Miranda Kapural

Serum S-100β as a possible marker of blood–brain barrier disruption

Two brain-specific proteins, S-100β and neuron-specific enolase (NSE), are released systemically after cerebral lesions, but S-100β levels sometimes rise in the absence of neuronal damage. We hypothesized that S-100β is a marker of blood–brain barrier (BBB) leakage rather than of neuronal damage. We measured both proteins in the plasma of patients undergoing iatrogenic BBB disruption with mannitol, followed by chemotherapy. Serum S-100β increased significantly after mannitol infusion (P<0.05) while NSE did not. This suggests that S-100β is an early marker of BBB opening that is not necessarily related to neuronal damage.

Cooled Radiofrequency System for the Treatment of Chronic Pain from Sacroiliitis: The First Case‐Series

▪ Abstract:  Sacroiliitis and sacroiliac (SI) joint dysfunction are frequent causes of the chronic lower back pain. Therapeutic solutions include intra‐atricular injections with short‐term pain relief and surgical fusion, which appears ineffective. Radiofrequency (RF) of the joint capsule or lateral branches has been previously reported with variable successes. Cooling tissue adjacent to the electrode (cooled RF) increases the radius of lesion. We present here the first retrospective data on pain relief and changes in function after such RF denervation.

Effects of transient loss of shear stress on blood-brain barrier endothelium : Role of nitric oxide and IL-6

Loss of blood-brain barrier (BBB) function may contribute to post-ischemic cerebral injury by yet unknown mechanisms. Ischemia is associated with anoxia, aglycemia and loss of flow (i.e. shearing forces). We tested the hypothesis that loss of shear stress alone does not acutely affect BBB function due to a protective cascade of mechanisms involving cytokines and nitric oxide (NO). To determine the relative contribution of shear stress on BBB integrity we used a dynamic in vitro BBB model based on co-culture of rat brain microvascular endothelial cells (RBMEC) and astrocytes. Trans-endothelial electrical resistance (TEER), IL-6 release and NO levels were measured from the lumenal and ablumenal compartments throughout the experiment. Flow-exposed RBMEC were challenged with 1 h of normoxic-normoglycemic flow cessation (NNFC) followed by reperfusion for 2 to 24 h. NNFC caused a progressive drop in nitric oxide production during flow cessation followed by a time-dependent increase in ablumenal IL-6 associated with a prolonged NO increase during reperfusion. The nitric oxide synthetase (NOS) inhibitor L-NAME (10 microM) abrogated all effects of NNFC, including changes in NO and cytokine production. BBB permeability did not increase during or after NNFC/reperfusion, but was increased by treatment with L-NAME or when the effects of IL-6 were blocked. Flow adapted RBMEC and astrocytes respond to NNFC/reperfusion by overproduction of IL-6, possibly secondary to increased production of NO during the reperfusion. Maintenance of BBB function during and following NNFC appears to depend on intact NO signaling and IL-6 release.

Botulinum toxin occipital nerve block for the treatment of severe occipital neuralgia: a case series.

▪ Abstract:  Persistent occipital neuralgia can produce severe headaches that are difficult to control by conservative or surgical approaches. We retrospectively describe a series of six patients with severe occipital neuralgia who received conservative and interventional therapies, including oral antidepressants, membrane stabilizers, opioids, and traditional occipital nerve blocks without significant relief. This group then underwent occipital nerve blocks using the botulinum toxin type A (BoNT‐A) BOTOX® Type A (Allergan, Inc., Irvine, CA, U.S.A.) 50 U for each block (100 U if bilateral). Significant decreases in pain Visual Analog Scale (VAS) scores and improvement in Pain Disability Index (PDI) were observed at four weeks follow‐up in five out of six patients following BoNT‐A occipital nerve block. The mean VAS score changed from 8 ± 1.8 (median score of 8.5) to 2 ± 2.7 (median score of 1), while PDI improved from 51.5 ± 17.6 (median 56) to 19.5 ± 21 (median 17.5) and the duration of the pain relief increased to an average of 16.3 ± 3.2 weeks (median 16) from an average of 1.9 ± 0.5 weeks (median 2) compared to diagnostic 0.5% bupivacaine block. Following block resolution, the average pain scores and PDI returned to similar levels as before BoNT‐A block. In conclusion, BoNT‐A occipital nerve blocks provided a much longer duration of analgesia than diagnostic local anesthetics. The functional capacity improvement measured by PDI was profound enough in the majority of the patients to allow patients to resume their regular daily activities for a period of time. ▪

Intervertebral Disc Biacuplasty for the Treatment of Lumbar Discogenic Pain: Results of a Six-Month Follow-Up

OBJECTIVE Intradiscal biacuplasty (IDB) is a novel bipolar cooled radiofrequency system for the treatment of degenerative disk disease. We present the results of a pilot trial with 6-month follow-up. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS: Fifteen patients, 22-55 years old, underwent one- or two-level IDB treatment of their painful lumbar discs. All had chronic low back pain >6 months, back pain exceeding leg pain, concordant pain on provocative discography, disc height >50% of control, and evidence of single- or two-level degenerative disc disease without evidence of additional changes on magnetic resonance imaging. IDB was performed under fluoroscopy using two radiofrequency probes positioned bilaterally in the intervertebral disc. Thirteen patients completed follow-up questionnaires at 1, 3, and 6 months. Pain disability was evaluated with Oswestry and Short Form (SF)-36 questionnaires. RESULTS Median visual analog scale pain scores were reduced from 7 (95% confidence interval [CI] 6, 8) to 4 (2, 5) cm at 1 month, and remained at 3 (2, 5) cm at 6 months. The Oswestry improved from 23.3 (SD 7.0) to 16.5 (6.8) points at 1 month and remained similar after 6 months. The SF-36 Physical Functioning scores improved from 51 (18) to 70 (16) points after 6 months, while the SF-36 Bodily Pain score improved from 38 (15) to 54 (23) points. Daily opioid use did not change significantly from baseline: from 40 (95% CI 40, 120) before IDB to 5 (0, 40) mg of morphine sulfate equivalent 6 months after IDB. No procedure-related complications were detected. CONCLUSIONS Patients showed improvements in several pain assessment measures after undergoing IDB for discogenic pain. A randomized controlled study is warranted and needed to address the efficacy of the procedure.

Tracheo-Innominate Artery Fistula After Tracheostomy

F istula formation between the trachea and the innominate artery is a rare complication of tracheostomy (1). The survival rate in patients who develop bleeding from a tracheo-innominate artery fistula (TIF) has been reported as 14.3%, and only patients who received immediate surgical treatment survived (2). Of those patients who develop a TIF, 78% do so within the first 3 wk after tracheostomy (3). One of the proposed mechanisms of fistula formation is mucosal necrosis due to pressure caused by the elbow, tip, or cuff of the tracheostomy tube (2). Clinical presentations and treatment of TIF have been described mainly in the surgical literature (1–7). However, because anesthesiologists may be involved in treating this emergency, they must be familiar with the therapeutic steps. We present a patient who developed a TIF and died as a consequence of massive hemorrhage into the tracheobronchial tree with asphyxia. We discuss potential preventative measures that should be followed to decrease the probability of formation of a tracheo-arterial fistula, as well as important diagnostic and therapeutic steps the anesthesiologist must take in managing this severe tracheostomy complication.

Histological Changes and Temperature Distribution Studies of a Novel Bipolar Radiofrequency Heating System in Degenerated and Nondegenerated Human Cadaver Lumbar Discs

OBJECTIVE AND STUDY DESIGN The purpose of this experimentation was to investigate the safety of a novel cooled bipolar radiofrequency system by examining histology and monitoring temperature distribution in the disc, epidural space, and adjacent to the nerve roots. In our study we used two human cadaver lumbar spines, one moderately to severely degenerated and the other mildly degenerated. SETTING AND INTERVENTIONS Radiofrequency ablation of the disc posterior annulus is a theoretically plausible technique to ablate the nociceptors and to modify collagen of the annulus fibrosus. A novel cooled bipolar radiofrequency system is used to perform a procedure called intervertebral disc biacuplasty to heat the posterior annulus for the treatment of discogenic pain. Four lumbar intervertebral discs were treated in each spine sample using the bipolar system while two lumbar discs of each spine were used as controls. RESULTS Temperatures developed in the posterior annulus of the disc were on average 52.35 +/- 5.07 degrees C, while in the intervertebral foramen and in the spinal canal were 38.84 +/- 1.7 degrees C and 38.29 +/- 2.04 degrees C, respectively. There was no histological evidence of damage to any other structures including vertebral end plates, epidural space, or nerve roots. Additionally, there were no histological changes in the posterior annulus that were consistent with heat-induced changes to collagen structure. CONCLUSIONS Temperatures reached in the posterior annulus during transdiscal biacuplasty were greater than required (45 degrees C) for neuroablation. Temperatures reached at the neural foramina and epidural were low enough to avoid neural damage.

Neuroprotective, anesthetic, and cardiovascular effects of the NMDA antagonist, CNS 5161A, in isoflurane-anesthetized lambs.

Background N-methyl-d-aspartate (NMDA) receptor antagonists are neuroprotective in animal models of cerebral ischemia, but adverse cardiovascular and neurobehavioral effects have precluded their clinical use. The authors present the neuroprotective, anesthetic, and cardiovascular effects of a novel NMDA antagonist, CNS 5161A. Methods Lambs, 4.0–6.5 kg, were anesthetized with isoflurane, intubated, and ventilated and had thermodilution catheters placed in the pulmonary artery and 20-g catheters placed in the femoral artery. The minimum alveolar concentration (MAC) of isoflurane was determined using the “bracketing technique.” CNS 5161A was given as a bolus and then as an infusion at three doses. Cardiovascular measurements were determined every 15 min. Other lambs (n = 25) were subjected to cardiopulmonary bypass (CPB) with hypothermic circulatory arrest (HCA) for 120 min. Eighteen received CNS 5161A, and seven received saline vehicle. One hour after CPB, brains were perfusion-fixed and removed for in situ hybridization and immunohistochemistry analysis in half of the animals. The other half survived 48 h before their brains were examined for neuronal degeneration. Results Isoflurane at MAC significantly decreased blood pressure, heart rate, cardiac output, and systemic vascular resistance by 30–48% (n = 16;P < 0.05). CNS 5161A (n = 12) had no significant cardiovascular effects. All concentrations of CNS 5161A caused a significant reduction (21–29%) of the MAC of isoflurane (n = 12;P < 0.05). CNS 5161A, at serum concentrations greater than 25 ng/ml, completely inhibited c-fos mRNA and c-FOS protein expression in hippocampal neurons after 120 min of HCA, attenuated neuronal degeneration, and improved functional outcome by 47% (P < 0.05). Conclusions CNS 5161A at neuroprotective concentrations before CPB–HCA significantly reduces the MAC of isoflurane without cardiovascular effects.