Aim: The patients in the permanent diabetes insipidus (DI) group are more likely to have more severe TBI, which is defined by a post-resuscitational and pre-sedational Glasgow Coma Scale (GCS) score of 8/15 or less. This study presents a case of permanent, central DI following mild traumatic brain injury with post-resuscitation GCS 13/15. Case report: A 17-year-old boy suffered from mild brain injury and experienced permanent DI without any anatomical changes on image in the early stage of traumatic brain injury. However, 1 year later, magnetic resonance imaging (MRI) of the brain in this patient has revealed some sequel of contusion. Moreover, the patient still has DI after treatment with diamino-8-D-arginine vasopressin (DDAVP). Conclusion: This patient had a rare clinical presentation of permanent, central DI, following a mild traumatic brain injury. Identification of head trauma as the aetiology of hypopituitarism may be overlooked if there is a long delay in onset after trauma. Since anterior hypopituitarism can develop decades after the episode of head trauma, monitoring for endocrine dysfunction during follow-up of these patients is important.

ABSTRACT: INTRODUCTION: The study was aimed at verifying whether the occurrence of hypernatremia during ICU stay increases the risk of death in patients with severe traumatic brain injury (TBI). We performed a retrospective study on a prospectively collected database including all patients consecutively admitted over a 3-year period with a diagnosis of TBI (post-resuscitation GCS < 8) to a general/neurotrauma ICU of a University Hospital, providing critical care services in a catchment area of about 1,200,000 inhabitants. METHODS: Demographic, clinical, and ICU laboratory data were prospectively collected; serum sodium was assessed on an average of 3 times per day. Hypernatremia was defined as two daily values of serum sodium above 145 mmol/L. The major outcome was death in the ICU after 14 days. Cox proportional-hazards regression models were used, with time-dependent variates designed to reflect exposure over time during the ICU stay: hypernatremia, desmopressin acetate (DDAVP) administration as a surrogate marker for the presence of Central Diabetes Insipidus, and urinary output. The same models were adjusted for potential confounding factors. RESULTS: We included in the study 130 TBI patients (mean age 52 yrs [SD 23]; males 74%; median GCS 3 [range 3-8]; mean SAPS II 50 [SD 15]; all were mechanically ventilated; 35 (26.9%) died within 14 days after ICU admission. Hypernatremia was detected in 51.5% of the patients and in 15.9% of the 1103 patient-day ICU follow-up. In most instances hypernatremia was mild (mean 150 mmol/L, interquartile range 148-152). The occurrence of hypernatremia was highest (P=0.003) in patients with suspected Central Diabetes Insipidus (25/130, 19.2%), a condition which was associated with increased severity of brain injury and ICU mortality. After adjustment for the baseline risk, the incidence of hypernatremia over the course of ICU stay was significantly related with increased mortality (hazard ratio 3.00 [95% CI: 1.34-6.51; P=0.003]). However, DDAVP use modified this relation (P=0.06), hypernatremia providing no additional prognostic information in the instances of suspected Central Diabetes Insipidus. CONCLUSIONS: Mild hypernatremia is associated with an increased risk of death in patients with severe TBI. In a proportion of the patients the association between hypernatremia and death is accounted for by the presence of Central Diabetes Insipidus.

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

Posttraumatic hypopituitarism is the failure of the hypothalamic-pituitary axis secondary to traumatic brain injury. It can clinically present as decreased muscle mass, concentration, libido, and fertility. It can also present as increased fatigue, depression, and cognitive deficits. In addition, electrolyte abnormalities such as hyponatremia can occur in hypopituitarism. As a result of heightened awareness of posttraumatic hypopituitarism, it is a phenomenon that is becoming more commonly diagnosed. Posttraumatic hypopituitarism is a diagnosis based on clinical evaluation, laboratory testing, and neuroimaging. Of the radiological techniques, magnetic resonance imaging is the preferred technique to image the pituitary gland. This article contains coronal and sagittal magnetic resonance imaging of the posterior fossa, illustrating the normal hypothalamus and pituitary gland as well as adjacent structures. The sequential enhancement pattern of the normal pituitary gland is consistent with its vascular supply. A colored illustration was created to display the vascular supply to the hypothalamus, pituitary stalk, and pituitary gland.

BACKGROUND: Disorders of water and sodium balance are frequently seen in patients with severe brain injury (SBI), and may worsen their prognosis. PURPOSE: To evaluate vasopressin (AVP) serum levels and sodium and water balance disorders during the first week post-injury in patients with SBI. METHOD: Thirty-six adult patients with SBI (admission Glasgow Coma Scale score < 8) and an estimated time of injury < 72 hours were prospectively studied. Clinical and laboratory data were recorded and AVP was measured in venous blood samples collected on the 1st, 2nd, 3rd and 5th days following inclusion. RESULTS: AVP serum levels remained within the normal range in SBI patients (either traumatic or non-traumatic), although tended to be greater in non-survivor than in survivor patients (p=0.025 at 3rd day). In-hospital mortality was 43%(15/36), and serum sodium and plasma osmolality variabilities were greater in non-survivor than in survivor patients during the observation period (p<0.001). CONCLUSION: AVP serum levels remained within the normal range values in these SBI patients, but those who died have shown higher incidence of abnormal sodium and water balance during the first week post-injury.

Background. Over the past decade new insights in our understanding of coagulation have identified the prominent role of tissue factor. The brain is rich in tissue factor, and injury to the brain may initiate disturbances in local and systemic coagulation. We aimed to review the current knowledge on the pathophysiology, incidence, nature, prognosis and treatment of coagulation disorders following traumatic brain injury (TBI). Methods. We performed a MEDLINE search from 1966 to April 2007 with various MESH headings, focusing on head trauma and coagulopathy. We identified 441 eligible English language studies. These were reviewed for relevance by two independent investigators. A meta-analysis was performed to calculate the frequencies of coagulopathy after TBI and to determine the association of coagulopathy and outcome, expressed as odds ratios. Results. Eighty-two studies were relevant for the purpose of this review. Meta-analysis of 34 studies reporting the frequencies of coagulopathy after TBI, showed an overall prevalence of 32.7%. The presence of coagulopathy after TBI was related both to mortality (OR 9.0; 95%CI: 7.3-11.6) and unfavourable outcome (OR 36.3; 95%CI: 18.7-70.5). Conclusions. We conclude that coagulopathy following traumatic brain injury is an important independent risk factor related to prognosis. Routine determination of the coagulation status should therefore be performed in all patients with traumatic brain injury. These data may have important implications in patient management. Well-performed prospective clinical trials should be undertaken as a priority to determine the beneficial effects of early treatment of coagulopathy.

Rehabilitation goals after traumatic brain injury are improving function, increasing the level of independence as high as possible, preventing complications and providing an acceptable environment to the patient. Several complications can be encountered during the rehabilitation period which lead to physical, cognitive and neurobehavioral impairments that cause major delay in functional improvement. This prospective study was designed in order to investigate the complications and their relations with functional recovery in patients that were included in the acute phase of a rehabilitation program. Thirty traumatic brain injured patients admitted to the Intensive Care Units of Uludag University School of Medicine were included in the study. Rehabilitation program consisted in appropriate positioning, range of motion exercises, postural drainage and respiratory exercises. Complications that were encountered during intensive care rehabilitation program were recorded. All patients were evaluated by Functional Independence Measure, Disability Rating Scale and Ranchos Los Amigos Levels of Cognitive Function Scale at admission and discharge. Improvement was observed in patients in terms of functional outcome and disability levels. Pneumonia, athelectasis, anemia and meningitis were the most frequent complications. Deterioration in functional outcome and disability levels was noted as the number of these complications increased. In conclusion, rehabilitation has an important role in the management of traumatic brain injured patients. Reduction of frequency of complications and improvement in functional outcome and disability levels can be achieved through rehabilitation programs. Long-term controlled studies with large number of patients are needed in order to obtain accurate data on factors associated with rehabilitation outcomes.

TBI is one of the most important public health problems in the world. Although the relationship between TBI and hypopituitarism has been known for a long time, neuroendocrine changes were investigated in detail recently. The prevalence of neuroendocrine abnormalities in patients with TBI is very high. Gonadotropin and GH deficiencies appear to be the most common defects. Although combative sports are very popular around the world, trauma due to sports is not generally considered as a cause of TBI in most of the epidemiological studies. All the studies regarding TBI in sports published so far in the literature based on neuropshycological or radiological assessment and no neuroendocrine changes were investigated. In a recent study, pituitary functions in amateur boxers have been investigated and it has been reported that boxing is a cause of TBI and isolated GH deficiency is very common among amateur boxers. It seems that acute or chronic head trauma in sports is a possible cause of hypopituitarism. In this review, current data regarding TBI in sports are discussed.

OBJECTIVE: To examine the prevalence of coronary artery disease (CAD) and its risk factors in people with posttraumatic vision loss (PTVL). DESIGN: Cross-sectional, controlled study. SETTING: The general community. PARTICIPANTS: Study groups included 82 subjects with PTVL, 49 siblings, 58 blind subjects with retinitis pigmentosa (RP), and the general population in Israel. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Sociodemographic and biomedical data collected by using a structured questionnaire and medical records. RESULTS: The prevalence of CAD among subjects with PTVL (24%) was 2 to 3 times higher than the control groups ( P <.001). However, the prevalence of the CAD risk factors in these subjects was similar to or lower than those in the control groups. For example, significantly fewer subjects with PTVL were physically inactive (16%) than patients with RP (55%, P <.01). The only variable that was significantly associated with CAD prevalence was the cause of blindness-that is, trauma versus disease; the odds of having CAD after traumatic vision loss was 3.75 times higher than after RP. CONCLUSIONS: People with PTVL exhibit elevated rates of risk for CAD similar to those of other groups with physical disability. The traumatic injury that caused vision loss might be an important factor underlying that risk.

BACKGROUND AND OBJECTIVES: Posterior pituitary function remains poorly investigated after traumatic brain injury (TBI). We report the results of a study designed to prospectively define the natural history of post-traumatic diabetes insipidus (DI) and syndrome of inappropriate antidiuretic hormone secretion (SIADH) using standard reliable methodology. DESIGN AND METHODS: 50 consecutive patients with severe or moderate TBI (initial Glasgow Coma Scale (GCS) score 3/15-13/15) were prospectively studied on three occasions: at the acute phase and at 6 months and at 12 months following TBI. In the acute phase, DI was diagnosed either by the presence of hypernatraemia in association with hypotonic polyuria or by the water-deprivation test (WDT) and, at 6 and 12 months by the WDT in all patients. Normative data on response to the WDT were obtained from healthy matched volunteers. Functional outcome was assessed using the Glasgow Outcome Scale (GOS). RESULTS: 13 patients (26%) had DI in the acute post-TBI phase, of whom nine patients recovered by 6 months and one additional patient recovered by 12 months. Of the remaining three patients with permanent DI, two had partial vasopressin deficiency. Acute-phase peak plasma osmolality correlated negatively with the initial GCS scores (r =-0.39, P = 0.005) and with the GOS scores (r =-0.45, P = 0.001). Seven patients had SIADH in the acute phase of TBI but none did at 6 or 12 months. No new cases of DI or SIADH were noted after the acute phase. CONCLUSION: This prospective study shows that posterior pituitary dysfunction is common following TBI. Most cases recover completely but there is an appreciable frequency of long-term DI which can be subtle and should be recognized and managed appropriately.

Knowledge of the relevant anatomy is important when developing a strategy for introducing screws into the lateral masses to secure internal fixation devices. This paper defines key bony landmarks and their relationship to critical neurovascular structures and identifies a location for safe placement of cervical articular pillar (lateral mass) screws. Measurements of anatomical landmarks in 10 spines from human cadavers aged 61 to 85 years were made by caliper and a metric ruler. Landmarks were the lateral facet line, rostrocaudal line, medial facet line, intrafacet line, and medial facet line-vertebral artery line. The average distances and ranges were recorded. Such great variance existed in measurements from spine to spine and within the same spine as to render averages clinically unreliable. Dissection revealed that division of the articular pillar into four quadrants leaves one, the superior lateral quadrant, under which there are no neurovascular structures; this may be considered the "safe quadrant" for placement of posterior screws and plates.

Ruboxistaurin is a selective protein kinase C beta inhibitor undergoing clinical investigation for treatment of diabetic microvascular complications. This study assessed a possible blood pressure (BP) interaction between ruboxistaurin and the exogenous nitric oxide donor, glyceryl trinitrate (GTN). Subjects (N=22) with chronic stable angina received placebo or ruboxistaurin 96 mg/day orally to steady state in a crossover design. Graded GTN (0, 5, 10, 20, 40, 80, and 120 mug/min) or 5% dextrose solution was then infused intravenously and BP was measured following each dose. Ruboxistaurin did not alter the slope of change in standing systolic BP (DeltasSBP/1n[GTN dose]) curve (P=0.272 analysis of covariance) or affect the DeltasSBP at the estimated GTN dose producing a 10-mm Hg reduction in sSBP from baseline on placebo (mean difference -0.9 mm Hg; 95% confidence of interval,-3.3-1.5). In conclusion, ruboxistaurin does not potentiate the acute BP-lowering effects of GTN.Clinical Pharmacology & Therapeutics advance online publication, 18 April 2007; doi:10.1038/sj.clpt.6100210.

Although reimplantation of severed limbs and other parts of the body has become prevalent in recent years, the questions of how best to preserve limbs for reimplantation and how to determine if a transected part is viable have not been fully answered. The problem of preservation involves combating direct anoxic damage to tissue as well as combating the changes in the vascular system that lead to the "no reflow phenomenon." Current information concerning kidney preservation as well as experimental and clinical reports on limb preservation are reviewed in this article, and suggestions are made for further investigations.

A new mouthprop for airway maintenance in the anesthetized rat, a vessel stabilizer and dilator, and a modification of the technique for end-to-end anastomosis in deep wounds are described.

Recently interest has been increasing in the anterior surgical approach for spinal cord decompression and bony stabilization of vertebral compression fractures. Our neurosurgical spine service routinely consults us to provide anterior operative exposure and wound closure for all levels of the thoracic and lumbar vertebral spine. Averaging about 30 exposures per year we have developed an excellent operative experience with these vertebral exposures. With no complete general surgery reference on anterior vertebral identified this summary of our "general surgical pearls" that we have learned and/or have developed should significantly aid other general and trauma surgeons who may be asked by their neurosurgical and/or orthopedic surgical colleagues for assistance with these operations.

Pharmacologic treatment may lead to diverse disturbances of water and electrolyte metabolism as adverse drug events. Diuretics are particularly likely to cause these complications typically including volume depletion, metabolic alkalosis, hyponatremia, and hypokalemia. Salt and water retention with edema formation is most frequently elicited by antihypertensives, steroid hormones, and nonsteroidal anti-inflammatory drugs. Drug-induced disorders of Na+ concentration may usually be attributed to altered antidiuretic hormone (ADH) effects, either as diabetes insipidus or as the syndrome of inappropriate ADH secretion. With hyper- and hypokalemia, redistribution between intra- and extracellular fluid as well as renal excretion play a role. Strategies to prevent these adverse drug reactions include careful consideration of risk factors and clinical and laboratory controls in the course of treatment.

Primary Acute Lung Injury (ALI) after lung resection (or "post-pneumonectomy pulmonary edema") is a rare form of acute respiratory failure characterized by dyspnea, hypoxemia, diffuse infiltrates on chest radiogram, and rapid evolution often unresponsive to therapy. ALI occurs almost exclusively following pneumonectomy, within 3 days from surgery and without a preceding cause. Factors implicated in its pathogenesis may include excessive fluid administration, alveolar injury during one-lung ventilation, pulmonary hypertension, and impaired lymph drainage. There is no specific therapy. Suggested measures in the perioperative care include the meticulous maintenance of physiological stability, judicious fluid restriction, and the limitation of ventilatory volumes and pressures.

OBJECT: Most craniocerebral injuries are caused by mechanisms of acceleration and/or deceleration. Traumatic injuries following progressive compression to the head are certainly unusual. The authors reviewed clinical and radiological features in a series of patients who had sustained a special type of cranial crush injury produced by the bilateral application of rather static forces to the temporal region. Their aim was to define the characteristic clinical features in this group of patients and to assess the mechanisms involved in the production of the cranial injuries and those of the associated cerebral and endocrine lesions found in this peculiar type of head injury. METHODS: Clinical records of 11 patients were analyzed with regard to the state of consciousness, cranial nerve involvement, findings on neuroimaging studies, endocrine symptoms, and outcome. Furthermore, an experimental model of bitemporal crush injury was developed by compressing a dried skull with a carpenter's vice. Seven of the 11 patients were 16 years old or younger. All patients presented with a characteristic clinical picture consisting of no loss of consciousness (six patients), epistaxis (nine patients), otorrhagia (11 patients), peripheral paralysis of the sixth and/or seventh cranial nerves (10 patients), hearing loss (five patients), skull base fractures (11 patients), pneumocephalus (11 patients), and diabetes insipidus (seven patients). Ten patients survived the injury and most recovered neurological function. CONCLUSIONS: Static forces applied to the head in a transverse axis produce fractures in the skull base that cross the midline structures without producing significant cerebral damage. Stretching of cranial nerves at the skull base explains the nearly universal finding of paralysis of these structures, whereas an increase in the vertical diameter of the skull accounts for the occurrence of diabetes insipidus in the presence of an intact function of the anterior pituitary lobe. The association of clinical, endocrine, and neuroimaging findings encountered in this peculiar type of head injury supports the idea that this subset of injured patients has a distinctive clinical condition, namely the syndrome of bitemporal crush injury to the head.

The purpose of our study was to evaluate the incidence and risk factors of SIADH (syndrome of inappropriate antidiuretic hormone) and diabetes insipidus after pituitary adenoma surgery in patients and report follow-up data collected in our department of endocrinology. This retrospective study included 78 patients seen in the last 5 years. Possible risk factors of SIADH and diabetes insipidus were studies: patient age and gender, type of secretion, tumor volume, surgical approach, presence of postoperative pituitary failure. The incidence of SIADH and diabetes insipidus were similar: 12.8%. We did not find any risk factor for SIADH associated with postoperative anterior pituitary failure. This study illustrates the importance of postoperative follow-up after pituitary adenoma surgery.

Individuals exhibiting precursor symptoms of diabetes mellitus or reaching diagnostic thresholds for diabetes are at increased risk of death due to cardiovascular disease (CVD). Moreover, patients with diabetes alone, as well as those who have diabetes paired with established CVD, remain undertreated for cardiovascular risk factors. The clear correlation between these disease processes has led many to speculate that they share common pathogenetic processes. Recent research has made it increasingly evident that the core metabolic defects that mark diabetes, including impaired glucose tolerance, insulin resistance, and proinflammatory and prothrombotic states, lead to endothelial dysfunction and accelerate atherogenesis. Moreover, increases in sympathetic tone with diabetes are associated with changes in cardiac and vascular function that lead to hypertension, left ventricular dysfunction, and cardiac autonomic neuropathy; such changes set the stage for arrhythmia, silent infarction, and sudden death. Furthermore, diabetes-related changes in metabolic and autonomic functioning, as well as increases in inflammatory and thrombotic signaling, compromise the ability of myocardial and vascular tissue to remodel after injury and to recover and sustain functionality. Because potentiation of atherogenesis and cardiac dysfunction occurs in the presence of early diabetic symptoms as well as in the established disease, early implementation of strategies to reduce cardiovascular risk factors and to slow diabetes progression may help to improve long-term outcomes for at-risk individuals. Such interventions may include well-established treatments for hypertension and dyslipidemia, diet improvements, weight loss, and exercise as well as novel pharmacologic interventions aimed at newly identified therapeutic targets.

This review focuses on the systemic complications of acromegaly. Mortality in this disease is increased mostly because of cardiovascular and respiratory diseases, although currently neoplastic complications have been questioned as a relevant cause of increased risk of death. Biventricular hypertrophy, occurring independently of hypertension and metabolic complications, is the most frequent cardiac complication. Diastolic and systolic dysfunction develops along with disease duration; and other cardiac disorders, such as arrhythmias, valve disease, hypertension, atherosclerosis, and endothelial dysfunction, are also common in acromegaly. Control of acromegaly by surgery or pharmacotherapy, especially somatostatin analogs, improves cardiovascular morbidity. Respiratory disorders, sleep apnea, and ventilatory dysfunction are also important contributors in increasing mortality and are beneficially advantaged by controlling GH and IGF-I hypersecretion. An increased risk of colonic polyps, which more frequently recur in patients not controlled after treatment, has been reported by several independent investigations, although malignancies in other organs have also been described, but less convincingly than at the gastrointestinal level. Finally, the most important cause of morbidity and functional disability of the disease is arthropathy, which can be reversed at an initial stage, but not if the disease is left untreated for several years.

Increased or reduced action of thyroid hormone on certain molecular pathways in the heart and vasculature causes relevant cardiovascular derangements. It is well established that overt hyperthyroidism induces a hyperdynamic cardiovascular state (high cardiac output with low systemic vascular resistance), which is associated with a faster heart rate, enhanced left ventricular (LV) systolic and diastolic function, and increased prevalence of supraventricular tachyarrhythmias - namely, atrial fibrillation - whereas overt hypothyroidism is characterized by the opposite changes. However, whether changes in cardiac performance associated with overt thyroid dysfunction are due mainly to alterations of myocardial contractility or to loading conditions remains unclear. Extensive evidence indicates that the cardiovascular system responds to the minimal but persistent changes in circulating thyroid hormone levels, which are typical of individuals with subclinical thyroid dysfunction. Subclinical hyperthyroidism is associated with increased heart rate, atrial arrhythmias, increased LV mass, impaired ventricular relaxation, reduced exercise performance, and increased risk of cardiovascular mortality. Subclinical hypothyroidism is associated with impaired LV diastolic function and subtle systolic dysfunction and an enhanced risk for atherosclerosis and myocardial infarction. Because all cardiovascular abnormalities are reversed by restoration of euthyroidism ("subclinical hypothyroidism") or blunted by beta-blockade and L-thyroxine (L-T4) dose tailoring ("subclinical hyperthyroidism"), timely treatment is advisable in an attempt to avoid adverse cardiovascular effects. Interestingly, some data indicate that patients with acute and chronic cardiovascular disorders and those undergoing cardiac surgery may have altered peripheral thyroid hormone metabolism that, in turn, may contribute to altered cardiac function. Preliminary clinical investigations suggest that administration of thyroid hormone or its analogue 3,5-diiodothyropropionic acid greatly benefits these patients, highlighting the potential role of thyroid hormone treatment in patients with acute and chronic cardiovascular disease.