Nerve tissue protein S-100 and neurone-specific enolase concentrations in cerebrospinal fluid and blood during carotid endarterectomy.

Nerve tissue protein S-100 and neurone-specific enolase levels in serum were studied in 10 patients before, during and for 2 days after elective carotid endarterectomy performed under general anaesthesia and using a Javid Shunt. In six patients, simultaneous cerebrospinal fluid samples were also obtained. Serum nerve tissue protein S-100 was normal throughout the operation, but in one patient with severe hypertension, levels increased to 1.38 microg. l-1 at 1 h postoperatively. Two patients showed an increase in cerebrospinal fluid nerve tissue protein S-100 during clamping: these patients also had neurological deficits at 6 months. Serum neurone-specific enolase increased from 5.8 to 9.3 microg.l-1 during shunting while cerebrospinal fluid neurone-specific enolase did not change. Uncomplicated carotid endarterectomy does not produce cerebral damage as measured by serum nerve tissue protein S-100; cerebrospinal fluid nerve tissue protein S-100 may be more sensitive for minor cerebral damage. Neurone-specific enolase appeared to be nonspecific. The lack of correlation between the neuroproteins may need to be explained before relying on these simple assays as diagnostic indicators of cerebral ischaemia.

Transanal MR imaging after repair of anorectal anomalies in children: appearances in pull-through versus posterior sagittal reconstructions.

OBJECTIVE: Our objective was to use transanal MR imaging to compare the anatomic appearance of the components of the anal sphincter and the pattern of scarring after a pull-through perineoplasty versus a posterior sagittal anorectoplasty. SUBJECTS AND METHODS: Sixteen children ranging in age from 10 months to 15 years (mean, 10 years) were imaged using transanal receiver coils appropriate to the size of the child. Five had low, four intermediate, and seven high anomalies. Seven had undergone a transanal pull-through procedure, and nine had undergone posterior sagittal reconstruction. The integrity of the muscles was assessed on T1-weighted and short inversion time inversion recovery transverse and coronal images using a qualitative MR imaging score. The pattern of scarring was also assessed. RESULTS: In the transanal pull-through group, four of seven patients showed external sphincter deficiency. A circumferential low-signal-intensity band was seen inferior to the sphincter in six patients. All posterior sagittal reconstructions had a long posterior midline scar. Five of nine patients showed external sphincter deficiency, whereas a further two had internal sphincter deficiency. No differences were seen in MR imaging scores for each operative procedure for all grades of severity of anorectal anomaly. However, a comparison between high and intermediate anomalies showed a small improvement in MR imaging score using the transanal pull-through procedure (Mann-Whitney U test = 3, p < .03). Manometric pressures obtained in 13 patients were poor. CONCLUSION: Transanal MR imaging identifies focal defects and patterns of scarring of the anal sphincter complex in infants and children and provides valuable information about individual muscle components.

Time course of neurone-specific enolase and S-100 protein release during and after coronary artery bypass grafting.

Serum neurone-specific enolase (NSE) and S-100 protein are well established as markers of cerebral injury, and have been used as markers of neuronal and glial cell damage, respectively, after cardiac surgery with cardiopulmonary bypass (CPB), but the speed of their increase during CPB has not been studied. Therefore, we have investigated the time course of NSE and S-100 release during and after CPB. We studied 18 adult patients undergoing elective coronary artery bypass grafting (CABG). Standard hypothermic (32 degrees C) pulsatile bypass with membrane oxygenation was used. Blood samples were obtained at induction, before bypass, before rewarming, at the end of rewarming, 10 min, 1 h and 8 h after bypass and 1, 2 and 3 days after surgery. NSE and S-100 were assayed using immunoradiometric assay kits (Sangtec Medical). NSE and S-100 release followed similar time courses. Both increased sharply during bypass, reached peak concentrations at the end of rewarming (mean 25.55 (SEM 2.79) and 1.65 (0.23) microgram litre-1, respectively), had decreased significantly by the end of operation and returned to pre-bypass concentrations by the second day after surgery. No patient developed a major neurological deficit. When using NSE and S-100 assays to study cerebral dysfunction in relation to CPB, postoperative samples miss peak (end-bypass) concentrations, and studies should be designed to include intraoperative samples.

Localised cerebral phosphorus-31 MR spectroscopy in man before and immediately after coronary bypass surgery with hypothermic cardiopulmonary bypass.

Coronary artery bypass surgery classically is undertaken with hypothermic cardiopulmonary bypass (CPB). There is a high incidence of neuropsychological defects after cardiac surgery, which may be related to cerebral ischaemia during the rewarming period. In this study, phosphorus-31 magnetic resonance spectroscopy (31P MRS) was used to identify changes in cerebral 31P MR spectra in patients before and immediately after hypothermic CPB. Four neurologically normal patients undergoing coronary artery bypass surgery were studied. Localised cerebral 31P MRS (TR 5000 ms) was performed at 1.5 Tesla on each patient the day before and within an hour of completion of surgery. Peak areas for phosphomonoesters (PME), inorganic phosphate (Pi), phosphodiesters (PDE), phosphocreatine (PCr) and beta ATP (betaATP) were measured. Metabolite peak area ratios and relative percentages of each 31P MR resonance with respect to the total 31P MR signal were calculated. In the post-operative MR spectra, each patient displayed a marked reduction in Pi/betaATP and increase in PCr/Pi ratios. Spectral changes in percentage metabolite signals following surgery varied both in magnitude and pattern between patients. In two patients there was an increased postoperative percentage PME and percentage PCr with a decrease in percentage betaATP. The converse was found in the other two patients, but all four subjects displayed a markedly decreased percentage Pi after CPB. These metabolite changes probably reflect rebound phosphorylation in the immediate postoperative period and suggest increased metabolic activity in the hyperaemic brain on rewarming from hypothermic CPB.

Magnetic resonance spectroscopy of high-energy phosphates and lactate immediately after coronary artery bypass surgery.

Hypothermic cardiopulmonary bypass (CPB) is associated with a high incidence of neuropsychological defects, marked cerebral swelling immediately after surgery and jugular bulb desaturation during rewarming. This suggests cerebral ischaemia may occur, but evidence is indirect. We studied four patients with 31P magnetic resonance spectroscopy (MRS) and four with 1H MRS before and immediately after coronary surgery. There was no visible lactate in 1H MR spectra. In 31P MR spectra, the ratio of phosphocreatine to adenosine triphosphate was maintained (before: 2.13 +/- 0.86 vs after: 2.57 +/- 1.31; mean +/- 1 SD) and there was no intracellular acidosis (intracellular pH: 7.1 +/- 0.04 vs 7.16 +/- 0.08), while phosphocreatine/inorganic phosphate was increased immediately after the operation (2.92 +/- 0.37 vs 6.39 +/- 2.67, p = 0.03). This suggests rebound replacement of energy stores following recovery from temporary cerebral ischaemia during CPB: intra-operative studies would be needed to test this hypothesis further.

Cerebral swelling after normothermic cardiopulmonary bypass.

BACKGROUND: Marked cerebral swelling visible on magnetic resonance images has been found immediately after hypothermic (28 degrees C) cardiopulmonary bypass. The mechanism is unknown, but indices of cerebral ischemia are seen during rewarming from hypothermic bypass that are not present with normothermic bypass (37 degrees C). METHODS: T1-weighted and fluid-attenuated inversion recovery magnetic resonance images were taken of seven patients undergoing routine coronary artery bypass surgery before, 1 h, and 7 days after the operation using normothermic bypass. RESULTS: Marked cerebral swelling was seen in fluid-attenuated inversion recovery images in five of seven patients 1 h after bypass. Scans in four patients taken 7 days after bypass showed that the cerebral swelling had returned to normal. There was no change in cerebral ventricular size, and all patients had uncomplicated postoperative courses. CONCLUSIONS: Normothermic bypass is followed by acute postoperative cerebral swelling. However, the amount of swelling was similar to that found in a previous study after hypothermic bypass. The mechanism of swelling is still obscure, and its relation to neurologic outcome is unknown.

Neurone-specific enolase and Sangtec 100 assays during cardiac surgery: Part I--The effects of heparin, protamine and propofol.

Neurone-specific enolase (NSE) and Sangtec 100 (S-100) (Sangtec Medical, Sweden) assays are designed for clotted samples, but when studying cerebral damage following cardiac surgery, perioperative samples will contain heparin and/or protamine. The lipid emulsion propofol is also frequently used during cardiac surgery and could affect the assays. We, therefore, studied the effects of heparin, protamine and propofol on the accuracy of NSE and S-100 assays in five healthy patients. Blood samples were taken and divided into four groups: normal saline was added to group A; heparin to group B; heparin followed by protamine to group C; and propofol to group D. NSE and S-100 concentrations were measured for all samples. Neither heparin, protamine nor propofol affected the accuracy of S-100 and NSE assays; therefore, samples can be taken throughout operations involving cardiopulmonary bypass without influencing the results.

Neurone-specific enolase and Sangtec 100 assays during cardiac surgery: Part II--Must samples be spun within 30 min?

Sangtec 100 (S-100) (Sangtec Medical, Sweden) and neurone-specific enolase (NSE) assays are showing promise in the assessment of cerebral damage following cardiopulmonary bypass (CBP). The manufacturer's instructions state, however, that samples must be spun and frozen within 30 min, which is inconvenient for serial studies. We, therefore, investigated whether strong blood samples at room temperature (RT) or 4 degrees C for up to 48 h affected the measured levels. Blood samples were taken before and after CBP in six patients and stored for 15 min, 4, 8, 24 or 48 h at RT or 4 degrees C. S-100 and NSE levels did not alter in either 'before surgery' or CPB samples when stored for up to 48 h at 4 degrees C. There was a small, nonsignificant rise when stored at RT. Samples may, therefore, be collected throughout long operations or stored overnight without affecting NSE or S-100 plasma levels.

Neurone-specific enolase and Sangtec 100 assays during cardiac surgery: Part III--Dose haemolysis affect their accuracy?

Neurone-specific enolase (NSE) and Sangtec 100 (S-100) are useful for detecting cerebral damage during cardiopulmonary bypass (CPB). However, red cells contain NSE, and the haemolysis frequently caused by CPB could produce a false rise in NSE; S-100 is not found in red cells and should not be affected. We, therefore, compared the effects of haemolysis on NSE and S-100 to see if correction was necessary and possible. From seven patients, serial dilutions of haemolysed red cells were added to plasma (1/64-1/2048), measured for absorption at 540 nm and assayed for NSE and S-100. S-100 concentrations showed no change with haemolysis. Measured NSE increased significantly with haemolysis > 1/512 (an increase of 6.6 micrograms/ml): a correction formula is presented. In 39/48 patients after CPB, mean haemolysis was < 1/256 and would not need any correction. NSE and S-100 assay can, therefore, be used throughout CPB, which allows both glial and neuronal damage to be studied.

Biochemical markers of cerebral damage.

Neuroprotective therapy is likely to be most effective in preventing or minimizing the effects of cerebral ischaemia when given as early as possible after the insult. Neuropsychological testing is the gold standard for assessing minor cerebral damage, but is carried out several days or weeks after surgery and is too late to be useful for instituting therapy. Current intraoperative cerebral monitors (EEG, CFAM, NIRS and TCD) can detect cerebral ischaemia with good sensitivity, and give immediate results, but their specificity for ischaemia is low. Biochemical markers offer the possibility of rapid and specific diagnosis of cerebral ischaemia which would allow the early institution of neuroprotective therapies.

Magnetic resonance spectroscopy of isoflurane kinetics in humans. Part I: Elimination from the head.

We describe the first human experiments to demonstrate wash-out of isoflurane using fluorine magnetic resonance spectroscopy. Using a surface receive coil, we found two-compartment kinetics within the head with decay half-times of 9.5 and 130 min, but the signal was too weak to localize the compartments. If the fast compartment is assumed to be the brain then our results match the predictions of the classical perfusion-limited pharmacokinetic model of inhalation anaesthesia.

Magnetic resonance spectroscopy of isoflurane kinetics in humans. Part II: Functional localization.

We describe the first experiments to relate the cerebral kinetics of isoflurane (determined by fluorine magnetic resonance spectroscopy) to cerebral function. Using a surface receive coil we found two-compartment kinetics within the head with equilibrium half-times of 3.5 min and approximately 1 h with respect to expired isoflurane concentrations. Using critical fusion flicker frequency as an objective measure of the cerebral effect of isoflurane, we found evidence to identify the fast component as the brain. Responsiveness to command was lost at a brain partial pressure of 0.3% isoflurane. We conclude that the measured cerebral kinetics of isoflurane exactly matched the predictions of the classical perfusion-limited model.

Laser ablation of the endometrium: MR appearance during and after treatment and the relation of MR appearance to clinical outcome.

OBJECTIVE: Our objective was to study the appearance of the uterus on MR images obtained during and 3 months after laser ablation of the endometrium and to determine if a correlation exists between the MR imaging findings and the subsequent clinical outcome. The appearance could then be used to guide the application of laser energy during the procedure to optimize the clinical result. SUBJECTS AND METHODS: Eight women 34-55 years old (mean, 42 years old) with symptoms of heavy, painful menses underwent laser ablation under epidural anesthesia. Imaging was done on a 0.5-T Picker Asset system with a pelvic phased-array receiver coil using conventional T1-weighted spin-echo, T2-weighted spin-echo, and gradient-recalled-echo sequences. Images were obtained preoperatively, after ablation of the anterior surface, after completion of the procedure, and 3 months later. Images were visually assessed for signal intensity changes in the endometrium and myometrium by two observers in conference. Images were quantitatively analyzed by measuring uterine volume and the width of the endometrium, junctional zone (JZ), and outer myometrium (OM) on the T2-weighted images. Preoperative and 3-month postoperative symptom scores including duration, amount of bleeding, and associated pain were recorded. RESULTS: MR images obtained immediately after treatment showed an increase in the volume of the uterus (mean, 21%). Endometrial thickness increased in five patients, and the JZ:OM ratio increased on the T2-weighted scans in six patients. The increase in the ratio probably represented myometrial edema. Two patients with persistent symptoms were treated with hysterectomy 6 weeks postoperatively. Of the remaining six patients, five showed an improvement in symptom scores after 3 months. The uterus returned to its preoperative size after 3 months in three patients, endometrial thinning was noted in two, and the JZ:OM ratio remained increased in two. The difference between the mean improvement in symptom scores at 3 months was significant in the patients with and without the endometrial swelling seen immediately after treatment. No statistically significant correlation existed between the amount of perioperative uterine swelling or the increase in JZ:OM ratio and the improvement in symptom scores at 3 months. CONCLUSION: On laser ablation of the endometrium, MR imaging showed significant immediate uterine swelling as well as an increase in the endometrial thickness and JZ:OM ratio. The presence of immediate endometrial swelling and the reduction in the JZ:OM ratio after 3 months correlated with a subsequent improvement in symptom scores. Perioperative endometrial swelling rather than myometrial changes is therefore an indicator of clinical outcome.

Endoscopic laser ablation of the prostate: MR appearances during and after treatment and their relation to clinical outcome.

OBJECTIVE: Endoscopic laser ablation is a new treatment for benign prostatic hypertrophy. The objectives of this study were to determine the appearances of the prostate on MR images obtained during, 1 week after, and 3 months after this procedure and to determine if a correlation exists between the MR findings and the clinical outcome. Such appearances could then be used to guide the application of laser energy during the procedure in order to optimize the clinical result. SUBJECTS AND METHODS: Eight consecutive men 58-74 years old with symptoms of bladder outflow obstruction caused by benign prostatic hypertrophy underwent endoscopic laser ablation of the prostate under spinal or epidural anaesthesia. Imaging was done on a 0.5-T Picker Asset system with an endorectal receiver coil and conventional T1-weighted spin-echo, T2-weighted spin-echo, and gradient-recalled-echo sequences. T1-weighted magnetization transfer images were obtained in three patients. Images were obtained preoperatively, after ablation of the left-sided quadrants, immediately after completion of the procedure, and 1 week and 3 months later. Preoperative and 3-month postoperative symptom scores, peak urine flow rates, and bladder residual volumes were studied. Images were visually assessed for signal-intensity changes and the presence of cavitation by three radiologists in conference. The results were quantitatively analyzed by measuring prostatic volumes on the gradient-recalled-echo images and by measuring the width and area of regions of signal-intensity change on the T2-weighted images. RESULTS: MR images made immediately after treatment showed an increase in the volume of the prostate (mean, 34%) and a poorly defined, low-signal-intensity region around the urethra on the T2-weighted images in six patients. This probably represented coagulative necrosis. The prostate was smaller on MR images made 1 week after treatment, and after 3 months the prostate returned to its preoperative size. After 1 week, the low-signal-intensity periurethral region on the T2-weighted images was less obvious, and at 3 months it was replaced in four patients by a well-demarcated low-signal-intensity ring on the T2-weighted and gradient-recalled-echo images. No evidence of cavity formation in the prostate was seen on MR images in any patient. Symptom scores and peak urinary flow rates improved after 3 months, with a significant difference between the mean increase in symptom scores in the patients with and without the periurethral changes seen immediately after treatment. However, we found no significant difference between the mean increase in peak urinary flow rates in the patients with and without periurethral changes seen either immediately or at 3 months after treatment. No statistically significant correlation was found between the amount of prostatic swelling and the improvement in symptom scores or peak urine flow rates. CONCLUSION: In patients who have had laser prostatectomy, MR imaging shows significant immediate glandular swelling, which may account for the delayed improvement in symptoms reported with this technique. The presence of the periurethral changes immediately after treatment was correlated with a subsequent improvement in symptom scores. After 3 months, no cavity could be seen in the prostate. This may account for the poorer long-term clinical outcome reported with endoscopic laser ablation of the prostate compared with transurethral prostatectomy.