Kashemi D. Rorie

Primary hyperparathyroidism, cognition, and health-related quality of life.

Objective:To provide a rigorous and critical review of studies in which formal neuropsychological (NP) testing and measurement of health-related quality of life (HRQL) were conducted pre- and post-parathyroidectomy for primary hyperparathyroidism (PHPT). These data contribute to the discussion on the utility of surgical intervention for nonclassic PHPT. Summary Background Data:PHPT is a complex endocrinopathy involving calcium metabolism and a potent hormone made by the parathyroid glands. Approximately 1.5% of Americans age 65 years and older, representing more than 3.9 million people, have PHPT, and the prevalence in postmenopausal women is estimated at 3.4%. Current National Institutes of Health guidelines for curative, surgical intervention of PHPT exclude 80% of patients with hyperparathyroid disease who have subjective neurobehavioral and physical symptoms that affect the quality of their lives. Methods:An electronic search was conducted of prospective studies in which cognitive functioning was measured with formal NP tests and HRQL was measured with valid and reliable instruments before and following parathyroidectomy for PHPT. Results:In studies conducted pre- and post-parathyroidectomy for PHPT, 6 small studies of cognitive functioning report inconsistent findings; however, 7 well-designed studies of HRQL report improvement across multiple domains following surgery. Conclusions:Surgical treatment of PHPT is a viable option for patients with laboratory diagnosed, “nonclassic” PHPT. Formal NP testing and evaluation of HRQL are useful tools that may assist physicians in choosing whom to refer for parathyroidectomy. Further longitudinal study of NP functioning and HRQL in patients with laboratory diagnosed PHPT is warranted.

Verbal Pragmatics Following Unilateral Stroke: Emotional Content and Valence

Verbal pragmatic aspects of discourse production were examined in 16 right brain-damaged (RBD), 16 left brain-damaged (LBD), and 16 normal control right-handed adults. The facilitation effect of emotional content, valence hypothesis, and relationship between pragmatics and emotion were evaluated. Participants produced monologues while recollecting emotional and nonemotional experiences. Transcribed monologues were rated for appropriateness on 6 pragmatic features: conciseness, lexical selection, quantity, relevancy, specificity, and topic maintenance. Overall, brain-damaged groups were rated as significantly less appropriate than normals. Consistent with the facilitation effect, emotional content enhanced pragmatic performance of LBD aphasic participants yet suppressed performance of RBD participants. Contrary to the valence hypothesis, RBD participants were more impaired for positive emotions and LBD participants for negative emotions. Pragmatic appropriateness was not strongly correlated with a measure of emotional intensity.

Clinical trial of the neuroprotectant clomethiazole in coronary artery bypass graft surgery: a randomized controlled trial.

BACKGROUND The neuroprotective property of clomethiazole has been demonstrated in several animal models of global and focal brain ischemia. In this study the authors investigated the effect of clomethiazole on cerebral outcome in patients undergoing coronary artery bypass surgery. METHODS Two hundred forty-five patients scheduled for coronary artery bypass surgery were recruited at two centers and prospectively randomized to clomethiazole edisilate (0.8%), 225 ml (1.8 mg) loading dose followed by a maintenance dose of 100 ml/h (0.8 mg/h) during surgery, or 0.9% NaCl (placebo) in a double-blind trial. Coronary artery grafting was completed during moderate hypothermic (28-32 degrees C) cardiopulmonary bypass. Plasma clomethiazole was measured at several intervals during and up to 24 h after the end of infusion. A battery of eight neuropsychological tests was administered preoperatively and repeated 4-7 weeks after surgery. Analysis of the change in neuropsychological test scores from baseline was used to determine the effect of treatment. RESULTS Neuropsychological assessments were completed in 219 patients (110 clomethiazole; 109 placebo). The mean plasma concentration of clomethiazole during surgery was 66.2 microm. There was no difference between the clomethiazole and placebo group in the postoperative change in neuropsychological test scores. CONCLUSION Clomethiazole did not improve cerebral outcome following coronary artery bypass surgery.

Neurophysiologic monitoring and outcomes in cardiovascular surgery

The first step to make in improving neurologic outcome is to recognize and accept neurologic injury occurs in all patient groups undergoing CPB. Fortunately, that stage has now been passed. Accurate detection and documentation of the incidence of brain injury is the next progression. At the same time, the cause of the injury needs to be established. Since the introduction of CPB, numerous improvements and refinements have been achieved, making it the acceptable, everyday clinical tool that has enabled the development of cardiac surgery. Despite these improvements, CPB-related morbidity persists. The advent of new technologic advances drives the quest for new techniques. New protective strategies for many end organs, including the heart, kidney, and brain, are evolving. No organ system should be viewed in isolation; otherwise, organ-specific protective strategies may arise in conflict. A strategy that confers absolute myocardial protection would be ideal, but at what cost to the protection of the kidneys, intestines, and brain? A neuroprotective strategy would ideally eliminate brain injury and be beneficial for all organs. The only way to continue to make progress is by the scientific evaluation of new techniques. The use of appropriate monitoring and outcome measures is fundamental to this process.

Preliminary report: Functional MRI of the brain may be the ideal tool for evaluating neuropsychologic and sleep complaints of patients with primary hyperparathyroidism

BackgroundThe incidence, pattern, and severity of sleep disturbance and cognitive dysfunction has not been well characterized for patients with primary hyperparathyroidism (PHPT). There is no agreement on the mechanism of the development or resolution of such symptoms, and in no previous study has cerebral activity been functionally assessed and change documented following surgical cure of patients with PHPT.MethodsWe undertook a prospective analysis to obtain pilot data on 6 patients with PHPT. Functional magnetic resonance imaging (fMRI), formal neuropsychologic (NP) tests, and health-related quality of life (HRQL) measures that included sleep assessments were performed on patients before and after parathyroidectomy. Changes in cortical activation under both conflict and neutral conditions (distracting tasks) were recorded.ResultsFunctional MRI demonstrated postoperative changes in medial prefrontal cortex activity during cognitive processing of conflict and nonconflict tasks. Further postoperative changes were noted in the dorsolateral prefrontal cortex and parietal cortex with shifts in activations. In addition to the fMRI findings, the patients demonstrated improvements in sleep and social behavior. They tended to experience less fatigue and their processing speed on cognitive tests improved.ConclusionsThese data support the feasibility and willingness of patients with PHPT to undergo fMRI assessment. Preliminary findings reflected a generalized improvement in processing efficiency postoperatively compared with a patient’s preoperative state, and the HRQL measures showed improved sleep. These findings mirror those expected with sleep dysfunction. Longitudinal assessment with advanced brain imaging technology, neuropsychological (NP), and sleep evaluations is warranted to further explore cognitive, sleep, and HRQL improvement after parathyroidectomy.

Microemboli and Neurologic Dysfunction After Cardiovascular Surgery

Several recent studies have shown that cardiac surgery poses significant risks for negative neurologic and neu ropsychological outcome. Death and major stroke have become uncommon consequences of cardiac surgery, but more than two-thirds of the patients show evidence of neuropsychological dysfunction postoperatively. The mechanisms contributing to postcardiopulmonary bypass neuropsychological deficits are uncertain, and potentially there are many possible causative factors that may play a significant role in perioperative neuro logic injury. However, two major interrelated factors, hypoperfusion and emboli, are suggested as probable culprits. Perfusion is important because the level of global and focal cerebral blood flow during periods of high embolic risk will determine the amount of brain embolization as well as the localization of the lesions. Ultrasonically detected macroemboli have been re ported to be the best predictor of neurobehavioral outcome. Microemboli found in autopsy specimens may also be important predictors of negative outcome. The relationship between microemboli and changes in brain function, as detected by magnetic resonance spectroscopy, may provide further insight into the prob ability of the clinical expression of a neurobehavioral dysfunction after cardiac surgery. The incidence and severity of neuropsychological defi cits after cardiac surgery appear to be related to the delivery of macroemboli. The composition of the embo lus may be the most important determinant of the level and volume of focal injury, but the time of occurrence (ie, rewarming) of macroemboli during cardiopulmo nary bypass may also be important in determining the effect of emboli on neuropsychological outcome. How ever, the key variable in the manifestation of neurobe havioral dysfunction remains the location of the lesion site.

Psychometric Aspects of Verbal Pragmatic Ratings

This study examined the psychometric aspects of a verbal pragmatic rating scale. The scale contained six pragmatic features (i.e., Conciseness, Lexical Selection, Quantity, Relevancy, Specificity, and Topic Maintenance) based on Grices cooperative principles. Fifteen right brain-damaged (RBD), 15 left brain-damaged (LBD), and 16 healthy normal control (NC) right-handed adult participants produced narratives while recollecting emotional and nonemotional experiences. Naive raters evaluated each pragmatic feature for appropriateness on a 5-point Likert scale. When reliability was examined, the overall internal consistency of the pragmatic scale was extremely high (alpha =.96). Factor analysis was conducted to examine the theoretical relations among the six pragmatic features. Three meaningful factors involving discourse content, conceptual unity, and parsimony were identified. Findings are discussed in light of Grices model and the construct validity of the scale.

The neuropsychologic deterioration seen in the placebo group may have been a result of rigorous exclusion criteria.

To the Editor:—In “Clinical Trial of the Neuroprotectant Clomethiazole in Coronary Artery Bypass Graft Surgery: A Randomized Controlled Trial,” by Kong et al., the authors assessed neuropsychologic deterioration following bypass surgery with cardiopulmonary bypass. They are to be congratulated for the rigorous design of their experiment and their willingness to report a “negative” result. Their topic is so important to our patients that model articles such as this, no matter what the result, are of the utmost significance. The authors monitored embolic load during surgery using Doppler ultrasound of the common carotid or middle cerebral artery. Using this measure, they found no difference between the embolic loads in the study and the control groups, nor, as noted, was the neuropsychologic outcome different between the groups. The authors comment, however, that, “the [neuropsychological] deterioration seen in the placebo group was less than anticipated at the planning stage. This may have been a result of the rigorous exclusion criteria. As a result, the study may have been underpowered.” In other words, both groups had an equivalent and better than expected outcome. If embolic load during coronary surgery using cardiopulmonary bypass is related to surgical technique, then this unexpectedly good outcome may be related to the presence of Doppler ultrasound monitoring. At least one article has suggested that surgeons, in the presence of a device that monitors emboli, improve their technique in an effort to avoid creating these emboli. I would say that this explanation is at least as compelling as the idea that the study was underpowered and that Clomethiazole actually is protective.