Upper-limb somatosensory evoked potential monitoring in lumbosacral spine surgery: a prognostic marker for position-related ulnar nerve injury.

BACKGROUND CONTEXT: Somatosensory evoked potential (SSEP) is used to monitor integrity of the brain, spinal cord, and nerve roots during spinal surgery. It records the electrical potentials from the scalp after electrical stimulation of the peripheral nerves of the upper or lower limbs. The standard monitoring modality in lumbosacral spine surgery includes lower-limb SSEP and electromyography (EMG). Upper-limb SSEP monitoring has also been used to detect and prevent brachial plexopathy and peripheral nerve injury in thoracic and lumbosacral spine surgeries. We routinely monitor lower-limb SSEP and EMG in lumbosacral spine procedures at our institution. However, a few patients experienced postoperative numbness and/or pain in their ulnar distribution with uneventful lower-limb SSEP and EMG. PURPOSE: We hypothesized that the postoperative upper extremity paresis in lumbosacral surgeries may result from compression and/or stretch of the brachial plexus and/or ulnar nerve while the patients were in prone position. Using upper-limb SSEP, we investigated whether we observe any significant change in the SSEP, and if so, whether we can prevent or reduce frequency of postoperative upper extremity deficits. STUDY DESIGN/SETTING: In this prospective study, we monitored upper-limb SSEP, in addition to lower-limb SSEP and EMG, in 230 elective, posterior lumbosacral spinal procedures. All operations were performed by a group of four neurosurgeons. PATIENT SAMPLE: One hundred and thirty-one female and 99 male with an age range of 28 to 86 years between January 2004 and December 2005 were studied. OUTCOME MEASURES: Amplitude and latency of upper-limb or ulnar SSEP were continuously compared with those of the baseline. A greater than or equal to 50% decrease in SSEPs amplitude and/or a greater than or equal to 10% increase in latency were considered to be significant. METHODS: After intubation, patients were positioned prone on Jackson or Andrews spinal table. Anesthesia was maintained with inhalant gas (desflurane or sevoflurane) and propofol infusion with and without minimal infusion of narcotics (fentanyl, sufentanyl, or remifentanil). Intraoperative neurophysiologic monitoring of upper-limb or ulnar SSEP was achieved by continuously recording cortical and subcortical responses after alternate stimulation of the ulnar nerve at the wrist. In our institutional protocol, a greater than or equal to 50% decrease in SSEPs amplitude and/or a greater than or equal to 10% increase in latency were considered to be significant to alert the operating surgeons. When significant changes occurred, the surgeon was immediately notified. Also, reevaluation of vital signs, depth of anesthesia, and patient's position, and technical troubleshootings were subsequently followed. RESULTS: We observed a greater than or equal to 50% decrease in amplitude of ulnar SSEP in 10 patients without significant changes in lower-limb SSEP (peroneal or posterior tibial nerve SSEP) or EMG during surgery. Eight patients had changes in unilateral limbs, and two patients had changes in bilateral limbs. Two patients with significant changes in unilateral limbs showed changes twice. The mean SSEP amplitude for the 14 changes was 29.2+/-3.1% (mean+/-SEM, standard error of mean) of the baseline value at the average surgical time of 60+/-1.5 minutes. With repositioning of the arms, the amplitudes were immediately restored with the average of 70.2+/-7.1% (n=14) of the baseline value. The mean amplitude of upper-limb SSEP was 73.4+/-8.7% (n=12) of the baseline at wound closure. The average surgical time was 154+/-29.2 minutes per case for the 10 patients. There was no documented postoperative upper extremity paresis in all 230 patients. CONCLUSIONS: The present study demonstrates that upper-limb SSEP monitoring could detect position-related ulnar neuropathy in 5.2% of the patients undergoing lumbosacral spine surgery.

Structure/function of the inhibition of human 3beta-hydroxysteroid dehydrogenase type 1 and type 2 by trilostane.

The human type 1 (placenta, breast tumors) and type 2 (gonads, adrenals) isoforms of 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD) are key enzymes in biosynthesis of all active steroid hormones. Human 3beta-HSD1 is a critical enzyme in the conversion of DHEA to estradiol in breast tumors and may be a major target enzyme for the treatment of breast cancer. 3beta-HSD2 participates in the production of cortisol and aldosterone in the human adrenal gland. The goals of this project are to evaluate the role of the 2alpha-cyano group on trilostane (2alpha-cyano-4alpha,5alpha-epoxy-17beta-ol-androstane-3-one) and determine which amino acids may be critical for 3beta-HSD1 specificity. Trilostane without the 2alpha-cyano group, 4alpha,5alpha-epoxy-testosterone, was synthesized. Using our structural model of 3beta-HSD1, trilostane or 4alpha,5alpha-epoxy-testosterone was docked in the active site using Autodock 3.0, and the potentially critical residues (Met187 and Ser124) were identified. The M187T and S124T mutants of 3beta-HSD1 were created, expressed and purified. Dixon analyses of the inhibition of wild-type 3beta-HSD1, 3beta-HSD2, M187T and S124T by trilostane and 4alpha,5alpha-epoxy-testosterone suggest that the 2alpha-cyano group of trilostane is anchored by Ser124 in both isoenzymes. Kinetic analyses of cofactor and substrate utilization as well as the inhibition kinetics of M187T and the wild-type enzymes suggest that the 16-fold higher-affinity inhibition of 3beta-HSD1 by trilostane may be related to the presence of Met187 in 3beta-HSD1 and Thr187 in 3beta-HSD2. This structure/function information may lead to the production of more highly specific inhibitors of 3beta-HSD1 to block the hormone-dependent growth of breast tumors.