Biplane fluoroscopy-guided percutaneous spinal cord stimulation.

OBJECTIVE: Fluoroscopy is useful for spinal cord stimulation (SCS) lead placement. We employed biplane fluoroscopy for SCS lead placement. In this study, we sought to confirm the validity of using biplane fluoroscopy for SCS lead placement and to establish whether biplane fluoroscopy safely reduces the duration of surgery. METHODS: Clinical data were retrospectively collected from the medical records of patients who underwent SCS lead placement under local anesthesia from 2015 to 2022. The duration of the surgical phase and the total radiation exposure time per case were recorded. RESULTS: Forty-six patients underwent percutaneous SCS lead implantation. Recording was completed in 41 cases: one lead was placed in 13 cases and two leads were placed in 28 cases. Monoplane and biplane fluoroscopy was used in 15 and 26 patients, respectively. Although the type of fluoroscopy did not significantly affect the mean duration of the surgical phase in patients in which one lead was placed, biplane fluoroscopy was associated with a significant reduction in the mean duration of the surgical phase in patients that underwent placement of two leads (P=0.002). No significant differences in the total radiation exposure time were observed between patients in the monoplane and biplane fluoroscopy groups that were implanted with one (P=0.21) or two leads (P=0.62). CONCLUSIONS: The use of biplane fluoroscopy reduced the duration of surgery necessary for the placement of two SCS leads. Biplane fluoroscopy represents a practical and safe adjustment to the current practice of SCS lead implantation.

Symptomatic epidural haematoma after cervical laminoplasty: a report of three cases.

Symptomatic epidural haematoma after cervical laminoplasty is rare. We report 3 patients who required emergency evacuation of an epidural haematoma. Timely diagnosis and removal of the haematoma is important to prevent neurological deficits. The causative factors in these patients were preoperative coagulopathy, hypertension, and the malfunction of a closed-suction drain.

Impact of sex incompatibility on the outcome of single-unit cord blood transplantation for adult patients with hematological malignancies.

Donor-recipient sex incompatibility has been associated with transplant outcomes in allogeneic hematopoietic SCT. Such outcomes might be because mHA encoded by Y chromosome genes could be immunological targets for allogeneic T cells and B cells to induce GVHD, GVL effect and graft failure. However, its effect on the outcome of cord blood transplantation (CBT) is yet to be clarified. We retrospectively analyzed 191 adult patients who received single-unit CBT after myeloablative conditioning for malignant disease in our institute. In multivariate analysis, male recipients with female donors had a higher incidence of extensive chronic GVHD (hazard ratio (HR) 2.97, P=0.02), and female recipients with male donors had a lower incidence of platelet engraftment (HR 0.56, P=0.02) compared with female recipients with female donors as the reference. Nevertheless, there was no increase in mortality following sex-incompatible CBT. These data suggested that donor-recipient sex compatibility does not have a significant impact on survival after myeloablative CBT for hematological malignancies.

Role of satellite cell-derived L-serine in the dorsal root ganglion in paclitaxel-induced painful peripheral neuropathy.

Paclitaxel is one of the most commonly used anti-neoplastic drugs for the treatment of solid tumors. Unfortunately, its use is often associated with dose-limiting painful peripheral neuropathy and subsequent neuropathic pain that is resistant to standard analgesics. However, there are few clinically available drugs or drug classes for the treatment of paclitaxel-induced neuropathy due to a lack of information regarding the mechanisms responsible for it. In this study, we examined the involvement of l-serine in paclitaxel-induced hyperalgesia/allodynia and decrease in sensory nerve conduction velocity (SNCV). We used a preclinical rat model of paclitaxel-induced painful peripheral neuropathy. Response to von Frey filaments, SNCV, 3-phosphoglycerate dehydrogenase (3PGDH) expression, and l-serine concentration were examined. Effects of l-serine administration were also investigated. Paclitaxel treatment induced mechanical allodynia/hyperalgesia and reduction of SNCV. Paclitaxel also decreased the l-serine concentration in the dorsal root ganglion (DRG) but not in the sciatic nerve or spinal cord. In addition, paclitaxel decreased expression of 3PGDH, a biosynthetic enzyme of l-serine, in the DRG. Immunohistochemistry showed that 3PGDH was localized in satellite cells but not in neurons in the DRG. Intraperitoneal administration of l-serine improved both paclitaxel-induced mechanical allodynia/hyperalgesia and the reduction of SNCV. These results suggest that satellite cell-derived l-serine in the DRG plays an important role in paclitaxel-induced painful peripheral neuropathy. These findings may lead to novel strategies for the treatment of paclitaxel-induced painful peripheral neuropathy.

SB366791, a TRPV1 antagonist, potentiates analgesic effects of systemic morphine in a murine model of bone cancer pain.

BACKGROUND: Bone cancer pain has a major impact on the quality of life of cancer patients but is difficult to treat. Therefore, development of a novel strategy for bone cancer pain is needed for improvement of the patient quality of life. In this study, we examined the analgesic effects of the combination of a transient receptor potential vanilloid subfamily 1 (TRPV1) antagonist and morphine on pain-related behaviours in a murine model of bone cancer pain. METHODS: C3H/HeJ mice underwent injection of osteolytic sarcoma cells into the intramedullary space of the femur. The analgesic effects of intraperitoneal morphine and the analgesic effect of a TRPV1 antagonist, SB366791 [N-(3-methoxyphenyl)-4-chlorocinnamide], on bone cancer pain-related behaviours were examined. The analgesic effects of the combination of SB366791 and morphine on bone cancer pain were also examined. RESULTS: Intraperitoneal morphine significantly reduced the number of spontaneous flinches and improved ambulation only at the highest dose of 10 mg kg(-1) whereas weight-bearing was not improved. Intraperitoneal SB366791 at doses of 0.3 and 1.0 mg kg(-1), but not at a dose of 0.1 mg kg(-1), reduced the number of spontaneous flinches, whereas neither weight-bearing nor ambulation was improved. Addition of a sub-analgesic dose of SB366791 (0.1 mg kg(-1)) to morphine significantly reduced the number of flinches and improved weight-bearing compared with the effects of morphine alone. CONCLUSIONS: Our findings showed that the combination of morphine and SB366791 has potent analgesic effects on bone cancer pain. The findings of this study may lead to novel strategies for the treatment of bone cancer pain.

Contribution of transient receptor potential vanilloid subfamily 1 to endothelin-1-induced thermal hyperalgesia.

Endothelin-1 (ET-1) plays an important role in peripheral pain processing. However, the mechanisms of the nociceptive action of ET-1 have not been fully elucidated. In this study, we investigated the contribution of transient receptor potential vanilloid subfamily 1 (TRPV1) to ET-1-induced thermal hyperalgesia. Intraplantar ET-1-induced thermal hyperalgesia was examined by assessing the paw withdrawal latency to noxious heat stimuli. In electrophysiological study, whole-cell patch-clamp recordings were performed to investigate the interaction of ET-1 and TRPV1 using human embryonic kidney 293 (HEK293) cells expressing endothelin type A receptor (ET(A)) and TRPV1. Intraplantar ET-1 (3, 10 and 30 pmol) produced thermal hyperalgesia in a dose-dependent manner. Thermal hyperalgesia was attenuated by the inhibition of ET(A) and protein kinase C (PKC) but not that of ET(B). ET-1-induced thermal hyperalgesia was significantly attenuated in TRPV1-deficient mice compared with that in wild-type mice. In voltage-clamp experiments, 10 nM capsaicin evoked small inward currents in HEK293 cells expressing TRPV1 and ET(A). In the presence of ET-1, capsaicin produced much larger current responses (P<0.05). Mutation at PKC-specific TRPV1 phosphorylation sites (S800A/S502A) and PKC inhibitors inhibited the potentiating effect of ET-1. In addition, ET-1 decreased the temperature threshold for TRPV1 activation in a PKC-dependent manner (from 41.0+/-0.4 degrees C to 32.6+/-0.6 degrees C). In addition, Western blot analysis was also performed to confirm ET-1-induced phosphorylation of TRPV1. Incubation of ET-1 and intraplantar ET-1 evoked phosphorylation of TRPV1 in HEK293 cells expressing TRPV1 and ET(A) and the skin, respectively. These results suggest that the sensitization of TRPV1 activity through an ET(A)-PKC pathway contributes to ET-1-induced thermal hyperalgesia.

Down-regulation of mu opioid receptor expression within distinct subpopulations of dorsal root ganglion neurons in a murine model of bone cancer pain.

Although micro opioid receptor (MOR) agonists are used for treatment of most types of pain, a recent study has suggested that the sensitivity of bone cancer pain to systemic morphine was lower than that of inflammatory pain. However, the reasons for this have remained unclear. In this study, MOR expression and the analgesic effects of morphine in a bone cancer model were compared with those in an inflammatory pain model. A bone cancer pain model and an inflammatory pain model were made by implantation of sarcoma cells into the intramedullary space of the femur and hind-paw injection of complete Freund's adjuvant (CFA), respectively. In a behavioral study, sarcoma-implanted mice showed flinching behavior of magnitude comparable to that induced by CFA injection. The flinching behavior of sarcoma-implanted mice was less sensitive to intrathecal morphine than that of CFA-injected mice. Western blot analysis showed that MOR expression in the dorsal root ganglion (DRG) ipsilateral to sarcoma implantation was significantly reduced, while that in the DRG ipsilateral to CFA injection was increased. In sarcoma-implanted mice, the percentage of MOR-positive DRG neuronal profiles was lower than that in control mice (30.3% vs. 45.2%). In particular, MOR expression was reduced among calcitonin gene-related peptide- and transient receptor potential vanilloid subfamily 1-positive DRG neuronal profiles, which are considered to be involved in the generation of bone cancer pain (from 61.5% to 41.5% and from 72.1% to 48.4%, respectively). These results suggest that down-regulation of MOR in the distinct populations of DRG neurons contributes to the fact that higher doses of morphine are needed to produce analgesia in bone cancer as compared with those used in non-malignant inflammatory situations.

Bone cancer increases transient receptor potential vanilloid subfamily 1 expression within distinct subpopulations of dorsal root ganglion neurons.

Bone cancer pain has a strong impact on the quality of life of patients but is difficult to treat. Therefore, the mechanisms of bone cancer pain require elucidation for the purpose of development of new therapeutics. A recent study showed that activation of transient receptor potential vanilloid subfamily 1 (TRPV1) was involved in bone cancer pain. In this study, we re-evaluated the analgesic effects of pharmacological blockade of TRPV1 using the potent TRPV1 antagonist 5-iodoresiniferatoxin (I-RTX) and examined whether bone cancer can change TRPV1 expression and distribution in the primary sensory neurons in a mouse model of bone cancer pain. Implantation of osteosarcoma into the femur induced ongoing and movement-evoked bone cancer-related pain behaviors. These behaviors were significantly reduced by i.p. administration of I-RTX, compared with vehicle. Western blot and reverse transcription-polymerase chain reaction (RT-PCR) analyses revealed that TRPV1 level was significantly increased in dorsal root ganglions (DRGs) ipsilateral to sarcoma implantation. Immunohistochemical analysis showed that implantation of osteosarcoma induced not only an increase in the percentage of TRPV1-positive neurons among DRG neurons (24.3+/-1.3% in sham mice and 31.2+/-1.3% in mice with osteosarcoma implantation, P<0.05) but also an overall shift in the distribution of area of profiles to the right. Colocalization study showed that the percentages of colocalization of TRPV1 with neurofilament 200 kD (NF200) and calcitonin gene-related peptide (CGRP) but not isolectin B4 (IB4) among DRG neurons in mice with osteosarcoma implantation were increased compared with those in sham mice (from 0.8+/-0.1% to 2.1+/-0.3% for TRPV1 and NF200 and from 21.1+/-1.3% to 26.5+/-0.2% for TRPV1 and CGRP). In conclusion, TRPV1 activation plays a critical role in the generation of bone cancer pain, and bone cancer increases TRPV1 expression within distinct subpopulation of DRG neurons. These findings may lead to novel strategies for the treatment of bone cancer pain.

Usefulness of intraoperative magnetic resonance imaging for glioma surgery.

BACKGROUND: Radical resection of gliomas can increase patient's survival. There is known concern, however, that aggressive tumour removal can result in neurological morbidity. The objective of the present study was to evaluate the usefulness of low magnetic field strength (0.3 Tesla) open intraoperative magnetic resonance imaging (iMRI) for complete resection of glioma with emphasis on functional outcome. METHODS: From 2000 to 2004, 96 patients with intracranial gliomas underwent tumour resection with the use of iMRI in Tokyo Women's Medical University. There were 50 men and 46 women; mean age was 39 years. Tumour volume varied from 1.2 ml to 198 ml (median: 36.5 mL). Resection rate and postoperative neurological status were compared between control group (46 cases, operated on during the initial period after installation of iMRI), and study group (50 most recent cases, in whom surgery was done using established treatment algorithm and improved image quality). FINDINGS: Overall, mean resection rate was 93%, and medial residual tumour volume was 0.17 ml. Total tumour removal was achieved in 44 cases (46%). Compared to control group, resection rate in the study group was significantly higher (91%, vs. 95%; P < 0.05), whereas residual tumour volume was significantly smaller (1.7 mL vs. 0.025 mL; P < 0.001). Nine patients in the control group (20%) and 24 in the study group (48%) experienced temporary postoperative neurological deterioration (P < 0.01), however, the rate of permanent morbidity evaluated 3 months after surgery did not differ significantly between the groups investigated (13% vs. 14%). CONCLUSIONS: Use of iMRI during surgery for intracranial gliomas permits to attain aggressive tumour resection with good functional outcome. Nevertheless, surgical experience with the iMRI system, establishment of treatment algorithm, and improvement of image quality are of paramount importance for optimal results.

Immunohistochemical analysis of acid-sensing ion channel 2 expression in rat dorsal root ganglion and effects of axotomy.

Several studies have suggested that acid-sensing ion channel 2 (ASIC2) plays a role in mechanoperception and acid sensing in the peripheral nervous system. We examined the expression and distribution of ASIC2 in the rat dorsal root ganglion, the co-localization of ASIC2 with tropomyosin-related kinase (trk) receptors, and the effects of axotomy on ASIC2 expression. ASIC2 immunoreactivity was observed in both neurons and satellite cells. ASIC2-positive neurons accounted for 16.5 +/- 2.4% of the total neurons in normal dorsal root ganglion. Most ASIC2-positive neurons were medium-to-large neurons and were labeled with neurofilament 200 kD (NF200). Within these neurons, ASIC2 was not evenly distributed throughout the cytoplasm, but rather was accumulated prominently in the cytoplasm adjacent to the axon hillock and axonal process. We next examined the co-localization of ASIC2 with trk receptors. trkA was expressed in few ASIC2-positive neurons, and trkB and trkC were observed in 85.2% and 53.4% of ASIC2-positive neurons, respectively, while only 6.9% of ASIC2-positive neurons were co-localized with trkC alone. Peripheral axotomy markedly reduced ASIC2 expression in the axotomized dorsal root ganglion neurons. On the other hand, intense ASIC2 staining was observed in satellite cells. These results show that ASIC2 is expressed in the distinct neurochemical population of sensory neurons as well as satellite cells, and that peripheral axotomy induced marked reductions in ASIC2 in neurons.

Surgical management of early massive edema caused by cerebral contusion in head trauma patients.

Early massive edema caused by severe cerebral contusion results in elevation of intracranial pressure (ICP) and clinical deterioration within 24-72 hours post-trauma. Previous studies indicate that cells in the central area of the contusion undergo shrinkage, disintegration, and homogenization, whereas cellular swelling is predominant in the peripheral area, suggesting that early massive edema is attributable to high osmolality within necrotic brain tissue and may generate an osmotic potential across central and peripheral areas. We analyzed the effects of surgical excision of necrotic brain tissue in 182 patients with cerebral contusion registered with Japan Neurotrauma Data Bank; 121 patients (66%; Group I) were treated conservatively, and 61 (34%; Group II) were treated surgically. Most Group II cases (90%) underwent complete excision of necrotic brain tissue and evacuation of clots. Group I demonstrated higher mortality at 6 months post-trauma compared to Group II (48%) vs. 23%; p = 0.0001; n = 182). Striking differences were observed in patients scoring 9 or more on Glasgow Coma Scale at admission (56% vs. 17%); p = 0.017; n = 45) and demonstrated "talk-and-deteriorate" (64% vs. 22%: p = 0.026; n = 29), supporting our hypothesis that early massive edema is caused by cerebral contusion accompanied by necrotic brain tissue, indicating that surgical excision of necrotic brain tissue provides satisfactory control of progressive elevation in ICP and clinical deterioration in many cases.

Acute hemispheric swelling associated with thin subdural hematomas: pathophysiology of repetitive head injury in sports.

INTRODUCTION: The most common head injury in sports is concussion, and repeated concussions occurring within a short period occasionally can be fatal. Acute subdural hematoma is the most common severe head injury and can be associated with severe neurologic disability and death in sports. We investigated severe brain damage resulting from repetitive head injury in sports, and evaluated the pathophysiology of sports-related repetitive injury. METHODS: We reviewed the literature containing detailed descriptions of repetitive severe sports-related head injury. In total, 18 cases were analyzed with regard to age, gender, type of sports, symptoms before second injury, and pathology of brain CT scans. RESULTS: The majority of cases involved young males aged 16 to 23 years old, who sustained a second head injury before symptoms from the first head injury had resolved. Ten of 15 cases did not suffer loss of consciousness at insult. Eight cases were confirmed on brain CT scans after the second injury, and all 8 cases revealed brain swelling associated with a thin subdural hematoma. CONCLUSIONS: Second impact syndrome is thought to occur because of loss of autoregulation of cerebral blood flow, leading to vascular engorgement, increased intracranial pressure, and eventual herniation. Our investigation suggests that the existence of subdural hematoma is a major cause of brain swelling following sports-related, repetitive head injury.

Matrix metalloproteinase-9 is associated with blood-brain barrier opening and brain edema formation after cortical contusion in rats.

Matrix metalloproteinases (MMPs) are associated with blood-brain opening and may be involved in the pathophysiology of acute brain injury. Previous research demonstrated that knockout mice deficient in MMP-9 subjected to transient focal cerebral ischemia had reduced blood-brain barrier (BBB) disruption and attenuated cerebral infarction. In this study, we examined MMP-9 up-regulation, BBB disruption, and brain edema formation after cortical impact injury in rats. Cortical contusion was induced by controlled cortical impact. Animals were sacrificed at intervals after injury. MMP up-regulation was assessed by gelatin zymography, and BBB integrity was evaluated using Evans blue dye with a spectrophotometric assay. Brain water content was measured by comparing wet and dry weights of each hemisphere as an indicator of brain edema. Zymograms showed elevated MMP-9 as early as at 3 hours after injury, reaching a maximum at 18 hours. Peak levels of BBB disruption occurred 6 hours after injury. Brain edema became progressively more severe, peaking 24 hours after injury. Compared to control group, treatment with MMP-inhibitor GM6001 significantly reduced BBB disruption 6 hours and brain water content (85.9 +/- 0.5% vs. 82.6 +/- 0.3%; p < 0.05) 24 hours after injury. These findings suggest that MMP-9 may contribute to BBB disturbance and subsequent brain edema after traumatic brain injury.

Endothelin-1 enhances capsaicin-evoked intracellular Ca2+ response via activation of endothelin a receptor in a protein kinase Cepsilon-dependent manner in dorsal root ganglion neurons.

Increasing evidence indicates that endothelin-1 has a role for peripheral nociceptive signaling in animals and humans. However, the mechanisms of the nociceptive effects of endothelin-1 have not been fully understood. The current study investigated the effects of endothelin-1 on the capsaicin-evoked intracellular Ca2+ response of cultured adult mice dorsal root ganglion neurons. Dorsal root ganglia were harvested from adult male C57B6N mice and were cultured. With a digital image analysis system, we detected the [Ca2+]i image of cultured dorsal root ganglion cells after loading with Fura-2 acetoxymethyl. In addition, co-localization of protein kinase Cepsilon with transient receptor potential V1 and the translocation of protein kinase Cepsilon were investigated using immunohistochemical methods. Endothelin-1 (10 nM) enhanced an increase in [Ca2+]i by capsaicin (10 nM) from 87.6+/-11.6 nM to 414.8+/-62.3 nM (71 of 156 neurons). The inhibition of endothelin A receptor (BQ-123) significantly suppressed the enhancing effect of endothelin-1. In addition, a nonselective protein kinase C inhibitor (bisindolylmaleimide I) significantly suppressed the enhancing effect of endothelin-1. A myristoyl-tagged membrane-permeant-protein kinase Cepsilon V1-2 inhibitory peptide also significantly suppressed the enhancing effect of endothelin-1. In the immunocytochemical study, protein kinase Cepsilon immunoreactivity was found in most of transient receptor potential V1-positive neurons. After endothelin-1 application, protein kinase Cepsilon immunoreactivity was observed to be translocated from the cytosol to the cell membrane in transient receptor potential V1-positive neurons. Our results indicate that endothelin-1 enhances the response of dorsal root ganglion neurons to capsaicin in a protein kinase Cepsilon-dependent manner. Our findings may lead to a new strategy to treat pain associated with endothelin-1.

Experimental model for investigating hyponatremia after subarachnoid hemorrhage in rats.

Hyponatremia is a common complication in patients with aneurysmal subarachnoid hemorrhage (SAH). Such patient demonstrates excessive natriuresis and an increased risk of symptomatic cerebral vasospasm. However, the precise mechanisms underlying SAH induced hyponatremia remain unclear. In the present study, in order to establish an experimental model of hyponatremia following SAH, we induced SAH in rats, and evaluated the serum sodium (Na) levels, Na excretion and physiological parameters. Twenty-four male Wistar rats were used. SAH was induced by an endovascular puncture method. The mean arterial pressure (MAP), intracranial pressure (ICP), and cerebral blood flow (CBF) were monitored continuously. The urine was collected cumulatively for 12 hours after SAH, and the urine Na concentration was determined with a spectrophotometer. The serum Na levels were measured at 12 hrs, 2 and 4 days following the SAH induction. The mean (+/- standard deviation) baseline ICP was 3.5 +/- 2.6 mmHg, and increased to 67.4 +/- 17.6 mmHg immediately following induction of SAH. CBF decreased rapidly, and then gradually recovered to 70-80% of baseline. The urine volume and total Na excretion were significantly increased in comparison to those of the sham (P < 0.05). The serum Na level was significantly decreased at 4 days following SAH (P < 0.05). The present results demonstrated for the first time that rats with SAH exhibited excessive natriuresis. The endovascular puncture model is suitable for investigating hyponatremia that occurs concomitantly with natriuresis and diuresis after SAH.

Extravascular application of an intravascular ultrasound (IVUS) catheter during carotid endarterectomy to verify distal ends of stenotic lesions.

BACKGROUND: Intravascular ultrasound (IVUS) has been developed initially for intravascular imaging of coronary arteries to investigate vascular structures. We applied the IVUS catheter extravascularly to the cervical carotid arteries to obtain intra-operative ultrasound images during carotid endarterectomy (CEA). Intra-operative assessments of the distal ends of the stenotic lesions as well as pathological vascular structures are important, not only for exposing the lesions sufficiently but also for placing the shunt system safely. METHOD: An IVUS catheter (3.2 French/30 MHz) was intra-operatively applied close to the outer surface of the cervical carotid arteries during CEA. Ultrasound transection vascular images were obtained in 33 consecutive patients (30 males and 3 females) with a mean age of 66.5 years. FINDINGS: In 32 of 33 cases, extravascular application of IVUS catheter before making arteriotomies correctly depicted the distal ends of the internal carotid artery (ICA) stenotic lesions as a thin layer of vascular wall [0.64 +/- 0.16 mm (mean +/- SD) compared with 1.66 +/- 0.42 mm for carotid plaque] with intravascular blood flow. Based on the IVUS findings, we were able to adequately expose the normal ICA portion distal to the stenotic lesion before making the arteriotomy even in cases with stenotic lesions at very high positions, and to insert shunts safely. Furthermore, the properties of lesions and blood flow were also verified. However, it was difficult to examine the far vascular wall. CONCLUSIONS: Extravascular application of IVUS catheter is efficient for intra-operative evaluation of the distal end of the stenotic lesion especially in cases with stenotic lesions at very high positions and cases in whom pre-operative angiograms did not clearly demonstrate the distal end. The findings also demonstrate the properties of lesions and completeness of CEA.

Pneumocephalus following an epidural blood patch.

Pneumocephalus is a rare complication of epidural block. We report a case of pneumocephalus complicating an epidural blood patch performed 3 days after unintentional dural puncture. Pneumocephalus may occur during an epidural blood patch procedure, even if the epidural needle tip is within the epidural space.