessary because of agitation and delirium. During this period, polyuria, severe dehydration, and hypernatremia developed, which responded to controlled hypotonic fluid infusions and was unresponsive to parenteral desmopressin. A diagnosis of nephrogenic diabetes insipidus was apparent. A parathyroid adenoma and multifocal papillary thyroid cancer were detected on histopathological examination. It was thought that nephrogenic diabetes insipidus was masked by hypercalcemia preoperatively. A patient on lithium treatment should be carefully followed up during or after surgery to prevent life-threatening complications of previously unrecognized nephrogenic diabetes insipidus, and the possibility of renal concentrating defects on long-term lithium use should be sought, particularly in patients with impaired consciousness. PMID:26504422

  6. Lithium-associated primary hyperparathyroidism complicated by nephrogenic diabetes insipidus.

    PubMed

    Aksakal, Nihat; Erçetin, Candaş; Özçınar, Beyza; Aral, Ferihan; Erbil, Yeşim

    2015-01-01

    Lithium-associated hyperparathyroidism is the leading cause of hypercalcemia in lithium-treated patients. Lithium may lead to exacerbation of pre-existing primary hyperparathyroidism or cause an increased set-point of calcium for parathyroid hormone suppression, leading to parathyroid hyperplasia. Lithium may cause renal tubular concentration defects directly by the development of nephrogenic diabetes insipidus or indirectly by the effects of hypercalcemia. In this study, we present a female patient on long-term lithium treatment who was evaluated for hypercalcemia. Preoperative imaging studies indicated parathyroid adenoma and multinodular goiter. Parathyroidectomy and thyroidectomy were planned. During the postoperative course, prolonged intubation was necessary because of agitation and delirium. During this period, polyuria, severe dehydration, and hypernatremia developed, which responded to controlled hypotonic fluid infusions and was unresponsive to parenteral desmopressin. A diagnosis of nephrogenic diabetes insipidus was apparent. A parathyroid adenoma and multifocal papillary thyroid cancer were detected on histopathological examination. It was thought that nephrogenic diabetes insipidus was masked by hypercalcemia preoperatively. A patient on lithium treatment should be carefully followed up during or after surgery to prevent life-threatening complications of previously unrecognized nephrogenic diabetes insipidus, and the possibility of renal concentrating defects on long-term lithium use should be sought, particularly in patients with impaired consciousness.

  7. Cerebral Malaria: An Unusual Cause of Central Diabetes Insipidus.

    PubMed

    Premji, Resmi; Roopnarinesingh, Nira; Cohen, Joshua; Sen, Sabyasachi

    2016-01-01

    Central diabetes insipidus is an uncommon feature of malaria. A previously healthy 72-year-old man presented with fever, rigors, and altered mental status after a recent trip to Liberia, a country known for endemic falciparum malaria. Investigations confirmed plasmodium falciparum parasitemia. Within one week after admission, the serum sodium rose to 166 mEq/L and the urine output increased to 7 liters/day. Other labs were notable for a high serum osmolality, low urine osmolality, and low urine specific gravity. The hypernatremia did not respond to hypotonic fluids. Diabetes insipidus was suspected and parenteral desmopressin was started with a prompt decrease in urinary output and improvement in mental status. Additional testing showed normal anterior pituitary hormones. The desmopressin was eventually tapered off with complete resolution of symptoms. Central diabetes insipidus occurred likely as a result of obstruction of the neurohypophyseal microvasculature. Other endocrinopathies that have been reported with malaria include hyponatremia, adrenal insufficiency, hypothyroidism, hypocalcemia, hypophosphatemia, hyper-, and hypoglycemia, but none manifested in our patient. Though diabetes insipidus is a rare complication of malaria, clinicians need to be aware of this manifestation, as failure to do so may lead to fatality particularly if the patient is dehydrated.

  8. Cerebral Malaria: An Unusual Cause of Central Diabetes Insipidus

    PubMed Central

    Premji, Resmi; Roopnarinesingh, Nira; Cohen, Joshua; Sen, Sabyasachi

    2016-01-01

    Central diabetes insipidus is an uncommon feature of malaria. A previously healthy 72-year-old man presented with fever, rigors, and altered mental status after a recent trip to Liberia, a country known for endemic falciparum malaria. Investigations confirmed plasmodium falciparum parasitemia. Within one week after admission, the serum sodium rose to 166 mEq/L and the urine output increased to 7 liters/day. Other labs were notable for a high serum osmolality, low urine osmolality, and low urine specific gravity. The hypernatremia did not respond to hypotonic fluids. Diabetes insipidus was suspected and parenteral desmopressin was started with a prompt decrease in urinary output and improvement in mental status. Additional testing showed normal anterior pituitary hormones. The desmopressin was eventually tapered off with complete resolution of symptoms. Central diabetes insipidus occurred likely as a result of obstruction of the neurohypophyseal microvasculature. Other endocrinopathies that have been reported with malaria include hyponatremia, adrenal insufficiency, hypothyroidism, hypocalcemia, hypophosphatemia, hyper-, and hypoglycemia, but none manifested in our patient. Though diabetes insipidus is a rare complication of malaria, clinicians need to be aware of this manifestation, as failure to do so may lead to fatality particularly if the patient is dehydrated. PMID:27242936

  9. Current perspective on the pathogenesis of central diabetes insipidus.

    PubMed

    Ghirardello, Stefano; Malattia, Clara; Scagnelli, Paola; Maghnie, Mohamad

    2005-07-01

    Diabetes insipidus is a heterogeneous condition characterised by polyuria and polydipsia caused by a lack of secretion of vasopressin, its physiological suppression following excessive water intake, or kidney resistance to its action. The clinical and laboratory diagnosis is confirmed by standard tests, but recent advances in molecular biology and imaging techniques have shed new light on the pathophysiology of this disease. In many patients, central diabetes insipidus is caused by a germinoma or craniopharyngioma; Langerhans' cell histiocytosis and sarcoidosis of the central nervous system; local inflammatory, autoimmune or vascular diseases; trauma from surgery or accident; and, rarely, genetic defects in vasopressin biosynthesis inherited as autosomal dominant or X-linked recessive traits. Thirty to fifty percent of cases are considered idiopathic. Tumour-associated central diabetes insipidus is uncommon in children younger than 5 years old. Biopsy of enlarged pituitary stalk should be reserved for patients with hypothalamic-pituitary mass and progressive thickening of the pituitary stalk since spontaneous recovery may occur. Molecular biology in selected patients may identify those with apparently idiopathic diabetes insipidus carrying the vasopressin-neurophysin II gene mutation.

  10. [Coexistence of autoimmune polyglandular syndrome type 3 with diabetes insipidus].

    PubMed

    Krysiak, Robert; Okopień, Bogusław

    2015-01-01

    Autoimmune polyglandular syndromes are conditions characterized by the combination of two or more organ-specific disorders. The underestimation oftheir real frequency probable results from physicians' inadequate knowledge of these clinical entities and sometimes their atypical clinical presentation. Because they comprise a wide spectrum of autoimmune disorders, autoimmune polyglandular syndromes are divided into four types, among which type-3 is the most common one. In this article, we report the case of a young female, initially diagnosed with diabetes mellitus who several years later developed full-blown autoimmune polyglandular syndrome type 3 consisting of autoimmune thyroid disorder and latent autoimmune diabetes in adults.The discussed case suggests that in selected patients diabetes insipidus may coexist with autoimmune endocrinopathies and nonendocrine autoimmunopathies, as well as that in some patients idiopathic diabetes insipidus may be secondary to lymphocytic infiltration and destruction of the hypothalamic supraoptic and paraventricular nuclei and/or the supraoptic-hypophyseal tract

  11. Lithium-induced nephrogenic diabetes insipidus after coronary artery bypass.

    PubMed

    Leeman, Matthew F; Vuylsteke, Alain; Ritchie, Andrew J

    2007-08-01

    We present a case of nephrogenic diabetes insipidus that occurred after on-pump coronary artery bypass grafting in a patient taking long-term lithium carbonate. Lithium toxicity (2.79 mmol/L) was identified on postoperative day 9. Serum sodium peaked at 175 mmol/L on postoperative day 21. Serum osmolality peaked at 384 mOsm/kg H2O, with a urinary osmolality of 403 mOsm/kg H2O. The patient was ultimately managed with hemofiltration and high-dose 1-desamino-8-D-arginine-vasopressin. Recommendations are made based on our experience of this case. In patients on long-term lithium therapy, the potentially life-threatening complication of lithium-induced nephrogenic diabetes insipidus should be specifically anticipated and managed.

  12. Ifosfamide-induced Fanconi syndrome with diabetes insipidus.

    PubMed

    Leem, Ah Young; Kim, Han Sang; Yoo, Byung Woo; Kang, Beo Deul; Kim, Min Hwan; Rha, Sun Young; Kim, Hyo Song

    2014-03-01

    Ifosfamide-induced Fanconi syndrome is a rare complication that typically occurs in young patients due to a cumulative dose of ifosfamide > 40-60 g/m(2), a reduction in kidney mass, or concurrent cisplatin treatment. It is usually characterized by severe and fatal progression accompanied by type II proximal renal tubular dysfunction, as evidenced by glycosuria, proteinuria, electrolyte loss, and metabolic acidosis. Diabetes insipidus is also a rare complication of ifosfamide-induced renal disease. We herein describe a case involving a 61-year-old man who developed ifosfamide-induced Fanconi syndrome accompanied by diabetes insipidus only a few days after the first round of chemotherapy. He had no known risk factors. In addition, we briefly review the mechanisms and possible therapeutic options for this condition based on other cases in the literature. Patients who receive ifosfamide must be closely monitored for renal impairment to avoid this rare but fatal complication.

  13. Erythroleukaemia, diabetes insipidus and hypophyseal damage: Two case reports.

    PubMed

    Piccin, A; Raimondi, R; Laspina, S; Marchi, M; Rodeghiero, F; Rovigatti, U

    2007-08-01

    We report on two cases of patients who developed diabetes insipidus (DI) before acute erythroleukaemia (EL). A brain MRI showed an empty sella turcica in one case and hypothalamo-hypophyseal peduncle damage in the second case. Reduced levels of TGF-beta1 and Vitamin D3, with associated EVI-1 over-expression and karyotypic abnormalities were documented. These two cases show specific chromosomal/molecular alterations in EL with DI. The hypothesis of pituitary involvement in erythroleukemogenesis is discussed.

  14. [Central diabetes insipidus as a first manifestation of lung adenocarcinoma].

    PubMed

    Granata, A; Figura, M; Gulisano, S; Romeo, G; Sicurezza, E; Failla, A; Scuderi, R

    2007-01-01

    The pituitary gland and infundibulum can be involved in a variety of medical conditions, including infiltrative diseases, fungal infections, tuberculosis, primary and metastatic tumors. Metastases to the pituitary gland are absolutely rare, and they are generally secondary to pulmonary carcinoma in men and breast carcinoma in women. Pituitary metastases more commonly affect the posterior lobe and the infundibulum than the anterior lobe. The posterior lobe involvement may explain why patients with pituitary metastases frequently present with diabetes insipidus. We are presenting a case report of a 48-year-old male patient with sudden onset of polyuria and persistent thirst. Laboratory results revealed central diabetes insipidus. Computed tomography (CT) scan of the brain showed a mass located in the sella turcica and suprasellar region. CT scan of the chest showed a mass in the right superior lobe with mediastinal lymphadenopathy. Bronchoscopy and biopsy demonstrated a pulmonary adenocarcinoma. Thus, we made a diagnosis of lung cancer with local and pituitary metastases. The patient received radiotherapy on the pituitary gland and adjuvant chemotherapy. As a result the intrasellar and suprasellar mass decreased in size and urinary output accordingly decreased. In conclusion, in patients presenting with sudden onset of diabetes insipidus pituitary metastases should be taken in account in differential diagnosis.

  15. Mechanisms of prolonged lithium therapy-induced nephrogenic diabetes insipidus.

    PubMed

    Behl, Tapan; Kotwani, Anita; Kaur, Ishneet; Goel, Heena

    2015-05-15

    Nephrogenic diabetes insipidus is a clinical sub-type of a diversely expounded disorder, named diabetes insipidus. It is characterized by inability of the renal cells to sense and respond to the stimulus of vasopressin. Amongst its various etiologies, one of the most inevitable causes includes lithium-induced instigation. Numerous studies reported marked histological damage to the kidneys upon long-term treatment with lithium. The recent researches have hypothesized many lithium-mediated mechanisms to explain the damage and dysfunction caused in the kidneys following lithium exposure. These mechanisms, widely, intend to justify the lithium-induced electrolyte imbalance, its interference with some vital proteins and a specific steroidal hormone, obstruction caused to a certain imperative transducer pathway and the renal tubular acidification defect produced on its prolonged therapy. Thorough study of such mechanisms aids in better understanding of the role of lithium in the pathophysiology of this disorder. Hence, the ameliorated knowledge regarding disease-pathology might prove beneficial in developing therapies that aim on disrupting the various lithium-mediated pathways. Hence, this may effectively lead to the demonstration of a novel treatment for nephrogenic diabetes insipidus, which is, at present, limited to the use of diuretics which block lithium reuptake into the body.

  16. Undiagnosed nephrogenic diabetes insipidus as a cause of acute urinary retention in a young soldier.

    PubMed

    Kim, Hyung Jin; Shin, Y S; Choi, H; Kim, M K; Jeong, Y B; Park, J K

    2016-10-01

    We present a case of undiagnosed nephrogenic diabetes insipidus as a cause of acute urinary retention in a 21-year-old male soldier. Soldiers live in close quarters, and have a regimented lifestyle that may not allow for frequent voiding; therefore, undiagnosed nephrogenic diabetes insipidus may result in acute urinary retention.

  17. Pulmonary Langerhans cell histiocytosis and diabetes insipidus in pregnant women: our experience.

    PubMed

    Fuks, Leonardo; Kramer, Mordechai R; Shitrit, David; Raviv, Yael

    2014-04-01

    Pulmonary Langerhans cell histiocytosis (PLCH) occurs predominantly in young adult smokers. Diabetes insipidus occurs in up to 15 % patients with PLCH. Information on PLCH in pregnancy is sparse, especially associated with diabetes insipidus. We report three patients with these conditions and describe the disease history and pregnancy outcomes.

  18. Quality of life in the patients with central diabetes insipidus assessed by Nagasaki Diabetes Insipidus Questionnaire.

    PubMed

    Nozaki, Aya; Ando, Takao; Akazawa, Satoru; Satoh, Tsuyoshi; Sagara, Ikuko; Horie, Ichiro; Imaizumi, Misa; Usa, Toshiro; Yanagisawa, Robert T; Kawakami, Atsushi

    2016-01-01

    Central diabetes insipidus (CDI) is characterized by polyuria and polydipsia due to a deficiency of vasopressin. Currently, the treatment goal for CDI is improvement of quality of life (QOL) by desmopressin (DDAVP) without developing hyponatremia. However, there is no reliable measure for QOL in CDI patients. We evaluate our original questionnaire for QOL, consisting of 12 questions focusing on polyuria, polydipsia, and DDAVP treatment, in CDI patients who underwent a switch from nasal spray to oral disintegrating tablets of DDAVP. Twenty-five CDI patients under nasal DDAVP treatment, six with newly developed CDI, and 18 healthy individuals without known polyuric/polydipsic disorders as control subjects were enrolled. QOL scores were determined by our questionnaire at the enrollment and 3 months after the start of oral DDAVP treatment and were examined by the Wilcoxon signed-rank test. Eleven questions detected improvement in QOL. The sum of the QOL scores of the eleven questions increased from 29.2 ± 5.6 under nasal to 36.8 ± 4.5 under oral DDAVP (p < 0.001). There were no clinically relevant changes in serum levels of Na. After eliminating two questions about DDAVP treatment, the sum of QOL scores was 15.3 ± 6.5 in untreated CDI patients, 24.4 ± 5.2 in those with nasal treatment, 28.9 ± 4.9 in those with oral DDAVP, and 29.5 ± 3.6 in healthy controls. The difference among groups was significant (p < 0.05 in Steel-Dwass test) except between patients treated with oral DDAVP and healthy controls. Our questionnaire can be used to accurately assess QOL in CDI patients.

  19. Bendamustine-Induced Nephrogenic Diabetes Insipidus in a Patient With AL Amyloidosis.

    PubMed

    Uwumugambi, Nsabimana A; Sanchorawala, Vaishali; Shelton, Anthony C; Stern, Lauren; Gordon, Craig E

    2017-02-01

    Nephrogenic diabetes insipidus is a condition characterized by polyuria with dilute urine due to the inability of the principal cells of the renal collecting ducts to respond to antidiuretic hormone and concentrate urine. Nephrogenic diabetes insipidus can be drug induced, and several chemotherapeutic agents have been reported to cause it. Bendamustine is a traditional chemotherapeutic agent being studied for treatment for relapsed systemic AL amyloidosis. We report a case of a 59-year-old man with AL amyloidosis who developed partial nephrogenic diabetes insipidus after receiving bendamustine for treatment of AL amyloidosis. The nephrogenic diabetes insipidus responded well to sodium restriction, hydrochlorothiazide, and desmopressin treatment, allowing the patient to receive subsequent bendamustine cycles without polyuria. Nephrogenic diabetes insipidus resolved shortly after completion of bendamustine therapy.

  20. Intracranial aggressive fibromatosis presenting as panhypopituitarism and diabetes insipidus.

    PubMed

    Gursoy, A; Cesur, M; Aktaş, B; Utkan, G; Gedik, V Tonyukuk; Erdogan, Mf; Kamel, N

    2005-01-01

    Aggressive fibromatosis (AF) is a rare, locally aggressive, proliferative fibroblastic lesion affecting musculoaponeurotic structures, most often, of the limbs and trunk. Intracranial AF is extremely rare and requires aggressive treatment to prevent recurrence. We present a case of a 34 year-old male with AF involving intracranial structures causing panhypopituitarism and diabetes insipidus. Patient was admitted to hospital because of polyuria, polydipsia, and loss of libido, impotence, hearing loss, and gait disturbance. On cranial magnetic resonance imaging, the lesion extended through the sphenoid sinus into the both pterygoid recesses, destroying the left lateral wall of the sphenoid sinus and invading the retroorbital area. There was also a distinct lesion in the hypothalamic area. The tumor was markedly isointense on both T2- and T1-weighted images relative to gray matter, and enhanced strongly after administration of gadolinium. The patient underwent partial resection of the lesion via a transcranial approach. The pathological examination of the mass was reported as AF. No other sites were found to be involved by thorax and abdominal tomography. Hormonal assessment of hypothalamic-pituitary dysfunction revealed panhypopituitarism with central diabetes insipidus. Replacement therapy was instituted. In this case, standard treatment of wide-field surgical resection was impossible. On the basis of reports that radiotherapy is an effective treatment for this kind of tumor, we administered radiation to the affected area, since chemotherapy and hormonal treatment of non-resectable tumors are not satisfactory. To our knowledge, this is the first reported case of AF presenting as panhypopituitarism with central diabetes insipidus.

  1. Utility of genetic testing in suspected familial cranial diabetes insipidus

    PubMed Central

    Srinivasan, Ramesh; Ball, Stephen; Ward-Platt, Martin; Bourn, David; McAnulty, Ciaron; Cheetham, Tim

    2013-01-01

    Summary Aim Differentiating familial cranial diabetes insipidus (CDI) from primary polydipsia can be difficult. We report the diagnostic utility of genetic testing as a means of confirming or excluding this diagnosis. Patient and methods The index case presented at 3 months with polydipsia. He was diagnosed with familial CDI based on a positive family history combined with what was considered to be suspicious symptomatology and biochemistry. He was treated with desmopressin (DDAVP) but re-presented at 5 months of age with hyponatraemia and the DDAVP was stopped. Gene sequencing of the vasopressin gene in father and his offspring was undertaken to establish the underlying molecular defect. Results Both father and daughter were found to have the pathogenic mutation c.242T>C (p.Leu81Pro) in exon 2 of the AVP gene consistent with a diagnosis of familial diabetes insipidus. The index case did not have the pathogenic mutation and the family could be reassured that he would not require intervention with DDAVP. Conclusions Gene sequencing of AVP gene can have a valuable role in predicting whether or not a child is at risk of developing CDI in future. This can help to prevent family uncertainty and unnecessary treatment with its associated risks. Learning points Differentiating patients with familial cranial diabetes insipidus from those with primary polydipsia is not always straightforward.Molecular genetic analysis of the vasopressin gene is a valuable way of confirming or refuting a diagnosis of familial CDI in difficult cases and is a valuable way of identifying individuals who will develop CDI in later childhood. This information can be of great value to families. PMID:24616780

  2. Acute Sheehan's syndrome presenting as central diabetes insipidus

    PubMed Central

    Robalo, Raquel; Pedroso, Célia; Agapito, Ana; Borges, Augusta

    2012-01-01

    Sheehan's syndrome occurs as a result of ischaemic pituitary necrosis due to severe postpartum haemorrhage. Improvements in obstetrical care have significantly reduced its incidence in developed countries, but postpartum pituitary infarction remains a common cause of hypopituitarism in developing countries. We report a case of severe postpartum haemorrhage followed by headache, central diabetes insipidus and failure to lactate, which prompted us to investigate and identify both anterior and posterior pituitary deficiency compatible with Sheehan's syndrome. A timely diagnosis allowed us to implement an adequate treatment and follow-up plan, which are known to improve clinical status and patient outcome. PMID:23131607

  3. Hyponatraemia associated with lamotrigine in cranial diabetes insipidus.

    PubMed

    Mewasingh, L; Aylett, S; Kirkham, F; Stanhope, R

    2000-08-19

    We report the cases of two children with cranial diabetes insipidus who were treated with lamotrigine for seizures and who had accompanying changes in desmopressin requirements. Lamotrigine is a new anticonvulsant chemically unrelated to other existing antiepileptic drugs. Studies suggest it acts at voltage-sensitive sodium channels and also decreases calcium conductance. Both of these mechanisms of action are shared by carbamazepine, which can cause hyponatraemia secondary to inappropriate secretion of antidiuretic hormone. It is possible that the effect of lamotrigine on fluid balance in the cases described is also centrally mediated.

  4. Acute Sheehan's syndrome presenting as central diabetes insipidus.

    PubMed

    Robalo, Raquel; Pedroso, Célia; Agapito, Ana; Borges, Augusta

    2012-11-06

    Sheehan's syndrome occurs as a result of ischaemic pituitary necrosis due to severe postpartum haemorrhage. Improvements in obstetrical care have significantly reduced its incidence in developed countries, but postpartum pituitary infarction remains a common cause of hypopituitarism in developing countries. We report a case of severe postpartum haemorrhage followed by headache, central diabetes insipidus and failure to lactate, which prompted us to investigate and identify both anterior and posterior pituitary deficiency compatible with Sheehan's syndrome. A timely diagnosis allowed us to implement an adequate treatment and follow-up plan, which are known to improve clinical status and patient outcome.

  5. Diabetes insipidus as a complication of Wegener's granulomatosis and its treatment with biologic agents.

    PubMed

    Cunnington, Joanna Rosalind; Jois, Ramesh; Zammit, Ivan; Scott, David; Isaacs, John

    2009-01-01

    Wegener's granulomatosis of the pituitary gland resulting in diabetes insipidus is a rare complication of the disease. Standard treatment for Wegener's granulomatosis involves a combination of prednisolone and cylophosphamide, however biologic agents are now being used in refractory cases. We report three cases of patients with diabetes insipidus as a complication of Wegener's granulomatosis who were treated with biologic agents. All three cases showed clinical response to treatment with biologic agents including rituximab and alemtuzumab and two cases demonstrated improvement in pituitary gland abnormalities by MRI. Clinicians should be aware that diabetes insipidus can present as a complication of Wegener's granulomatosis and that biologic therapies may be effective in refractory cases.

  6. Clinical characteristics of eight patients with congenital nephrogenic diabetes insipidus.

    PubMed

    Mizuno, Haruo; Sugiyama, Yukari; Ohro, Yoichiro; Imamine, Hiroki; Kobayashi, Masanori; Sasaki, Sei; Uchida, Sinichi; Togari, Hajime

    2004-06-01

    Congenital nephrogenic diabetes insipidus (NDI) is characterized by the insensitivity of the distal nephron to arginine vasopressin. Clinical knowledge of this disease is based largely on case reports. For this study, we investigated the clinical findings of eight patients in terms of age at onset, age at diagnosis, main complaint, results of physical examination, the diagnosis, the effect of treatment, kidney function, and presence or absence of gene defects. The main complaints of all eight cases at initial examination were unknown fever, failure to thrive, and short stature. Polyuria and polydipsia are not always the chief complaints with congenital NDI. In one case, diabetes insipidus could be diagnosed based only on the results of a 5% hypertonic saline test. In six cases, we found abnormalities in the V2 receptor gene. Initially, trichlormethiazide therapy was shown to have a significant effect on polyuria; however, this effect decreased over time. In one patient with partial NDI, the addition of trichlormethiazide twice a day to 1-desamino-8-D-arginine vasopressin increased urine osmolality in the morning and caused nocturia to disappear. Results of 99mTc-diethylenetriamine pentaacetic acid kidney scintigraphy revealed a slight decrease in glomerular filtration rate in three patients. No patient experienced serious renal dysfunction.

  7. Heterogeneous AVPR2 gene mutations in congenital nephrogenic diabetes insipidus.

    PubMed Central

    Wildin, R. S.; Antush, M. J.; Bennett, R. L.; Schoof, J. M.; Scott, C. R.

    1994-01-01

    Mutations in the AVPR2 gene encoding the receptor for arginine vasopressin in the kidney (V2 ADHR) have been reported in patients with congenital nephrogenic diabetes insipidus, a predominantly X-linked disorder of water homeostasis. We have used restriction-enzyme analysis and direct DNA sequencing of genomic PCR product to evaluate the AVPR2 gene in 11 unrelated affected males. Each patient has a different DNA sequence variation, and only one matches a previously reported mutation. Cosegregation of the variations with nephrogenic diabetes insipidus was demonstrated for two families, and a de novo mutation was documented in two additional cases. Carrier detection was accomplished in one family. All the variations predict frameshifts, truncations, or nonconservative amino acid substitutions in evolutionarily conserved positions in the V2 ADHR and related receptors. Of interest, a 28-bp deletion is found in one patient, while another, unrelated patient has a tandem duplication of the same 28-bp segment, suggesting that both resulted from the same unusual unequal crossing-over mechanism facilitated by 9-mer direct sequence repeats. Since the V2 ADHR is a member of the seven-transmembrane-domain, G-protein-coupled receptor superfamily, the loss-of-function mutations from this study and others provide important clues to the structure-function relationship of this and related receptors. Images Figure 1 Figure 2 Figure 3 PMID:7913579

  8. Pituitary apoplexy precipitating diabetes insipidus after living donor liver transplantation.

    PubMed

    Matsusaki, Takashi; Morimatsu, Hiroshi; Matsumi, Junya; Matsuda, Hiroaki; Sato, Tetsufumi; Sato, Kenji; Mizobuchi, Satoshi; Yagi, Takahito; Morita, Kiyoshi

    2011-02-01

    Pituitary apoplexy occurring after surgery is a rare but life-threatening acute clinical condition that follows extensive hemorrhagenous necrosis within a pituitary adenoma. Pituitary apoplexy has been reported to occur spontaneously in the majority of cases or in association with various inducing factors. Reported is a case of pituitary apoplexy complicated by diabetes insipidus following living donor liver transplantation (LDLT). To the best of our knowledge, this has not been previously reported. A 56-year-old woman with nonalcoholic steatohepatitis underwent LDLT from her daughter. The patient also required dopamine support and transfusions because of massive intraoperative bleeding. Postoperatively, her coagulopathy continued, and she underwent a second laparotomy because of unknown bleeding on postoperative day 7, when she needed transfusions and dopamine support to maintain her vital signs. She complained of severe headache, excessive thirst, frequent urination, and diplopia from postoperative day 10. She also had polyuria greater than 300 ml/h and was diagnosed with pituitary apoplexy precipitating diabetes insipidus on postoperative day 13. She was treated conservatively without surgery because of the hormonally inactive status and slight mass effect of her tumor. It is important for anesthesiologists and critical care personnel in LDLT settings to take into consideration this complication as a differential diagnosis.

  9. [Perioperative management of a child with congenital nephrogenic diabetes insipidus].

    PubMed

    Mizushima, T; Kitamura, S; Kinouchi, K; Taniguchi, A; Fukumitsu, K

    2001-03-01

    The key point in perioperative management of a patient with congenital nephrogenic diabetes insipidus is fluid and electrolytes management. Since the urine of these patients consists mainly of solute free water, replacement fluids should be fluids which provide free water. A 2-year-old girl with congenital nephrogenic diabetes insipidus was scheduled for dental extraction. Her daily fluid intake was 10 liter. She had a history of recurrent fever, polyuria and polydipsia since 2 months of age. Her previous perioperative course for gastric volvulus at another hospital was complicated with postoperative hyponatremia and convulsion. A venous line was secured the day before surgery and 5% dextrose in water was infused at a rate of 12 ml.kg-1.hr-1. Intraoperative infusion was mainly with 5% dextrose in water combined with maintenance fluid. Five hours after surgery oral intake was started. Her intraoperative electrolytes levels were low (Na 133 mEq.l-1, K 2.8 mEq.l-1), but otherwise her perioperative course was uneventful.

  10. [Congenital nephrogenic diabetes insipidus: about a case report].

    PubMed

    Esselmani, Hicham; Yassine, Asmaa; Bouabdellah, Mounya; Benchekroun, Laila; Handor, Najat; Elalami, Sanae; Chabraoui, Layachi

    2013-01-01

    Congenital nephrogenic diabetes insipidus is a rare, hereditary in nature, characterized by an inability of the kidney to concentrate urine, secondary to the manifold resistance to the action of vasopressin. X-linked forms of transmission (90%) are expressed in boys, from the neonatal period in general, by polyuria and polydipsia. Symptomatology in transmissive girls is variable but can sometimes be quite marked. These forms are secondary to mutations in the gene encoding the vasopressin V2 receptor, located at position Xq28, responsible for a loss of function of this receptor. Some of these mutations may cause a partial phenotype, less severe. Forms of autosomal, recessive or dominant are more rare (10%). Treatment is symptomatic, sometimes difficult in infants. It aims to avoid episodes of dehydration. It is based on a conventional diet hypo-osmotic and administration of hydrochlorothiazide and indomethacin. We report here the case of a child with congenital nephrogenic diabetes insipidus hospitalized at Children's Hospital of Rabat and throughout this case we review the pathophysiology and clinical and biological characteristics of the disease and including importance of contribution of clinical biochemistry laboratory in the diagnosis and monitoring of this disease.

  11. [Etiological diagnosis of central diabetes insipidus: about 41 cases].

    PubMed

    Chaker, Fatma; Chihaoui, Melika; Yazidi, Meriem; Slimane, Hedia

    2016-01-01

    The occurrence of polyuria-polydipsia syndrome with hypotonic urine requires careful diagnostic strategy. This study aims to evaluate diagnostic modalities for central diabetes insipidus. We conducted a retrospective study of 41 cases with central diabetes insipidus (CDI). Data were collected at the Department of Endocrinology, University Hospital La Rabta, Tunis, from 1990 to 2013. We identified the circumstances for detecting CDI, the abnormalities in anterior pituitary assessment and pituitary imaging. CDI occurred in the postoperative period in 20 patients. The average urine 24-hour volume was significantly higher in patients with CDI outside a surgical setting. Water deprivation test was successful in all patients who benefited from it. Outside of neurosurgery, infiltration causes were found in 6 patients and tumor causes were found in 6 patients. CDI was associated with empty sella turcica in 1 case and idiopathic sella turcica in 3 patients. Hypothalamic-pituitary magnetic resonance imaging and anterior pituitary balance sheet are systematic outside pituitary surgery setting and obvious primary polydipsia.

  12. Recurrent pregnancy-induced diabetes insipidus in a woman with hemochromatosis.

    PubMed

    Krysiak, Robert; Kobielusz-Gembala, Iwona; Okopien, Boguslaw

    2010-01-01

    Diabetes insipidus is a rare disorder in pregnant women, predating pregnancy or appearing for the first time during gestation. In pregnancy it usually affects women with HELLP syndrome or acute fatty liver of pregnancy and results from the reduced hepatic degradation of placental vasopressinase leading to its increased activity. Although infiltrative diseases have been found to cause diabetes insipidus in non-pregnant population, very few studies showed that these disorders may manifest for the first time during gestation. We describe here the case of transient diabetes insipidus in two subsequent pregnancies of a female with hemochromatosis. The first symptoms of this disease appeared for the first time at the beginning of the third trimester of her second pregnancy, and diagnosis was established on the basis of typical clinical presentation, confirmed by a water deprivation test. Diabetes insipidus resulted from the increased activity of vasopressinase, caused by hemochromatosis-induced liver dysfunction, the presence of which was confirmed between the pregnancies by liver biopsy and identification of the HFE gene mutation. Subsequent desferrioxamine treatment resulted in a less severe clinical course of diabetes insipidus in the last patient's pregnancy. In both pregnancies, the patient was successfully treated with oral desmopressin, which is resistant to degradation by placental vasopressinase. Although unrecognized pituitary disorders may pose a serious health problem to the mother and fetus, hemochromatosis-induced diabetes insipidus, as the case of our patient demonstrates, if effectively diagnosed and treated, cannot be regarded as a contraindication for pregnancy.

  13. Inherited secondary nephrogenic diabetes insipidus: concentrating on humans.

    PubMed

    Bockenhauer, D; Bichet, D G

    2013-04-15

    The study of human physiology is paramount to understanding disease and developing rational and targeted treatments. Conversely, the study of human disease can teach us a lot about physiology. Investigations into primary inherited nephrogenic diabetes insipidus (NDI) have contributed enormously to our understanding of the mechanisms of urinary concentration and identified the vasopressin receptor AVPR2, as well as the water channel aquaporin-2 (AQP2), as key players in water reabsorption in the collecting duct. Yet, there are also secondary forms of NDI, for instance as a complication of lithium treatment. The focus of this review is secondary NDI associated with inherited human diseases, such as Bartter syndrome or apparent mineralocorticoid excess. Currently, the underlying pathophysiology of this inherited secondary NDI is unclear, but there appears to be true AQP2 deficiency. To better understand the underlying mechanism(s), collaboration between clinical and experimental physiologists is essential to further investigate these observations in appropriate experimental models.

  14. Neurosarcoidosis-associated central diabetes insipidus masked by adrenal insufficiency.

    PubMed

    Non, Lemuel; Brito, Daniel; Anastasopoulou, Catherine

    2015-01-22

    Central diabetes insipidus (CDI) is an infrequent complication of neurosarcoidosis (NS). Its presentation may be masked by adrenal insufficiency (AI) and uncovered by subsequent steroid replacement. A 45-year-old woman with a history of NS presented 2 weeks after abrupt cessation of prednisone with nausea, vomiting, decreased oral intake and confusion. She was diagnosed with secondary AI and intravenous hydrocortisone was promptly begun. Over the next few days, however, the patient developed severe thirst and polyuria exceeding 6 L of urine per day, accompanied by hypernatraemia and hypo-osmolar urine. She was presumed to have CDI due to NS, and intranasal desmopressin was administered. This eventually normalised her urine output and serum sodium. The patient was discharged improved on intranasal desmopressin and oral prednisone. AI may mask the manifestation of CDI because low serum cortisol impairs renal-free water clearance. Steroid replacement reverses this process and unmasks an underlying CDI.

  15. Acute myeloid leukemia and diabetes insipidus with monosomy 7.

    PubMed

    Harb, Antoine; Tan, Wei; Wilding, Gregory E; Battiwalla, Minoo; Sait, Sheila N J; Wang, Eunice S; Wetzler, Meir

    2009-04-15

    The predisposition of monosomy 7 to diabetes insipidus (DI) in acute myeloid leukemia (AML) led us to ask whether AML associated with monosomy 7 and DI will differ from AML associated with other karyotype aberrations and DI and whether the outcome of patients with AML and DI will differ from those without DI. We describe 2 patients from Roswell Park Cancer Institute and discuss 29 additional cases from the literature. AML with monosomy 7 and DI (n = 25) had a trend towards a lower complete remission (p = 0.0936) and worse survival (p = 0.0480) than AML with other karyotype changes and DI (n = 6). Further, AML with monosomy 7 and DI had worse complete remission rate and overall survival than AML with monosomy 7 but without DI. In conclusion, it appears that AML with monosomy 7 and DI is a disease entity with specifically poor outcome.

  16. Pulmonary langerhans cell histiocytosis case with diabetes insipidus and tuberculosis.

    PubMed

    Ugurlu, E; Altinisik, G; Aydogmus, U; Bir, F

    2017-04-01

    A 19-year-old male patient was observed due to having central diabetes insipidus (DI) for five years. He had a history of smoking 5-10 cigarettes a day for two years, but stopped smoking from the last month. The computerized tomography revealed thin-walled cystic lesions in different sizes more dominantly in the upper lobes and consolidated areas in the left upper and lower lobes. The wedge resection from the right lower lobe revealed pulmonary langerhans cell histiocytosis. Follow-up acid-fast bacteria (AFB) examinations revealed (+++) and antituberculous treatment was started. On the 40th day of the anti-tuberculosis treatment, the patient applied once again due to fever and chest pain. Although infiltrations persisted in the left upper and middle zones in the postero-anterior lung rontgenogram, right-sided pneumothorax was detected. The case is considered tuberculosis and the patient continued to receive anti-TB treatment under the close supervision.

  17. A novel therapeutic effect of statins on nephrogenic diabetes insipidus.

    PubMed

    Bonfrate, Leonilde; Procino, Giuseppe; Wang, David Q-H; Svelto, Maria; Portincasa, Piero

    2015-02-01

    Statins competitively inhibit hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase, resulting in reduced plasma total and low-density lipoprotein cholesterol levels. Recently, it has been shown that statins exert additional 'pleiotropic' effects by increasing expression levels of the membrane water channels aquaporin 2 (AQP2). AQP2 is localized mainly in the kidney and plays a critical role in determining cellular water content. This additional effect is independent of cholesterol homoeostasis, and depends on depletion of mevalonate-derived intermediates of sterol synthetic pathways, i.e. farnesylpyrophosphate and geranylgeranylpyrophosphate. By up-regulating the expression levels of AQP2, statins increase water reabsorption by the kidney, thus opening up a new avenue in treating patients with nephrogenic diabetes insipidus (NDI), a hereditary disease that yet lacks high-powered and limited side effects therapy. Aspects related to water balance determined by AQP2 in the kidney, as well as standard and novel therapeutic strategies of NDI are discussed.

  18. Mechanisms underlying progressive polyuria in familial neurohypophysial diabetes insipidus.

    PubMed

    Arima, H; Oiso, Y

    2010-07-01

    Familial neurohypophysial diabetes insipidus (FNDI), an autosomal dominant disorder, is mostly caused by mutations in the gene of neurophysin II (NPII), the carrier protein of arginine vasopressin (AVP). The analyses of knock-in mice expressing a mutant NPII that causes FNDI in humans demonstrated that polyuria progressed substantially in the absence of loss of AVP neurones. Morphological analyses revealed that inclusion bodies were present in the AVP neurones in the supraoptic nucleus and that the size and numbers of inclusion bodies gradually increased in parallel with the increases in urine volume. Electron microscopic analyses showed that aggregates existed in the endoplasmic reticulum (ER) of AVP neurones. These data suggest that cell death is not the primary cause of polyuria in FNDI, and that the aggregate formation in the ER is likely to be related to the pathogenesis of the progressive polyuria.

  19. Lymphocytic hypophysitis in a dog with diabetes insipidus.

    PubMed

    Meij, B P; Voorhout, G; Gerritsen, R J; Grinwis, G C M; Ijzer, J

    2012-11-01

    An 8-year-old male German longhaired pointer was referred for diabetes insipidus responsive to treatment with desmopressin. The dog had polyuria and polydipsia, exercise intolerance and a dull hair coat. Plasma concentrations of thyroid-stimulating hormone, thyroxine, growth hormone (GH) and insulin-like growth factor-1 were decreased; plasma adrenocorticotropic hormone (ACTH) was slightly elevated and plasma α-melanocyte-stimulating hormone (MSH) was within the reference range. Computed tomography revealed a heterogeneously contrast-enhancing pituitary mass compressing the hypothalamus. Transsphenoidal hypophysectomy was performed and microscopical examination of the surgical biopsy samples revealed hypophysitis without evidence of pituitary adenoma. The hypophysitis was characterized by marked lymphocytic infiltration of the adenohypophysis that contained a mixed population of neuroendocrine cells expressing GH, ACTH or α-MSH. The lymphocytes were identified as T cells, resulting in a final diagnosis of lymphocytic hypophysitis strongly resembling human primary lymphocytic hypophysitis.

  20. Management of diabetes insipidus and adipsia in the child.

    PubMed

    Di Iorgi, Natascia; Morana, Giovanni; Napoli, Flavia; Allegri, Anna Elsa Maria; Rossi, Andrea; Maghnie, Mohamad

    2015-06-01

    Central diabetes insipidus (CDI) is a complex and heterogeneous clinical syndrome affecting the hypothalamic-neurohypophyseal network and water balance. A recent national surveillance in Denmark showed a prevalence rate of twenty-three CDI patients per 100,000 inhabitants in five years. The differential diagnosis between several presenting conditions with polyuria and polydipsia is puzzling, and the etiological diagnosis of CDI remains a challenge before the identification of an underlying cause. For clinical practice, a timely diagnosis for initiating specific treatment in order to avoid central nervous system damage, additional pituitary defects and the risk of dissemination of germ cell tumor is advisable. Proper etiological diagnosis can be achieved via a series of steps that start with careful clinical observation of several signs and endocrine symptoms and then progress to more sophisticated imaging tools. This review summarizes the best practice and approach for the diagnosis and treatment of patients with CDI.

  1. Post-operative diabetes insipidus after endoscopic transsphenoidal surgery.

    PubMed

    Schreckinger, Matthew; Walker, Blake; Knepper, Jordan; Hornyak, Mark; Hong, David; Kim, Jung-Min; Folbe, Adam; Guthikonda, Murali; Mittal, Sandeep; Szerlip, Nicholas J

    2013-12-01

    Diabetes insipidus (DI) after endoscopic transsphenoidal surgery (ETSS) can lead to increased morbidity, longer hospital stays, and increased medication requirements. Predicting which patients are at high risk for developing DI can help direct services to ensure adequate care and follow-up. The objective of this study was to review our institution's experience with ETSS and determine which clinical/laboratory variables are associated with DI in this patient population. The authors wanted to see if there was an easily determined single value that would help predict which patients develop DI. This represents the largest North American series of this type. We retrospectively reviewed the charts of patients who had undergone ETSS for resection of sellar and parasellar pathology between 2006 and 2011. We examined patient and tumor characteristics and their relationship to postoperative DI. Out of 172 endoscopic transsphenoidal surgeries, there were 15 cases of transient DI (8.7%) and 14 cases of permanent DI (8.1%). Statistically significant predictors of postoperative DI (p < 0.05) included tumor volume and histopathology (Rathke's cleft cyst and craniopharyngioma). Significant indicators of development of DI were postoperative serum sodium, preoperative to postoperative change in sodium level, and urine output prior to administration of 1-deamino-8-D-arginine vasopressin. An increase in serum sodium of ≥2.5 mmol/L is a positive marker of development of DI with 80% specificity, and a postoperative serum sodium of ≥145 mmol/L is a positive indicator with 98% specificity. Identifying perioperative risk factors and objective indicators of DI after ETSS will help physicians care for patients postoperatively. In this large series, we demonstrated that there were multiple perioperative risk factors for the development of DI. These findings, which are consistent with other reports from microscopic surgical series, will help identify patients at risk for diabetes insipidus

  2. Diabetes insipidus: celebrating a century of vasopressin therapy.

    PubMed

    Qureshi, Sana; Galiveeti, Sneha; Bichet, Daniel G; Roth, Jesse

    2014-12-01

    Diabetes mellitus, widely known to the ancients for polyuria and glycosuria, budded off diabetes insipidus (DI) about 200 years ago, based on the glucose-free polyuria that characterized a subset of patients. In the late 19th century, clinicians identified the posterior pituitary as the site of pathology, and pharmacologists found multiple bioactivities there. Early in the 20th century, the amelioration of the polyuria with extracts of the posterior pituitary inaugurated a new era in therapy and advanced the hypothesis that DI was due to a hormone deficiency. Decades later, a subset of patients with polyuria unresponsive to therapy were recognized, leading to the distinction between central DI and nephrogenic DI, an early example of a hormone-resistant condition. Recognition that the posterior pituitary had 2 hormones was followed by du Vigneaud's Nobel Prize winning isolation, sequencing, and chemical synthesis of oxytocin and vasopressin. The pure hormones accelerated the development of bioassays and immunoassays that confirmed the hormone deficiency in vasopressin-sensitive DI and abundant levels of hormone in patients with the nephrogenic disorder. With both forms of the disease, acquired and inborn defects were recognized. Emerging concepts of receptors and of genetic analysis led to the recognition of patients with mutations in the genes for 1) arginine vasopressin (AVP), 2) the AVP receptor 2 (AVPR2), and 3) the aquaporin 2 water channel (AQP2). We recount here the multiple skeins of clinical and laboratory research that intersected frequently over the centuries since the first recognition of DI.

  3. Hypernatremia in a non insulin dependent (type 2) diabetic patient with central diabetes insipidus.

    PubMed

    Kavelaars, J; Tamsma, J T; Meinders, A E

    2001-03-01

    We describe a patient with central diabetes insipidus who presented with hyperosmolar, non-ketotic hyperglycaemia. The role in this case of reduced thirst sensation with decreased water intake and abnormal AVP production illustrates the importance of these protective mechanisms in normal physiology regarding maintenance of normal plasma osmolality. Despite the complex pathophysiology in this patient, fluid resuscitation aimed at normalisation of the water deficit resulted in full recovery.

  4. Combined central diabetes insipidus and cerebral salt wasting syndrome in children.

    PubMed

    Lin, Jainn-Jim; Lin, Kuang-Lin; Hsia, Shao-Hsuan; Wu, Chang-Teng; Wang, Huei-Shyong

    2009-02-01

    Central diabetes insipidus, a common consequence of acute central nervous system injury, causes hypernatremia; cerebral salt wasting syndrome can cause hyponatremia. The two conditions occurring simultaneous are rarely described in pediatric patients. Pediatric cases of combined diabetes insipidus and cerebral salt wasting after acute central nervous system injury between January 2000 and December 2007 were retrospectively reviewed, and clinical characteristics were systemically assessed. Sixteen patients, aged 3 months to 18 years, met study criteria: 11 girls and 5 boys. The most common etiologies were severe central nervous system infection (n = 7, 44%) and hypoxic-ischemic event (n = 4, 25%). In 15 patients, diabetes insipidus was diagnosed during the first 3 days after acute central nervous system injury. Onset of cerebral salt wasting syndrome occurred 2-8 days after the onset of diabetes insipidus. In terms of outcome, 13 patients died (81%) and 3 survived under vegetative status (19%). Central diabetes insipidus and cerebral salt wasting syndrome may occur after acute central nervous system injury. A combination of both may impede accurate diagnosis. Proper differential diagnoses are critical, because the treatment strategy for each entity is different.

  5. A case of primary aldosteronism combined with acquired nephrogenic diabetes insipidus.

    PubMed

    Kim, Kitae; Lee, Jae Hyoung; Kim, Sun Chul; Cha, Dae Ryong; Kang, Young Sun

    2014-12-01

    Aldosterone-producing adrenal adenoma can induce various clinical manifestations as a result of chronic exposure to aldosterone. We report a rare case of a 37-year-old man who complained of general weakness and polyuria. He was diagnosed with aldosterone-producing adrenal adenoma and nephrogenic diabetes insipidus. Aldosterone enhances the secretion of potassium in the collecting duct, which can lead to hypokalemia. By contrast, nephrogenic diabetes insipidus, which manifests as polyuria and polydipsia, can occur in several clinical conditions such as acquired tubular disease and those attributed to toxins and congenital causes. Among them, hypokalemia can also damage tubular structures in response to vasopressin. The patient's urine output was >3 L/d and was diluted. Owing to the ineffectiveness of vasopressin, we eventually made a diagnosis of nephrogenic diabetes insipidus. Laparoscopic adrenalectomy and intraoperative kidney biopsy were subsequently performed. The pathologic finding of kidney biopsy revealed a decrease in aquaporin-2 on immunohistochemical stain.

  6. Temporary diabetes insipidus in 2 men after on-pump coronary artery bypass grafting.

    PubMed

    Uyar, Ihsan Sami; Sahin, Veysel; Akpinar, Besir; Yurtman, Volkan; Abacilar, Feyzi; Okur, Faik Fevzi; Ates, Mehmet

    2013-01-01

    Many complications have been reported after cardiopulmonary bypass. A common physiologic change during the early postoperative period after cardiopulmonary bypass is increased diuresis. In patients whose urine output is increased, postoperative diabetes insipidus can develop, although reports of this are rare. We present the cases of 2 patients who underwent on-pump coronary artery bypass grafting (with cardiopulmonary bypass). Each was diagnosed with diabetes insipidus postoperatively: a 54-year-old man on the 3rd day, and a 66-year-old man on the 4th day. Each patient recovered from the condition after 6 hours of intranasal therapy with synthetic vasopressin (antidiuretic hormone). The diagnosis of diabetes insipidus should be considered in patients who produce excessive urine early after cardiac surgery in which cardiopulmonary bypass has been used.

  7. Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus.

    PubMed

    Bockenhauer, Detlef; Bichet, Daniel G

    2015-10-01

    Healthy kidneys maintain fluid and electrolyte homoeostasis by adjusting urine volume and composition according to physiological needs. The final urine composition is determined in the last tubular segment: the collecting duct. Water permeability in the collecting duct is regulated by arginine vasopressin (AVP). Secretion of AVP from the neurohypophysis is regulated by a complex signalling network that involves osmosensors, barosensors and volume sensors. AVP facilitates aquaporin (AQP)-mediated water reabsorption via activation of the vasopressin V2 receptor (AVPR2) in the collecting duct, thus enabling concentration of urine. In nephrogenic diabetes insipidus (NDI), inability of the kidneys to respond to AVP results in functional AQP deficiency. Consequently, affected patients have constant diuresis, resulting in large volumes of dilute urine. Primary forms of NDI result from mutations in the genes that encode the key proteins AVPR2 and AQP2, whereas secondary forms are associated with biochemical abnormalities, obstructive uropathy or the use of certain medications, particularly lithium. Treatment of the disease is informed by identification of the underlying cause. Here we review the clinical aspects and diagnosis of NDI, the various aetiologies, current treatment options and potential future developments.

  8. Evaluation of patients with intracranial tumors and central diabetes insipidus.

    PubMed

    Varan, Ali; Atas, Erman; Aydın, Burça; Yalçın, Bilgehan; Akyüz, Canan; Kutluk, Tezer; Büyükpamukçu, Münevver

    2013-10-01

    The aim of the study is to evaluate the etiologic and clinical characteristics, treatment regimens, and outcome of the patients with intracranial tumors presenting with central diabetes insipidus (DI). Sixty-nine patients with intracranial tumors presenting with central DI between 1972 and 2012 were retrospectively evaluated. Fifty-three out of 69 patients were included in the analysis. Male/female ratio was 1.52, median age was 7.6 years. Of 53 patients, 37 patients (69.8%) were diagnosed with Langerhans cell histiocytosis, 14 patients (26.4%) with germinoma, 1 (1.9%) with astrocytoma, and 1 (1.9%) with optic glioma. 10-year overall survival (OS) rate and disease-free survival rate for all patients were 91.7% and 52%. 10-year OS rate according to diagnostic criteria was 91% for Langerhans cell histiocytosis (LCH) cases, 79% for intracranial germinoma, which was statistically significant (P = .0001). Central DI may be very important clinical presentation of serious underlying disease in children. Intracranial tumors are the most frequent cause of DI. Most frequent diagnosis were LCH and germ cell tumors in our series.

  9. [Kluver Bucy syndrome and central diabetes insipidus: two uncommon complications of herpes simplex encephalitis].

    PubMed

    Locatelli, C; Vergine, G; Ciambra, R; Leone, V; Facchini, S; Suprani, T; Casadei, G; Pocecco, M

    2003-01-01

    Herpes Simplex Encephalitis (HSE) is an uncommon but severe disease with high mortality and morbidity. The major clinical manifestations are deteriorating consciousness with confusion, drowsiness or coma, altered behaviour, convulsions and a variety of neurological signs (hemiplegia, aphasia, ataxia, etc.). An uncommon complication of HSE is Kluver Bucy syndrome (KBS), characterized by hyperorality, bulimia and changes in emotional behaviour. Neuroimaging studies frequently show an involvement of the temporal lobes and limbic areas. Another uncommon complication of HSE is central diabetes insipidus as a result of herpes simplex infection of the hypothalamus. We report two pediatric cases of HSE complicated with Kluver Bucy syndrome and central diabetes insipidus.

  10. A history of diabetes insipidus: paving the road to internal water balance.

    PubMed

    Eknoyan, Garabed

    2010-12-01

    Diabetes insipidus is an ancient disease considered under the rubric of diabetes, the Greek descriptive term for polyuria, which was unrecognized even after the sweetness of urine was reported as a characteristic of diabetes mellitus in the 17th century. It would be another century before diabetes insipidus was identified from the insipid rather than saccharine taste of urine in cases of polyuria. After its increased recognition, pathologic observations and experimental studies connected diabetes insipidus to the pituitary gland in the opening decades of the 20th century. Simultaneously, posterior pituitary lobe extracts were shown to be vasoconstrictive (vasopressin) and antidiuretic (antidiuretic hormone). As vasopressin was purified and synthesized and its assay became available, it was shown to be released in response to both osmotic and volume stimuli that are integrated in the hypothalamus, and vasopressin thereby was essential to maintaining internal water balance. The antidiuretic properties of vasopressin to treat the rare cases of diabetes insipidus were of limited clinical utility until its vasoconstrictive effects were resuscitated in the 1970s, with the consequent increasing wider use of vasopressin for the treatment of compromised hemodynamic states. In addition, the discovery of antidiuretic hormone receptor blockers has led to their increasing use in managing hypo-osmolar states.

  11. Metformin improves urine concentration in rodents with nephrogenic diabetes insipidus

    PubMed Central

    Efe, Orhan; Klein, Janet D.; LaRocque, Lauren M.; Ren, Huiwen; Sands, Jeff M.

    2016-01-01

    Urine concentration is regulated by vasopressin. Congenital nephrogenic diabetes insipidus (NDI) is caused by vasopressin type 2 receptor (V2R) mutations. We studied whether metformin could improve urine concentration in rodent models of congenital NDI by stimulating AMPK. To block the V2R in rats, tolvaptan (10 mg/kg/d) was given by oral gavage with or without metformin (800 mg/kg/d). Control rats received vehicle with or without metformin. Tamoxifen-induced V2R KO mice were given metformin (600 mg/kg) or vehicle twice daily. Urine osmolality in tolvaptan-treated rats (1,303 ± 126 mOsM) was restored to control levels by metformin (2,335 ± 273 mOsM) within 3 days and was sustained for up to 10 days. Metformin increased protein abundance of inner medullary urea transporter UT-A1 by 61% and aquaporin 2 (AQP2) by 44% in tolvaptan-treated rats, and immunohistochemistry showed increased membrane accumulation of AQP2 with acute and chronic AMPK stimulation. Outer medullary Na+-K+-2Cl– cotransporter 2 (NKCC2) abundance increased (117%) with AMPK stimulation in control rats but not in V2R-blocked rats. Metformin increased V2R KO mouse urine osmolality within 3 hours, and the increase persisted for up to 12 hours. Metformin increased AQP2 in the V2R KO mice similar to the tolvaptan-treated rats. These results indicate that AMPK activators, such as metformin, might provide a promising treatment for congenital NDI. PMID:27478876

  12. Acetazolamide Attenuates Lithium-Induced Nephrogenic Diabetes Insipidus.

    PubMed

    de Groot, Theun; Sinke, Anne P; Kortenoeven, Marleen L A; Alsady, Mohammad; Baumgarten, Ruben; Devuyst, Olivier; Loffing, Johannes; Wetzels, Jack F; Deen, Peter M T

    2016-07-01

    To reduce lithium-induced nephrogenic diabetes insipidus (lithium-NDI), patients with bipolar disorder are treated with thiazide and amiloride, which are thought to induce antidiuresis by a compensatory increase in prourine uptake in proximal tubules. However, thiazides induced antidiuresis and alkalinized the urine in lithium-NDI mice lacking the sodium-chloride cotransporter, suggesting that inhibition of carbonic anhydrases (CAs) confers the beneficial thiazide effect. Therefore, we tested the effect of the CA-specific blocker acetazolamide in lithium-NDI. In collecting duct (mpkCCD) cells, acetazolamide reduced the cellular lithium content and attenuated lithium-induced downregulation of aquaporin-2 through a mechanism different from that of amiloride. Treatment of lithium-NDI mice with acetazolamide or thiazide/amiloride induced similar antidiuresis and increased urine osmolality and aquaporin-2 abundance. Thiazide/amiloride-treated mice showed hyponatremia, hyperkalemia, hypercalcemia, metabolic acidosis, and increased serum lithium concentrations, adverse effects previously observed in patients but not in acetazolamide-treated mice in this study. Furthermore, acetazolamide treatment reduced inulin clearance and cortical expression of sodium/hydrogen exchanger 3 and attenuated the increased expression of urinary PGE2 observed in lithium-NDI mice. These results show that the antidiuresis with acetazolamide was partially caused by a tubular-glomerular feedback response and reduced GFR. The tubular-glomerular feedback response and/or direct effect on collecting duct principal or intercalated cells may underlie the reduced urinary PGE2 levels with acetazolamide, thereby contributing to the attenuation of lithium-NDI. In conclusion, CA activity contributes to lithium-NDI development, and acetazolamide attenuates lithium-NDI development in mice similar to thiazide/amiloride but with fewer adverse effects.

  13. Neurobrucellosis associated with syndrome of inappropriate antidiuretic hormone with resultant diabetes insipidus and hypothyroidism.

    PubMed

    Sturniolo, Giuseppe; Mondello, Placido; Bruno, Salvatore; Bonfatto, Orsola Elena; Frattima, Sabrina; Albanese, Antonio; Restivo, Roberta; Liberti, Giuseppe; Pasquali, Paolo; Marianelli, Cinzia

    2010-10-01

    Neurological involvement of the central nervous system in brucellosis is uncommon. We describe a rare case of meningoencephalitis due to Brucella melitensis infection, associated with the syndrome of inappropriate antidiuretic hormone secretion and leading to diabetes insipidus and hypothyroidism. Neurobrucellosis, although rare, should be considered in cases of neurological disease of unknown etiology.

  14. The value of urine specific gravity in detecting diabetes insipidus in a patient with uncontrolled diabetes mellitus: urine specific gravity in differential diagnosis.

    PubMed

    Akarsu, Ersin; Buyukhatipoglu, Hakan; Aktaran, Sebnem; Geyik, Ramazan

    2006-11-01

    When a patient with diabetes mellitus presents with worsening polyuria and polydipsia, what is a sensible, cost-effective approach? We report the unique coincidence of type 2 diabetes mellitus and diabetes insipidus. A 46-year-old woman with poorly controlled type 2 diabetes complained of polyuria with a daily output of 5 L. Although urinalysis demonstrated significant glucosuria, diabetes insipidus was suspected owing to a low urine specific gravity (1.008). The low specific gravity persisted during a water deprivation test. Ultimately, diabetes insipidus was confirmed when urine specific gravity and urine osmolality normalized following desmopressin administration. This case emphasizes the importance of accurately interpreting the urine specific gravity in patients with polyuria and diabetes mellitus to detect diabetes insipidus.

  15. Diabetes insipidus due to herpes encephalitis in a patient with diffuse large cell lymphoma. A case report.

    PubMed

    Scheinpflug, K; Schalk, E; Reschke, K; Franke, A; Mohren, M

    2006-01-01

    The major causes of central diabetes insipidus are neoplastic or infiltrative lesions of the hypothalamus or pituitary, severe head injuries and pituitary or hypothalamic surgery. Central diabetes insipidus caused by viral infections has been rarely reported in immunosuppressed patients, such as those with acquired immunodeficiency syndrome or Cushing's syndrome. We report the case of a 48-year-old woman suffering from diffuse large cell lymphoma, who developed hypotonic polyuria, hypernatriaemia and somnolence after the first course of chemotherapy with CHOEP and rituximab. Diabetes insipidus was diagnosed by low urine osmolarity and an undetectable vasopressin concentration. MRI revealed no pituitary abnormalities but encephalitis, and lumbar punction confirmed herpes zoster infection. To the best of our knowledge this is the first description of central diabetes insipidus in a lymphoma patient caused by an opportunistic CNS-infection.

  16. Diabetes insipidus as a rare cause of acute cognitive impairment in multiple sclerosis.

    PubMed

    Tiedje, V; Schlamann, M; Führer, D; Moeller, L C

    2013-10-01

    Multiple sclerosis (MS) is a complex neurodegenerative disease presenting with a diversity of clinical symptoms including palsy and cognitive impairment. We present a 59-year-old woman with a history of secondary progressive MS since 1987, who was referred to our department because of recent onset of confusion and polydipsia. Initial lab tests showed mildly elevated serum sodium levels and low urine osmolality. Under water deprivation, diuresis and low urine osmolality persisted and serum sodium levels rose above 150 mmol/l. Oral desmopressin resulted in normalisation of serum sodium as well as urine osmolarity, confirming a diagnosis of central diabetes insipidus. As drug-induced diabetes could be excluded, pituitary magnetic resonance imaging (MRI) was performed. A demyelinating lesion was detected in the hypothalamus. The patient was started on oral desmopressin treatment (0.2 mg/day). Fluid intake and serum sodium levels have since remained normal. In summary, we report the rare case of a patient presenting with diabetes insipidus due to progressive MS. Diabetes insipidus should be considered in MS patients who develop new onset of polydipsia.

  17. Congenital Nephrogenic Diabetes Insipidus Presented With Bilateral Hydronephrosis and Urinary Infection: A Case Report.

    PubMed

    Zheng, Kewen; Xie, Yi; Li, Hanzhong

    2016-05-01

    Nephrogenic diabetes insipidus (NDI) is a condition resulting from the kidney's impaired response to circulating antidiuretic hormone (ADH), leading to polydipsia and polyuria. Urinary tract dilatation caused by NDI is a rare situation. Here, we report a case of congenital NDI presented with bilateral hydronephrosis.A 15-year-old boy complaining a history of intermittent fever was admitted to Peking Union Medical College Hospital. He voided 10 to 15 L of urine daily. Radiographic examination revealed severe dilatation of bilateral renal pelvis, ureter, and bladder. Urinalysis shows hyposthenuria.He was diagnosed NDI since born. Transient insertion of a urethral catheter helped to relieve fever. Medical therapy of hydrochlorothiazide and amiloride was prescribed and effective.Dilatation of urinary tract caused by diabetes insipidus is rare, but may be present in severe condition. Therefore, it is crucial for clinicians to perform early treatment to avoid impairment of renal function.

  18. A Case of Rathke's Cleft Cyst Associated with Transient Central Adrenal Insufficiency and Masked Diabetes Insipidus

    PubMed Central

    Chin, Rina; Niitsu, Yoshihiro; Sekine, Tetsuo; Niwa, Arisa; Ogawa, Yoshihiro; Hirata, Yukio

    2014-01-01

    A 73-year-old woman admitted to our hospital because of headache, poor appetite, malaise, weight loss, and vomiting was found to have central adrenal insufficiency and thyrotoxicosis due to silent thyroiditis. Polyuria developed after replacement with glucocorticoid (masked diabetes insipidus), which was controlled with nasal administration of desmopressin. Magnetic resonance imaging of the brain showed a large cystic pituitary mass (18 × 18 × 12 mm) extending suprasellarly to the optic chiasm. Transsphenoidal surgery revealed that the pituitary tumor was Rathke's cleft cyst. Following surgery, replacement with neither glucocorticoid nor desmopressin was needed any more. Therefore, it is suggested that Rathke's cleft cyst is responsible for the masked diabetes insipidus and the central insufficiency. Furthermore, it is speculated that thyrotoxicosis with painless thyroiditis might induce changes from subclinical adrenal insufficiency to transiently overt insufficiency. PMID:25431697

  19. Invasive pneumococcal disease complicated by cerebral vasculitis, transient diabetes insipidus and spondylodiscitis.

    PubMed

    Ribeiro, Sofia; Domingues, Vital; Faria, Raquel M; Mendonça, Teresa

    2013-08-19

    Invasive pneumococcal disease (IPD) is a potential life-threatening situation that requires immediate recognition and treatment. Cerebrovascular complications are uncommon and have been reported less frequently in adults than in children. We report a case of 59-year-old man with IPD complicated by cerebral vasculitis, transient central diabetes insipidus and spondylodiscitis. Each of these complications is rare and needs specific approach. Their association is even rarer and to the best of our knowledge this is the first case reported.

  20. Spontaneous intermittent MRI changes of a pituitary stalk lesion causing diabetes insipidus and amenorrhea.

    PubMed

    Curtò, Lorenzo; Trimarchi, Francesco; Cannavo, Salvatore

    2017-04-01

    Lymphocytic infundibulo-neurohypophysitis is a rare disorder. We report the case of a 29 year-old woman with diabetes insipidus and amenorrhea, in whom the magnetic resonance imaging demonstration of a pituitary stalk lesion was intermittent. We suggest that, in patients with endocrine dysfunction and positivity of circulating antipituitary antibodies at high title, magnetic resonance imaging should be repeated after few months, if negative.

  1. Value of Renal Biopsy in Diagnosing Infantile Nephropathic Cystinosis Associated With Secondary Nephrogenic Diabetes Insipidus.

    PubMed

    Joyce, Emily; Ho, Jacqueline; El-Gharbawy, Areeg; Salgado, Cláudia M; Ranganathan, Sarangarajan; Reyes-Múgica, Miguel

    2017-01-01

    Cystinosis is the most common cause of inherited renal Fanconi syndrome in young children, and typically presents with laboratory findings of a proximal tubulopathy and corneal crystals by one year of age. We describe here renal biopsy findings in a 20-month-old patient with an atypical presentation of distal renal tubular acidosis, diabetes insipidus, and the absence of corneal crystals. Although renal biopsy is usually not necessary to establish the diagnosis of cystinosis, when the patient presents with atypical signs and symptoms, a renal biopsy may be extremely valuable. A 20-month-old boy presented with failure to thrive, polyuria, polydipsia, and rickets. He initially showed evidence of a renal tubular acidosis, mild renal insufficiency, and nephrogenic diabetes insipidus. His initial ophthalmologic examination did not demonstrate corneal crystals. His subsequent workup revealed phosphaturia, suggesting a partial proximal tubulopathy. Concomitantly, a renal biopsy revealed prominent podocytes with an immature glomerular appearance, and electron microscopy analysis showed numerous intracellular crystals within tubular epithelial cells. Subsequent laboratory and genetic testing confirmed a diagnosis of infantile nephropathic cystinosis. This case highlights the variability in the clinical presentation of cystinosis, resulting in an uncommon clinical picture of a rare disease. Given that treatment is available to prolong renal function and minimize the extra-renal manifestations of this disorder, early diagnosis is essential. It is important to raise the index of suspicion of cystinosis by recognizing its subtle morphological changes in young patients, and that nephrogenic diabetes insipidus can be secondary to this disorder.

  2. Newly developed central diabetes insipidus following kidney transplantation: a case report.

    PubMed

    Kim, K M; Kim, S M; Lee, J; Lee, S Y; Kwon, S K; Kim, H-Y

    2013-09-01

    Polyuria after kidney transplantation is a common, usually self-limiting disorder. However, persistent polyuria can cause not only patient discomfort, including polyuria and polydipsia, but also volume depletion that can produce allograft dysfunction. Herein, we have report a case of central diabetes insipidus newly diagnosed after kidney transplantation. A 45-year-old woman with end-stage kidney disease underwent deceased donor kidney transplantation. Two months after the transplantation, she was admitted for persistent polyuria, polydipsia, and nocturia with urine output of more than 4 L/d. Urine osmolarity was 100 mOsm/kg, which implied that the polyuria was due to water rather than solute diuresis. A water deprivation test was compatible with central diabetes insipidus; desmopressin treatment resulted in immediate symptomatic relief. Brain magnetic resonance imaging (MRI) demonstrated diffuse thickening of the pituitary stalk, which was considered to be nonspecific finding. MRI 12 months later showed no change in the pituitary stalk, although the patient has been in good health without polyuria or polydipsia on desmopressin treatment. The possibility of central diabetes insipidus should be considered in patients presenting with persistent polyuria after kidney transplantation.

  3. The clinical pattern of diabetes Insipidus in a large university hospital in the Middle East.

    PubMed

    Babiker, Amir M I; Al Jurayyan, Nasir A M; Al Jurayyan, Rushaid N A; Al Gadi, Iman; Drop, Stenvert L S

    2015-04-01

    Diabetes insipidus is a rare but serious endocrine disorder. Paediatric patients were evaluated for polyuria at King Khalid University Hospital, Riyadh, Saudi Arabia, over a decade (2000-13). Relevant clinical examination and/or a triad of high serum osmolality, hypernatremia and low urine osmolality due to increased urine output confirmed the diagnosis. Water deprivation test was required in some cases with non-classic presentations. Appropriate brain imaging was performed whenever central diabetes insipidus (CDI) was suspected. Twenty-eight patients, 15 males (53.6%) and 13 females (46.4%), aged 0-17 years (mean: 6 years) were included. The calculated period prevalence was 7 in 10,000. In our cohort, 60.7% (17 of 28 patients) had CDI, 21.4% (6 of 28) were diagnosed with nephrogenic diabetes insipidus (NDI) and 17.9% (5 of 30) had psychogenic polydipsia. CDI was due to variable aetiology. Though CDI was the commonest, NDI was not a rare encounter in our community, possibly because of high consanguineous marriages.

  4. An unusual case of central diabetes insipidus & hyperglycemic hyperosmolar state following cardiorespiratory arrest

    PubMed Central

    2013-01-01

    Background We are describing an unusual case of severe hyperglycemia and hypernatremia, resistant to treatment. Case presentation A thirty year old female with adenocarcinoma of rectum was admitted with increasing lethargy, headache and drowsiness. She deteriorated rapidly and had cardiac arrest, following which she remained comatose. Her initial serum glucose and sodium were normal, but after receiving dexamethasone and mannitol, the serum glucose progressively increased to 54.7 mmol/L and sodium to 175 mmol/L, despite receiving very high dose of intravenous (IV) insulin infusion. She was evaluated for diabetes insipidus because of continued polyuria even after correction of hyperglycemia. Her serum osmolality was 337 mmol/kg, and urine osmolality was 141 mmol/kg which rose to 382 mmol/kg, after receiving 4 mcg of IV Desmopressin. Conclusion Our patient developed central diabetes insipidus post cardiac arrest and severe dehydration because of diabetes insipidus. Stress of critical illness, dehydration, dexamethasone and IV dextrose infusion were likely responsible for this degree of severe and resistant to treatment hyperglycemia. PMID:23947429

  5. Pulmonary Langerhans Cell Histiocytosis in an Adult Male Presenting with Central Diabetes Insipidus and Diabetes Mellitus: A Case Report.

    PubMed

    Choi, Yeun Seoung; Lim, Jung Soo; Kwon, Woocheol; Jung, Soon-Hee; Park, Il Hwan; Lee, Myoung Kyu; Lee, Won Yeon; Yong, Suk Joong; Lee, Seok Jeong; Jung, Ye-Ryung; Choi, Jiwon; Choi, Ji Sun; Jeong, Joon Taek; Yoo, Jin Sae; Kim, Sang-Ha

    2015-10-01

    Pulmonary Langerhans cell histiocytosis is an uncommon diffuse cystic lung disease in adults. In rare cases, it can involve extrapulmonary organs and lead to endocrine abnormalities such as central diabetes insipidus. A 42-year-old man presented with polyphagia and polydipsia, as well as a dry cough and dyspnea on exertion. Magnetic resonance imaging of the hypothalamic-pituitary system failed to show the posterior pituitary, which is a typical finding in patients with central diabetes insipidus. This condition was confirmed by a water deprivation test, and the patient was also found to have type 2 diabetes mellitus. Computed tomographic scanning of the lungs revealed multiple, irregularly shaped cystic lesions and small nodules bilaterally, with sparing of the costophrenic angles. Lung biopsy through video-assisted thoracoscopic surgery revealed pulmonary Langerhans cell histiocytosis. On a follow-up visit, only 1 year after the patient had quit smoking, clinical and radiological improvement was significant. Here, we report an uncommon case of pulmonary Langerhans cell histiocytosis that simultaneously presented with diabetes insipidus and diabetes mellitus.

  6. Animal models of Central Diabetes Insipidus: Human relevance of acquired beyond hereditary syndromes and the role of oxytocin.

    PubMed

    Bernal, Antonio; Mahía, Javier; Puerto, Amadeo

    2016-07-01

    The aim of this study was to review different animal models of Central Diabetes Insipidus, a neurobiological syndrome characterized by the excretion of copious amounts of diluted urine (polyuria), a consequent water intake (polydipsia), and a rise in the serum sodium concentration (hypernatremia). In rodents, Central Diabetes Insipidus can be caused by genetic disorders (Brattleboro rats) but also by various traumatic/surgical interventions, including neurohypophysectomy, pituitary stalk compression, hypophysectomy, and median eminence lesions. Regardless of its etiology, Central Diabetes Insipidus affects the neuroendocrine system that secretes arginine vasopressin, a neurohormone responsible for antidiuretic functions that acts trough the renal system. However, most Central Diabetes Insipidus models also show disorders in other neurobiological systems, specifically in the secretion of oxytocin, a neurohormone involved in body sodium excretion. Although the hydromineral behaviors shown by the different Central Diabetes Insipidus models have usually been considered as very similar, the present review highlights relevant differences with respect to these behaviors as a function of the individual neurobiological systems affected. Increased understanding of the relationship between the neuroendocrine systems involved and the associated hydromineral behaviors may allow appropriate action to be taken to correct these behavioral neuroendocrine deficits.

  7. Polyuria with the Concurrent manifestation of Central Diabetes Insipidus (CDI) & Type 2 Diabetes Mellitus (DM).

    PubMed

    Shin, Hyun-Jong; Kim, Jae-Ha; Yi, Joo-Hark; Han, Sang-Woong; Kim, Ho-Jung

    2012-12-01

    We report a rare case of the concurrent manifestation of central diabetes insipidus (CDI) and type 2 diabetes mellitus (DM). A 56 year-old man was diagnosed as a type 2 DM on the basis of hyperglycemia with polyuria and polydipsia at a local clinic two months ago and started an oral hypoglycemic medication, but resulted in no symptomatic improvement at all. Upon admission to the university hospital, the patient's initial fasting blood sugar level was 140 mg/dL, and he showed polydipsic and polyuric conditions more than 8 L urine/day. Despite the hyperglycemia controlled with metformin and diet, his symptoms persisted. Further investigations including water deprivation test confirmed the coexisting CDI of unknown origin, and the patient's symptoms including an intense thirst were markedly improved by desmopressin nasal spray (10 µg/day). The possibility of a common origin of CDI and type 2 DM is raised in a review of the few relevant adult cases in the literature.

  8. Autoimmune central diabetes insipidus in a patient with ureaplasma urealyticum infection and review on new triggers of immune response.

    PubMed

    Murdaca, Giuseppe; Russo, Rodolfo; Spanò, Francesca; Ferone, Diego; Albertelli, Manuela; Schenone, Angelo; Contatore, Miriam; Guastalla, Andrea; De Bellis, Annamaria; Garibotto, Giacomo; Puppo, Francesco

    2015-12-01

    Diabetes insipidus is a disease in which large volumes of dilute urine (polyuria) are excreted due to vasopressin (AVP) deficiency [central diabetes insipidus (CDI)] or to AVP resistance (nephrogenic diabetes insipidus). In the majority of patients, the occurrence of CDI is related to the destruction or degeneration of neurons of the hypothalamic supraoptic and paraventricular nuclei. The most common and well recognized causes include local inflammatory or autoimmune diseases, vascular disorders, Langerhans cell histiocytosis (LCH), sarcoidosis, tumors such as germinoma/craniopharyngioma or metastases, traumatic brain injuries, intracranial surgery, and midline cerebral and cranial malformations. Here we have the opportunity to describe an unusual case of female patient who developed autoimmune CDI following ureaplasma urealyticum infection and to review the literature on this uncommon feature. Moreover, we also discussed the potential mechanisms by which ureaplasma urealyticum might favor the development of autoimmune CDI.

  9. Severe hypernatraemia due to nephrogenic diabetes insipidus - a life-threatening side effect of chronic lithium therapy.

    PubMed

    Sze, L; Ulrich, B; Brändle, M

    2006-11-01

    Renal toxicity of long-term lithium therapy is a common problem. Nephrogenic diabetes insipidus is the most frequently encountered complication, but often remains unrecognised because of the rather benign symptoms. We present a patient with long-term lithium therapy who developed life-threatening hypernatraemia due to insufficient oral fluid intake after elective spinal surgery. Careful daily substitution of up to 25 l of hypotonic fluids led to full recovery within 9 days. Nephrogenic diabetes insipidus should always be considered in lithium-treated patients undergoing elective surgery in order to avoid severe hypernatraemia.

  10. Fanconi's syndrome and nephrogenic diabetes insipidus in an adult treated with ifosfamide.

    PubMed

    Ingemi, Amanda I; Bota, Vasile M; Peguero, Anyeri; Charpentier, Margaret

    2012-01-01

    Fanconi's syndrome is a serious condition characterized by type II proximal renal tubular dysfunction, with urinary loss of glucose, amino acids, phosphate, bicarbonate, and potassium. Ifosfamide-induced Fanconi's syndrome is reported in about 1.4-5% of children being treated for solid tumors, yet only a few cases have been reported in adults. We describe a 54-year-old man who came to the hospital with symptoms of neutropenic fever 4 days after his fourth cycle of ifosfamide and doxorubicin treatment for recurrent sarcoma with metastases to the lung. During admission, he was noted to have severe renal tubular dysfunction; ifosfamide-induced nephrogenic diabetes insipidus and Fanconi's syndrome were suspected. He received supportive therapy that resulted in incomplete resolution of signs and symptoms. The patient was discharged after a 5-day hospital stay when his white blood cell count increased from 0.1-2.5 × 10(3) /mm(3) and his fever had resolved. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 7) between the patient's development of diabetes insipidus and Fanconi's syndrome and his use of ifosfamide. This dual diagnosis of diabetes insipidus and Fanconi's syndrome in an adult makes this case unusual, as well as therapeutically challenging. We conducted a review of the existing literature regarding ifosfamide-induced Fanconi's syndrome and describe the proposed mechanisms and therapeutic options. This case suggests that patients treated with ifosfamide should be monitored closely for renal function to identify, and perhaps prevent, these rare adverse events. Preliminary animal models show promise for adding N-acetylcysteine to ifosfamide treatment, but more research is necessary before using this drug as a therapeutic option.

  11. Response to low dose indomethacin in two children with nephrogenic diabetes insipidus.

    PubMed

    Dayal, Devi; Verma Attri, Savita; Kumar Bhalla, Anil; Kumar, Rakesh

    2015-01-01

    Two children with nephrogenic diabetes insipidus (NDI) were treated with oral indomethacin (0.75-1.2 mg/kg/day) three times a day for a mean duration of 3 yrs. Remission occurred in both patients in terms of achieving a normal fluid balance and body growth and the drug was withdrawn in one patient after 2 yrs. The treatment was well tolerated and no side effects were noted. The mean duration of follow-up was 6.5 yrs. These long-term observations of a favourable response to low dose indomethacin in 2 children with NDI need to be tested on larger number of patients.

  12. Permanent central diabetes insipidus as a complication of sphenoid sinus mucocele.

    PubMed

    Saylam, Güleser; Bayır, Omer; Girgin, Derya; Arslan, Müyesser Saykı; Tatar, Emel Çadallı; Ozdek, Ali; Delibaşı, Tuncay; Korkmaz, Mehmet Hakan

    2014-01-01

    Although mucocele is a benign lesion, its unavoidable expansions may result in irreversible damages in adjacent organs. In spheno-ethmoid mucoceles which are extremely rare, this condition may cause more severe problems. Central diabetes insipidus, developed secondary to sphenoid sinus mucocele, was detected in a 54-year-old male patient, who underwent endoscopic sinus surgery 2 times due to nasal polyposis. Endoscopic sphenoid mucocele marsupialization was performed to the patient, but despite partial regression in the 1-year follow up, complete recovery was not observed.

  13. Central diabetes insipidus: an unusual complication in a child with juvenile myelomonocytic leukemia and monosomy 7.

    PubMed

    Surapolchai, Pacharapan; Ha, Shau-Yin; Chan, Godfrey Chi-Fung; Lukito, Johannes B; Wan, Thomas S K; So, Chi-Chiu; Chiang, Alan Kwok-Shing

    2013-03-01

    Central diabetes insipidus (DI) is well-documented as a presenting feature of myelodysplastic syndrome and acute myeloid leukemia in adults. However, DI is unusual in pediatric patients with myeloid malignancies. We report here this rare complication in a child with neurofibromatosis type 1 who developed juvenile myelomonocytic leukemia and monosomy 7. Our case and previously reported cases of DI arising as a complication in myeloid malignancies demonstrate a close association with deletion of chromosome 7. The clinical characteristics and outcomes of these uncommon cases in children are reviewed and discussed.

  14. Transient Intraoperative Central Diabetes Insipidus in Moyamoya Patients Undergoing Revascularization Surgery: A Mere Coincidence?

    PubMed

    Hong, Joe C; Ramos, Emilio; Copeland, Curtis C; Ziv, Keren

    2016-04-15

    We present 2 patients with Moyamoya disease undergoing revascularization surgery who developed transient intraoperative central diabetes insipidus with spontaneous resolution in the immediate postoperative period. We speculate that patients with Moyamoya disease may be predisposed to a transient acute-on-chronic insult to the arginine vasopressin-producing portion of their hypothalamus mediated by anesthetic agents. We describe our management, discuss pertinent literature, and offer possible mechanisms of this transient insult. We hope to improve patient safety by raising awareness of this potentially catastrophic complication.

  15. Unusual Presentation of Central Diabetes Insipidus in a Patient With Neurosarcoidosis.

    PubMed

    Sanghi, Vedha; Kapoor, Aanchal

    2016-01-01

    Hypernatremia is a frequent cause of intensive care unit admission. The patient presented in this article had hypernatremia refractory to D5W (dextrose 5% water) therapy, which led to a complex investigation. Workup revealed central diabetes insipidus most likely secondary to flare up of neurosarcoidosis. The challenge in terms of diagnosis was a presentation with low urine output in the setting of hypernatremia resistant to treatment with desmopressin. This case unfolded the role of hypothyroidism causing secondary renal dysfunction and hence needed continued treatment with thyroxine in addition to treatment for hypernatremia.

  16. Hypothalamic type of hypopituitarism and central diabetes insipidus probably linked to Rathke's cleft cyst.

    PubMed

    Asano, Tomoko; Yamada, Hodaka; Yoshida, Masashi; Aoki, Atsushi; Ikoma, Aki; Kusaka, Ikuyo; Toyoshima, Hideo; Kakei, Masafumi; Ishikawa, San-E

    2015-01-01

    A 73-year-old woman was admitted due to weight loss and generalized malaise. The basal levels of all the anterior pituitary hormones, except for prolactin, were reduced. However, they were all elevated in response to exogenous hypothalamic hormones. After starting hydrocortisone replacement, the patient had polyuria of >5,000 mL/day. T1-weighted MRI depicted a low signal of an oval mass in the sella turcica and an iso-intense signal of another mass at the pituitary stalk. These findings indicate a hypothalamic type of hypopituitarism and masked central diabetes insipidus which possibly derived from the atypical occupation of Rathke's cleft cyst at the pituitary stalk.

  17. Exacerbation of pre-existing diabetes insipidus during pregnancy, mechanisms and management.

    PubMed

    Tack, Lloyd J W; T'Sjoen, Guy; Lapauw, Bruno

    2016-09-22

    During pregnancy, physiological changes in osmotic homeostasis cause water retention. If excessive, this can cause gestational diabetes insipidus (DI), particularly in patients with already impaired vasopressin secretion. We present the case of a 34-year-old patient with pre-existing hypopituitarism who experienced a transient exacerbation of her DI during a twin pregnancy. In contrast to typical gestational DI, polyuria and polydipsia occurred during the first trimester and remained stable thereafter. This case highlights a challenging clinical entity of which pathophysiology, diagnostic approach and treatment will be discussed.

  18. Unusual Presentation of Central Diabetes Insipidus in a Patient With Neurosarcoidosis

    PubMed Central

    Sanghi, Vedha; Kapoor, Aanchal

    2016-01-01

    Hypernatremia is a frequent cause of intensive care unit admission. The patient presented in this article had hypernatremia refractory to D5W (dextrose 5% water) therapy, which led to a complex investigation. Workup revealed central diabetes insipidus most likely secondary to flare up of neurosarcoidosis. The challenge in terms of diagnosis was a presentation with low urine output in the setting of hypernatremia resistant to treatment with desmopressin. This case unfolded the role of hypothyroidism causing secondary renal dysfunction and hence needed continued treatment with thyroxine in addition to treatment for hypernatremia. PMID:27652275

  19. Central Diabetes Insipidus and Cisplatin-Induced Renal Salt Wasting Syndrome: A Challenging Combination.

    PubMed

    Cortina, Gerard; Hansford, Jordan R; Duke, Trevor

    2016-05-01

    We describe a 2-year-old female with a suprasellar primitive neuroectodermal tumor and central diabetes insipidus (DI) who developed polyuria with natriuresis and subsequent hyponatremia 36 hr after cisplatin administration. The marked urinary losses of sodium in combination with a negative sodium balance led to the diagnosis of cisplatin-induced renal salt wasting syndrome (RSWS). The subsequent clinical management is very challenging. Four weeks later she was discharged from ICU without neurological sequela. The combination of cisplatin-induced RSWS with DI can be confusing and needs careful clinical assessment as inaccurate diagnosis and management can result in increased neurological injury.

  20. A case of thymic Langerhans cell histiocytosis with diabetes insipidus as the first presentation.

    PubMed

    Chen, Xiaoyan; Huang, Xiaochun; Qiu, Yuan; Chen, Hanzhang; Fu, Yingyu; Li, Xinchun

    2013-03-01

    Langerhans cell histiocytosis (LCH) is an idiopathic group of reactive proliferative diseases linked to aberrant immunity, pathologically characterized by clonal proliferation of Langerhans cells. LCH rarely involves the thymus. We report a case of thymic LCH with diabetes insipidus as the first presentation, without evidence of myasthenia gravis and without evidenced involvement of the skin, liver, spleen, bones, lungs and superficial lymph nodes. This present case may have important clinical implications. In screening for LCH lesions, attention should be attached to rarely involved sites in addition to commonly involved organs. Follow-up and imageological examination are very important to a final diagnosis.

  1. A very rare entity of diabetes insipidus associated with Edwards syndrome.

    PubMed

    Demir, Nihat; Doğan, Murat; Peker, Erdal; Bulan, Keziban; Tuncer, Oğuz

    2013-08-01

    Edwards syndrome is the second most commonly seen trisomy. It was first described by John Hamilton Edwards in 1960. Although most cases result in termination or foetal loss, live births have been documented in 5%. Edwards syndrome is characterized by multisystem anomalies, of which holoprosencephaly (HPE) is observed in 4-8% of cases. The clinical findings correspond to the degree of HPE malformation. Convulsions and endocrinopathies are among the severe clinical findings. The most common endocrinopathies are central diabetes insipidus (DI), hypothyroidism, hypocortisolism and growth hormone deficiency. The coexistence of holoproencephaly and DI in Edwards syndrome was discussed under the light of literature.

  2. Severe obesity and diabetes insipidus in a patient with PCSK1 deficiency.

    PubMed

    Frank, Graeme R; Fox, Joyce; Candela, Ninfa; Jovanovic, Zorica; Bochukova, Elena; Levine, Jeremiah; Papenhausen, Peter R; O'Rahilly, Stephen; Farooqi, I Sadaf

    2013-01-01

    Non-synonymous mutations affecting both alleles of PCSK1 (proprotein convertase 1/3) are associated with obesity and impaired prohormone processing. We report a proband who was compound heterozygous for a maternally inherited frameshift mutation and a paternally inherited 474kb deletion that encompasses PCSK1, representing a novel genetic mechanism underlying this phenotype. Although pro-vasopressin is not a known physiological substrate of PCSK1, the development of central diabetes insipidus in this proband suggests that PCSK1 deficiency can be associated with impaired osmoregulation.

  3. Diabetes insipidus and Langerhans cell histiocytosis: a case report of reversibility with 2-chlorodeoxyadenosine.

    PubMed

    Ottaviano, Fabio; Finlay, Jonathan L

    2003-07-01

    Diabetes insipidus (DI) is the most common manifestation of central nervous system involvement in Langerhans cell histiocytosis (LCH). Patients with LCH involving the head and neck region are reported to have about a 40% lifetime chance of developing DI. The clinical and biochemical diagnosis of DI is sometimes supported by the absence of the posterior pituitary bright signal on magnetic resonance images. Cladribine (2-chlorodeoxyadenosine, 2-CDA) has been reported as an active drug in children and adults with relapsed or refractory LCH. The authors report the successful reversal of DI in a 3-year-old child with established LCH using 2-CDA.

  4. Bilateral Ossified Chronic Subdural Hematoma Presenting as Diabetes Insipidus-Case Report and Literature Review.

    PubMed

    Siddiqui, Saquib A; Singh, Pankaj Kumar; Sawarkar, Dattaraj; Singh, Manmohanjit; Sharma, Bhawani S

    2017-02-01

    Calcified chronic subdural hematomas are an occurrence rarely seen in neurosurgical clinical practice. And when they occur bilaterally, the radiologic image they present is fascinating, as is the clinical presentation, but their management may be challenging. They have been reported to present with a multitude of neurologic deficits but never with diabetes insipidus, which is described here. Due to the rarity of this pathology, the management protocol is not well defined, though there have been quite a few papers on this condition. This review article gathers information published over the years on this rare entity to suggest a treatment protocol.

  5. [Case of distal renal tubular acidosis complicated with renal diabetes insipidus, showing aggravation of symptoms with occurrence of diabetes mellitus].

    PubMed

    Liu, Hexing; Tomoda, Fumihiro; Koike, Tsutomu; Ohara, Maiko; Nakagawa, Taizo; Kagitani, Satoshi; Inoue, Hiroshi

    2011-01-01

    We report herein a 27-year-old male case of inherited distal renal tubular acidosis complicated with renal diabetes insipidus, the symptoms of which were aggravated by the occurrence of diabetes mellitus. At 2 months after birth, he was diagnosed as having inherited distal renal tubular acidosis and thereafter supplementation of both potassium and alkali was started to treat his hypokalemia and metabolic acidosis. At the age of 4 years, calcification of the bilateral renal medulla was detected by computed tomography. Subsequently his urinary volume gradually increased and polyuria of approximately 4 L/day persisted. At the age of 27 years, he became fond of sugar-sweetened drinks and also often forgot to take the medicine. He was admitted to our hospital due to polyuria of more than 10 L day, muscle weakness and gait disturbance. Laboratory tests disclosed worsening of both hypokalemia and metabolic acidosis in addition to severe hyperglycemia. It seemed likely that occurrence of diabetes mellitus and cessation of medications can induce osmotic diuresis and aggravate hypokalemia and metabolic acidosis. Consequently, severe dehydration, hypokalemia-induced damage of his urinary concentration ability and enhancement of the renin angiotensin system occurred and thereby possibly worsened his hypokalemia and metabolic acidosis. As normalization of hyperglycemia and metabolic acidosis might have exacerbated hypokalemia further, dehydration and hypokalemia were treated first. Following intensive treatment, these abnormalities were improved, but polyuria persisted. Elevated plasma antidiuretic hormone (12.0 pg/mL) and deficit of renal responses to antidiuretic hormone suggested that the polyuria was attributable to the preexisting renal diabetes insipidus possibly caused by bilateral renal medulla calcification. Thiazide diuretic or nonsteroidal anti-inflammatory drugs were not effective for the treatment of diabetes insipidus in the present case.

  6. Enteroviral Meningoencephalitis Complicated by Central Diabetes Insipidus in a Neonate: A Case Report and Review of the Literature.

    PubMed

    Jones, Garrett; Muriello, Michael; Patel, Aloka; Logan, Latania

    2015-06-01

    Enterovirus is a known cause of central nervous system infection in the neonatal population and typically has a benign course; however, neurologic complications have been reported. We describe what we believe to be the first documented case of enteroviral meningoencephalitis complicated by central diabetes insipidus in a neonate.

  7. Amiloride blocks lithium entry through the sodium channel thereby attenuating the resultant nephrogenic diabetes insipidus.

    PubMed

    Kortenoeven, Marleen L A; Li, Yuedan; Shaw, Stephen; Gaeggeler, Hans-Peter; Rossier, Bernard C; Wetzels, Jack F M; Deen, Peter M T

    2009-07-01

    Lithium therapy frequently induces nephrogenic diabetes insipidus; amiloride appears to prevent its occurrence in some clinical cases. Amiloride blocks the epithelial sodium channel (ENaC) located in the apical membrane of principal cells; hence one possibility is that ENaC is the main entry site for lithium and the beneficial effect of amiloride may be through inhibiting lithium entry. Using a mouse collecting duct cell line, we found that vasopressin caused an increase in Aquaporin 2 (AQP2) expression which was reduced by clinically relevant lithium concentrations similar to what is seen with in vivo models of this disease. Further amiloride or benzamil administration prevented this lithium-induced downregulation of AQP2. Amiloride reduced transcellular lithium transport, intracellular lithium concentration, and lithium-induced inactivation of glycogen synthase kinase 3beta. Treatment of rats with lithium downregulated AQP2 expression, reduced the principal-to-intercalated cell ratio, and caused polyuria, while simultaneous administration of amiloride attenuated all these changes. These results show that ENaC is the major entry site for lithium in principal cells both in vitro and in vivo. Blocking lithium entry with amiloride attenuates lithium-induced diabetes insipidus, thus providing a rationale for its use in treating this disorder.

  8. Evolutionary Influenced Interaction Pattern as Indicator for the Investigation of Natural Variants Causing Nephrogenic Diabetes Insipidus.

    PubMed

    Grunert, Steffen; Labudde, Dirk

    2015-01-01

    The importance of short membrane sequence motifs has been shown in many works and emphasizes the related sequence motif analysis. Together with specific transmembrane helix-helix interactions, the analysis of interacting sequence parts is helpful for understanding the process during membrane protein folding and in retaining the three-dimensional fold. Here we present a simple high-throughput analysis method for deriving mutational information of interacting sequence parts. Applied on aquaporin water channel proteins, our approach supports the analysis of mutational variants within different interacting subsequences and finally the investigation of natural variants which cause diseases like, for example, nephrogenic diabetes insipidus. In this work we demonstrate a simple method for massive membrane protein data analysis. As shown, the presented in silico analyses provide information about interacting sequence parts which are constrained by protein evolution. We present a simple graphical visualization medium for the representation of evolutionary influenced interaction pattern pairs (EIPPs) adapted to mutagen investigations of aquaporin-2, a protein whose mutants are involved in the rare endocrine disorder known as nephrogenic diabetes insipidus, and membrane proteins in general. Furthermore, we present a new method to derive new evolutionary variations within EIPPs which can be used for further mutagen laboratory investigations.

  9. Altered cerebral glucose metabolism in an animal model of diabetes insipidus: a micro-PET study.

    PubMed

    Idbaih, Ahmed; Burlet, Arlette; Adle-Biassette, Homa; Boisgard, Raphaël; Coulon, Christine; Paris, Sophie; Marie, Yannick; Donadieu, Jean; Hoang-Xuan, Khê; Ribeiro, Maria-Joao

    2007-07-16

    The Brattleboro rat is an animal model of genetically induced central diabetes insipidus. These rats show cognitive and behavioral disorders, but no neurodegenerative disease has been observed. We studied brain glucose uptake, a marker of neuronal activity, in 6 Brattleboro rats, in comparison with 6 matched Long-Evans (LE) control rats. A group of 3 Brattleboro rats and 3 Long-Evans rats was studied in vivo and another group of animals was studied ex vivo. In vivo studies were performed using fluorodeoxyglucose labeled with fluorine 18 ((18)F-FDG) and a dedicated small-animal PET device. At 30 min and 60 min p.i., (18)F-FDG uptake was significantly higher in the frontal cortex, striatum, thalamus and cerebellum of Brattleboro rats than in LE rats when measured by PET in vivo (p<0.05), but only a trend towards higher values was found ex vivo. Our results show for the first time that brain glucose metabolism is modified in Brattleboro rats. This altered brain glucose metabolism in Brattleboro rats may be related to the observed cognitive and behavioral disorders. Functional analyses of brain metabolism are promising to investigate cognitive behavioral disturbances observed in Brattleboro rats and their link to diabetes insipidus.

  10. An unusual case of hereditary nephrogenic diabetes insipidus (HNDI) affecting mother and daughter.

    PubMed

    Giri, Dinesh; Hart, Rachel; Jones, Caroline; Ellis, Ian; Ramakrishnan, Renuka

    2016-01-01

    Hereditary nephrogenic diabetes iInsipidus (HNDI) is an uncommon disorder due to a resistance to anti-diuretic hormone leading to a reduced urinary concentrating ability. The X-linked form is fully expressed in hemizygous male patients, but diabetes insipidus may also present in heterozygous females where it must be distinguished from autosomal and other secondary causes. We report a mother and daughter in the same family with HNDI due to a heterozygous deletion in exon 1 of the AVPR2 gene, not previously described in the literature. A 5-year-old girl was referred for investigation of polyuria and polydipsia. The patient had a water deprivation test elsewhere at the age of 3 that was inconclusive. A degree of water restriction was imposed leading to headaches. The thyroid, cortisol, renal, and calcium profiles were normal. Her mother showed similar symptoms that had not been previously investigated. AQP2 (Aquaporin) and initial AVPR2 gene sequencing had not identified a mutation, but subsequent quantitative polymerase chain reaction analysis revealed a heterozygous large exon 1 deletion of the AVPR2 gene. The same deletion was also found in the child's mother. The patient's symptoms have significantly improved on appropriate treatment. Further analysis revealed skewed X inactivation in mother and daughter.

  11. Wilms tumor arising in a child with X-linked nephrogenic diabetes insipidus.

    PubMed

    El-Kares, Reyhan; Hueber, Pierre-Alain; Blumenkrantz, Miriam; Iglesias, Diana; Ma, Kim; Jabado, Nada; Bichet, Daniel G; Goodyer, Paul

    2009-07-01

    We report on a child with X-linked nephrogenic diabetes insipidus (NDI) who developed Wilms tumor (WT). Nephrogenic diabetes insipidus is caused by mutations of the arginine vasopressin receptor (AVPR2) or aquaporin-II (AQP2) genes. Wilms tumor is also genetically heterogeneous and is associated with mutations of WT1 (15-20%), WTX (20-30%) and other loci. The boy presented at 5 months with failure to thrive, polyuria, hypernatremia and abdominal mass. Analysis of leukocyte DNA showed a novel missense mutation (Q174H) of the AVPR2 gene, which was not present in his mother. In cells (WitS) isolated from the tumor, WTX mRNA expression and coding sequence were intact. However, we identified a 44-kb homozygous deletion of the WT1 gene spanning exons 4 to 10. The WT1 deletion was not present in leukocyte DNA from the patient or his mother. We also noted strong beta-catenin (CTNNB1) expression in the tumor cells and identified a heterozygote missense Ser45Cys mutation of exon 3 of CTNNB1. However, the mutation was absent both in the constitutional DNA of the patient and his mother. The concurrence of WT and NDI has not been previously reported and may be unrelated. Nevertheless, this case nicely illustrates the sequence of events leading to sporadic Wilms tumor.

  12. [Importance of long-term follow-up of diabetes insipidus; from lymphocytic hypophysitis to germinoma].

    PubMed

    Amat Madramany, A; Gastaldo Simeón, E; Revert Ventura, A; Escobar Hoyos, L A; Riesgo Suárez, P

    2015-01-01

    A case is presented of a 10-year old boy who had a hypothalamic-pituitary axis disorder. He initially presented with diabetes insipidus that progressed to panhypopituitarism. A hidden hypothalamic lesion should be suspected in all these cases, and should be followed up. New lesions were found in the pituitary stem three years later. Although tumor markers were negative, there was an increase in size, and a biopsy was performed. The histopathology reported a Lymphocytic Hypophysitis. There were increases in the tumor markers during the follow-up, thus a second biopsy was performed, with the diagnosis of Germinoma. Lymphocytic Hypophysitis is an uncommon diagnosis in children. Few cases have been reported, and in some cases, they were later diagnosed with Germinoma. We believe this case highlights the importance of the follow-up of children with Central Diabetes Insipidus with a normal MRI, as well as not taking the diagnosis of Lymphocytic Hypophysitis/lymphocytic Infundibular neurohypophysitis as definitive, as it is a rare diagnosis at this age, and could mask a Germinoma, as recorded in some cases.

  13. The Value Of Renal Biopsy In Diagnosing Infantile Nephropathic Cystinosis Associated With Secondary Nephrogenic Diabetes Insipidus.

    PubMed

    Joyce, Emily; Ho, Jacqueline; El-Gharbawy, Areeg; Salgado, Cláudia M; Ranganathan, Sarangarajan; Reyes-Múgica, Miguel

    2015-11-18

    Cystinosis is a rare autosomal recessive disorder and the most common cause of inherited renal Fanconi syndrome in young children. Renal biopsy is usually not necessary to establish the diagnosis, but when the patient presents with atypical signs and symptoms, a renal biopsy may be extremely valuable. We describe here renal biopsy findings in a patient with cystinosis. A 20-month-old male presented with failure to thrive, polyuria, polydipsia and rickets. He initially showed evidence of a renal tubular acidosis, mild renal insufficiency and nephrogenic diabetes insipidus. His initial ophthalmologic exam did not demonstrate corneal crystals. His subsequent workup revealed phosphaturia, suggesting a partial proximal tubulopathy. Concomitantly, a renal biopsy revealed prominent podocytes with an immature glomerular appearance and electron microscopy analysis showed numerous intracellular crystals within tubular epithelial cells. Subsequent laboratory and genetic testing confirmed a diagnosis of infantile nephropathic cystinosis. This case highlights the variability in the clinical presentation of cystinosis, resulting in an uncommon clinical picture of a rare disease. Given that treatment is available to prolong renal function and minimize the extra-renal manifestations of this disorder, early diagnosis is essential. It is important to raise the index of suspicion of cystinosis by recognizing its subtle morphological changes in young patients, and that nephrogenic diabetes insipidus can be secondary to this disorder.

  14. Diabetic Neuropathy and Axon Reflex-Mediated Neurogenic Vasodilatation in Type 1 Diabetes

    PubMed Central

    Bril, Vera; Orszag, Andrej; Ng, Eduardo; Nwe, Patti; Perkins, Bruce A.

    2012-01-01

    Objective Axon reflex-mediated neurogenic vasodilatation in response to cutaneous heating may reflect early, pre-clinical small fibre dysfunction. We aimed to evaluate the distribution of the vascular flare area measured by laser doppler imaging (“LDIFLARE area”) in type 1 diabetes and in healthy volunteers. Research and Methods Concurrent with clinical and electrophysiological examination to classify diabetic sensorimotor polyneuropathy (DSP), LDIFLARE area (cm2) was determined in 89 type 1 diabetes subjects matched to 64 healthy volunteers. We examined the association and diagnostic performance of LDI with clinical and subclinical measures of DSP and its severity. Results Compared to the 64 healthy volunteers, the 56 diabetes controls without DSP had significantly lower LDIFLARE area (p = 0.006). The 33 diabetes cases with DSP had substantially lower LDIFLARE area as compared to controls without DSP (p = 0.002). There was considerable overlap in LDIFLARE area between all groups such that the ROC curve had an AUC of 0.72 and optimal sensitivity of 70% for the detection of clinical DSP. Use of a subclinical definition for DSP, according to subclinical sural nerve impairment, was associated with improved AUC of 0.75 and sensitivity of 79%. In multivariate analysis higher HbA1c and body mass index had independent associations with smaller LDIFLARE area. Conclusions Axon reflex-mediated neurogenic vasodilatation in response to cutaneous heating is a biomarker of early nerve dysfunction in DSP. Its independent association with glycemic exposure in diabetes subjects and both glycemic exposure and BMI in healthy volunteers highlights the existence of small-fibre dysfunction in the natural history of DSP. PMID:22529938

  15. Iatrogenic water intoxication during pelvic ultrasonography in a patient with diabetes insipidus.

    PubMed

    Derinöz, Okşan; Emeksiz, Hamdi Cihan; Kalkan, Gökhan; Camurdan, Orhun

    2012-01-01

    Pelvic ultrasonography (US) is a simple and non-invasive radiologic test to evaluate the pelvic organs. It requires a full bladder for better visualization. Our case is a 14-year-old female with diabetes insipidus (DI) who admitted to the pediatric emergency service with the complaints of seizure and agitation after drinking 4 liters of water in one hour for a pelvic US examination due to work-up for delayed puberty. Her biochemical and clinical evaluation revealed water intoxication (WI). To our knowledge, this is the first WI case developed in a patient with DI. Here, we discuss the underlying factors leading to this complication and recommended an approach to obtain a better sonographic image without necessitating oral water intake to fill the urinary bladder.

  16. Acute myeloid leukemia, the 3q21q26 syndrome and diabetes insipidus: a case presentation.

    PubMed

    Curley, Cameron; Kennedy, Glen; Haughton, Anne; Love, Amanda; McCarthy, Catherine; Boyd, Andrew

    2010-06-01

    Diabetes insipidus (DI) is a rare presenting complication of acute myeloid leukaemia (AML). Typically, the combination of DI and AML is associated with structural abnormalities of the neurohypophysis. We present a case of AML and DI presenting without any abnormalities of the neurohypophysis on radiological scanning and with normal cerebrospinal fluid examination. The AML karyotype at presentation was characterized by the presence of a t(3; 3)(q21; q26) translocation and monosomy 7. After treatment with induction chemotherapy, the patient achieved a complete remission and his DI resolved. At subsequent AML relapse, characterized by a complex karyotype without the t(3; 3)(q21; q26) translocation or monosomy 7, DI did not recur. Our case provides clinical support to the hypothesis that the t(3; 3)(q21; q26) translocation and/or monosomy 7 in AML may directly result in dysregulation of transcription factors resulting in development of DI in AML patients.

  17. Growth hormone deficiency and diabetes insipidus as a complication of endoscopic third ventriculostomy.

    PubMed

    Tafuri, Kimberly S; Wilson, Thomas A

    2012-12-01

    Endoscopic third ventriculostomy (ETV) has become the procedure of choice for the treatment of obstructive hydrocephalus in children and adults. Endocrinological complications of ETV in children are rare. Diabetes insipidus (DI) is the most common and accounts for only 0.5% of complications from ETV. The majority of documented cases are transient. To date, there are no documented cases of multiple pituitary hormone deficiencies. We present here a 6-year-old girl with growth hormone deficiency and permanent DI which developed as a complication of ETV. This patient is unique in both demonstrating multiple pituitary hormone deficiencies and the classical triphasic response of DI after ETV. We postulate that these complications were caused by compression of the pituitary stalk and hypothalamic injury during the procedure. We compare our case presentation to experimental studies conducted in rats.

  18. Hyperactivation of Nrf2 in early tubular development induces nephrogenic diabetes insipidus

    PubMed Central

    Suzuki, Takafumi; Seki, Shiori; Hiramoto, Keiichiro; Naganuma, Eriko; Kobayashi, Eri H.; Yamaoka, Ayaka; Baird, Liam; Takahashi, Nobuyuki; Sato, Hiroshi; Yamamoto, Masayuki

    2017-01-01

    NF-E2-related factor-2 (Nrf2) regulates cellular responses to oxidative and electrophilic stress. Loss of Keap1 increases Nrf2 protein levels, and Keap1-null mice die of oesophageal hyperkeratosis because of Nrf2 hyperactivation. Here we show that deletion of oesophageal Nrf2 in Keap1-null mice allows survival until adulthood, but the animals develop polyuria with low osmolality and bilateral hydronephrosis. This phenotype is caused by defects in water reabsorption that are the result of reduced aquaporin 2 levels in the kidney. Renal tubular deletion of Keap1 promotes nephrogenic diabetes insipidus features, confirming that Nrf2 activation in developing tubular cells causes a water reabsorption defect. These findings suggest that Nrf2 activity should be tightly controlled during development in order to maintain renal homeostasis. In addition, tissue-specific ablation of Nrf2 in Keap1-null mice might create useful animal models to uncover novel physiological functions of Nrf2. PMID:28233855

  19. Hyperactivation of Nrf2 in early tubular development induces nephrogenic diabetes insipidus.

    PubMed

    Suzuki, Takafumi; Seki, Shiori; Hiramoto, Keiichiro; Naganuma, Eriko; Kobayashi, Eri H; Yamaoka, Ayaka; Baird, Liam; Takahashi, Nobuyuki; Sato, Hiroshi; Yamamoto, Masayuki

    2017-02-24

    NF-E2-related factor-2 (Nrf2) regulates cellular responses to oxidative and electrophilic stress. Loss of Keap1 increases Nrf2 protein levels, and Keap1-null mice die of oesophageal hyperkeratosis because of Nrf2 hyperactivation. Here we show that deletion of oesophageal Nrf2 in Keap1-null mice allows survival until adulthood, but the animals develop polyuria with low osmolality and bilateral hydronephrosis. This phenotype is caused by defects in water reabsorption that are the result of reduced aquaporin 2 levels in the kidney. Renal tubular deletion of Keap1 promotes nephrogenic diabetes insipidus features, confirming that Nrf2 activation in developing tubular cells causes a water reabsorption defect. These findings suggest that Nrf2 activity should be tightly controlled during development in order to maintain renal homeostasis. In addition, tissue-specific ablation of Nrf2 in Keap1-null mice might create useful animal models to uncover novel physiological functions of Nrf2.

  20. A case of transient central diabetes insipidus after aorto-coronary bypass operation.

    PubMed

    Yu, Chung-Hoon; Cho, Jang-Hee; Jung, Hee-Yeon; Lim, Jeong-Hoon; Jin, Mi-Kyung; Kwon, Owen; Hong, Kyung-Deuk; Choi, Ji-Young; Yoon, Se-Hee; Kim, Chan-Duck; Kim, Yong-Lim; Kim, Gun-Jik; Park, Sun-Hee

    2012-09-01

    Diabetes insipidus (DI) is characterized by excessive urination and thirst. This disease results from inadequate output of antidiuretic hormone (ADH) from the pituitary gland or the absence of the normal response to ADH in the kidney. We present a case of transient central DI in a patient who underwent a cardiopulmonary bypass (CPB) for coronary artery bypass grafting (CABG). A 44-yr-old male underwent a CABG operation. An hour after the operation, the patient developed polyuria and was diagnosed with central DI. The patient responded to desmopressin and completely recovered five days after surgery. It is probable that transient cerebral ischemia resulted in the dysfunction of osmotic receptors in the hypothalamus or hypothalamus-pituitary axis during CPB. It is also possible that cardiac standstill altered the left atrial non-osmotic receptor function and suppressed ADH release. Therefore, we suggest that central DI is a possible cause of polyuria after CPB.

  1. Holoprosencephaly and diabetes insipidus in a 3-month-old infant.

    PubMed

    Kourti, Maria; Pavlou, Evaggelos; Rousso, Israel; Economou, Ippolyti; Athanassiadou, Fani

    2008-01-01

    Holoprosencephaly is a developmental defect caused by incomplete cleavage of the embryonic forebrain structures during early embryogenesis. We describe a 3-month-old boy with median cleft palate, surgically reconstructed cleft lip, hypotelorism with a flat nose, cryptorchidism, clubfoot, and microcephaly. During the laboratory investigation, his blood sodium level was 154 mmol/L and urine specific gravity was 1.007. Serum osmolarity was 317 mOsm/kg and urine osmolarity was 268 mOsm/kg. Given these findings and the clinical response to vasopressin, diagnosis of central diabetes insipidus was made. Magnetic resonance imaging revealed semilobar holoprosencephaly. The patient responded very well to vasopressin treatment with restoration of serum electrolytes, which remained within normal limits on follow-up. In case of midline facial defects accompanied by hypotelorism with or without developmental delay, the brain should be imaged to confirm its morphology and investigations should be directed by a high index of suspicion of associated endocrinologic dysfunctions.

  2. Dysregulation of renal aquaporins and epithelial sodium channel in lithium-induced nephrogenic diabetes insipidus.

    PubMed

    Nielsen, Jakob; Kwon, Tae-Hwan; Christensen, Birgitte Mønster; Frøkiaer, Jørgen; Nielsen, Søren

    2008-05-01

    Lithium is used commonly to treat bipolar mood disorders. In addition to its primary therapeutic effects in the central nervous system lithium has a number of side effects in the kidney. The side effects include nephrogenic diabetes insipidus with polyuria, mild sodium wasting, and changes in acid/base balance. These functional changes are associated with marked structural changes in collecting duct cell composition and morphology, likely contributing to the functional changes. Over the past few years, investigations of lithium-induced renal changes have provided novel insight into the molecular mechanisms that are responsible for the disturbances in water, sodium, and acid/base metabolism. This includes dysregulation of renal aquaporins, epithelial sodium channel, and acid/base transporters. This review focuses on these issues with the aim to present this in context with clinically relevant features.

  3. Coexistence of autoimmune polyglandular syndrome type 2 and diabetes insipidus in pregnancy.

    PubMed

    Krysiak, Robert; Samborek, Malgorzata

    2011-11-01

    Autoimmune polyglandular syndromes are rarely diagnosed conditions characterized by the association of at least 2 organ-specific autoimmune disorders. Very few cases of these syndromes have been described during pregnancy. The authors report a case of a patient diagnosed with autoimmune thyroiditis and a history of HELLP (hemolysis, elevated liver enzymes and low platelet) syndrome in a prior pregnancy. After increasing the levothyroxine dose, she developed Addisonian crisis. Normalization of adrenal cortex function resulted in the appearance of diabetes insipidus. This report shows that pregnancy may influence the course of preexisting endocrine disorders and lead to their unmasking. Although the risk of the development of autoimmune polyglandular syndromes during pregnancy is small, they may pose a serious health problem. The possible presence of these clinical entities should be considered in every woman with 1 or more endocrine disturbances.

  4. Adipsic diabetes insipidus and venous thromboembolism (VTE): recommendations for addressing its hypercoagulability.

    PubMed

    Miljic, Dragana; Miljic, Predrag; Doknic, Mirjana; Pekic, Sandra; Stojanovic, Marko; Petakov, Milan; Popovic, Vera

    2014-01-01

    Adipsic diabetes insipidus (ADI) is a rare disorder. It can occur after transcranial surgery for craniopharyngeoma, suprasellar pituitary adenoma and anterior communicating artery aneurysm but also with head injury, toluene exposure and developmental disorders. It is often associated with significant hypothalamic dysfunction and complications like obesity, sleep apnea, thermoregulatory disorders, seizures and venous thromboembolism (VTE). Morbidity and mortality data have been reported as single case reports with only one large series suggesting increased risk for VTE in patients with ADI. Here we report a mini-series of four patients with ADI and VTE. Post-surgery immobilization, obesity, infection, with prolonged hospitalization, hemoconcentration and changes in coagulation which might be induced by inadequate hormone treatment in the postoperative period (high doses of glucocorticoids, sex steroids and DDAVP replacement) may all contribute to the pathogenesis of VTE. Thromboprophylactic treatment after pituitary surgery and during episodes of hypernatremia is therefore warranted.

  5. Objective assessment of thirst recovery in patients with adipsic diabetes insipidus.

    PubMed

    Sinha, A; Ball, S; Jenkins, A; Hale, J; Cheetham, T

    2011-12-01

    Adipsic diabetes insipidus (ADI) is characterised by impaired thirst and defective AVP secretion. We have assessed the thirst response to graded osmotic stimulation using a visual analog scale (VAS) in patients with a history of ADI following surgery for a craniopharyngioma. The patients were thought to be regaining their thirst response but we wanted to confirm that this was the case objectively before relaxing their strict fluid balance regimen. Three patients with adipisa in the presence of hypernatremia following surgery for a craniopharyngioma are described. Their median age at surgery was 13 years (range 11-15 years). All patients had previously demonstrated no desire to drink despite a serum osmolality in excess of 300 mOsmol/kg. Fluid balance was maintained postoperatively with a regimen involving a fixed daily fluid intake and DDAVP dose together with daily weights and regular assessment of capillary sodium concentrations. Patients were thought to be regaining thirst sensation and so were assessed by hypertonic saline infusion (HSI) with thirst measured using a VAS. Patients underwent a HSI test 4, 6 and 9 months post surgery. All had abnormally low AVP production at raised plasma osmolalities but the visual analogue scale confirmed partial or complete thirst recovery. The intensive regimen used to maintain stable serum sodium concentrations was relaxed without the patients subsequently developing a significant hyperosmolar state. We have shown objective recovery of thirst perception in patients with adipsia within 9 months of surgery, despite persistence of cranial diabetes insipidus. These observations indicate that both osmoreceptors regulating thirst and their efferent pathways demonstrate more plasticity than those regulating AVP production. The HSI and thirst VAS are an objective way of assessing patients known to have ADI who are thought to be recovering thirst perception.

  6. Lymphocytic hypophysitis causing hypopituitarism and diabetes insipidus, and associated with autoimmune thyroiditis, in a non-pregnant woman.

    PubMed Central

    Paja, M.; Estrada, J.; Ojeda, A.; Ramón y Cajal, S.; García-Uría, J.; Lucas, T.

    1994-01-01

    A 25 year old non-pregnant woman presented with a one-year history of amenorrhoea and polyuria. Three months before her admission, she had suffered lymphocytic meningitis. Hormonal studies revealed hypopituitarism and central diabetes insipidus, with associated primary autoimmune hypothyroidism. Computed tomographic scan and magnetic resonance imaging showed a pituitary mass with suprasellar extension and thickened stalk. Transsphenoidal surgery was performed and the histological study revealed fibrosis and diffuse lymphocytic infiltration with predominance of CD4 lymphocytes. This further case of lymphocytic hypophysitis was not related to pregnancy and produced diabetes insipidus, two uncommon associations. We discuss the features that can lead to a preoperative suspicion of this rare disorder. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7910396

  7. Emphysematous Pyelonephritis Caused by Citrobacter freundii in a Patient with Type 2 Diabetes and Neurogenic Bladder.

    PubMed

    Kim, Min Jeong; Park, Ji Sang; Lim, Hye Jin; Jung, Jihye; Shin, Dong Geum; Lee, Ki-Deok; Jung, Yoon Young; Min, Kyung Wan; Han, Kyung-Ah

    2013-09-01

    Emphysematous pyelonephritis (EPN) is a rare, life-threatening complication of upper urinary tract infections that is characterized by the presence of gas in the renal parenchyma and perirenal space. It commonly occurs in diabetic patients. Escherichia coli are the most common causative organisms, with few reports implicating Citrobacter freundii as the etiologic agent in EPN. A 57-year-old woman with diabetes and neurogenic bladder visited at our department with confused mentality, myalgia, and general weakness. Further investigation revealed that the patient suffered from unilateral EPN with sepsis caused by C. freundii. The patient's condition was improved considerably with percutaneous drainage and use of intravenous antibiotics for several weeks. However, renal function eventually deteriorated to permanent renal failure, which required hemodialysis. In conclusion, C. freundii may be the causative pathogen of EPN in a patient with type 2 diabetes and neurogenic bladder.

  8. Idiopathic central diabetes insipidus presenting in a very low birth weight infant successfully managed with lyophilized sublingual desmopressin.

    PubMed

    Hanta, Deniz; Törer, Birgin; Temiz, Fatih; Kılıçdağ, Hasan; Gökçe, Mahmut; Erdoğan, Özlem

    2015-01-01

    Neonatal central diabetes insipidus (DI) is an extremely rare disorder that can cause severe morbidity and mortality. We have reported a very low birth weight infant with idiopathic central DI presenting in the first month of life who was successfully treated with sublingual desmopressin therapy. In this report, we emphasize that central DI should be kept in mind in an infant with unexplained hypernatremia and polyuria. Timely diagnosis and treatment with lyophilized desmopressin may prevent severe morbidity and mortality.

  9. Diabetes insipidus

    MedlinePlus

    ... This is a small gland just below the base of the brain. DI caused by a lack ... Wisse, MD, Associate Professor of Medicine, Division of Metabolism, Endocrinology & Nutrition, University of Washington School of Medicine, ...

  10. Diabetes Insipidus

    MedlinePlus

    ... provider's office, or at a commercial facility. A health care provider tests the sample in the same location or sends ... urine sample. A formal fluid deprivation test. A health care provider performs this test in a hospital to continuously monitor the patient ...

  11. Diabetes Insipidus

    MedlinePlus

    ... y Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ... Clinical Trials Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ...

  12. Diabetes Insipidus

    MedlinePlus

    ... Hormones Do? Infographics Myth vs Fact Scientific Statements Social Media Resources Peer Support Resources Diseases and Conditions Adrenal ... Hormones Do? Infographics Myth vs Fact Scientific Statements Social Media Resources Peer Support Resources Diseases and Conditions Adrenal ...

  13. [Acute myeloid leukemia with monosomy 7 and inv(3)(q21q26.2) complicated with central diabetes insipidus].

    PubMed

    Nanno, Satoru; Hagihara, Kiyoyuki; Sakabe, Manami; Okamura, Hiroshi; Inaba, Akiko; Nagata, Yuki; Nishimoto, Mitsutaka; Koh, Hideo; Nakao, Yoshitaka; Nakane, Takahiko; Nakamae, Hirohisa; Shimono, Taro; Hino, Masayuki

    2013-04-01

    A 20-year-old female presented with thirst, polyposia, and polyuria and was referred to our hospital because of leukocytosis and anemia. Bone marrow aspiration revealed 66.8% myeloperoxidase-positive blasts and trilineage myelodysplasia. The karyotype was 45, XX, inv(3)(q21q26.2), -7[19]. Therefore, a diagnosis of AML with inv(3)(q21q26.2) complicated by -7 was made. Moreover, hyposthenuria and a low anti-diuretic hormone (ADH) level were observed. Although cerebrospinal fluid analysis was normal, magnetic resonance imaging (MRI) revealed the absence of hyperintensity in the neurohypophysis in T1-weighted images. Therefore, she was also diagnosed with diabetes insipidus. After she was administered a desmopressin nasal spray, the volume of urine produced decreased. Following treatment with second induction therapy containing high-dose cytarabine for AML, she achieved complete remission in the bone marrow. Moreover, when the abnormality on MRI and the volume of urine were normalized, she discontinued desmopressin. Although diabetes insipidus is a rare complication of AML, the majority of AML patients who have diabetes insipidus have the abnormal karyotypes with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and monosomy 7. Further study is required to clarify the pathogenesis and develop a strategy for the treatment of this category of AML.

  14. Mutations in the AVPR2, AVP-NPII, and AQP2 genes in Turkish patients with diabetes insipidus.

    PubMed

    Duzenli, Duygu; Saglar, Emel; Deniz, Ferhat; Azal, Omer; Erdem, Beril; Mergen, Hatice

    2012-12-01

    The aim of this study was to identify mutations in three different genes, the arginine-vasopressin-neurophysin II (AVP-NPII) gene, the arginine-vasopressin receptor 2 (AVPR2) gene, and the vasopressin-sensitive water channel aquaporin-2 (AQP2) gene in Turkish patients affected by central diabetes insipidus or nephrogenic diabetes insipidus. This study included 15 patients from unrelated families. Prospective clinical data were collected for all patients including the patients underwent a water deprivation-desmopressin test. The coding regions of the AVPR2, AQP2, and AVP-NPII genes were amplified by polymerase chain reaction and submitted to direct sequence analysis. Of the 15 patients with diabetes insipidus referred to Gulhane Military Medical Academy, Department of Endocrinology and Metabolism, eight patients have AVPR2 mutations, five patients have AQP2 mutations and two patients have AVP-NPII mutations. Of the patients, which have AVPR2 mutations, one is compound heterozygous for AVPR2 gene. Seven of these mutations are novel. Comparison of the clinical outcomes of these mutations may facilitate in understanding the functions of AVP-NPII, AQP2, and AVPR2 genes in future studies.

  15. A novel mutation affecting the arginine-137 residue of AVPR2 in dizygous twins leads to nephrogenic diabetes insipidus and attenuated urine exosome aquaporin-2.

    PubMed

    Hinrichs, Gitte R; Hansen, Louise H; Nielsen, Maria R; Fagerberg, Christina; Dieperink, Hans; Rittig, Søren; Jensen, Boye L

    2016-04-01

    Mutations in the vasopressin V2 receptor gene AVPR2 may cause X-linked nephrogenic diabetes insipidus by defective apical insertion of aquaporin-2 in the renal collecting duct principal cell. Substitution mutations with exchange of arginine at codon 137 can cause nephrogenic syndrome of inappropriate antidiuresis or congenital X-linked nephrogenic diabetes insipidus. We present a novel mutation in codon 137 within AVPR2 with substitution of glycine for arginine in male dizygotic twins. Nephrogenic diabetes insipidus was demonstrated by water deprivation test and resistance to vasopressin administration. While a similar urine exosome release rate was shown between probands and controls by western blotting for the marker ALIX, there was a selective decrease in exosome aquaporin-2 versus aquaporin-1 protein in probands compared to controls.

  16. Adipsia increases risk of death in patients with central diabetes insipidus.

    PubMed

    Arima, Hiroshi; Wakabayashi, Toshihiko; Nagatani, Tetsuya; Fujii, Masazumi; Hirakawa, Akihiro; Murase, Takashi; Yambe, Yuko; Yamada, Tsutomu; Yamakawa, Fumiko; Yamamori, Ikuo; Yamauchi, Masako; Oiso, Yutaka

    2014-01-01

    Central diabetes insipidus (CDI) is caused by deficiency of arginine vasopressin, an antidiuretic hormone. Patients with CDI manifest polyuria which is usually compensated for by increases in water intake. However, some patients are not able to sense thirst due to the destruction of osmoreceptors in the hypothalamus. These adipsic CDI patients are easily dehydrated and the consequent dehydration could be life-threatening. The objective of this study was to investigate the prognosis of adipsic CDI patients. We have reviewed 149 patients with CDI in three hospitals using databases of the electronic medical recording systems, and examined whether adipsia could affect the morbidity and mortality in CDI patients with multivariable analyses. Twenty-three patients with CDI were adipsic while the remaining 126 patients were non-adipsic. The multivariate analyses showed that the incidence of serious infections which required hospitalization was significantly higher in the adipsic CDI patients compared to that in non-adipsic CDI patients (p <0.001). A total of 6 patients with CDI died during the follow-up (median duration; 60 months, range 1 to 132 months). Four of them were adipsic, three of whom died of infection. The statistical analyses revealed that the risk of death in adipsic CDI patients was significantly higher than in non-adipsic patients (p =0.007). It is thus suggested that adipsic CDI patients were susceptible to serious infections which could be the causes of death.

  17. Occult Langerhans Cell Histiocytosis Presenting with Papillary Thyroid Carcinoma, a Thickened Pituitary Stalk and Diabetes Insipidus.

    PubMed

    Gordon, Michael S; Gordon, Murray B

    2016-01-01

    Etiologies of a thickened stalk include inflammatory, neoplastic, and idiopathic origins, and the underlying diagnosis may remain occult. We report a patient with a thickened pituitary stalk (TPS) and papillary thyroid carcinoma (PTC) whose diagnosis remained obscure until a skin lesion appeared. The patient presented with PTC, status postthyroidectomy, and I(131) therapy. PTC molecular testing revealed BRAF mutant (V600E, GTC>GAG). She had a 5-year history of polyuria/polydipsia. Overnight dehydration study confirmed diabetes insipidus (DI). MRI revealed TPS with loss of the posterior pituitary bright spot. Evaluation showed hypogonadotropic hypogonadism and low IGF-1. Chest X-ray and ACE levels were normal. Radiographs to evaluate for extrapituitary sites of Langerhans Cell Histiocytosis (LCH) were unremarkable. Germinoma studies were negative: normal serum and CSF beta-hCG, alpha-fetoprotein, and CEA. Three years later, the patient developed vulvar labial lesions followed by inguinal region skin lesions, biopsy of which revealed LCH. Reanalysis of thyroid pathology was consistent with concurrent LCH, PTC, and Hashimoto's thyroiditis within the thyroid. This case illustrates that one must be vigilant for extrapituitary manifestations of systemic diseases to diagnose the etiology of TPS. An activating mutation of the protooncogene BRAF is a potential unifying etiology of both PTC and LCH.

  18. Novel AQP2 mutation causing congenital nephrogenic diabetes insipidus: challenges in management during infancy.

    PubMed

    Rugpolmuang, Rottanat; Deeb, Asma; Hassan, Yousef; Deekajorndech, Tawatchai; Shotelersuk, Vorasuk; Sahakitrungruang, Taninee

    2014-01-01

    Congenital nephrogenic diabetes insipidus (NDI) is a rare inherited disorder, mostly caused by AVPR2 mutations. Less than 10% of cases are due to mutations in the aquaporin-2 (AQP2) gene. Diagnosis and management of this condition remain challenging especially during infancy. Here, we report two unrelated patients, a 6-month-old Thai boy and a 5-year-old Emirati girl, with a history of failure to thrive, chronic fever, polydipsia, and polyuria presented in early infancy. The results of water deprivation test were compatible with a diagnosis of NDI. The entire coding regions of the AVPR2 and AQP2 gene were amplified by polymerase chain reaction and sequenced. Patient 1 was homozygous for a novel missense AQP2 mutation p.G96E, inherited from both parents. Patient 2 harbored a previously described homozygous p.T126M mutation in the AQP2 gene. Both patients were treated with a combination of thiazide diuretics and amiloride. Patient 1 developed paradoxical hyponatremia and severe dehydration 2 weeks after medical treatment began. In conclusion, we report a novel mutation of the AQP2 gene and highlight an important role of genetic testing for definite diagnosis. Vigilant monitoring of the fluid status and electrolytes after beginning the therapy is mandatory in infants with NDI.

  19. Stiletto stabbing: penetrating injury to the hypothalamus with hyperacute diabetes insipidus.

    PubMed

    Itshayek, Eyal; Gomori, John Moshe; Spektor, Sergey; Cohen, José E

    2010-12-01

    Diabetes insipidus (DI) is a well documented complication observed after traumatic head injuries. We report a case of hyperacute onset DI in a 19-year-old male who sustained a hypothalamic-pituitary injury when he was stabbed in the head with a 30-cm long thin-bladed knife. At CT, our patient showed significant hemorrhagic contusions of the lower hypothalamus. He developed polydipsia, polyuria, and mild hypernatremia in the Emergency Department. Diagnostic digital subtraction angiography showed a hypervascular congestive pituitary gland with prominent draining veins. On the third day his hypernatremia became severe (183mEq/L). He was managed with parenteral fluids and a regimen of intranasal DDAVP (1-desamino 8-d-arginine vasopressin), leading to improved plasmatic sodium levels, urine output, and urinary specific gravity. In patients presenting with hyperacute posttraumatic DI, emergency room physicians and neurosurgeons should rule out direct injury to the hypothalamus and/or the posterior lobe of the pituitary, and initiate early pharmacological treatment.

  20. Comparison of incidence of hyponatremia between intranasal and oral desmopressin in patients with central diabetes insipidus.

    PubMed

    Kataoka, Yuko; Nishida, Sachi; Hirakawa, Akihiro; Oiso, Yutaka; Arima, Hiroshi

    2015-01-01

    Central diabetes insipidus (CDI), which is characterized by polyuria and polydipsia, is caused by a deficiency of the antidiuretic hormone arginine vasopressin (AVP). While CDI is treated with desmopressin, an analogue of AVP, the intranasal formulation is inconvenient and CDI patients reportedly prefer the oral formulation to the intranasal one. In Japan, intranasal desmopressin had been the only formulation for the treatment of CDI until 2012, when the desmopressin orally disintegrating tablet (ODT) was approved for treatment. In this study we analyzed 26 patients with CDI in whom intranasal desmopressin was switched to desmopressin ODT. The mean daily dose of intranasal desmopressin was 10 ± 8 μg/day, and that of desmopressin ODT was 142 ± 59 μg/day. The mean serum sodium levels were 140 ± 5 mmol/L and 140 ± 3 mmol/L with intranasal desmopressin and desmopressin ODT, respectively, and there were no significant differences between these values. The frequency of hyponatremia (<135 mmol/L) with intranasal desmopressin was 11.7% and that with desmopressin ODT was 7.6%, while the frequency of hyponatremia (<130 mmol/L) with intranasal desmopressin was 4.2% and that with desmopressin ODT was 1.3%. Statistical analyses revealed that incidence of hyponatremia was significantly decreased after the switch to desmopressin ODT. Thus, it is suggested that water balance is better controlled with desmopressin ODT than with intranasal desmopressin in patients with CDI.

  1. [Systemic necrotizing vasculitis presenting as gangrene combined with diabetes insipidus: a case report].

    PubMed

    Huang, Qing; Liu, Yu-lan

    2015-12-18

    The male patient reported here presented as gangrene and central diabetes insipidus (CDI), who had characteristics of vasculitis. The patient complained about polydipsia and polyuria half a year ago, and then developed tingling, pain and blackish discoloration of some fingers and toes 3 month ago. He also had Raynaud's phenomenon. After admission, his laboratory examination showed the rise of erythrocyte sedimentation rate, C-reactive protein, immunoglobulin, β2-glycoprotein I and the activity of rheumatoid factors, lupus anticoagulant test. his pituitary gland showed loss of posterior signal on magnetic resonance imaging. In addition, his vasopressin test was active. However, there was no sufficient evidence to diagnose any specific disease; as a consequence the patient was diagnosed as idiopathic systemic necrotizing vasculitis (SNV). For SNV, the patient was treated with glucocorticoid 40 mg/d and impact therapy of cyclophosphamide 0.4 g every 2 weeks. He also received symptomatic treatment for gangrene and CDI. Cutaneous involvement leading to gangrene was widely reported in SNV, however pituitary involvement in SNV leading to CDI was rare. The prognosis of this patient was poor.

  2. Cholesteatoma in the Sellar Region Presenting as Hypopituitarism and Diabetes Insipidus.

    PubMed

    Kong, Xiangyi; Wu, Huanwen; Ma, Wenbin; Li, Yongning; Xing, Bing; Kong, Yanguo; Wang, Renzhi

    2016-03-01

    Clinically significant sellar cysts unrelated to pituitary adenomas are uncommon. Intracranial cholesteatomas are also rare and are most common in the middle ear and mastoid region. We report an even rarer case of cholesteatoma in the sellar region-a challenging diagnosis guided by clinical presentations, radiological signs, and biopsy, aiming at emphasize the importance of considering cholesteatoma when making differential diagnoses of sellar lesions.We present a case of cholesteatoma in the sellar region in a 56-year-old man with hypopituitarism, diabetes insipidus, and cystic imaging findings. It was difficult to make an accurate diagnosis before surgery. We present detailed analysis of the patient's disease course and review pertinent literature.The patient underwent a surgical exploration and tumor resection through a transsphenoidal approach. Pathologic results revealed a cholesteatoma. The patient's symptoms improved a lot after surgery, and the postoperative period was uneventful. Taken together, the lesion's imaging appearance, pathological characteristics, and clinical features were all unique features that lead to a diagnosis of cholesteatoma.As we did not see such reports by Pubmed and EMBASE, we believe this is the first reported case of sellar cholesteatoma presenting in this manner. This article emphasized that cholesteatomas, although rare, should be considered part of the differential diagnosis of sellar lesions.

  3. Congenital nephrogenic diabetes insipidus with a novel mutation in the aquaporin 2 gene.

    PubMed

    Park, Youn Jong; Baik, Haing Woon; Cheong, Hae Il; Kang, Ju Hyung

    2014-07-01

    Congenital nephrogenic diabetes insipidus (CNDI) is a rare disorder caused by mutations of the arginine vasopressin (AVP) V2 receptor or aquaporin 2 (AQP2) genes. The current study presented the case of CNDI in a 1-month-old male with a novel mutation in the AQP2 gene. The patient was referred due to the occurrence of hypernatremia and mild-intermittent fever since birth. An AVP stimulation test was compatible with CNDI as there was no significant response to desmopressin. Molecular genetic analysis demonstrated two mutations in exon 1 of the AQP2 gene: C to T transition, which resulted in a missense mutation of (108)Thr (ACG) to Met (ATG); and a 127, 128 delCA, which resulted in a deletion mutation of glutamine in position 43 at codon CAG as the first affected amino acid, with the new reading frame endign in a termination codon at position 62. The molecular genetic analysis of the parents showed that the missense mutation was inherited maternally and the deletion mutation was inherited paternally. The parents showed no signs or symptoms of CNDI, indicating autosomal recessive inheritance. The (108)Thr (ACG) to Met (ATG) mutation was confirmed as a novel mutation. Therefore, the molecular identification of the AQP2 gene has clinical significance, as early recognition of CNDI in infants that show only non-specific symptoms, can be facilitated. Thus, repeated episodes of dehydration, which may cause physical and mental retardation can be avoided.

  4. A Case of IgG4-Related Hypophysitis Presented with Hypopituitarism and Diabetes Insipidus.

    PubMed

    Harano, Yumi; Honda, Kazufumi; Akiyama, Yurika; Kotajima, Lisa; Arioka, Hiroko

    2015-01-01

    Immunoglobulin (Ig) G4-related systemic syndrome is a recently described entity characterized by elevated serum IgG4 and tissue infiltration of IgG4-positive plasma cells. Pituitary gland can be involved as hypophysitis. We report a case of a 72-year-old man, who presented with general fatigue and weakness. Laboratory tests revealed diabetes insipidus as well as hypopituitarism including adrenal insufficiency, hypogonadism, and hypothyroidism. His serum IgG4 was elevated. MR images showed enlargement of the pituitary stalk. Multiple nodules in bilateral kidneys were pointed out in the abdominal CT. Histological examination of the nodules showed increased IgG4-positive plasma cells. We diagnosed him with IgG4-related kidney disease and hypophysitis. After treatment with hydrocortisone, his symptoms improved. The follow-up images showed that almost all renal nodules disap-peared and his pituitary stalk was shrinking. Our case appears to be very sensitive to glucocorticoid and suggests the possibility of treating IgG4-related hypophysitis successfully with a lower dose of glucocorticoid.

  5. Mouse model of inducible nephrogenic diabetes insipidus produced by floxed aquaporin-2 gene deletion.

    PubMed

    Yang, Baoxue; Zhao, Dan; Qian, Liman; Verkman, A S

    2006-08-01

    Transgenic mouse models of defective urinary concentrating ability produced by deletion of various membrane transport or receptor proteins, including aquaporin-2 (AQP2), are associated with neonatal mortality from polyuria. Here, we report an inducible mouse model of AQP2 gene deletion with severe polyuria in adult mice. LoxP sequences were inserted into introns 1 and 2 in the mouse AQP2 gene by homologous recombination in embryonic stem cells. Mating of germ-line AQP2-loxP mice with tamoxifen-inducible Cre-expressing mice produced offspring with inducible homozygous Cre-AQP2-loxP, which had a normal phenotype. Tamoxifen injections over 10 days resulted in AQP2 gene excision, with undetectable full-length AQP2 transcript in kidney and a >95% reduction in immunoreactive AQP2 protein. Urine osmolality decreased from approximately 2,000 to <500 mosmol/kgH(2)O after 4-5 days, with urine output increasing from 2 to 25 ml/day. Urine osmolality did not increase after water deprivation. Interestingly, AQP3 protein expression in the collecting duct was increased by about fivefold after AQP2 gene excision. Mild renal damage was seen after 6 wk of polyuria, with collecting duct dilatation, yet normal creatinine clearance and serum chemistries. These results establish the first adult model of nephrogenic diabetes insipidus (NDI) caused by AQP2 deficiency, with daily urine output comparable to body weight, although remarkable preservation of renal function compared with non-inducible NDI models.

  6. Nephrogenic diabetes insipidus: essential insights into the molecular background and potential therapies for treatment.

    PubMed

    Moeller, Hanne B; Rittig, Søren; Fenton, Robert A

    2013-04-01

    The water channel aquaporin-2 (AQP2), expressed in the kidney collecting ducts, plays a pivotal role in maintaining body water balance. The channel is regulated by the peptide hormone arginine vasopressin (AVP), which exerts its effects through the type 2 vasopressin receptor (AVPR2). Disrupted function or regulation of AQP2 or the AVPR2 results in nephrogenic diabetes insipidus (NDI), a common clinical condition of renal origin characterized by polydipsia and polyuria. Over several years, major research efforts have advanced our understanding of NDI at the genetic, cellular, molecular, and biological levels. NDI is commonly characterized as hereditary (congenital) NDI, arising from genetic mutations in the AVPR2 or AQP2; or acquired NDI, due to for exmple medical treatment or electrolyte disturbances. In this article, we provide a comprehensive overview of the genetic, cell biological, and pathophysiological causes of NDI, with emphasis on the congenital forms and the acquired forms arising from lithium and other drug therapies, acute and chronic renal failure, and disturbed levels of calcium and potassium. Additionally, we provide an overview of the exciting new treatment strategies that have been recently proposed for alleviating the symptoms of some forms of the disease and for bypassing G protein-coupled receptor signaling.

  7. Unmasking of undiagnosed pre-existing central diabetes insipidus after renal transplantation.

    PubMed

    Kim, David D W; Holdaway, Ian M

    2012-03-01

    Acquired central diabetes insipidus (CDI) often occurs abruptly after a cranial event causing hypothalamic or pituitary damage. We present a case of a patient with pre-existing and clinically unapparent CDI which was unmasked after renal transplantation. A 60 year old woman with end-stage renal failure due to autosomal dominant polycystic kidney disease (ADPKD) underwent renal transplantation. She was noted to be markedly polyuric and polydipsic after the transplant. A fluid deprivation test was unequivocally positive for CDI, and desmopressin treatment resulted in immediate symptom relief. Neuroimaging revealed a midline defect in the region of the hypothalamus. She had a history of an intracerebral aneurysm that had ruptured, requiring extensive neurosurgery many years previously. This case demonstrates a rare instance of pre-existing but clinically unapparent CDI unmasked by renal transplantation. It is likely that renal failure due to ADPKD disguised her CDI prior to transplantation. A previous intracerebral insult from an aneurysmal bleed is the likely cause of her vasopressin deficiency.

  8. Diabetes insipidus contributes to traumatic brain injury pathology via CD36 neuroinflammation.

    PubMed

    Diamandis, Theo; Gonzales-Portillo, Chiara; Gonzales-Portillo, Gabriel S; Staples, Meaghan; Borlongan, Mia C; Hernandez, Diana; Acosta, Sandra; Borlongan, Cesar V

    2013-11-01

    Each year, over one million people in the United States are affected by traumatic brain injury (TBI). Symptoms of both acute and chronic neuroinflammation follow TBI, coinciding with a robust immune response and activation of the brain's endogenous repair mechanisms. TBI can lead to endocrine failure as a result of damage to the thalamic region of the brain, evidenced by excessive thirst and polyuria often accompanying TBI. These symptoms indicate the presence of diabetes insipidus (DI), a disruption of water homeostasis due to antidiuretic hormone deficiency. This deficiency accompanies a mechanical or neuroinflammatory damage to the thalamic region during TBI, evidenced by increased expression of inflammatory microglial marker MHCII in this brain region. Excessive thirst and urinations, which are typical DI symptoms, in our chronic TBI rats also suggest a close connection between TBI and DI. We seek to bridge this gap between TBI and DI through investigation of the Cluster of Differentiation 36 (CD36) receptor. This receptor is associated with Low-Density Lipoprotein (LDL) deregulation, pro-inflammatory events, and innate immunity regulation. We posit that CD36 exacerbates TBI through immune activation and subsequent neuroinflammation. Indeed, scientific evidence already supports pathological interaction of CD36 in other neurological disorders including stroke and Alzheimer's disease. We propose that DI contributes to TBI pathology via CD36 neuroinflammation. Use of CD36 as a biomarker may provide insights into treatment and disease pathology of TBI and DI. This unexplored avenue of research holds potential for a better understanding and treatment of TBI and DI.

  9. Progressive polyuria without vasopressin neuron loss in a mouse model for familial neurohypophysial diabetes insipidus.

    PubMed

    Hayashi, Masayuki; Arima, Hiroshi; Ozaki, Noriyuki; Morishita, Yoshiaki; Hiroi, Maiko; Ozaki, Nobuaki; Nagasaki, Hiroshi; Kinoshita, Noriaki; Ueda, Masatsugu; Shiota, Akira; Oiso, Yutaka

    2009-05-01

    Familial neurohypophysial diabetes insipidus (FNDI), an autosomal dominant disorder, is mostly caused by mutations in the gene of neurophysin II (NPII), the carrier protein of arginine vasopressin (AVP). Previous studies suggest that loss of AVP neurons might be the cause of polyuria in FNDI. Here we analyzed knockin mice expressing mutant NPII that causes FNDI in humans. The heterozygous mice manifested progressive polyuria as do patients with FNDI. Immunohistochemical analyses revealed that inclusion bodies that were not immunostained with antibodies for mutant NPII, normal NPII, or AVP were present in the AVP cells in the supraoptic nucleus (SON), and that the size of inclusion bodies gradually increased in parallel with the increases in urine volume. Electron microscopic analyses showed that aggregates existed in the endoplasmic reticulum (ER) as well as in the nucleus of AVP neurons in 1-mo-old heterozygous mice. At 12 mo, dilated ER filled with aggregates occupied the cytoplasm of AVP cells, while few aggregates were found in the nucleus. Analyses with in situ hybridization revealed that expression of AVP mRNA was significantly decreased in the SON in the heterozygous mice compared with that in wild-type mice. Counting cells expressing AVP mRNA in the SON indicated that polyuria had progressed substantially in the absence of neuronal loss. These data suggest that cell death is not the primary cause of polyuria in FNDI, and that the aggregates accumulated in the ER might be involved in the dysfunction of AVP neurons that lead to the progressive polyuria.

  10. X-linked recessive nephrogenic diabetes insipidus: a clinico-genetic study.

    PubMed

    Hong, Che Ry; Kang, Hee Gyung; Choi, Hyun Jin; Cho, Min Hyun; Lee, Jung Won; Kang, Ju Hyung; Park, Hye Won; Koo, Ja Wook; Ha, Tae-Sun; Kim, Su-Yung; Il Cheong, Hae

    2014-01-01

    A retrospective genotype and phenotype analysis of X-linked congenital nephrogenic diabetes insipidus (NDI) was conducted on a nationwide cohort of 25 (24 male, 1 female) Korean children with AVPR2 gene mutations, comparing non-truncating and truncating mutations. In an analysis of male patients, the median age at diagnosis was 0.9 years old. At a median follow-up of 5.4 years, urinary tract dilatations were evident in 62% of patients and their median glomerular filtration rate was 72 mL/min/1.73 m2. Weights and heights were under the 3rd percentile in 22% and 33% of patients, respectively. One patient had low intelligence quotient and another developed end-stage renal disease. No statistically significant genotype-phenotype correlation was found between non-truncating and truncating mutations. One patient was female; she was analyzed separately because inactivation and mosaicism of the X chromosome may influence clinical manifestations in female patients. Current unsatisfactory long-term outcome of congenital NDI necessitates a novel therapeutic strategy.

  11. Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus.

    PubMed

    Khositseth, Sookkasem; Uawithya, Panapat; Somparn, Poorichaya; Charngkaew, Komgrid; Thippamom, Nattakan; Hoffert, Jason D; Saeed, Fahad; Michael Payne, D; Chen, Shu-Hui; Fenton, Robert A; Pisitkun, Trairak

    2015-12-17

    Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization, and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI.

  12. Membrane Protein Stability Analyses by Means of Protein Energy Profiles in Case of Nephrogenic Diabetes Insipidus

    PubMed Central

    Heinke, Florian; Labudde, Dirk

    2012-01-01

    Diabetes insipidus (DI) is a rare endocrine, inheritable disorder with low incidences in an estimated one per 25,000–30,000 live births. This disease is characterized by polyuria and compensatory polydypsia. The diverse underlying causes of DI can be central defects, in which no functional arginine vasopressin (AVP) is released from the pituitary or can be a result of defects in the kidney (nephrogenic DI, NDI). NDI is a disorder in which patients are unable to concentrate their urine despite the presence of AVP. This antidiuretic hormone regulates the process of water reabsorption from the prourine that is formed in the kidney. It binds to its type-2 receptor (V2R) in the kidney induces a cAMP-driven cascade, which leads to the insertion of aquaporin-2 water channels into the apical membrane. Mutations in the genes of V2R and aquaporin-2 often lead to NDI. We investigated a structure model of V2R in its bound and unbound state regarding protein stability using a novel protein energy profile approach. Furthermore, these techniques were applied to the wild-type and selected mutations of aquaporin-2. We show that our results correspond well to experimental water ux analysis, which confirms the applicability of our theoretical approach to equivalent problems. PMID:22474537

  13. Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus

    PubMed Central

    Khositseth, Sookkasem; Uawithya, Panapat; Somparn, Poorichaya; Charngkaew, Komgrid; Thippamom, Nattakan; Hoffert, Jason D.; Saeed, Fahad; Michael Payne, D.; Chen, Shu-Hui; Fenton, Robert A.; Pisitkun, Trairak

    2015-01-01

    Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization, and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI. PMID:26674602

  14. Disorders of water metabolism: diabetes insipidus and the syndrome of inappropriate antidiuretic hormone secretion.

    PubMed

    Verbalis, Joseph G

    2014-01-01

    Disorders of body fluids are among the most commonly encountered problems in the practice of clinical medicine. This is in large part because many different disease states can potentially disrupt the finely balanced mechanisms that control the intake and output of water and solute. It therefore behooves clinicians treating such patients to have a good understanding of the pathophysiology, the differential diagnosis and the management of these disorders. Since body water is the primary determinant of the osmolality of the extracellular fluid (ECF), disorders of body water homeostasis can be divided into hypoosmolar disorders, in which there is an excess of body water relative to body solute, and hyperosmolar disorders, in which there is a deficiency of body water relative to body solute. The classical hyperosmolar disorder is diabetes insipidus (DI), and the classical hypoosmolar disorder is the syndrome of inappropriate antidiuretic hormone secretion (SIADH). This chapter first reviews the regulatory mechanisms underlying water and sodium metabolism, the two major determinants of body fluid homeostasis. The major disorders of water metabolism causing hyperosmolality and hypoosmolality, DI and SIADH, are then discussed in detail, including the pathogenesis, differential diagnosis and treatment of these disorders.

  15. Identification of five novel arginine vasopressin gene mutations in patients with familial neurohypophyseal diabetes insipidus.

    PubMed

    Tian, Dan; Cen, Jing; Nie, Min; Gu, Feng

    2016-10-01

    Familial neurohypophyseal diabetes insipidus (FNDI) is a genetic disorder presenting with polyuria and polydipsia and is caused by mutations in the arginine vasopressin-neurophysin II (AVP-NPII) gene. The clinical manifestations of this disorder vary greatly depending on different mutations. The present study reports the genetic, clinical and biochemical characteristics of patients with FNDI caused by five novel mutations. Ten patients encompassing two pedigrees and four individual cases diagnosed with FNDI were included. Biochemical markers and magnetic resonance imaging (MRI) were evaluated and genomic DNA was sequenced. The results revealed that age at onset ranged from 1.0 to 11.0 years. Daily urine volumes ranged from 2.0 to 12.0 liters. One patient had mental retardation and three patients had puberty retardation; one patient had nausea, vomiting and mental retardation; and two patients had fever. Treatments, if given, included desmopressin and vasopressin tannate. Posterior pituitary T1-weighted MRI high-intensity signals were absent in two cases and present in four cases. Sequencing revealed five novel mutations in the AVP-NPII gene. On the whole, the findings of the present study indicate that FNDI exhibits different clinical manifestations and a diverse age at onset. Posterior pituitary MRI does not provide a definite diagnosis of FNDI. We also identified five novel AVP-NPII mutations. Thus, an enhanced understanding of FNDI pathogenesis may provide a basis for the development of presymptomatic FNDI diagnotic tools.

  16. [Vasopressin V2 receptor-related pathologies: congenital nephrogenic diabetes insipidus and nephrogenic syndrome of inappropiate antidiuresis].

    PubMed

    Morin, Denis

    2014-12-01

    Congenital nephrogenic diabetes insipidus is a rare hereditary disease with mainly an X-linked inheritance (90% of the cases) but there are also autosomal recessive and dominant forms. Congenital nephrogenic diabetes insipidus is characterized by a resistance of the renal collecting duct to the action of the arginine vasopressin hormone responsible for the inability of the kidney to concentrate urine. The X-linked form is due to inactivating mutations of the vasopressin 2 receptor gene leading to a loss of function of the mutated receptors. Affected males are often symptomatic in the neonatal period with a lack of weight gain, dehydration and hypernatremia but mild phenotypes may also occur. Females carrying the mutation may be asymptomatic but, sometimes, severe polyuria is found due to the random X chromosome inactivation. The autosomal recessive and dominant forms, occurring in both genders, are linked to mutations in the aquaporin-2 gene. The treatment remains difficult, especially in infants, and is based on a low osmotic diet with increased water intake and the use of thiazides and indomethacin. The main goal is to avoid hypernatremic episodes and maintain a good hydration state. Potentially, specific treatment, in some cases of X-linked congenital nephrogenic diabetes insipidus, with pharmacological chaperones such as non-peptide vasopressin-2 receptor antagonists will be available in the future. Conversely, the nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is linked to a constitutive activation of the V(2)-receptor due to activating mutations with clinical and biological features of inappropriate antidiuresis but with low or undetectable plasma arginine vasopressin hormone levels.

  17. Proximal tubular dysfunction associated with tenofovir and didanosine causing Fanconi syndrome and diabetes insipidus: a report of 3 cases.

    PubMed

    Irizarry-Alvarado, Joan M; Dwyer, Jamie P; Brumble, Lisa M; Alvarez, Salvador; Mendez, Julio C

    2009-03-01

    We report 3 cases of patients with HIV/AIDS in whom Fanconi syndrome and nephrogenic diabetes insipidus developed secondary to use of an antiretroviral regimen containing tenofovir disoproxil fumarate and didanosine. These patients presented with a history of polydipsia, polyuria, weight loss, anorexia, and wasting. Interestingly, 1 patient was not taking protease inhibitors. This response is a well-documented yet uncommon complication of tenofovir use in the HIV population. We recommend continued monitoring for renal toxicity when using NRTI combination of tenofovir and didanosine.

  18. Myelodysplastic syndrome complicated by central diabetes insipidus and cerebral salt wasting syndrome with peculiar change in magnetic resonance images.

    PubMed

    Sano, Soichi; Yamagami, Keiko; Morikawa, Takashi; Yoshioka, Katsunobu

    2010-01-01

    Central diabetes insipidus (CDI) could occurs in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), because of infiltration of leukemic cells into the neurohypophysis or some other reason and it is closely associated with abnormalities of chromosome 7. We report a case of MDS with abnormalities of chromosome 7, presenting as CDI followed by deterioration of polyuria and hyponatremia with a decreased extracellular fluid volume. Magnetic resonance imaging (MRI) revealed symmetrically enhanced lesions in the hypothalamus. Fludrocortisone treatment normalized his serum sodium level and cerebral salt wasting syndrome (CSWS) was suspected.

  19. From idiopathic diabetes insipidus to neurodegenerative Langerhans cell histiocytosis--an unusual presentation and progression of disease.

    PubMed

    Hayward, Rachel M; Nicolin, Gary; Kennedy, Charles; Joy, Harriet; Davies, Justin H

    2011-01-01

    Diabetes insipidus (DI) is rare in childhood and has a wide-ranging aetiology including the involvement of uncontrolled proliferation of dendritic cells in the hypothalamic-pituitary axis, characteristic of Langerhans cell histiocytosis (LCH). DI may manifest as a sequela of multisystem LCH disease involving skin, bone, liver, spleen and lymph nodes. In very rare cases patients diagnosed with LCH exhibit neurodegenerative changes, such as severe ataxia, tremor, dysarthria and intellectual impairment. We report a 2 1/2-year-old boy who presented initially with apparent idiopathic DI, developed anterior pituitary hormone deficiency and progressive neurological deterioration secondary to neurodegenerative LCH.

  20. Transient polyuria related to central diabetes insipidus caused by lymphocytic infundibulo-neurohypophysitis in a patient treated for Graves' disease.

    PubMed

    Yamazaki, Masanori; Sato, Ai; Nishio, Shin-ichi; Uehara, Takeshi; Komatsu, Mitsuhisa

    2010-01-01

    A 45-year-old man was hospitalized because of weight loss, finger tremor, thirst, polydipsia and increased urinary frequency. He was diagnosed with Graves' disease (GD) and central diabetes insipidus (CDI). Magnetic resonance imaging revealed the enlarged posterior pituitary with thickened stalk. Histological examination obtained from biopsy of the pituitary revealed lymphocytic infundibulo-neurohypophysitis. He received treatment with thiamazole (MMI) for GD and desmopressin acetate (DDAVP) for CDI. However, DDAVP administration could be discontinued as GD was gradually improved. This course indicates that not only the recovered renal response to arginine-vasopressin but also the immunomodulative effects of MMI might attribute to the improvement of polyuria.

  1. Clinical guidelines for management of diabetes insipidus and syndrome of inappropriate antidiuretic hormone secretion after pituitary surgery.

    PubMed

    Lamas, Cristina; del Pozo, Carlos; Villabona, Carles

    2014-04-01

    Changes in water metabolism and regulation of vasopressin (AVP) or antidiuretic hormone (ADH) are common complications of pituitary surgery. The scarcity of studies comparing different treatment and monitoring strategies for these disorders and the lack of prior clinical guidelines makes it difficult to provide recommendations following a methodology based on grades of evidence. This study reviews the pathophysiology of diabetes insipidus and inappropriate ADH secretion after pituitary surgery, and is intended to serve as a guide for their diagnosis, differential diagnosis, treatment, and monitoring.

  2. Recurring dominant-negative mutations in the AVP-NPII gene cause neurohypophyseal diabetes insipidus

    SciTech Connect

    Repaske, D.R.; Phillips, J.A.; Krishnamani, M.R.S.

    1994-09-01

    Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a familial form of arginine vasopressin (or antidiuretic hormone) deficiency that is usually manifest in early childhood with polyuria, polydipsia and an antidiuretic response to exogenous vasopressin or its analogs. The phenotype is postulated to arise from gliosis and depletion of the magnocellular neurons that produce vasopressin in the supraoptic and paraventricular nuclei of the hypothalamus. ADNDI is caused by heterozygosity for a variety of mutations in the AVP-NPII gene which encodes vasopressin, its carrier protein (NPII) and a glycoprotein (copeptin) of unknown function. These mutations include: (1) Ala 19{r_arrow}Thr (G279A) in AVP`s signal peptide, (2) Gly 17{r_arrow}Val (G1740T), (3) Pro 24{r_arrow}Leu (C1761T), (4) Gly 57{r_arrow}Ser (G1859A) and (5) del Glu 47({delta}AGG 1824-26), all of which occur in NPII. In characterizing the AVP-NPII mutations in five non-related ADNDI kindreds, we have detected two kindreds having mutation 1 (G279A), two having mutation 3 (C1761T) and one having mutation 4 (G1859A) without any other allelic changes being detected. Two of these recurring mutations (G279A and G1859A) are transitions that occur at CpG dinucleotides while the third (C1761T) does not. Interestingly, families with the same mutations differed in their ethnicity or in their affected AVP-NPII allele`s associated haplotype of closely linked DNA polymorphisms. Our data indicated that at least three of five known AVP-NPII mutations causing ADNDI tend to recur but the mechanisms by which these dominant-negative mutations cause variable or progressive expression of the ADNDI phenotype remain unclear.

  3. Desmopressin duration of antidiuretic action in patients with central diabetes insipidus.

    PubMed

    Juul, Kristian Vinter; Bichet, Daniel G; Nørgaard, Jens Peter

    2011-08-01

    The key question answered by this study is whether it is possible to deliver a pharmacokinetic and pharmacodynamic duration of antidiuretic action long enough to ensure adequate antidiuresis with two daily administrations of desmopressin in patients with central diabetes insipidus (CDI). We studied the efficacy and safety of desmopressin i.v. in 13 CDI patients using two 3-way crossover designs, in the doses 30, 60, 125 ng, and 125, 250 and 500 ng. Duration of action, minimum output rate, max osmolality and average osmolality during action (AUC osmolality) were measured every 30 min for the first 2 h during the infusion, and then every hour or every second hour until the urine output rate was greater than 2 ml/kg/30 min. The duration of antidiuretic action was 4, 8 and 11 h, respectively, for 125, 250, and 500 ng, increasing from 250 to 500 ng but for the remaining secondary dynamic efficacy parameters no difference could be detected based on descriptive statistics between the doses 250 and 500 ng, indicating that the upper plateau region of the dose-response curve had been reached. All treatment emergent adverse events were classified as unrelated or unlikely related to trial medication. No serious adverse events occurred. Data on duration of action indicates that it is possible to achieve antidiuretic control with 500 ng i.v. corresponding to 160 μg orodispersible tablets twice daily in CDI patients. Today, the Minirin Melt label recommends the majority of CDI patients a dose of 60 to 120 μg t.i.d.

  4. X-linked nephrogenic diabetes insipidus: From the ship Hopewell to RFLP studies

    SciTech Connect

    Bichet, D.G.; Lonergan, M.; Arthus, M.F.; Ligier, S.; Kluge, R. ); Hendy, G.N.; Pausova, Z.; Zingg, H.; Morgan, K.; Saenger, P. )

    1992-11-01

    Nephrogenic diabetes insipidus (NDI; designated 304800 in Mendelian Inheritance in Man) is an X-linked disorder with abnormal renal and extrarenal V[sub 2] vasopression receptor responses. The mutant gene has been mapped to Xq28 by analysis of RFLPs, and tight linkage between DXS52 and DNI has been reported. In 1969, Bode and Crawford proposed, under the term, the Hopewell hypothesis' that most cases in North America could be traced to descendants of Ulster Scots who arrived in Nova Scotia in 1761 on the ship Hopewell. They also suggested a link between this family and a large Mormon pedigree. DNA samples obtained from 13 independent affected families, including 42 members of the Hopewell and Mormon pedigrees, were analyzed with probes in the Xq28 region. Genealogical reconstructions were performed. Linkage between NDI and DXS304 (probe U6:2.spl), DXS305 (St35-691), DXS52 (St14-1), DXS15 (DX13), and F8C (F814) showed no recombination in 12 families, with a maximum lod score of 13.5 for DXS52. A recombinant between NDI and DXS304, DXS305, was identified in one family. The haplotype segregating with the disease in the Hopewell pedigree was not shared by other North American families. PCR analysis of the St14 VNTR allowed the distinction of two alleles that were not distinguishable by Southern analysis. Carrier status was predicted in 24 of 26 at-risk females. The Hopewell hypothesis cannot explain the origin of NDI in many of the North American families, since they have no apparent relationship with the Hopewell earlier settlers, either by haplotype or by genealogical analysis. PCR analysis of the DXS52 VNTR in NDI families is very useful for carrier testing and presymptomatic diagnosis, which can prevent the first manifestations of dehydration. 39 refs., 7 figs., 3 tabs.

  5. Surgical biopsies in patients with central diabetes insipidus and thickened pituitary stalks.

    PubMed

    Jian, Fangfang; Bian, Liuguan; Sun, Shouyue; Yang, Jun; Chen, Xiao; Chen, Yufan; Ma, Qinyun; Miao, Fei; Wang, Weiqing; Ning, Guang; Sun, Qingfang

    2014-09-01

    Thickened pituitary stalks (TPSs) on magnetic resonance imaging (MRI) result from diverse pathologies; therefore, it is essential to make specific diagnoses for clinical decision-making. The diagnoses and indications for surgical biopsies in patients with central diabetes insipidus (CDI) and TPSs are thoroughly discussed in this paper. Thirty-seven patients with CDI and TPSs were retrospectively reviewed. The mean age at the diagnosis of CDI was 29.0 ± 15.9 years (range 8.0-63.3), and the median duration of follow-up was 5.5 ± 2.8 years (range 0.7-13.0). Anterior pituitary hormone deficiencies were documented in 26 (70.3 %) patients. All patients had a TPS on MRI at the diagnosis of CDI, and 21 (56.8 %) patients exhibited radiological changes during the follow-up. Of these 21 patients, 11 exhibited increases in the thickness of the stalk, and two patients exhibited reversals of the TPSs. Involvements of the hypothalamus, pituitary gland, basal ganglia or supersellar, and pineal gland were found in four, three, one, and 1 patient, respectively. Ultimately, clear diagnoses were established in 17 patients who underwent biopsies, nine of whom had germinomas, six of whom had Langerhans cell histiocytosis, one of whom had a granular cell tumor, and one of whom had Erdheim-Chester disease. Patients with CDI and TPSs should submit to periodic clinic follow-ups with serial MRI assessments to establish anterior pituitary deficiencies and to detect radiological progressions that are appropriate for surgical biopsies. Endoscopic-assisted microsurgery via the supraorbital keyhole approach is a good choice for the biopsy of pituitary stalk lesions.

  6. Role of adenylyl cyclase 6 in the development of lithium-induced nephrogenic diabetes insipidus.

    PubMed

    Poulsen, Søren Brandt; Kristensen, Tina Bøgelund; Brooks, Heddwen L; Kohan, Donald E; Rieg, Timo; Fenton, Robert A

    2017-04-06

    Psychiatric patients treated with lithium (Li(+)) may develop nephrogenic diabetes insipidus (NDI). Although the etiology of Li(+)-induced NDI (Li-NDI) is poorly understood, it occurs partially due to reduced aquaporin-2 (AQP2) expression in the kidney collecting ducts. A mechanism postulated for this is that Li(+) inhibits adenylyl cyclase (AC) activity, leading to decreased cAMP, reduced AQP2 abundance, and less membrane targeting. We hypothesized that Li-NDI would not develop in mice lacking AC6. Whole-body AC6 knockout (AC6(-/-)) mice and potentially novel connecting tubule/principal cell-specific AC6 knockout (AC6(loxloxCre)) mice had approximately 50% lower urine osmolality and doubled water intake under baseline conditions compared with controls. Dietary Li(+) administration increased water intake and reduced urine osmolality in control, AC6(-/-), and AC6(loxloxCre) mice. Consistent with AC6(-/-) mice, medullary AQP2 and pS256-AQP2 abundances were lower in AC6(loxloxCre) mice compared with controls under standard conditions, and levels were further reduced after Li(+) administration. AC6(loxloxCre) and control mice had a similar increase in the numbers of proliferating cell nuclear antigen-positive cells in response to Li(+). However, AC6(loxloxCre) mice had a higher number of H(+)-ATPase B1 subunit-positive cells under standard conditions and after Li(+) administration. Collectively, AC6 has a minor role in Li-NDI development but may be important for determining the intercalated cell-to-principal cell ratio.

  7. Aquaporin-2: new mutations responsible for autosomal-recessive nephrogenic diabetes insipidus-update and epidemiology.

    PubMed

    Bichet, Daniel G; El Tarazi, Abdulah; Matar, Jessica; Lussier, Yoann; Arthus, Marie-Françoise; Lonergan, Michèle; Bockenhauer, Detlef; Bissonnette, Pierre

    2012-06-01

    It is clinically useful to distinguish between two types of hereditary nephrogenic diabetes insipidus (NDI): a 'pure' type characterized by loss of water only and a complex type characterized by loss of water and ions. Patients with congenital NDI bearing mutations in the vasopressin 2 receptor gene, AVPR2, or in the aquaporin-2 gene, AQP2, have a pure NDI phenotype with loss of water but normal conservation of sodium, potassium, chloride and calcium. Patients with hereditary hypokalemic salt-losing tubulopathies have a complex phenotype with loss of water and ions. They have polyhydramnios, hypercalciuria and hypo- or isosthenuria and were found to bear KCNJ1 (ROMK) and SLC12A1 (NKCC2) mutations. Patients with polyhydramnios, profound polyuria, hyponatremia, hypochloremia, metabolic alkalosis and sensorineural deafness were found to bear BSND mutations. These clinical phenotypes demonstrate the critical importance of the proteins ROMK, NKCC2 and Barttin to transfer NaCl in the medullary interstitium and thereby to generate, together with urea, a hypertonic milieu. This editorial describes two new developments: (i) the genomic information provided by the sequencing of the AQP2 gene is key to the routine care of these patients, and, as in other genetic diseases, reduces health costs and provides psychological benefits to patients and families and (ii) the expression of AQP2 mutants in Xenopus oocytes and in polarized renal tubular cells recapitulates the clinical phenotypes and reveals a continuum from severe loss of function with urinary osmolalities <150 mOsm/kg H2O to milder defects with urine osmolalities >200 mOsm/kg H2O.

  8. 4-PBA improves lithium-induced nephrogenic diabetes insipidus by attenuating ER stress.

    PubMed

    Zheng, Peili; Lin, Yu; Wang, Feifei; Luo, Renfei; Zhang, Tiezheng; Hu, Shan; Feng, Pinning; Liang, Xinling; Li, Chunling; Wang, Weidong

    2016-10-01

    Endoplasmic reticulum (ER) stress has been implicated in some types of glomerular and tubular disorders. The objectives of this study were to elucidate the role of ER stress in lithium-induced nephrogenic diabetes insipidus (NDI) and to investigate whether attenuation of ER stress by 4-phenylbutyric acid (4-PBA) improves urinary concentrating defect in lithium-treated rats. Wistar rats received lithium (40 mmol/kg food), 4-PBA (320 mg/kg body wt by gavage every day), or no treatment (control) for 2 wk, and they were dehydrated for 24 h before euthanasia. Lithium treatment resulted in increased urine output and decreased urinary osmolality, which was significantly improved by 4-PBA. 4-PBA also prevented reduced protein expression of aquaporin-2 (AQP2), pS256-AQP2, and pS261-AQP2 in the inner medulla of kidneys from lithium-treated rats after 24-h dehydration. Lithium treatment resulted in increased expression of ER stress markers in the inner medulla, which was associated with dilated cisternae and expansion of ER in the inner medullary collecting duct (IMCD) principal cells. Confocal immunofluorescence studies showed colocalization of a molecular chaperone, binding IgG protein (BiP), with AQP2 in principal cells. Immunohistochemistry demonstrated increased intracellular expression of BiP and decreased AQP2 expression in IMCD principal cells of kidneys from lithium-treated rats. 4-PBA attenuated expression of ER stress markers and recovered ER morphology. In IMCD suspensions isolated from lithium-treated rats, 4-PBA incubation was also associated with increased AQP2 expression and ameliorated ER stress. In conclusion, in experimental lithium-induced NDI, 4-PBA improved the urinary concentrating defect and increased AQP2 expression, likely via attenuating ER stress in IMCD principal cells.

  9. Role of adenylyl cyclase 6 in the development of lithium-induced nephrogenic diabetes insipidus

    PubMed Central

    Poulsen, Søren Brandt; Kristensen, Tina Bøgelund; Brooks, Heddwen L.; Kohan, Donald E.; Rieg, Timo

    2017-01-01

    Psychiatric patients treated with lithium (Li+) may develop nephrogenic diabetes insipidus (NDI). Although the etiology of Li+-induced NDI (Li-NDI) is poorly understood, it occurs partially due to reduced aquaporin-2 (AQP2) expression in the kidney collecting ducts. A mechanism postulated for this is that Li+ inhibits adenylyl cyclase (AC) activity, leading to decreased cAMP, reduced AQP2 abundance, and less membrane targeting. We hypothesized that Li-NDI would not develop in mice lacking AC6. Whole-body AC6 knockout (AC6–/–) mice and potentially novel connecting tubule/principal cell–specific AC6 knockout (AC6loxloxCre) mice had approximately 50% lower urine osmolality and doubled water intake under baseline conditions compared with controls. Dietary Li+ administration increased water intake and reduced urine osmolality in control, AC6–/–, and AC6loxloxCre mice. Consistent with AC6–/– mice, medullary AQP2 and pS256-AQP2 abundances were lower in AC6loxloxCre mice compared with controls under standard conditions, and levels were further reduced after Li+ administration. AC6loxloxCre and control mice had a similar increase in the numbers of proliferating cell nuclear antigen–positive cells in response to Li+. However, AC6loxloxCre mice had a higher number of H+-ATPase B1 subunit–positive cells under standard conditions and after Li+ administration. Collectively, AC6 has a minor role in Li-NDI development but may be important for determining the intercalated cell–to–principal cell ratio.

  10. Hypercalcemia induces targeted autophagic degradation of aquaporin-2 at the onset of nephrogenic diabetes insipidus.

    PubMed

    Khositseth, Sookkasem; Charngkaew, Komgrid; Boonkrai, Chatikorn; Somparn, Poorichaya; Uawithya, Panapat; Chomanee, Nusara; Payne, D Michael; Fenton, Robert A; Pisitkun, Trairak

    2017-01-27

    Hypercalcemia can cause renal dysfunction such as nephrogenic diabetes insipidus (NDI), but the mechanisms underlying hypercalcemia-induced NDI are not well understood. To elucidate the early molecular changes responsible for this disorder, we employed mass spectrometry-based proteomic analysis of inner medullary collecting ducts (IMCD) isolated from parathyroid hormone-treated rats at onset of hypercalcemia-induced NDI. Forty-one proteins, including the water channel aquaporin-2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the downregulated proteins were associated with cytoskeletal protein binding, regulation of actin filament polymerization, and cell-cell junctions. Targeted LC-MS/MS and immunoblot studies confirmed the downregulation of 16 proteins identified in the initial proteomic analysis and in additional experiments using a vitamin D treatment model of hypercalcemia-induced NDI. Evaluation of transcript levels and estimated half-life of the downregulated proteins suggested enhanced protein degradation as the possible regulatory mechanism. Electron microscopy showed defective intercellular junctions and autophagy in the IMCD cells from both vitamin D- and parathyroid hormone-treated rats. A significant increase in the number of autophagosomes was confirmed by immunofluorescence labeling of LC3. Colocalization of LC3 and Lamp1 with aquaporin-2 and other downregulated proteins was found in both models. Immunogold electron microscopy revealed aquaporin-2 in autophagosomes in IMCD cells from both hypercalcemia models. Finally, parathyroid hormone withdrawal reversed the NDI phenotype, accompanied by termination of aquaporin-2 autophagic degradation and normalization of both nonphoshorylated and S256-phosphorylated aquaporin-2 levels. Thus, enhanced autophagic degradation of proteins plays an important role in the initial mechanism of hypercalcemic-induced NDI.

  11. Defective Store-Operated Calcium Entry Causes Partial Nephrogenic Diabetes Insipidus.

    PubMed

    Mamenko, Mykola; Dhande, Isha; Tomilin, Viktor; Zaika, Oleg; Boukelmoune, Nabila; Zhu, Yaming; Gonzalez-Garay, Manuel L; Pochynyuk, Oleh; Doris, Peter A

    2016-07-01

    Store-operated calcium entry (SOCE) is the mechanism by which extracellular signals elicit prolonged intracellular calcium elevation to drive changes in fundamental cellular processes. Here, we investigated the role of SOCE in the regulation of renal water reabsorption, using the inbred rat strain SHR-A3 as an animal model with disrupted SOCE. We found that SHR-A3, but not SHR-B2, have a novel truncating mutation in the gene encoding stromal interaction molecule 1 (STIM1), the endoplasmic reticulum calcium (Ca(2+)) sensor that triggers SOCE. Balance studies revealed increased urine volume, hypertonic plasma, polydipsia, and impaired urinary concentrating ability accompanied by elevated circulating arginine vasopressin (AVP) levels in SHR-A3 compared with SHR-B2. Isolated, split-open collecting ducts (CD) from SHR-A3 displayed decreased basal intracellular Ca(2+) levels and a major defect in SOCE. Consequently, AVP failed to induce the sustained intracellular Ca(2+) mobilization that requires SOCE in CD cells from SHR-A3. This effect decreased the abundance of aquaporin 2 and enhanced its intracellular retention, suggesting impaired sensitivity of the CD to AVP in SHR-A3. Stim1 knockdown in cultured mpkCCDc14 cells reduced SOCE and basal intracellular Ca(2+) levels and prevented AVP-induced translocation of aquaporin 2, further suggesting the effects in SHR-A3 result from the expression of truncated STIM1. Overall, these results identify a novel mechanism of nephrogenic diabetes insipidus and uncover a role of SOCE in renal water handling.

  12. Expression of a dominant negative PKA mutation in the kidney elicits a diabetes insipidus phenotype.

    PubMed

    Gilbert, Merle L; Yang, Linghai; Su, Thomas; McKnight, G Stanley

    2015-03-15

    PKA plays a critical role in water excretion through regulation of the production and action of the antidiuretic hormone arginine vasopressin (AVP). The AVP prohormone is produced in the hypothalamus, where its transcription is regulated by cAMP. Once released into the circulation, AVP stimulates antidiuresis through activation of vasopressin 2 receptors in renal principal cells. Vasopressin 2 receptor activation increases cAMP and activates PKA, which, in turn, phosphorylates aquaporin (AQP)2, triggering apical membrane accumulation, increased collecting duct permeability, and water reabsorption. We used single-minded homolog 1 (Sim1)-Cre recombinase-mediated expression of a dominant negative PKA regulatory subunit (RIαB) to disrupt kinase activity in vivo and assess the role of PKA in fluid homeostasis. RIαB expression gave rise to marked polydipsia and polyuria; however, neither hypothalamic Avp mRNA expression nor urinary AVP levels were attenuated, indicating a primary physiological effect on the kidney. RIαB mice displayed a marked deficit in urinary concentrating ability and greatly reduced levels of AQP2 and phospho-AQP2. Dehydration induced Aqp2 mRNA in the kidney of both control and RIαB-expressing mice, but AQP2 protein levels were still reduced in RIαB-expressing mutants, and mice were unable to fully concentrate their urine and conserve water. We conclude that partial PKA inhibition in the kidney leads to posttranslational effects that reduce AQP2 protein levels and interfere with apical membrane localization. These findings demonstrate a distinct physiological role for PKA signaling in both short- and long-term regulation of AQP2 and characterize a novel mouse model of diabetes insipidus.

  13. Nephrogenic diabetes insipidus in mice caused by deleting COOH-terminal tail of aquaporin-2.

    PubMed

    Shi, Peijun P; Cao, Xiao R; Qu, Jing; Volk, Ken A; Kirby, Patricia; Williamson, Roger A; Stokes, John B; Yang, Baoli

    2007-05-01

    In mammals, the hormonal regulation of water homeostasis is mediated by the aquaporin-2 water channel (Aqp2) of the collecting duct (CD). Vasopressin induces redistribution of Aqp2 from intracellular vesicles to the apical membrane of CD principal cells, accompanied by increased water permeability. Mutations of AQP2 gene in humans cause both recessive and dominant nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin. In this study, we generated a line of mice with the distal COOH-terminal tail of the Aqp2 deleted (Aqp2(Delta230)), including the protein kinase A phosphorylation site (S256), but still retaining the putative apical localization signal (221-229) at the COOH-terminal. Mice heterozygous for the truncation appear normal. Homozygotes are viable to adulthood, with reduced urine concentrating capacity, increased urine output, decreased urine osmolality, and increased daily water consumption. Desmopressin increased urine osmolality in wild-type mice but had no effect on Aqp2(Delta230/Delta230) mice. Kidneys from affected mice showed CD and pelvis dilatation and papillary atrophy. By immunohistochemical and immunoblot analyses using antibody against the NH(2)-terminal region of the protein Aqp2(Delta230/Delta230) mice had a markedly reduced protein abundance. Expression of the truncated protein in MDCK cells was consistent with a small amount of functional expression but no stimulation. Thus we have generated a mouse model of NDI that may be useful in studying the physiology and potential therapy of this disease.

  14. Absence of PKC-alpha attenuates lithium-induced nephrogenic diabetes insipidus.

    PubMed

    Sim, Jae H; Himmel, Nathaniel J; Redd, Sara K; Pulous, Fadi E; Rogers, Richard T; Black, Lauren N; Hong, Seongun M; von Bergen, Tobias N; Blount, Mitsi A

    2014-01-01

    Lithium, an effective antipsychotic, induces nephrogenic diabetes insipidus (NDI) in ∼40% of patients. The decreased capacity to concentrate urine is likely due to lithium acutely disrupting the cAMP pathway and chronically reducing urea transporter (UT-A1) and water channel (AQP2) expression in the inner medulla. Targeting an alternative signaling pathway, such as PKC-mediated signaling, may be an effective method of treating lithium-induced polyuria. PKC-alpha null mice (PKCα KO) and strain-matched wild type (WT) controls were treated with lithium for 0, 3 or 5 days. WT mice had increased urine output and lowered urine osmolality after 3 and 5 days of treatment whereas PKCα KO mice had no change in urine output or concentration. Western blot analysis revealed that AQP2 expression in medullary tissues was lowered after 3 and 5 days in WT mice; however, AQP2 was unchanged in PKCα KO. Similar results were observed with UT-A1 expression. Animals were also treated with lithium for 6 weeks. Lithium-treated WT mice had 19-fold increased urine output whereas treated PKCα KO animals had a 4-fold increase in output. AQP2 and UT-A1 expression was lowered in 6 week lithium-treated WT animals whereas in treated PKCα KO mice, AQP2 was only reduced by 2-fold and UT-A1 expression was unaffected. Urinary sodium, potassium and calcium were elevated in lithium-fed WT but not in lithium-fed PKCα KO mice. Our data show that ablation of PKCα preserves AQP2 and UT-A1 protein expression and localization in lithium-induced NDI, and prevents the development of the severe polyuria associated with lithium therapy.

  15. Targeting renal purinergic signalling for the treatment of lithium-induced nephrogenic diabetes insipidus.

    PubMed

    Kishore, B K; Carlson, N G; Ecelbarger, C M; Kohan, D E; Müller, C E; Nelson, R D; Peti-Peterdi, J; Zhang, Y

    2015-06-01

    Lithium still retains its critical position in the treatment of bipolar disorder by virtue of its ability to prevent suicidal tendencies. However, chronic use of lithium is often limited by the development of nephrogenic diabetes insipidus (NDI), a debilitating condition. Lithium-induced NDI is due to resistance of the kidney to arginine vasopressin (AVP), leading to polyuria, natriuresis and kaliuresis. Purinergic signalling mediated by extracellular nucleotides (ATP/UTP), acting via P2Y receptors, opposes the action of AVP on renal collecting duct (CD) by decreasing the cellular cAMP and thus AQP2 protein levels. Taking a cue from this phenomenon, we discovered the potential involvement of ATP/UTP-activated P2Y2 receptor in lithium-induced NDI in rats and showed that P2Y2 receptor knockout mice are significantly resistant to Li-induced polyuria, natriuresis and kaliuresis. Extension of these studies revealed that ADP-activated P2Y12 receptor is expressed in the kidney, and its irreversible blockade by the administration of clopidogrel bisulphate (Plavix(®)) ameliorates Li-induced NDI in rodents. Parallel in vitro studies showed that P2Y12 receptor blockade by the reversible antagonist PSB-0739 sensitizes CD to the action of AVP. Thus, our studies unravelled the potential beneficial effects of targeting P2Y2 or P2Y12 receptors to counter AVP resistance in lithium-induced NDI. If established in further studies, our findings may pave the way for the development of better and safer methods for the treatment of NDI by bringing a paradigm shift in the approach from the current therapies that predominantly counter the anti-AVP effects to those that enhance the sensitivity of the kidney to AVP action.

  16. Hydrochlorothiazide attenuates lithium-induced nephrogenic diabetes insipidus independently of the sodium-chloride cotransporter.

    PubMed

    Sinke, Anne P; Kortenoeven, Marleen L A; de Groot, Theun; Baumgarten, Ruben; Devuyst, Olivier; Wetzels, Jack F M; Loffing, Johannes; Deen, Peter M T

    2014-03-01

    Lithium is the most common cause of nephrogenic diabetes insipidus (Li-NDI). Hydrochlorothiazide (HCTZ) combined with amiloride is the mainstay treatment in Li-NDI. The paradoxical antidiuretic action of HCTZ in Li-NDI is generally attributed to increased sodium and water uptake in proximal tubules as a compensation for increased volume loss due to HCTZ inhibition of the Na-Cl cotransporter (NCC), but alternative actions for HCTZ have been suggested. Here, we investigated whether HCTZ exerted an NCC-independent effect in Li-NDI. In polarized mouse cortical collecting duct (mpkCCD) cells, HCTZ treatment attenuated the Li-induced downregulation of aquaporin-2 (AQP2) water channel abundance. In these cells, amiloride reduces cellular Li influx through the epithelial sodium channel (ENaC). HCTZ also reduced Li influx, but to a lower extent. HCTZ increased AQP2 abundance on top of that of amiloride and did not affect the ENaC-mediated transcellular voltage. MpkCCD cells did not express NCC mRNA or protein. These data indicated that in mpkCCD cells, HCTZ attenuated lithium-induced downregulation of AQP2 independently of NCC and ENaC. Treatment of Li-NDI NCC knockout mice with HCTZ revealed a significantly reduced urine volume, unchanged urine osmolality, and increased cortical AQP2 abundance compared with Li-treated NCC knockout mice. HCTZ treatment further resulted in reduced blood Li levels, creatinine clearance, and alkalinized urinary pH. Our in vitro and in vivo data indicate that part of the antidiuretic effect of HCTZ in Li-NDI is NCC independent and may involve a tubuloglomerular feedback response-mediated reduction in glomerular filtration rate due to proximal tubular carbonic anhydrase inhibition.

  17. Prasugrel suppresses development of lithium-induced nephrogenic diabetes insipidus in mice.

    PubMed

    Zhang, Yue; Peti-Peterdi, János; Brandes, Anna U; Riquier-Brison, Anne; Carlson, Noel G; Müller, Christa E; Ecelbarger, Carolyn M; Kishore, Bellamkonda K

    2017-02-23

    Previously, we localized ADP-activated P2Y12 receptor (R) in rodent kidney and showed that its blockade by clopidogrel bisulfate (CLPD) attenuates lithium (Li)-induced nephrogenic diabetes insipidus (NDI). Here, we evaluated the effect of prasugrel (PRSG) administration on Li-induced NDI in mice. Both CLPD and PRSG belong to the thienopyridine class of ADP receptor antagonists. Groups of age-matched adult male B6D2 mice (N = 5/group) were fed either regular rodent chow (CNT), or with added LiCl (40 mmol/kg chow) or PRSG in drinking water (10 mg/kg bw/day) or a combination of LiCl and PRSG for 14 days and then euthanized. Water intake and urine output were determined and blood and kidney tissues were collected and analyzed. PRSG administration completely suppressed Li-induced polydipsia and polyuria and significantly prevented Li-induced decreases in AQP2 protein abundance in renal cortex and medulla. However, PRSG either alone or in combination with Li did not have a significant effect on the protein abundances of NKCC2 or NCC in the cortex and/or medulla. Immunofluorescence microscopy revealed that PRSG administration prevented Li-induced alterations in cellular disposition of AQP2 protein in medullary collecting ducts. Serum Li, Na, and osmolality were not affected by the administration of PRSG. Similar to CLPD, PRSG administration had no effect on Li-induced increase in urinary Na excretion. However, unlike CLPD, PRSG did not augment Li-induced increase in urinary arginine vasopressin (AVP) excretion. Taken together, these data suggest that the pharmacological inhibition of P2Y12-R by the thienopyridine group of drugs may potentially offer therapeutic benefits in Li-induced NDI.

  18. Targeting Renal Purinergic Signalling for the Treatment of Lithium-induced Nephrogenic Diabetes Insipidus

    PubMed Central

    Kishore, B. K.; Carlson, N. G.; Ecelbarger, C. M.; Kohan, D. E.; Müller, C. E.; Nelson, R. D.; Peti-Peterdi, J.; Zhang, Y.

    2015-01-01

    Lithium still retains its critical position in the treatment of bipolar disorder by virtue of its ability to prevent suicidal tendencies. However, chronic use of lithium is often limited by the development nephrogenic diabetes insipidus (NDI), a debilitating condition. Lithium-induced NDI is due to resistance of the kidney to arginine vasopressin (AVP), leading to polyuria, natriuresis and kaliuresis. Purinergic signalling mediated by extracellular nucleotides (ATP/UTP), acting via P2Y receptors, opposes the action of AVP on renal collecting duct (CD) by decreasing the cellular cAMP and thus AQP2 protein levels. Taking a cue from this phenomenon, we discovered the potential involvement of ATP/UTP-activated P2Y2 receptor in lithium-induced NDI in rats, and showed that P2Y2 receptor knockout mice are significantly resistant to Li-induced polyuria, natriuresis and kaliuresis. Extension of these studies revealed that ADP-activated P2Y12 receptor is expressed in the kidney, and its irreversible blockade by the administration of clopidogrel bisulfate (Plavix®) ameliorates Li-induced NDI in rodents. Parallel in vitro studies showed that P2Y12 receptor blockade by the reversible antagonist PSB-0739 sensitizes CD to the action of AVP. Thus, our studies unraveled the potential beneficial effects of targeting P2Y2 or P2Y12 receptors to counter AVP resistance in lithium-induced NDI. If established in further studies, our findings may pave the way for the development of better and safer methods for the treatment of NDI by bringing a paradigm shift in the approach from the current therapies that predominantly counter the anti-AVP effects to those that enhance the sensitivity of the kidney to AVP action. PMID:25877068

  19. Aliskiren Increases Aquaporin-2 Expression and Attenuates Lithium-induced Nephrogenic Diabetes Insipidus.

    PubMed

    Lin, Yu; Zhang, Tiezheng; Feng, Pinning; Qiu, Miaojuan; Liu, Qiaojuan; Li, Suchun; Zheng, Peili; Kong, Yonglun; Levi, Moshe; Li, Chunling; Wang, Weidong

    2017-02-22

    The direct renin inhibitor aliskiren has been shown to retain and persist in medullary collecting ducts even after treatment was discontinued, suggesting a new mechanism of action for this drug. The purpose of the present study was to investigate whether aliskiren regulates renal aquaporin expression in the collecting ducts and improves urinary concentrating defect induced by lithium in mice. The mice were either fed with normal chow or LiCl diet (40mM/kg dry food/day for 4 days and 20mM/kg dry food/day for last 3 days) for seven days. Some mice were intraperitoneally injected with aliskiren (50mg/kg BW/day in saline). Aliskiren significantly increased protein abundance of AQP2 in the kidney inner medulla in mice. In inner medulla collecting duct cell suspension, aliskiren markedly increased AQP2 and pS256-AQP2 protein abundance which was significantly inhibited either by adenylyl cyclase inhibitor MDL-12330A or by PKA inhibitor H89, indicating an involvement of the cAMP-PKA signaling pathway in aliskiren-induced increased AQP2 expression. Aliskiren treatment improved urinary concentrating defect in lithium-treated mice, and partially prevented the decrease of AQP2 and pS256-AQP2 protein abundance in inner medulla of the kidney. In conclusion, the direct renin inhibitor aliskiren upregulates AQP2 protein expression in inner medullary collecting duct principal cells and prevents lithium-induced nephrogenic diabetes insipidus (NDI) likely via cAMP-PKA pathways.

  20. CENTRAL DIABETES INSIPIDUS: CLINICAL CHARACTERISTICS AND LONG-TERM COURSE IN A LARGE COHORT OF ADULTS.

    PubMed

    Masri-Iraqi, Hiba; Hirsch, Dania; Herzberg, Dana; Lifshitz, Avner; Tsvetov, Gloria; Benbassat, Carlos; Shimon, Ilan

    2017-02-22

    Purpose Central diabetes insipidus (CDI) is a rare heterogeneous condition with various underlying causes. This study sought to increase the still-limited data on the clinical characteristics and long-term course in adults diagnosed with CDI. Methods Data on demographics, presentation, imaging findings, affected pituitary axes, treatment, and complications were collected retrospectively from the files of 70 adult patients with CDI followed at a referral endocrine clinic. Results 40 women and 30 men were included. Mean age was 46.8±15 years at the time of this study and 29.3±20 years at CDI diagnosis. Twenty-eight patients were diagnosed in childhood. Forty patients (57%) acquired CDI following surgery. Main sellar pathologies were: craniopharyngioma, 17 patients (11 diagnosed in childhood); Langerhans histiocytosis, 10 patients (5 diagnosed in childhood); 7 patients (all diagnosed as adults) had a growth-hormone-secreting adenoma; twelve patients (17%; 6 diagnosed in childhood) had idiopathic CDI. At least one anterior pituitary axis was affected in 73% of the cohort: 59% had growth hormone deficiency, 56% hypogonadism, 55% central hypothyroidism, 44% ACTH-cortisol deficiency. Patients with post-operative/trauma CDI (n=44) tended to have multiple anterior pituitary axes deficits compared to the non-surgical group of patients. All patients were treated with vasopressin preparations, mostly nasal spray. Hyponatremia developed in 32 patients, more in women and was severe (<125 mEq/l) in 10. Hypernatremia (>150 mEq/l) was noticed in 5 patients. Overall, the calculated complication rate was 22/1250 treatment-years. Conclusions Most adult patients with CDI have anterior pituitary dysfunction. Stability is usually achieved with long-term treatment. Women were more susceptible to desmopressin complications, albeit with an overall relatively low complication rate.

  1. Vasopressin-independent targeting of aquaporin-2 by selective E-prostanoid receptor agonists alleviates nephrogenic diabetes insipidus.

    PubMed

    Olesen, Emma T B; Rützler, Michael R; Moeller, Hanne B; Praetorius, Helle A; Fenton, Robert A

    2011-08-02

    In the kidney, the actions of vasopressin on its type-2 receptor (V2R) induce increased water reabsorption alongside polyphosphorylation and membrane targeting of the water channel aquaporin-2 (AQP2). Loss-of-function mutations in the V2R cause X-linked nephrogenic diabetes insipidus. Treatment of this condition would require bypassing the V2R to increase AQP2 membrane targeting, but currently no specific pharmacological therapy is available. The present study examined specific E-prostanoid receptors for this purpose. In vitro, prostaglandin E2 (PGE2) and selective agonists for the E-prostanoid receptors EP2 (butaprost) or EP4 (CAY10580) all increased trafficking and ser-264 phosphorylation of AQP2 in Madin-Darby canine kidney cells. Only PGE2 and butaprost increased cAMP and ser-269 phosphorylation of AQP2. Ex vivo, PGE2, butaprost, or CAY10580 increased AQP2 phosphorylation in isolated cortical tubules, whereas PGE2 and butaprost selectively increased AQP2 membrane accumulation in kidney slices. In vivo, a V2R antagonist caused a severe urinary concentrating defect in rats, which was greatly alleviated by treatment with butaprost. In conclusion, EP2 and EP4 agonists increase AQP2 phosphorylation and trafficking, likely through different signaling pathways. Furthermore, EP2 selective agonists can partially compensate for a nonfunctional V2R, providing a rationale for new treatment strategies for hereditary nephrogenic diabetes insipidus.

  2. Novel mutations in the V2 vasopressin receptor gene in two pedigrees with congenital nephrogenic diabetes insipidus

    SciTech Connect

    Yuasa, Hiromitsu; Ito, Masafumi; Oiso, Yutaka; Kurokawa, Masaei; Saito, Hidehiko; Watanabe, Tohru; Oda, Yoshihiko; Ishizuka, Toshie; Tani, Nagayuki; Ito, Seiki; Shibata, Akira

    1994-08-01

    Novel mutations in the V2 vasopressin receptor gene were identified in two Japanese pedigrees with X-linked congenital nephrogenic diabetes insipidus. The V2 receptor belongs to the family of G-protein-coupled receptors that contain seven distinct transmembrane domains, and the V2 receptor gene is encoded by three exons. The coding regions amplified by polymerase chain reaction were directly sequenced. In a pedigree, one of four consecutive guanine sequences (nucleotides 528-531) in the second exon was deleted (528delG). This deletion mutation results in a frame shift beginning at codon 154 in the second intracellular domain and a premature termination at codon 161. In another pedigree, a missense mutation (A{yields}G) was identified at nucleotide position 310 in the second exon. This point mutation, H80R, changes a histidine at codon 80 in the second transmembrane domain to an arginine that is more positively charged than histidine under the neutral environment. Each mutation cosegregated with the phenotype of diabetes insipidus and supposed to be a cause for resistance to arginine vasopressin. 35 refs., 4 figs., 2 tabs.

  3. Novel mutations in aquaporin-2 gene in female siblings with nephrogenic diabetes insipidus: evidence of disrupted water channel function.

    PubMed

    Goji, K; Kuwahara, M; Gu, Y; Matsuo, M; Marumo, F; Sasaki, S

    1998-09-01

    Novel mutations of the aquaporin-2 (AQP2) gene have been detected in Japanese female siblings with autosomal-recessive nephrogenic diabetes insipidus. The patients were compound heterozygote for point mutations at nucleotide position 374 (C374T) and at position 523 (G523A) in exon 2 of the AQP2 gene, resulting in substitution of methionine for threonine at codon 125 (T125M) and arginine for glycine at codon 175 (G175R). The water permeability (Pf) of oocytes injected with wild-type complementary RNA increased 9.0-fold compared with the Pf of water-injected oocytes, whereas the increases in the Pf of oocytes injected with T125M and G175R complementary RNA were only 1.7-fold and 1.5-fold, respectively. Immunoblot and immunocytochemistry indicated that the plasma membrane expressions of T125M and G175R AQP2 proteins were comparable to that of the wild-type, suggesting that although neither the T125M nor G175R mutation had a significant effect on plasma membrane expression, they both distorted the structure and function of the aqueous pore of AQP2. These results provide evidence that the nephrogenic diabetes insipidus in patients with T125M and G175R mutations is attributable not to the misrouting of AQP2, but to the disrupted water channel function.

  4. A novel AVPR2 gene mutation of X-linked congenital nephrogenic diabetes insipidus in an Asian pedigree.

    PubMed

    Guo, Wei-Hong; Li, Qiang; Wei, Hong-Yan; Lu, Hong-Yan; Qu, Hui-Qi; Zhu, Mei

    2016-08-25

    Polyuria and polydipsia are the characteristics of congenital nephrogenic diabetes insipidus (CNDI). Approximately 90% of all patients with CNDI have X-linked hereditary disease, which is due to a mutation of the arginine vasopressin receptor 2 (AVPR2) gene. This case report describes a 54-year-old male with polyuria and polydipsia and several male members of his pedigree who had the same symptoms. The proband was diagnosed with diabetes insipidus using a water-deprivation and arginine vasopressin stimulation test. Genomic DNA from the patient and his family members was extracted and the AVPR2 gene was sequenced. A novel missense mutation of a cytosine to guanine transition at position 972 (c.972C > G) was found, which resulted in the substitution of isoleucine for methionine at amino acid position 324 (p.I324M) in the seventh transmembrane domain of the protein. The proband's mother and daughter were heterozygous for this mutation. The novel mutation of the AVPR2 gene further broadens the phenotypic spectrum of the AVPR2 gene.

  5. Central diabetes insipidus associated with impaired renal aquaporin-1 expression in mice lacking liver X receptor β.

    PubMed

    Gabbi, Chiara; Kong, Xiaomu; Suzuki, Hitoshi; Kim, Hyun-Jin; Gao, Min; Jia, Xiao; Ohnishi, Hideo; Ueta, Yoichi; Warner, Margaret; Guan, Youfei; Gustafsson, Jan-Åke

    2012-02-21

    The present study demonstrates a key role for the oxysterol receptor liver X receptor β (LXRβ) in the etiology of diabetes insipidus (DI). Given free access to water, LXRβ(-/-) but not LXRα(-/-) mice exhibited polyuria (abnormal daily excretion of highly diluted urine) and polydipsia (increased water intake), both features of diabetes insipidus. LXRβ(-/-) mice responded to 24-h dehydration with a decreased urine volume and increased urine osmolality. To determine whether the DI was of central or nephrogenic origin, we examined the responsiveness of the kidney to arginine vasopressin (AVP). An i.p. injection of AVP to LXRβ(-/-) mice revealed a partial kidney response: There was no effect on urine volume, but there was a significant increase of urine osmolality, suggesting that DI may be caused by a defect in central production of AVP. In the brain of WT mice LXRβ was expressed in the nuclei of magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus. In LXRβ(-/-) mice the expression of AVP was markedly decreased in the magnocellular neurons as well as in urine collected over a 24-h period. The persistent high urine volume after AVP administration was traced to a reduction in aquaporin-1 expression in the kidney of LXRβ(-/-) mice. The LXR agonist (GW3965) in WT mice elicited an increase in urine osmolality, suggesting that LXRβ is a key receptor in controlling water balance with targets in both the brain and kidney, and it could be a therapeutic target in disorders of water balance.

  6. Cooperative mechanisms involved in chronic antidiuretic response to bendroflumethiazide in rats with lithium-induced nephrogenic diabetes insipidus.

    PubMed

    Moosavi, S M S; Karimi, Z

    2014-03-01

    Previous studies of central diabetes insipidus suggested that thiazides acutely exerted a paradoxical antidiuresis by either indirectly activating volume-homeostatic reflexes to decrease distal fluid-delivery, or directly stimulating distal water-reabsorption. This study investigated whether the direct and indirect actions of bendroflumethiazide (BFTZ) simultaneously cooperated and also whether the renal nerves were involved in inducing long-term antidiuresis in nephrogenic diabetes insipidus (NDI). BFTZ or vehicle was gavaged into bilateral renal denervated and innervated rats with lithium-induced NDI for 10 days, constituting four groups. At one day before (D0) and one, five and ten days after starting administration of BFTZ or vehicle, rats were placed in metabolic cages to collect urine for 6 hours. BFTZ-treatment in both renal innervated and denervated rats caused equivalent reductions in urine-flow, creatinine clearance, lithium clearance and free-water clearance, but rises in urine-osmolality, fractional proximal reabsorption and fractional distal reabsorption at all days compared to D0, as well as to those of their relevant vehicle-received group. Therefore, the chronic antidiuretic response to BFTZ in conscious NDI rats was exerted through a concomitant cooperation of its direct distal effect of stimulating water-reabsorption and its indirect effect of reducing distal fluid-delivery by activating volume-homeostatic mechanisms, which appeared independent of the renal nerves.

  7. Thickened pituitary stalk on magnetic resonance imaging in children with central diabetes insipidus.

    PubMed

    Czernichow, P; Garel, C; Léger, J

    2000-01-01

    Magnetic resonance imaging (MRI) has revealed isolated pituitary stalk thickening (PST) in certain cases of idiopathic or secondary central diabetes insipidus (DI) due to infiltrative processes. Twenty-six children with DI and PST underwent cerebral MRI at the age of 8 +/- 4 years and were followed (n = 25) by clinical and MRI evaluation for 5.5 +/- 3.6 and 3.0 +/- 2 years, respectively, but given no treatment other than hormonal substitutive therapy. Patients were subdivided into groups according to the etiology of the DI: germinoma (n = 4), Langerhans' histiocytosis (n = 5) or 'idiopathic' DI with PST (n = 17). Complete anterior pituitary evaluation in 24 of the 26 patients revealed that 14 children were suffering from associated growth hormone deficiency and 7 had multiple hormone deficiencies. At the first MRI evaluation, pituitary stalk enlargement varied from 2.2 to 9.0 mm. The anterior pituitary gland was found to be normal (n = 12), small (n = 8) or enlarged (n = 6). At the final evaluation, a change in MRI features had occurred in 16 patients: morphological and/or signal changes in the PST (n = 16; 6 of whom showed an increase in PST) and changes in anterior pituitary gland size (n = 8; 3 of whom had increased and 5 had decreased). The presence of a growing suprasellar mass with a progressively enlarging pituitary stalk was demonstrated in the 6 patients who had shown increased pituitary stalk enlargement 1.8 +/- 1.6 years after the first MRI. In 4 of these patients, a diagnosis of germinoma was made 1.3 +/- 0.6 years after PST identification by MRI at the onset of DI, but the other 2 patients showing a suprasellar mass were still categorized as 'idiopathic' at the final clinical evaluation performed 7.8 and 12.3 years after DI onset. In 10 patients (all but 1 with Langerhans' histiocytosis, showing 'idiopathic' DI) the pituitary stalk enlargement was diminished after 2.0 +/- 1.9 years of MRI follow-up, and there was a complete reversal of pituitary stalk

  8. Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus.

    PubMed

    Robben, Joris H; Knoers, Nine V A M; Deen, Peter M T

    2006-08-01

    In the renal collecting duct, water reabsorption is regulated by the antidiuretic hormone vasopressin (AVP). Binding of this hormone to the vasopressin V2 receptor (V2R) leads to insertion of aquaporin-2 (AQP2) water channels in the apical membrane, thereby allowing water reabsorption from the pro-urine to the interstitium. The disorder nephrogenic diabetes insipidus (NDI) is characterized by the kidney's inability to concentrate pro-urine in response to AVP, which is mostly acquired due to electrolyte disturbances or lithium therapy. Alternatively, NDI is inherited in an X-linked or autosomal fashion due to mutations in the genes encoding V2R or AQP2, respectively. This review describes the current knowledge of the cell biological causes of NDI and how these defects may explain the patients' phenotypes. Also, the increased understanding of these cellular defects in NDI has opened exciting initiatives in the development of novel therapies for NDI, which are extensively discussed in this review.

  9. Nephrogenic diabetes insipidus partially responsive to oral desmopressin in a subject with lithium-induced multiple endocrinopathy.

    PubMed

    Kamath, C; Govindan, J; Premawardhana, A D; Wood, S J; Adlan, M A; Premawardhana, L D

    2013-08-01

    Lithium (Li) may cause multiple endocrinopathies, including hypercalcaemia, thyroid dysfunction and nephrogenic diabetes insipidus (NDI), but rarely in the same patient. The management of NDI remains a challenge. We report on a patient on long-term Li who had simultaneous NDI (paired serum and urine samples had abnormal osmolalities, typical of NDI, and treatment with parenteral desmopressin failed to affect urinary volume and serum osmolality), 'destructive' thyroiditis (hyperthyroidism, absent radioiodine uptake and absent thyrotrophin receptor antibodies) and primary hyperparathyroidism (compatible biochemistry, urine calcium excluding 'set point' anomalies and hypocalciuric hypercalcaemia, and normal parathyroid imaging). The thyroiditis resolved spontaneously and hypercalcaemia responded to reduction of Li dose. The NDI was unresponsive to amiloride, thiazides and ibuprofen in combination. However, urine output was reduced by 50% when a high dose of oral desmopressin was given. We conclude that Li-induced multiple endocrinopathy remains rare and, although NDI is difficult to manage, high dose oral desmopressin should be tried when other medications fail.

  10. Two novel mutations in the coding region for neurophysin-II associated with familial central diabetes insipidus

    SciTech Connect

    Nagasaki, Hiroshi; Ito, Masafumi; Yuasa, Hiromitsu

    1995-04-01

    Familial central diabetes insipidus is an autosomal dominant disease caused by a deficiency of arginine vasopressin (AVP). We previously reported three distinct mutations in the AVP gene in Japanese familial central diabetes insipidus pedigrees that result in substitution of Ser for Gly{sup 57} in the neurophysin-II (NPII) moiety of the AVP precursor, a substitution of Thr for Ala at the COOH-terminus of the signal peptide, and a deletion of Glu{sup 47} in the NPII moiety. In this study, we analyzed the AVP gene in two pedigrees by direct sequencing of the polymerase chain reaction-amplified DNA and found two novel mutations in exon 2, which encodes the central part of the NPII moiety of the precursor. The mutation in one pedigree was a C to A transition at nucleotide position 1891, which replaces Cys{sup 67} (TGC) with stop codon (TGA). As the premature termination eliminates part of the COOH domain of the NPII moiety and the glycoprotein moiety, the conformation of the truncated protein is likely to be markedly different from that of normal precursor. In another pedigree, a G to T transversion was detected at nucleotide position 1874, which substitutes polar Trp (TGG) for hydrophobic Gly{sup 62}(GGG). It is possible that mutated NPII molecules, as a consequence of a conformational change, cannot bind AVP or self-associate to form higher oligomer complexes. Interestingly, all mutations we have identified to date, with the exception of the signal peptide mutation, are located in exon 2, suggesting the importance of the highly conserved central part of the NPII molecules and/or the NPII moiety in the precursor for AVP synthesis. 21 refs., 5 figs., 2 tabs.

  11. A large deletion of the AVPR2 gene causing severe nephrogenic diabetes insipidus in a Turkish family.

    PubMed

    Saglar, Emel; Deniz, Ferhat; Erdem, Beril; Karaduman, Tugce; Yönem, Arif; Cagiltay, Eylem; Mergen, Hatice

    2014-05-01

    X-linked nephrogenic diabetes insipidus (NDI) is a rare hereditary disease caused by mutations in arginine vasopressin type 2 receptor (AVPR2) and characterized by the production of large amounts of urine and an inability to concentrate urine in response to the antidiuretic hormone vasopressin. We have identified a novel 388 bp deletion starting in intron 1 and ending in exon 2 in the AVPR2 gene in a patient with NDI and in his family. We have revealed that this mutation is a de novo mutation for the mother of the proband patient. Prospective clinical data were collected for all family members. The water deprivation test confirmed the diagnosis of diabetes insipidus. The patient has severe symptoms like deep polyuria nocturia, polydipsia, and fatigue. He was given arginine vasopressin treatment while he was a child. However, he could not get well due to his nephrogenic type of illness. Both of his nephews have the same complains in addition to failure to grow. We have sequenced all exons and intron-exon boundaries of the AVPR2 gene of all family members. The analyses of bioinformatics and comparative genomics of the deletion were done via considering the DNA level damage. AVPR2 gene mutation results in the absence of the three transmembrane domains, two extracellular domains, and one cytoplasmic domain. Three-dimensional protein structure prediction was shown. We concluded that X-linked NDI and severity of illness in this family is caused by a novel 388 bp deletion in the AVPR2 gene that is predicted to truncate the receptor protein, and also this deletion may lead to dysfunctioning in protein activity and inefficient or inadequate binding abilities.

  12. Cooperative mechanisms of acute antidiuretic response to bendroflumethiazide in rats with lithium-induced nephrogenic diabetes insipidus.

    PubMed

    Moosavi, S Mostafa Shid; Haghani, Masoud

    2010-12-01

    The exact mechanism underlying thiazides-induced paradoxical antidiuresis in diabetes insipidus is still elusive, but it has been hypothesized that it is exerted either via Na+-depletion activating volume-homeostatic reflexes to decrease distal delivery, or direct stimulation of distal water reabsorption. This study examined how these two proposed mechanisms actually cooperate to induce an acute bendroflumethiazide (BFTZ)-antidiuretic effect in nephrogenic diabetes insipidus (NDI). Anaesthetized rats with lithium (Li)-induced NDI were prepared in order to measure their renal functional parameters, and in some of them, bilateral renal denervation (DNX) was induced. After a 30 min control clearance period, we infused either BFTZ into 2 groups, NDI+BFTZ and NDI/DNX+BFTZ, or its vehicle into a NDI+V group, and six 30 min experimental clearance periods were taken. During BFTZ infusion in the NDI+BFTZ group, transiently elevated Na+ excretion was associated with rapidly increased urinary osmolality and decreased free water clearance, but Li clearance and urine flow declined in the later periods. However, in the NDI/DNX+BFTZ group, there was persistently elevated Na+ excretion with unchanged Li clearance and urine flow during the experimental period, while alterations in free water clearance and urinary osmolality resembled those in the NDI+BFTZ group. In conclusion, BFTZ initially exerted two direct effects of natriuresis-diuresis and stimulating free water reabsorption at the distal nephron in NDI, which together elevated Na+ excretion and urinary osmolality but kept the urine volume unchanged in the first hour. Thereafter, the resultant sodium depletion led to the activation of neural reflexes that reduced distal fluid delivery to compensate for BFTZ-induced natriuresis-diuresis which, in cooperation with the direct distal BFTZ-antidiuretic effect, resulted in excretion of urine with a low volume, high osmolality, and normal sodium.

  13. Bulbocavernosus Reflex Test for Diagnosis of Pudendal Nerve Injury in Female Patients with Diabetic Neurogenic Bladder

    PubMed Central

    Niu, Xiaoting; Wang, Xun; Huang, Huanjie; Ni, Peiqi; Lin, Yuanshao; Shao, Bei

    2016-01-01

    The study was designed to investigate the clinical application and significance of the bulbocavernosus reflex (BCR) test for diagnosing diabetic neurogenic bladder (DNB) in female subjects. In this study, 68 female patients with DNB and 40 female normal controls were subjected to a nerve conduction study (NCS) of all four limbs and the BCR test. The data were analyzed and compared, and the corresponding diagnostic sensitivities were discussed. Mean BCR latency for female DNB patients was significantly prolonged, compared to that of the control group, suggesting pudendal nerve injuries in female DNB patients. Moreover, DNB patients were categorized according to the diabetes course. Compared to that of Group A (diabetes course < 5 y), the mean BCR latency was significantly prolonged in Group B (diabetes course between 5 and 10 y) and then further prolonged in Group C (diabetes course > 10 y), which were all longer than the control group. Furthermore, compared with that of the controls, the mean BCR latency was prolonged in DNB patients with or without NCS abnormalities in limbs. Nevertheless, no significant difference was observed in BCR latency between DNB patients with and without NCS abnormalities. Significantly increasing trends were also observed in the NCS and BCR abnormality rates along with increased diabetes course. Most importantly, compared with the NCS of limbs, the BCR test was more sensitive in diagnosing DNB in the female subjects. Overall, our findings suggest that the BCR test would help to assess the pudendal nerve injury in female DNB patients, which might be a potential diagnostic tool in the clinic. PMID:28053822

  14. Thickened pituitary stalk on magnetic resonance imaging in children with central diabetes insipidus.

    PubMed

    Leger, J; Velasquez, A; Garel, C; Hassan, M; Czernichow, P

    1999-06-01

    Magnetic resonance imaging (MRI) has revealed isolated pituitary stalk (PS) thickening (PST) in certain cases of idiopathic or secondary central diabetes insipidus (DI) due to infiltrative processes. Twenty-six children with DI and PST underwent cerebral MRI at the age of 8 +/- 4 yr and were followed (n = 24) by clinical and MRI evaluation, respectively, for 5.5 +/- 3.6 and 3.0 +/- 2 yr in the absence of any treatment other than hormonal substitutive therapy. Patients were subdivided into groups according to the etiology of the DI: germinoma (n = 4), Langerhans' histiocytosis (n = 5), or idiopathic DI with PST (n = 17). Complete anterior pituitary evaluation for 24 of the 26 patients revealed those suffering from associated GH deficiency (n = 14; with germinoma, n = 1; histiocytosis, n = 3; idiopathic, n = 10) and from multiple hormone deficiencies (n = 7; with germinoma, n = 3; histiocytosis, n = 1; idiopathic, n = 3). At the first MRI evaluation, PS enlargement varied from 2.2-9.0 mm at a proximal (n = 10), distal (n = 2), or middle (n = 6) PS level or along the entire PS (n = 8). The intrasellar content, which usually reflects the anterior pituitary gland, was normal (n = 12), small (n = 8), or enlarged (n = 6). At the last evaluation, a change in MRI features was found in 16 patients; morphological and/or signal changes in the PST (n = 16, of whom 6 showed an increase in PST) and changes in anterior pituitary gland size (n = 8; increased, n = 3; decreased, n = 5) were noted. The presence of a growing suprasellar mass with progressively enlarging PS was demonstrated in the 6 patients who had shown increased PS enlargement 1.8 +/- 1.6 yr after the first MRI. For 4 of them, a diagnosis of germinoma was made 1.3 +/- 0.6 yr after PST identification by MRI performed after the onset of DI, but the other 2 patients showing a suprasellar mass were still categorized as idiopathic at the final clinical evaluation performed 7.8 and 12.3 yr, respectively, after DI onset. In

  15. Dilatative uropathy as a manifestation of neurohypophyseal diabetes insipidus due to a novel mutation in the arginine vasopressin-neurophysin-II gene.

    PubMed

    Lindenthal, V; Mainberger, A; Morris-Rosendahl, D J; Löning, L; Mayer, W; Müller, H L

    2013-12-01

    Polydypsia and polyuria are frequent symptoms in patients with sellar masses caused by neurohypophyseal diabetes insipidus. Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI), a disorder caused by mutations in the arginine vasopressin (AVP) -neurophysin II (NPII) gene, should be considered as a rare differential diagnosis. A delayed diagnosis bears the risk of life-threatening electrolyte imbalances and permanent urinary tract damage, leading to impaired quality of life.We present a Caucasian kindred of at least 4 generations with FNDI.Clinical histories, endocrine para-meters, and results of molecular analyses of the AVP gene are presented with a review of the literature on diabetes insipidus (DI) related urinary tract dilatation.Polyuria and polydipsia were only reported based on explicit and thorough interrogation after more than 4 years of clinical follow-up. A novel heterozygous mutation in the AVP gene was found in all examined symptomatic subjects (c.1-33_c.4del37nt). A literature review revealed that non-obstructive hydronephrosis (NOH) is a rare but known complication of DI.Since increased fluid intake is often a typical familial pattern in adFNDI, it is frequently missed as being pathologic in affected patients, therefore a detailed clinical history of drinking volumes is of critical importance. AVP gene testing is an important component in the confirmation of the diagnosis. Otherwise unexplainable NOH should lead to further investigations and evaluation of rare diseases like FNDI.

  16. X-ray structure of human aquaporin 2 and its implications for nephrogenic diabetes insipidus and trafficking

    PubMed Central

    Frick, Anna; Eriksson, Urszula Kosinska; de Mattia, Fabrizio; Öberg, Fredrik; Hedfalk, Kristina; Neutze, Richard; de Grip, Willem J.; Deen, Peter M. T.; Törnroth-Horsefield, Susanna

    2014-01-01

    Human aquaporin 2 (AQP2) is a water channel found in the kidney collecting duct, where it plays a key role in concentrating urine. Water reabsorption is regulated by AQP2 trafficking between intracellular storage vesicles and the apical membrane. This process is tightly controlled by the pituitary hormone arginine vasopressin and defective trafficking results in nephrogenic diabetes insipidus (NDI). Here we present the X-ray structure of human AQP2 at 2.75 Å resolution. The C terminus of AQP2 displays multiple conformations with the C-terminal α-helix of one protomer interacting with the cytoplasmic surface of a symmetry-related AQP2 molecule, suggesting potential protein–protein interactions involved in cellular sorting of AQP2. Two Cd2+-ion binding sites are observed within the AQP2 tetramer, inducing a rearrangement of loop D, which facilitates this interaction. The locations of several NDI-causing mutations can be observed in the AQP2 structure, primarily situated within transmembrane domains and the majority of which cause misfolding and ER retention. These observations provide a framework for understanding why mutations in AQP2 cause NDI as well as structural insights into AQP2 interactions that may govern its trafficking. PMID:24733887

  17. Coexistence of central diabetes insipidus and salt wasting: the difficulties in diagnosis, changes in natremia, and treatment.

    PubMed

    Laredo, S; Yuen, K; Sonnenberg, B; Halperin, M L

    1996-12-01

    Both central diabetes insipidus (DI) and a high rate of excretion of sodium (Na) and chloride (Cl) contributed to the development of polyuria and dysnatremia in two patients during the acute postoperative period after neurosurgery. To minimize difficulties in diagnosis and projections for therapy, two available (but not often used) clinical tools were helpful. First, the osmole excretion rate early on revealed the co-existence of central DI and an osmotic diuresis. The osmoles excreted were largely Na salts; after antidiuretic hormone acted, this electrolyte diuresis caused the urine flow rate to be much higher than otherwise anticipated. Interestingly, part of this saline diuresis occurred when the extracellular fluid volume was contracted. The tool to explain the basis for the dysnatremias was a tonicity balance. Hypernatremia, which developed before treatment of central DI, was primarily a result of a positive balance for Na rather than a large negative balance for water. Moreover, hyponatremia that developed once antidiuretic hormone acted was primarily a result of a negative balance for Na; the urine volume was large and its Na concentration was hypertonic. To prevent a further decline in the plasma Na concentration, either the Na concentration in the urine should be decreased by provision of urea or a loop diuretic while replacing all unwanted water and electrolyte losses; alternatively, the fluid infused should have a similar Na concentration and volume as the urine (infuse hypertonic saline).

  18. Acute myeloid leukemia with monosomy 7, ectopic virus integration site-1 overexpression and central diabetes insipidus: A case report.

    PubMed

    Ma, Hongbing; Yang, Jing; Xiang, Bing; Jia, Yongqian

    2015-06-01

    Central diabetes insipidus (DI) is a rare complication in patients with acute myeloid leukemia (AML), typically occurring in patients with abnormalities of chromosomes 3 or 7. The association between AML with monosomy 7 and DI has been described in a number of studies; however, DI has been rarely reported in cases of ectopic virus integration site-1 (EVI1)-positive AML with monosomy 7. The current study reports a case of AML with monosomy 7 and EVI1 overexpression, with central DI as the initial symptom. The patient was an 18-year-old female who presented with polyuria and polydipsia. Bone marrow aspiration revealed 83.5% myeloperoxidase-positive blasts without trilineage myelodysplasia. The karyotype was 45,XX,-7, and the patient presented monosomy 7 and EVI1 overexpression (-7/EVI1(+)) without 3q aberration. Treatment with induction therapy was unsuccessful. To the best of our knowledge, this is the second case of DI-AML with -7/EVI1(+) and without a 3q aberration. The possible mechanisms associated with EVI1, monosomy 7 and DI were investigated.

  19. [Perioperative management of a child with central diabetes insipidus who underwent two surgeries before and after desmopressin administration].

    PubMed

    Kiriyama, Keiji; Tachibana, Kazuya; Nishimura, Nobuyuki; Takeuchi, Muneyuki; Kinouchi, Keiko

    2013-03-01

    A 14-year-old girl weighing 32 kg was diagnosed with suprasellar tumor causing hydrocephalus, hypothyroidism, adrenal dysfunction and central diabetes insipidus. She was treated with levothyroxine and hydrocortisone and urged to take fluid to replace urine. She was scheduled to undergo ventricular drainage to relieve hydrocephalus prior to tumor resection. For the first surgery, desmopressin was not started and urine output reached 4,000 to 6,000 ml x day(-1), urine osmolality 64 mOsm x l(-1) and urine specific gravity 1.002. Anesthesia was induced with sevoflurane and maintained with propofol and remifentanil. Maintenance fluid was with acetated Ringer's solution and urine loss was replaced with 5% dextrose. Bradycardia and hypotension occurred after intubation, which was treated with volume load. Infusion volume was 750 ml and urine output was 1100 ml during 133 min of anesthesia. Postoperative day 1 nasal desmopressin was started. Ten days later, partial tumor resection was performed. Anesthesia was induced with propofol and fentanyl and maintained with sevoflurane and remifentanil. Infusion volume was 610 ml, urine output 380 ml, and blood loss 151 ml during 344 min of anesthesia. Hemodynamic parameters were stable throughout the procedure. Pathology of the tumor was revealed to be germinoma. Bradycardia and hypotension experienced during the first surgery was suspected to be caused by preoperative hypovolemia brought by polyuria. Desmopressin was proved to be effective to treat excessive urine output and to maintain good perioperative water balance.

  20. Exome Sequencing Finds a Novel PCSK1 Mutation in a Child With Generalized Malabsorptive Diarrhea and Diabetes Insipidus

    PubMed Central

    Yourshaw, Michael; Solorzano-Vargas, R. Sergio; Pickett, Lindsay A.; Lindberg, Iris; Wang, Jiafang; Cortina, Galen; Pawlikowska-Haddal, Anna; Baron, Howard; Venick, Robert S.; Nelson, Stanley F.; Martín, Martín G.

    2014-01-01

    Objectives Congenital diarrhea disorders are a group of genetically diverse and typically autosomal recessive disorders that have yet to be well characterized phenotypically or molecularly. Diagnostic assessments are generally limited to nutritional challenges and histologic evaluation, and many subjects eventually require a prolonged course of intravenous nutrition. Here we describe next-generation sequencing techniques to investigate a child with perplexing congenital malabsorptive diarrhea and other presumably unrelated clinical problems; this method provides an alternative approach to molecular diagnosis. Methods We screened the diploid genome of an affected individual, using exome sequencing, for uncommon variants that have observed protein-coding consequences. We assessed the functional activity of the mutant protein, as well as its lack of expression using immunohistochemistry. Results Among several rare variants detected was a homozygous nonsense mutation in the catalytic domain of the proprotein convertase subtilisin/kexin type 1 gene. The mutation abolishes prohormone convertase 1/3 endoprotease activity as well as expression in the intestine. These primary genetic findings prompted a careful endocrine reevaluation of the child at 4.5 years of age, and multiple significant problems were subsequently identified consistent with the known phenotypic consequences of proprotein convertase subtilisin/kexin type 1 (PCSK1) gene mutations. Based on the molecular diagnosis, alternate medical and dietary management was implemented for diabetes insipidus, polyphagia, and micropenis. Conclusions Whole-exome sequencing provides a powerful diagnostic tool to clinicians managing rare genetic disorders with multiple perplexing clinical manifestations. PMID:24280991

  1. A novel SLC12A1 gene mutation associated with hyperparathyroidism, hypercalcemia, nephrogenic diabetes insipidus, and nephrocalcinosis in four patients.

    PubMed

    Wongsaengsak, Sariya; Vidmar, Alaina P; Addala, Ananta; Kamil, Elaine S; Sequeira, Paola; Fass, Benjamin; Pitukcheewanont, Pisit

    2017-04-01

    Solute Carrier Family 12 member 1 (SLC12A1) gene encodes the sodium-potassium-chloride co-transporter (NKCC2) at the apical membrane of the thick ascending loop of Henle (TAL). Bartter's syndrome (BS) type I is a rare, autosomal recessive, renal tubular disorder associated with mutation of the SLC12A1 gene. Presenting features include: hypokalemic metabolic alkalosis, hypercalciuria and nephrocalcinosis. The many allelic variants reported present with a spectrum of phenotypes, biochemical abnormalities and clinical severities. However, to date, only two reports have described hyperparathyroidism and hypercalcemia in patients with SLC12A1 gene mutations. We describe 4 patients with 4 novel mutation variants in the SLC12A1 gene (c.735C>G, c.1137del, c.2498-2499del, and c.1833delT) presenting with variable degrees of hyperparathyroidism, hypercalcemia, hypokalemic metabolic alkalosis, nephrocalcinosis, and nephrogenic diabetes insipidus. The link between calcium and parathyroid hormone abnormalities in patients with SLC12A1 mutations is unclear; the cases described suggest an association between primary hyperparathyroidism and loss of function mutation of SLC12A1, which may result in an aberrant threshold of the calcium sensing receptor at the level of the kidney.

  2. Genetic forms of nephrogenic diabetes insipidus (NDI): Vasopressin receptor defect (X-linked) and aquaporin defect (autosomal recessive and dominant).

    PubMed

    Bichet, Daniel G; Bockenhauer, Detlef

    2016-03-01

    Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP). Polyuria with hyposthenuria and polydipsia are the cardinal clinical manifestations of the disease. About 90% of patients with congenital NDI are males with X-linked NDI who have mutations in the vasopressin V2 receptor (AVPR2) gene encoding the vasopressin V2 receptor. In less than 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance with mutations in the aquaporin-2 (AQP2) gene. When studied in vitro, most AVPR2 and AQP2 mutations lead to proteins trapped in the endoplasmic reticulum and are unable to reach the plasma membrane. Prior knowledge of AVPR2 or AQP2 mutations in NDI families and perinatal mutation testing is of direct clinical value and can avert the physical and mental retardation associated with repeated episodes of dehydration.

  3. The influence of vasopressin deficiency and acute desmopressin administration on melatonin secretion in patients with central diabetes insipidus.

    PubMed

    Catrina, S B; Rotarus, R; Wivall, I-L; Coculescu, M; Brismar, K

    2004-01-01

    Melatonin secretion is modulated by the light-dark schedule, mainly through a sympathetic input to the pineal gland. Besides this, arginine vasopressin (AVP) has been found in the pineal glands of several animal species and there is experimental evidence that AVP modulates melatonin secretion in animals. However, the interaction between vasopressin and melatonin secretion in humans has not been systematically investigated. We proposed to study the nocturnal melatonin pattern in patients with central diabetes insipidus (CDI) who lack endogenous secretion of AVP, and the effect on their melatonin secretion of the agonist for V2 type receptors: desmopressin (1-Desamino [8-D Arginine] vasopressin). Plasma melatonin levels were measured in 14 patients with CDI, every 2 h starting from 22:00 h until 06:00 h, following iv injection of saline (day 1) and 3 microg desmopressin (day 2) at 20:00 h. The lights were turned off at 22:30 h and the samples were taken in a dim light. The plasma melatonin secretion pattern was normal in patients with CDI. Desmopressin at a dose 3 times higher than the antidiuretic one did not modify the melatonin levels or the time of the peak secretion. In conclusion melatonin secretion is not modulated by AVP in humans.

  4. X-ray structure of human aquaporin 2 and its implications for nephrogenic diabetes insipidus and trafficking.

    PubMed

    Frick, Anna; Eriksson, Urszula Kosinska; de Mattia, Fabrizio; Oberg, Fredrik; Hedfalk, Kristina; Neutze, Richard; de Grip, Willem J; Deen, Peter M T; Törnroth-Horsefield, Susanna

    2014-04-29

    Human aquaporin 2 (AQP2) is a water channel found in the kidney collecting duct, where it plays a key role in concentrating urine. Water reabsorption is regulated by AQP2 trafficking between intracellular storage vesicles and the apical membrane. This process is tightly controlled by the pituitary hormone arginine vasopressin and defective trafficking results in nephrogenic diabetes insipidus (NDI). Here we present the X-ray structure of human AQP2 at 2.75 Å resolution. The C terminus of AQP2 displays multiple conformations with the C-terminal α-helix of one protomer interacting with the cytoplasmic surface of a symmetry-related AQP2 molecule, suggesting potential protein-protein interactions involved in cellular sorting of AQP2. Two Cd(2+)-ion binding sites are observed within the AQP2 tetramer, inducing a rearrangement of loop D, which facilitates this interaction. The locations of several NDI-causing mutations can be observed in the AQP2 structure, primarily situated within transmembrane domains and the majority of which cause misfolding and ER retention. These observations provide a framework for understanding why mutations in AQP2 cause NDI as well as structural insights into AQP2 interactions that may govern its trafficking.

  5. Prenatal growth restriction, retinal dystrophy, diabetes insipidus and white matter disease: expanding the spectrum of PRPS1-related disorders.

    PubMed

    Al-Maawali, Almundher; Dupuis, Lucie; Blaser, Susan; Heon, Elise; Tarnopolsky, Mark; Al-Murshedi, Fathiya; Marshall, Christian R; Paton, Tara; Scherer, Stephen W; Roelofsen, Jeroen; van Kuilenburg, André B P; Mendoza-Londono, Roberto

    2015-03-01

    PRPS1 codes for the enzyme phosphoribosyl pyrophosphate synthetase-1 (PRS-1). The spectrum of PRPS1-related disorders associated with reduced activity includes Arts syndrome, Charcot-Marie-Tooth disease-5 (CMTX5) and X-linked non-syndromic sensorineural deafness (DFN2). We describe a novel phenotype associated with decreased PRS-1 function in two affected male siblings. Using whole exome and Sanger sequencing techniques, we identified a novel missense mutation in PRPS1. The clinical phenotype in our patients is characterized by high prenatal maternal α-fetoprotein, intrauterine growth restriction, dysmorphic facial features, severe intellectual disability and spastic quadraparesis. Additional phenotypic features include macular coloboma-like lesions with retinal dystrophy, severe short stature and diabetes insipidus. Exome sequencing of the two affected male siblings identified a shared putative pathogenic mutation c.586C>T p.(Arg196Trp) in the PRPS1 gene that was maternally inherited. Follow-up testing showed normal levels of hypoxanthine in urine samples and uric acid levels in blood serum. The PRS activity was significantly reduced in erythrocytes of the two patients. Nucleotide analysis in erythrocytes revealed abnormally low guanosine triphosphate and guanosine diphosphate. This presentation is the most severe form of PRPS1-deficiency syndrome described to date and expands the spectrum of PRPS1-related disorders.

  6. A case of central diabetes insipidus following probable type A/H1N1 influenza infection.

    PubMed

    Kobayashi, Takaaki; Miwa, Takashi; Odawara, Masato

    2011-01-01

    The major causes of central diabetes insipidus (CDI) are neoplastic or infiltrative lesions of the hypothalamus or pituitary gland, severe head injuries, or pituitary or hypothalamic surgery. Lymphocytic infundibuloneurophysitis (LINH) is associated with autoimmune inflammatory disease of the pituitary gland, but the exact etiology is unknown. CDI caused by viral infections has been rarely reported. Here, we describe the case of a 22-year-old man who was in good health until 2 months prior to admission, presented with acute development of polyuria and polydipsia, and showed increased urinary volume up to 9000 mL/day. The patient showed elevated serum osmolality and low urine osmolality, with a low level of antidiuretic hormone. Endocrinological findings revealed CDI, but his arterial pituitary function appeared normal. Magnetic resonance imaging revealed significant enlargement of the pituitary stalk. We suspected CDI due to LINH based on non-transsphenoidal biopsy findings. He was diagnosed as type A influenza,and given oral therapeutic agents. However, acute onset of polyuria and polydipsia occurred 10 days after the influenza diagnosis. The available epidemiological information regarding the outbreak of influenza around that time strongly suggested that the patient was infected with the A/H1N1 influenza virus, although this virus had not been detected on polymerase chain reaction testing. In the present case, the autoimmune mechanism of LINH may have been associated with novel influenza A/H1N1 virus infection.

  7. Combination of secretin and fluvastatin ameliorates the polyuria associated with X-linked nephrogenic diabetes insipidus in mice.

    PubMed

    Procino, Giuseppe; Milano, Serena; Carmosino, Monica; Barbieri, Claudia; Nicoletti, Maria C; Li, Jian H; Wess, Jürgen; Svelto, Maria

    2014-07-01

    X-linked nephrogenic diabetes insipidus (X-NDI) is a disease caused by inactivating mutations of the vasopressin (AVP) type 2 receptor (V2R) gene. Loss of V2R function prevents plasma membrane expression of the AQP2 water channel in the kidney collecting duct cells and impairs the kidney concentration ability. In an attempt to develop strategies to bypass V2R signaling in X-NDI, we evaluated the effects of secretin and fluvastatin, either alone or in combination, on kidney function in a mouse model of X-NDI. The secretin receptor was found to be functionally expressed in the kidney collecting duct cells. Based on this, X-NDI mice were infused with secretin for 14 days but urinary parameters were not altered by the infusion. Interestingly, secretin significantly increased AQP2 levels in the collecting duct but the protein primarily accumulated in the cytosol. Since we previously reported that fluvastatin treatment increased AQP2 plasma membrane expression in wild-type mice, secretin-infused X-NDI mice received a single injection of fluvastatin. Interestingly, urine production by X-NDI mice treated with secretin plus fluvastatin was reduced by nearly 90% and the urine osmolality was doubled. Immunostaining showed that secretin increased intracellular stores of AQP2 and the addition of fluvastatin promoted AQP2 trafficking to the plasma membrane. Taken together, these findings open new perspectives for the pharmacological treatment of X-NDI.

  8. Identification of a Novel Deletion in AVP-NPII Gene in a Patient with Central Diabetes Insipidus.

    PubMed

    Deniz, Ferhat; Acar, Ceren; Saglar, Emel; Erdem, Beril; Karaduman, Tugce; Yonem, Arif; Cagiltay, Eylem; Ay, Seyit Ahmet; Mergen, Hatice

    2015-01-01

    Central Diabetes Insipidus (CDI) is caused by a deficiency of antidiuretic hormone and characterized by polyuria, polydipsia and inability to concentrate urine. Our objective was to present the results of the molecular analyses of AVP-neurophysin II (AVP-NPII) gene in a large familial neurohypophyseal (central) DI pedigree. A male patient and his family members were analyzed and the prospective clinical data were collected. The proband applied to hospital for eligibility to be a recruit in Armed Forces. The patient had severe polyuria (20 L/day), polydipsia (20.5 L/day), fatique, and deep thirstiness. CDI was confirmed with the water deprivation-desmopressin test according to an increase in urine osmolality from 162 mOsm/kg to 432 mOsm/kg after desmopressin acetate injection. To evaluate the coding regions of AVP-NPII gene, polymerase chain reactions were performed and amplified regions were submitted to direct sequence analysis. We detected a heterozygous three base pair deletion at codon 69-70 (207_209delGGC) in exon 2, which lead to a deletion of the amino acid alanine. A three-dimensional protein structure prediction was shown for the deleted AVP-NPII and compared with the wild type. The three base pair deletion may yield an abnormal AVP precursor in neurophysin moiety, but further functional analyses are needed to understand the function of the deleted protein.

  9. Lack of effect of Pitressin on the learning ability of Brattleboro rats with diabetes insipidus using positively reinforced operant conditioning.

    PubMed

    Laycock, J F; Gartside, I B

    1985-08-01

    Brattleboro rats with hereditary hypothalamic diabetes insipidus (BDI) received daily subcutaneous injections of vasopressin in the form of Pitressin tannate (0.5 IU/24 hr). They were initially deprived of food and then trained to work for food reward in a Skinner box to a fixed ratio of ten presses for each pellet received. Once this schedule had been learned the rats were given a discrimination task daily for seven days. The performances of these BDI rats were compared with those of rats of the parent Long Evans (LE) strain receiving daily subcutaneous injections of vehicle (arachis oil). Comparisons were also made between these two groups of treated animals and untreated BDI and LE rats studied under similar conditions. In the initial learning trial, both control and Pitressin-treated BDI rats performed significantly better, and manifested less fear initially, than the control or vehicle-injected LE rats when first placed in the Skinner box. Once the initial task had been learned there was no marked difference in the discrimination learning between control or treated BDI and LE animals. These results support the view that vasopressin is not directly involved in all types of learning behaviour, particularly those involving positively reinforced operant conditioning.

  10. Staphylococcus saprophyticus native valve endocarditis in a diabetic patient with neurogenic bladder: A case report.

    PubMed

    Magarifuchi, Hiroki; Kusaba, Koji; Yamakuchi, Hiroki; Hamada, Yohei; Urakami, Toshiharu; Aoki, Yosuke

    2015-09-01

    A 61-year-old man was admitted to our hospital with 2-day history of malaise and dyspnea. He had mitral prolapse and type II diabetes mellitus with neurogenic bladder, which was cared for by catheterization on his own. On arrival the patient was in septic condition with hypoxemia, and physical examination revealed systolic murmur at the apex. Transthoracic echocardiography revealed vegetation of the mitral and the aortic valve. The presence of continuous bacteremia was confirmed by multiple sets of blood culture, whereby gram-positive cocci was retrieved and identified as Staphylococcus saprophyticus (S. saprophyticus) both phenotypically and genetically. Because two major criteria of the Modified Duke Criteria were met, the patient was diagnosed with native valve endocarditis due to S. saprophyticus. The urine culture was also positive for gram-positive cocci, phenotypically identified as Staphylococcus warneri, which was subsequently identified as S. saprophyticus with the use of 16S rRNA gene sequence analysis and MALDI-TOF MS (matrix-assisted laser desorption ionization time of flight mass spectrometry), indicating strongly that the intermittent catheterization-associated urinary tract infection resulted in bacteremia that eventually lead to infective endocarditis. This patient was treated with vancomycin and clindamycin. Because of multiple cerebral infarctions, the patient underwent mitral and aortic valve replacement on hospital day 5. Blood culture turned negative at 6th hospital day. Antibiotic therapy was continued for six weeks after surgery. The patient's clinical course was uneventful thereafter, and was discharged home. This is the first case report of native valve endocarditis caused by S. saprophyticus of confirmed urinary origin.

  11. Central diabetes insipidus in an HHV6 encephalitis patient with a posterior pituitary lesion that developed after tandem cord blood transplantation.

    PubMed

    Kawamoto, Shinichiro; Hatanaka, Kazuo; Imakita, Masami; Tamaki, Toshiharu

    2013-01-01

    A 60-year-old myelodysplastic syndrome patient underwent tandem cord blood transplantation. The primary cord blood graft was rejected, and human herpesvirus 6 (HHV6) encephalitis developed after engraftment of secondary cord blood. Polyuria and adipsic hypernatremia were observed during treatment of the encephalitis. The patient died of bacteremia caused by methicillin-resistant Streptococcus epidermis. HHV6 infection in the posterior pituitary was confirmed on autopsy, as was infection of the hippocampus, but not of the hypothalamus. This is the first case report of central diabetes insipidus caused by an HHV6 posterior pituitary infection demonstrated on a pathological examination.

  12. The AQP2 mutation V71M causes nephrogenic diabetes insipidus in humans but does not impair the function of a bacterial homolog.

    PubMed

    Klein, Noreen; Kümmerer, Nadine; Hobernik, Dominika; Schneider, Dirk

    2015-01-01

    Several point mutations have been identified in human aquaporins, but their effects on the function of the respective aquaporins are mostly enigmatic. We analyzed the impact of the aquaporin 2 mutation V71M, which causes nephrogenic diabetes insipidus in humans, on aquaporin structure and activity, using the bacterial aquaglyceroporin GlpF as a model. Importantly, the sequence and structure around the V71M mutation is highly conserved between aquaporin 2 and GlpF. The V71M mutation neither impairs substrate flux nor oligomerization of the aquaglyceroporin. Therefore, the human aquaporin 2 mutant V71M is most likely active, but cellular trafficking is probably impaired.

  13. Acute myeloid leukemia presenting with panhypopituitarism or diabetes insipidus: a case series with molecular genetic analysis and review of the literature.

    PubMed

    Cull, Elizabeth H; Watts, Justin M; Tallman, Martin S; Kopp, Peter; Frattini, Mark; Rapaport, Franck; Rampal, Raajit; Levine, Ross; Altman, Jessica K

    2014-09-01

    Central diabetes insipidus (DI) is a rare finding in patients with acute myeloid leukemia (AML), usually occurring in patients with chromosome 3 or 7 abnormalities. We describe four patients with AML and concurrent DI and a fifth patient with AML and panhypopituitarism. Four of five patients had monosomy 7. Three patients had chromosome 3q21q26/EVI-1 gene rearrangements. The molecular genotype of patients with AML and DI is not known. Therefore, we performed gene sequencing of 30 genes commonly mutated in AML in three patients with available leukemia cell DNA. One patient had no identifiable mutations, and two had RUNX1 F158S mutations.

  14. Diabetes insipidus caused by pituitary gland metastasis accompanied by iris metastasis of small cell lung cancer: case presentation and review of the literature.

    PubMed

    Alacacioğlu, Ahmet; Oztop, Ilhan; Fidan, Fatma; Akkoçlu, Atila; Kargi, Aydanur; Osma, Emine; Ada, Emel; Yilmaz, Uğur

    2008-01-01

    Metastasis to the pituitary gland and iris is rarely seen in cancer patients. Breast cancer and lung cancer are the most common tumors that metastasize to these sites. Most lung cancer patients have non-small cell lung cancer and metastasis of small cell lung cancer to the pituitary gland and iris have been very rarely reported in the literature. Here we present a case of iris metastasis and pituitary gland metastasis which caused diabetes insipidus in a patient with small cell lung cancer.

  15. Desmopressin orally disintegrating tablet in Japanese patients with central diabetes insipidus: a retrospective study of switching from intranasal desmopressin.

    PubMed

    Murakami, Takaaki; Hatoko, Tomonobu; Nambu, Takuo; Matsuda, Yuki; Matsuo, Koji; Yonemitsu, Shin; Muro, Seiji; Oki, Shogo

    2014-01-01

    Central diabetes insipidus (CDI) is a rare disease characterized by polyuria and polydipsia. Patients with CDI have been successfully treated with desmopressin administered either by intranasal instillation or oral tablets. Recently, a desmopressin orally disintegrating tablet (ODT) was approved as the first oral desmopressin tablet for CDI treatment in Japan. We conducted a retrospective single-center study of 15 Japanese CDI patients treated with desmopressin ODT therapy, which aimed to evaluate the efficacy and safety of switching to desmopressin ODT and to analyze the clinical factors that affect the desmopressin ODT dose in Japanese patients. The daily mean dose of desmopressin ODT was 104 ± 46.30 μg and the mean ratio of oral to nasal desmopressin dose was 17.0 ± 7.6, both of which are considerably smaller than those of previous dose-titration study. Moreover, the nasal spray group needed significantly smaller ratios of nasal to oral desmopressin than the nasal drop group (11.7 ± 6.5 vs 21.0 ± 5.5, p = 0.02). The ratio of oral to nasal desmopressin dose had a significant inverse correlation with the required nasal desmopressin dose. Multiple regression analysis demonstrated the ratios of nasal to oral desmopressin dose depended on intranasal formulations. In conclusion, desmopressin ODT was safe and effective in the treatment of Japanese adult CDI patients. When switching to ODT, we should care about the possibility that patients require smaller ODT doses than what was initially expected based on previously published data and also nasal formulations in terms of their differences of expected switching ratio.

  16. Hsp90 inhibitor partially corrects nephrogenic diabetes insipidus in a conditional knock-in mouse model of aquaporin-2 mutation.

    PubMed

    Yang, Baoxue; Zhao, Dan; Verkman, A S

    2009-02-01

    Mutations in aquaporin-2 (AQP2) that interfere with its cellular processing can produce autosomal recessive nephrogenic diabetes insipidus (NDI). Prior gene knock-in of the human NDI-causing AQP2 mutation T126M produced mutant mice that died by age 7 days. Here, we used a novel "conditional gene knock-in" strategy to generate adult, AQP2-T126M mutant mice. Mice separately heterozygous for floxed wild-type AQP2 and AQP2-T126M were bred to produce hemizygous mice, which following excision of the wild-type AQP2 gene by tamoxifen-induced Cre-recombinase gave AQP2(T126M/-) mice. AQP2(T126M/-) mice were polyuric (9-14 ml urine/day) compared to AQP2(+/+) mice (1.6 ml/day) and had reduced urine osmolality (400 vs. 1800 mosmol). Kidneys of AQP2(T126M/-) mice expressed core-glycosylated AQP2-T126M protein in an endoplasmic reticulum pattern. Screening of candidate protein folding "correctors" in AQP2-T126M-transfected kidney cells showed increased AQP2-T126M plasma membrane expression with the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG). 17-AAG increased urine osmolality in AQP2(T126M/-) mice by >300 mosmol but had no effect in AQP2(-/-) mice. Kidneys of 17-AAG-treated AQP2(T126M/-) mice showed partial rescue of defective AQP2-T126M cellular processing. Our results establish an adult mouse model of NDI and demonstrate partial restoration of urinary concentration function by a compound currently in clinical trials for other indications.

  17. Diabetes Insipidus as an Initial Presentation of Myelodysplastic Syndrome: Diagnosis with Single-Nucleotide Polymorphism Array-Based Karyotyping.

    PubMed

    Sun, Ruixue; Wang, Chun; Zhong, Xushu; Wu, Yu

    2016-01-01

    Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic diseases characterized by cytopenia, dysplasia and increased risk of development to acute myeloid leukemia (AML). Unfavorable cytogenetic changes such as complex karyotypes or chromosome 7 anomalies are predictive of the progression to AML and poor prognosis. Central diabetes insipidus (CDI) is the result of a deficiency of arginine vasopressin, and its major causes are idiopathic, primary or secondary tumors, neurosurgery and trauma. Importantly, CDI is a rare complication of MDS. To date, only 5 cases of MDS co-occurring with CDI have been reported; 3 of 5 had cytogenetic abnormalities uncovered by metaphase cytogenetics and 3 of 5 evolved to AML. Here, we describe a 74-year-old woman who presented with CDI as her initial symptom of MDS and eventually progressed to AML. The metaphase cytogenetics, combined with the single-nucleotide polymorphism array (SNP-A)-based karyotyping, with superiority in resolution and detecting copy number variation, revealed a complex karyotype that included monosomy of chromosome 7, deletion of 20q, and absence of heterogeneity (AOH) in more than one chromosome. To the best of our knowledge, this is the first case report of MDS co-occurring with CDI with numerous cytogenetic abnormalities revealed by the SNP-A-based karyotyping. Our case supports that the cytogenetic abnormalities may be associated with the clinical features and the prognosis of MDS co-occurring with CDI. The SNP-A-based karyotyping is helpful in revealing more subtle cytogenetic abnormalities and unveiling their roles in the pathogenesis of MDS.

  18. Vasopressin Bolus Protocol Compared to Desmopressin (DDAVP) for Managing Acute, Postoperative Central Diabetes Insipidus and Hypovolemic Shock.

    PubMed

    Shukla, Anukrati; Alqadri, Syeda; Ausmus, Ashley; Bell, Robert; Nattanmai, Premkumar; Newey, Christopher R

    2017-01-01

    Introduction. Management of postoperative central diabetes insipidus (DI) can be challenging from changes in volume status and serum sodium levels. We report a case successfully using a dilute vasopressin bolus protocol in managing hypovolemic shock in acute, postoperative, central DI. Case Report. Patient presented after bifrontal decompressive craniotomy for severe traumatic brain injury. He developed increased urine output resulting in hypovolemia and hypernatremia. He was resuscitated with intravenous fluids including a dilute vasopressin bolus protocol. This protocol consisted of 1 unit of vasopressin in 1 liter of 0.45% normal saline. This protocol was given in boluses based on the formula: urine output minus one hundred. Initial serum sodium was 148 mmol/L, and one-hour urine output was 1 liter. After 48 hours, he transitioned to 1-desamino-8-D-arginine vasopressin (DDAVP). Pre-DDAVP serum sodium was 149 mmol/L and one-hour urine output 320 cc. Comparing the bolus protocol to the DDAVP protocol, the average sodium was 143.8 ± 3.2 and 149.6 ± 3.2 mmol/L (p = 0.0001), average urine output was 433.2 ± 354.4 and 422.3 ± 276.0 cc/hr (p = 0.90), and average specific gravity was 1.019 ± 0.009 and 1.016 ± 0.01 (p = 0.42), respectively. Conclusion. A protocol using dilute vasopressin bolus can be an alternative for managing acute, central DI postoperatively, particularly in setting of hypovolemic shock resulting in a consistent control of serum sodium.

  19. Vasopressin Bolus Protocol Compared to Desmopressin (DDAVP) for Managing Acute, Postoperative Central Diabetes Insipidus and Hypovolemic Shock

    PubMed Central

    Shukla, Anukrati; Alqadri, Syeda; Ausmus, Ashley; Bell, Robert; Nattanmai, Premkumar

    2017-01-01

    Introduction. Management of postoperative central diabetes insipidus (DI) can be challenging from changes in volume status and serum sodium levels. We report a case successfully using a dilute vasopressin bolus protocol in managing hypovolemic shock in acute, postoperative, central DI. Case Report. Patient presented after bifrontal decompressive craniotomy for severe traumatic brain injury. He developed increased urine output resulting in hypovolemia and hypernatremia. He was resuscitated with intravenous fluids including a dilute vasopressin bolus protocol. This protocol consisted of 1 unit of vasopressin in 1 liter of 0.45% normal saline. This protocol was given in boluses based on the formula: urine output minus one hundred. Initial serum sodium was 148 mmol/L, and one-hour urine output was 1 liter. After 48 hours, he transitioned to 1-desamino-8-D-arginine vasopressin (DDAVP). Pre-DDAVP serum sodium was 149 mmol/L and one-hour urine output 320 cc. Comparing the bolus protocol to the DDAVP protocol, the average sodium was 143.8 ± 3.2 and 149.6 ± 3.2 mmol/L (p = 0.0001), average urine output was 433.2 ± 354.4 and 422.3 ± 276.0 cc/hr (p = 0.90), and average specific gravity was 1.019 ± 0.009 and 1.016 ± 0.01 (p = 0.42), respectively. Conclusion. A protocol using dilute vasopressin bolus can be an alternative for managing acute, central DI postoperatively, particularly in setting of hypovolemic shock resulting in a consistent control of serum sodium. PMID:28127476

  20. New autosomal recessive mutations in aquaporin-2 causing nephrogenic diabetes insipidus through deficient targeting display normal expression in Xenopus oocytes.

    PubMed

    Leduc-Nadeau, Alexandre; Lussier, Yoann; Arthus, Marie-Françoise; Lonergan, Michèle; Martinez-Aguayo, Alejandro; Riveira-Munoz, Eva; Devuyst, Olivier; Bissonnette, Pierre; Bichet, Daniel G

    2010-06-15

    Aquaporin-2 (AQP2), located at the luminal side of the collecting duct principal cells, is a water channel responsible for the final concentration of urine. Lack of function, often occurring through mistargeting of mutated proteins, induces nephrogenic diabetes insipidus (NDI), a condition characterized by large urinary volumes. In the present study, two new mutations (K228E and V24A) identified in NDI-affected individuals from distinct families along with the already reported R187C were analysed in comparison to the wild-type protein (AQP2-wt) using Xenopus laevis oocytes and a mouse collecting duct cell-line (mIMCD-3). Initial data in oocytes showed that all mutations were adequately expressed at reduced levels when compared to AQP2-wt. K228E and V24A were found to be properly targeted at the plasma membrane and exhibited adequate functionality similar to AQP2-wt, as opposed to R187C which was retained in internal stores and was thus inactive. In coexpression studies using oocytes, R187C impeded the functionality of all other AQP2 variants while combinations with K228E, V24A and AQP2-wt only showed additive functionalities. When expressed in mIMCD-3 cells, forskolin treatment efficiently promoted the targeting of AQP2-wt at the plasma membrane (>90%) while K228E only weakly responded to the same treatment (approximately 20%) and both V24A and R187C remained completely insensitive to the treatment. We concluded that both V24A and K228E are intrinsically functional water channels that lack a proper response to vasopressin, which leads to NDI as found in both compound mutations studied (K228E + R187C and V24A + R187C). The discrepancies in plasma membrane targeting response found in both expression systems stress the need to evaluate such data using mammalian cell systems.

  1. Diabetes insipidus in pediatric germinomas of the suprasellar region: characteristic features and significance of the pituitary bright spot.

    PubMed

    Kilday, John-Paul; Laughlin, Suzanne; Urbach, Stacey; Bouffet, Eric; Bartels, Ute

    2015-01-01

    The pituitary bright spot is acknowledged to indicate functional integrity of the posterior pituitary gland, whilst its absence supports a diagnosis of central diabetes insipidus (DI). This feature was evaluated, together with the incidence and clinical characteristics of DI in children with suprasellar/neurohypophyseal germinomas. We performed a review of all suprasellar (SS) or bifocal (BF) germinoma pediatric patients treated in Toronto since 2000. Demographics, symptomatology, treatment outcome and imaging were evaluated. Nineteen patients fulfilled inclusion criteria (10 SS, 9 BF; median age 12.5 years (6.2-16.8 years)). All remained alive at 6.4 years median follow-up (1.2-13.7 years) after receiving chemotherapy and radiotherapy (13 focal/ventricular, four whole brain, two neuraxis), with only one progression. All had symptoms of DI at presentation with a symptom interval above one year in eight cases (42 %). Desmopressin was commenced and maintained in 16 patients (84 %). The pituitary bright spot was lost in most diagnostic interpretable cases, but was appreciated in three patients (18 %) who had normal serum sodium values compared to 'absent' cases (p = 0.013). For two such cases, spots remained visible until last follow-up (range 0.4-3.3 years), with one still receiving desmopressin. No case of bright spot recovery was observed following therapy. Protracted symptom intervals for germinoma-induced central DI may reflect poor clinical awareness. Explanations for persistence of the pituitary bright spot in symptomatic patients remain elusive. Desmopressin seldom reverses the clinical features of germinoma-induced DI to allow discontinuation, nor does treatment cause bright spot recovery.

  2. Activation of vasopressin neurons leads to phenotype progression in a mouse model for familial neurohypophysial diabetes insipidus.

    PubMed

    Hiroi, Maiko; Morishita, Yoshiaki; Hayashi, Masayuki; Ozaki, Nobuaki; Sugimura, Yoshihisa; Nagasaki, Hiroshi; Shiota, Akira; Oiso, Yutaka; Arima, Hiroshi

    2010-02-01

    Familial neurohypophysial diabetes insipidus (FNDI) is a rare disease that is inherited in an autosomal dominant manner. In a previous study, we made a mouse model for FNDI, which showed progressive polyuria accompanied by inclusion bodies in the arginine vasopressin (AVP) neurons formed by aggregates in the endoplasmic reticulum. The present study was conducted to determine whether the activities of AVP neurons are related to the phenotype progression in the FNDI model. In the first experiment, female heterozygous mice were administered either desmopressin (dDAVP) or a vehicle (control) subcutaneously with osmotic minipumps for 30 days. The dDAVP treatment significantly decreased the urine volume, AVP mRNA expression, and inclusion bodies in the AVP neurons. Urine volume in the dDAVP group remained significantly less than the control for 14 days even after the minipumps were removed. In the second experiment, the males were fed either a 0.2% Na or 2.0% Na diet for 6 mo. Urine AVP excretion was significantly increased in the 2.0% Na group compared with the 0.2% Na group for the first 2 mo but gradually decreased thereafter. Throughout the experiments, urine volume increased progressively in the 2.0% Na group but not in the 0.2% Na group. Immunohistochemical analyses revealed that inclusion bodies in the AVP cells had significantly increased in the 2.0% Na compared with the 0.2% Na group. These data demonstrated that activation of AVP neurons could accelerate the aggregate formation as well as the progression of the polyuria in the FNDI model mice.

  3. Arginine vasopressin neuronal loss results from autophagy-associated cell death in a mouse model for familial neurohypophysial diabetes insipidus.

    PubMed

    Hagiwara, D; Arima, H; Morishita, Y; Wenjun, L; Azuma, Y; Ito, Y; Suga, H; Goto, M; Banno, R; Sugimura, Y; Shiota, A; Asai, N; Takahashi, M; Oiso, Y

    2014-03-27

    Familial neurohypophysial diabetes insipidus (FNDI) characterized by progressive polyuria is mostly caused by mutations in the gene encoding neurophysin II (NPII), which is the carrier protein of the antidiuretic hormone, arginine vasopressin (AVP). Although accumulation of mutant NPII in the endoplasmic reticulum (ER) could be toxic for AVP neurons, the precise mechanisms of cell death of AVP neurons, reported in autopsy studies, remain unclear. Here, we subjected FNDI model mice to intermittent water deprivation (WD) in order to promote the phenotypes. Electron microscopic analyses demonstrated that, while aggregates are confined to a certain compartment of the ER in the AVP neurons of FNDI mice with water access ad libitum, they were scattered throughout the dilated ER lumen in the FNDI mice subjected to WD for 4 weeks. It is also demonstrated that phagophores, the autophagosome precursors, emerged in the vicinity of aggregates and engulfed the ER containing scattered aggregates. Immunohistochemical analyses revealed that expression of p62, an adapter protein between ubiquitin and autophagosome, was elicited on autophagosomal membranes in the AVP neurons, suggesting selective autophagy induction at this time point. Treatment of hypothalamic explants of green fluorescent protein (GFP)-microtubule-associated protein 1 light chain 3 (LC3) transgenic mice with an ER stressor thapsigargin increased the number of GFP-LC3 puncta, suggesting that ER stress could induce autophagosome formation in the hypothalamus of wild-type mice as well. The cytoplasm of AVP neurons in FNDI mice was occupied with vacuoles in the mice subjected to WD for 12 weeks, when 30-40% of AVP neurons are lost. Our data thus demonstrated that autophagy was induced in the AVP neurons subjected to ER stress in FNDI mice. Although autophagy should primarily be protective for neurons, it is suggested that the organelles including ER were lost over time through autophagy, leading to autophagy

  4. Excretion of Water and Electrolytes During the Osmotic Diuresis of Dogs with Experimental Diabetes Insipidus,

    DTIC Science & Technology

    ELECTROLYTES(PHYSIOLOGY), *BODY FLUIDS, ELECTROLYTES(PHYSIOLOGY), EXCRETION, PITUITARY HORMONES , OSMOSIS, TRANSPORT PROPERTIES, MEMBRANES(BIOLOGY...BLOOD PLASMA, DIABETES, WATER, SECRETION, SODIUM, POTASSIUM, URINE, CELLS(BIOLOGY), KIDNEY FUNCTION TESTS, BIOLOGICAL ABSORPTION.

  5. Secondary nocturnal enuresis related to central diabetes insipidus as an early manifestation of intracranial germinomatous germ cell tumors in a series of male youngsters.

    PubMed

    Papaefthimiou, Apostolos; Kyrgios, Ioannis; Kotanidou, Eleni P; Maggana, Ioanna; Mouzaki, Konstantina; Galli-Tsinopoulou, Assimina

    2015-02-01

    Nocturnal enuresis is a common symptom in children. It is usually attributed to benign causes and diagnostic evaluation is not carried out. We report three male young patients initially presenting with short stature and nocturnal enuresis, related to diabetes insipidus, caused by intracranial germinomatous germ cell tumors. In all three cases, water deprivation tests confirmed diabetes insipidus. Extensive endocrinological investigation also showed further hormone deficiencies. Magnetic resonance imaging of the brain revealed the presence of a central nervous system lesion and histology confirmed the final diagnosis. Surgery, radiation with or without chemotherapy was conducted and the patients were treated with hormone replacement therapies. The patients after a long follow-up were free of disease. We present these cases to alert clinicians to bear in mind that the presence of an intracranial germinomatous germ cell tumor should at least be considered in a child presenting with bed wetting, especially if additional symptoms and signs, including late onset puberty and growth delay or morning hypernatremia, may coexist.

  6. Unmasking of Partial Diabetes Insipidus during Stress but Not Maintenance Dosing of Glucocorticoids in an Infant with Septo-Optic Dysplasia

    PubMed Central

    2011-01-01

    Background. It is well acknowledged that glucocorticoid (GC) replacement can unmask diabetes insipidus (DI) in subjects with hypopituitarism. Objective. To increase the awareness and monitoring for transient and symptomatic DI in children with partial hypopituitarism during periods in which increased GC needs are required. Methods/Case. A 2-month-old female infant with septo-optic dysplasia (SOD; on thyroid and maintenance GC replacement therapy at 8 mg/m2/day) developed transient DI during 2 separate episodes of stress (one hypothermia, one febrile) when stress dosing of GC (25 mg/m2/day) was instituted. Conclusion. Children not diagnosed with DI during initial evaluation for hypopituitarism may benefit from rescreening of serum sodium levels during acute periods of stress that demand "stress" GC dosing. This will permit treatment and/or increased vigilance for ensuing permanent DI. PMID:21603211

  7. Renal compensatory adaptation for water handling in a patient with adipsic diabetes insipidus after clipping of a ruptured aneurysm of the anterior communicating artery
.

    PubMed

    Imai, Eri; Kaneko, Shuzo; Tsukamoto, Yusuke

    2017-04-04

    A 38-year-old Japanese man who had undergone clipping surgery for a ruptured aneurysm of the anterior communicating artery 2 days prior, suddenly developed refractory hypernatremia (serum sodium (Na) 156 - 162 mmol/L). Symptoms included low plasma vasopressin, fluctuating urine osmolality (120 - 710 mOsm/kg) and lack of thirst, all suggesting adipsic diabetes insipidus (ADI). Hypernatremia was corrected by scheduled water intake with desmopressin administration. During 1-year follow-up after the surgery, his serum Na level normalized despite the suspension of desmopressin, but neither thirst nor osmolality-dependent vasopressin release recovered. Meanwhile, his urine osmolality shifted to a constant high level. The present case suggests that renal compensatory adaptation, apparently independent of the circulating vasopressin level, plays a major role in water handling in longitudinal ADI.
.

  8. Acute presentation of gestational diabetes insipidus with pre-eclampsia complicated by cerebral vasoconstriction: a case report and review of the published work.

    PubMed

    Mor, Amir; Fuchs, Yael; Zafra, Kathleen; Haberman, Shoshana; Tal, Reshef

    2015-08-01

    Gestational diabetes insipidus (GDI) is a rare, self-limited complication of pregnancy. As it is related to excess placental vasopressinase enzyme activity, which is metabolized in the liver, GDI is more common in pregnancies complicated by conditions associated with liver dysfunction. We present a case of a 41-year-old woman at 38 weeks' gestation who presented with pre-eclampsia with severe features, including impaired liver function and renal insufficiency. Following cesarean section she was diagnosed with GDI, which was further complicated by cerebral vasoconstriction as demonstrated by magnetic resonance angiography. This case raises the possibility that cerebral vasoconstriction may be related to the cause of GDI. A high index of suspicion of GDI should be maintained in patients who present with typical signs and symptoms, especially in the setting of pregnancy complications associated with liver dysfunction.

  9. Overlap of Post-obstructive Diuresis and Unmasked Diabetes Insipidus in a Case of IgG4-related Retroperitoneal Fibrosis and Tuberoinfundibular Hypophysitis: A Case Report and Review of the Literature

    PubMed Central

    Sasaki Yatabe, Midori; Watanabe, Kimio; Hayashi, Yoshimitsu; Yatabe, Junichi; Morimoto, Satoshi; Ichihara, Atsuhiro; Nakayama, Masaaki; Watanabe, Tsuyoshi

    2017-01-01

    The clinical picture of IgG4-related disease (IgG4-RD) is diverse because various organs can be affected. We describe the case of a 56-year-old man with acute renal failure and tuberoinfundibular hypophysitis due to IgG4-RD. Steroid therapy lowered the serum IgG4 level and ameliorated renal dysfunction, bilateral hydronephrosis and retroperitoneal fibrosis. However, polyuria from post-obstructive diuresis and unmasked central diabetes insipidus ensued. The patient's polyuria continued despite the administration of a therapeutic dose of glucocorticoid; the patient's pituitary swelling and anterior pituitary dysfunction were partially ameliorated. The pituitary swelling recurred seven months later. In patients with IgG4-RD, the manifestation of polyuria after steroid therapy should prompt suspicion of post-obstructive diuresis and the unmasking of central diabetes insipidus. PMID:28049999

  10. Overlap of Post-obstructive Diuresis and Unmasked Diabetes Insipidus in a Case of IgG4-related Retroperitoneal Fibrosis and Tuberoinfundibular Hypophysitis: A Case Report and Review of the Literature.

    PubMed

    Sasaki Yatabe, Midori; Watanabe, Kimio; Hayashi, Yoshimitsu; Yatabe, Junichi; Morimoto, Satoshi; Ichihara, Atsuhiro; Nakayama, Masaaki; Watanabe, Tsuyoshi

    The clinical picture of IgG4-related disease (IgG4-RD) is diverse because various organs can be affected. We describe the case of a 56-year-old man with acute renal failure and tuberoinfundibular hypophysitis due to IgG4-RD. Steroid therapy lowered the serum IgG4 level and ameliorated renal dysfunction, bilateral hydronephrosis and retroperitoneal fibrosis. However, polyuria from post-obstructive diuresis and unmasked central diabetes insipidus ensued. The patient's polyuria continued despite the administration of a therapeutic dose of glucocorticoid; the patient's pituitary swelling and anterior pituitary dysfunction were partially ameliorated. The pituitary swelling recurred seven months later. In patients with IgG4-RD, the manifestation of polyuria after steroid therapy should prompt suspicion of post-obstructive diuresis and the unmasking of central diabetes insipidus.

  11. Diabetes insipidus - central

    MedlinePlus

    ... given either as a nasal spray, tablets, or injections. This controls urine output and fluid balance and prevents dehydration . In mild cases, drinking more water may be all that is needed. If the ...

  12. Neurogenic Bladder

    PubMed Central

    Dorsher, Peter T.; McIntosh, Peter M.

    2012-01-01

    Congenital anomalies such as meningomyelocele and diseases/damage of the central, peripheral, or autonomic nervous systems may produce neurogenic bladder dysfunction, which untreated can result in progressive renal damage, adverse physical effects including decubiti and urinary tract infections, and psychological and social sequelae related to urinary incontinence. A comprehensive bladder-retraining program that incorporates appropriate education, training, medication, and surgical interventions can mitigate the adverse consequences of neurogenic bladder dysfunction and improve both quantity and quality of life. The goals of bladder retraining for neurogenic bladder dysfunction are prevention of urinary incontinence, urinary tract infections, detrusor overdistension, and progressive upper urinary tract damage due to chronic, excessive detrusor pressures. Understanding the physiology and pathophysiology of micturition is essential to select appropriate pharmacologic and surgical interventions to achieve these goals. Future perspectives on potential pharmacological, surgical, and regenerative medicine options for treating neurogenic bladder dysfunction are also presented. PMID:22400020

  13. Chronic treatment with taurine ameliorates diabetes-induced dysfunction of nitric oxide-mediated neurogenic and endothelium-dependent corpus cavernosum relaxation in rats.

    PubMed

    Dalaklioglu, Selvinaz; Kuscu, Nilay; Celik-Ozenci, Ciler; Bayram, Zeliha; Nacitarhan, Cahit; Ozdem, Sadi Satilmis

    2014-08-01

    This study was aimed to examine the effect of chronic taurine treatment on corpus cavernosum dysfunction in diabetic rats and to investigate possible underlying mechanisms. Thirty male rats were randomized to three groups of 10 each, including control, diabetic, and taurine-treated diabetic. Diabetes was induced in rats by streptozotocin (STZ, single intraperitoneal dose of 50 mg/kg body weight). Taurine was administered orally for 12 weeks (1% w/v in drinking water) from the day on which STZ was injected. At the end of the 12th week, strips of corpus cavernosum were suspended in an organ bath system for functional studies. Nitric oxide (NO)-mediated endothelium-dependent and neurogenic corpus cavernosum relaxation were evaluated by acetylcholine (ACh, 0.1-100 μm) and electrical field stimulation (EFS, 30 V, 5 ms, 2-32 Hz), respectively. The expressions of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS) (Ser-1177), neuronal nitric oxide synthase (nNOS), NADPH oxidase subunit gp91(phox) , Rho A, and Rho kinase in corpus cavernosum were semi-quantitatively assessed by immunohistochemistry. Induction of diabetes resulted in significant inhibition of NO-mediated endothelium-dependent and neurogenic corpus cavernosum relaxation. Furthermore, eNOS, p-eNOS, and nNOS expressions decreased significantly in diabetic rats compared to controls, while gp91(phox) , RhoA and Rho kinase expressions increased significantly. The diminished relaxation response to ACh and EFS as well as diabetes-related changes in expressions of these proteins in corpus cavernosum of diabetic rats was significantly improved by taurine. Taurine treatment improves NO-mediated relaxations of corpus cavernosum in diabetic rats probably by inhibiting NADPH oxidase/Rho kinase pathways.

  14. Neurogenic cough.

    PubMed

    Altman, Kenneth W; Noordzij, J Pieter; Rosen, Clark A; Cohen, Seth; Sulica, Lucian

    2015-07-01

    We review contemporary concepts of the pathophysiology of neurogenic cough, and its evaluation and treatment based on scientific publications addressing neurogenic cough. Neurogenic cough is thought to be the result of sensory neuropathy, most commonly idiopathic. Because it is principally a sensory phenomenon, clinical evaluation is challenging, the diagnosis most often being made by exclusion. Identification of motor paresis, either by laryngoscopy or laryngeal electromyography, may suggest the presence of sensory neuropathy. The utility of amitriptyline and gabapentin has been demonstrated in randomized clinical trials, and retrospective series and case reports have suggested efficacy of pregabalin, baclofen, and botulinum toxin. Sensory neuropathy appears to be an important cause of chronic refractory cough, and appears amenable to treatment with a variety of pharmacologic agents.

  15. Ovulation induction with pulsatile gonadotropin-releasing hormone (GnRH) or gonadotropins in a case of hypothalamic amenorrhea and diabetes insipidus.

    PubMed

    Georgopoulos, N A; Markou, K B; Pappas, A P; Protonatariou, A; Vagenakis, G A; Sykiotis, G P; Dimopoulos, P A; Tzingounis, V A

    2001-12-01

    Hypothalamic amenorrhea is a treatable cause of infertility. Our patient was presented with secondary amenorrhea and diabetes insipidus. Cortisol and prolactin responded normally to a combined insulin tolerance test (ITT) and thyrotropin-releasing hormone (TRH) challenge, while thyroid-stimulating hormone (TSH) response to TRH was diminished, and no response of growth hormone to ITT was detected. Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels increased following gonadotropin-releasing hormone (GnRH) challenge. No response of LH to clomiphene citrate challenge was detected. Magnetic resonance imaging findings demonstrated a midline mass occupying the inferior hypothalamus, with posterior lobe not visible and thickened pituitary stalk. Ovulation induction was carried out first with combined human menopausal gonadotropins (hMG/LH/FSH) (150 IU/day) and afterwards with pulsatile GnRH (150 ng/kg/pulse). Ovulation was achieved with both pulsatile GnRH and combine gonadotropin therapy. Slightly better results were achieved with the pulsatile GnRH treatment.

  16. Glu-47, which forms a salt bridge between neurophysin-II and arginine vasopressin, is deleted in patients with familial central diabetes insipidus

    SciTech Connect

    Yuasa, Hiromitsu; Ito, Masafumi; Nagasaki, Hiroshi; Oiso, Yutaka; Saito, Hidehiko ); Miyamoto, S.; Sasaki, N. )

    1993-09-01

    The arginine vasopressin (AVP) gene was sequenced in a pedigree with familial central diabetes insipidus (DI). When polymerase chain reaction-amplified DNAs from affected subjects were subjected to polyacrylamide gel electrophoresis, fragments including exon 2 displayed two additional, slower migrating bands. These extra bands represented DNA heteroduplexes, indicating that there was a deletion or insertion mutation in exon 2. As the region with such a mutation was identified by direct sequence analysis, polymerase chain reaction-amplified fragments including the region were subcloned and sequenced. A 3-basepair deletion (AGG) out of two consecutive AGG sequences (nucleotides 1824-1829) was identified in one of two alleles. The cosegregation of the mutation with the DI phenotype in the family was confirmed by restriction enzyme analyses. This mutation should yield an abnormal AVP precursor lacking Glu[sup 47] in its neurophysin-II (NP) moiety. Since Glu[sup 47] is essential for NP molecules to form a salt bridge with AVP, it is very likely that the function of NP as a carrier protein for AVP would be impaired. The authors suggest that AVP would undergo accelerated proteolytic degradation, and this mechanism would be involved in the pathogenesis of DI in this pedigree. 34 refs., 4 figs., 2 tabs.

  17. Potential of nonpeptide (ant)agonists to rescue vasopressin V2 receptor mutants for the treatment of X-linked nephrogenic diabetes insipidus.

    PubMed

    Los, E L; Deen, P M T; Robben, J H

    2010-05-01

    According to the body's need, water is reabsorbed from the pro-urine that is formed by ultrafiltration in the kidney. This process is regulated by the antidiuretic hormone arginine-vasopressin (AVP), which binds to its type 2 receptor (V2R) in the kidney. Mutations in the gene encoding the V2R often lead to the X-linked inheritable form of nephrogenic diabetes insipidus (NDI), a disorder in which patients are unable to concentrate their urine despite the presence of AVP. Many of these mutations are missense mutations that do not interfere with the intrinsic functionality of V2R, but cause its retention in the endoplasmic reticulum (ER), making it unavailable for AVP binding. Because the current treatments for NDI relieve its symptoms to some extent, but do not cure the disorder, cell-permeable antagonists (pharmacological chaperones) have been successfully used to stabilise the mutant receptors and restore their plasma membrane localisation. Recently, cell-permeable agonists also were shown to rescue ER-retained V2R mutants, leading to increased cAMP levels and translocation of aquaporin-2 to the apical membrane. This makes V2R-specific cell-permeable agonists very promising therapeutics for NDI as a result of misfolded V2R receptors.

  18. Novel treatment for lithium-induced nephrogenic diabetes insipidus rat model using the Sendai-virus vector carrying aquaporin 2 gene.

    PubMed

    Suga, Hidetaka; Nagasaki, Hiroshi; Kondo, Taka-Aki; Okajima, Yoshiki; Suzuki, Chizuko; Ozaki, Nobuaki; Arima, Hiroshi; Yamamoto, Tokunori; Ozaki, Noriyuki; Akai, Masaro; Sato, Aiko; Uozumi, Nobuyuki; Inoue, Makoto; Hasegawa, Mamoru; Oiso, Yutaka

    2008-11-01

    Congenital nephrogenic diabetes insipidus (NDI) is a chronic disorder involving polyuria and polydipsia that results from unresponsiveness of the renal collecting ducts to the antidiuretic hormone vasopressin. Either of the genetic defects in vasopressin V2 receptor or the water channel aquaporin 2 (AQP2) cause the disease, which interfere the water reabsorption at the epithelium of the collecting duct. An unconscious state including a perioperative situation can be life threatening because of the difficulty to regulate their water balance. The Sendai virus (SeV) vector system deleting fusion protein (F) gene (SeV/DeltaF) is considered most suitable because of the short replication cycle and nontransmissible character. An animal model for NDI with reduced AQP2 by lithium chloride was used to develop the therapy. When the SeV/DeltaF vector carrying a human AQP2 gene (AQP2-SeV/DeltaF) was administered retrogradely via ureter to renal pelvis, AQP2 was expressed in the renal collecting duct to reduce urine output and water intake by up to 40%. In combination with the retorograde administration to pelvis, this system could be the cornerstone for the applicable therapies on not only NDI patients but also other diseases associate with the medullary collecting duct.

  19. Delayed recovery of adipsic diabetes insipidus (ADI) caused by elective clipping of anterior communicating artery and left middle cerebral artery aneurysms.

    PubMed

    Tan, Jeffrey; Ndoro, Samuel; Okafo, Uchenna; Garrahy, Aoife; Agha, Amar; Rawluk, Danny

    2016-12-16

    Adipsic diabetes insipidus (ADI) is an extremely rare complication following microsurgical clipping of anterior communicating artery aneurysm (ACoA) and left middle cerebral artery (MCA) aneurysm. It poses a significant challenge to manage due to an absent thirst response and the co-existence of cognitive impairment in our patient. Recovery from adipsic DI has hitherto been reported only once. A 52-year-old man with previous history of clipping of left posterior communicating artery aneurysm 20 years prior underwent microsurgical clipping of ACoA and left MCA aneurysms without any intraoperative complications. Shortly after surgery, he developed clear features of ADI with adipsic severe hypernatraemia and hypotonic polyuria, which was associated with cognitive impairment that was confirmed with biochemical investigations and cognitive assessments. He was treated with DDAVP along with a strict intake of oral fluids at scheduled times to maintain eunatremia. Repeat assessment at six months showed recovery of thirst and a normal water deprivation test. Management of ADI with cognitive impairment is complex and requires a multidisciplinary approach. Recovery from ADI is very rare, and this is only the second report of recovery in this particular clinical setting.

  20. Sialadenosis of the major salivary glands in a patient with central diabetes insipidus--implications of aquaporin water channels in the pathomechanism of sialadenosis.

    PubMed

    Mandic, R; Teymoortash, A; Kann, P H; Werner, J A

    2005-04-01

    Sialadenosis, also referred to as sialosis, is a disease of unknown aetiology. It regularly manifests itself as a massive swelling in both parotid regions involving the major salivary glands, preferably the parotid glands and is characterized by lack of any detectable, underlying pathologies. In this case report we describe a 24-year-old white female patient with diabetes insipidus who developed sialadenosis of the major salivary glands during a period of enhanced water requirement, which the patient tried to compensate for by more frequent nasal ADH application. Since ADH acts on aquaporins (AQPs) in the kidney, we were interested if AQP expression in the patients salivary glands was affected. Surprisingly, compared to normal control tissues we observed an extensively high signal for AQP5, which is the dominant AQP found in salivary acinar cells. Interestingly, previous studies on AQP5 knock out mice found AQP5 to be required for cell volume regulation. We therefore suggest that aquaporin water channels and antidiuretic hormone together with a disturbance in the body's water household are potential key-factors in the pathophysiological events leading to the development of the disease entity called sialadenosis.

  1. V2 vasopressin receptor (V2R) mutations in partial nephrogenic diabetes insipidus highlight protean agonism of V2R antagonists.

    PubMed

    Takahashi, Kazuhiro; Makita, Noriko; Manaka, Katsunori; Hisano, Masataka; Akioka, Yuko; Miura, Kenichiro; Takubo, Noriyuki; Iida, Atsuko; Ueda, Norishi; Hashimoto, Makiko; Fujita, Toshiro; Igarashi, Takashi; Sekine, Takashi; Iiri, Taroh

    2012-01-13

    Inactivating mutations of the V2 vasopressin receptor (V2R) cause cross-linked congenital nephrogenic diabetes insipidus (NDI), resulting in renal resistance to the antidiuretic hormone AVP. In two families showing partial NDI, characterized by an apparently normal response to diagnostic tests and an increase in the basal ADH levels suggesting AVP resistance, we have identified two V2R mutations, Ser-333del and Y128S. Both mutant V2Rs, when expressed in COS-7 cells, show partial defects in vasopressin-stimulated cAMP accumulation and intracellular localization. The inhibition of internalization does not rescue their localization. In contrast, the non-peptide V2R antagonists OPC41061 and OPC31260 partially rescue the membrane localization and basal function of these V2R mutants, whereas they inhibit the basal activity of the wild-type V2R. These results indicate that a partial loss of function of Ser-333del and Y128S mutant V2Rs results from defective membrane trafficking. These findings further indicate that V2R antagonists can act as protean agonists, serving as pharmacological chaperones for inactivating V2R mutants and also as inverse agonists of wild-type receptors. We speculate that this protean agonism could underlie the possible dual beneficial effects of the V2R antagonist: improvement of hyponatremia with heart failure or polycystic kidney disease and potential rescue of NDI.

  2. [A case of possible immunoglobulin G4-related disease (IgG4-RD) with retroperitoneal fibrosis and central diabetes insipidus due to infundibulohypophysitis].

    PubMed

    Tanaka, Jun; Arai, Atsushi; Hayashi, Shigeto; Sakagami, Yoshio; Araki, Kota; Kakiuchi, Seiji; Nomura, Tetsuhiko; Kuwamura, Keiichi; Kohmura, Eiji

    2014-06-01

    We report a case of possible immunoglobulin G4-related disease(IgG4-RD)that resulted in complications such as retroperitoneal fibrosis and infundibulohypophysitis. The patient was a 72-year-old male who presented with polyuria and polydipsia. Magnetic resonance imaging(MRI)revealed a thickened pituitary stalk and contrast enhancement with gadolinium. T1-weighted imaging revealed that the posterior pituitary high-signal zone had disappeared. Central diabetes insipidus was diagnosed on the basis of results of the hypertonic saline test. In addition, pressure due to retroperitoneal fibrosis resulted in hydronephrosis and elevated serum IgG4 levels. Because it was determined that the patient could have IgG4-RD, he was administered prednisolone, following which a decrease in the size of the pituitary stalk and retroperitoneal fibrosis was observed. IgG4-RD is characterized by elevated serum IgG4 levels and the infiltration of IgG4-positive plasma cells into various organs, including the central nervous system. Recently, IgG4-RD research teams organized by the Ministry of Health, Labour and Welfare established guidelines for the diagnosis of IgG4-RD. According to these guidelines, this case would fall under the category of "possible IgG4-RD." This case suggested that when infundibulohypophysitis is detected by neuroradiology, further investigation into the possibility of IgG4-RD should be recommended.

  3. Analysis of 43 cases of Langerhans cell histiocytosis (LCH)-induced central diabetes insipidus registered in the JLSG-96 and JLSG-02 studies in Japan.

    PubMed

    Shioda, Yoko; Adachi, Souichi; Imashuku, Shinsaku; Kudo, Kazuko; Imamura, Toshihiko; Morimoto, Akira

    2011-12-01

    To determine the ability of recent systemic chemotherapy protocols to reduce the incidence of central diabetes insipidus (CDI) in Langerhans cell histiocytosis (LCH), 43 CDI cases that belonged to a cohort of 348 pediatric patients with multi-focal LCH who were treated with the JLSG-96/-02 protocols were analyzed. The overall incidence of CDI was 12.4%, but in 24 cases CDI was already present at the time LCH was diagnosed. Thus, CDI developed during or after systemic chemotherapy over a follow-up period of 5.0 (0.2-14.7) years in only 19 patients (5.9%), with 7.4% at 5-year cumulative risk by Kaplan-Meier analysis. In two cases, complete resolution of CDI was noted. Anterior pituitary hormone deficiency was detected in 13 cases, while CDI-associated neurodegenerative disease was observed in six cases. The JLSG-96/-02 protocol appears to effectively reduce the occurrence of CDI. However, novel therapeutic measures are required to reverse pre-existing CDI and to prevent CDI-associated neurological complications.

  4. A selective EP4 PGE2 receptor agonist alleviates disease in a new mouse model of X-linked nephrogenic diabetes insipidus.

    PubMed

    Li, Jian Hua; Chou, Chung-Lin; Li, Bo; Gavrilova, Oksana; Eisner, Christoph; Schnermann, Jürgen; Anderson, Stasia A; Deng, Chu-Xia; Knepper, Mark A; Wess, Jürgen

    2009-10-01

    X-linked nephrogenic diabetes insipidus (XNDI) is a severe kidney disease caused by inactivating mutations in the V2 vasopressin receptor (V2R) gene that result in the loss of renal urine-concentrating ability. At present,no specific pharmacological therapy has been developed for XNDI, primarily due to the lack of suitable animal models. To develop what we believe to be the first viable animal model of XNDI, we generated mice in which the V2R gene could be conditionally deleted during adulthood by administration of 4-OH-tamoxifen.Radioligand-binding studies confirmed the lack of V2R-binding sites in kidneys following 4-OH-tamoxifen treatment, and further analysis indicated that upon V2R deletion, adult mice displayed all characteristic symptoms of XNDI, including polyuria, polydipsia, and resistance to the antidiuretic actions of vasopressin. Gene expression analysis suggested that activation of renal EP4 PGE2 receptors might compensate for the lack of renal V2R activity in XNDI mice. Strikingly, both acute and chronic treatment of the mutant mice with a selective EP4 receptor agonist greatly reduced all major manifestations of XNDI, including changes in renal morphology.These physiological improvements were most likely due to a direct action on EP4 receptors expressed on collecting duct cells. These findings illustrate the usefulness of the newly generated V2R mutant mice for elucidating and testing new strategies for the potential treatment of humans with XNDI.

  5. Endoplasmic reticulum stress in vasopressin neurons of familial diabetes insipidus model mice: aggregate formation and mRNA poly(A) tail shortening.

    PubMed

    Arima, Hiroshi; Morishita, Yoshiaki; Hagiwara, Daisuke; Hayashi, Masayuki; Oiso, Yutaka

    2014-01-01

    The immunoglobulin heavy chain binding protein (BiP) is an endoplasmic reticulum (ER) chaperone, which binds to newly synthesized secretory and transmembrane proteins to facilitate protein folding. BiP mRNA is expressed in the arginine vasopressin (AVP) neurons in the supraoptic nucleus of wild-type mice even in basal conditions, and the expression levels increase in response to dehydration. These data suggest that AVP neurons are subjected to ER stress. Familial neurohypophysial diabetes insipidus (FNDI) is caused by mutations in the gene locus of AVP. The mutant proteins could accumulate in the ER and possibly increase ER stress in the AVP neurons. We bred mice possessing a mutation causing FNDI, which manifested progressive polyuria, as do the patients with FNDI. Electron microscopic analyses demonstrated that aggregates accumulated in the ER of AVP neurons in FNDI mice. Despite polyuria, which could potentially induce dehydration, AVP mRNA expression was decreased in the supraoptic nucleus, and the AVP mRNA poly(A) tail length was shortened in FNDI mice compared with wild-type mice. Incubation of hypothalamic explants of wild-type mice with ER stressors caused shortening of the poly(A) tail length of AVP mRNA, accompanied by decreases in the expression. These data revealed a mechanism by which ER stress decreases poly(A) tail length of AVP mRNA, and this reduces the load of unfolded proteins that form the aggregates in ER of the AVP neurons in FNDI mice.

  6. A case of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated hypertrophic pachymeningitis presenting with multiple cranial nerve palsies and diabetes insipidus.

    PubMed

    Yasuda, Ken; Sainouchi, Makoto; Goto, Masahiro; Murase, Nagako; Ohtani, Ryo; Nakamura, Michikazu

    2016-05-31

    A 61-year-old woman developed hearing difficulties and became thirsty after experiencing cold symptoms. A neurological examination revealed a loss of odor sensation, facial palsy, dysphasia, and dysarthria. Vocal cord palsy was observed during pharyngoscopy. Brain magnetic resonance imaging (MRI) showed a thickened pituitary stalk and swelling of the pituitary gland, but no high signal intensity regions were seen in the posterior portion of the pituitary gland. Gadolinium-enhanced MRI demonstrated a thickened dura mater over the anterior cranial fossa. A biopsy specimen of the thickened dura mater showed fibrosis, granulomatous inflammation, and necrotic foci. Blood tests detected myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA). The patient's urine osmolarity was low even though she exhibited hypernatremia. We diagnosed her with hypertrophic pachymeningitis associated with MPO-ANCA and diabetes insipidus. The patient received two courses of 5-day high-dose intravenous methylprednisolone (1.0 g/day), and was subsequently administered oral prednisolone, which gradually relieved her symptoms. However, the patient's symptoms recurred despite the high-dose prednisolone treatment. It was difficult to control the patient's symptoms in this case with oral prednisolone monotherapy, but combined treatment with cyclosporine resulted in sustained remission. It is considered that patients with MPO-ANCA-positive hypertrophic pachymeningitis require combination therapy with prednisolone and immunosuppressive agents at an early stage.

  7. Long-term replacement of a mutated nonfunctional CNS gene: reversal of hypothalamic diabetes insipidus using an EIAV-based lentiviral vector expressing arginine vasopressin.

    PubMed

    Bienemann, Alison S; Martin-Rendon, Enca; Cosgrave, Anna S; Glover, Colin P J; Wong, Liang-Fong; Kingsman, Susan M; Mitrophanous, Kyriacos A; Mazarakis, Nicholas D; Uney, James B

    2003-05-01

    Due to the complexity of brain function and the difficulty in monitoring alterations in neuronal gene expression, the potential of lentiviral gene therapy vectors to treat disorders of the CNS has been difficult to fully assess. In this study, we have assessed the utility of a third-generation equine infectious anemia virus (EIAV) in the Brattleboro rat model of diabetes insipidus, in which a mutation in the arginine vasopressin (AVP) gene results in the production of nonfunctional mutant AVP precursor protein. Importantly, by using this model it is possible to monitor the success of the gene therapy treatment by noninvasive assays. Injection of an EIAV-CMV-AVP vector into the supraoptic nuclei of the hypothalamus resulted in expression of functional AVP peptide in magnocellular neurons. This was accompanied by a 100% recovery in water homeostasis as assessed by daily water intake, urine production, and urine osmolality lasting for a 1-year measurement period. These data show that a single gene defect leading to a neurological disorder can be corrected with a lentiviral-based strategy. This study highlights the potential of using viral gene therapy for the long-term treatment of disorders of the CNS.

  8. Long-term gene therapy in the CNS: reversal of hypothalamic diabetes insipidus in the Brattleboro rat by using an adenovirus expressing arginine vasopressin.

    PubMed

    Geddes, B J; Harding, T C; Lightman, S L; Uney, J B

    1997-12-01

    The ability of adenovirus (Ad) to transfect most cell types efficiently has already resulted in human gene therapy trials involving the systemic administration of adenoviral constructs. However, because of the complexity of brain function and the difficulty in noninvasively monitoring alterations in neuronal gene expression, the potential of Ad gene therapy strategies for treating disorders of the CNS has been difficult to assess. In the present study, we have used an Ad encoding the arginine vasopressin cDNA (AdAVP) in an AVP-deficient animal model of diabetes insipidus (the Brattleboro rat), which allowed us to monitor chronically the success of the gene therapy treatment by noninvasive assays. Injection of AdAVP into the supraoptic nuclei (SON) of the hypothalamus resulted in expression of AVP in magnocellular neurons. This was accompanied by reduced daily water intake and urine volume, as well as increased urine osmolality lasting 4 months. These data show that a single gene defect leading to a neurological disorder can be corrected with an adenovirus-based strategy. This study highlights the potential of using Ad gene therapy for the long-term treatment of disorders of the CNS.

  9. Retrograde pyelonephritis and lumbar spondylitis as a result of Salmonella typhi in a type 2 diabetes patient with neurogenic bladder.

    PubMed

    Fukuda, Tatsuya; Bouchi, Ryotaro; Minami, Isao; Ohara, Norihiko; Nakano, Yujiro; Nishitani, Rie; Murakami, Masanori; Takeuchi, Takato; Akihisa, Momoko; Fujita, Masamichi; Izumiyama, Hajime; Hashimoto, Koshi; Yoshimoto, Takanobu; Ogawa, Yoshihiro

    2016-05-01

    We present a case of a 62-year-old diabetic woman with acute pyelonephritis and spondylitis caused by Salmonella typhi. She was admitted to Tokyo Medical Dental University Hospital, Tokyo, Japan, because of unconsciousness and was diagnosed with sepsis by retrograde pyelonephritis as a result of Salmonella typhi. Antibiotics treatment was immediately started; however, she subsequently developed lumbar spondylitis, and long-term conservative treatment with antibiotics and a fixing device were required. This is the first report of a diabetic patient who developed retrograde urinary tract infection with Salmonella typhi, followed by sepsis and spondylitis. The infection could be a result of diabetic neuropathy, presenting neurogenic bladder and hydronephrosis. The patient was successfully treated with antibiotics and became asymptomatic with normal inflammatory marker levels, and no clinical sign of recurrence was observed in the kidney and spine at 4 months.

  10. Efficacy of Hydrochlorothiazide and low renal solute feed in Neonatal Central Diabetes Insipidus with transition to Oral Desmopressin in early infancy

    PubMed Central

    2014-01-01

    Background The treatment of central diabetes insipidus (DI) with desmopressin in the neonatal period is challenging because of the significant risk of hyponatremia with this agent. The fixed anti-diuresis action of desmopressin and the obligate high fluid intake with milk feeds lead to considerable risk of water intoxication and hyponatremia. To reduce this risk, thiazide diuretics, part of the treatment of nephrogenic DI, were used in conjunction with low renal solute feed and were effective in a single case series of neonatal central DI. Aim We evaluated the efficacy of early treatment of neonatal central DI with hydrochlorothiazide with low solute feed and investigated the clinical indicators for transition to desmopressin during infancy. Methods A retrospective chart review was conducted at Princess Margaret Hospital, Perth of neonates diagnosed with central DI and treated with hydrochlorothiazide, between 2007 and 2013. Four newborns were identified. Mean sNa and mean change in sNa with desmopressin and hydrochlorothiazide treatment were recorded along with episodes of hyponatremia and hypernatremia. Length and weight trajectories during the first 12 months were assessed. Results The mean change in sNa per day with hydrochlorothiazide and low renal solute feed was 2.5 - 3 mmol/L; on desmopressin treatment, the mean change in sNa was 6.8-7.9 mmol/L. There was one episode of symptomatic hyponatremia with intranasal desmopressin with no episodes of hyponatremia or hypernatremia during treatment with hydrochlorothiazide or following transition to oral desmopressin. Transition to oral desmopressin between 3 to 12 months of age was associated with good control of DI. Following introduction of solids, sNa remained stable but weight gain was slow. This improved following transition to desmopressin in one infant. Conclusions Hydrochlorothiazide with low renal solute feed is a safe and effective treatment option in neonatal central DI. However, transition to

  11. Efficacy and safety of desmopressin orally disintegrating tablet in patients with central diabetes insipidus: results of a multicenter open-label dose-titration study.

    PubMed

    Arima, Hiroshi; Oiso, Yutaka; Juul, Kristian Vinter; Nørgaard, Jens Peter

    2013-01-01

    Central diabetes insipidus (CDI) is associated with arginine vasopressin (AVP) deficiency with resultant polyuria and polydipsia. Intranasal desmopressin provides physiological replacement but oral formulations are preferred for their ease of administration. This study aimed to demonstrate the efficacy and safety of desmopressin orally disintegrating tablet (ODT) in the treatment of Japanese patients with CDI, and confirm that antidiuresis is maintained on switching from intranasal desmopressin to desmopressin ODT. A total of 20 patients aged 6-75 years with CDI were included in this 4-week multicenter, open-label study. Following observation, patients switched from intranasal desmopressin to desmopressin ODT with titration to optimal dose over ≤5 days at the study site. Following three consecutive doses with stable patient fluid balance, patients were discharged with visits at Weeks 2 and 4. Following titration from intranasal desmopressin to ODT, the mean 24-hour urine volume was unchanged, indicating similar antidiuresis with both formulations. The proportion of patients with endpoint measurements (urine osmolality, 24-hour urine volume, hourly diuresis rate and urine-specific gravity) within normal range at Days 1-2 (intranasal desmopressin) and Week 4 (desmopressin ODT) was similar. The mean daily dose ratio of intranasal desmopressin to desmopressin ODT (Week 4) was 1:24 but a wide range was observed across individuals to maintain adequate antidiuretic effect. Hyponatraemia was generally mild and managed by dose titration. Desmopressin ODT achieved sufficient antidiuretic control compared to intranasal therapy and was well tolerated over long-term treatment. The wide range of intranasal:ODT dose ratios underline the importance of individual titration.

  12. Identification and characterization of a novel X-linked AVPR2 mutation causing partial nephrogenic diabetes insipidus: a case report and review of the literature.

    PubMed

    Neocleous, Vassos; Skordis, Nicos; Shammas, Christos; Efstathiou, Elisavet; Mastroyiannopoulos, Nikolaos P; Phylactou, Leonidas A

    2012-07-01

    X-linked nephrogenic diabetes insipidus (NDI) is a rare disease characterized by a malfunctioning renal response to the antidiuretic hormone arginine vasopressin (AVP) due to mutations in the AVPR2 gene. A limited number of mutations in the AVPR2 gene resulting in partial phenotype have been described so far. In this mini-review the retrospective analysis of 13 known AVPR2 mutations that have been previously shown in vitro to partially abolish AVPR2 function is described, along with a novel mutation diagnosed in a kindred with partial NDI. In the present study, a 14 year old male and his 73 year old maternal grandfather were diagnosed with partial NDI based on the clinical phenotype, the water deprivation test and the inadequate response to 1-desamino-8-d-arginine vasopressin (DDAVP) administration. Sequencing analysis of the AVPR2 gene revealed the novel missense mutation p.N317S (g.1417A > G) in both patients. This mutation was re-created by site directed mutagenesis in an AVPR2 cDNA expression vector and was functionally characterized, in terms of arginine vasopressin (AVP) and DDAVP response. AVPR2 activity of the p.N317S mutant receptor after the AVP and DDAVP administration, as assessed by cAMP production was reduced and impaired when compared to cells that expressed the wild type AVPR2 gene. In conclusion, the affected members of this family have X-linked NDI with partial resistance to AVP, due to a missense mutation in the AVPR2 gene.

  13. The water deprivation test and a potential role for the arginine vasopressin precursor copeptin to differentiate diabetes insipidus from primary polydipsia.

    PubMed

    de Fost, M; Oussaada, S M; Endert, E; Linthorst, G E; Serlie, M J; Soeters, M R; DeVries, J H; Bisschop, P H; Fliers, E

    2015-06-01

    The water deprivation test is the gold standard test to differentiate central or nephrogenic diabetes insipidus (DI) from primary polydipsia (PP) in patients with polyuria and polydipsia. Few studies have addressed the diagnostic performance of this test. The aim of this retrospective cohort study was to evaluate the diagnostic performance of the standard water deprivation test, including plasma arginine vasopressin (AVP) measurements, in 40 consecutive patients with polyuria. We compared initial test results with the final clinical diagnosis, i.e., no DI, central DI, or nephrogenic DI. The median length of follow-up was 8 years. In a subset of ten patients, the novel marker copeptin (CP) was measured in plasma. Using the final diagnosis as a gold standard, a threshold for urine osmolality of >800 mOsmol/kg after water deprivation yielded a sensitivity and specificity of 96 and 100%, respectively, for diagnosing PP. Sensitivity increased to 100% if the cut-off value for urine osmolality was set at 680 mOsmol/kg. Plasma AVP levels did not differ between patient groups and did not differentiate among central DI, nephrogenic DI, or PP. In all three patients with central DI, plasma CP was <2.5 pmol/l with plasma osmolality >290 mOsmol/kg, and >2.5 pmol/l in patients without DI. The optimal cut-off value for differentiating PP from DI during a water deprivation test was urine osmolality >680 mOsmol/kg. Differentiating between central and nephrogenic DI should be based on clinical judgment as AVP levels did not discriminate.

  14. Pregnancy may favour the development of severe autoimmune central diabetes insipidus in women with vasopressin cell antibodies: description of two cases.

    PubMed

    Bellastella, Giuseppe; Bizzarro, Antonio; Aitella, Ernesto; Barrasso, Mariluce; Cozzolino, Domenico; Di Martino, Sergio; Esposito, Katherine; De Bellis, Annamaria

    2015-03-01

    Recently, an increased incidence of central diabetes insipidus (CDI) in pregnancy, and less frequently in the post partum period, has been reported, most probably favoured by some conditions occurring in pregnancy. This study was aimed at investigating the influence of pregnancy on a pre-existing potential/subclinical hypothalamic autoimmunity. We studied the longitudinal behaviour of arginine-vasopressin cell antibodies (AVPcAbs) and post-pituitary function in two young women with a positive history of autoimmune disease and presence of AVPcAbs, but without clinical CDI, and who became pregnant 5 and 7 months after our first observation. The behaviour of post-pituitary function and AVPcAbs (by immunofluorescence) was evaluated at baseline, during pregnancy and for 2 years after delivery. AVPcAbs, present at low/middle titres at baseline in both patients, showed a titre increase during pregnancy in one patient and after delivery in the other patient, with development of clinically overt CDI. Therapy with 1-deamino-8-d-arginine vasopressin (DDAVP) caused a prompt clinical remission. After a first unsuccessful attempt of withdrawal, the therapy was definitively stopped at the 6th and the 7th month of post partum period respectively, when AVPcAbs disappeared, accompanied by post-pituitary function recovery, persisting until the end of the follow-up. The determination of AVPcAbs is advisable in patients with autoimmune diseases planning their pregnancy, because they could be considered good predictive markers of gestational or post partum autoimmune CDI. The monitoring of AVPcAb titres and post-pituitary function during pregnancy in these patients may allow for an early diagnosis and an early replacement therapy, which could induce the disappearance of these antibodies with consequent complete remission of CDI.

  15. Diabetes insipidus and, partially, low anxiety-related behaviour are linked to a SNP-associated vasopressin deficit in LAB mice.

    PubMed

    Kessler, Melanie S; Murgatroyd, Chris; Bunck, Mirjam; Czibere, Ludwig; Frank, Elisabeth; Jacob, Wolfgang; Horvath, Charlotte; Muigg, Patrik; Holsboer, Florian; Singewald, Nicolas; Spengler, Dietmar; Landgraf, Rainer

    2007-11-01

    Following secretion from the posterior pituitary, the neuropeptide vasopressin (AVP) stimulates the kidney to retain water, and when released centrally it can contribute to anxiety- and depression-like behaviours. We hypothesized that CD1 mice bred for low trait anxiety (LAB) suffer from a deficit in AVP. Both osmotically stimulated peripheral secretion and intra-paraventricular nucleus (PVN) release of AVP were found decreased in LAB animals compared with normal anxiety (NAB) or high anxiety (HAB) controls. Consequently, in addition to their extreme non-anxiety, LAB mice showed signs of central diabetes insipidus (cDI), including increased fluid intake and reduced urine osmolality, as well as a pathological increase in plasma osmolality upon water deprivation. These cDI symptoms were attenuated by administration of a selective AVP V2 receptor agonist. A single nucleotide polymorphism (SNP) in exon 1 (C(+40)T) of the Avp gene of LAB animals causes an amino acid substitution in the signal peptide of the AVP precursor, and is likely to impair processing and trafficking of the precursor, as suggested by reduced axonal transport of AVP from the hypothalamic PVN, finally contributing to cDI symptoms and low trait anxiety. In an F2 panel, this SNP co-segregated with fluid intake and showed a partial contribution to low anxiety-related behaviour, indicated by its co-segregation with time spent on the open arms of the elevated plus-maze in a subset of F2 mice. Thus, the SNP-associated deficit in plasma and central AVP contributes to signs of cDI and, at least partially, to low trait anxiety, both features being typical of LAB animals.

  16. P2Y12 Receptor Localizes in the Renal Collecting Duct and Its Blockade Augments Arginine Vasopressin Action and Alleviates Nephrogenic Diabetes Insipidus.

    PubMed

    Zhang, Yue; Peti-Peterdi, Janos; Müller, Christa E; Carlson, Noel G; Baqi, Younis; Strasburg, David L; Heiney, Kristina M; Villanueva, Karie; Kohan, Donald E; Kishore, Bellamkonda K

    2015-12-01

    P2Y12 receptor (P2Y12-R) signaling is mediated through Gi, ultimately reducing cellular cAMP levels. Because cAMP is a central modulator of arginine vasopressin (AVP)-induced water transport in the renal collecting duct (CD), we hypothesized that if expressed in the CD, P2Y12-R may play a role in renal handling of water in health and in nephrogenic diabetes insipidus. We found P2Y12-R mRNA expression in rat kidney, and immunolocalized its protein and aquaporin-2 (AQP2) in CD principal cells. Administration of clopidogrel bisulfate, an irreversible inhibitor of P2Y12-R, significantly increased urine concentration and AQP2 protein in the kidneys of Sprague-Dawley rats. Notably, clopidogrel did not alter urine concentration in Brattleboro rats that lack AVP. Clopidogrel administration also significantly ameliorated lithium-induced polyuria, improved urine concentrating ability and AQP2 protein abundance, and reversed the lithium-induced increase in free-water excretion, without decreasing blood or kidney tissue lithium levels. Clopidogrel administration also augmented the lithium-induced increase in urinary AVP excretion and suppressed the lithium-induced increase in urinary nitrates/nitrites (nitric oxide production) and 8-isoprostane (oxidative stress). Furthermore, selective blockade of P2Y12-R by the reversible antagonist PSB-0739 in primary cultures of rat inner medullary CD cells potentiated the expression of AQP2 and AQP3 mRNA, and cAMP production induced by dDAVP (desmopressin). In conclusion, pharmacologic blockade of renal P2Y12-R increases urinary concentrating ability by augmenting the effect of AVP on the kidney and ameliorates lithium-induced NDI by potentiating the action of AVP on the CD. This strategy may offer a novel and effective therapy for lithium-induced NDI.

  17. P2Y12 Receptor Localizes in the Renal Collecting Duct and Its Blockade Augments Arginine Vasopressin Action and Alleviates Nephrogenic Diabetes Insipidus

    PubMed Central

    Zhang, Yue; Peti-Peterdi, Janos; Müller, Christa E.; Carlson, Noel G.; Baqi, Younis; Strasburg, David L.; Heiney, Kristina M.; Villanueva, Karie; Kohan, Donald E.

    2015-01-01

    P2Y12 receptor (P2Y12-R) signaling is mediated through Gi, ultimately reducing cellular cAMP levels. Because cAMP is a central modulator of arginine vasopressin (AVP)-induced water transport in the renal collecting duct (CD), we hypothesized that if expressed in the CD, P2Y12-R may play a role in renal handling of water in health and in nephrogenic diabetes insipidus. We found P2Y12-R mRNA expression in rat kidney, and immunolocalized its protein and aquaporin-2 (AQP2) in CD principal cells. Administration of clopidogrel bisulfate, an irreversible inhibitor of P2Y12-R, significantly increased urine concentration and AQP2 protein in the kidneys of Sprague–Dawley rats. Notably, clopidogrel did not alter urine concentration in Brattleboro rats that lack AVP. Clopidogrel administration also significantly ameliorated lithium-induced polyuria, improved urine concentrating ability and AQP2 protein abundance, and reversed the lithium-induced increase in free-water excretion, without decreasing blood or kidney tissue lithium levels. Clopidogrel administration also augmented the lithium-induced increase in urinary AVP excretion and suppressed the lithium-induced increase in urinary nitrates/nitrites (nitric oxide production) and 8-isoprostane (oxidative stress). Furthermore, selective blockade of P2Y12-R by the reversible antagonist PSB-0739 in primary cultures of rat inner medullary CD cells potentiated the expression of AQP2 and AQP3 mRNA, and cAMP production induced by dDAVP (desmopressin). In conclusion, pharmacologic blockade of renal P2Y12-R increases urinary concentrating ability by augmenting the effect of AVP on the kidney and ameliorates lithium-induced NDI by potentiating the action of AVP on the CD. This strategy may offer a novel and effective therapy for lithium-induced NDI. PMID:25855780

  18. [A 29-year-old man with diabetes insipidus and cerebellar ataxia and development of spinal cord swelling 15 years after the onset].

    PubMed

    Ohkuma, Y; Sato, K; Ohtomo, T; Ohishi, H; Mitsuoka, H; Mori, H; Hirai, S; Takubo, H; Takeda, N; Sato, K; Mizuno, Y

    1997-05-01

    We report a 29-year-old man with diabetes insipidus and cerebellar ataxia who developed spinal cord swelling 15 years after the onset. He was well until 14 years of the age when he noted dizziness. Two years after there was an onset of gait disturbance and slurred speech. He also noted polydipsia and polyuria. He was evaluated at the neurosurgery service of our hospital when he was 17 years of the age. Neurologic examination at that time revealed memory loss, horizontal nystagmus, cerebellar ataxic gait, dysmetria and decomposition more on the left. Cranial CT scan revealed a mass lesion involving the left subthalamic region and the head of the caudate area. Spinal fluid was unremarkable, however, human chorionic gonadotropin was increased to 27 mIU/ml. He was treated by radiation therapy (3,000 rads for total brain area and 5,460 rads for focal region). His CT scan and memory loss improved, however, cerebellar ataxia was unchanged. Three years after the radiation, he started to show choreic movement in his neck and left upper extremity. He was admitted to our service in August 14, 1995 when he was 29 years of the age. On admission, he was alert but disoriented to time; calculation was also poor. Higher cerebral functions were intact. The optic fundi were normal without papilledema. Visual field appeared intact. Gaze nystagmus was observed in all the directions, but more prominent in the horizontal direction. Speech was slurred. Otherwise, cranial nerves were unremarkable. Motor wise, he showed marked truncal and gait ataxia; he was unable to walk because of ataxia. Muscle atrophy and marked weakness was noted in both upper extremities more on the left side. Deep tendon reflexes were diminished in the upper extremities but active in the lower extremities. He was polyuric; urinary specific gravity was low. Spinal fluid contained 6 cells/cmm and 113 mg/ dl of protein; Queckenstedt was positive. MRI revealed swelling of the cervical cord; in addition, the entire

  19. Neuromodulation in neurogenic bladder

    PubMed Central

    Sanford, Melissa T.

    2016-01-01

    While neuromodulation is a well-established treatment option for patients with non-neurogenic overactive bladder and urinary retention, its applicability to the neurogenic bladder population has only recently been examined more in depth. In this article we will discuss the outcomes, contraindications, and special considerations of sacral and percutaneous tibial nerve stimulation (PTNS) in patients with neurogenic lower urinary tract dysfunction. PMID:26904417

  20. Analysis of the V2 Vasopressin Receptor (V2R) Mutations Causing Partial Nephrogenic Diabetes Insipidus Highlights a Sustainable Signaling by a Non-peptide V2R Agonist.

    PubMed

    Makita, Noriko; Sato, Tomohiko; Yajima-Shoji, Yuki; Sato, Junichiro; Manaka, Katsunori; Eda-Hashimoto, Makiko; Ootaki, Masanori; Matsumoto, Naoki; Nangaku, Masaomi; Iiri, Taroh

    2016-10-21

    Disease-causing mutations in G protein-coupled receptor (GPCR) genes, including the V2 vasopressin receptor (V2R) gene, often cause misfolded receptors, leading to a defect in plasma membrane trafficking. A novel V2R mutation, T273M, identified in a boy with partial nephrogenic diabetes insipidus (NDI), shows intracellular localization and partial defects similar to the two mutants we described previously (10). Although non-peptide V2R antagonists have been shown to rescue the membrane localization of V2R mutants, their level of functional rescue is weak. Interestingly, it has been reported that a non-peptide agonist, OPC51803, activates misfolded V2R mutants intracellularly without degradation, thus potentially serving as a therapeutic agent against NDI (14). In our current experiments, however, a peptide antagonist blocked arginine vasopressin (AVP)- or OPC51803-stimulated cAMP accumulation both in COS-7 and MDCK cells, suggesting that OPC51803 mainly stimulates cell surface V2R mutants. In addition, our analyses revealed that OPC51803 works not only as a non-peptide agonist that causes activation/β-arrestin-dependent desensitization of V2R mutants expressed at the plasma membrane but also as a pharmacochaperone that promotes the endoplasmic reticulum-retained mutant maturation and trafficking to the plasma membrane. The ratio of the pharmacochaperone effect to the desensitization effect likely correlates negatively with the residual function of the tested mutants, suggesting that OPC5 has a more favorable effect on the V2R mutants with a less residual function. We speculated that the canceling of the desensitization effect of OPC51803 by the pharmacochaperone effect after long-term treatment may produce sustainable signaling, and thus pharmacochaperone agonists such as OPC51803 may serve as promising therapeutics for NDI caused by misfolded V2R mutants.

  1. Neurogenic muscle cramps.

    PubMed

    Katzberg, Hans D

    2015-08-01

    Muscle cramps are sustained, painful contractions of muscle and are prevalent in patients with and without medical conditions. The objective of this review is to present updates on the mechanism, investigation and treatment of neurogenic muscle cramps. PubMed and Embase databases were queried between January 1980 and July 2014 for English-language human studies. The American Academy of Neurology classification of studies (classes I-IV) was used to assess levels of evidence. Mechanical disruption, ephaptic transmission, disruption of sensory afferents and persistent inward currents have been implicated in the pathogenesis of neurogenic cramps. Investigations are directed toward identifying physiological triggers or medical conditions predisposing to cramps. Although cramps can be self-limiting, disabling or sustained muscle cramps should prompt investigation for underlying medical conditions. Lifestyle modifications, treatment of underlying conditions, stretching, B-complex vitamins, diltiezam, mexiletine, carbamazepine, tetrahydrocannabinoid, leveteracitam and quinine sulfate have shown evidence for treatment.

  2. Wolfram Syndrome presenting with optic atrophy and diabetes mellitus: two case reports.

    PubMed

    Manaviat, Masoud Reza; Rashidi, Maryam; Mohammadi, Seyed Mohammad

    2009-12-19

    Wolfram syndrome is the constellation of juvenile onset diabetes mellitus and optic atrophy, known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness).Patients demonstrate diabetes mellitus followed by optic atrophy in the first decade, diabetes insipidus and sensorineural deafness in the second decade, dilated renal outflow tracts early in the third decade, and multiple neurological abnormalities early in the fourth decade.This study reports two siblings with late diagnosed wolfram syndrome with diabetes insipidus, diabetes mellitus, optic atrophy, deafness and severe urological abnormalities.In conclusion, cases having early onset insulin-dependent diabetes mellitus and optic atrophy together need to be evaluated with respect to Wolfram.

  3. Primary neurogenic orthostatic hypotension

    PubMed Central

    Hughes, R. C.; Cartlidge, N. E. F.; Millac, P.

    1970-01-01

    Eight further cases of neurogenic orthostatic hypotension are described together with a necropsy study on one case. Three cases showed evidence of autonomic dysfunction in isolation, while in five cases this was accompanied by evidence of more diffuse central nervous system degeneration. (Parkinsonism, cerebellar ataxia, dementia, pyramidal signs, bulbar weakness, and muscular wasting were all seen in varying proportions.) The various clinical presentations, investigations, pathology, treatment, and prognosis are discussed. In the experience of the authors, when assessed, an abnormal Valsalva response is invariable, confirming the breakdown of the circulatory reflex. A normal vasopressor response is likewise invariable, eliminating an abnormality of blood vessels themselves, and confirming the lesion as neurogenic. The demonstration of loss of sweating to indirect body heating, which also is usual suggests that the defect is central or on the efferent side of the reflex and a normal pilo-erector response to acetylcholine confirms this as preganglionic. Emphasis is laid on the non-specificity of many accepted physiological tests in this disorder and on the delay in diagnosis consequent upon the variable presentation. PMID:5431725

  4. Augmentation cystoplasty in neurogenic bladder

    PubMed Central

    Kocjancic, Ervin; Demirdağ, Çetin

    2016-01-01

    The aim of this review is to update the indications, contraindications, technique, complications, and the tissue engineering approaches of augmentation cystoplasty (AC) in patients with neurogenic bladder. PubMed/MEDLINE was searched for the keywords "augmentation cystoplasty," "neurogenic bladder," and "bladder augmentation." Additional relevant literature was determined by examining the reference lists of articles identified through the search. The update review of of the indications, contraindications, technique, outcome, complications, and tissue engineering approaches of AC in patients with neurogenic bladder is presented. Although some important progress has been made in tissue engineering AC, conventional AC still has an important role in the surgical treatment of refractory neurogenic lower urinary tract dysfunction. PMID:27617312

  5. Neurogenic bladder in Hunter's syndrome.

    PubMed Central

    Koyama, K; Moda, Y; Sone, A; Tanaka, H; Hino, Y

    1994-01-01

    We encountered a rare patient with Hunter's syndrome who exhibited urinary retention as a result of a neurogenic bladder, uninhibited detrusor contractions, and detrusor-sphincter dyssynergia. Neurological findings were consistent with cervical myelopathy and cervical MR imaging showed very narrow segments at the cord level C2-4. We speculate that this Hunter's syndrome patient has cervical myelopathy and that this neurological dysfunction causes the neurogenic bladder. PMID:8014981

  6. [Neurogenic foot deformities].

    PubMed

    Senst, S

    2010-01-01

    There is a multitude of neurological diseases which may lead to neuro-orthopaedic problems and subsequently to neurogenic foot deformities. For this reason the diagnostician will be consistently surprised that there is a great multitude of different foot abnormalities and that not only the typical spastic talipes equines dominates. Of particular significance here is that these deformities almost always develop progressively, whereas most diseases persist per se, cerebral palsy being a typical case in point. However, in MMC (myelomeningocele) patients, there is also the danger of a worsening of the basic problem in the case of tethered cord syndrome. Unlike congenital talipes equinovarus, neuro-orthopaedic talipes equinovarus often shows over- or undercorrection postoperatively due to a shift in muscle imbalance. It is important, therefore, that the basis of conservative therapy include regular physiotherapy and orthoses during the day and, if necessary, at night. Botulinum toxin has been established as an additional measure for spasticity; however, this cannot always prevent surgical intervention, but is able to delay this to a better point in the development of the child/patient. The present article describes the diversity of neurological deformities and presents conservative as well as surgical therapeutic approaches.

  7. [Neurogenic stunned myocardium].

    PubMed

    Ruiz Bailén, M; Rucabado Aguilar, L; López Martínez, A

    2006-01-01

    The existence of stunned myocardium and reversible myocardial dysfunction is widely described and accepted in patients suffering ischemic heart disease. However, it cannot be exclusive to coronary disease. Classically, the appearance of electrocardiographic changes in the critical neurological disease has been described. However, at present, it seems to be observed that some of these patients with critical neurological disease could have variable grades of myocardial dysfunction, which is generally reversible in the surviving patients. This myocardial dysfunction, which could affect critically ill neurological patients, has traits similar to stunned myocardium generated in coronary patients since: a) it is generally associated to electrocardiographic changes, b) it can be accompanied by segmental contractility disorders and even c) it may be accompanied by a certain increase of cardiac biomarkers. Although its etiopathogeny is unknown, it could be related with the severity of the primary neurological disease. Its prophylaxis and prognosis are also unknown. It could be related with neurogenic edema, with hemodynamic instability, and could also play a very important role in brain death and in organ donation.

  8. Diabetes

    MedlinePlus

    ... version of this page please turn Javascript on. Diabetes What is Diabetes? Too Much Glucose in the Blood Diabetes means ... high, causing pre-diabetes or diabetes. Types of Diabetes There are three main kinds of diabetes: type ...

  9. Understanding migraine: Potential role of neurogenic inflammation

    PubMed Central

    Malhotra, Rakesh

    2016-01-01

    Neurogenic inflammation, a well-defined pathophysiologial process is characterized by the release of potent vasoactive neuropeptides, predominantly calcitonin gene-related peptide (CGRP), substance P (SP), and neurokinin A from activated peripheral nociceptive sensory nerve terminals (usually C and A delta-fibers). These peptides lead to a cascade of inflammatory tissue responses including arteriolar vasodilation, plasma protein extravasation, and degranulation of mast cells in their peripheral target tissue. Neurogenic inflammatory processes have long been implicated as a possible mechanism involved in the pathophysiology of various human diseases of the nervous system, respiratory system, gastrointestinal tract, urogenital tract, and skin. The recent development of several innovative experimental migraine models has provided evidence suggestive of the involvement of neuropeptides (SP, neurokinin A, and CGRP) in migraine headache. Antidromic stimulation of nociceptive fibers of the trigeminal nerve resulted in a neurogenic inflammatory response with marked increase in plasma protein extravasation from dural blood vessels by the release of various sensory neuropeptides. Several clinically effective abortive antimigraine medications, such as ergots and triptans, have been shown to attenuate the release of neuropeptide and neurogenic plasma protein extravasation. These findings provide support for the validity of using animal models to investigate mechanisms of neurogenic inflammation in migraine. These also further strengthen the notion of migraine being a neuroinflammatory disease. In the clinical context, there is a paucity of knowledge and awareness among physicians regarding the role of neurogenic inflammation in migraine. Improved understanding of the molecular biology, pharmacology, and pathophysiology of neurogenic inflammation may provide the practitioner the context-specific feedback to identify the novel and most effective therapeutic approach to treatment

  10. Droxidopa in neurogenic orthostatic hypotension

    PubMed Central

    Kaufmann, Horacio; Norcliffe-Kaufmann, Lucy; Palma, Jose-Alberto

    2015-01-01

    Neurogenic orthostatic hypotension (nOH) is a fall in blood pressure on standing due to reduced norepinephrine release from sympathetic nerve terminals. nOH is a feature of several neurological disorders that affect the autonomic nervous system, most notably Parkinson disease (PD), multiple system atrophy, pure autonomic failure and other autonomic neuropathies. Droxidopa, an orally active synthetic amino acid that is converted to norepinephrine by the enzyme aromatic L-amino acid decarboxylase (dopa-decarboxylase), was recently approved by the FDA for the short-term treatment of nOH. It is presumed to raise blood pressure by acting at the neurovascular junction to increase vascular tone. This review summarizes the pharmacological properties of droxidopa, its mechanism of action, and the efficacy and safety results of clinical trials. PMID:26092297

  11. [Disorders of bladder compliance and neurogenic bladder].

    PubMed

    Chartier-Kastler, E; Comperat, E; Ruffion, A

    2007-05-01

    Bladder compliance is defined as the relationship between change in bladder volume and change in detrusor pressure (DV/DP). The pathophysiology of neurogenic disorders of bladder compliance is still poorly understood. Experimental reduction of blood flow in the bladder wall, bilateral hypogastric nerve section in rats, the study of spinalized rat bladders, and reduction of oestrogen impregnation show that these conditions induce loss of the viscoelastic properties of the bladder. With the arrival of new treatments active on afferent and/or efferent pathways or on the central nervous system, it is very important to improve our understanding of the pathophysiology of neurogenic disorders of bladder compliance. The reversibility of these disorders constitutes a major therapeutic challenge and their functional consequences constitute a crucial prognostic element of neurogenic bladder. Disorders of bladder compliance can be assessed clinically from two points of view: 1) The natural history of onset of these disorders in neurogenic bladder. Clinical experience demonstrates certain risk factors for the development of these disorders, such as the voiding mode (intermittent self-catheterization or by a carer versus indwelling catheter), the level of the spinal cord lesion (suprasacral versus sacral, incomplete versus complete, and cauda equina lesions), and the presence of myelomeningocele. 2) Data derived from conservative management of these disorders in patients with neurogenic bladder: urethral dilatation, various types of sphincterotomy, vesical denervation, alpha-blockers, sympatholytics, vanilloids (resiniferatoxin and capsaicin), intra-detrusor botulinum toxin and intrathecal baclofen have been shown to improve disorders of compliance of neurogenic bladder.

  12. Cervicobrachial pain - How Often is it Neurogenic?

    PubMed Central

    Nair, N. Sreekumaran; Bhat, Anil K; Solomon, John M

    2016-01-01

    Introduction Neck pain associated with pain in the arm (cervicobrachial pain) is a common complaint in patients seeking physiotherapy management. The source of symptoms for this complaint is commonly presumed to be neural. However, this pain pattern could also result from various other innervated tissue structures of the upper quarter. Knowledge about frequency of neural structures being a predominant source of symptoms would help in implementing appropriate therapeutic strategies such as neural tissue mobilization along with other complimentary therapies for optimal outcomes. Aim To determine the frequency of cervicobrachial pain being neurogenic. Materials and Methods Participants (n=361) aged between 20-65 years, reporting cervicobrachial pain were screened for neurogenic nature of symptoms. These physical signs included: active and passive movement dysfunction, adverse responses to neural tissue provocation tests, tenderness on palpating nerve trunks and related cutaneous tissues and evidence of a related local area of pathology (Clinical/radiological). The consistency of all these signs was checked to identify a significant neural involvement. Results Descriptive statistics were used to analyse data. Of 361 participants, 206 were males (44.6 ±10.8 years) and 155 were females (41.8 ± 11.2 years). The frequency of neurogenic cervicobrachial pain was determined to be 19.9% (n=72) and the non-neurogenic sources for symptoms were attributed to 80.1% (n=289) of screened participants. Conclusion Lower frequency of cervicobrachial pain being neurogenic indicates thorough screening for appropriate therapeutic interventions to be successful. PMID:27134988

  13. Cystic fibrosis presenting as diabetes insipidus unresponsive to desmopressin.

    PubMed

    Vande Velde, S; Van Biervliet, S; Robberecht, E

    2007-01-01

    The diagnosis of cystic fibrosis (CF) can be confusing when only a part of the typical symptoms is present. In children, CF is usually suspected when dealing with chronic pulmonary symptoms (chronic productive cough, recurrent pneumonia or bronchiolitis). The pediatric gastroenterologist will exclude CF in all children with a meconium ileus, rectal prolaps or a poor weight gain. Atypical CF symptoms are hypochloremic alkalosis, recurrent pancreatitis and increased appetite to compensate for the pancreatic insufficiency. This case report shows how a diagnosis can be delayed when you are mislead by atypical symptoms. It shows the importance of looking in napkins and argues for the inclusion of CF in the differential diagnosis of polyuria in infants.

  14. Introduction to Neurogenic Communication Disorders. Fifth Edition.

    ERIC Educational Resources Information Center

    Brookshire, Robert H.

    This book provides an overview of the causes and symptoms, and the typical courses, treatments, and outcomes of neurogenic communication disorders. Chapter 1 reviews the human nervous system and neurologic causes of adult communication disorders. Chapter 2 discusses the neurologic assessment and arriving at a diagnosis, including the neurologist's…

  15. Evaluation and Management of Neurogenic Bladder: What Is New in China?

    PubMed Central

    Liao, Limin

    2015-01-01

    Neurogenic bladder (NB) or neurogenic lower urinary tract dysfunction (NLUTD), a dysfunction of the urinary bladder and urethra due to disease of the central nervous system or peripheral nerves, is a major global medical and social problem. Numerous nervous system abnormalities, such as: stroke, Alzheimer’s and Parkinson’s diseases, traumatic spinal cord injury, spinal cord tumors, congenital spina bifida, and diabetes, can cause NB/NLUTD. There are two major types of bladder control problems associated with NB/NLUTD: the bladder becomes either overactive or underactive depending on the nature, level, and extent of nerve damage. This review specifically focuses on the diagnosis and management of NB/NLUTD in China as well as on recent efforts to treat this disease. PMID:26266405

  16. Neurogenic stunned myocardium in subarachnoid hemorrhage.

    PubMed

    Kerro, Ali; Woods, Timothy; Chang, Jason J

    2017-04-01

    "Stunned myocardium," characterized by reversible left ventricular dysfunction, was first described via animal models using transient coronary artery occlusion. However, this phenomenon has also been noted with neurologic pathologies and collectively been labeled "neurogenic stunned myocardium" (NSM). Neurogenic stunned myocardium resulting from subarachnoid hemorrhage (SAH) is a challenging pathology due to its diagnostic uncertainty. Traditional diagnostic criteria for NSM after SAH focus on electrocardiographic and echocardiographic abnormalities and troponemia. However, tremendous heterogeneity still exists. Traditional pathophysiological mechanisms for NSM encompassed hypothalamic and myocardial perivascular lesions. More recently, research on pathophysiology has centered on myocardial microvascular dysfunction and genetic polymorphisms. Catecholamine surging as a mechanism has also gained attention with particular focus placed on the role of adrenergic blockade in both the prehospital and acute settings. Management remains largely supportive with case reports acknowledging the utility of inotropes such as dobutamine and milrinone and intra-aortic balloon pump when NSM is accompanied by cardiogenic shock. Neurogenic stunned myocardium that follows SAH can result in many complications such as arrhythmias, pulmonary edema, and prolonged intubation, which can negatively impact long-term recovery from SAH and increase morbidity and mortality. This necessitates the need to accurately diagnose and treat NSM.

  17. Prolonged Cardiac Dysfunction After Intraparenchymal Hemorrhage and Neurogenic Stunned Myocardium

    PubMed Central

    Krishnamoorthy, Vijay; Wilson, Thomas; Sharma, Deepak; Vavilala, Monica S.

    2015-01-01

    Cardiac dysfunction occurring secondary to neurologic disease, termed neurogenic stunned myocardium, is an incompletely understood phenomenon that has been described after several distinct neurologic processes. We present a case of neurogenic stunned myocardium, discovered intraoperatively after anesthetic induction, in a patient who presented to our operating room with a recent intraparenchymal hemorrhage. We discuss the longitudinal cardiac functional course after neurogenic stunned myocardium. Lastly, we discuss the pathophysiology of neurogenic stunned myocardium, as well as its implications for anesthesiologists caring for neurosurgical patients. PMID:26462162

  18. [Neurogenic urinary incontinence. Value of surgical management].

    PubMed

    Kutzenberger, J

    2008-06-01

    Damage to the CNS, the cauda equina, and the pelvic nerval structures causes neurogenic bladder dysfunction with neurogenic urinary incontinence (NUI). The definitive diagnosis of NUI is made with urodynamic examination methods. The most frequent cause of NUI is neurogenic detrusor overactivity (NDO). The treatment concept must take into account the physical and emotional restrictions. The treatment of NUI due to NDO is a domain of conservative therapy, i.e., mostly antimuscarinics and intermittent catheterization (IC). In about 30%, there is a good chance for therapy failures. An advancement in therapy is the injection of BTX-A into the detrusor. The missing drug approval is a disadvantage.Operative treatments are considered if conservative and minimally invasive therapies are unsuccessful. Sacral deafferentation (SDAF) and sacral anterior root stimulator implantation (SARSI) are available as organ-preserving techniques only for paraplegics with NDO and reflex urinary incontinence and neuromodulation for the other forms of NDO provided that a successful percutaneous nerve evaluation (PNE) test has previously taken place. Augmentation cystoplasty is indicated if SDAF and neuromodulation cannot be used and the bladder wall is damaged irreversibly by fibrosis. Kidney function of at least 25% and acceptance of IC are prerequisites. Myectomy (autoaugmentation) has an indication similar to augmentation cystoplasty but there must not be any fibrosis. Bladder neck insufficiency (BNI) caused by paralysis or iatrogenically can be treated by the implantation of an alloplastic sphincter high at the bladder neck. A stable reservoir function is required. If not all methods are possible, the ileum conduit or the suprapubic bladder fistula can be the last resort.

  19. A role for the Drosophila neurogenic genes in mesoderm differentiation.

    PubMed

    Corbin, V; Michelson, A M; Abmayr, S M; Neel, V; Alcamo, E; Maniatis, T; Young, M W

    1991-10-18

    The neurogenic genes of Drosophila have long been known to regulate cell fate decisions in the developing ectoderm. In this paper we show that these genes also control mesoderm development. Embryonic cells that express the muscle-specific gene nautilus are overproduced in each of seven neurogenic mutants (Notch, Delta, Enhancer of split, big brain, mastermind, neuralized, and almondex), at the apparent expense of neighboring, nonexpressing mesodermal cells. The mesodermal defect does not appear to be a simple consequence of associated neural hypertrophy, suggesting that the neurogenic genes may function similarly and independently in establishing cell fates in both ectoderm and mesoderm. Altered patterns of beta 3-tubulin and myosin heavy chain gene expression in the mutants indicate a role for the neurogenic genes in development of most visceral and somatic muscles. We propose that the signal produced by the neurogenic genes is a general one, effective in both ectoderm and mesoderm.

  20. Diabetes.

    PubMed

    2014-09-23

    Essential facts Type 1 and type 2 diabetes affect 3.2 million people in the UK. Diabetes is associated with serious complications, including heart disease and stroke, which can lead to disability and premature death. It is the leading cause of preventable sight loss in people of working age in the UK. A quarter of people with diabetes will have kidney disease at some point in their lives, and the condition increases the risk of amputation. Good diabetes management has been shown to reduce the incidence of these serious complications.

  1. Neurogenic bladder in spinal cord injury patients

    PubMed Central

    Taweel, Waleed Al; Seyam, Raouf

    2015-01-01

    Neurogenic bladder dysfunction due to spinal cord injury poses a significant threat to the well-being of patients. Incontinence, renal impairment, urinary tract infection, stones, and poor quality of life are some complications of this condition. The majority of patients will require management to ensure low pressure reservoir function of the bladder, complete emptying, and dryness. Management typically begins with anticholinergic medications and clean intermittent catheterization. Patients who fail this treatment because of inefficacy or intolerability are candidates for a spectrum of more invasive procedures. Endoscopic managements to relieve the bladder outlet resistance include sphincterotomy, botulinum toxin injection, and stent insertion. In contrast, patients with incompetent sphincters are candidates for transobturator tape insertion, sling surgery, or artificial sphincter implantation. Coordinated bladder emptying is possible with neuromodulation in selected patients. Bladder augmentation, usually with an intestinal segment, and urinary diversion are the last resort. Tissue engineering is promising in experimental settings; however, its role in clinical bladder management is still evolving. In this review, we summarize the current literature pertaining to the pathology and management of neurogenic bladder dysfunction in patients with spinal cord injury. PMID:26090342

  2. Diabetes.

    PubMed

    Lomberk, Gwen

    2009-01-01

    Pancreatologists have often divided research of the pancreas based upon the origin of the function or disease, namely the endocrine or exocrine pancreas. In fact, as a result, many of our meetings and conferences have followed separate paths. Interestingly, among patients with chronic pancreatitis and pancreatic cancer, both disorders of the exocrine pancreas, diabetes is common. However, the clinical features of the diabetes associated with these two differ. Peripheral insulin resistance and hyperinsulinemia are the predominant diabetic traits in pancreatic cancer, while reduced islet cell mass and impaired insulin secretion are observed more often in chronic pancreatitis. The causal relationship between diabetes and pancreatic cancer remains an intriguing but unanswered question. Since diabetes often precedes pancreatic cancer, it is regarded as a potential risk factor for malignancy. On the other hand, there remains the possibility that pancreatic cancer secretes diabetogenic factors. Regardless of how the science ultimately illuminates this issue, there is increasing interest in utilizing screening for diabetes to aid early detection of pancreatic tumor lesions. Therefore, in this issue of Pancreatology and the Web, we explore the topic of diabetes to keep us alert to this very important association, even if we study diseases of the exocrine pancreas.

  3. Neurovascular aspects of skin neurogenic inflammation.

    PubMed

    Aubdool, Aisah A; Brain, Susan D

    2011-12-01

    Neurogenic inflammation is involved in skin inflammation. It is hypothesized that it is involved in the pathogenesis of the common chronic cutaneous vascular disorder rosacea, but the exact mechanism of action is currently unknown. Transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) are widely expressed on primary sensory neuron endings and non-neuronal cells such as keratinocytes. Here we describe the potential for TRPV1 and TRPA1 receptors to be involved in the pathophysiology of rosacea due to their polymodal activation, including cold and hot temperature, pungent products from vegetable and spices, reactive oxygen species, and mechanical stimuli. We discuss the role of both receptors and the sensory neuropeptides that they release in inflammation and pain sensation and evidence suggesting that both TRPV1 and TRPA1 receptors may be promising therapeutic targets for the treatment of the inflammatory symptoms of rosacea.

  4. Urinary tract infection in the neurogenic bladder.

    PubMed

    Vigil, Humberto R; Hickling, Duane R

    2016-02-01

    There is a high incidence of urinary tract infection (UTI) in patients with neurogenic lower urinary tract function. This results in significant morbidity and health care utilization. Multiple well-established risk factors unique to a neurogenic bladder (NB) exist while others require ongoing investigation. It is important for care providers to have a good understanding of the different structural, physiological, immunological and catheter-related risk factors so that they may be modified when possible. Diagnosis remains complicated. Appropriate specimen collection is of paramount importance and a UTI cannot be diagnosed based on urinalysis or clinical presentation alone. A culture result with a bacterial concentration of ≥10(3) CFU/mL in combination with symptoms represents an acceptable definition for UTI diagnosis in NB patients. Cystoscopy, ultrasound and urodynamics should be utilized for the evaluation of recurrent infections in NB patients. An acute, symptomatic UTI should be treated with antibiotics for 5-14 days depending on the severity of the presentation. Antibiotic selection should be based on local and patient-based resistance patterns and the spectrum should be as narrow as possible if there are no concerns regarding urosepsis. Asymptomatic bacteriuria (AB) should not be treated because of rising resistance patterns and lack of clinical efficacy. The most important preventative measures include closed catheter drainage in patients with an indwelling catheter and the use of clean intermittent catheterization (CIC) over other methods of bladder management if possible. The use of hydrophilic or impregnated catheters is not recommended. Intravesical Botox, bacterial interference and sacral neuromodulation show significant promise for the prevention of UTIs in higher risk NB patients and future, multi-center, randomized controlled trials are required.

  5. Neurogenic Pulmonary Edema in Aneurysmal Subarachnoid Hemorrhage.

    PubMed

    Saracen, A; Kotwica, Z; Woźniak-Kosek, A; Kasprzak, P

    2016-01-01

    Neurogenic pulmonary edema (NPE) is observed in cerebral injuries and has an impact on treatment results, being a predictor of fatal prognosis. In this study we retrospectively reviewed medical records of 250 consecutive patients with aneurysmal subarachnoid hemorrhage (SAH) for the frequency and treatment results of NPE. The following factors were taken under consideration: clinical status, aneurysm location, presence of NPE, intracranial pressure (ICP), and mortality. All patients had plain- and angio-computer tomography performed. NPE developed most frequently in case of the aneurysm located in the anterior communicating artery. The patients with grades I-III of SAH, according to the World Federation of Neurosurgeons staging, were immediately operated on, while those with poor grades IV and V had only an ICP sensor's implantation procedure performed. A hundred and eighty five patients (74.4 %) were admitted with grades I to III and 32 patients (12.8 %) were with grade IV and V each. NPE was not observed in SAH patients with grade I to III, but it developed in nine patients with grade IV and 11 patients with grade V. Of the 20 patients with NPE, 19 died. Of the 44 poor grade patients (grades IV-V) without NPE, 20 died. All poor grade patients had elevated ICP in a range of 24-56 mmHg. The patients with NPE had a greater ICP than those without NPE. Gender and age had no influence on the occurrence of NPE. We conclude that the development of neurogenic pulmonary edema in SAH patients with poor grades is a fatal prognostic as it about doubles the death rate to almost hundred percent.

  6. Urinary tract infection in the neurogenic bladder

    PubMed Central

    Vigil, Humberto R.

    2016-01-01

    There is a high incidence of urinary tract infection (UTI) in patients with neurogenic lower urinary tract function. This results in significant morbidity and health care utilization. Multiple well-established risk factors unique to a neurogenic bladder (NB) exist while others require ongoing investigation. It is important for care providers to have a good understanding of the different structural, physiological, immunological and catheter-related risk factors so that they may be modified when possible. Diagnosis remains complicated. Appropriate specimen collection is of paramount importance and a UTI cannot be diagnosed based on urinalysis or clinical presentation alone. A culture result with a bacterial concentration of ≥103 CFU/mL in combination with symptoms represents an acceptable definition for UTI diagnosis in NB patients. Cystoscopy, ultrasound and urodynamics should be utilized for the evaluation of recurrent infections in NB patients. An acute, symptomatic UTI should be treated with antibiotics for 5–14 days depending on the severity of the presentation. Antibiotic selection should be based on local and patient-based resistance patterns and the spectrum should be as narrow as possible if there are no concerns regarding urosepsis. Asymptomatic bacteriuria (AB) should not be treated because of rising resistance patterns and lack of clinical efficacy. The most important preventative measures include closed catheter drainage in patients with an indwelling catheter and the use of clean intermittent catheterization (CIC) over other methods of bladder management if possible. The use of hydrophilic or impregnated catheters is not recommended. Intravesical Botox, bacterial interference and sacral neuromodulation show significant promise for the prevention of UTIs in higher risk NB patients and future, multi-center, randomized controlled trials are required. PMID:26904414

  7. [Neurogenic stunned myocardium in Pediatrics. A case report].

    PubMed

    Alados Arboledas, F J; Millán-Miralles, L; Millán-Bueno, M P; Expósito-Montes, J F; Santiago-Gutierrez, C; Martínez Padilla, M C

    2015-10-01

    Neurogenic stunned myocardium is an unusual clinical entity. It mimics an acute coronary syndrome with electrocardiographic abnormalities, cardiac dysfunction and elevated cardiac enzymes with absence of obstructive coronary disease. It may occur after a neurosurgical procedure. A case is presented of neurogenic stunned myocardium occurring in a child after removal of a posterior fossa medulloblastoma. The patient developed nodal tachycardia with hemodynamic impairment. The clinical course was satisfactory due to antiarrhythmic therapy, with biochemical, echocardiographic, and clinical improvement within a week.

  8. DIABETES

    PubMed Central

    Natarajan, Loki

    2015-01-01

    A new study shows that statin therapy before diagnosis of diabetes mellitus is not associated with an increased risk of microvascular disease and might even be beneficial for retinopathy and neuropathy. These data suggest a potential protective effect of statins in specific complications, which should be further investigated in randomized controlled trials. PMID:25366041

  9. Diabetes

    MedlinePlus

    ... retinopathy gets worse, it may lead to blindness.Laser surgery can often be used to treat or slow down retinopathy, especially if the problem is found early. People who have diabetes should have an eye exam once a year.Warning signs of eye problemsCall your doctor if you ...

  10. [Primary neurogenic and myogenic disorders of posture].

    PubMed

    Schranz, C; Meinck, H-M

    2004-05-01

    Disturbance of posture may occur in a variety of neurological disorders and occasionally is the presenting or even the only sign. In the majority of cases, the head or the trunk or both are bent forward (bent spine syndrome, dropped head syndrome). A feature of these primary neurogenic or myogenic postural disturbances that is in contrast to antalgic contraction or ankylosis is that they are not fixed, but the trunk or head are easily erected by the examiner and show a characteristic sagging. Neuromuscular disorders are a frequent cause. They may be confined to the paraspinal muscles. Axial computed tomography of the spine, electromyography of the involved muscles, and muscle biopsy help to make the diagnosis. However, also central movement disorders may lead to a sagging of the head or trunk or of both due to a lessened tone of the head and trunk extensors. This is frequently seen in the various parkinsonian syndromes which may, however, occur in association with a focal myopathy of the paraspinal muscles. Occasionally, sagging of the trunk is seen as a side effect of neuropharmacologic medication. Sagging of the trunk or head should be differentiated from a pathologically increased innervation of the ventral muscles in dystonic movement disorders such as antecollis or camptocormia. Pathologic reclination of the head or trunk or both is a rare disturbance of posture. It may occur in dystonia (retrocollis) or, occasionally, as a consequence of musculotendinous contractures secondary to certain neuromuscular disorders such as the rigid spine syndrome.

  11. Microglia participate in neurogenic regulation of hypertension.

    PubMed

    Shen, Xiao Z; Li, You; Li, Liang; Shah, Kandarp H; Bernstein, Kenneth E; Lyden, Patrick; Shi, Peng

    2015-08-01

    Hypertension is associated with neuroinflammation and increased sympathetic tone. Interference with neuroinflammation by an anti-inflammatory reagent or overexpression of interleukin-10 in the brain was found to attenuate hypertension. However, the cellular mechanism of neuroinflammation, as well as its impact on neurogenic regulation of blood pressure, is unclear. Here, we found that hypertension, induced by either angiotensin II or l-N(G)-nitro-l-arginine methyl ester, is accompanied by microglial activation as manifested by microgliosis and proinflammatory cytokine upregulation. Targeted depletion of microglia significantly attenuated neuroinflammation, glutamate receptor expression in the paraventricular nucleus, plasma vasopressin level, kidney norepinephrine concentration, and blood pressure. Furthermore, when microglia were preactivated and transferred into the brains of normotensive mice, there was a significantly prolonged pressor response to intracerebroventricular injection of angiotensin II, and inactivation of microglia eliminated these effects. These data demonstrate that microglia, the resident immune cells in the brain, are the major cellular factors in mediating neuroinflammation and modulating neuronal excitation, which contributes to the elevated blood pressure.

  12. AAEM minimonograph #46: neurogenic muscle hypertrophy.

    PubMed

    Gutmann, L

    1996-07-01

    Muscle hypertrophy occurs uncommonly in several neurogenic disorders including neuropathies, radiculopathies, spinal muscular atrophy, and post-polio syndrome. Its pathogenesis varies in different circumstances. In the presence of generalized myokymia and neuromyotonia (Isaacs' syndrome), symmetrical hypertrophy appears to be the result of continuous spontaneous electrical stimulation of myofibers and, in some cases, results in type 1 myofiber preponderance. Focal hypertrophy occurring with radiculopathies and mononeuropathies was associated with complex repetitive discharges (CRDs) in approximately half the cases. CRDs may play a role in the pathogenesis of myofiber hypertrophy by continuous myofiber stimulation, but in some cases, with and without CRDs, myofiber hypertrophy may be related to mechanical events. Muscle enlargement seen in old polio appears to involve a significant degree of pseudohypertrophy, although some myofiber hypertrophy occurs. The symmetrical occurrence of hypertrophy in genetically determined disorders, such as spinal muscular atrophy, and hereditary motor and sensory neuropathy types 1 and 2 may have both a genetic and a mechanical basis in addition to pseudohypertrophy in some cases.

  13. [Neurogenic bladder: pathophysiology of the disorder of compliance].

    PubMed

    Chartier-Kastler, Emmanuel; Ayoub, Nadim; Even-Schneider, Alexia; Richard, François; Soler, Jean-Marc; Denys, Pierre

    2004-09-01

    Bladder compliance is defined by the ratio of the increase of intravesical pressures to the increase of volume (_V/_P). The pathophysiology of disorders of compliance in neurogenic bladder is still poorly elucidated. It can be evaluated in terms of three elements: 1) The natural history of the appearance of these disorders in neurogenic bladders. Clinical experience shows the existence of prognostic factors that determine the development of these disorders, such as the voiding mode adopted (self-catheterization/hetero-catheterization versus indwelling catheter), the level of the spinal cord lesion (suprasacral versus sacral, incomplete versus complete, and cauda equina lesions), and the presence of meningomyelocele. 2). Data derived from conservative management of these disorders in neurogenic bladders: urethral dilatation, various sphincterotomies, bladder disafferentation, alpha-blockers, vanilloids (resiniferatoxin and capsaicin), intra-detrusor botulinum toxin and intrathecal baclofen, have demonstrated a marked improvement of disorders of compliance associated with neurogenic bladder 3). Data derived from experimentations. Morphometric studies on animal or human bladder strips have demonstrated an increased expression of proteolytic enzymes and endogenous tissue inhibitors of metalloproteinases (MMP-1) and type III collagen mRNA in hypocompliant neurogenic bladders. Reduction of bladder wall blood flow, bilateral section of hypogastric nerves in rats, study of the bladders of spinalized rats, and reduction of oestrogenic hormone impregnation, show that these conditions induce loss of the viscoelastic properties of the bladder With the arrival of new treatments, active on afferent and/or efferent pathways or even on the central nervous system, it is very important to further our understanding of the pathophysiology of disorders of compliance in neurogenic bladders. Reversibility of these disorders constitutes a major therapeutic challenge and its functional

  14. Hereditary sensory radicular neuropathy: defective neurogenic inflammation.

    PubMed

    Westerman, R A; Block, A; Nunn, A; Delaney, C A; Hahn, A; Dennett, X; Carr, R W

    1992-01-01

    Hereditary sensory radicular neuropathy exhibits autosomal dominant inheritance with complete penetrance in males and incomplete penetrance in females. Newer tests of small sensory nerve function were used in screening 8 family members aged between 14 and 66 years. All exhibited some frequent features of the disorder with an onset in the 2nd or 3rd decade, foot ulceration, foot callus, loss of pin prick, thermal and light touch sensation, and some reduction in vibration acuity and proprioception in the lower limbs. The hands were involved in 3 of 8, muscle involvement was present in 5 of 8, but deafness was not detected by audiometry. Nerve conduction velocity, sensory action potentials, latency and amplitude, thermal acuity, vibration acuity and axon reflex flares were measured in all patients. One sural nerve biopsy confirmed the presence of peripheral fibre loss in this predominantly sensory neuropathy. Chemically evoked axon reflex tests were used to evaluate the extent of primary sensory nerve fibre involvement. All patients were tested using a Moor MBF 3-D dual channel laser Doppler velocimeter. Acetylcholine or phenylephrine iontophoretically applied as 16 mC doses evoked absent or tiny axon reflexes in areas of impaired pin prick sensation. By contrast, direct microvascular dilator responses to nitroprusside (smooth muscle dependent) and acetylcholine (endothelium-dependent) were present but somewhat reduced in areas with defective neurogenic inflammation. These results differ significantly from the responses obtained in age-matched healthy controls (P < 0.05). Foot pressure analysis was performed for orthoses in 2 affected members with foot ulceration using the Musgrave Footprint system.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. [Visual impairment in juvenile diabetes mellitus due to optic atrophy: Wolfram's syndrome].

    PubMed

    Immink, Annelies; Reeser, H Maarten; Brus, Frank

    2010-01-01

    Wolfram's syndrome is a rare neurodegenerative disorder, which usually first manifests itself around the age of 6 years. The diagnosis can be made based on the characteristics incorporated in the 'DIDMOAD' acronym: diabetes insipidus, diabetes mellitus, optic atrophy and deafness. We present 2 boys, diagnosed with diabetes mellitus at the age of 5 and 4 years respectively. Both children developed optic atrophy over the years. These 2 cases illustrate that alongside diabetic retinopathy, possible syndromes, such as Wolfram's syndrome, should also be considered in children with diabetes mellitus and visual impairment.

  16. SUSCEPTIBILITY TO POLLUTANT-INDUCED AIRWAY INFLAMMATION IS NEUROGENICALLY MEDIATED.

    EPA Science Inventory

    Neurogenic inflammation in the airways involves the activation of sensory irritant receptors (capsaicin, VR1) by noxious stimuli and the subsequent release of neuropeptides (e.g., SP, CGRP, NKA) from these fibers. Once released, these peptides initiate and sustain symptoms of ...

  17. Neurogenic hypertension related to basilar impression. Case report.

    PubMed

    Dickinson, L D; Papadopoulos, S M; Hoff, J T

    1993-12-01

    The authors report the resolution of essential hypertension following transoral odontoidectomy and medullary decompression in a 39-year-old woman with basilar invagination. Current understanding of central regulation of the cardiovascular system is discussed and the pertinent neuroanatomy illustrated. Experimental and clinical evidence supporting the role of neurogenic mechanisms in the pathogenesis of hypertension is reviewed.

  18. Neurogenic tumors of the duodenum in patients with neurofibromatosis

    SciTech Connect

    Tishler, J.M.; Han, S.Y.; Colcher, H.; Halpern, N.B.

    1983-10-01

    Neurogenic tumors of the duodenum may occur in patients with neurofibromatosis. They may be solitary or multiple and are located distal to the duodenal bulb. The presenting complaints may be hematemesis, vomiting, or jaundice. The lesions are generally benign and have a low potential for malignant degenertion. Four cases are reported.

  19. Bartter's syndrome with type 2 diabetes mellitus.

    PubMed

    See, Ting-Ting; Lee, Siu-Pak

    2009-02-01

    We report a rare case of Bartter's syndrome in a 35-year-old woman with type 2 diabetes mellitus. The patient presented with leg weakness, fatigue, polyuria and polydipsia. Hypokalemia, metabolic alkalosis, and high renin and aldosterone concentrations were present, but the patient was normotensive. Gitelman's syndrome was excluded because of the presence of hypercalciuria, secondary hyperparathyroidism and bilateral nephrocalcinosis. The patients condition improved upon administration of a prostaglandin synthetase inhibitor (acemetacin), oral potassium chloride and potassium-sparing diuretics. Five months later, the patient discontinued acemetacin because of epigastric discomfort; at the same time, severe hypokalemia and hyperglycemia developed. Glucagon stimulation and water deprivation tests were performed. Type 2 diabetes mellitus with nephrogenic diabetes insipidus was diagnosed. To avoid further gastrointestinal complications, the patient was treated with celecoxib, a selective cyclooxygenase 2 inhibitor. This case serves as a reminder that Bartter's syndrome is associated with various metabolic derangements including nephrogenic diabetes insipidus, nephrocalcinosis and diabetes mellitus. When treating Bartter's syndrome, it is also prudent to remember that the long-term use of nonsteroidal anti-inflammatory drugs and potassium-sparing diuretics may result in serious adverse reactions.

  20. Not all neurogenic bladders are the same: a proposal for a new neurogenic bladder classification system

    PubMed Central

    2016-01-01

    Neurogenic bladder (NGB) has long been defined as a clinical entity that describes a heterogeneous collection of syndromes. The common theme is a bladder disorder concomitant with a neurologic disorder. This definition does not give the clinician much information about the bladder disorder, nor how to treat it, or even what the natural history of the disorder is likely to be. It may be time for a new classification scheme to better define the bladder defect and prognosis, as well as inform treatment. We propose a classification system based on seven categories, each having a neurologic defect in a distinct anatomic location. This is termed SALE (Stratify by Anatomic Location and Etiology). In addition, the presence or absence of bowel dysfunction and autonomic dysreflexia will be reported. In the future, as more definite prognostic information can be gleaned from biomarkers, we anticipate adding urinary nerve growth factor (NGF) and urinary brain-derived neurotrophic factor (BDNF) levels to the definition. We expect the SALE system to efficiently describe a patient suffering from NGB and simultaneously inform the most appropriate treatment, follow-up regimen, and long-term prognosis. PMID:26904408

  1. The treatment of erectile dysfunction in patients with neurogenic disease

    PubMed Central

    Brant, William O.

    2016-01-01

    Erectile dysfunction (ED) related to compromise of the nervous system is an increasingly common occurrence. This may be due to the multifactorial nature of ED, the myriad of disorders affecting the neurotransmission of erectogenic signals, and improved awareness and diagnosis of ED. Nevertheless, neurogenic ED remains poorly understood and characterized. Disease related factors such as depression, decreased physical and mental function, the burden of chronic illness, and loss of independence may preclude sexual intimacy and lead to ED as well. The amount of data regarding treatment options in subpopulations of differing neurologic disorders remains scarce except for men with spinal cord injury. The treatment options including phosphodiesterase inhibitors, intracavernosal or intraurethral vasoactive agents, vacuum erection devices (VED) and penile prosthetic implantation remain constant. This review discusses the options in specific neurologic conditions, and briefly provides insight into new and future developments that may reshape the management of neurogenic ED. PMID:26904415

  2. Neurogenic muscle hypertrophy in a 12-year-old girl.

    PubMed

    Zutelija Fattorini, Matija; Gagro, Alenka; Dapic, Tomislav; Krakar, Goran; Marjanovic, Josip

    2017-01-01

    Muscular hypertrophy secondary to denervation is very rare, but well-documented phenomena in adults. This is the first report of a child with neurogenic unilateral hypertrophy due to S1 radiculopathy. A 12-year-old girl presented with left calf hypertrophy and negative history of low back pain or trauma. The serum creatinine kinase level and inflammatory markers were normal. Magnetic resonance imaging showed muscle hypertrophy of the left gastrocnemius and revealed a protruded lumbar disc at the L5-S1 level. The protruded disc abuts the S1 root on the left side. Electromyography showed mild left S1 radiculopathy. Passive stretching and work load might clarify the origin of neurogenic hypertrophy but there is still a need for further evidence. Clinical, laboratory, magnetic resonance imaging and electromyography findings showed that S1 radiculopathy could be a cause of unilateral calf swelling in youth even in the absence of a history of back or leg pain.

  3. Effects of Radiation Therapy on Established Neurogenic Heterotopic Ossification

    PubMed Central

    2016-01-01

    Heterotopic ossification (HO) is frequently seen on rehabilitation units after spinal cord injuries, fractures, brain injuries, and limb amputations. Currently, there is no effective treatment for HO other than prophylaxis with anti-inflammatory medications, irradiation, and bisphosphonate administration. These prophylactic treatments are not effective for managing ectopic bone once it has formed. Here we describe three cases of established neurogenic HO treated with radiation therapy (RT). All patients had decreased serum alkaline phosphatase (ALP) and bone-specific ALP levels with decreased pain but increased range of motion immediately after RT. Post-treatment X-rays revealed no further growth of the HO. All patients maintained clinical and laboratory improvements 4 or 6 months after the RT. Our results suggest that RT is safe and effective in decreasing pain and activity of neurogenic HO. PMID:28119846

  4. Neurogenic neuroinflammation in fibromyalgia and complex regional pain syndrome.

    PubMed

    Littlejohn, Geoffrey

    2015-11-01

    Although fibromyalgia and complex regional pain syndrome (CRPS) have distinct clinical phenotypes, they do share many other features. Pain, allodynia and dysaesthesia occur in each condition and seem to exist on a similar spectrum. Fibromyalgia and CRPS can both be triggered by specific traumatic events, although fibromyalgia is most commonly associated with psychological trauma and CRPS is most often associated with physical trauma, which is frequently deemed routine or minor by the patient. Fibromyalgia and CRPS also seem to share many pathophysiological mechanisms, among which the most important are those involving central effects. Nonetheless, peripheral effects, such as neurogenic neuroinflammation, are also important contributors to the clinical features of each of these disorders. This Review highlights the differing degrees to which neurogenic neuroinflammation might contribute to the multifactorial pathogenesis of both fibromyalgia and CRPS, and discusses the evidence suggesting that this mechanism is an important link between the two disorders, and could offer novel therapeutic targets.

  5. Pharmacotherapy in Pediatric Neurogenic Bladder Intravesical Botulinum Toxin Type A

    PubMed Central

    Sager, Cristian; Burek, Carol; Durán, Victor; Corbetta, Juan Pablo; Weller, Santiago; Juan, Bortagaray; López, Juan Carlos

    2012-01-01

    When the neurogenic bladder is refractory to anticholinergics, botulinum toxin type A is used as an alternative. The neurotoxin type A reduces bladder pressure and increases its capacity and wall compliance. Additionally, it contributes to improving urinary continence and quality of life. This novel therapy is ambulatory with a low incidence of adverse effects. Due to its transitory effect, it is necessary to repeat the injections in order to sustain its therapeutic effect. In these review article we talk about Mechanism of Action, Indications, effects, administration and presentations of the Botulinum Neurotoxin Type A in pediatric patients. Also, we make references to controversial issues surrounding its use. A bibliographic search was done selecting articles and revisions from Pubmed. The key words used were botulinum toxin A, neurogenic bladder, and children. The search was limited to patients younger than 18 years of age and reports written in English in the past ten years. PMID:22720170

  6. Medical management of neurogenic bladder with oral therapy

    PubMed Central

    2016-01-01

    This is a review of the most current literature on medical management of the neurogenic bladder (NGB) to treat detrusor overactivity (DO), improve bladder compliance and treat urinary incontinence. The use of antimuscarinics, alpha blockers, tricyclic antidepressants, desmopressin and mirabegron will be discussed along with combination therapy to improve efficacy. These medical therapies will be the focus of this review with surgical therapy and botulinum toxin injections being the subject of other articles in this series. PMID:26904412

  7. A dangerous Cushing response in a child: neurogenic heart damage.

    PubMed

    Ruggieri, Francesco; Calvi, Maria Rosa; Beretta, Luigi

    2014-04-01

    Cushing response, which acts to preserve cerebral blood flow by inducing arterial hypertension, could induce neurogenic heart damage through hyperactivation of autonomic nervous system. Most of clinical reports describe neurogenic heart damage as a self-limiting condition clinically characterized by electrocardiographic abnormalities in the setting of an acute neurologic insult. Here we describe a case of life-threatening cardiac dysfunction immediately after a massive intracerebral hemorrhage in a healthy 7-year-old child. The low probability of ischemic heart disease, the poor increase of cardiac necrosis markers, the localization of regional wall motion abnormalities that are not typical for coronary artery disease, and reversibility after brain surgical decompression are consistent all with neurogenic heart damage. Acute decrease of brain oxygen delivery caused by cardiac dysfunction worsens secondary brain injury in the setting of an acute neurologic insult. Thus, Cushing response, which is a physiological mechanism of cerebral protection, could become a double-edged sword when massive sympathetic activation makes the myocardium stunned.

  8. Exosomes as Novel Regulators of Adult Neurogenic Niches

    PubMed Central

    Bátiz, Luis Federico; Castro, Maite A.; Burgos, Patricia V.; Velásquez, Zahady D.; Muñoz, Rosa I.; Lafourcade, Carlos A.; Troncoso-Escudero, Paulina; Wyneken, Ursula

    2016-01-01

    Adult neurogenesis has been convincingly demonstrated in two regions of the mammalian brain: the sub-granular zone (SGZ) of the dentate gyrus (DG) in the hippocampus, and the sub-ventricular zone (SVZ) of the lateral ventricles (LV). SGZ newborn neurons are destined to the granular cell layer (GCL) of the DG, while new neurons from the SVZ neurons migrate rostrally into the olfactory bulb (OB). The process of adult neurogenesis persists throughout life and is supported by a pool of neural stem cells (NSCs), which reside in a unique and specialized microenvironment known as “neurogenic niche”. Neurogenic niches are structured by a complex organization of different cell types, including the NSC-neuron lineage, glial cells and vascular cells. Thus, cell-to-cell communication plays a key role in the dynamic modulation of homeostasis and plasticity of the adult neurogenic process. Specific cell-cell contacts and extracellular signals originated locally provide the necessary support and regulate the balance between self-renewal and differentiation of NSCs. Furthermore, extracellular signals originated at distant locations, including other brain regions or systemic organs, may reach the niche through the cerebrospinal fluid (CSF) or the vasculature and influence its nature. The role of several secreted molecules, such as cytokines, growth factors, neurotransmitters, and hormones, in the biology of adult NSCs, has been systematically addressed. Interestingly, in addition to these well-recognized signals, a novel type of intercellular messengers has been identified recently: the extracellular vesicles (EVs). EVs, and particularly exosomes, are implicated in the transfer of mRNAs, microRNAs (miRNAs), proteins and lipids between cells and thus are able to modify the function of recipient cells. Exosomes appear to play a significant role in different stem cell niches such as the mesenchymal stem cell niche, cancer stem cell niche and pre-metastatic niche; however, their

  9. Exosomes as Novel Regulators of Adult Neurogenic Niches.

    PubMed

    Bátiz, Luis Federico; Castro, Maite A; Burgos, Patricia V; Velásquez, Zahady D; Muñoz, Rosa I; Lafourcade, Carlos A; Troncoso-Escudero, Paulina; Wyneken, Ursula

    2015-01-01

    Adult neurogenesis has been convincingly demonstrated in two regions of the mammalian brain: the sub-granular zone (SGZ) of the dentate gyrus (DG) in the hippocampus, and the sub-ventricular zone (SVZ) of the lateral ventricles (LV). SGZ newborn neurons are destined to the granular cell layer (GCL) of the DG, while new neurons from the SVZ neurons migrate rostrally into the olfactory bulb (OB). The process of adult neurogenesis persists throughout life and is supported by a pool of neural stem cells (NSCs), which reside in a unique and specialized microenvironment known as "neurogenic niche". Neurogenic niches are structured by a complex organization of different cell types, including the NSC-neuron lineage, glial cells and vascular cells. Thus, cell-to-cell communication plays a key role in the dynamic modulation of homeostasis and plasticity of the adult neurogenic process. Specific cell-cell contacts and extracellular signals originated locally provide the necessary support and regulate the balance between self-renewal and differentiation of NSCs. Furthermore, extracellular signals originated at distant locations, including other brain regions or systemic organs, may reach the niche through the cerebrospinal fluid (CSF) or the vasculature and influence its nature. The role of several secreted molecules, such as cytokines, growth factors, neurotransmitters, and hormones, in the biology of adult NSCs, has been systematically addressed. Interestingly, in addition to these well-recognized signals, a novel type of intercellular messengers has been identified recently: the extracellular vesicles (EVs). EVs, and particularly exosomes, are implicated in the transfer of mRNAs, microRNAs (miRNAs), proteins and lipids between cells and thus are able to modify the function of recipient cells. Exosomes appear to play a significant role in different stem cell niches such as the mesenchymal stem cell niche, cancer stem cell niche and pre-metastatic niche; however, their roles

  10. Our patients followed up with a diagnosis of neurogenic pulmonary edema

    PubMed Central

    Sarı, Mehmet Yusuf; Yıldızdaş, Rıza Dinçer; Yükselmiş, Ufuk; Horoz, Özden Ögür

    2015-01-01

    Neurogenic pulmonary edema is a clinical situation which developes as a result of central nervous system injury. It is rare in the childhood. Neurogenic pulmonary edema is a clinical diagnosis. Although the pathogenesis is not elucidated well, there is increase in pulmonary interstitial and alveolar fluid. The main principle in treatment of neurogenic pulmonary edema is supportive treatment and decreasing intracranial pressure as in acute respiratory distress syndrome. In this article, clinical properties of our two patients diagnosed with neurogenic pulmonary edema developed as a result of central nervous system injury are presented. PMID:26884694

  11. The subtle signs of Wolfram (DIDMOAD) syndrome: not all juvenile diabetes is type 1 diabetes.

    PubMed

    Boettcher, Claudia; Brosig, Burkhard; Zimmer, Klaus P; Wudy, Stefan A

    2011-01-01

    Wolfram syndrome (also known as DIDMOAD = diabetes insipidus, diabetes mellitus, optic atrophy, deafness) is an autosomal recessive disorder characterized by the association of childhood non-immune insulin-dependent diabetes mellitus (DM) with progressive bilateral optic atrophy. Additional symptoms including signs of severe neurodegeneration and psychiatric illness are likely to evolve over time resulting in premature death. We report on two siblings of Turkish origin from our diabetes clinic who were diagnosed with Wolfram syndrome after 6 years and 2 years duration of DM, respectively. Subtle symptoms such as attitude changes, growing reading difficulties in the history of children or adolescents with antibody negative and ketone negative DM should alert the treating physician and lead to re-evaluation of the diagnosis, keeping in mind that not all juvenile DM is type 1 DM.

  12. Renal function in children with congenital neurogenic bladder

    PubMed Central

    Olandoski, Karen Previdi; Koch, Vera; Trigo‐Rocha, Flavio Eduardo

    2011-01-01

    AIMS: Preservation of renal function in children with congenital neurogenic bladder is an important goal of treatment for the disease. This study analyzed the evolution of renal function in patients with congenital neurogenic bladder. METHODS: We reviewed the records of 58 pediatric patients with respect to the following attributes: gender, age, etiology of neurogenic bladder, reason for referral, medical/surgical management, episodes of treated urinary tract infections, urodynamics, DMSA scintigraphy, weight, height, blood pressure, glomerular filtration rate, microalbuminuria and metabolic acidosis. Statistical analysis was performed, adopting the 5% significance level. RESULTS: The mean age at presentation was 4.2 ± 3.5 years. Myelomeningocele was the most frequent etiology (71.4%). Recurrent urinary tract infection was the reason for referral in 82.8% of the patients. Recurrent urinary tract infections were diagnosed in 84.5% of the patients initially; 83.7% of those patients experienced improvement during follow‐up. The initial mean glomerular filtration rate was 146.7 ± 70.1 mL/1.73 m2/min, and the final mean was 193.6 ± 93.6 mL/1.73 m2/min, p  =  0.0004. Microalbuminuria was diagnosed in 54.1% of the patients initially and in 69% in the final evaluation. Metabolic acidosis was present in 19% of the patients initially and in 32.8% in the final assessment. CONCLUSIONS: Patient referral to a pediatric nephrologist was late. A reduction in the number of urinary tract infections was observed with adequate treatment, but microalbuminuria and metabolic acidosis occurred frequently despite adequate management. PMID:21484032

  13. Curative effect assessment of bandage contact lens in neurogenic keratitis

    PubMed Central

    Sun, Yu-Zhao; Guo, Lei; Zhang, Fu-Sheng

    2014-01-01

    AIM To observe the curative effect of bandage contact lens in neurogenic keratitis. METHODS Twenty cases of neurogenic keratitis were studied at the Department of Ophthalmology, the first Affiliated Hospital of China Medical University, between October 2012 and June 2013. These included 13 males and 7 females, aged from 35 to 88y. Patients were voluntarily divided into an experimental group (lens wearing group, n=10) and control group (drug therapy, n=10). In experimental group patients wore silicone hydrogel bandage soft contact lens. Both groups used the following eyedrops: 0.5% levofloxacin TID; 0.5% Sodium carboxymethyl cellulose QID; fibroblast growth factor BID; ganciclovir BID [cases complicated with herpes simplex virus (HSV)]; compound tropicamide BID (cases concurrent hypopyon). The healing time of corneal ulcer and complication rates were observed in the two groups. RESULTS The healing time of corneal ulcer in the experimental group was 10.80±4.44d versus 46.70±13.88d in the control group (P<0.05). No complications occurred in the experimental group, except for the lens falling off twice in one case, the patient recovered eight days after rewearing the lens. While in the control group, all cases vascularized, 2 cases were complicated with descemetocele that recovered with amniotic membrane transplantation and 1 case was complicated with corneal perforation that recovered by autologous conjunctival flap covering. CONCLUSION Bandage contact lens is a safe and effective method of treating neurogenic keratitis and significantly shortened the healing time of corneal ulcer. PMID:25540750

  14. Neurogenic pulmonary edema: successful treatment with IV phentolamine.

    PubMed

    Davison, Danielle L; Chawla, Lakhmir S; Selassie, Leelie; Tevar, Rahul; Junker, Christopher; Seneff, Michael G

    2012-03-01

    Neurogenic pulmonary edema (NPE) is a clinical syndrome characterized by the acute onset of pulmonary edema following a significant CNS insult. The cause is believed to be a surge of catecholamines that results in cardiopulmonary dysfunction. Although there are myriad case reports describing CNS events that are associated with this syndrome, few studies have identified specific treatment modalities. We present a case of NPE caused by an intracranial hemorrhage from a ruptured arteriovenous malformation. We uniquely document a rise and fall of serum catecholamine levels correlating with disease activity and a dramatic clinical response to IV phentolamine.

  15. Urofacial syndrome: a subset of neurogenic bladder dysfunction syndromes?

    PubMed

    Stamatiou, K; Tyritzis, S; Karakos, C; Skolarikos, A

    2011-10-01

    The urofacial syndrome (Ochoa syndrome) is considered to represent a subgroup of the non-neurogenic bladder dysfunction, characterized by non-neuropathic bladder-sphincter dysfunction, along with a characteristic inversion of the facial expression with laughing. Recent research suggests that it is probably a genetic inherited disease transmitted in an autosomal recessive fashion and might represent a distinct entity. We report a case of this syndrome in a 14-year-old boy who presented with left pyelonephritis, hydronephrosis, and bladder dilation.

  16. Congenital contractural arachnodactyly with neurogenic muscular atrophy: case report.

    PubMed

    Scola, R H; Werneck, L C; Iwamoto, F M; Ribas, L C; Raskin, S; Correa Neto, Y

    2001-06-01

    We report the case of a 3-(1/2)-year-old girl with hypotonia, multiple joint contractures, hip luxation, arachnodactyly, adducted thumbs, dolichostenomelia, and abnormal external ears suggesting the diagnosis of congenital contractural arachnodactyly (CCA). The serum muscle enzymes were normal and the needle electromyography showed active and chronic denervation. The muscle biopsy demonstrated active and chronic denervation compatible with spinal muscular atrophy. Analysis of exons 7 and 8 of survival motor neuron gene through polymerase chain reaction did not show deletions. Neurogenic muscular atrophy is a new abnormality associated with CCA, suggesting that CCA is clinically heterogeneous.

  17. [Advance of neurogenic erectile dysfunction therapy by stem cells].

    PubMed

    Shen, Han-Jian; Zhu, Guang-You

    2010-06-01

    Neurogenic erectile dysfunction (NED) commonly results from erectile nerve damage. Recent researches have focused on the preclinical study of stem cell-based therapies targeted at repairing and protecting nervi erigentes. In this paper, researches of NESCs, MDSCs, ASCs and MSCs in NED are reviewed. Early studies have demonstrated that stem cells and gene modified stem cells were effective to the therapy of ED, even likely to cure ED. Stem cells are expected to be applied in the clinical therapy of NED. Stem cells as a new therapy technique will bring up a new challenge in forensic clinical medicine.

  18. A One Year Prospective Study of Neurogenic Stuttering Following Stroke: Incidence and Co-Occurring Disorders

    ERIC Educational Resources Information Center

    Theys, C.; van Wieringen, A.; Sunaert, S.; Thijs, V.; De Nil, L. F.

    2011-01-01

    In this prospective study, data on incidence, stuttering characteristics, co-occurring speech disorders, and recovery of neurogenic stuttering in a large sample of stroke participants were assessed. Following stroke onset, 17 of 319 participants (5.3%; 95% CI, 3.2-8.3) met the criteria for neurogenic stuttering. Stuttering persisted in at least…

  19. High-dose insulin therapy for neurogenic-stunned myocardium after stroke

    PubMed Central

    Devos, Justine; Peeters, André; Wittebole, Xavier; Hantson, Philippe

    2012-01-01

    A 44-year-old woman with a history of complicated type 2 diabetes mellitus presented with a diagnosis of right-hemispheric ischaemic stroke. She developed acute respiratory distress with radiological evidence of pulmonary oedema. The ECG showed poorly significant ST-segment changes, with a minimal increase of cardiac biomarkers. Echocardiography showed a severely depressed left ventricular function, with also low values of cardiac output at invasive monitoring. The possibility of neurogenic-stunned myocardium was discussed and a metabolic resuscitation with high-dose insulin was proposed. An intravenous bolus of 80 units of insulin (0.72 IU/kg) was followed by a continuous infusion at the rate of 160 IU/h (1.45 IU/kg/h). The treatment led to a rapid and sustained improvement of the haemodynamic condition and was well tolerated. In comparison with dobutamine, insulin had significant inotropic effects without tachycardia. The patient unfortunately died on day 35, from respiratory complications after poor neurological recovery. PMID:23175002

  20. Carotid body overactivity induces respiratory neurone channelopathy contributing to neurogenic hypertension.

    PubMed

    Moraes, Davi J A; Machado, Benedito H; Paton, Julian F R

    2015-07-15

    Why sympathetic activity rises in neurogenic hypertension remains unknown. It has been postulated that changes in the electrical excitability of medullary pre-sympathetic neurones are the main causal mechanism for the development of sympathetic overactivity in experimental hypertension. Here we review recent data suggesting that enhanced sympathetic activity in neurogenic hypertension is, at least in part, dependent on alterations in the electrical excitability of medullary respiratory neurones and their central modulation of sympatho-excitatory networks. We also present results showing a critical role for carotid body tonicity in the aetiology of enhanced central respiratory modulation of sympathetic activity in neurogenic hypertension. We propose a novel hypothesis of respiratory neurone channelopathy induced by carotid body overactivity in neurogenic hypertension that may contribute to sympathetic excess. Moreover, our data support the notion of targeting the carotid body as a potential novel therapeutic approach for reducing sympathetic vasomotor tone in neurogenic hypertension.

  1. Neurogenic gene regulatory pathways in the sea urchin embryo.

    PubMed

    Wei, Zheng; Angerer, Lynne M; Angerer, Robert C

    2016-01-15

    During embryogenesis the sea urchin early pluteus larva differentiates 40-50 neurons marked by expression of the pan-neural marker synaptotagmin B (SynB) that are distributed along the ciliary band, in the apical plate and pharyngeal endoderm, and 4-6 serotonergic neurons that are confined to the apical plate. Development of all neurons has been shown to depend on the function of Six3. Using a combination of molecular screens and tests of gene function by morpholino-mediated knockdown, we identified SoxC and Brn1/2/4, which function sequentially in the neurogenic regulatory pathway and are also required for the differentiation of all neurons. Misexpression of Brn1/2/4 at low dose caused an increase in the number of serotonin-expressing cells and at higher dose converted most of the embryo to a neurogenic epithelial sphere expressing the Hnf6 ciliary band marker. A third factor, Z167, was shown to work downstream of the Six3 and SoxC core factors and to define a branch specific for the differentiation of serotonergic neurons. These results provide a framework for building a gene regulatory network for neurogenesis in the sea urchin embryo.

  2. [Neurological Signs and Symptoms of True Neurogenic Thoracic Outlet Syndrome].

    PubMed

    Higashihara, Mana; Konoeda, Fumie; Sonoo, Masahiro

    2016-05-01

    Thoracic outlet syndrome (TOS) is a well-known disorder, but many aspects of its pathology, including its definition, has been disputed. True neurogenic TOS (TN-TOS) is a rare but well-defined clinical condition. TN-TOS results from the compression of the C8/T1 roots (dominant for the T1 root) or the proximal lower trunk of the brachial plexus by a fibrous band. The band extends from the first rib to either the tip of an elongated C7 transverse process or a rudimentary cervical rib. The most common presenting symptoms of TN-TOS are insidious-onset atrophy and weakness of the intrinsic hand muscles, predominantly in the thenar eminence and radial digit flexors. Nerve conduction studies demonstrate pathognomonic findings: severely attenuated compound muscle action potential of the abductor pollicis brevis muscle, and usually, loss of the sensory nerve action potential of the medial antebrachial cutaneous nerve. Numbness and sensory loss are typically observed, mainly in the medial forearm, although they are usually mild, and may be absent in some patients. Severe pain or paresthesia proximal to the elbow is not observed. The classical concept of TOS underlie nonspecific neurogenic TOS. It has been primarily diagnosed using provocative maneuvers. However, there is controversy regarding its pathological conceptualization and existence, as objective evidence of the disease is still lacking.

  3. Epigenetic regulation of stemness maintenance in the neurogenic niches

    PubMed Central

    Montalbán-Loro, Raquel; Domingo-Muelas, Ana; Bizy, Alexandra; Ferrón, Sacri R

    2015-01-01

    In the adult mouse brain, the subventricular zone lining the lateral ventricles and the subgranular zone in the dentate gyrus of the hippocampus are two zones that contain neural stem cells (NSCs) with the capacity to give rise to neurons and glia during the entire life of the animal. Spatial and temporal regulation of gene expression in the NSCs population is established and maintained by the coordinated interaction between transcription factors and epigenetic regulators which control stem cell fate. Epigenetic mechanisms are heritable alterations in genome function that do not involve changes in DNA sequence itself but that modulate gene expression, acting as mediators between the environment and the genome. At the molecular level, those epigenetic mechanisms comprise chemical modifications of DNA such as methylation, hydroxymethylation and histone modifications needed for the maintenance of NSC identity. Genomic imprinting is another normal epigenetic process leading to parental-specific expression of a gene, known to be implicated in the control of gene dosage in the neurogenic niches. The generation of induced pluripotent stem cells from NSCs by expression of defined transcription factors, provide key insights into fundamental principles of stem cell biology. Epigenetic modifications can also occur during reprogramming of NSCs to pluripotency and a better understanding of this process will help to elucidate the mechanisms required for stem cell maintenance. This review takes advantage of recent studies from the epigenetic field to report knowledge regarding the mechanisms of stemness maintenance of neural stem cells in the neurogenic niches. PMID:26029342

  4. Neurogenic gene regulatory pathways in the sea urchin embryo

    PubMed Central

    Wei, Zheng; Angerer, Lynne M.; Angerer, Robert C.

    2016-01-01

    During embryogenesis the sea urchin early pluteus larva differentiates 40-50 neurons marked by expression of the pan-neural marker synaptotagmin B (SynB) that are distributed along the ciliary band, in the apical plate and pharyngeal endoderm, and 4-6 serotonergic neurons that are confined to the apical plate. Development of all neurons has been shown to depend on the function of Six3. Using a combination of molecular screens and tests of gene function by morpholino-mediated knockdown, we identified SoxC and Brn1/2/4, which function sequentially in the neurogenic regulatory pathway and are also required for the differentiation of all neurons. Misexpression of Brn1/2/4 at low dose caused an increase in the number of serotonin-expressing cells and at higher dose converted most of the embryo to a neurogenic epithelial sphere expressing the Hnf6 ciliary band marker. A third factor, Z167, was shown to work downstream of the Six3 and SoxC core factors and to define a branch specific for the differentiation of serotonergic neurons. These results provide a framework for building a gene regulatory network for neurogenesis in the sea urchin embryo. PMID:26657764

  5. Midline synovial and ganglion cysts causing neurogenic claudication

    PubMed Central

    Pindrik, Jonathan; Macki, Mohamed; Bydon, Mohamad; Maleki, Zahra; Bydon, Ali

    2013-01-01

    Typically situated posterolateral in the spinal canal, intraspinal facet cysts often cause radicular symptoms. Rarely, the midline location of these synovial or ganglion cysts may cause thecal sac compression leading to neurogenic claudication or cauda equina syndrome. This article summarizes the clinical presentation, radiographic appearance, and management of three intraspinal, midline facet cysts. Three patients with symptomatic midline intraspinal facet cysts were retrospectively reviewed. Documented clinical visits, operative notes, histopathology reports, and imaging findings were investigated for each patient. One patient presented with neurogenic claudication while two patients developed partial, subacute cauda equina syndrome. All 3 patients initially responded favorably to lumbar decompression and midline cyst resection; however, one patient required surgical stabilization 8 mo later. Following the three case presentations, we performed a thorough literature search in order to identify articles describing intraspinal cystic lesions in lateral or midline locations. Midline intraspinal facet cysts represent an uncommon cause of lumbar stenosis and thecal sac compression. Such entities should enter the differential diagnosis of midline posterior cystic lesions. Midline cysts causing thecal sac compression respond favorably to lumbar surgical decompression and cyst resection. Though laminectomy is a commonly performed operation, stabilization may be required in cases of spondylolisthesis or instability. PMID:24364023

  6. Analysis of carbonated thin liquids in pediatric neurogenic dysphagia

    PubMed Central

    Lundine, Jennifer P.; Bates, David G.; Yin, Han

    2015-01-01

    Background Aspiration of liquids is a serious complication of neurological impairments such as traumatic brain injury or stroke. Carbonated liquids have been examined as a possible alternative to thickened liquids to help reduce aspiration in cases of dysphagia in adults, but no published literature to the best of our knowledge has evaluated this technique in children. If carbonated liquids result in safer swallowing in children, they could provide a preferred alternative to thickened liquids. Objective This pilot study examined whether carbonated thin liquids (CARB) improved swallowing compared to noncarbonated thin liquids (NOCARB) for children with neurogenic dysphagia. Materials and methods Twenty-four children admitted to a level I trauma center for acute neurological injury/disease were evaluated via videofluoroscopic swallow studies. Four descriptive outcome measures were contrasted. Results CARB significantly decreased pooling (P=0.0006), laryngeal penetration/aspiration (P=0.0044) and Penetration-Aspiration Scale scores (P=0.0127) when compared to NOCARB. On average, CARB improved scores on the Penetration-Aspiration Scale by 3.7 points for participants who aspirated NOCARB. There was no significant difference in pharyngeal residue noted between CARB and NOCARB (P=0.0625). Conclusion These findings support the hypothesis that carbonated thin liquids may provide an alternative to thickened liquids for children with neurogenic dysphagia. Implications for future research and clinical practice are discussed. PMID:25758792

  7. Midline synovial and ganglion cysts causing neurogenic claudication.

    PubMed

    Pindrik, Jonathan; Macki, Mohamed; Bydon, Mohamad; Maleki, Zahra; Bydon, Ali

    2013-12-16

    Typically situated posterolateral in the spinal canal, intraspinal facet cysts often cause radicular symptoms. Rarely, the midline location of these synovial or ganglion cysts may cause thecal sac compression leading to neurogenic claudication or cauda equina syndrome. This article summarizes the clinical presentation, radiographic appearance, and management of three intraspinal, midline facet cysts. Three patients with symptomatic midline intraspinal facet cysts were retrospectively reviewed. Documented clinical visits, operative notes, histopathology reports, and imaging findings were investigated for each patient. One patient presented with neurogenic claudication while two patients developed partial, subacute cauda equina syndrome. All 3 patients initially responded favorably to lumbar decompression and midline cyst resection; however, one patient required surgical stabilization 8 mo later. Following the three case presentations, we performed a thorough literature search in order to identify articles describing intraspinal cystic lesions in lateral or midline locations. Midline intraspinal facet cysts represent an uncommon cause of lumbar stenosis and thecal sac compression. Such entities should enter the differential diagnosis of midline posterior cystic lesions. Midline cysts causing thecal sac compression respond favorably to lumbar surgical decompression and cyst resection. Though laminectomy is a commonly performed operation, stabilization may be required in cases of spondylolisthesis or instability.

  8. [Nursing care of a patient with bipolar disorder and lithium-induced nephrogenic diabetes insipidus].

    PubMed

    García de la Orden, Lucía; García Carretero, Rafael

    2015-01-01

    Bipolar disorder is one of the most common, severe and persistent mental disorders. The evaluation of all data and variables related to bipolar disorder is a difficult task, because there is no clear agreement on what should be included in this category. One of the traditional treatments for this disease is the lithium metal that is administered in the form of lithium salt. Lithium has a narrow therapeutic window and there is a significant risk of complications arising from its use, mainly neurological and renal. In the case presented, the preparation of a care plan is described for a patient diagnosed with bipolar disorder who suffered a complication with lithium treatment. To do this, it was decided to use a standardized care plan and later completed it with diagnostic, objectives and interventions to the specific needs of the patient, aimed at achieving optimal levels of independence.

  9. Intractable Polyuria Mimicking Diabetes Insipidus-Source Traced to Vecuronium Infusion.

    PubMed

    Haldar, Rudrashish; Samanta, Sukhen; Singla, Ankush

    2016-01-01

    Continuous infusion of vecuronium is a commonly used technique for patients requiring prolonged neuromuscular blockade for mechanical ventilation. As compared with older neuromuscular blocking agents, it confers the advantages of rapid excretion and intermediate duration of action. Prolongation of neuromuscular blockade and muscle weakness are the known complications of continuous vecuronium infusion. This report attempts to describe polyuria, as a hitherto unknown complication of vecuronium infusion, which can occur due to the mannitol present in commercially available preparation of vecuronium bromide.

  10. Wegener's granulomatosis complicated by central diabetes insipidus and peripheral neutrophy with normal pituitary in a patient.

    PubMed

    Xue, Jing; Wang, Huiying; Wu, Huaxiang; Jin, Qiaofei

    2009-08-01

    Wegener's granulomatosis (WG) is a necrotizing systemic vasculitis that any organ system can be involved in. We report a patient who was hospitalized with recurrent nodules in pulmonary computed tomograph and symptoms such as intermitted fever, polydipsia, insensibility and pain on extremities. Laboratory investigation showed positive antineutrophil cytoplasmic antibody in a cytoplastic pattern. The histopathologic result of the lung nodule revealed multiloci necrosis of lung tissue accompanied with large amount of neutrophils. She was diagnosed as WG with multi-systemic involvements and almost recovered on 6 months' prednisone and cyclophosphamide treatment.

  11. Pathophysiology of diabetic sexual dysfunction.

    PubMed

    Morano, S

    2003-01-01

    Sexual dysfunction is common in patients with diabetes mellitus. Vascular, neurological and hormonal alterations are involved in this complication. Many studies showed altered endothelium-dependent and neurogenic relaxations in corpus cavernosum from diabetic patients with erectile dysfunction (ED). This finding has been associated with a lack of nitric oxyde (NO) production and a significant increase in NO synthase (NOS) binding sites in penile tissues, induced by diabetes. Advanced glycation endproducts (AGEs) concur to diabetic vascular complications by quenching NO activity and by increasing the expression of mediators of vascular damage such as vascular endothelial growth factor (VEGF), possessing permeabilizing and neoangiogenic effects, and endothelin-1 (ET-1), with vaso-constricting and mitogenic action. Moreover, the differential gene expression for various growth factors in penile tissues may be involved in the pathophysiology of ED associated with diabetes. Neuropathy is also likely to be an important cause of diabetic ED: morphological alterations of autonomic nerve fibers in cavernosal tissue of patients with diabetic ED have been demonstrated. Finally, androgens enhance nNOS gene expression in the penile corpus cavernosum of rats, suggesting that they play a role in maintaining NOS activity. However, sexual dysfunctions in women with diabetes has received less attention in clinical research. Several studies suggest an increased prevalence of deficient vaginal lubrication, making sexual intercourse unpleasant. Sexual dysfunction is associated with lower overall quality of marital relation and more depressive symptoms in diabetic women.

  12. Bendamustine-induced nephrogenic diabetes insipidus
.

    PubMed

    Derman, Benjamin A; Jain, Milli; McAninch, Elizabeth A; Gashti, Casey

    2017-01-01

    A 59-year-old man presented with polyuria and polydipsia immediately following his sixth cycle of rituximab and bendamustine for chronic lymphocytic leukemia. He initially compensated by increasing his oral fluid intake at home, but later developed septic shock and was admitted with orders to be kept nil per os (NPO). This prompted an episode of acute hypernatremia during which he exhibited continued polyuria with inappropriately dilute urine. Desmopressin challenge yielded no response in the urine osmolality, indicating a nephrogenic source of his diabetes insipidus (DI). He had no known exposure to other causative agents and had demonstrated a robust response to chemotherapy. The patient became eunatremic once oral intake was resumed and his infection was treated. Two months after presentation, he remained symptomatic. A trial with hydrochlorothiazide resulted in a significant increase in urine osmolality and subsequent decrease in urine output. To our knowledge, this is the first case of nephrogenic diabetes insipidus after rituximab and bendamustine exposure. We propose that bendamustine, similar to the alkylating agent ifosfamide, is toxic to the glomerulus and proximal tubule cells and is the most likely cause of the patient's nephrogenic DI.
.

  13. Urofacial syndrome: A subset of neurogenic bladder dysfunction syndromes?

    PubMed Central

    Stamatiou, K. N.; Karakos, C. D.

    2010-01-01

    The urofacial syndrome is probably a subset of neurogenic bladder dysfunction syndromes characterized by detrusor-sphincter discoordination along with a characteristic inversion of facial expression with laughing. This characteristic facial expression can facilitate early detection of this disorder, which leads to poor bladder emptying with high residual urine, hydro-nephrosis with vesico-ureteral reflux and potentially renal failure if left untreated. The etiology of the urofacial syndrome is unknown. In our case, a 12-year-old boy of Middle-Eastern origin presented to the Outpatient Department of our hospital with left pyelonephritis, hydronephrosis and bladder dilatation. Voiding cystourethrography performed 15 days later revealed left vesicoureteral reflux. Cystoscopy revealed bladder trabeculation however an anatomic urethral obstruction was not noticed. Both, neurological examination and radiography of the lumbosacral spine were normal. Urodynamic evaluation revealed the typical findings of detrusor-sphincter discoordination. PMID:21369396

  14. Urofacial syndrome: A subset of neurogenic bladder dysfunction syndromes?

    PubMed

    Stamatiou, K N; Karakos, C D

    2010-10-01

    The urofacial syndrome is probably a subset of neurogenic bladder dysfunction syndromes characterized by detrusor-sphincter discoordination along with a characteristic inversion of facial expression with laughing. This characteristic facial expression can facilitate early detection of this disorder, which leads to poor bladder emptying with high residual urine, hydro-nephrosis with vesico-ureteral reflux and potentially renal failure if left untreated. The etiology of the urofacial syndrome is unknown. In our case, a 12-year-old boy of Middle-Eastern origin presented to the Outpatient Department of our hospital with left pyelonephritis, hydronephrosis and bladder dilatation. Voiding cystourethrography performed 15 days later revealed left vesicoureteral reflux. Cystoscopy revealed bladder trabeculation however an anatomic urethral obstruction was not noticed. Both, neurological examination and radiography of the lumbosacral spine were normal. Urodynamic evaluation revealed the typical findings of detrusor-sphincter discoordination.

  15. Neurogenic inflammation in the gastrointestinal tract of the rat.

    PubMed

    Sann, H; Dux, M; Schemann, M; Jancsó, G

    1996-11-29

    In contrast to the skin and some visceral organs the capability of capsaicin-sensitive sensory nerves of evoking an inflammatory response in the gastrointestinal tract is equivocal. We have therefore investigated the neurogenic plasma extravasation induced by local application of capsaicin to the stomach, duodenum, jejunum, ileum and colon of the rat. Permeable vessels were visualised histologically with the vascular labelling technique using colloidal silver. In the smooth muscle layer of the small intestine, capsaicin elicited a 3-fold increase in the density of labelled blood vessels (diameter, 7-35 microns). Significant capsaicin-evoked plasma extravasation was also observed in the submucosa of the jejunum and ileum, and in the basal layer of the jejunal mucosa. Capsaicin-induced extravasation was not noted in the stomach and the colon. The data suggest the involvement of capsaicin-sensitive afferents in inflammatory processes in the rat small intestine.

  16. Persistent neurogenic bladder dysfunction due to infantile botulism.

    PubMed

    Breinbjerg, Anders; Rittig, Søren; Kamperis, Konstantinos

    2014-01-13

    We present a child, 5 months of age, diagnosed with infantile botulism, showing the signs of neurogenic bladder dysfunction. The patient presented with progressive muscle weakness, hypotonia, suckling and swallowing problems and absent peripheral reflexes at clinical examination. Botulinum neurotoxin type A was detected in her serum, confirming the diagnosis. Starting at day 6, the girl presented with a urinary retention initially necessitating free bladder drainage and subsequently intermittent catheterisation. After 6 weeks in intensive care, the patient recovered but the bladder underactivity persisted. Four months following recovery, a urodynamic evaluation was performed, showing a near normal detrusor activity and normal bladder emptying, and the catheterisation was ceased. At 6 months, the girl was diagnosed with a urinary tract infection and bladder emptying problems, which persisted, and clean intermittent catheterisation was started. The final urodynamic evaluation, a year and a half after her initial presentation, revealed a normal detrusor activity and an adequate bladder emptying.

  17. Neurogenic cardiomyopathy in rabbits with experimentally induced rabies.

    PubMed

    Kesdangsakonwut, S; Sunden, Y; Yamada, K; Nishizono, A; Sawa, H; Umemura, T

    2015-05-01

    Cardiomyopathies have been rarely described in rabbits. Here we report myocardial necrosis of the ventricular wall in rabbits with experimentally induced rabies. Myocardial lesions were found only in rabbits with brain lesions, and the severity of the cardiac lesions was proportional to that of the brain lesions. Neither the frequency nor the cumulative dose of anesthesia was related to the incidence or the severity of the myocardial lesions. The myocardial lesions were characterized by degeneration and/or necrosis of myocardial cells and were accompanied by contraction band necrosis, interstitial fibrosis, and infiltration of inflammatory cells. The brain lesions due to rabies virus infection were most prominent in the cerebral cortex, thalamus, hypothalamus, brainstem, and medulla. Rabies virus antigen was not found in the hearts of any rabbits. Based on these findings, the myocardial lesions were classified as neurogenic cardiomyopathy.

  18. Unlocking the Neurogenic Potential of Mammalian Müller Glia

    PubMed Central

    Xia, Xiaohuan; Ahmad, Iqbal

    2016-01-01

    Müller glia (MG) are the primary support cells in the vertebrate retina, regulating homeostasis in one of the most metabolically active tissues. In lower vertebrates such as fish, they respond to injury by proliferating and reprogramming to regenerate retinal neurons. In mammals, MG may also react to injury by proliferating, but they fail to initiate regeneration. The barriers to regeneration could be intrinsic to mammalian MG or the function of the niche that cannot support the MG reprogramming required for lineage conversion or both. Understanding these mechanisms in light of those being discovered in fish may lead to the formulation of strategies to unlock the neurogenic potential of MG and restore regeneration in the mammalian retina. PMID:27572710

  19. Diabetes and Stem Cell Function

    PubMed Central

    Fujimaki, Shin; Wakabayashi, Tamami; Takemasa, Tohru; Asashima, Makoto; Kuwabara, Tomoko

    2015-01-01

    Diabetes mellitus is one of the most common serious metabolic diseases that results in hyperglycemia due to defects of insulin secretion or insulin action or both. The present review focuses on the alterations to the diabetic neuronal tissues and skeletal muscle, including stem cells in both tissues, and the preventive effects of physical activity on diabetes. Diabetes is associated with various nervous disorders, such as cognitive deficits, depression, and Alzheimer's disease, and that may be caused by neural stem cell dysfunction. Additionally, diabetes induces skeletal muscle atrophy, the impairment of energy metabolism, and muscle weakness. Similar to neural stem cells, the proliferation and differentiation are attenuated in skeletal muscle stem cells, termed satellite cells. However, physical activity is very useful for preventing the diabetic alteration to the neuronal tissues and skeletal muscle. Physical activity improves neurogenic capacity of neural stem cells and the proliferative and differentiative abilities of satellite cells. The present review proposes physical activity as a useful measure for the patients in diabetes to improve the physiological functions and to maintain their quality of life. It further discusses the use of stem cell-based approaches in the context of diabetes treatment. PMID:26075247

  20. Medial antebrachial cutaneous sensory studies in the evaluation of neurogenic thoracic outlet syndrome.

    PubMed

    Kothari, M J; Macintosh, K; Heistand, M; Logigian, E L

    1998-05-01

    Over 3 years, we studied 8 patients with neurogenic thoracic outlet syndrome (TOS) and tested the medial antebrachial sensory response (MASR) to determine its diagnostic value. The MASR and ulnar sensory response (USR) were abnormal in all 8 patients. Seven had a low median motor response (MMR) with a low USR. In 1, the MASR and USR were abnormal but the MMR was normal. We conclude that the MASR is of diagnostic value in patients with neurogenic TOS.

  1. Drinking to near death--acute water intoxication leading to neurogenic stunned myocardium.

    PubMed

    Losonczy, Lia I; Lovallo, Emily; Schnorr, C Daniel; Mantuani, Daniel

    2016-01-01

    Neurogenic stunned myocardium is a rare disease entity that has been typically described as a consequence of subarachnoid hemorrhage and, less commonly, seizures. Here we describe a case of a healthy young woman who drank excessive free water causing acute hyponatremia complicated by cerebral edema and seizure, leading to cardiogenic shock from neurogenic stunned myocardium. Two days later, she had complete return of her normal cardiac function.

  2. [A case of death due to neurogenic shock].

    PubMed

    Ogata, M; Ago, K; Ago, M; Tsuganezawa, O

    1992-04-01

    An autopsy case of death due probably to neurogenic shock (primary shock) is reported. A 14-year-old boy got into a fight with his elder brother and received blows against the chest and abdomen. The young boy fell down senseless on the floor and had a spasm. An ambulance was called, but he was dead on arrival at a hospital. An autopsy revealed no external injuries on the chest and abdomen. There was no evidence of preexisting disease. On histological examination, there were signs of acute cardiac failure; edema of the lungs, liver and gall bladder, partial myofibrillar degeneration and cytoplasmic vacuoles in the media of a small coronary artery. Thus, the autopsy did not give any explanation of the fatality. It seems probable, however, that the blow(s) against the abdomen (the solar plexus) caused a fatal shock (vagal inhibition). In addition, the adrenal cortices (especially the zona fasciculata) were narrowed and the aorta was slightly narrow in caliber. It is likely that these hypoplasia might affect the fatal shock consequent to very slight injuries.

  3. Stem cells with neurogenic potential and steroid hormones.

    PubMed

    Velasco, Iván

    2011-01-01

    Pluripotent and multipotent stem cells with differentiation potential to neural phenotypes have been described and characterized in the last decades. Embryonic stem cells, as well as neural stem cells from developing and adult nervous system, can differentiate into different types of neurons, astrocytes or oligodendrocytes. Although the initially identified actions of estradiol, progesterone and testosterone are related to sexual reproductive functions, recent evidence shows that these steroid hormones modulate development, physiology and survival of nerve cells. Furthermore, neurosteroids can be synthesized in the developing and adult nervous system. A description of the molecular modulatory actions of sex steroid hormones on the Central Nervous System is presented. The main focus of this review is to summarize the described effects of steroid hormones (progesterone, allopregnanolone, dehydroepiandrosterone, estradiol and androgens) on cell parameters relevant to stem cells, both in vitro and in vivo. The overall conclusion is that steroid hormones influence stem cell behavior by several mechanisms, namely regulation of gene expression by binding to their cognate receptors, activation of intracellular pathways involving kinases or intracellular calcium signaling, and modulation of receptors for neurotransmitters; in some instances, these hormones can substitute or modulate the action of growth factors, and also directly influence self-renewal, proliferation, differentiation or cell death of neurogenic stem cells.

  4. Botulinum toxin injections for treating neurogenic detrusor overactivity

    PubMed Central

    Bayrak, Ömer; Sadioğlu, Erkan; Onur, Rahmi

    2015-01-01

    Neurogenic detrusor overactivity (NDO) is a disorder that can cause high intravesical pressure, decreased capacity, decreased bladder compliance, and upper urinary system damage. The current treatment options for NDO are established on the basis of agents that block parasympathetic innervation of the detrusor and inhibit involuntary bladder contractions. Several side effects, such as dryness of mouth, constipation, dyspepsia, changes in visual accommodation, somnolence, and being unable to obtain consistently favorable results, caused by anticholinergic agents, which are frequently used for this purpose, decrease the patient’s compliance to treatment. Procedures such as neuromodulation, auto-augmentation, and enterocystoplasty are surgical options, and they could be used as the last alternative. Thus, botulinum toxin (BTX) injections to the detrusor have been commonly performed in recent years and lead to satisfactory results. The mechanism of action of BTX in NDO is based on the principal of smooth muscle relaxation in the bladder by the transient inhibition of neuromuscular nerve signals. The aim is to decrease acetylcholine secretion by blocking presynaptic vesicles in the neuromuscular junction. When studies were evaluated, it was observed that BTX injections to the detrusor muscle are a necessary and effective option in patients with incontinence caused by NDO. This treatment option could be indicated in situations where anticholinergic agents are not effective or could not be tolerated, and it could be a valuable alternative to major surgical treatments. In this review, we evaluated the effectiveness and reliability of BTX in patients with NDO. PMID:26623152

  5. A novel ALMS1 splice mutation in a non-obese juvenile-onset insulin-dependent syndromic diabetic patient.

    PubMed

    Sanyoura, May; Woudstra, Cédric; Halaby, George; Baz, Patrick; Senée, Valérie; Guillausseau, Pierre-Jean; Zalloua, Pierre; Julier, Cécile

    2014-01-01

    Insulin-dependent juvenile-onset diabetes may occur in the context of rare syndromic presentations suggesting monogenic inheritance rather than common multifactorial autoimmune type 1 diabetes. Here, we report the case of a Lebanese patient diagnosed with juvenile-onset insulin-dependent diabetes presenting ketoacidosis, early-onset retinopathy with optic atrophy, hearing loss, diabetes insipidus, epilepsy, and normal weight and stature, who later developed insulin resistance. Despite similarities with Wolfram syndrome, we excluded the WFS1 gene as responsible for this disease. Using combined linkage and candidate gene study, we selected ALMS1, responsible for Alström syndrome, as a candidate gene. We identified a novel splice mutation in intron 18 located 3 bp before the intron-exon junction (IVS18-3T>G), resulting in exon 19 skipping and consequent frameshift generating a truncated protein (V3958fs3964X). The clinical presentation of the patient significantly differed from typical Alström syndrome by the absence of truncal obesity and short stature, and by the presence of ketoacidotic insulin-dependent diabetes, optic atrophy and diabetes insipidus. Our observation broadens the clinical spectrum of Alström syndrome and suggests that ALMS1 mutations may be considered in patients who initially present with an acute onset of insulin-dependent diabetes.

  6. Skin blood flow response to locally applied mechanical and thermal stresses in the diabetic foot.

    PubMed

    Jan, Yih-Kuen; Shen, Sa; Foreman, Robert D; Ennis, William J

    2013-09-01

    Diabetic foot ulcers are one of the most common complications in diabetics, causing significant disabilities and decreasing the quality of life. Impaired microvascular reactivity contributes to the development of diabetic foot ulcers. However, underlying physiological mechanisms responsible for the impaired microvascular reactivity in response to extrinsic causative factors of foot ulcers such as mechanical and thermal stresses have not been well investigated. A total of 26 participants were recruited into this study, including 18 type 2 diabetics with peripheral neuropathy and 8 healthy controls. Laser Doppler flowmetry was used to measure skin blood flow at the first metatarsal head in response to a mechanical stress at 300mmHg and a fast thermal stress at 42°C. Wavelet analysis of skin blood flow oscillations was used to assess metabolic, neurogenic and myogenic controls. Our results indicated that diabetics have significantly decreased metabolic, neurogenic and myogenic responses to thermal stress, especially in the neurogenic and myogenic controls during the first vasodilatory response and in the metabolic control during the second vasodilatory response. Diabetics have a significantly decreased myogenic response to mechanical stress during reactive hyperemia. Our findings demonstrate that locally applied mechanical and thermal stresses can be used to assess microvascular reactivity and risk of diabetic foot ulcers.

  7. Wolfram Syndrome: a rare optic neuropathy in youth with type 1 diabetes.

    PubMed

    Bucca, Brian C; Klingensmith, Georgeanna; Bennett, Jeffrey L

    2011-11-01

    Wolfram Syndrome (WS) is a rare, autosomal recessive disorder that causes non-autoimmune type 1 diabetes. The etiology involves a single gene mutation of the wolframin protein inducing endoplasmic reticulum stress and apoptosis in selected cell types with resultant diabetes insipidus, diabetes mellitus, optic atrophy, and sensory-neural deafness. Symptoms are initially absent and signs within the posterior segment of the eye are usually the earliest indicator of WS.These cases characterize unusual and poorly described findings of pigmentary maculopathy in WS and illustrate the importance of collaboration between diabetes and eye care providers; especially in cases of non-autoimmune type 1 diabetes exhibiting atypical human leukocyte-associated antigen haplotypes.

  8. Characterization of the spectrum of hemodynamic profiles in trauma patients with acute neurogenic shock☆

    PubMed Central

    Summers, Richard L.; Baker, Stephen D.; Sterling, Sarah A.; Porter, John M; Jones, Alan E.

    2014-01-01

    Objective Neurogenic shock considered a distributive type of shock secondary to loss of sympathetic outflow to the peripheral vasculature. In this study, we examine the hemodynamic profiles of a series of trauma patients with a diagnosis of neurogenic shock. Methods Hemodynamic data were collected on a series of trauma patients determined to have spinal cord injuries with neurogenic shock. A well-established integrated computer model of human physiology was used to analyze and categorize the hemodynamic profiles from a system analysis perspective. A differentiation between these categories was presented as the percent of total patients. Results Of the 9 patients with traumatic neurogenic shock, the etiology of shock was decrease in peripheral vascular resistance (PVR) in 3 (33%; 95% confidence interval, 12%–65%), loss of vascular capacitance in 2 (22%; 6%–55%) and mixed peripheral resistance and capacitance responsible in 3 (33%; 12%–65%), and purely cardiac in 1 (11%; 3%–48%). The markers of sympathetic outflow had no correlation to any of the elements in the patients' hemodynamic profiles. Conclusions Results from this study suggest that hypotension of neurogenic shock can have multiple mechanistic etiologies and represents a spectrum of hemodynamic profiles. This understanding is important for the treatment decisions in managing these patients. PMID:23566731

  9. Neurogenic Fever after Acute Traumatic Spinal Cord Injury: A Qualitative Systematic Review

    PubMed Central

    Savage, Katherine E.; Oleson, Christina V.; Schroeder, Gregory D.; Sidhu, Gursukhman S.; Vaccaro, Alexander R.

    2016-01-01

    Study Design  Systematic review. Objective  To determine the incidence, pathogenesis, and clinical outcomes related to neurogenic fevers following traumatic spinal cord injury (SCI). Methods  A systematic review of the literature was performed on thermodysregulation secondary to acute traumatic SCI in adult patients. A literature search was performed using PubMed (MEDLINE), Cochrane Central Register of Controlled Trials, and Scopus. Using strict inclusion and exclusion criteria, seven relevant articles were obtained. Results  The incidence of fever of all origins (both known and unknown) after SCI ranged from 22.5 to 71.7% with a mean incidence of 50.6% and a median incidence of 50.0%. The incidence of fever of unknown origin (neurogenic fever) ranged from 2.6 to 27.8% with a mean incidence of 8.0% and a median incidence of 4.7%. Cervical and thoracic spinal injuries were more commonly associated with fever than lumbar injuries. In addition, complete injuries had a higher incidence of fever than incomplete injuries. The pathogenesis of neurogenic fever after acute SCI is not thoroughly understood. Conclusion  Neurogenic fevers are relatively common following an acute SCI; however, there is little in the scientific literature to help physicians prevent or treat this condition. The paucity of research underscored by this review demonstrates the need for further studies with larger sample sizes, focusing on incidence rate, clinical outcomes, and pathogenesis of neurogenic fever following acute traumatic SCI. PMID:27556002

  10. Non-neurogenic SVZ-like niche in dolphins, mammals devoid of olfaction.

    PubMed

    Parolisi, Roberta; Cozzi, Bruno; Bonfanti, Luca

    2017-02-25

    Adult neurogenesis has been implicated in brain plasticity and brain repair. In mammals, it is mostly restricted to specific brain regions and specific physiological functions. The function and evolutionary history of mammalian adult neurogenesis has been elusive so far. The largest neurogenic site in mammals (subventricular zone, SVZ) generates neurons destined to populate the olfactory bulb. The SVZ neurogenic activity appears to be related to the dependence of the species on olfaction since it occurs at high rates throughout life in animals strongly dependent on this function for their survival. Indeed, it dramatically decreases in humans, who do not depend so much on it. This study investigates whether the SVZ neurogenic site exists in mammals devoid of olfaction and olfactory brain structures, such as dolphins. Our results demonstate that a small SVZ-like region persists in these aquatic mammals. However, this region seems to have lost its neurogenic capabilities since neonatal stages. In addition, instead of the typical newly generated neuroblasts, some mature neurons were observed in the dolphin SVZ. Since cetaceans evolved from terrestrial ancestors, non-neurogenic SVZ may indicate extinction of adult neurogenesis in the absence of olfactory function, with the retention of an SVZ-like anatomical region either vestigial or of still unknown role.

  11. PET imaging of neurogenic activity in the adult brain: Toward in vivo imaging of human neurogenesis.

    PubMed

    Tamura, Yasuhisa; Kataoka, Yosky

    2017-01-01

    Neural stem cells are present in 2 neurogenic regions, the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG), and continue to generate new neurons throughout life. Adult hippocampal neurogenesis is linked to a variety of psychiatric disorders such as depression and anxiety, and to the therapeutic effects of antidepressants, as well as learning and memory. In vivo imaging for hippocampal neurogenic activity may be used to diagnose psychiatric disorders and evaluate the therapeutic efficacy of antidepressants. However, these imaging techniques remain to be established until now. Recently, we established a quantitative positron emission tomography (PET) imaging technique for neurogenic activity in the adult brain with 3'-deoxy-3'-[(18)F]fluoro-L-thymidine ([(18)F]FLT) and probenecid, a drug transporter inhibitor in blood-brain barrier. Moreover, we showed that this PET imaging technique can monitor alterations in neurogenic activity in the hippocampus of adult rats with depression and following treatment with an antidepressant. This PET imaging method may assist in diagnosing depression and in monitoring the therapeutic efficacy of antidepressants. In this commentary, we discuss the possibility of in vivo PET imaging for neurogenic activity in adult non-human primates and humans.

  12. Urodynamic and physiologic patterns associated with the common causes of neurogenic bladder in adults.

    PubMed

    Allio, Bryce Andrew; Peterson, Andrew Charles

    2016-02-01

    The clinical presentation of the neurogenic bladder can be as vast as the pathologic causes however urodynamics (UDS) can help guide clinical decision-making and help simplify a complex disease state. UDS may be considered as the gold standard in helping to break down complex and multifactorial voiding dysfunction into manageable goals; these include protecting the upper tracts, limiting urinary tract infections (UTI) via avoiding urinary stasis, and maintaining quality of life. Included within are examples of normal to pathologic tracings including normal filling and voiding, detrusor sphincteric coordination, changes in compliance, etc. Additionally we have provided expected UDS findings based on neurogenic disease process, including but not limited to, Parkinson's, dementia, multiple sclerosis (MS) and spinal cord injury based on lesion location. Pattern recognition and understanding of UDS can help lead to quality of life improvements and optimal management for the patient with neurogenic bladder dysfunction.

  13. Urodynamic and physiologic patterns associated with the common causes of neurogenic bladder in adults

    PubMed Central

    Peterson, Andrew Charles

    2016-01-01

    The clinical presentation of the neurogenic bladder can be as vast as the pathologic causes however urodynamics (UDS) can help guide clinical decision-making and help simplify a complex disease state. UDS may be considered as the gold standard in helping to break down complex and multifactorial voiding dysfunction into manageable goals; these include protecting the upper tracts, limiting urinary tract infections (UTI) via avoiding urinary stasis, and maintaining quality of life. Included within are examples of normal to pathologic tracings including normal filling and voiding, detrusor sphincteric coordination, changes in compliance, etc. Additionally we have provided expected UDS findings based on neurogenic disease process, including but not limited to, Parkinson’s, dementia, multiple sclerosis (MS) and spinal cord injury based on lesion location. Pattern recognition and understanding of UDS can help lead to quality of life improvements and optimal management for the patient with neurogenic bladder dysfunction. PMID:26904410

  14. A comparison of hyperalgesia and neurogenic inflammation induced by melittin and capsaicin in humans.

    PubMed

    Sumikura, H; Andersen, O K; Drewes, A M; Arendt-Nielsen, L

    2003-02-13

    Melittin (a main compound of bee venom) and capsaicin were injected intradermally in healthy human volunteers: (1) to study secondary mechanical hyperalgesia (static hyperalgesia and dynamic hyperalgesia) around the injection site; and (2) to correlate the sensory changes to the neurogenic inflammation assessed by laser-doppler blood flowmetry. Melittin 50 microg and capsaicin 10 microg induced comparable spontaneous pain and increased blood flow (neurogenic inflammation). Intradermal injection of melittin induced regions of secondary mechanical hyperalgesia around the injection site, however, they were not as large as the hyperalgesia induced by capsaicin. This is the first report studying mechanical hyperalgesia induced by melittin in humans, and the results were in agreement with the previous observations in rats. Melittin seems to be a valuable model to study a possible contribution of neurogenic inflammation to hyperalgesia in humans.

  15. Characterization of multiciliated ependymal cells that emerge in the neurogenic niche of the aged zebrafish brain.

    PubMed

    Ogino, Takashi; Sawada, Masato; Takase, Hiroshi; Nakai, Chiemi; Herranz-Pérez, Vicente; Cebrián-Silla, Arantxa; Kaneko, Naoko; García-Verdugo, José Manuel; Sawamoto, Kazunobu

    2016-10-15

    In mammals, ventricular walls of the developing brain maintain a neurogenic niche, in which radial glial cells act as neural stem cells (NSCs) and generate new neurons in the embryo. In the adult brain, the neurogenic niche is maintained in the ventricular-subventricular zone (V-SVZ) of the lateral wall of lateral ventricles and the hippocampal dentate gyrus. In the neonatal V-SVZ, radial glial cells transform into astrocytic postnatal NSCs and multiciliated ependymal cells. On the other hand, in zebrafish, radial glial cells continue to cover the surface of the adult telencephalic ventricle and maintain a higher neurogenic potential in the adult brain. However, the cell composition of the neurogenic niche of the aged zebrafish brain has not been investigated. Here we show that multiciliated ependymal cells emerge in the neurogenic niche of the aged zebrafish telencephalon. These multiciliated cells appear predominantly in the dorsal part of the ventral telencephalic ventricular zone, which also contains clusters of migrating new neurons. Scanning electron microscopy and live imaging analyses indicated that these multiple cilia beat coordinately and generate constant fluid flow within the ventral telencephalic ventricle. Analysis of the cell composition by transmission electron microscopy revealed that the neurogenic niche in the aged zebrafish contains different types of cells, with ultrastructures similar to those of ependymal cells, transit-amplifying cells, and migrating new neurons in postnatal mice. These data suggest that the transformation capacity of radial glial cells is conserved but that its timing is different between fish and mice. J. Comp. Neurol. 524:2982-2992, 2016. © 2016 Wiley Periodicals, Inc.

  16. The recommendations of a consensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension.

    PubMed

    Gibbons, Christopher H; Schmidt, Peter; Biaggioni, Italo; Frazier-Mills, Camille; Freeman, Roy; Isaacson, Stuart; Karabin, Beverly; Kuritzky, Louis; Lew, Mark; Low, Phillip; Mehdirad, Ali; Raj, Satish R; Vernino, Steven; Kaufmann, Horacio

    2017-01-03

    Neurogenic orthostatic hypotension (nOH) is common in patients with neurodegenerative disorders such as Parkinson's disease, multiple system atrophy, pure autonomic failure, dementia with Lewy bodies, and peripheral neuropathies including amyloid or diabetic neuropathy. Due to the frequency of nOH in the aging population, clinicians need to be well informed about its diagnosis and management. To date, studies of nOH have used different outcome measures and various methods of diagnosis, thereby preventing the generation of evidence-based guidelines to direct clinicians towards 'best practices' when treating patients with nOH and associated supine hypertension. To address these issues, the American Autonomic Society and the National Parkinson Foundation initiated a project to develop a statement of recommendations beginning with a consensus panel meeting in Boston on November 7, 2015, with continued communications and contributions to the recommendations through October of 2016. This paper summarizes the panel members' discussions held during the initial meeting along with continued deliberations among the panel members and provides essential recommendations based upon best available evidence as well as expert opinion for the (1) screening, (2) diagnosis, (3) treatment of nOH, and (4) diagnosis and treatment of associated supine hypertension.

  17. Melatonin-receptor-1-deficiency affects neurogenic differentiation factor immunoreaction in pancreatic islets and enteroendocrine cells of mice.

    PubMed

    Shalabi, Andree; Fischer, Claudia; Korf, Horst-Werner; von Gall, Charlotte

    2013-09-01

    Neurogenic differentiation factor (NeuroD) is a transcription factor involved in the differentiation of neurons and in the control of energy balance and metabolism. It plays a key role in type 1 and type 2 diabetes. Melatonin is an important rhythmic endocrine signal within the circadian system of mammals and modulates insulin secretion and glucose metabolism. In the mouse pars tuberalis, NeuroD mRNA levels show day/night variation, which is independent of the molecular clock gene mPER1 but depends on the functional melatonin receptor 1 (MT1). So far, little is known about the effect of melatonin on NeuroD synthesis in the gastrointestinal tract. Thus, NeuroD protein levels and cellular localization were analyzed by immunohistochemistry in pancreatic islets and duodenal enteroendocrine cells of MT1- and mPER1-deficienct mice. In addition, the localization of NeuroD-positive cells was analyzed by double-immunofluorescence and confocal laser microscopy. In duodenal enteroendocrine cells and pancreatic islets of WT and PER1-deficient mice, NeuroD immunoreaction showed a peak during the early subjective night. In contrast, this peak was absent in MT1-deficent mice. These data suggest that melatonin, by acting on MT1 receptors, affects NeuroD expression in the gastrointestinal tract and thus might contribute to circadian regulation in metabolic functions.

  18. Improving Outcomes in Patients With Refractory Idiopathic and Neurogenic Detrusor Overactivity: Management Strategies.

    PubMed

    Ginsberg, David A; Schneider, Lynne Kolton; Watanabe, Thomas K

    2015-09-01

    Neurogenic detrusor overactivity (NDO) is a lower urinary tract dysfunction commonly seen in rehabilitation settings. The emotional, medical, and financial consequences of NDO can be substantial and management typically requires a multidisciplinary team approach. Physiatrists need to be able to identify patients who require referral to specialists for diagnostic testing or higher-tiered treatment and need to engender open lines of communication between their patients and all treating clinicians. This requires an understanding of the evaluation, diagnosis, and treatment of neurogenic lower urinary tract dysfunctions.

  19. Testing of diabetes-associated WFS1 polymorphisms in the Diabetes Prevention Program

    PubMed Central

    Florez, J. C.; Jablonski, K. A.; McAteer, J.; Sandhu, M. S.; Wareham, N. J.; Barroso, I.; Franks, P. W.; Altshuler, D.; Knowler, W. C.

    2008-01-01

    Aims/hypothesis Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) is caused by mutations in the WFS1 gene. Recently, single nucleotide polymorphisms (SNPs) in WFS1 have been reproducibly associated with type 2 diabetes. We therefore examined the effects of these variants on diabetes incidence and response to interventions in the Diabetes Prevention Program (DPP), in which a lifestyle intervention or metformin treatment was compared with placebo. Methods We genotyped the WFS1 SNPs rs10010131, rs752 854 and rs734312 (H611R) in 3,548 DPP participants and performed Cox regression analysis using genotype, intervention and their interactions as predictors of diabetes incidence. We also evaluated the effect of these SNPs on insulin resistance and beta cell function at 1 year. Results Although none of the three SNPs was associated with diabetes incidence in the overall cohort, white homozygotes for the previously reported protective alleles appeared less likely to develop diabetes in the lifestyle arm. Examination of the publicly available Diabetes Genetics Initiative genome-wide association dataset revealed that rs10012946, which is in strong linkage disequilibrium with the three WFS1 SNPs (r2=0.88–1.0), was associated with type 2 diabetes (allelic odds ratio 0.85, 95% CI 0.75–0.97, p=0.026). In the DPP, we noted a trend towards increased insulin secretion in carriers of the protective variants, although for most SNPs this was seen as compensatory for the diminished insulin sensitivity. Conclusions/interpretation The previously reported protective effect of select WFS1 alleles may be magnified by a lifestyle intervention. These variants appear to confer an improvement in beta cell function. PMID:18060660

  20. False diagnosis of type 1 diabetes mellitus and its complications in Wolfram syndrome--is it the reason for the low number of reported cases of this abnormality?

    PubMed

    Homa, Katarzyna; Stefański, Adam; Zmysłowska, Agnieszka; Molęda, Piotr; Bryśkiewicz, Marta Ewa; Majkowska, Liliana

    2014-01-01

    Wolfram syndrome (WS), also known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness), is a rare autosomal recessive syndrome (1/770,000 in the United Kingdom), characterised by juvenile onset of diabetes mellitus, optic nerve atrophy, diabetes insipidus, sensorineural deafness, renal tract and neurological abnormalities, and primary gonadal atrophy. WS is caused mainly by biallelic mutations in the WFS1 gene, which encodes wolframin. Wide tissue distribution of wolframin and many mutations in the wolframin gene resulting in Wolfram syndrome may contribute to different phenotypes and the unusual combinations of clinical features. We describe a female patient with Wolfram syndrome diagnosed at the age of 25, with a previous false diagnosis of type 1 diabetes mellitus and misdiagnosed diabetic complications. The patient was found to be a compound heterozygote for two novel mutations in exon 8 of WFS1 gene: a 2-bp deletion AT at nt 1539 leading to a frameshift (Y513fs) and a single-base substitution 1174C > T resulting in a stop codon (Q392X). A detailed analysis of the patient's medical history and a review of the literature suggest that many cases of Wolfram syndrome may remain undiagnosed due to misdiagnosis as type 1 diabetes mellitus and incorrect interpretation of clinical symptoms of neurodegenerative abnormalities, especially in their early stages.

  1. Diabetes - resources

    MedlinePlus

    Resources - diabetes ... The following sites provide further information on diabetes: American Diabetes Association -- www.diabetes.org Juvenile Diabetes Research Foundation International -- www.jdrf.org National Center for Chronic Disease Prevention and Health Promotion -- ...

  2. Neurogenic Language Disorders in Children. International Association of Logopedics and Phoniatrics

    ERIC Educational Resources Information Center

    Fabbro, Franco, Ed.

    2004-01-01

    Language disorders in children are one of the most frequent causes of difficulties in communication, social interaction, learning and academic achievement. It has been estimated that over 5% of children present with some kind of language disorder. This volume illustrates the state of the art in neurogenic language disorders in children. The most…

  3. Central Neurogenic Hyperventilation Related to Post-Hypoxic Thalamic Lesion in a Child

    PubMed Central

    Gençpinar, Pinar; Karaali, Kamil; Haspolat, Şenay; Dursun, Oğuz

    2016-01-01

    Central neurogenic hyperventilation (CNH) is a rare clinical condition, whose mechanism is still unclear. Here, we report a 3-year-old male patient, who had bilateral thalamic, putaminal and globus pallideal infarction resulted in CNH without brainstem involvement. This case may illustrate a possible role for the thalamus in regulating ventilation. PMID:27127601

  4. Comprehensive Expression Map of Transcription Regulators in the Adult Zebrafish Telencephalon Reveals Distinct Neurogenic Niches

    PubMed Central

    Diotel, Nicolas; Rodriguez Viales, Rebecca; Armant, Olivier; März, Martin; Ferg, Marco; Rastegar, Sepand; Strähle, Uwe

    2015-01-01

    The zebrafish has become a model to study adult vertebrate neurogenesis. In particular, the adult telencephalon has been an intensely studied structure in the zebrafish brain. Differential expression of transcriptional regulators (TRs) is a key feature of development and tissue homeostasis. Here we report an expression map of 1,202 TR genes in the telencephalon of adult zebrafish. Our results are summarized in a database with search and clustering functions to identify genes expressed in particular regions of the telencephalon. We classified 562 genes into 13 distinct patterns, including genes expressed in the proliferative zone. The remaining 640 genes displayed unique and complex patterns of expression and could thus not be grouped into distinct classes. The neurogenic ventricular regions express overlapping but distinct sets of TR genes, suggesting regional differences in the neurogenic niches in the telencephalon. In summary, the small telencephalon of the zebrafish shows a remarkable complexity in TR gene expression. The adult zebrafish telencephalon has become a model to study neurogenesis. We established the expression pattern of more than 1200 transcription regulators (TR) in the adult telencephalon. The neurogenic regions express overlapping but distinct sets of TR genes suggesting regional differences in the neurogenic potential. J. Comp. Neurol. 523:1202–1221, 2015. © 2015 Wiley Periodicals, Inc. PMID:25556858

  5. A Clinician Survey of Speech and Non-Speech Characteristics of Neurogenic Stuttering

    ERIC Educational Resources Information Center

    Theys, Catherine; van Wieringen, Astrid; De Nil, Luc F.

    2008-01-01

    This study presents survey data on 58 Dutch-speaking patients with neurogenic stuttering following various neurological injuries. Stroke was the most prevalent cause of stuttering in our patients, followed by traumatic brain injury, neurodegenerative diseases, and other causes. Speech and non-speech characteristics were analyzed separately for…

  6. Leiomyosarcoma of the Oropharynx and Neurogenic Tumors in a Young Patient With Turner's Syndrome

    PubMed Central

    Apice, Gaetano; Silvestro, Giustino; Losito, Simona; Botti, Gerardo; Ionna, Francesco; De Rosa, Vincenzo; Borghese, Annamaria; Ninfo, Vito

    2001-01-01

    Patient: A case of Turner's syndrome developing a leiomyosarcoma of the oropharynx and metachronous neurogenic tumors (mediastinal ‘ganglioneuroblastoma intermixed’, subcutaneous neurilemoma) is described. Discussion: To our knowledge, this case is the second reported leiomyosarcoma in a patient with Turner's syndrome. Also the site of involvement (palate and oropharynx) is particularly unusual for the already rare leiomyosarcomas in the young age. PMID:18521442

  7. Paroxetine Can Enhance Neurogenesis during Neurogenic Differentiation of Human Adipose-derived Stem Cells

    PubMed Central

    Jahromi, Maliheh; Razavi, Shahnaz; Amirpour, Nushin; Khosravizadeh, Zahra

    2016-01-01

    Background: Some antidepressant drugs can promote neuronal cell proliferation in vitro as well as hippocampal neurogenesis in human and animal models. Furthermore, adipose tissue is an available source of adult stem cells with the ability to differentiate in to multiple lineages. Therefore, human Adipose-Derived Stem Cells (hAD-SCs) may be a suitable source for regenerative medical applications. Since there is no evidence for the effect of Paroxetine as the most commonly prescribed antidepressant drug for neurogenic potential of hADSCs, an attempt was made to determine the effect of Paroxetine on proliferation and neural differentiation of hADSCs. Methods: ADSCs were isolated from human abdominal fat. These cells differentiated to neuron-like cells and were treated with Paroxetine. 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay and immunofluorescence technique were used for assessment of cell proliferation and neurogenic differentiation potential of induced cells, respectively. Results: MTT assay analysis showed that Paroxetine significantly increased the proliferation rate of induced hADSCs (p<0.05), while immunofluorescent staining indicated that Paroxetine treatment during neurogenic differentiation could enhance the mean percentage of Nestin and MAP2 (Microtubule-associated protein-2) positive cells but the mean percentage of GFAP (Glial acidic fibrillary protein) positive cells significantly decreased relative to control group (p<0.05). Conclusion: Our results provide evidence that Paroxetine can promote proliferation and differentiation rate during neurogenic differentiation of hADSCs. Moreover, Paroxetine can reduce gliogenesis of induced hADSCs during neurogenic differentiation. PMID:27920882

  8. Differential expression of neurogenes among breast cancer subtypes identifies high risk patients

    PubMed Central

    Fernández-Nogueira, Patricia; Bragado, Paloma; Almendro, Vanessa; Ametller, Elisabet; Rios, Jose; Choudhury, Sibgat

    2016-01-01

    The nervous system is now recognized to be a relevant component of the tumor microenvironment. Receptors for neuropeptides and neurotransmitters have been identified in breast cancer. However, very little is known about the role of neurogenes in regulating breast cancer progression. Our purpose was to identify neurogenes associated with breast cancer tumorigenesis with a potential to be used as biomarker and/or targets for treatment. We used three databases of human genes: GeneGo, GeneCards and Eugenes to generate a list of 1266 relevant neurogenes. Then we used bioinformatics tools to interrogate two published breast cancer databases SAGE and MicMa (n=96) and generated a list of 7 neurogenes that are differentially express among breast cancer subtypes. The clinical potential was further investigated using the GOBO database (n=1881). We identified 6 neurogenes that are differentially expressed among breast cancer subtypes and whose expression correlates with prognosis. Histamine receptor1 (HRH1), neuropilin2 (NRP2), ephrin-B1 (EFNB1), neural growth factor receptor (NGFR) and amyloid precursor protein (APP) were differentially overexpressed in basal and HER2-enriched tumor samples and syntaxin 1A (STX1A) was overexpressed in HER2-enriched and luminal B tumors. Analysis of HRH1, NRP2, and STX1A expression using the GOBO database showed that their expression significantly correlated with a shorter overall survival (p < 0.0001) and distant metastasis-free survival (p < 0.0001). In contrast, elevated co-expression of NGFR, EFNB1 and APP was associated with longer overall (p < 0.0001) and metastasis-free survival (p < 0.0001). We propose that HRH1, NRP2, and STX1A can be used as prognostic biomarkers and therapeutic targets for basal and HER2-enriched breast cancer subtypes. PMID:26673618

  9. Deletion of protein tyrosine phosphatase 1b in proopiomelanocortin neurons reduces neurogenic control of blood pressure and protects mice from leptin- and sympatho-mediated hypertension.

    PubMed

    Bruder-Nascimento, Thiago; Butler, Benjamin R; Herren, David J; Brands, Michael W; Bence, Kendra K; Belin de Chantemèle, Eric J

    2015-12-01

    Protein tyrosine phosphatase 1b (Ptp1b), which represses leptin signaling, is a promising therapeutic target for obesity. Genome wide deletion of Ptp1b, increases leptin sensitivity, protects mice from obesity and diabetes, but alters cardiovascular function by increasing blood pressure (BP). Leptin-control of metabolism is centrally mediated and involves proopiomelanocortin (POMC) neurons. Whether these neurons contribute to leptin-mediated increases in BP remain unclear. We hypothesized that increasing leptin signaling in POMC neurons with Ptp1b deletion will sensitize the cardiovascular system to leptin and enhance neurogenic control of BP. We analyzed the cardiovascular phenotype of Ptp1b+/+ and POMC-Ptp1b-/- mice, at baseline and after 7 days of leptin infusion or sympatho-activation with phenylephrine. POMCPtp1b deletion did not alter baseline cardiovascular hemodynamics (BP, heart rate) but reduced BP response to ganglionic blockade and plasma catecholamine levels that suggests a decreased neurogenic control of BP. In contrast, POMC-Ptp1b deletion increased vascular adrenergic reactivity and aortic α-adrenergic receptors expression. Chronic leptin treatment reduced vascular adrenergic reactivity and blunted diastolic and mean BP increases in POMC-Ptp1b-/- mice only. Similarly POMC-Ptp1b-/- mice exhibited a blunted increased in diastolic and mean BP accompanied by a gradual reduction in adrenergic reactivity in response to chronic vascular sympatho-activation with phenylephrine. Together these data rule out our hypothesis but suggest that deletion of Ptp1b in POMC neurons protects from leptin- and sympatho-mediated increases in BP. Vascular adrenergic desensitization appears as a protective mechanism against hypertension, and POMC-Ptp1b as a key therapeutic target for the treatment of metabolic and cardiovascular dysfunctions associated with obesity.

  10. Circadian Kinetics of Cell Cycle Progression in Adult Neurogenic Niches of a Diurnal Vertebrate.

    PubMed

    Akle, Veronica; Stankiewicz, Alexander J; Kharchenko, Vasili; Yu, Lili; Kharchenko, Peter V; Zhdanova, Irina V

    2017-02-15

    The circadian system may regulate adult neurogenesis via intracellular molecular clock mechanisms or by modifying the environment of neurogenic niches, with daily variation in growth factors or nutrients depending on the animal's diurnal or nocturnal lifestyle. In a diurnal vertebrate, zebrafish, we studied circadian distribution of immunohistochemical markers of the cell division cycle (CDC) in 5 of the 16 neurogenic niches of adult brain, the dorsal telencephalon, habenula, preoptic area, hypothalamus, and cerebellum. We find that common to all niches is the morning initiation of G1/S transition and daytime S-phase progression, overnight increase in G2/M, and cycle completion by late night. This is supported by the timing of gene expression for critical cell cycle regulators cyclins D, A2, and B2 and cyclin-dependent kinase inhibitor p20 in brain tissue. The early-night peak in p20, limiting G1/S transition, and its phase angle with the expression of core clock genes, Clock1 and Per1, are preserved in constant darkness, suggesting intrinsic circadian patterns of cell cycle progression. The statistical modeling of CDC kinetics reveals the significant circadian variation in cell proliferation rates across all of the examined niches, but interniche differences in the magnitude of circadian variation in CDC, S-phase length, phase angle of entrainment to light or clock, and its dispersion. We conclude that, in neurogenic niches of an adult diurnal vertebrate, the circadian modulation of cell cycle progression involves both systemic and niche-specific factors.SIGNIFICANCE STATEMENT This study establishes that in neurogenic niches of an adult diurnal vertebrate, the cell cycle progression displays a robust circadian pattern. Common to neurogenic niches located in diverse brain regions is daytime progression of DNA replication and nighttime mitosis, suggesting systemic regulation. Differences between neurogenic niches in the phase and degree of S-phase entrainment to the

  11. Circadian Kinetics of Cell Cycle Progression in Adult Neurogenic Niches of a Diurnal Vertebrate

    PubMed Central

    Stankiewicz, Alexander J.; Kharchenko, Vasili; Yu, Lili; Kharchenko, Peter V.

    2017-01-01

    The circadian system may regulate adult neurogenesis via intracellular molecular clock mechanisms or by modifying the environment of neurogenic niches, with daily variation in growth factors or nutrients depending on the animal's diurnal or nocturnal lifestyle. In a diurnal vertebrate, zebrafish, we studied circadian distribution of immunohistochemical markers of the cell division cycle (CDC) in 5 of the 16 neurogenic niches of adult brain, the dorsal telencephalon, habenula, preoptic area, hypothalamus, and cerebellum. We find that common to all niches is the morning initiation of G1/S transition and daytime S-phase progression, overnight increase in G2/M, and cycle completion by late night. This is supported by the timing of gene expression for critical cell cycle regulators cyclins D, A2, and B2 and cyclin-dependent kinase inhibitor p20 in brain tissue. The early-night peak in p20, limiting G1/S transition, and its phase angle with the expression of core clock genes, Clock1 and Per1, are preserved in constant darkness, suggesting intrinsic circadian patterns of cell cycle progression. The statistical modeling of CDC kinetics reveals the significant circadian variation in cell proliferation rates across all of the examined niches, but interniche differences in the magnitude of circadian variation in CDC, S-phase length, phase angle of entrainment to light or clock, and its dispersion. We conclude that, in neurogenic niches of an adult diurnal vertebrate, the circadian modulation of cell cycle progression involves both systemic and niche-specific factors. SIGNIFICANCE STATEMENT This study establishes that in neurogenic niches of an adult diurnal vertebrate, the cell cycle progression displays a robust circadian pattern. Common to neurogenic niches located in diverse brain regions is daytime progression of DNA replication and nighttime mitosis, suggesting systemic regulation. Differences between neurogenic niches in the phase and degree of S-phase entrainment to

  12. The use of laser acupuncture for the treatment of neurogenic pruritus in a child--a case history.

    PubMed

    Stellon, Anthony

    2005-03-01

    This report describes the successful treatment using laser acupuncture of a six year old girl with neurogenic pruritus of the abdomen. It is the first case report of neurogenic pruritus treated by laser acupuncture. The main advantage of using low energy laser, as opposed to acupuncture needles, to stimulate points, is that low energy laser causes little or no sensation, which is particularly useful when treating children.

  13. Diabetic Retinopathy

    MedlinePlus

    ... version of this page please turn Javascript on. Diabetic Retinopathy What Is Diabetic Retinopathy? Click for more information Can Cause Vision ... vision loss and even blindness can result. Other Diabetic Eye Diseases In addition to diabetic retinopathy, other ...

  14. Diabetes Medicines

    MedlinePlus

    ... Problems Diabetes & Sexual & Urologic Problems Insulin, Medicines, & Other Diabetes Treatments Taking insulin or other diabetes medicines is ... also available. What medicines might I take for diabetes? The medicine you take will vary by your ...

  15. Diminished Neurogenic Femoral Artery Vasoconstrictor Response in a Zucker Obese Rat Model: Differential Regulation of NOS and COX Derivatives

    PubMed Central

    Martínez, Ana Cristina; Hernández, Medardo; Novella, Susana; Martínez, María Pilar; Pagán, Rosa María; Hermenegildo, Carlos; García-Sacristán, Albino; Prieto, Dolores; Benedito, Sara

    2014-01-01

    Objective Peripheral arterial disease is one of the macrovascular complications of type 2 diabetes mellitus. This study addresses femoral artery regulation in a prediabetic model of obese Zucker rats (OZR) by examining cross-talk between endothelial and neural factors. Methods and Results Arterial preparations from lean (LZR) and OZR were subjected to electrical field stimulation (EFS) on basal tone. Nitric oxide synthase (NOS) and cyclooxygenase (COX) isoform expression patterns were determined by immunohistochemical labelling and Western blotting. Results indicate significantly reduced noradrenergic contractions in preparations from OZR compared with those of LZR. Functional inhibition of endothelial NOS (eNOS) indicated a predominant role of this isoform in LZR and its modified activity in OZR. Neural (nNOS) and inducible NOS (iNOS) were activated and their expression was higher in femoral arteries from OZR. Neurotransmission modulated by large-conductance Ca2+-activated (BKCa) or voltage-dependent (KV) K+ channels did not seem compromised in the obese animals. Endothelial COX-1 and COX-2 were expressed in LZR and an additional adventitial location of COX-2 was also observed in OZR, explaining the higher COX-2 protein levels detected in this group. Prostanoids derived from both isoforms helped maintain vasoconstriction in LZR while in OZR only COX-2 was active. Superoxide anion inhibition reduced contractions in endothelium-intact arteries from OZR. Conclusions Endothelial dysfunction led to reduced neurogenic vasoconstriction in femoral arteries from OZR. In a setting of obesity, NO-dependent nNOS and iNOS dilation activity could be an alternative mechanism to offset COX-2- and reactive oxygen species-mediated vasoconstriction, along with impaired endothelial NO relaxation. PMID:25216050

  16. Neurogenic pathways in remote ischemic preconditioning induced cardioprotection: Evidences and possible mechanisms

    PubMed Central

    Aulakh, Amritpal Singh; Randhawa, Puneet Kaur; Singh, Nirmal

    2017-01-01

    Remote ischemic preconditioning (RIPC) is an intrinsic phenomenon whereby 3~4 consecutive ischemia-reperfusion cycles to a remote tissue (noncardiac) increases the tolerance of the myocardium to sustained ischemiareperfusion induced injury. Remote ischemic preconditioning induces the local release of chemical mediators which activate the sensory nerve endings to convey signals to the brain. The latter consequently stimulates the efferent nerve endings innervating the myocardium to induce cardioprotection. Indeed, RIPC-induced cardioprotective effects are reliant on the presence of intact neuronal pathways, which has been confirmed using nerve resection of nerves including femoral nerve, vagus nerve, and sciatic nerve. The involvement of neurogenic signaling has been further substantiated using various pharmacological modulators including hexamethonium and trimetaphan. The present review focuses on the potential involvement of neurogenic pathways in mediating remote ischemic preconditioning-induced cardioprotection. PMID:28280407

  17. Neurogenic inflammation and the peripheral nervous system in host defense and immunopathology.

    PubMed

    Chiu, Isaac M; von Hehn, Christian A; Woolf, Clifford J

    2012-07-26

    The peripheral nervous and immune systems are traditionally thought of as serving separate functions. The line between them is, however, becoming increasingly blurred by new insights into neurogenic inflammation. Nociceptor neurons possess many of the same molecular recognition pathways for danger as immune cells, and, in response to danger, the peripheral nervous system directly communicates with the immune system, forming an integrated protective mechanism. The dense innervation network of sensory and autonomic fibers in peripheral tissues and high speed of neural transduction allows rapid local and systemic neurogenic modulation of immunity. Peripheral neurons also seem to contribute to immune dysfunction in autoimmune and allergic diseases. Therefore, understanding the coordinated interaction of peripheral neurons with immune cells may advance therapeutic approaches to increase host defense and suppress immunopathology.

  18. Precocious puberty: clinical and endocrine profile and factors indicating neurogenic precocity in Indian children.

    PubMed

    Bajpai, Anurag; Sharma, Jyoti; Kabra, Madhulika; Kumar Gupta, Arun; Menon, P S N

    2002-01-01

    The objective of this study was to evaluate the clinical and endocrine profile of patients with precocious puberty followed up in a tertiary care hospital. Records of 140 patients (114 girls, 26 boys) with precocious puberty were reviewed. Clinical features including age of onset, stage of pubertal development, presenting symptoms, features suggestive of CNS involvement and family history were analyzed. Endocrine investigations included basal and GnRH-stimulated levels of LH and FSH as well as 17OHP, DHEA, hCG and thyroid profile. Abdominal and pelvic ultrasonography and CNS imaging were correlated with clinical features. Girls outnumbered boys in this series (4.4:1). Neurogenic central isosexual precocious puberty (CIPP) was more common in boys (10 out of 18, 55.6%) than girls (16 out of 77, 20.8%). The most common cause of neurogenic CIPP was hypothalamic hamartoma present in five girls and four boys. Other causes of neurogenic CIPP included neurotuberculosis, pituitary adenoma, hydrocephalus, post radiotherapy, CNS tumors and malformations. Peripheral precocious puberty (PPP) was secondary to adrenal causes in boys and ovarian cysts in girls. Benign variants of precocious puberty, such as premature thelarche and premature adrenarche, were present in 23 and six girls, respectively. Hypothyroidism was present in four girls and McCune-Albright syndrome in one girl. Girls with neurogenic CIPP had a lower age of onset as compared to idiopathic CIPP (3.6 +/- 2.7 years vs 5.4 +/- 2.5 years, p = 0.014). The lowest age of onset was seen in girls with hypothalamic hamartoma (1.6 +/- 0.9 years). Forty-seven girls with CIPP (seven neurogenic and 40 idiopathic) presented after the age of 6 years. Features of CNS involvement, in the form of seizures, mental retardation, raised intracranial tension or focal neurological deficits, were present in seven girls (43.8%) and four boys (40%), and gelastic seizures were present in three children. Girls with CIPP had greater bone age

  19. [A case of true neurogenic thoracic outlet syndrome accompanied by an aberrant right subclavian artery].

    PubMed

    Sekiguchi, Kenji; Saito, Takanori; Yokota, Ichiro; Kowa, Hisatomo; Kanda, Fumio; Toda, Tatsushi

    2015-01-01

    A 65-year-old woman experienced progressive intrinsic muscle wasting on the right hand over a period of 7 years. The distribution of muscular atrophy and weakness was consistent with the area innervated by the right C8 and Th1 nerve roots. Neurophysiological examination suggested a right lower trunk lesion. An elongated right transverse process of the C7 vertebra and an aberrant subclavian artery were detected on computed tomography images, and the right lower trunk of the brachial plexus appeared to be lifted upward on magnetic resonance images. The patient was diagnosed with true neurogenic thoracic outlet syndrome. A fibrous band extending from the elongated transverse process was found during surgery, and symptoms did not progress further after resection of the band. True neurogenic thoracic outlet syndrome can cause monomelic amyotrophy, and localized neuroimaging and detailed neurophysiological examination were useful for diagnosis.

  20. A Case of Neuro-Behcet’s Disease Presenting with Central Neurogenic Hyperventilation

    PubMed Central

    Alkhachroum, Ayham M.; Saeed, Saba; Kaur, Jaspreet; Shams, Tanzila; De Georgia, Michael A.

    2016-01-01

    Patient: Female, 46 Final Diagnosis: Central hyperventilation Symptoms: Hyperventilation Medication: — Clinical Procedure: None Specialty: Neurology Objective: Unusual clinical course Background: Behcet’s disease is a chronic inflammatory disorder usually characterized by the triad of oral ulcers, genital ulcers, and uveitis. Central to the pathogenesis of Behcet’s disease is an autoimmune vasculitis. Neurological involvement, so called “Neuro-Behcet’s disease”, occurs in 10–20% of patients, usually from a meningoencephalitis or venous thrombosis. Case Report: We report the case of a 46-year-old patient with Neuro-Behcet’s disease who presented with central neurogenic hyperventilation as a result of brainstem involvement from venulitis. Conclusions: To the best of our knowledge, central neurogenic hyperventilation has not previously been described in a patient with Neuro-Behcet’s disease. PMID:26965646

  1. Women and Diabetes -- Diabetes Medicines

    MedlinePlus

    ... Audience For Women Women's Health Topics Women and Diabetes - Diabetes Medicines Share Tweet Linkedin Pin it More sharing ... 1-800-332-1088 to request a form. Diabetes Medicines The different kinds of diabetes medicines are ...

  2. Spinal TRPA1 ion channels contribute to cutaneous neurogenic inflammation in the rat.

    PubMed

    Wei, Hong; Koivisto, Ari; Pertovaara, Antti

    2010-08-02

    In the spinal dorsal horn, TRPA1 ion channels on central terminals of peptidergic primary afferent nerve fibers regulate transmission to glutamatergic and GABAergic interneurons. Here we determine the cutaneous anti-inflammatory effect of a spinally administered TRPA1 channel antagonist to test the hypothesis that spinal TRPA1 channels contribute to cutaneous neurogenic inflammation induced by sustained noxious stimulation. According to the hypothesis, spinal TRPA1 channels facilitate transmission of injury discharge to GABAergic interneurons that induce a dorsal root reflex, which results in increased release of proinflammatory compounds in the skin. Intraplantar capsaicin, a TRPV1 channel agonist, was used to induce neurogenic inflammation in anesthetized rats that were pretreated intrathecally (i.t.), intraplantarly (i.pl.) or intraperitoneally (i.p.) with vehicle or Chembridge-5861526 (CHEM, a TRPA1 channel antagonist). For assessment of neurogenic inflammation, the capsaicin-induced increase of cutaneous blood flow was determined adjacent to the capsaicin-treated skin site with a laser Doppler flowmeter. Capsaicin-induced a marked increase in cutaneous blood flow. The capsaicin-induced blood flow increase was attenuated in a dose-related fashion by i.t. pretreatment with CHEM (3-10microg). Pretreatment with CHEM at a dose of 3mg/kg i.p. or 20microg i.pl. failed to attenuate the capsaicin-induced increase of blood flow. The results indicate that spinal TRPA1 channels contribute to cutaneous neurogenic inflammation adjacent to the injury site, probably by facilitating a dorsal root reflex in peptidergic primary afferent nerve fibers.

  3. Brain ACE2 shedding contributes to the development of neurogenic hypertension

    PubMed Central

    Chhabra, Kavaljit H.; Lazartigues, Eric

    2015-01-01

    Rationale Over-activity of the brain Renin Angiotensin System (RAS) is a major contributor to neurogenic hypertension. While over-expression of Angiotensin-Converting Enzyme type 2 (ACE2) has been shown to be beneficial in reducing hypertension by transforming Angiotensin (Ang)-II into Ang-(1-7), several groups have reported decreased brain ACE2 expression and activity during the development of hypertension. Objective We hypothesized that ADAM17-mediated ACE2 shedding results in decreased membrane-bound ACE2 in the brain, thus promoting the development of neurogenic hypertension. Methods and Results To test this hypothesis, we used the DOCA-salt model of neurogenic hypertension in non-transgenic (NT) and syn-hACE2 mice over-expressing ACE2 in neurons. DOCA-salt treatment in NT mice led to significant increases in blood pressure, hypothalamic Ang-II levels, inflammation, impaired baroreflex sensitivity, autonomic dysfunction, as well as decreased hypothalamic ACE2 activity and expression, while these changes were blunted or prevented in syn-hACE2 mice. In addition, reduction of ACE2 expression and activity in the brain paralleled a rise in ACE2 activity in the cerebrospinal fluid of NT mice following DOCA-salt treatment and was accompanied by enhanced ADAM17 expression and activity in the hypothalamus. Chronic knockdown of ADAM17 in the brain blunted the development of hypertension and restored ACE2 activity and baroreflex function. Conclusions Our data provide the first evidence that ADAM17-mediated shedding impairs brain ACE2 compensatory activity, thus contributing to the development of neurogenic hypertension. PMID:24014829

  4. Inhibition by ketamine and amphetamine analogs of the neurogenic nitrergic vasodilations in porcine basilar arteries.

    PubMed

    Chen, Mei-Fang; Lai, Su-Yu; Kung, Po-Cheng; Lin, Yo-Cheng; Yang, Hui-I; Chen, Po-Yi; Liu, Ingrid Y; Lua, Ahai Chang; Lee, Tony Jer-Fu

    2016-08-15

    The abuse of ketamine and amphetamine analogs is associated with incidence of hypertension and strokes involving activation of sympathetic activities. Large cerebral arteries at the base of the brain from several species receive dense sympathetic innervation which upon activation causes parasympathetic-nitrergic vasodilation with increased regional blood flow via axo-axonal interaction mechanism, serving as a protective mechanism to meet O2 demand in an acutely stressful situation. The present study was designed to examine effects of ketamine and amphetamine analogs on axo-axonal interaction-mediated neurogenic nitrergic vasodilation in porcine basilar arteries using techniques of blood-vessel myography, patch clamp and two-electrode voltage clamp, and calcium imaging. In U46619-contracted basilar arterial rings, nicotine (100μM) and electrical depolarization of nitrergic nerves by transmural nerve stimulation (TNS, 8Hz) elicited neurogenic nitrergic vasodilations. Ketamine and amphetamine analogs concentration-dependently inhibited nicotine-induced parasympathetic-nitrergic vasodilation without affecting that induced by TNS, nitroprusside or isoproterenol. Ketamine and amphetamine analogs also concentration-dependently blocked nicotine-induced inward currents in Xenopus oocytes expressing α3β2-nicotinic acetylcholine receptors (nAChRs), and nicotine-induced inward currents as well as calcium influxes in rat superior cervical ganglion neurons. The potency in inhibiting both inward-currents and calcium influxes is ketamine>methamphetamine>hydroxyamphetamine. These results indicate that ketamine and amphetamine analogs, by blocking nAChRs located on cerebral perivascular sympathetic nerves, reduce nicotine-induced, axo-axonal interaction mechanism-mediated neurogenic dilation of the basilar arteries. Chronic abuse of these drugs, therefore, may interfere with normal sympathetic-parasympathetic interaction mechanism resulting in diminished neurogenic vasodilation

  5. Droxidopa and Reduced Falls in a Trial of Parkinson Disease Patients With Neurogenic Orthostatic Hypotension

    PubMed Central

    Hauser, Robert A.; Heritier, Stephane; Rowse, Gerald J.; Hewitt, L. Arthur; Isaacson, Stuart H.

    2016-01-01

    Objectives Droxidopa is a prodrug of norepinephrine indicated for the treatment of orthostatic dizziness, lightheadedness, or the “feeling that you are about to black out” in adult patients with symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure including Parkinson disease (PD). The objective of this study was to compare fall rates in PD patients with symptomatic neurogenic orthostatic hypotension randomized to droxidopa or placebo. Methods Study NOH306 was a 10-week, phase 3, randomized, placebo-controlled, double-blind trial of droxidopa in PD patients with symptomatic neurogenic orthostatic hypotension that included assessments of falls as a key secondary end point. In this report, the principal analysis consisted of a comparison of the rate of patient-reported falls from randomization to end of study in droxidopa versus placebo groups. Results A total of 225 patients were randomized; 222 patients were included in the safety analyses, and 197 patients provided efficacy data and were included in the falls analyses. The 92 droxidopa patients reported 308 falls, and the 105 placebo patients reported 908 falls. In the droxidopa group, the fall rate was 0.4 falls per patient-week; in the placebo group, the rate was 1.05 falls per patient-week (prespecified Wilcoxon rank sum P = 0.704; post hoc Poisson-inverse Gaussian test P = 0.014), yielding a relative risk reduction of 77% using the Poisson-inverse Gaussian model. Fall-related injuries occurred in 16.7% of droxidopa-treated patients and 26.9% of placebo-treated patients. Conclusions Treatment with droxidopa appears to reduce falls in PD patients with symptomatic neurogenic orthostatic hypotension, but this finding must be confirmed. PMID:27332626

  6. GABAergic signalling in a neurogenic niche of the turtle spinal cord

    PubMed Central

    Reali, Cecilia; Fernández, Anabel; Radmilovich, Milka; Trujillo-Cenóz, Omar; Russo, Raúl E

    2011-01-01

    Abstract The region that surrounds the central canal (CC) in the turtle spinal cord is a neurogenic niche immersed within already functional circuits, where radial glia expressing brain lipid binding protein (BLBP) behave as progenitors. The behaviour of both progenitors and neuroblasts within adult neurogenic niches must be regulated to maintain the functional stability of the host circuit. In the brain, GABA plays a major role in this kind of regulation but little is known about GABAergic signalling in neurogenic niches of the postnatal spinal cord. Here we explored the action of GABA around the CC of the turtle spinal cord by combining patch-clamp recordings of CC-contacting cells, immunohistochemistry for key components of GABAergic signalling and Ca2+ imaging. Two potential sources of GABA appeared around the CC: GABAergic terminals and CC-contacting neurones. GABA depolarized BLBP+ progenitors via GABA transporter-3 (GAT3) and/or GABAA receptors. In CC-contacting neurones, GABAA receptor activation generated responses ranging from excitation to inhibition. This functional heterogeneity appeared to originate from different ratios of activity of the Na+–K+–2Cl− co-transporter (NKCC1) and the K+–Cl− co-transporter (KCC2). In both progenitors and immature neurones, GABA induced an increase in intracellular Ca2+ that required extracellular Ca2+ and was blocked by the selective GABAA receptor antagonist gabazine. Our study shows that GABAergic signalling around the CC shares fundamental properties with those in the embryo and adult neurogenic niches, suggesting that GABA may be part of the mechanisms regulating the production and integration of neurones within operational spinal circuits in the turtle. PMID:21911613

  7. Neurogenic period of ascending tract neurons in the upper lumbar spinal cord of the rat

    SciTech Connect

    Nandi, K.N.; Beal, J.A.; Knight, D.S. )

    1990-02-01

    Although the neurogenic period for neurons in the lumbar spinal cord has been clearly established (Days 12 through 16 of gestation), it is not known when the neurogenesis of ascending tract neurons is completed within this period. The purpose of the present study was to determine the duration of the neurogenic period for projection neurons of the ascending tracts. To label neurons undergoing mitosis during this period, tritiated thymidine was administered to fetal rats on Embryonic (E) Days E13 through E16 of gestation. Ascending tract neurons of the lumbar cord were later (Postnatal Days 40-50) labeled in each animal with a retrograde tracer, Fluoro-Gold, applied at the site of a hemisection at spinal cord segment C3. Ascending tract neurons which were undergoing mitosis in the upper lumbar cord were double labeled, i.e., labeled with both tritiated thymidine and Fluoro-Gold. On Day E13, 89-92% of the ascending tract neurons were double labeled; on Day E14, 35-37%; and on Day E15, 1-4%. Results showed, then, that some ascending tract neurons were double labeled through Day E15 and were, therefore, proliferating in the final one-third of the neurogenic period. Ascending tract neurons proliferating on Day E15 were confined to laminae III, IV, V, and X and the nucleus dorsalis. Long tract neurons in the superficial dorsal horn (laminae I and II), on the other hand, were found to have completed neurogenesis on Day E14 of gestation. Results of the present study show that spinal neurogenesis of ascending projection neurons continues throughout most of the neurogenic period and does not completely follow the well-established ventral to dorsal gradient.

  8. Botulinum toxin type A reduces capsaicin-evoked pain and neurogenic vasodilatation in human skin.

    PubMed

    Tugnoli, Valeria; Capone, Jay Guido; Eleopra, Roberto; Quatrale, Rocco; Sensi, Mariachiara; Gastaldo, Ernesto; Tola, Maria Rosaria; Geppetti, Pierangelo

    2007-07-01

    The effect of Botulinum Toxin type A (BoNT/A) on pain and neurogenic vasodilatation induced by application to the human skin of thermal stimuli and capsaicin was evaluated in a double blind study. A capsaicin cream (0.5 ml of a 0.075%) was applied to the skin of both forearms of eighteen subjects randomly pretreated with either BoNT/A (Botox) or 0.9% saline (NS). Capsaicin was applied to a skin area either inside (protocol A) or adjacent to the BoNT/A treated area (protocol B). Pre-treatment with BoNT/A did not affect thermal-specific and thermal-pain thresholds (by quantitative sensory testing). However, capsaicin-induced pain sensation (by a visual analogue scale), flare area (by acetate sheet) and changes in cutaneous blood flow (CBF, by laser Doppler flowmetry) were reduced when capsaicin was administered inside (protocol A) the BoNT/A treated area. In Protocol B, capsaicin-induced pain was unchanged, and capsaicin-induced flare/increase in CBF were reduced only in the area treated with BoNT/A, but not in the BoNT/A untreated area. Results indicate that (i) BoNT/A reduces capsaicin-induced pain and neurogenic vasodilatation without affecting the transmission of thermal and thermal-pain modalities; (ii) reduction in capsaicin-induced pain occurs only if capsaicin is administered into the BoNT/A pretreated area; (iii) reduction in neurogenic vasodilatation by BoNT/A does not contribute to its analgesic action. BoNT/A could be tested for the treatment of conditions characterised by neurogenic inflammation and inflammatory pain.

  9. A molecular analysis of neurogenic placode and cranial sensory ganglion development in the shark, Scyliorhinus canicula.

    PubMed

    O'Neill, P; McCole, R B; Baker, C V H

    2007-04-01

    In order to gain insight into the evolution of the genetic control of the development of cranial neurogenic placodes and cranial sensory ganglia in vertebrates, we cloned and analysed the spatiotemporal expression pattern of six transcription factor genes in a chondrichthyan, the shark Scyliorhinus canicula (lesser-spotted dogfish/catshark). As in other vertebrates, NeuroD is expressed in all cranial sensory ganglia. We show that Pax3 is expressed in the profundal placode and ganglion, strongly supporting homology between the separate profundal ganglion of elasmobranchs and basal actinopterygians and the ophthalmic trigeminal placode-derived neurons of the fused amniote trigeminal ganglion. We show that Pax2 is a conserved pan-gnathostome marker for epibranchial and otic placodes, and confirm that Phox2b is a conserved pan-gnathostome marker for epibranchial placode-derived neurons. We identify Eya4 as a novel marker for the lateral line system throughout its development, expressed in lateral line placodes, sensory ridges and migrating primordia, neuromasts and electroreceptors. We also identify Tbx3 as a specific marker for lateral line ganglia in shark embryos. We use the spatiotemporal expression pattern of these genes to characterise the development of neurogenic placodes and cranial sensory ganglia in the dogfish, with a focus on the epibranchial and lateral line placodes. Our findings demonstrate the evolutionary conservation across all gnathostomes of at least some of the transcription factor networks underlying neurogenic placode development.

  10. Effect of sertraline on proliferation and neurogenic differentiation of human adipose-derived stem cells

    PubMed Central

    Razavi, Shahnaz; Jahromi, Maliheh; Amirpour, Nushin; Khosravizadeh, Zahra

    2014-01-01

    Background: Antidepressant drugs are commonly employed for anxiety and mood disorders. Sertraline is extensively used as antidepressant in clinic. In addition, adipose tissue represents an abundant and accessible source of adult stem cells with the ability to differentiate in to multiple lineages. Therefore, human adipose-derived stem cells (hADSCs) may be useful for autologous transplantation. Materials and Methods: In the present study, we assessed the effect of antidepressant drug Sertraline on the proliferation and neurogenic differentiation of hADSCs using MTT assay and immunofluorescence technique respectively. Results: MTT assay analysis showed that 0.5 μM Sertraline significantly increased the proliferation rate of hADSCs induced cells (P < 0.05), while immunofluorescent staining indicated that Sertraline treatment during neurogenic differentiation could be decreased the percentage of glial fibrillary acidic protein and Nestin-positive cells, but did not significantly effect on the percentage of MAP2 positive cells. Conclusion: Overall, our data show that Sertraline can be promoting proliferation rate during neurogenic differentiation of hADSCs after 6 days post-induction, while Sertraline inhibits gliogenesis of induced hADSCs. PMID:24800186

  11. Changes of neural markers expression during late neurogenic differentiation of human adipose-derived stem cells

    PubMed Central

    Razavi, Shahnaz; Khosravizadeh, Zahra; Bahramian, Hamid; Kazemi, Mohammad

    2015-01-01

    Background: Different studies have been done to obtain sufficient number of neural cells for treatment of neurodegenerative diseases, spinal cord, and traumatic brain injury because neural stem cells are limited in central nerves system. Recently, several studies have shown that adipose-derived stem cells (ADSCs) are the appropriate source of multipotent stem cells. Furthermore, these cells are found in large quantities. The aim of this study was an assessment of proliferation and potential of neurogenic differentiation of ADSCs with passing time. Materials and Methods: Neurosphere formation was used for neural induction in isolated human ADSCs (hADSCs). The rate of proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and potential of neural differentiation of induced hADSCs was evaluated by immunocytochemical and real-time reverse transcription polymerase chain reaction analysis after 10 and 14 days post-induction. Results: The rate of proliferation of induced hADSCs increased after 14 days while the expression of nestin, glial fibrillary acidic protein, and microtubule-associated protein 2 was decreased with passing time during neurogenic differentiation. Conclusion: These findings showed that the proliferation of induced cells increased with passing time, but in early neurogenic differentiation of hADSCs, neural expression was higher than late of differentiation. Thus, using of induced cells in early differentiation may be suggested for in vivo application. PMID:26605238

  12. Development of mechanisms associated with neurogenic-mediated skin inflammation during the growth of rats.

    PubMed

    Ohshima, Mihoko; Miyake, Mio; Takeda, Masanori; Muto, Taichiro; Ueda, Norishi; Ito, Komei; Sakamoto, Tatsuo

    2010-04-01

    Neurogenic-mediated inflammation may be associated with several inflammatory skin diseases including atopic dermatitis. However, age-dependent differences in neurogenic-mediated skin responses are not fully understood. We compared skin plasma leakage in rats aged 2 and 8 wk, which was induced by topical capsaicin, topical formalin, and intracutaneous substance P, whose effects are mediated via tachykinin NK1 receptors. Evans blue dye extravasation served as an index of the increase in skin vascular permeability. Capsaicin, formalin, and substance P caused a skin response in a dose-dependent manner in both age groups. However, the skin response was much greater in adults than in pups. In addition, the localization of sensory C-fibers and tachykinin NK1 receptors in the skin was investigated by immunofluorescent staining with antisubstance P and antitachykinin NK1 receptor antibodies, respectively. Substance P-immunoreactive nerves were detected throughout the dermis and tachykinin NK1 receptors were mainly detected in blood vessel walls in the dermis in both age groups. However, they were more sparsely distributed in pups. In conclusion, the weak neurogenic-mediated skin inflammation in pups is probably because of immature neural mechanisms associated with skin inflammation such as reduced innervation of sensory C-fibers and low expression of tachykinin NK1 receptors.

  13. Neurogenic and myogenic motor patterns of rabbit proximal, mid, and distal colon.

    PubMed

    Dinning, P G; Costa, M; Brookes, S J; Spencer, N J

    2012-07-01

    The rabbit colon consists of four distinct regions. The motility of each region is controlled by myogenic and neurogenic mechanisms. Associating these mechanisms with specific motor patterns throughout all regions of the colon has not previously been achieved. Three sections of the colon (the proximal, mid, and distal colon) were removed from euthanized rabbits. The proximal colon consists of a triply teniated region and a single tenia region. Spatio-temporal maps were constructed from video recordings of colonic wall diameter, with associated intraluminal pressure recorded from the aboral end. Hexamethonium (100 μM) and tetrodotoxin (TTX; 0.6 μM) were used to inhibit neural activity. Four distinct patterns of motility were detected: 1 myogenic and 3 neurogenic. The myogenic activity consisted of circular muscle (CM) contractions (ripples) that occurred throughout the colon and propagated in both antegrade (anal) and retrograde (oral) directions. The neural activity of the proximal colon consisted of slowly (0.1 mm/s) propagating colonic migrating motor complexes, which were abolished by hexamethonium. These complexes were observed in the region of the proximal colon with a single band of tenia. In the distal colon, tetrodotoxin-sensitive, thus neurally mediated, but hexamethonium-resistant, peristaltic (anal) and antiperistaltic (oral) contractions were identified. The distinct patterns of neurogenic and myogenic motor activity recorded from isolated rabbit colon are specific to each anatomically distinct region. The regional specificity motor pattern is likely to facilitate orderly transit of colonic content from semi-liquid to solid composition of feces.

  14. Neurogenic pruritus: an unrecognised problem? A retrospective case series of treatment by acupuncture.

    PubMed

    Stellon, Anthony

    2002-12-01

    Intractable localised segmental pruritus without a rash has been reported over the years under various titles depending on the area of the body affected. Notalgia paresthetica and brachioradial pruritus are the two terms used for what is believed to be a form of neuropathy. The clinical observations reported here suggest that other localised cases of pruritus exist that share common clinical features, and the term neurogenic pruritus is suggested to encompass these under one clinical condition. Acupuncture has been used to treat skin conditions, of which pruritus is one symptom. This retrospective study looked at the symptomatic relief of neurogenic pruritus in 16 patients using acupuncture. In 12 cases the affected dermatomes of the body were innervated by cervical spinal nerves, seven innervated by dorsal spinal nerves and four innervated by the lumbar spinal nerves. Seven patients had areas affected by two different regions of the spine. Restricted neck or back movements were noted in patients as were areas of paravertebral spasm or tenderness of the muscles. Total resolution of symptoms as judged by VAS occurred in 75% of patients. Relapse occurred in 37% of patients within 1-12 months following treatment. Acupuncture appeared to be effective in alleviating the distressing symptom of itching in patients presenting with neurogenic pruritus.

  15. Diabetes - tests and checkups

    MedlinePlus

    ... High blood pressure Microalbuminuria test Type 1 diabetes Type 2 diabetes Patient Instructions ACE inhibitors Diabetes and exercise Diabetes - eye care Diabetes - foot ulcers Diabetes - keeping ...

  16. Inflammatory Myofibroblastic Tumor Presenting with Diabetes Insipidus in an Eight-Year-Old Boy: A Case Report

    PubMed Central

    Sarı, Erkan; Ataş, Erman; Bulut, Engin Burak; Sarı, Sebahattin; Akın, Onur; Saldır, Mehmet; Karslıoğlu, Yıldırım; Yeşilkaya, Ediz

    2015-01-01

    Inflammatory myofibroblastic tumors (IMT) develop as a non-neoplastic proliferation of myofibroblasts in a myxoid to collagenous stroma admixed with inflammatory cells. The symptoms depend on the specific location of the tumor, which can be anywhere, but is particularly in the respiratory system. Thus, patients with IMT can present with a variety of findings. A pediatric patient with IMT who presented with cough, breathlessness, polyuria-polydipsia, and convulsions is described in this report. PMID:26777048

  17. Proteomic analysis of lithium-induced nephrogenic diabetes insipidus: Mechanisms for aquaporin 2 down-regulation and cellular proliferation

    PubMed Central

    Nielsen, Jakob; Hoffert, Jason D.; Knepper, Mark A.; Agre, Peter; Nielsen, Søren; Fenton, Robert A.

    2008-01-01

    Lithium is a commonly prescribed mood-stabilizing drug. However, chronic treatment with lithium induces numerous kidney-related side effects, such as dramatically reduced aquaporin 2 (AQP2) abundance, altered renal function, and structural changes. As a model system, inner medullary collecting ducts (IMCD) isolated from rats treated with lithium for either 1 or 2 weeks were subjected to differential 2D gel electrophoresis combined with mass spectrometry and bioinformatics analysis to identify (i) signaling pathways affected by lithium and (ii) unique candidate proteins for AQP2 regulation. After 1 or 2 weeks of lithium treatment, we identified 6 and 74 proteins with altered abundance compared with controls, respectively. We randomly selected 17 proteins with altered abundance caused by lithium treatment for validation by immunoblotting. Bioinformatics analysis of the data indicated that proteins involved in cell death, apoptosis, cell proliferation, and morphology are highly affected by lithium. We demonstrate that members of several signaling pathways are activated by lithium treatment, including the PKB/Akt-kinase and the mitogen-activated protein kinases (MAPK), such as extracellular regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38. Lithium treatment increased the intracellular accumulation of β-catenin in association with increased levels of phosphorylated glycogen synthase kinase type 3β (GSK3β). This study provides a comprehensive analysis of the proteins affected by lithium treatment in the IMCD and, as such, provides clues to potential lithium targets in the brain. PMID:18296634

  18. Acute fatty liver of pregnancy with hypoglycaemia, diabetes insipidus and pancreatitis, preceded by intrahepatic cholestasis of pregnancy.

    PubMed

    English, Nicola; Rao, Jegajeeva

    2015-04-15

    We present the case of a 33-year-old woman in her first pregnancy. She presented with pruritus at 34 weeks gestation. A diagnosis of intrahepatic cholestasis of pregnancy was made based on elevated bile acids and elevated liver transaminases. She re-presented 4 days later, jaundiced with abdominal pain and nausea, and was hypertensive. Her bilirubin was now elevated and her creatinine had doubled. The differential diagnosis-included pre-eclampsia and Hemolysis Elevated Liver enzymes Low Platelet count (HELLP) syndrome, and delivery was expedited. Postnatally, the patient became coagulopathic, though not thrombocytopaenic; she had persistent hypoglycaemia, hyponatraemia, developed acute pancreatitis and had profound ascites and peripheral oedema. Management was supportive with multidisciplinary care and over a period of 3 weeks she made a full clinical and biochemical recovery.

  19. Evaluation of cellular plasticity in the collecting duct during recovery from lithium-induced nephrogenic diabetes insipidus.

    PubMed

    Trepiccione, Francesco; Capasso, Giovambattista; Nielsen, Søren; Christensen, Birgitte Mønster

    2013-09-15

    The cellular morphology of the collecting duct is altered by chronic lithium treatment. We have previously shown that lithium increases the fraction of type-A intercalated cells and lowers the fraction of principal cells along the collecting duct. Moreover, type-A intercalated cells acquire a long-row distribution pattern along the tubules. In the present study, we show that these morphological changes reverse progressively after discontinuation of lithium and finally disappear after 19 days from lithium suspension. In this time frame we have identified for the first time, in vivo, a novel cellular type positive for both intercalated and principal cells functional markers, as recognized by colabeling with H(+)-ATPase/aquaporin-4 (AQP4) and anion exchanger-1 (AE-1)/AQP2 and Foxi1/AQP4. This cell type is mainly present after 6 days of lithium washout, and it disappears in parallel with the long-row pattern of the type-A intercalated cells. It usually localizes either in the middle or at the edge of the long-row pattern. Its ultrastructure resembles the intercalated cells as shown both by differential interference contrast and by electron microscopy. The time course of appearance, the localization along the collecting duct, and the ultrastructure suggest that the cells double labeled for principal and intercalated cells markers could represent a transition element driving the conversion of intercalated cells into principal cells.

  20. [Influence of preventive use of vasopressin tannate on diabetes insipidus and serum sodium at the early postoperation of craniopharyngioma].

    PubMed

    Xiong, Tao; Wanggou, Siyi; Li, Xuejun; Liu, Qing; Jiang, Xingjun; Peng, Zefeng; Yuan, Xianrui

    2016-10-28

    目的:分析探讨预防性使用长效尿崩停(鞣酸加压素针)对颅咽管瘤开颅术后早期尿崩及血钠的影响。
方法:回顾性分析2010至2014年行单侧额下开颅显微手术治疗的83例颅咽管瘤患者,分为预防性使用长效尿崩停组(使用组)和未使用组,对使用组及未使用组的术后早期尿崩情况及血钠变化趋势进行对比分析。结果:与未使用组比较,使用组整体术后早期尿崩的发生率少(P<0.05);垂体柄切除及肿瘤与三脑室底粘连紧密的患者术后尿崩发生率高(P<0.05),但在这两种情况中,使用组较未使用组术后早期尿崩的发生率少(P<0.05)。术后高钠者为37例(44.6%),术后出现低钠者共60例(72.3%),高钠、低钠出现的平均时间为术后1.4和3.7 d。术后高钠、低钠交替出现的有19例(22.9%)。使用组与未使用组在术后第1天血钠分布上差异有统计学意义(P<0.05),使用组术后第1天高钠出现百分比低于未使用组,差异有统计学意义(P<0.05)。结论:术中或术后早期预防性使用长效尿崩停可以有效减少颅咽管瘤患者术后早期尿崩及高钠血症的发生率。.

  1. Inflammatory Myofibroblastic Tumor Presenting with Diabetes Insipidus in an Eight-Year-Old Boy: A Case Report.

    PubMed

    Sarı, Erkan; Ataş, Erman; Bulut, Engin Burak; Sarı, Sebahattin; Akın, Onur; Saldır, Mehmet; Karslıoğlu, Yıldırım; Yeşilkaya, Ediz

    2015-12-01

    Inflammatory myofibroblastic tumors (IMT) develop as a non-neoplastic proliferation of myofibroblasts in a myxoid to collagenous stroma admixed with inflammatory cells. The symptoms depend on the specific location of the tumor, which can be anywhere, but is particularly in the respiratory system. Thus, patients with IMT can present with a variety of findings. A pediatric patient with IMT who presented with cough, breathlessness, polyuria-polydipsia, and convulsions is described in this report.

  2. A case of diabetic amyotrophy with severe atrophy and weakness of shoulder girdle muscles showing good response to intravenous immune globulin.

    PubMed

    Wada, Yuko; Yanagihara, Chie; Nishimura, Yo; Oka, Nobuyuki

    2007-01-01

    A 45-year-old man with insulin-dependent diabetic mellitus developed progressive asymmetrical weakness and atrophy of both shoulder girdle muscles within 1 year. In the last month, he also developed slight weakness of both thighs. Neuropathology of the sural nerve showed an axonal degeneration and perivascular inflammation and electromyography revealed neurogenic changes. Because of a diagnosis of suspected diabetic amyotrophy, intravenous immunoglobulin was administered. This treatment produced marked improvement. Physicians should take into account the possibility of diabetic amyotrophy in patients with diabetic mellitus showing primary involvement of shoulder girdle muscles marked by weakness and atrophy.

  3. Diabetic Nephropathy without Diabetes

    PubMed Central

    López-Revuelta, Katia; Méndez Abreu, Angel A.; Gerrero-Márquez, Carmen; Stanescu, Ramona-Ionela; Martínez Marín, Maria Isabel; Pérez Fernández, Elia

    2015-01-01

    Diabetic nephropathy without diabetes (DNND), previously known as idiopathic nodular glomerulosclerosis, is an uncommon entity and thus rarely suspected; diagnosis is histological once diabetes is discarded. In this study we describe two new cases of DNND and review the literature. We analyzed all the individualized data of previous publications except one series of attached data. DNND appears to be favored by recognized cardiovascular risk factors. However, in contrast with diabetes, apparently no factor alone has been demonstrated to be sufficient to develop DNND. Other factors not considered as genetic and environmental factors could play a role or interact. The most plausible hypothesis for the occurrence of DNND would be a special form of atherosclerotic or metabolic glomerulopathy than can occur with or without diabetes. The clinical spectrum of cardiovascular risk factors and histological findings support this theory, with hypertension as one of the characteristic clinical features. PMID:26239683

  4. A crucial role for the cortico-striato-cortical loop in the pathogenesis of stroke-related neurogenic stuttering.

    PubMed

    Theys, Catherine; De Nil, Luc; Thijs, Vincent; van Wieringen, Astrid; Sunaert, Stefan

    2013-09-01

    Neurogenic stuttering is an acquired speech disorder characterized by the occurrence of stuttering-like dysfluencies following brain damage. Because the onset of stuttering in these patients is associated with brain lesions, this condition provides a unique opportunity to study the neural processes underlying speech dysfluencies. Lesion localizations of 20 stroke subjects with neurogenic stuttering and 17 control subjects were compared using voxel-based lesion symptom mapping. The results showed nine left-hemisphere areas associated with the presence of neurogenic stuttering. These areas were largely overlapping with the cortico-basal ganglia-cortical network comprising the inferior frontal cortex, superior temporal cortex, intraparietal cortex, basal ganglia, and their white matter interconnections through the superior longitudinal fasciculus and internal capsule. These results indicated that stroke-induced neurogenic stuttering is not associated with neural dysfunction in one specific brain area but can occur following one or more lesion throughout the cortico-basal ganglia-cortical network. It is suggested that the onset of neurogenic stuttering in stroke subjects results from a disintegration of neural functions necessary for fluent speech.

  5. Diabetic Neuropathy

    MedlinePlus

    ... of diabetic neuropathy may become severe enough to cause depression in some patients. × Prognosis The prognosis for diabetic ... of diabetic neuropathy may become severe enough to cause depression in some patients. View Full Prognosis Clinical Trials ...

  6. Diabetes Medicines

    MedlinePlus

    Diabetes means your blood glucose, or blood sugar, levels are too high. If you can't control your diabetes with wise food choices and physical activity, you may need diabetes medicines. The kind of medicine you take depends ...

  7. Organization and cellular arrangement of two neurogenic regions in the adult ferret (Mustela putorius furo) brain.

    PubMed

    Takamori, Yasuharu; Wakabayashi, Taketoshi; Mori, Tetsuji; Kosaka, Jun; Yamada, Hisao

    2014-06-01

    In the adult mammalian brain, two neurogenic regions have been characterized, the subventricular zone (SVZ) of the lateral ventricle (LV) and the subgranular zone (SGZ) of the dentate gyrus (DG). Despite remarkable knowledge of rodents, the detailed arrangement of neurogenic regions in most mammals is poorly understood. In this study, we used immunohistochemistry and cell type-specific antibodies to investigate the organization of two germinal regions in the adult ferret, which belongs to the order Carnivora and is widely used as a model animal with a gyrencephalic brain. From the SVZ to the olfactory bulb, doublecortin-positive cells tended to organize in chain-like clusters, which are surrounded by a meshwork of astrocytes. This structure is homologous to the rostral migratory stream (RMS) described in other species. Different from rodents, the horizontal limb of the RMS emerges directly from the LV, and the anterior region of the LV extends rostrally and reached the olfactory bulb. In the DG, glial fibrillary acidic protein-positive cells with long radial processes as well as doublecortin-positive cells are oriented in the SGZ. In both regions, doublecortin-positive cells showed characteristic morphology and were positive for polysialylated-neural cell adhesion molecule, beta-III tubulin, and lamin B1 (intense staining). Proliferating cells were detected in both regions using antibodies against proliferating cell nuclear antigen and phospho-histone H3. These observations demonstrate that the two neurogenic regions in ferrets have a similar cellular composition as those of other mammalian species despite anatomical differences in the brain.

  8. A mathematical model of salt-sensitive hypertension: the neurogenic hypothesis.

    PubMed

    Averina, Viktoria A; Othmer, Hans G; Fink, Gregory D; Osborn, John W

    2015-07-15

    Salt sensitivity of arterial pressure (salt-sensitive hypertension) is a serious global health issue. The causes of salt-sensitive hypertension are extremely complex and mathematical models can elucidate potential mechanisms that are experimentally inaccessible. Until recently, the only mathematical model for long-term control of arterial pressure was the model of Guyton and Coleman; referred to as the G-C model. The core of this model is the assumption that sodium excretion is driven by renal perfusion pressure, the so-called 'renal function curve'. Thus, the G-C model dictates that all forms of hypertension are due to a primary shift of the renal function curve to a higher operating pressure. However, several recent experimental studies in a model of hypertension produced by the combination of a high salt intake and administration of angiotensin II, the AngII-salt model, are inconsistent with the G-C model. We developed a new mathematical model that does not limit the cause of salt-sensitive hypertension solely to primary renal dysfunction. The model is the first known mathematical counterexample to the assumption that all salt-sensitive forms of hypertension require a primary shift of renal function: we show that in at least one salt-sensitive form of hypertension the requirement is not necessary. We will refer to this computational model as the 'neurogenic model'. In this Symposium Review we discuss how, despite fundamental differences between the G-C model and the neurogenic model regarding mechanisms regulating sodium excretion and vascular resistance, they generate similar haemodynamic profiles of AngII-salt hypertension. In addition, the steady-state relationships between arterial pressure and sodium excretion, a correlation that is often erroneously presented as the 'renal function curve', are also similar in both models. Our findings suggest that salt-sensitive hypertension is not due solely to renal dysfunction, as predicted by the G-C model, but may

  9. Neurogenic bowel management after spinal cord injury: A systematic review of the evidence

    PubMed Central

    Krassioukov, Andrei; Eng, Janice J.; Claxton, Geri; Sakakibara, Brodie M.; Shum, Serena

    2011-01-01

    OBJECTIVE To systematically review evidence for the management of neurogenic bowel in individuals with spinal cord injuries (SCI). DATA SOURCES Literature searches were conducted for relevant articles, as well as practice guidelines, using numerous electronic databases. Manual searches of retrieved articles from 1950 to July 2009 were also conducted to identify literature. STUDY SELECTION Randomized controlled trials, prospective cohort, case-control, and pre-post studies, and case reports that assessed pharmacological and non-pharmacological intervention for the management of the neurogenic bowel in SCI were included. DATA EXTRACTION Two independent reviewers evaluated each study’s quality, using the PEDro scale for RCTs and the Downs & Black scale for all other studies. Results were tabulated and levels of evidence assigned. DATA SYNTHESIS 2956 studies were found as a result of the literature search. Upon review of the titles and abstracts, 52 studies met the inclusion criteria. Multi-faceted programs are the first approach to neurogenic bowel and are supported by lower levels of evidence. Of the non-pharmacological (conservative and non-surgical) interventions, transanal irrigation is a promising treatment to reduce constipation and fecal incontinence. When conservative management is not effective, pharmacological interventions (e.g., prokinetic agents) are supported by strong evidence for the treatment of chronic constipation. When conservative and pharmacological treatments are not effective, surgical interventions may be considered and are supported by lower levels of evidence in reducing complications. CONCLUSIONS Often, more than one procedure is necessary to develop an effective bowel routine. Evidence is low for non-pharmacological approaches and high for pharmacological interventions. PMID:20212501

  10. Quantifiable diagnosis of muscular dystrophies and neurogenic atrophies through network analysis

    PubMed Central

    2013-01-01

    Background The diagnosis of neuromuscular diseases is strongly based on the histological characterization of muscle biopsies. However, this morphological analysis is mostly a subjective process and difficult to quantify. We have tested if network science can provide a novel framework to extract useful information from muscle biopsies, developing a novel method that analyzes muscle samples in an objective, automated, fast and precise manner. Methods Our database consisted of 102 muscle biopsy images from 70 individuals (including controls, patients with neurogenic atrophies and patients with muscular dystrophies). We used this to develop a new method, Neuromuscular DIseases Computerized Image Analysis (NDICIA), that uses network science analysis to capture the defining signature of muscle biopsy images. NDICIA characterizes muscle tissues by representing each image as a network, with fibers serving as nodes and fiber contacts as links. Results After a ‘training’ phase with control and pathological biopsies, NDICIA was able to quantify the degree of pathology of each sample. We validated our method by comparing NDICIA quantification of the severity of muscular dystrophies with a pathologist’s evaluation of the degree of pathology, resulting in a strong correlation (R = 0.900, P <0.00001). Importantly, our approach can be used to quantify new images without the need for prior ‘training’. Therefore, we show that network science analysis captures the useful information contained in muscle biopsies, helping the diagnosis of muscular dystrophies and neurogenic atrophies. Conclusions Our novel network analysis approach will serve as a valuable tool for assessing the etiology of muscular dystrophies or neurogenic atrophies, and has the potential to quantify treatment outcomes in preclinical and clinical trials. PMID:23514382

  11. Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches

    PubMed Central

    Pérez-Martín, Margarita; Rivera, Patricia; Blanco, Eduardo; Lorefice, Clara; Decara, Juan; Pavón, Francisco J.; Serrano, Antonia; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2016-01-01

    Peroxisome proliferator-activated receptor alpha (PPARα) ligands have been shown to modulate recovery after brain insults such as ischemia and irradiation by enhancing neurogenesis. In the present study, we investigated the effect of the genetic deletion of PPARα receptors on the proliferative rate of neural precursor cells (NPC) in the adult brain. The study was performed in aged Pparα−/− mice exposed to nutritional (treats) and environmental (games) enrichments for 20 days. We performed immunohistochemical analyses of cells containing the replicating cell DNA marker 5-bromo-2′-deoxyuridine (BrdU+) and the immature neuronal marker doublecortin (Dcx+) in the main neurogenic zones of the adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ), and/or hypothalamus. Results indicated a reduction in the number of BrdU+ cells in the neurogenic zones analyzed as well as Dcx+ cells in the SGZ during aging (2, 6, and 18 months). Pparα deficiency alleviated the age-related reduction of NPC proliferation (BrdU+ cells) in the SVZ of the 18-months-old mice. While no genotype effect on NPC proliferation was detected in the SGZ during aging, an accentuated reduction in the number of Dcx+ cells was observed in the SGZ of the 6-months-old Pparα−/− mice. Exposing the 18-months-old mice to nutritional and environmental enrichments reversed the Pparα−/−-induced impairment of NPC proliferation in the neurogenic zones analyzed. The enriched environment did not modify the number of SGZ Dcx+ cells in the 18 months old Pparα−/− mice. These results identify PPARα receptors as a potential target to counteract the naturally observed decline in adult NPC proliferation associated with aging and impoverished environments. PMID:27013951

  12. Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches.

    PubMed

    Pérez-Martín, Margarita; Rivera, Patricia; Blanco, Eduardo; Lorefice, Clara; Decara, Juan; Pavón, Francisco J; Serrano, Antonia; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2016-01-01

    Peroxisome proliferator-activated receptor alpha (PPARα) ligands have been shown to modulate recovery after brain insults such as ischemia and irradiation by enhancing neurogenesis. In the present study, we investigated the effect of the genetic deletion of PPARα receptors on the proliferative rate of neural precursor cells (NPC) in the adult brain. The study was performed in aged Pparα(-/-) mice exposed to nutritional (treats) and environmental (games) enrichments for 20 days. We performed immunohistochemical analyses of cells containing the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) and the immature neuronal marker doublecortin (Dcx+) in the main neurogenic zones of the adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ), and/or hypothalamus. Results indicated a reduction in the number of BrdU+ cells in the neurogenic zones analyzed as well as Dcx+ cells in the SGZ during aging (2, 6, and 18 months). Pparα deficiency alleviated the age-related reduction of NPC proliferation (BrdU+ cells) in the SVZ of the 18-months-old mice. While no genotype effect on NPC proliferation was detected in the SGZ during aging, an accentuated reduction in the number of Dcx+ cells was observed in the SGZ of the 6-months-old Pparα(-/-) mice. Exposing the 18-months-old mice to nutritional and environmental enrichments reversed the Pparα(-/-)-induced impairment of NPC proliferation in the neurogenic zones analyzed. The enriched environment did not modify the number of SGZ Dcx+ cells in the 18 months old Pparα(-/-) mice. These results identify PPARα receptors as a potential target to counteract the naturally observed decline in adult NPC proliferation associated with aging and impoverished environments.

  13. Brain-targeted ACE2 overexpression attenuates neurogenic hypertension by inhibiting COX mediated inflammation

    PubMed Central

    Sriramula, Srinivas; Xia, Huijing; Xu, Ping; Lazartigues, Eric

    2014-01-01

    Overactivity of the renin angiotensin system (RAS), oxidative stress, and cyclooxygenases (COX) in the brain are implicated in the pathogenesis of hypertension. We previously reported that Angiotensin-Converting Enzyme 2 (ACE2) overexpression in the brain attenuates the development of DOCA-salt hypertension, a neurogenic hypertension model with enhanced brain RAS and sympathetic activity. To elucidate the mechanisms involved, we investigated whether oxidative stress, mitogen activated protein kinase signaling and cyclooxygenase (COX) activation in the brain are modulated by ACE2 in neurogenic hypertension. DOCA-salt hypertension significantly increased expression of Nox-2 (+61 ±5 %), Nox-4 (+50 ±13 %) and nitrotyrosine (+89 ±32 %) and reduced activity of the antioxidant enzymes, catalase (−29 ±4 %) and SOD (−31 ±7 %), indicating increased oxidative stress in the brain of non-transgenic mice. This increased oxidative stress was attenuated in transgenic mice overexpressing ACE2 in the brain. DOCA-salt-induced reduction of nNOS expression (−26 ±7 %) and phosphorylated eNOS/total eNOS (−30 ±3 %), and enhanced phosphorylation of Akt and ERK1/2 in the paraventricular nucleus (PVN), were reversed by ACE2 overexpression. In addition, ACE2 overexpression blunted the hypertension-mediated increase in gene and protein expression of COX-1 and COX-2 in the PVN. Furthermore, gene silencing of either COX-1 or COX-2 in the brain, reduced microglial activation and accompanied neuro-inflammation, ultimately attenuating DOCA-salt hypertension. Together, these data provide evidence that brain ACE2 overexpression reduces oxidative stress and COX-mediated neuro-inflammation, improves anti-oxidant and nitric oxide signaling, and thereby attenuates the development of neurogenic hypertension. PMID:25489058

  14. Neurogenic claudication and root claudication treated with calcitonin. A double-blind trial.

    PubMed

    Porter, R W; Miller, C G

    1988-09-01

    Forty-two patients with either neurogenic claudication or unilateral root claudication were analyzed in a double-blind comparison of salmon calcitonin (SCT) and placebo, receiving either 100 IU SCT or 1 ml saline four times a week for 8 weeks. Five of 20 SCT and one of 22 placebo patients were classified as responders. There was no statistically significant difference between the treatment groups in the proportion of responders. Seven of eighteen of the placebo group who later received salmon calcitonin improved their walking distance. The authors have not established that this is an organic response.

  15. Transient Receptor Potential Ankyrin 1 (TRPA1) Channel and Neurogenic Inflammation in Pathogenesis of Asthma

    PubMed Central

    Yang, Hang; Li, ShuZhuang

    2016-01-01

    Asthma is characterized by airway inflammation, airway obstruction, and airway hyperresponsiveness (AHR), and it affects 300 million people worldwide. However, our current understanding of the molecular mechanisms that underlie asthma remains limited. Recent studies have suggested that transient receptor potential ankyrin 1 (TRPA1), one of the transient receptor potential cation channels, may be involved in airway inflammation in asthma. The present review discusses the relationship between TRPA1 and neurogenic inflammation in asthma, hoping to enhance our understanding of the mechanisms of airway inflammation in asthma. PMID:27539812

  16. How botulinum toxin in neurogenic detrusor overactivity can reduce upper urinary tract damage?

    PubMed Central

    Baron, Maximilien; Grise, Philippe; Cornu, Jean-Nicolas

    2016-01-01

    Intradetrusor injections of botulinum toxin are the cornerstone of medical treatment of neurogenic detrusor overactivity. The primary aim of this treatment is to ensure a low pressure regimen in the urinary bladder, but the mechanisms leading to long-term protection of the urinary tract remain poorly understood. In this paper, we highlight the potential benefits of intradetrusor injections of botulinum toxin regarding local effects on the bladder structures, urinary tract infections, stone disease, vesico ureteral reflux, hydronephrosis, renal function based on a comprehensive literature review. PMID:26981445

  17. Back Pain, Neurogenic Symptoms, and Physical Function in Relation to Spondylolisthesis among Elderly Men

    PubMed Central

    Denard, Patrick J.; Holton, Kathleen F.; Miller, Jessica; Fink, Howard A.; Kado, Deborah M.; Marshall, Lynn M.; Yoo, Jung U.

    2010-01-01

    Background Context Degenerative spondylolisthesis is a presumed cause of back pain. Previous studies of spondylolisthesis and back pain included only women or combined results for men and women. Comparisons of the frequency of back pain, neurogenic symptoms, and functional limitations specifically among elderly men with and without spondylolisthesis are needed. Purpose To determine associations of prevalent spondylolisthesis with back pain symptoms, neurogenic symptoms, and functional limitations among elderly men. Study Design/ Setting: Cross-sectional epidemiologic study conducted within the Osteoporotic Fractures in Men (MrOS) cohort. The MrOS cohort is comprised of 5,995 community dwelling men ages ≥65 years who were recruited at 6 US academic medical centers. Extensive self-reported data and lumbar spine radiographs were obtained for all MrOS participants at baseline. Patient Sample For this study, 300 men were selected at random specifically for the evaluation of spondylolisthesis on the baseline spine radiographs. Outcome Measures Standardized questionnaires were used to assess self-reported back pain, leg pain (radiculopathy), lower extremity numbness (paresthesias) and lower extremity weakness occurring in the past 12 months, and to ascertain current difficulty with activities of daily living. Methods In the present study, radiographic spondylolisthesis was classified as forward slip of ≥5%. Prevalence of back pain, neurogenic symptoms and difficulty with activities of daily living were compared between men with and without spondylolisthesis using chisquare or Fisher’s exact tests. Results Spondylolisthesis was present among 92 (31%) men. Among men with and without spondylolisthesis, back pain (63% vs. 67%, p=0.46) and moderate/severe back pain (41% vs. 38%, p=0.76) were reported with similar frequency. Men with spondylolisthesis more often reported radiculopathy (33% vs. 22%, p=0.06), paresthesias (18% vs. 11%, p= 0.10) and weakness (18% vs. 9%, p=0

  18. H3 receptor-mediated inhibition of the neurogenic vasopressor response in pithed rats.

    PubMed

    Malinowska, B; Schlicker, E

    1991-12-03

    In pithed rats, the H3 agonist R-(-)-alpha-methylhistamine (R alpha MeHA) inhibited the electrically induced increase in blood pressure without affecting the vasopressor response to exogenous noradrenaline. The effect of R alpha MeHA was not affected by the H1 and H2 antagonists dimetindene and ranitidine, but attenuated by the H3 antagonist thioperamide. At higher doses, R alpha MeHA itself increased basal blood pressure; this effect was not affected by the H1, H2 and H3 antagonists. In conclusion, the neurogenic vasopressor response can be modulated via H3 receptors, probably located presynaptically on postganglionic sympathetic nerve fibres.

  19. [Neurogenic oropharyngeal dysphagia is a frequent condition in patients admitted to the ICU].

    PubMed

    Pedersen, Anette Barbre; Kjærsgaard, Annette; Larsen, Jens Kjærgaard Rolighed; Nielsen, Lars Hedemann

    2015-03-02

    Neurogenic oropharyngeal dysphagia (NOD) is a frequent condition in neurological patients admitted to the ICU, particularly in patients with brainstem lesions. The CNS damage itself can predispose to dysphagia, but also the treatment and preventive measures may predispose to and exacerbate the condition. Frequent pneumonia in a neurological patient is a warning signal that should cause screening for dysphagia. Complications are serious and can be fatal. Neurological patients should be examined for NOD before decannulation. Treatment is difficult, so prevention and multidisciplinary neurological rehabilitation is important.

  20. Congenital causes of neurogenic bladder and the transition to adult care

    PubMed Central

    Loftus, Christopher J.

    2016-01-01

    The population of patients with congenital genitourinary disorders has unique healthcare demands that require an additional interpersonal and medical skillset. Adults with congenital neurogenic bladder may have complex urinary anatomy, abnormal bladder function and atypical voiding mechanisms. While initial surgery and care of these patients is typically managed by a pediatric urologist, growth and development into adulthood necessitates transition of care to an adult care team. Failure of transition to adult care has been demonstrated to result in lower quality healthcare and increased risk of developing preventable complications. PMID:26904411

  1. The vascular and neurogenic factors associated with erectile dysfunction in patients after pelvic fractures

    PubMed Central

    Guan, Yong; Wendong, Sun; Zhao, Shengtian; Liu, Tongyan; Liu, Yuqiang; Zhang, Xiulin; Yuan, Mingzhen

    2015-01-01

    ABSTRACT Erectile dysfunction (ED) is a common complication of pelvic fractures. To identify the vascular and neurogenic factors associated with ED, 120 patients admitted with ED after traumatic pelvic fracture between January 2009 and June 2013 were enrolled in this study. All patients answered the International Index of Erectile Function (IIEF-5) questionnaire. Nocturnal penile tumescence (NPT) testing confirmed the occurrence of ED in 96 (80%) patients on whom penile duplex ultrasound and neurophysiological testing were further performed. Of these ED patients 29 (30%) were demonstrated only with vascular abnormality, 41 (42.7%) were detected only with neural abnormality, 26 (27.1%) revealed mixed abnormalities. Of the 55 patients (29+26) with vascular problems, 7 patients (12.7%) with abnormal arterial response to intracavernous injection of Bimix (15mg papaverine and 1mg phentolamine), 31 (56.4%) with corporal veno-occlusive dysfunction and 17 (30.9%) had both problems. Of the 67 (41+26) patients with abnormal neurophysiological outcomes, 51 (76.1%) with abnormal bulbocavernosus reflex (BCR), 20 (29.9%) with pathological pudendal nerve evoked potentials (PDEPs) and 25 (37.3%) with abnormal posterior tibial somatosensory nerve evoked potentials (PTSSEPs). Our observation indicated that neurogenic factors are important for the generation of ED in patients with pelvic fracture; venous impotence is more common than arteriogenic ED. PMID:26689522

  2. Lithium Accumulates in Neurogenic Brain Regions as Revealed by High Resolution Ion Imaging

    PubMed Central

    Zanni, Giulia; Michno, Wojciech; Di Martino, Elena; Tjärnlund-Wolf, Anna; Pettersson, Jean; Mason, Charlotte Elizabeth; Hellspong, Gustaf; Blomgren, Klas; Hanrieder, Jörg

    2017-01-01

    Lithium (Li) is a potent mood stabilizer and displays neuroprotective and neurogenic properties. Despite extensive investigations, the mechanisms of action have not been fully elucidated, especially in the juvenile, developing brain. Here we characterized lithium distribution in the juvenile mouse brain during 28 days of continuous treatment that result in clinically relevant serum concentrations. By using Time-of-Flight Secondary Ion Mass Spectrometry- (ToF-SIMS) based imaging we were able to delineate temporospatial lithium profile throughout the brain and concurrent distribution of endogenous lipids with high chemical specificity and spatial resolution. We found that Li accumulated in neurogenic regions and investigated the effects on hippocampal neurogenesis. Lithium increased proliferation, as judged by Ki67-immunoreactivity, but did not alter the number of doublecortin-positive neuroblasts at the end of the treatment period. Moreover, ToF-SIMS revealed a steady depletion of sphingomyelin in white matter regions during 28d Li-treatment, particularly in the olfactory bulb. In contrast, cortical levels of cholesterol and choline increased over time in Li-treated mice. This is the first study describing ToF-SIMS imaging for probing the brain-wide accumulation of supplemented Li in situ. The findings demonstrate that this technique is a powerful approach for investigating the distribution and effects of neuroprotective agents in the brain. PMID:28098178

  3. Lithium Accumulates in Neurogenic Brain Regions as Revealed by High Resolution Ion Imaging.

    PubMed

    Zanni, Giulia; Michno, Wojciech; Di Martino, Elena; Tjärnlund-Wolf, Anna; Pettersson, Jean; Mason, Charlotte Elizabeth; Hellspong, Gustaf; Blomgren, Klas; Hanrieder, Jörg

    2017-01-18

    Lithium (Li) is a potent mood stabilizer and displays neuroprotective and neurogenic properties. Despite extensive investigations, the mechanisms of action have not been fully elucidated, especially in the juvenile, developing brain. Here we characterized lithium distribution in the juvenile mouse brain during 28 days of continuous treatment that result in clinically relevant serum concentrations. By using Time-of-Flight Secondary Ion Mass Spectrometry- (ToF-SIMS) based imaging we were able to delineate temporospatial lithium profile throughout the brain and concurrent distribution of endogenous lipids with high chemical specificity and spatial resolution. We found that Li accumulated in neurogenic regions and investigated the effects on hippocampal neurogenesis. Lithium increased proliferation, as judged by Ki67-immunoreactivity, but did not alter the number of doublecortin-positive neuroblasts at the end of the treatment period. Moreover, ToF-SIMS revealed a steady depletion of sphingomyelin in white matter regions during 28d Li-treatment, particularly in the olfactory bulb. In contrast, cortical levels of cholesterol and choline increased over time in Li-treated mice. This is the first study describing ToF-SIMS imaging for probing the brain-wide accumulation of supplemented Li in situ. The findings demonstrate that this technique is a powerful approach for investigating the distribution and effects of neuroprotective agents in the brain.

  4. Recent Advances in Neurogenic Small Molecules as Innovative Treatments for Neurodegenerative Diseases.

    PubMed

    Herrera-Arozamena, Clara; Martí-Marí, Olaia; Estrada, Martín; de la Fuente Revenga, Mario; Rodríguez-Franco, María Isabel

    2016-09-01

    The central nervous system of adult mammals has long been considered as a complex static structure unable to undergo any regenerative process to refurbish its dead nodes. This dogma was challenged by Altman in the 1960s and neuron self-renewal has been demonstrated ever since in many species, including humans. Aging, neurodegenerative, and some mental diseases are associated with an exponential decrease in brain neurogenesis. Therefore, the controlled pharmacological stimulation of the endogenous neural stem cells (NSCs) niches might counteract the neuronal loss in Alzheimer's disease (AD) and other pathologies, opening an exciting new therapeutic avenue. In the last years, druggable molecular targets and signalling pathways involved in neurogenic processes have been identified, and as a consequence, different drug types have been developed and tested in neuronal plasticity. This review focuses on recent advances in neurogenic agents acting at serotonin and/or melatonin systems, Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase (NAMPT) and nuclear erythroid 2-related factor (Nrf2).

  5. ASCL1 reprograms mouse Müller glia into neurogenic retinal progenitors

    PubMed Central

    Pollak, Julia; Wilken, Matthew S.; Ueki, Yumi; Cox, Kristen E.; Sullivan, Jane M.; Taylor, Russell J.; Levine, Edward M.; Reh, Thomas A.

    2013-01-01

    Non-mammalian vertebrates have a robust ability to regenerate injured retinal neurons from Müller glia (MG) that activate the gene encoding the proneural factor Achaete-scute homolog 1 (Ascl1; also known as Mash1 in mammals) and de-differentiate into progenitor cells. By contrast, mammalian MG have a limited regenerative response and fail to upregulate Ascl1 after injury. To test whether ASCL1 could restore neurogenic potential to mammalian MG, we overexpressed ASCL1 in dissociated mouse MG cultures and intact retinal explants. ASCL1-infected MG upregulated retinal progenitor-specific genes and downregulated glial genes. Furthermore, ASCL1 remodeled the chromatin at its targets from a repressive to an active configuration. MG-derived progenitors differentiated into cells that exhibited neuronal morphologies, expressed retinal subtype-specific neuronal markers and displayed neuron-like physiological responses. These results indicate that a single transcription factor, ASCL1, can induce a neurogenic state in mature MG. PMID:23637330

  6. A case of small round cell tumor of the thoracopulmonary region with myogenic and neurogenic elements.

    PubMed

    Goji, J; Sano, K; Murakami, R; Nakamura, H; Ninomiya, M; Ito, H

    1992-02-01

    We here report a unique case of a young boy with an intrathoracic tumor which consisted of neurogenic and myogenic elements. The initial pathological diagnosis was alveolar rhabdomyosarcoma. The tumor tissue from surgical resection was composed of three parts, each showing a different histological appearance, i.e. a monotonous small cell area, an alveolar area, and an area consisting of pleomorphic rhabdomyoblasts. The small round cells in the monotonous area were immunoreactive with the antibodies for Leu7, neuron-specific enolase (NSE), neurofilament proteins (NFP), and beta 2 microglobulin, but not with the antibody for desmin. These cells also had dense core granules. The tumor cells in the alveolar area were immunoreactive with the antibodies for Leu7 and desmin, but not with the antibody for NFP. Pleomorphic rhabdomyoblasts were immunoreactive with the antibody for desmin, but not with the antibodies for Leu7 and NFP. These findings imply that this tumor consisted of neurogenic and myogenic elements and is considered to be a special type of rhabdomyosarcoma.

  7. Are neural crest stem cells the missing link between hematopoietic and neurogenic niches?

    PubMed Central

    Coste, Cécile; Neirinckx, Virginie; Gothot, André; Wislet, Sabine; Rogister, Bernard

    2015-01-01

    Hematopoietic niches are defined as cellular and molecular microenvironments that regulate hematopoietic stem cell (HSC) function together with stem cell autonomous mechanisms. Many different cell types have been characterized as contributors to the formation of HSC niches, such as osteoblasts, endothelial cells, Schwann cells, and mesenchymal progenitors. These mesenchymal progenitors have themselves been classified as CXC chemokine ligand (CXCL) 12-abundant reticular (CAR) cells, stem cell factor expressing cells, or nestin-positive mesenchymal stem cells (MSCs), which have been recently identified as neural crest-derived cells (NCSCs). Together, these cells are spatially associated with HSCs and believed to provide appropriate microenvironments for HSC self-renewal, differentiation, mobilization and hibernation both by cell-cell contact and soluble factors. Interestingly, it appears that regulatory pathways governing the hematopoietic niche homeostasis are operating in the neurogenic niche as well. Therefore, this review paper aims to compare both the regulation of hematopoietic and neurogenic niches, in order to highlight the role of NCSCs and nervous system components in the development and the regulation of the hematopoietic system. PMID:26136659

  8. The current state of the neurogenic theory of depression and anxiety.

    PubMed

    Miller, Bradley R; Hen, René

    2015-02-01

    Newborn neurons are continuously added to the adult hippocampus. Early studies found that adult neurogenesis is impaired in models of depression and anxiety and accelerated by antidepressant treatment. This led to the theory that depression results from impaired adult neurogenesis and restoration of adult neurogenesis leads to recovery. Follow up studies yielded a complex body of often inconsistent results, and the veracity of this theory is uncertain. We propose five criteria for acceptance of this theory, we review the recent evidence for each criterion, and we draw the following conclusions: Diverse animal models of depression and anxiety have impaired neurogenesis. Neurogenesis is consistently boosted by antidepressants in animal models only when animals are stressed. Ablation of neurogenesis in animal models impairs cognitive functions relevant to depression, but only a minority of studies find that ablation causes depression or anxiety. Recent human neuroimaging and postmortem studies are consistent with the neurogenic theory, but they are indirect. Finally, a novel drug developed based on the neurogenic theory is promising in animal models.

  9. Effects of sangre de drago in an in vitro model of cutaneous neurogenic inflammation.

    PubMed

    Pereira, Ulysse; Garcia-Le Gal, Caridad; Le Gal, Grégoire; Boulais, Nicholas; Lebonvallet, Nicolas; Dorange, Germaine; Lefeuvre, Luc; Gougerot, Agnés; Misery, Laurent

    2010-09-01

    Sangre de drago (SD) is a viscous bright red resin collected from Croton lechleri trees that grow in the South American jungle. This sap is used extensively in the native pharmacopoeia to treat skin disorders. Its effectiveness as an inhibitor of neurogenic inflammation has been recently demonstrated. To understand the underlying mechanisms of these effects, we examined the ability of SD to reduce substance P (SP) release in an in vitro model of cutaneous neurogenic inflammation (CNI). This model is based on an enzyme immunoassay of SP (an inducer of CNI) in a porcine co-culture of dorsal root ganglion neurons and keratinocytes. After incubation with different concentrations of SD, we noted an immediate and significant dose-dependent decrease in basal SP release, with average values of 32% at 1% SD (v/v) and 26% at 0.1% (v/v). On the other hand, pretreatment (72 or 1 h) of the co-culture with 1% SD (v/v) was sufficient to induce a 111% (72 h) or 65% (1 h) inhibition of capsaicin-induced SP release, while 0.1% SD (v/v) triggered a 109% (72 h) or 30% (1 h) inhibition. We conclude that sangre de drago is a potent inhibitor of CNI through direct inhibition of neuropeptide release by sensory afferent nerves.

  10. SVCT2 vitamin C transporter expression in progenitor cells of the postnatal neurogenic niche

    PubMed Central

    Pastor, Patricia; Cisternas, Pedro; Salazar, Katterine; Silva-Alvarez, Carmen; Oyarce, Karina; Jara, Nery; Espinoza, Francisca; Martínez, Agustín D.; Nualart, Francisco

    2013-01-01

    Known as a critical antioxidant, recent studies suggest that vitamin C plays an important role in stem cell generation, proliferation and differentiation. Vitamin C also enhances neural differentiation during cerebral development, a function that has not been studied in brain precursor cells. We observed that the rat neurogenic niche is structurally organized at day 15 of postnatal development, and proliferation and neural differentiation increase at day 21. In the human brain, a similar subventricular niche was observed at 1-month of postnatal development. Using immunohistochemistry, sodium-vitamin C cotransporter 2 (SVCT2) expression was detected in the subventricular zone (SVZ) and rostral migratory stream (RMS). Low co-distribution of SVCT2 and βIII-tubulin in neuroblasts or type-A cells was detected, and minimal co-localization of SVCT2 and GFAP in type-B or precursor cells was observed. Similar results were obtained in the human neurogenic niche. However, BrdU-positive cells also expressed SVCT2, suggesting a role of vitamin C in neural progenitor proliferation. Primary neurospheres prepared from rat brain and the P19 teratocarcinoma cell line, which forms neurospheres in vitro, were used to analyze the effect of vitamin C in neural stem cells. Both cell types expressed functional SVCT2 in vitro, and ascorbic acid (AA) induced their neural differentiation, increased βIII-tubulin and SVCT2 expression, and amplified vitamin C uptake. PMID:23964197

  11. Microneedle Electrode Array for Electrical Impedance Myography to Characterize Neurogenic Myopathy.

    PubMed

    Li, Zhao; Li, Yi; Liu, Mingsheng; Cui, Liying; Yu, Yude

    2016-05-01

    Electrical impedance myography (EIM) is a noninvasive technique for neuromuscular assessment, wherein a low-intensity alternating current is applied to a muscle, and the consequent surface voltage patterns are evaluated. Commercial wet electrodes are most commonly used for EIM. However, these electrodes are not suitable for use on small muscles, as they do not effectively solve the problem of high electrode-skin contact impedance (ESCI) that negatively influences the quality of recorded biopotentials. To address this problem, we fabricated a novel microneedle electrode array (MEA) that consists of 124-µm-long microneedles. Compared to wet electrodes, the MEA could pierce through the outer skin surface in a painless and micro-invasive manner, and could thus effectively reduce ESCI. The MEA has excellent test-retest reproducibility, with intraclass correlation coefficients exceeding 0.920. When used in combination with EIM, the MEA differentiated the affected muscles from the unaffected muscles in patients with neurogenic myopathy, by using EIM parameters of reactance and phase (p = 0.023 and 0.008, respectively). Thus, the novel MEA is a practical and reusable device for EIM assessment in cases of neurogenic myopathy. However, further refinement of the electrode is needed to enhance the clinical application of the system.

  12. p73 is required for ependymal cell maturation and neurogenic SVZ cytoarchitecture.

    PubMed

    Gonzalez-Cano, L; Fuertes-Alvarez, S; Robledinos-Anton, N; Bizy, A; Villena-Cortes, A; Fariñas, I; Marques, M M; Marin, Maria C

    2016-07-01

    The adult subventricular zone (SVZ) is a highly organized microenvironment established during the first postnatal days when radial glia cells begin to transform into type B-cells and ependymal cells, all of which will form regenerative units, pinwheels, along the lateral wall of the lateral ventricle. Here, we identify p73, a p53 homologue, as a critical factor controlling both cell-type specification and structural organization of the developing mouse SVZ. We describe that p73 deficiency halts the transition of the radial glia into ependymal cells, leading to the emergence of immature cells with abnormal identities in the ventricle and resulting in loss of the ventricular integrity. p73-deficient ependymal cells have noticeably impaired ciliogenesis and they fail to organize into pinwheels, disrupting SVZ niche structure and function. Therefore, p73 is essential for appropriate ependymal cell maturation and the establishment of the neurogenic niche architecture. Accordingly, lack of p73 results in impaired neurogenesis. Moreover, p73 is required for translational planar cell polarity establishment, since p73 deficiency results in profound defects in cilia organization in individual cells and in intercellular patch orientation. Thus, our data reveal a completely new function of p73, independent of p53, in the neurogenic architecture of the SVZ of rodent brain and in the establishment of ependymal planar cell polarity with important implications in neurogenesis. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 730-747, 2016.

  13. [Diabetic neuropathy].

    PubMed

    Lechleitner, Monika; Abrahamian, Heidemarie; Francesconi, Claudia; Kofler, Markus

    2016-04-01

    These are the guidelines for diagnosis and treatment of diabetic neuropathy. This diabetic late complication comprises a number of mono- and polyneuropathies, plexopathies, radiculopathies and autonomic neuropathy. The position statement summarizes characteristic clinical symptoms and techniques for diagnostic assessment of diabetic neuropathy. Recommendations for the therapeutic management of diabetic neuropathy, especially for the control of pain in sensorimotor neuropathy, are provided.

  14. Dimethyl sulfoxide modulation of diabetes onset in NOD mice.

    PubMed

    Klandorf, H; Chirra, A R; DeGruccio, A; Girman, D J

    1989-02-01

    Dimethyl sulfoxide (DMSO), a hydroxyl radical scavenger, is known as an immunosuppressive agent and can reduce autoantibody levels in experimental autoimmune diseases. Because classic diabetogens damage the DNA and membrane of the beta-cell by the generation of free radicals, the purpose of these investigations was to determine whether the intake of DMSO or its derivatives methylsulfonylmethane (MSM) and dimethylsulfide (DMS) could prevent the expression of autoimmune diabetes in the spontaneously diabetic NOD mouse. DMSO (2.5%), MSM (2.5%), and DMS (0.25%) were added to the drinking water of female NOD mice immediately after weaning. Control animals were maintained on regular drinking water. The presence of overt diabetes was monitored from the age of 2 mo by weekly urinary glucose testing until the animals either became overtly glucosuric or were greater than 240 days of age. In contrast to what we expected, DMSO (2.5%) markedly increased the rate at which the animals expressed overt diabetes (P less than .0004, log-rank test). MSM had no effect, whereas DMS reduced the incidence and rate of diabetes onset. When DMSO (2.5%) was administered to male NOD mice and control strains of mice (BALB/c and ICR), the control group did not develop glucosuria or insipidus, whereas DMSO increased the incidence of diabetes in the male NOD mice from 21 to 79%. In contrast, when DMSO was fed to female NOD mice on a purified AIN-76 diet, diabetes onset was reduced to 36%. We conclude that DMSO accelerates the uptake of dietary diabetogens into the beta-cell of genetically susceptible animals (NOD mice). The protective effect of the purified diet in such animals may be due to a lack of putative diabetogens in purified diet, or alternatively, the diet itself contains factor(s) that protect the beta-cell from autoimmune attack and/or destruction.

  15. Diabetic neuropathy.

    PubMed

    Vinik, Aaron I; Nevoret, Marie-Laure; Casellini, Carolina; Parson, Henri

    2013-12-01

    Diabetic neuropathy (DN) is the most common and troublesome complication of diabetes mellitus, leading to the greatest morbidity and mortality and resulting in a huge economic burden for diabetes care. The clinical assessment of diabetic peripheral neuropathy and its treatment options are multifactorial. Patients with DN should be screened for autonomic neuropathy, as there is a high degree of coexistence of the two complications. A review of the clinical assessment and treatment algorithms for diabetic neuropathy, painful neuropathy, and autonomic dysfunction is provided.

  16. A comprehensive review of urologic complications in patients with diabetes.

    PubMed

    Arrellano-Valdez, Fernando; Urrutia-Osorio, Marta; Arroyo, Carlos; Soto-Vega, Elena

    2014-01-01

    Diabetes Mellitus (DM) is a chronic disease characterized by hyperglycemia, as a result of abnormal insulin production, insulin function, or both. DM is associated with systemic complications, such as infections, neuropathy and angiopathy, which involve the genitourinary tract. The three most significant urologic complications include: bladder cystopathy, sexual dysfunction and urinary tract infections. Almost half of the patients with DM have bladder dysfunction or cystopathy, which can be manifested in women as hypersensitivity (in 39-61% of the diabetic women) or neurogenic bladder. In males it can be experienced as lower urinary tract symptoms (in 25% of diabetic males with a nearly twofold increased risk when seen by age groups). Additionally, an increased prostate volume affects their micturition as well as their urinary tract. Involving sexual dysfunction in women, it includes reduced libido, decreased arousal, clitoral erectile dysfunction and painful or non-sensitive intercourse; and in diabetic males it varies from low libido, ejaculatory abnormalities and erectile dysfunction. Globally, sexual disorders have a prevalence of 18-42%. Erectile dysfunction is ranked as the third most important complication of DM. Urinary tract infections are observed frequently in diabetic patients, and vary from emphysematous infections, Fournier gangrene, staghorn infected lithiasis to repetitive bacterial cystitis. The most frequent finding in diabetic women has been lower urinary tract infections. Because of the high incidence of obesity worldwide and its association with diabetes, it is very important to keep in mind the urologic complication associated with DM in patients, in order to better diagnose and treat this population.

  17. Effects of electroacupuncture combined with bladder training on the bladder function of patients with neurogenic bladder after spinal cord injury

    PubMed Central

    Xia, Li-Ping; Fan, Fan; Tang, Ai-Ling; Ye, Wen-Qin

    2014-01-01

    Neurogenic bladder is a common complication of spinal cord injury and results in urinary bladder dysfunction through lost control of micturition, or urination. Although several treatment options exist, the efficacies of many of these treatments are unknown. In particular, electroacupuncture and bladder training have had some success as individual treatments. The aim of this study was to explore effects of electroacupuncture combined with bladder training on bladder function of patients with neurogenic bladder after spinal cord injury (SCI) above the sacral segment. Forty-two patients with neurogenic bladder after SCI were evenly divided into two groups (n=21) and given only bladder function training (control group) or electroacupuncture combined with bladder function training (treatment group). Urodynamic changes, IPSS score, and therapeutic efficacy were compared between groups pre- and post-treatment. After either treatment, patients had higher bladder volume and bladder compliance, but lower residual urine volume, bladder pressure, rectal pressure, and detrusor pressure, compared to pre-treatment (P<0.05). Compared to controls, treatment group patients had significantly increased bladder volume and bladder compliance, but significantly decreased residual urine volume, bladder pressure, rectal pressure, and detrusor pressure (P<0.05). Treatment group patients had lower IPSS scores post-treatment (P<0.05) and better therapeutic efficacy (P<0.05) than control group patients. Altogether, our results suggest that electroacupuncture combined with bladder function training can clinically improve bladder function of patients with neurogenic bladder after SCI above the sacral segment. PMID:24995093

  18. Inhibitory effect of botulinum toxin type A on the NANC system in rat respiratory models of neurogenic inflammation.

    PubMed

    Chien, Chiang-Ting; Lee, Hsin-Min; Wu, Chia-Ching Josh; Li, Ping-Chia

    2012-08-15

    This study investigated whether botulinum toxin type A (BTX-A) inhibits respiratory neurogenic inflammation in the non-adrenergic, non-cholinergic (NANC) transmitter system in rats. Neurogenic inflammation models were induced in Sprague Dawley (SD) rats through bilateral cerebral artery occlusion (BCAO) for different times (0, 30 and 60 min) or by stimulation with capsaicin at different doses (5 or 15 g/kg). Pre-Bötzinger Complex-Spikes and the expression of substance P, synaptosomal-associated protein-25 (SNAP-25), and reactive oxygen species (ROS) were detected with or without pretreatment of rats with BTX-A (15 or 30 U/kg). BCAO reduced pre-Bot C spike activity (spike/s) and increased the breath rate (breaths/s) in an unstable pattern in comparison to controls, while pretreatment with BTX-A slightly reduced this phenomenon. Pretreatment with BTX-A inhibited BCAO- or capsaicin-induced increases in expression of SNAP-25, substance P, and ROS in a dose-dependent manner in brainstem and lung tissue. BTX-A exerts a suppressive effect on neurogenic inflammation via non-adrenergic, non-cholinergic transmitters. These results add to the body of evidence elucidating the non-cholinergic effects of BTX-A in the context of neurogenic inflammation.

  19. Neurogenic bladder

    MedlinePlus

    ... cause skin to break down and lead to pressure sores Kidney damage if the bladder becomes too full, ... More Tumor Patient Instructions Multiple sclerosis - discharge Preventing pressure ulcers Review Date 5/30/2016 Updated by: Amit ...

  20. Neurogenic Stuttering

    MedlinePlus

    ... even depression about the difficulty they encounter in speaking. This may be accompanied by other behaviors, which ... speech production; movements of head or limbs while speaking; reduced eye contact; Postponement or delay in attempting ...

  1. The selective PAC1 receptor agonist maxadilan inhibits neurogenic vasodilation and edema formation in the mouse skin.

    PubMed

    Banki, E; Hajna, Zs; Kemeny, A; Botz, B; Nagy, P; Bolcskei, K; Toth, G; Reglodi, D; Helyes, Zs

    2014-10-01

    We have earlier shown that PACAP-38 decreases neurogenic inflammation. However, there were no data on its receptorial mechanism and the involvement of its PAC1 and VPAC1/2 receptors (PAC1R, VPAC1/2R) in this inhibitory effect. Neurogenic inflammation in the mouse ear was induced by topical application of the Transient Receptor Potential Ankyrin 1 (TRPA1) receptor activator mustard oil (MO). Consequent neurogenic edema, vasodilation and plasma leakage were assessed by measuring ear thickness with engineer's micrometer, detecting tissue perfusion by laser Doppler scanning and Evans blue or indocyanine green extravasation by intravital videomicroscopy or fluorescence imaging, respectively. Myeloperoxidase activity, an indicator of neutrophil infiltration, was measured from the ear homogenates with spectrophotometry. The selective PAC1R agonist maxadilan, the VPAC1/2R agonist vasoactive intestinal polypeptide (VIP) or the vehicle were administered i.p. 15 min before MO. Substance P (SP) concentration of the ear was assessed by radioimmunoassay. Maxadilan significantly diminished MO-induced neurogenic edema, increase of vascular permeability and vasodilation. These inhibitory effects of maxadilan may be partially due to the decreased substance P (SP) levels. In contrast, inhibitory effect of VIP on ear swelling was moderate, without any effect on MO-induced plasma leakage or SP release, however, activation of VPAC1/2R inhibited the increased microcirculation caused by the early arteriolar vasodilation. Neither the PAC1R, nor the VPAC1/2R agonist influenced the MO-evoked increase in tissue myeloperoxidase activity. These results clearly show that PAC1R activation inhibits acute neurogenic arterial vasodilation and plasma protein leakage from the venules, while VPAC1/2R stimulation is only involved in the attenuation of vasodilation.

  2. Neurogenic pulmonary edema combined with febrile seizures in early childhood-A report of two cases.

    PubMed

    Tasaka, Keiji; Matsubara, Kousaku; Hori, Masayuki; Nigami, Hiroyuki; Iwata, Aya; Isome, Kenichi; Kawasaki, Yu; Nagai, Sadayuki

    2016-01-01

    Neurogenic pulmonary edema (NPE) is a clinical entity that can occur following central nervous system disorders. However, NPE occurs quite rarely in early childhood, and there has only been one report about pediatric NPE associated with febrile seizures. Two cases are reported here. One case involved a 2-year-old girl who presented with febrile seizures, which rapidly progressed to severe NPE. Since the NPE occurred in the emergency department room, the patient was able to be resuscitated via immediate endotracheal intubation. The other case involved an 11-month-old boy who developed respiratory distress following a 50-min episode of febrile status epilepticus. Both patients required respiratory management in the intensive care unit. However their conditions were dramatically improved within several days and fully recovered without any sequelae.

  3. TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins.

    PubMed

    Meseguer, Victor; Alpizar, Yeranddy A; Luis, Enoch; Tajada, Sendoa; Denlinger, Bristol; Fajardo, Otto; Manenschijn, Jan-Albert; Fernández-Peña, Carlos; Talavera, Arturo; Kichko, Tatiana; Navia, Belén; Sánchez, Alicia; Señarís, Rosa; Reeh, Peter; Pérez-García, María Teresa; López-López, José Ramón; Voets, Thomas; Belmonte, Carlos; Talavera, Karel; Viana, Félix

    2014-01-01

    Gram-negative bacterial infections are accompanied by inflammation and somatic or visceral pain. These symptoms are generally attributed to sensitization of nociceptors by inflammatory mediators released by immune cells. Nociceptor sensitization during inflammation occurs through activation of the Toll-like receptor 4 (TLR4) signalling pathway by lipopolysaccharide (LPS), a toxic by-product of bacterial lysis. Here we show that LPS exerts fast, membrane delimited, excitatory actions via TRPA1, a transient receptor potential cation channel that is critical for transducing environmental irritant stimuli into nociceptor activity. Moreover, we find that pain and acute vascular reactions, including neurogenic inflammation (CGRP release) caused by LPS are primarily dependent on TRPA1 channel activation in nociceptive sensory neurons, and develop independently of TLR4 activation. The identification of TRPA1 as a molecular determinant of direct LPS effects on nociceptors offers new insights into the pathogenesis of pain and neurovascular responses during bacterial infections and opens novel avenues for their treatment.

  4. Vertebrate neurogenic placode development: historical highlights that have shaped our current understanding.

    PubMed

    Stark, Michael R

    2014-10-01

    With the flood of published research encountered today, it is important to occasionally reflect upon how we arrived at our current understanding in a particular scientific discipline, thereby positioning new discoveries into proper context with long-established models. This historical review highlights some of the important scientific contributions in the field of neurogenic placode development. By viewing cumulatively the rich historical data, we can more fully appreciate and apply what has been accomplished. Early descriptive work in fish and experimental approaches in amphibians and chick yielded important conceptual models of placode induction and cellular differentiation. Current efforts to discover genes and their molecular functions continue to expand our understanding of the placodes. Carefully considering the body of work may improve current models and help focus modern experimental design.

  5. TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins

    NASA Astrophysics Data System (ADS)

    Meseguer, Victor; Alpizar, Yeranddy A.; Luis, Enoch; Tajada, Sendoa; Denlinger, Bristol; Fajardo, Otto; Manenschijn, Jan-Albert; Fernández-Peña, Carlos; Talavera, Arturo; Kichko, Tatiana; Navia, Belén; Sánchez, Alicia; Señarís, Rosa; Reeh, Peter; Pérez-García, María Teresa; López-López, José Ramón; Voets, Thomas; Belmonte, Carlos; Talavera, Karel; Viana, Félix

    2014-01-01

    Gram-negative bacterial infections are accompanied by inflammation and somatic or visceral pain. These symptoms are generally attributed to sensitization of nociceptors by inflammatory mediators released by immune cells. Nociceptor sensitization during inflammation occurs through activation of the Toll-like receptor 4 (TLR4) signalling pathway by lipopolysaccharide (LPS), a toxic by-product of bacterial lysis. Here we show that LPS exerts fast, membrane delimited, excitatory actions via TRPA1, a transient receptor potential cation channel that is critical for transducing environmental irritant stimuli into nociceptor activity. Moreover, we find that pain and acute vascular reactions, including neurogenic inflammation (CGRP release) caused by LPS are primarily dependent on TRPA1 channel activation in nociceptive sensory neurons, and develop independently of TLR4 activation. The identification of TRPA1 as a molecular determinant of direct LPS effects on nociceptors offers new insights into the pathogenesis of pain and neurovascular responses during bacterial infections and opens novel avenues for their treatment.

  6. Brain Ischemia Suppresses Immunity in the Periphery and Brain via Different Neurogenic Innervations.

    PubMed

    Liu, Qiang; Jin, Wei-Na; Liu, Yaou; Shi, Kaibin; Sun, Haoran; Zhang, Fang; Zhang, Chao; Gonzales, Rayna J; Sheth, Kevin N; La Cava, Antonio; Shi, Fu-Dong

    2017-03-21

    Brain ischemia inhibits immune function systemically, with resulting infectious complications. Whether in stroke different immune alterations occur in brain and periphery and whether analogous mechanisms operate in these compartments remains unclear. Here we show that in patients with ischemic stroke and in mice subjected to middle cerebral artery occlusion, natural killer (NK) cells display remarkably distinct temporal and transcriptome profiles in the brain as compared to the periphery. The activation of catecholaminergic and hypothalamic-pituitary-adrenal axis leads to splenic atrophy and contraction of NK cell numbers in the periphery through a modulated expression of SOCS3, whereas cholinergic innervation-mediated suppression of NK cell responses in the brain involves RUNX3. Importantly, pharmacological or genetic ablation of innervation preserved NK cell function and restrained post-stroke infection. Thus, brain ischemia compromises NK cell-mediated immune defenses through mechanisms that differ in the brain versus the periphery, and targeted inhibition of neurogenic innervation limits post-stroke infection.

  7. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer.

    PubMed

    Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R; Tang, Dean G

    2016-02-29

    The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.

  8. Self-maintenance of neurogenic inflammation contributes to a vicious cycle in skin.

    PubMed

    Gouin, Olivier; Lebonvallet, Nicolas; L'Herondelle, Killian; Le Gall-Ianotto, Christelle; Buhé, Virginie; Plée-Gautier, Emmanuelle; Carré, Jean-Luc; Lefeuvre, Luc; Misery, Laurent

    2015-10-01

    Cutaneous neurogenic inflammation (CNI) is frequently associated with skin disorders. CNI is not limited to the retrograde signalling of nociceptive sensory nerve endings but can instead be regarded as a multicellular phenomenon. Thus, soluble mediators participating in communication among sensory nerves, skin and immune cells are key components of CNI. These interactions induce the self-maintenance of CNI, promoting a vicious cycle. Certain G protein-coupled receptors (GPCRs) play a prominent role in these cell interactions and contribute to self-maintenance. Protease-activated receptors 2 and 4 (PAR-2 and PAR-4, respectively) and Mas-related G protein-coupled receptors (Mrgprs) are implicated in the synthesis and release of neuropeptides, proteases and soluble mediators from most cutaneous cells. Regulation of the expression and release of these mediators contributes to the vicious cycle of CNI. The authors propose certain hypothetical therapeutic options to interrupt this cycle, which might reduce skin symptoms and improve patient quality of life.

  9. Endocannabinoids via CB1 receptors act as neurogenic niche cues during cortical development

    PubMed Central

    Díaz-Alonso, Javier; Guzmán, Manuel; Galve-Roperh, Ismael

    2012-01-01

    During brain development, neurogenesis is precisely regulated by the concerted action of intrinsic factors and extracellular signalling systems that provide the necessary niche information to proliferating and differentiating cells. A number of recent studies have revealed a previously unknown role for the endocannabinoid (ECB) system in the control of embryonic neuronal development and maturation. Thus, the CB1 cannabinoid receptor in concert with locally produced ECBs regulates neural progenitor (NP) proliferation, pyramidal specification and axonal navigation. In addition, subcellularly restricted ECB production acts as an axonal growth cone signal to regulate interneuron morphogenesis. These findings provide the rationale for understanding better the consequences of prenatal cannabinoid exposure, and emphasize a novel role of ECBs as neurogenic instructive cues involved in cortical development. In this review the implications of altered CB1-receptor-mediated signalling in developmental disorders and particularly in epileptogenesis are briefly discussed. PMID:23108542

  10. Neurogenic thoracic outlet syndrome: current diagnostic criteria and advances in MRI diagnostics.

    PubMed

    Magill, Stephen T; Brus-Ramer, Marcel; Weinstein, Philip R; Chin, Cynthia T; Jacques, Line

    2015-09-01

    Neurogenic thoracic outlet syndrome (nTOS) is caused by compression of the brachial plexus as it traverses from the thoracic outlet to the axilla. Diagnosing nTOS can be difficult because of overlap with other complex pain and entrapment syndromes. An nTOS diagnosis is made based on patient history, physical exam, electrodiagnostic studies, and, more recently, interpretation of MR neurograms with tractography. Advances in high-resolution MRI and tractography can confirm an nTOS diagnosis and identify the location of nerve compression, allowing tailored surgical decompression. In this report, the authors review the current diagnostic criteria, present an update on advances in MRI, and provide case examples demonstrating how MR neurography (MRN) can aid in diagnosing nTOS. The authors conclude that improved high-resolution MRN and tractography are valuable tools for identifying the source of nerve compression in patients with nTOS and can augment current diagnostic modalities for this syndrome.

  11. Traumatic Brain Injury Activation of the Adult Subventricular Zone Neurogenic Niche

    PubMed Central

    Chang, Eun Hyuk; Adorjan, Istvan; Mundim, Mayara V.; Sun, Bin; Dizon, Maria L. V.; Szele, Francis G.

    2016-01-01

    Traumatic brain injury (TBI) is common in both civilian and military life, placing a large burden on survivors and society. However, with the recognition of neural stem cells in adult mammals, including humans, came the possibility to harness these cells for repair of damaged brain, whereas previously this was thought to be impossible. In this review, we focus on the rodent adult subventricular zone (SVZ), an important neurogenic niche within the mature brain in which neural stem cells continue to reside. We review how the SVZ is perturbed following various animal TBI models with regards to cell proliferation, emigration, survival, and differentiation, and we review specific molecules involved in these processes. Together, this information suggests next steps in attempting to translate knowledge from TBI animal models into human therapies for TBI. PMID:27531972

  12. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer

    PubMed Central

    Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R.; Tang, Dean G.

    2016-01-01

    The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. PMID:26924072

  13. Long-term outcomes of urinary tract reconstruction in patients with neurogenic urinary tract dysfunction.

    PubMed

    Johnson, E U; Singh, Gurpreet

    2013-10-01

    The advent of specialized spinal units and better understanding of the pathophysiology of neurogenic urinary tract dysfunction has made long-term survival of these patients a reality. This has, in turn, led to an increase in quality and choice of management modalities offered to these patients including complex anatomic urinary tract reconstructive procedures tailored to the unique needs of each individual with variable outcomes. We performed a literature review evaluating the long-term outcomes of these reconstructive procedures. To achieve this, we conducted a world-wide electronic literature search of long-term outcomes published in English. As the premise of this review is long-term outcomes, we have focused on pathologies where evidence of long-term outcome is available such as patients with spinal injuries and spina bifida. Therapeutic success following urinary tract reconstruction is usually measured by preservation of renal function, improvement in quality-of-life, the satisfactory achievement of agreed outcomes and the prevention of serious complications. Prognostic factors include neuropathic detrusor overactivity; sphincter dyssynergia; bladder over distension; high pressure storage and high leak point pressures; vesicoureteric reflex, stone formation and urinary tract infections. Although, the past decade has witnessed a reduction in the total number of bladder reconstructive surgeries in the UK, these procedures are essentially safe and effective; but require long-term clinical and functional follow-up/monitoring. Until tissue engineering and gene therapy becomes more mainstream, we feel there is still a place for urinary tract reconstruction in patients with neurogenic lower urinary tract dysfunction.

  14. Long-term outcomes of urinary tract reconstruction in patients with neurogenic urinary tract dysfunction

    PubMed Central

    Johnson, E. U.; Singh, Gurpreet

    2013-01-01

    The advent of specialized spinal units and better understanding of the pathophysiology of neurogenic urinary tract dysfunction has made long-term survival of these patients a reality. This has, in turn, led to an increase in quality and choice of management modalities offered to these patients including complex anatomic urinary tract reconstructive procedures tailored to the unique needs of each individual with variable outcomes. We performed a literature review evaluating the long-term outcomes of these reconstructive procedures. To achieve this, we conducted a world-wide electronic literature search of long-term outcomes published in English. As the premise of this review is long-term outcomes, we have focused on pathologies where evidence of long-term outcome is available such as patients with spinal injuries and spina bifida. Therapeutic success following urinary tract reconstruction is usually measured by preservation of renal function, improvement in quality-of-life, the satisfactory achievement of agreed outcomes and the prevention of serious complications. Prognostic factors include neuropathic detrusor overactivity; sphincter dyssynergia; bladder over distension; high pressure storage and high leak point pressures; vesicoureteric reflex, stone formation and urinary tract infections. Although, the past decade has witnessed a reduction in the total number of bladder reconstructive surgeries in the UK, these procedures are essentially safe and effective; but require long-term clinical and functional follow-up/monitoring. Until tissue engineering and gene therapy becomes more mainstream, we feel there is still a place for urinary tract reconstruction in patients with neurogenic lower urinary tract dysfunction. PMID:24235796

  15. Hippocampal transcriptional and neurogenic changes evoked by combination yohimbine and imipramine treatment.

    PubMed

    Husain, Basma Fatima Anwar; Nanavaty, Ishira N; Marathe, Swananda V; Rajendran, Rajeev; Vaidya, Vidita A

    2015-08-03

    Adjunct α2-adrenoceptor antagonism is a potential strategy to accelerate the behavioral effects of antidepressants. Co-administration of the α2-adrenoceptor antagonist yohimbine hastens the behavioral and neurogenic effects of the antidepressant imipramine. We examined the transcriptional targets of short duration (7days), combination treatment of yohimbine and imipramine (Y+I) within the adult rat hippocampus. Using microarray and qPCR analysis we observed functional enrichment of genes involved in intracellular signaling cascades, plasma membrane, cellular metal ion homeostasis, multicellular stress responses and neuropeptide signaling pathways in the Y+I transcriptome. We noted reduced expression of the α2A-adrenoceptor (Adra2a), serotonin 5HT2C receptor (Htr2c) and the somatostatin receptor 1 (Sstr1), which modulate antidepressant action. Further, we noted a regulation of signaling pathway genes like inositol monophosphatase 2 (Impa2), iodothyronine deiodinase 3 (Dio3), regulator of G-protein signaling 4 (Rgs4), alkaline ceramidase 2 (Acer2), doublecortin-like kinase 2 (Dclk2), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (Nfkbia) and serum/glucocorticoid-regulated kinase 1 (Sgk1), several of which are implicated in the pathophysiology of mood disorders. Comparative analysis revealed an overlap in the hippocampal regulation of Acer2, Nfkbia, Sgk1 and Impa2 between Y+I treatment, the fast-acting electroconvulsive seizure (ECS) paradigm, and the slow-onset chronic (21days) imipramine treatment. Further, Y+I treatment enhanced the quiescent neural progenitor pool in the hippocampal neurogenic niche similar to ECS, and distinct from chronic imipramine treatment. Taken together, our results provide insight into the molecular and cellular targets of short duration Y+I treatment, and identify potential leads for the development of rapid-action antidepressants.

  16. Stroke Increases Neural Stem Cells and Angiogenesis in the Neurogenic Niche of the Adult Mouse

    PubMed Central

    Zhang, Rui Lan; Chopp, Michael; Roberts, Cynthia; Liu, Xianshuang; Wei, Min; Nejad-Davarani, Siamak P.; Wang, Xinli; Zhang, Zheng Gang

    2014-01-01

    The unique cellular and vascular architecture of the adult ventricular-subventricular zone (V/SVZ) neurogenic niche plays an important role in regulating neural stem cell function. However, the in vivo identification of neural stem cells and their relationship to blood vessels within this niche in response to stroke remain largely unknown. Using whole-mount preparation of the lateral ventricle wall, we examined the architecture of neural stem cells and blood vessels in the V/SVZ of adult mouse over the course of 3 months after onset of focal cerebral ischemia. Stroke substantially increased the number of glial fibrillary acidic protein (GFAP) positive neural stem cells that are in contact with the cerebrospinal fluid (CSF) via their apical processes at the center of pinwheel structures formed by ependymal cells residing in the lateral ventricle. Long basal processes of these cells extended to blood vessels beneath the ependymal layer. Moreover, stroke increased V/SVZ endothelial cell proliferation from 2% in non-ischemic mice to 12 and 15% at 7 and 14 days after stroke, respectively. Vascular volume in the V/SVZ was augmented from 3% of the total volume prior to stroke to 6% at 90 days after stroke. Stroke-increased angiogenesis was closely associated with neuroblasts that expanded to nearly encompass the entire lateral ventricular wall in the V/SVZ. These data indicate that stroke induces long-term alterations of the neural stem cell and vascular architecture of the adult V/SVZ neurogenic niche. These post-stroke structural changes may provide insight into neural stem cell mediation of stroke-induced neurogenesis through the interaction of neural stem cells with proteins in the CSF and their sub-ependymal neurovascular interaction. PMID:25437857

  17. Cancer stem cells from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall

    PubMed Central

    2012-01-01

    Background The cancer stem cell (CSC) hypothesis posits that deregulated neural stem cells (NSCs) form the basis of brain tumors such as glioblastoma multiforme (GBM). GBM, however, usually forms in the cerebral white matter while normal NSCs reside in subventricular and hippocampal regions. We attempted to characterize CSCs from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall. Methods We described isolating CSCs from a GBM involving the lateral ventricles and characterized these cells with in vitro molecular biomarker profiling, cellular behavior, ex vivo and in vivo techniques. Results The patient’s MRI revealed a heterogeneous mass with associated edema, involving the left subventricular zone. Histological examination of the tumor established it as being a high-grade glial neoplasm, characterized by polygonal and fusiform cells with marked nuclear atypia, amphophilic cytoplasm, prominent nucleoli, frequent mitotic figures, irregular zones of necrosis and vascular hyperplasia. Recurrence of the tumor occurred shortly after the surgical resection. CD133-positive cells, isolated from the tumor, expressed stem cell markers including nestin, CD133, Ki67, Sox2, EFNB1, EFNB2, EFNB3, Cav-1, Musashi, Nucleostemin, Notch 2, Notch 4, and Pax6. Biomarkers expressed in differentiated cells included Cathepsin L, Cathepsin B, Mucin18, Mucin24, c-Myc, NSE, and TIMP1. Expression of unique cancer-related transcripts in these CD133-positive cells, such as caveolin-1 and −2, do not appear to have been previously reported in the literature. Ex vivo organotypic brain slice co-culture showed that the CD133+ cells behaved like tumor cells. The CD133-positive cells also induced tumor formation when they were stereotactically transplanted into the brains of the immune-deficient NOD/SCID mice. Conclusions This brain tumor involving the neurogenic lateral ventricular wall was comprised of tumor-forming, CD133-positive cancer stem cells, which are likely

  18. Reconstitution of experimental neurogenic bladder dysfunction using skeletal muscle-derived multipotent stem cells.

    PubMed

    Nitta, Masahiro; Tamaki, Tetsuro; Tono, Kayoko; Okada, Yoshinori; Masuda, Maki; Akatsuka, Akira; Hoshi, Akio; Usui, Yukio; Terachi, Toshiro

    2010-05-15

    BACKGROUND.: Postoperative neurogenic bladder dysfunction is a major complication of radical hysterectomy for cervical cancer and is mainly caused by unavoidable damage to the bladder branch of the pelvic plexus (BBPP) associated with colateral blood vessels. Thus, we attempted to reconstitute disrupted BBPP and blood vessels using skeletal muscle-derived multipotent stem cells that show synchronized reconstitution capacity of vascular, muscular, and peripheral nervous systems. METHODS.: Under pentobarbital anesthesia, intravesical pressure by electrical stimulation of BBPP was measured as bladder function. The distal portion of BBPP with blood vessels was then cut unilaterally (experimental neurogenic bladder model). Measurements were performed before, immediately after, and at 4 weeks after transplantation as functional recovery. Stem cells were obtained from the right soleus and gastrocnemius muscles after enzymatic digestion and cell sorting as CD34/45 (Sk-34) and CD34/45 (Sk-DN). Suspended cells were autografted around the damaged region, whereas medium alone and CD45 cells were transplanted as control groups. To determine the morphological contribution of the transplanted cells, stem cells obtained from green fluorescent protein transgenic mouse muscles were transplanted into a nude rat model and were examined by immunohistochemistry and immunoelectron microscopy. RESULTS.: At 4 weeks after surgery, the transplantation group showed significantly higher functional recovery ( approximately 80%) than the two controls ( approximately 28% and 24%). The transplanted cells showed an incorporation into the damaged peripheral nerves and blood vessels after differentiation into Schwann cells, perineurial cells, vascular smooth muscle cells, pericytes, and fibroblasts around the bladder. CONCLUSION.: Transplantation of multipotent Sk-34 and Sk-DN cells is potentially useful for the reconstitution of damaged BBPP.

  19. Evaluation of educational content of YouTube videos relating to neurogenic bladder and intermittent catheterization

    PubMed Central

    Ho, Matthew; Stothers, Lynn; Lazare, Darren; Tsang, Brian; Macnab, Andrew

    2015-01-01

    Introduction: Many patients conduct internet searches to manage their own health problems, to decide if they need professional help, and to corroborate information given in a clinical encounter. Good information can improve patients’ understanding of their condition and their self-efficacy. Patients with spinal cord injury (SCI) featuring neurogenic bladder (NB) require knowledge and skills related to their condition and need for intermittent catheterization (IC). Methods: Information quality was evaluated in videos accessed via YouTube relating to NB and IC using search terms “neurogenic bladder intermittent catheter” and “spinal cord injury intermittent catheter.” Video content was independently rated by 3 investigators using criteria based on European Urological Association (EAU) guidelines and established clinical practice. Results: In total, 71 videos met the inclusion criteria. Of these, 12 (17%) addressed IC and 50 (70%) contained information on NB. The remaining videos met inclusion criteria, but did not contain information relevant to either IC or NB. Analysis indicated poor overall quality of information, with some videos with information contradictory to EAU guidelines for IC. High-quality videos were randomly distributed by YouTube. IC videos featuring a healthcare narrator scored significantly higher than patient-narrated videos, but not higher than videos with a merchant narrator. About half of the videos contained commercial content. Conclusions: Some good-quality educational videos about NB and IC are available on YouTube, but most are poor. The videos deemed good quality were not prominently ranked by the YouTube search algorithm, consequently user access is less likely. Study limitations include the limit of 50 videos per category and the use of a de novo rating tool. Information quality in videos with healthcare narrators was not higher than in those featuring merchant narrators. Better material is required to improve patients

  20. Mesenchymal stem cells secretome as a modulator of the neurogenic niche: basic insights and therapeutic opportunities

    PubMed Central

    Salgado, Antonio J.; Sousa, Joao C.; Costa, Bruno M.; Pires, Ana O.; Mateus-Pinheiro, António; Teixeira, F. G.; Pinto, Luisa; Sousa, Nuno

    2015-01-01

    Neural stem cells (NSCs) and mesenchymal stem cells (MSCs) share few characteristics apart from self-renewal and multipotency. In fact, the neurogenic and osteogenic stem cell niches derive from two distinct embryonary structures; while the later originates from the mesoderm, as all the connective tissues do, the first derives from the ectoderm. Therefore, it is highly unlikely that stem cells isolated from one niche could form terminally differentiated cells from the other. Additionally, these two niches are associated to tissues/systems (e.g., bone and central nervous system) that have markedly different needs and display diverse functions within the human body. Nevertheless they do share common features. For instance, the differentiation of both NSCs and MSCs is intimately associated with the bone morphogenetic protein family. Moreover, both NSCs and MSCs secrete a panel of common growth factors, such as nerve growth factor (NGF), glial derived neurotrophic factor (GDNF), and brain derived neurotrophic factor (BDNF), among others. But it is not the features they share but the interaction between them that seem most important, and worth exploring; namely, it has already been shown that there are mutually beneficially effects when these cell types are co-cultured in vitro. In fact the use of MSCs, and their secretome, become a strong candidate to be used as a therapeutic tool for CNS applications, namely by triggering the endogenous proliferation and differentiation of neural progenitors, among other mechanisms. Quite interestingly it was recently revealed that MSCs could be found in the human brain, in the vicinity of capillaries. In the present review we highlight how MSCs and NSCs in the neurogenic niches interact. Furthermore, we propose directions on this field and explore the future therapeutic possibilities that may arise from the combination/interaction of MSCs and NSCs. PMID:26217178