Pituitary dysfunction due to sports-related traumatic brain injury

Pituitary - After traumatic brain injury was accepted as an important etiologic factor of pituitary dysfunction (PD), awareness of risk of developing PD following sports-related traumatic brain...     

The role of autoimmunity in pituitary dysfunction due to traumatic brain injury

Purpose

Traumatic brain injury (TBI) is one of the most common causes of mortality and long-term disability and it is associated with an increased prevalence of neuroendocrine dysfunctions. Post-traumatic hypopituitarism (PTHP) results in major physical, psychological and social consequences leading to impaired quality of life. PTHP can occur at any time after traumatic event, evolving through various ways and degrees of deficit, requiring appropriate screening for early detection and treatment. Although the PTHP pathophysiology remains to be elucitated, on the basis of proposed hypotheses it seems to be the result of combined pathological processes, with a possible role played by hypothalamic–pituitary autoimmunity (HPA). This review is aimed at focusing on this possible role in the development of PTHP and its potential clinical consequences, on the basis of the data so far appeared in the literature and of some results of personal studies on this issue.

Methods

Scrutinizing the data so far appeared in literature on this topic, we have found only few studies evaluating the autoimmune pattern in affected patients, searching in particular for antipituitary and antihypothalamus autoantibodies (APA and AHA, respectively) by simple indirect immunofluorescence.

Results

The presence of APA and/or AHA at high titers was associated with an increased risk of onset/persistence of PTHP.

Conclusions

HPA seems to contribute to TBI-induced pituitary damage and related PTHP. However, further prospective studies in a larger cohort of patients are needed to define etiopathogenic and diagnostic role of APA/AHA in development of post-traumatic hypothalamic/pituitary dysfunctions after a TBI.

     

Systemic lupus erythematosus with myocardial dysfunction due to microvasculopathy

A 25-year-old Japanese woman with systemic lupus erythematosus (SLE) had myocardial dysfunction. Heart catheterization showed normal coronary anatomy. Left ventricular cineangiography demonstrated hypokinesis in the anterior and posterior segments. Myocardial scintigraphy revealed patchy defects in the regions unrelated to coronary arteries. These data suggested that the myocardial dysfunction was due to microvasculopthy. In addition, it was speculated that the microvasculopathy was caused by vasculitis but not by thrombi, since she did not have antiphospholipid syndrome. In support of this speculation, corticosteroid therapy without any thrombolytic agents was effective. This report represents the first live patient with SLE in whom myocardial dysfunction due to microvasculopathy has been demonstrated.     

Reversal of chronic ischemic myocardial dysfunction after transluminal coronary angioplasty

From a cohort of patients referred for elective transluminal coronary angioplasty, a subset of patients was evaluated to determine whether revascularization using coronary angioplasty could salvage chronically ischemic myocardium. Reversible chronic ischemic left ventricular dysfunction was identified by a severe wall motion abnormality at rest and at least one of the following: 1) persistent angina pectoris; 2) postextrasystolic ventricular contraction potentiation of motion in the asynergic zone on baseline ventriculogram; and 3) thallium-201 uptake in the asynergic zone. Twelve patients were identified as having reversible chronic ischemia and underwent coronary angioplasty. Their mean age was 63 +/- 11 years and duration of symptoms 8.3 +/- 9.7 weeks. Immediate pre- and postangioplasty left ventriculograms were obtained. Regional wall motion was analyzed using a radial axis model, and global ejection fraction was calculated. After angioplasty, tension development (heart rate-systolic pressure product) increased in the absence of an increase in left ventricular end-diastolic pressure. Global ejection fraction increased from 46 +/- 20 to 62 +/- 19% (p less than 0.005). The percent of left ventricular diastolic perimeter showing asynergy decreased from 29 +/- 11 to 10 +/- 13% (p less than 0.005). During follow-up ranging from 6 to 51 months, sudden death occurred in one patient who had had no improvement in wall motion after angioplasty, repeat angioplasty was performed in three patients and eight patients remained asymptomatic. Application of easily obtainable clinical data identifies a subset of patients with chronically ischemic myocardium. Coronary angioplasty in such patients is useful in salvaging hibernating myocardium.     

Relation of coronary microvascular dysfunction in hypertrophic cardiomyopathy to contractile dysfunction independent from myocardial injury

We studied the spatial relations among hyperemic myocardial blood flow (hMBF), contractile function, and morphologic tissue alterations in 19 patients with hypertrophic cardiomyopathy (HC). All patients were studied with oxygen-15 water positron emission tomography during rest and adenosine administration to assess myocardial perfusion. Cardiovascular magnetic resonance was performed to derive delayed contrast-enhanced images and to calculate contractile function (E(cc)) with tissue tagging. Eleven healthy subjects underwent similar positron emission tomographic and cardiovascular magnetic resonance scanning protocols and served as a control group. In the HC group, hMBF averaged 2.46 ± 0.91 ml/min/g and mean E(cc) was -14.7 ± 3.4%, which were decreased compared to the control group (3.97 ± 1.48 ml/min/g and -17.7 ± 3.2%, respectively, p <0.001 for the 2 comparisons). Delayed contrast enhancement (DCE) was present only in patients with HC, averaging 6.2 ± 10.3% of left ventricular mass. In the HC group, E(cc) and DCE in the septum (-13.7 ± 3.6% and 10.2 ± 13.6%) significantly differed from the lateral wall (-16.0 ± 2.8% and 2.4 ± 5.9%, p <0.001 for the 2 comparisons). In general, hMBF and E(cc) were decreased in segments displaying DCE compared to nonenhanced segments (p <0.001 for the comparisons). In the HC group, univariate analysis revealed relations of hMBF to E(cc) (r = -0.45, p <0.001) and DCE (r = -0.31, p <0.001). Multivariate analysis revealed that E(cc) was independently related to hMBF (beta -0.37, p <0.001) and DCE (beta 0.28, p <0.001). In conclusion, in HC hMBF is impaired and related to contractile function independent from presence of DCE. When present, DCE reflected a progressed disease state as characterized by an increased perfusion deficit and contractile dysfunction.     

Cell therapy in patients with left ventricular dysfunction due to myocardial infarction

Objectives: The purpose of this study was to determine the impact of autologous transplantation of mononuclear bone marrow cells on myocardial function in patients with left ventricular (LV) dysfunction due to an acute myocardial infarction. Methods: The randomized study included 82 patients with a first acute myocardial infarction treated with a stent implantation. This presentation is a subanalysis of 47 patients with left ventricular dysfunction–EF (ejection fraction) ≤ 40%. Group H patients (n = 17) received higher number (100,000,000) of cells; Group L patients (n = 13) received lower number (10,000,000) of cells. The patients of control Group C (n = 17) were not treated with cells. The Doppler tissue imaging and single photon emission computed tomography were performed before cell transplantation and 3 months later. Results: At 3 months of follow‐up, the baseline EF of 35%, 36%, 35% in Groups H, L, and C increased by 6% (P < 0.01 vs. baseline), 5% (P < 0.01 vs. baseline), and 4% (P = NS vs. baseline), respectively, as assessed by single photon emission computed tomography (P = NS between groups). The baseline number of akinetic segments of 6.9, 7.0, and 6.2 in H, L, and C groups decreased by 1.7 (P < 0.01 vs. baseline), 1.5 (P < 0.01 vs. baseline), and 0.7 (P = NS vs. baseline, P = NS between groups), respectively, as demonstrated by echocardiography. Conclusion: In our study, the statistically important effect of transplantation of mononuclear bone marrow cells on myocardial function was not found. Only an insignificant trend toward the improvement of global LV EF fraction was found at 3‐month follow‐up.     

Posterior pituitary dysfunction after traumatic brain injury

Disorders of water balance are well recognized after traumatic brain injury (TBI), but there are no reliable data on their true prevalence in post-TBI patients. We aimed to evaluate the prevalence of posterior pituitary dysfunction in a large cohort of survivors of TBI. One hundred two consecutive patients (85 males) who suffered severe or moderate TBI were evaluated for diabetes insipidus (DI) at a median of 17 months (range 6-36 months) after the event, using the 8-h water deprivation test (WDT). Their results were compared against normative data obtained from 27 matched, healthy controls. Patients' medical records were retrospectively reviewed for the presence of abnormalities of salt and water balance in the immediate post-TBI period. Twenty-two patients (21.6%) developed DI in the immediate post-TBI period (acute DI group), of whom five had abnormal WDT on later testing. In total, seven patients (6.9%) had abnormal WDT (permanent DI group), five of whom had partial DI. Patients in the acute and permanent DI groups were more likely to have more severe TBI, compared with the rest of the cohort (P < 0.05). In the immediate post-TBI period, 13 patients (12.9%) had syndrome of inappropriate secretion of antidiuretic hormone, which persisted in one patient, and one other patient developed cerebral salt wasting. Diabetes insipidus and syndrome of inappropriate secretion of antidiuretic hormone were common in the immediate post-TBI period. Permanent DI was present in 6.9% of patients who survived severe or moderate TBI, which is higher than traditionally thought. Identification of patients with partial posttraumatic DI is important because appropriate treatment may reduce morbidity and optimize the potential for recovery.     

Ataxia due to injury of the cortico-ponto-cerebellar tract in patients with mild traumatic brain injury

Introduction:The cortico-ponto-cerebellar tract (CPCT) is involved in coordination of movement; injury of the CPCT can therefore be accompanied by ataxia. In this study, using diffusion tensor tractography (DTT), we investigated injury of the CPCT in patients with mild traumatic brain injury (TBI).Methods:We recruited 45 consecutive patients with ataxia following mild TBI and 20 normal control subjects. The score of assessment and rating of ataxia (SARA) was used to evaluate of ataxia. The patients were classified into 2 groups based on the SARA; patient group A had with post-traumatic ataxia and patient group B had without post-traumatic ataxia. The fractional anisotropy (FA) value and fiber number (FN) of the CPCT was measured.Results:Significant differences were observed in the FA and FN values of the CPCT between patient group A and the control group and between patient groups A and B (P < .05). In addition, a significant difference was observed in the FA value only of the CPCT between patient group B and the control group (P < .05). However, no significant difference was observed in the FN value of the CPCT between patient group B and the control group (P > .05).Conclusion:By using DTT, injury of the CPCT was demonstrated in patients who showed ataxia following mild TBI. These results suggest that DTT would be useful for evaluation of the CPCT in patients with ataxia after mTBI because mTBI usually does not show any abnormalities on conventional brain MRI.     

重视急性脑损伤后非神经系统器官损伤和功能障碍的防治

严重急性脑损伤后常并发心、肺和胃肠等颅外非神经器官损伤和功能障碍,是影响急性脑损伤患者早期死亡的主要因素。本文总结了急性脑损伤后心、肺和胃肠并发症的发生率和危害、病理生理和防治策略,以引起临床医师的重视,加强急性脑损伤后颅外非神经器官损伤和功能障碍的防治。     

Reduced myocardial injury due to exogenous oxidants in pressure induced heart hypertrophy

Changes in myocardial function, structure, high energy phosphates and lipid peroxide content were examined in hypertrophied hearts exposed to partially reduced forms of oxygen (PRFO) in an ex vivo system. Heart hypertrophy in rats was produced by narrowing of the abdominal aorta for 6, 12, 24, and 48 weeks. During this period, a stable hypertrophy and hyperfunction with no clinical signs of heart failure is reported to be accompanied by an increase in myocardial superoxide dismutase and glutathione peroxidase activities and a decrease in lipid peroxide content (Gupta and Singal, Circ. Res. 64:398–406, 1989). A 10-min perfusion of sham control hearts with PRFO caused a significant decline in the developed force, ± dF/dt and a rise in resting tension. These changes due to PRFO were significantly less in all groups of hypertrophied hearts. PRFO produced 80.8 ± 4.2 % increase in malondialdehyde (MDA) content in sham controls, while different groups of hypertrophied hearts showed significantly lesser increase (range 45–50 %) in MDA. PRFO resulted in loss of myocardial ATP and CP in control and hypertrophied groups, but this loss was significantly less in all groups of hypertrophied hearts. Both quantitative and qualitative ultrastructural changes due to PRFO were also found to be less in hypertrophied hearts. There were no significant differences among 6- to 48-week hypertrophy groups in their response to PRFO. The study suggests that endogenous antioxidants may serve as putative stabilizers of myocardial subcellular as well as contractile functions against oxidative stress.     

The history of pituitary dysfunction after traumatic brain injury

Pituitary - To estimate the total number of articles on traumatic brain injury (TBI)-related hypopituitarism and patients (including children and adolescents) with such disorder that were published...     

Anterior pituitary dysfunction in survivors of traumatic brain injury

Recent data suggest that anterior pituitary dysfunction after traumatic brain injury (TBI) is common. We sought to confirm the results of earlier studies in a larger cohort of patients with dynamic testing of pituitary function.We studied 102 consecutive TBI survivors (85 males; median age 28, range 15-65 yr) who had survived severe or moderate TBI (initial Glasgow Coma Scale score 3-13) at a median of 17 months (range 6-36) post event. GH and ACTH reserves were initially assessed using the glucagon stimulation test (GST). Normative data on GH and cortisol responses to the GST were obtained from 31 matched healthy controls. Patients with subnormal GH or cortisol responses were further evaluated, using the insulin tolerance test (ITT) or arginine + GHRH test for GH assessment and the ITT or 250-microg short synacthen test for the assessment of ACTH reserve. Patients were considered to be GH or ACTH deficient if they failed both the GST and the second provocative test. Baseline thyroid function, prolactin, IGF-I, gonadotropins, testosterone, or estradiol was performed in all patients and compared with local reference ranges.In controls, normal response to the GST was a stimulated GH peak of greater than 5 microg/liter and cortisol peak greater than 450 nmol/liter (16 microg/dl). Eighteen TBI patients (17.6%) had GH response to the GST less than 5 microg/liter, 11 of whom also failed the ITT or the arginine + GHRH tests. GH-deficient patients had significantly higher body mass index (P = 0.003), and lower IGF-I concentrations (P < 0.001), than GH-sufficient patients. Twenty-three patients (22.5%) had cortisol responses to GST less than 450 nmol/liter, 13 of whom also failed the ITT or short synacthen test. GH or ACTH deficiencies were not related to age, Glasgow Coma Scale score, or the presence of other pituitary hormone abnormalities (P > 0.05). Twelve patients (11.8%) had gonadotropin and one (1%) had thyrotrophin deficiencies. Twelve patients (11.8%) had hyperprolactinemia. Twenty-nine patients (28.4%) had at least one anterior pituitary hormone deficiency.This is the largest study, to date, of hypopituitarism after TBI and confirms a high prevalence of undiagnosed anterior pituitary hormone abnormalities in survivors of TBI. Hypopituitarism is a treatable cause of morbidity after TBI. In addition to conventional pituitary hormone replacement, the potential of GH treatment to enhance recovery needs to be examined in a prospective study.     

Reversal of brain dysfunction with UV-A1 irradiation in a patient with systemic lupus

Low-dose ultraviolet A-1 (UV-A1; 340-400 nm) bodily irradiation significantly reduces clinical manifestations of systemic lupus erythematosus (SLE). As neuropsychiatric-like symptoms respond prominently, a single patient was selected to undergo positron emission tomography (PET) before and after therapy to determine the effects of the therapy on the brain. The functional changes in 18F-deoxyglucose uptake as determined by PET imaging in this SLE patient indicated that improvement in brain function paralleled the reversal of cognitive deficits noted after the administration 160 kJ of bodily UV-A1 irradiation administered three times a week. Also of interest is that the UV-A1 irradiation, for the first time, ameliorated discoid lupus rashes, presumably due to a systemic action, as the lesions were for the first time covered during therapy.     

心肌酶谱和肌红蛋白在早期反映射频消融心肌损伤中的评价

目的：比较肌红蛋白与心肌酶谱在反映心肌损伤中的敏感性，探讨心肌损伤与射频消融能量之间的关系。方法：73例室上性心动过速（室上速）患者分别在血管穿刺术后、心内电生理检查后，射频消融术后即刻和术后第3天检测心肌酶学指标与肌红蛋白，计算各个亚组的消融总能量。结果：射频肖融术后，AST、LDH、HBDH和Mb浓度升高，且以Mb的升高幅度最大，LDH次之，而CK及CK－MB在整体上没有差别。术后第3天，所有指标均恢复到基线水平。LDH、HB－DH和Mb的升高主要表现在右侧旁路组和AVNRT组中，而且血浆水平与各个亚组的射频消融总能量成正比，结论：心肌酶学指标可以反映射频肖融产生的心肌损伤，早期反映射频消融后心肌损伤的指标以肌红蛋白最敏感，LDH次之，然后为HBDH和AST，而CK和CK－MB变化不大；心肌酶学指标的升高程度与消频消融总量成正比，右心消融（右侧旁道和AVNRT）的心肌损伤程度重于左心消融（左侧旁道）。