Possible involvement of activated locus coeruleus-noradrenergic neurons in pain-related sleep disorders.

The locus coeruleus (LC) is a noradrenergic brainstem structure that is considered to play a role in promoting arousal. To further clarify the role of LC noradrenergic neurons, we performed an optogenetic assay by injecting AAV-channelrhodopsin-2 (ChR2) into the LC of cre-tyrosine hydrolase (TH) mice. We found here that the specific activation of LC noradrenergic neurons produced a significant increase in wakefulness and a significant decrease in non-rapid eye movement (NREM) sleep during photostimulation. On the other hand, neuropathic pain is believed to significantly interfere with sleep, and inadequate sleep may contribute to the stressful negative consequences of living with pain. In the present study, sciatic nerve ligation, which produced significant thermal hyperalgesia, significantly increased the levels of noradrenaline released in the prefrontal cortex (PFC) by the weak electrical stimulation of neurons in the LC. Under these conditions, the systemic administration of adrenaline α and ß inhibitor cocktail at 7 days after sciatic nerve ligation restored the increased wakefulness and decreased NREM sleep to normal levels. These results suggest that neuropathic pain may accelerate neurons in the LC, and its overactivation may be, at least in part, associated with sleep disturbance under neuropathic pain.

Astrocytic activation in the anterior cingulate cortex is critical for sleep disorder under neuropathic pain.

Insomnia, depression, and anxiety disorder are common problems for people with neuropathic pain. In this study, mild noxious heat stimuli increased the duration and number of spontaneous pain-like behaviors in sciatic nerve-ligated mice. We used functional magnetic resonance imaging to visualize the increased blood oxygenation level-dependent signal intensity in the anterior cingulate cortex (ACC) of mice with sciatic nerve ligation under mild noxious stimuli. Such stimuli significantly increased the release of glutamate in the ACC of nerve-ligated mice. In addition, sciatic nerve ligation and mild noxious stimuli changed the morphology of astrocytes in the ACC. Treatment of cortical astrocytes with glutamate caused astrocytic activation, as detected by a stellate morphology. Furthermore, glutamate induced the translocation of GAT-3 to astrocyte cell membranes using primary cultured glial cells from the mouse cortex. Moreover, the GABA level at the synaptic cleft in the ACC of nerve-ligated mice was significantly decreased exposure to mild noxious stimuli. Finally, we investigated whether astrocytic activation in the ACC could directly mediate sleep disorder. With the optogenetic tool channel rhodopsin-2 (ChR2), we demonstrated that selective photostimulation of these astrocytes in vivo triggered sleep disturbance. Taken together, these results suggest that neuropathic pain-like stimuli activated astrocytes in the ACC and decreased the extracellular concentration of GABA via an increase in the release of glutamate. Furthermore, these findings provide novel evidence that astrocytic activation in the ACC can mimic sleep disturbance in mice.

Analysis of sleep disorders under pain using an optogenetic tool: possible involvement of the activation of dorsal raphe nucleus-serotonergic neurons.

BACKGROUND: Several etiological reports have shown that chronic pain significantly interferes with sleep. Inadequate sleep due to chronic pain may contribute to the stressful negative consequences of living with pain. However, the neurophysiological mechanism by which chronic pain affects sleep-arousal patterns is as yet unknown. Although serotonin (5-HT) was proposed to be responsible for sleep regulation, whether the activity of 5-HTergic neurons in the dorsal raphe nucleus (DRN) is affected by chronic pain has been studied only infrequently. On the other hand, the recent development of optogenetic tools has provided a valuable opportunity to regulate the activity in genetically targeted neural populations with high spatial and temporal precision. In the present study, we investigated whether chronic pain could induce sleep dysregulation while changing the activity of DRN-5-HTergic neurons. Furthermore, we sought to physiologically activate the DRN with channelrhodopsin-2 (ChR2) to identify a causal role for the DRN-5-HT system in promoting and maintaining wakefulness using optogenetics. RESULTS: We produced a sciatic nerve ligation model by tying a tight ligature around approximately one-third to one-half the diameter of the sciatic nerve. In mice with nerve ligation, we confirmed an increase in wakefulness and a decrease in non-rapid eye movement (NREM) sleep as monitored by electroencephalogram (EEG). Microinjection of the retrograde tracer fluoro-gold (FG) into the prefrontal cortex (PFC) revealed several retrogradely labeled-cells in the DRN. The key finding of the present study was that the levels of 5-HT released in the PFC by the electrical stimulation of DRN neurons were significantly increased in mice with sciatic nerve ligation. Using optogenetic tools in mice, we found a causal relationship among DRN neuron firing, cortical activity and sleep-to-wake transitions. In particular, the activation of DRN-5-HTergic neurons produced a significant increase in wakefulness and a significant decrease in NREM sleep. The duration of NREM sleep episodes was significantly decreased during photostimulation in these mice. CONCLUSIONS: These results suggest that neuropathic pain accelerates the activity of DRN-5-HTergic neurons. Although further loss-of-function experiments are required, we hypothesize that this activation in DRN neurons may, at least in part, correlate with sleep dysregulation under a neuropathic pain-like state.

Changes in the circadian rhythm of mRNA expression for µ-opioid receptors in the periaqueductal gray under a neuropathic pain-like state.

Variation in the production of opioid receptors over a 24-h period is considered to contribute to circadian alterations in neuropathic pain. In this study, we investigated the possible changes in the circadian rhythm of mRNA expression for µ-opioid receptor (MOR), κ-opioid receptor (KOR), and adrenaline α2a receptor (α2a) in the periaqueductal gray, frontal cortex, thalamus, and spinal cord following sciatic nerve ligation in mice. In sham-operated mice, the latencies of hind paw-withdrawal in response to thermal stimuli at 14:00 and 20:00 were significantly greater than that at 8:00 and the latency at 2:00 was significantly less than those at 14:00 and 20:00, indicating a "rest" period-dominant circadian rhythm for thermal pain-thresholds. In sciatic nerve-ligated mice, the latencies of hind paw-withdrawal in response to thermal stimuli at 14:00 and 20:00 were significantly less than that at 8:00, and the latency at 2:00 was significantly greater than those at 14:00 and 20:00. A correlative tendency between the time-variation of pain latency and the time-variation of MOR mRNA expression was observed in the periaqueductal gray of sham-operated and sciatic nerve-ligated mice. In contrast, neither mouse showed a strong circadian rhythm for the expressions of KOR and α2a mRNAs in any region. The present data suggest that changes in MOR mRNA expression in the periaqueductal gray may be synchronized with the circadian rhythm for the pain threshold for noxious thermal stimuli. In contrast, neuropathic pain in mice exhibited a negative circadian pattern for the expression of MOR, KOR, and α2a receptors in the frontal cortex, thalamus, and spinal cord.

Multivariate analysis of C-5 palsy incidence after cervical posterior fusion with instrumentation.

OBJECT: Postoperative C-5 palsy is a significant complication resulting from cervical decompression procedures. Moreover, when cervical degenerative diseases are treated with a combination of decompression and posterior instrumented fusion, patients are at increased risk for C-5 palsy. However, the clinical and radiological features of this condition remain unclear. Therefore, the purpose of this study was to clarify the risk factors for developing postoperative C-5 palsy. METHODS: Eighty-four patients (mean age 60.1 years) who had undergone posterior instrumented fusion using cervical pedicle screws to treat nontraumatic lesions were independently reviewed. The authors analyzed the medical records of some of these patients who developed postoperative C-5 palsy, paying particular attention to their plain radiographs, MRI studies, and CT scans. Risk factors for postoperative C-5 palsy were assessed using multivariate logistic regression analysis. The cutoff values for the pre- and postoperative width of the intervertebral foramen (C4-5) were determined by receiver operating characteristic curve analysis. RESULTS: Ten (11.9%) of 84 patients developed postoperative C-5 palsy. Seven patients recovered fully from the neurological complications. The pre- and postoperative C4-5 angles showed significant kyphosis in the C-5 palsy group. The pre- and postoperative diameters of the C4-5 foramen on the palsy side were significantly smaller than those on the opposite side in the C-5 palsy group and those bilaterally in the non-C5 palsy group. Risk factors identified by multivariate logistic regression analysis were as follows: 1) ossification of the posterior longitudinal ligament (relative risk [RR] 7.22 [95% CI 1.03-50.55]); 2) posterior shift of the spinal cord (C4-5) (RR 1.73 [95% CI 1.00-2.98]); and 3) postoperative width of the C-5 intervertebral foramen (RR 0.33 [95% CI 0.14-0.79]). The cutoff values of the pre- and postoperative widths of the C-5 intervertebral foramen for C-5 palsy were 2.2 and 2.3 mm, respectively. CONCLUSIONS: Patients with preoperative foraminal stenosis, posterior shift of the spinal cord, and additional iatrogenic foraminal stenosis due to cervical alignment correction were more likely to develop postoperative C-5 palsy after posterior instrumentation with fusion. Prophylactic foraminotomy at C4-5 might be useful when preoperative foraminal stenosis is present on CT. Furthermore, it might be useful for treating postoperative C-5 palsy. To prevent excessive posterior shift of the spinal cord, the authors recommend that appropriate kyphosis reduction should be considered carefully.

Effects of mirtazapine on sleep disturbance under neuropathic pain-like state.

Sleep disturbance has been reported to be one of the most frequent symptoms in patients suffered from severe pain. Benzodiazepines are effective and reduce anxiety in the hours after use, but the induced sleep tends to be less than ideal in quality, with increased Stages I-II and reduces Stages III-IV sleep. In the present study, we investigated sleep disturbance under a neuropathic pain-like state in mice using electroencephalogram (EEG)/electromyogram (EMG). In a model of neuropathic pain, sciatic nerve ligation caused a marked decrease in the latency of paw withdrawal in response to a thermal stimulus only on the ipsilateral side. Under this condition, sciatic nerve-ligated animals showed a statistically significant increase in wakefulness and a decrease in non-rapid eye movement (NREM) sleep during the light phase. Mirtazapine (MTZ) is an antidepressant, which is considered to enhance noradrenergic and serotonergic neurotransmission via antagonistic action at central α2-adrenergic autoreceptors and heteroreceptors. In the present binding study, MTZ showed higher affinity for histamine H1 and serotonin 5-HT(2A/2C) receptors than other receptors, including α2-adrenergic receptor, in the mouse brain tissue. The thermal hyperalgesia and sleep disturbance following nerve ligation were almost completely alleviated by MTZ. These findings suggest that MTZ may improve the quality of sleep as well as control pain in patients with neuropathic pain mainly through histamine H1- and serotonin 5-HT2-receptor antagonistic actions.

Complications of cervical pedicle screw fixation for nontraumatic lesions: a multicenter study of 84 patients.

OBJECT: The cervical pedicle screw (PS) provides strong stabilization but poses a potential risk to the neurovascular system, which may be catastrophic. In particular, vertebrae with degenerative changes complicate the process of screw insertion, and PS misplacement and subsequent complications are more frequent. The purpose of this study was to evaluate the peri- and postoperative complications of PS fixation for nontraumatic lesions and to determine the risk factors of each complication. METHODS: Eighty-four patients who underwent cervical PS fixation for nontraumatic lesions were independently reviewed to identify associated complications. The mean age of the patients was 60.1 years, and the mean follow-up period was 4.1 years (range 6-168 months). Pedicle screw malpositioning was classified on postoperative CT scans as Grade I (< 50% of the screw outside the pedicle) or Grade II (≥ 50% of the screw outside the pedicle). Risk factors of each complication were evaluated using a multivariate analysis. RESULTS: Three hundred ninety cervical PSs and 24 lateral mass screws were inserted. The incidence of PS misplacement was 19.5% (76 screws); in terms of malpositioning, 60 screws (15.4%) were classified as Grade I and 16 (4.1%) as Grade II. In total, 33 complications were observed. These included postoperative neurological complications in 11 patients in whom there was no evidence of screw misplacement (C-5 palsy in 10 and C-7 palsy in 1), implant failure in 11 patients (screw loosening in 5, broken screws in 4, and loss of reduction in 2), complications directly attributable to screw insertion in 5 patients (nerve root injury by PS in 3 and vertebral artery injury in 2), and other complications in 6 patients (pseudarthrosis in 2, infection in 1, transient dyspnea in 1, transient dysphagia in 1, and adjacent-segment degeneration in 1). The multivariate analysis showed that a primary diagnosis of cerebral palsy was a risk factor for postoperative implant failure (HR 10.91, p = 0.03) and that the presence of preoperative cervical spinal instability was a risk factor for both Grade I and Grade II screw misplacement (RR 2.12, p = 0.03), while there were no statistically significant risk factors for postoperative neurological complications in the absence of evidence of screw misplacement or complications directly attributable to screw insertion. CONCLUSIONS: In the present study, misplacement of cervical PSs and associated complications occurred more often than in previous studies. The rates of screw-related neurovascular complications and neurological deterioration unrelated to PSs were high. Insertion of a PS for nontraumatic lesions is surgically more challenging than that for trauma; consequently, experienced surgeons should use PS fixation for nontraumatic cervical lesions only after thorough preoperative evaluation of each patient's cervical anatomy and after considering the risk factors specified in the present study.

Change in microRNAs associated with neuronal adaptive responses in the nucleus accumbens under neuropathic pain.

Neuropathic pain is the most difficult type of pain to control, and patients lose their motivation for the purposive pursuit with a decrease in their quality of life. Using a functional magnetic resonance imaging analysis, we demonstrated that blood oxygenation level-dependent signal intensity was increased in the ipsilateral nucleus accumbens (N.Acc.) following peripheral nerve injury. microRNAs are small, noncoding RNA molecules that direct the post-transcriptional suppression of gene expression, and play an important role in regulating synaptic plasticity. In this study, we found that sciatic nerve ligation induced a drastic decrease in the expression of miR200b and miR429 in N.Acc. neurons. The expression of DNA methyltransferase 3a (DNMT3a), which is the one of the predicted targets of miR200b/429, was significantly increased in the limbic forebrain including N.Acc. at 7 d after sciatic nerve ligation. Double-immunolabeling with antibodies specific to DNMT3a and NR1 showed that DNMT3a-immunoreactivity in the N.Acc. was located in NR1-labeled neurons, indicating that increased DNMT3a proteins were dominantly expressed in postsynaptic neurons in the N.Acc. area under a neuropathic pain-like state. The results of these analyses provide new insight into an epigenetic modification that is accompanied by a dramatic decrease in miR200b and miR429 along with the dysfunction of "mesolimbic motivation/valuation circuitry" under a neuropathic pain-like state. These phenomena may result in an increase in DNMT3a in neurons of the N.Acc. under neuropathic pain, which leads to the long-term transcription-silencing of several genes.

An arterial pulse examination is not sufficient for diagnosis of peripheral arterial disease in lumbar spinal canal stenosis: a prospective multicenter study.

STUDY DESIGN: Prospective, multicenter study. OBJECTIVE: To conduct peripheral arterial disease (PAD) screening on intermittent claudication (IC) in patients with lumbar spinal canal stenosis (LSCS) to examine the relationships among combined LSCS and PAD, symptoms, and physical findings. SUMMARY OF BACKGROUND DATA: IC occurs due to two underlying diseases, LSCS and PAD, and has an increasing prevalence with the aging of society. Reliable diagnosis of PAD is critical for appropriate conservative management of IC patients with LSCS in an Orthopedic Surgery Outpatient Department (OSOPD). METHODS: PAD tests were prospectively conducted in 201 patients with IC and LSCS who initially visited an OSOPD at a hospital affiliated with the Nogoya Spine Group. Occurrence of PAD as a complication was assessed using ankle brachial pressure index (ABI) and toe brachial pressure index (TBI) tests. PAD was diagnosed in patients with ABI ≤ 0.9 or TBI ≤ 0.6, and the relationship of the occurrence of PAD with symptoms and physical findings such as abnormal arterial pulses was investigated. RESULTS: Combined LSCS and PAD was found in 52 patients (26%), with 45 cases (22%) diagnosed on the basis of TBI test in patients with a normal ABI. Of the patients with PAD, many suffered from risk factors for PAD, with a significantly higher frequency of PAD in patients with hyperlipidemia (P < 0.05). PAD also occurred significantly more frequently in patients with abnormal pulses in the popliteal (P < 0.05), posterior tibial (P < 0.0001), and dorsal pedis (P < 0.0001) arteries; however, the sensitivity of these tests for PAD diagnosis was relatively low, at 34%, 60% and 68%, respectively. CONCLUSION: The results of the prospective study define the rate of occurrence of combined LSCS and PAD using ABI and TBI tests for the first time, and the findings suggest that screening for PAD should be conducted in LSCS patients. ABI and TBI tests are necessary for PAD screening in outpatients, whereas observation of the arterial pulse in the lower extremities is necessary but not sufficient for PAD diagnosis.

Effects of gabapentin on brain hyperactivity related to pain and sleep disturbance under a neuropathic pain-like state using fMRI and brain wave analysis.

Neuropathic pain is the most difficult pain to manage in the pain clinic, and sleep problems are common among patients with chronic pain including neuropathic pain. In the present study, we tried to visualize the intensity of pain by assessing neuronal activity and investigated sleep disturbance under a neuropathic pain-like state in mice using functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG)/electromyogram (EMG), respectively. Furthermore, we investigated the effect of gabapentin (GBP) on these phenomena. In a model of neuropathic pain, sciatic nerve ligation caused a marked decrease in the latency of paw withdrawal in response to a thermal stimulus only on the ipsilateral side. Under this condition, fMRI showed that sciatic nerve ligation produced a significant increase in the blood oxygenation level-dependent (BOLD) signal intensity in the pain matrix, which was significantly decreased 2 h after the i.p. injection of GBP. Based on the results of an EEG/EMG analysis, sciatic nerve-ligated animals showed a statistically significant increase in wakefulness and a decrease in non-rapid eye movement (NREM) sleep during the light phase, and the sleep disturbance was almost completely alleviated by a higher dose of GBP in nerve-ligated mice. These findings suggest that neuropathic pain associated with sleep disturbance can be objectively assessed by fMRI and EEG/EMG analysis in animal models. Furthermore, GBP may improve the quality of sleep as well as control pain in patients with neuropathic pain.

Intraoperative spinal cord monitoring of C5 palsy after cervical laminoplasty.

STUDY DESIGN: Retrospective study of C5 palsy after laminoplasty for cervical myelopathy. OBJECTIVE: The objectives of this study were to investigate the morphologic characteristic of C5 palsy patients undergoing cervical laminoplasty with the intraoperative motor-evoked potential (MEP). SUMMARY OF BACKGROUND DATA: A study reported prophylactic foraminotomy for C5 paralysis after laminoplasty for cervical myelopathy. However, no indications have been established. There have been few reports on the intraoperative monitoring of the C5 palsy. This palsy is reported to happen a few days after the surgery in many cases, and the possibility of its detection by intraoperative spinal cord monitoring is unclear. METHODS: Of 153 patients with cervical myelopathy, 9 showed a decrease in upper muscle strength by 1 grade or more by postoperative manual muscle test. Of the 9 patients, 4 patients underwent segmental monitoring of upper limbs by MEP and were included in the paralysis group. Of the 153 patients, 74 (444 muscles) in whom both preoperative and postoperative manual muscle test of the upper limbs showed grade 5, and in whom the MEP monitoring of all these muscles was performed, were included in the nonparalysis group. We investigated the presence of intraoperative changes in 4 MEP parameters: amplitude, latency, duration, and waveform pattern, and the presence of foraminal stenosis in the cross-sectional view of preoperative myelographic computed tomography. RESULTS: In the paralysis group (9 muscles) and nonparalysis group (444 muscles), delay in latency was not observed in any muscle (0% and 0%), and 50% or more reduction of amplitude in 1 muscle (11%) and 22 (5%), prolongation of duration in 1 (11%) and 6 (1%), changes of waveform pattern in 3 (33%) and 40 (9%), and foraminal stenosis in 5 (56%) and 80 (18%), respectively. CONCLUSIONS: In the paralysis group, the incidences of waveform pattern change on intraoperative MEP and stenosis of the intervertebral foramen were higher than those in the nonparalysis group.

Prediction of clinical results of laminoplasty for cervical myelopathy focusing on spinal cord motion in intraoperative ultrasonography and postoperative magnetic resonance imaging.

STUDY DESIGN: Retrospective analysis of preoperative imaging and clinical data from patients undergoing cervical expansive laminoplasty for cervical myelopathy. OBJECTIVE: To investigate preoperative parameters that predict the floating status of the spinal cord at the anterior elements of the cervical spine in both intraoperative ultrasonography (US) and postoperative magnetic resonance imaging (MRI), and to evaluate the association between clinical outcome and spinal cord floating. SUMMARY OF BACKGROUND DATA: Intraoperative US has been used to evaluate the status of the spinal cord after cervical laminoplasty for cervical myelopathy. Few studies have evaluated the predictive preoperative parameters for intraoperative US results. METHODS: Imaging and clinical outcome data were collected from 101 consecutive patients who underwent cervical expansive laminoplasty for cervical myelopathy at Kaikoukai Nagoya Kyouritsu Hospital, Japan, from April 2004 to April 2008. The preoperative parameters associated with spinal cord floating in intraoperative US and postoperative MR images were investigated. Predictive parameters for the rate of recovery according to the Japanese Orthopedic Association score for cervical myelopathy at each follow-up session were also investigated. RESULTS: Predictive parameters for spinal cord floating after decompression in intraoperative US were the cervical vertebrae 2 to 7 (C2-C7) sagittal alignment in the standing neutral position on preoperative plain radiograph radiography (cut-off value=3 degrees) and the C5/6 "beak angle" in preoperative MRI (cut-off value=20 degrees). A predictive parameter for spinal cord floating in postoperative MRI was the C5/6 beak angle in preoperative MRI (cut-off value=21 degrees). The preoperative Japanese Orthopedic Association score and spinal cord floating at anterior elements of the cervical spine in intraoperative US were predictive parameters for clinical outcome. CONCLUSION: Intraoperative US was more useful than postoperative MRI for predicting the clinical outcome of cervical expansive laminoplasty. Knowledge of the predictive parameters for spinal cord floating after cervical expansive laminoplasty could help evaluate the limitations of posterior decompression.

Surgical results of intramedullary spinal cord tumor with spinal cord monitoring to guide extent of resection.

OBJECT: The authors investigated the outcome of intramedullary spinal cord tumor surgery, focusing on the effect of preoperative neurological status on postoperative mobility and the extent of tumor excision guided by intraoperative spinal cord monitoring prospectively. METHODS: Intramedullary spinal cord tumor surgery was performed in 131 patients between 1997 and 2007. The authors compared the pre- and postoperative neurological status and examined the type of surgery in 106 of these patients. A modified McCormick Scale (Grades I-V) was used to assess ambulatory ability (I = normal ambulation; II = mild motor sensory deficit, independent without external aid; III = independent with external aid; IV = care required; and V = wheelchair required). The type of surgery was classified into 4 levels: total resection, subtotal resection, partial resection, and biopsy. RESULTS: The 106 patients consisted of 47 females and 59 males, whose average age was 42.5 years (range 6-75 years). The mean follow-up period was 7.3 years (range 2.5 months-21 years). The tumor types included astrocytoma (12 cases), ependymoma (46 cases), hemangioblastoma (16 cases), cavernous hemangioma (17 cases), and others (15 cases overall: gangliocytoma, 1; germ cell tumor, 1; lymphoma, 3; neurinoma, 1; meningioma, 1; oligodendroglioma, 1; sarcoidosis, 2; glioma, 1; and unknown, 4). Initial total excision, subtotal resection, partial resection, biopsy, and duraplasty were performed in 59, 12, 22, 12, and 1 patients, respectively. According to the preoperative McCormick Scale, ambulatory status was classified as Grades I, II, III, IV, and V in 41(38%), 30 (28%), 14 (13%), 19 (19%), and 2 (2%) patients, respectively. Thirty-three (31%) of 106 patients suffered postoperative neurological deterioration. The number of patients who did not lose ambulatory ability or who achieved an ambulatory status of Grade I or II postoperatively was 33 (80%), 21 (70%), 10 (71%), 8 (42%), and 1 (50%) in patients with preoperative Grades I, II, III, IV, and V, respectively. Total excision was performed in 31 (79%) of 39 patients with preoperative Grade I, 12 (40%) of 30 patients with Grade II, 7 (50%) of 14 patients with Grade III, and 9 of 21 patients (38%) with Grade IV or V, indicating that the rate of total excision was significantly higher in patients with Grade I status. CONCLUSIONS: The postoperative ambulatory ability was excellent in patients with a good preoperative neurological status. Total excision in patients with Grade I or II ambulation was associated with a good prognosis for postoperative mobility. However, the rate of postoperative deterioration was 31.5%, which is relatively high, and patients should be fully informed of this concern prior to intramedullary spinal cord tumor surgery.

The relationship between the type of destructive spondyloarthropathy and its 10 years ago cervical spine alignment.

The objective of this retrospective study was to analyze the relationship between the type of destructive spondyloarthropathy (DSA) and its 10 years ago cervical spine alignment. DSA was reported as a serious complication of long-term hemodialysis. Although previous reports in regard to risk factor of DSA dealt with the period of hemodialysis and the patient's age upon commencement of hemodialysis, we could not find any reports of the relationship between the type of DSA and its 10 years ago cervical spine alignment. In 96 DSA patients who were the subjects of our study, 8 patients were defined as stage 1, 39 patients as stage 2, 5 patients as stage 3 type A, 11 patients as stage 3 type B, and 33 patients as stage 3 type D. The C2/C7 angle of stage 3 type B was statistically low. The number of the abnormal local cervical alignment was larger in stage 3 types A and B. Multivariate analysis revealed that the risk factors of stage 3 types A and B were the C2/C7 angle and the existence of local abnormal alignment. Fifty-four patients were symptomatic due to DSA and treated at our hospital. Forty-four patients were treated conservatively with medications, physiotherapy, or wearing cervical brace. Ten patients underwent surgical treatment. The loss of physiological lordosis of cervical spine promoted the progression of DSA. Furthermore, the number of the abnormalities of local cervical alignment was statistically larger in stage 3 types A and B; they were the crucial factor promoting the progression of DSA stage 3 types A and B.

MR T2 image classification in cervical compression myelopathy: predictor of surgical outcomes.

STUDY DESIGN: Prospective imaging study of patients undergoing surgery for cervical compressive myelopathy. OBJECTIVES.: To investigate whether the classification of increased signal intensity (ISI) on magnetic resonance imaging (MRI) in patients with cervical compressive myelopathy reflects the severity of symptoms and surgical outcome. SUMMARY OF BACKGROUND DATA: The association between ISI and surgical outcome in cervical myelopathy remains controversial. The degree of ISI has not been well discussed. METHODS: A total of 104 patients with cervical compressive myelopathy were prospectively enrolled. All were treated with cervical expansive laminoplasty. MRI was performed in all patients before surgery. ISI of spinal cord was classified into three groups based on sagittal T2-weighted images as follows: Grade 0, none; Grade 1, light (obscure); and Grade 2, intense (bright). The severity of myelopathy was evaluated according to the Japanese Orthopedic Association (JOA) score for cervical myelopathy. RESULTS: Eighty-six patients (83%) showed ISI before surgery. Patients with ISI were significantly older, and had a longer duration of disease, a lower postoperative JOA score, and a worse postoperative recovery rate of JOA score than those without ISI. Preoperative MRI showed 18 patients in Grade 0, 49 patients in Grade 1, and 37 in Grade 2. Duration of disease was the shortest in Grade 0 and longest in Grade 2. Although there was no significant difference in preoperative JOA scores among the three groups, Grade 0 patients had a higher postoperative JOA score and the best postoperative recovery, and Grade 2 had a lower postoperative JOA score and the worst postoperative recovery. CONCLUSION: Preoperative ISI on T2-weighted sagittal MRI was correlated with patient age, duration of disease, postoperative JOA score, and postoperative recovery rate. Patients with the greatest ISI had the worst postop erative recovery. Classification of ISI can be a predictor of surgical outcome.

Cervical pedicle screw fixation in 100 cases of unstable cervical injuries: pedicle axis views obtained using fluoroscopy.

OBJECT: The authors conducted a study to introduce the imaging technique in which pedicle axis views are obtained using fluoroscopy to match the screw entry point with pedicle orientation and to report the clinical results and safety of cervical pedicle screw fixation (PSF) in patients treated for unstable cervical injuries. METHODS: One hundred consecutive patients with unstable cervical injuries underwent PSF in which the authors used fluoroscopic imaging to acquire pedicle axis views. There were 87 men and 13 women whose mean age was 42.5 years. The accuracy of PS placement was examined postoperatively using axial computed tomography (CT) and oblique radiography. Screw malpositioning was classified either as screw exposure (< 50% of the screw outside the pedicle) or pedicle perforation (> 50% of the screw outside the pedicle boundaries). The mean operative time was 97.6 minutes, and the mean estimated blood loss was 221 ml. Local vertebral alignment around the injured segment measured 6.0 degrees of kyphosis preoperatively and 6.7 degrees of lordosis postoperatively. Solid posterior bone fusion was achieved in all but three patients who died shortly after surgery. There was no secondary dislodgment of instrumentation in 95% of these 97 cases. Of the 419 cervical PSs, 43 (10.3%) were of the screw-exposure type and 17 (4.0%) of the pedicle-perforation type. There were two surgery-related complications: one penetration of a probe into the vertebral artery and one radiculopathy. There were six postoperative complications: two cases of instrumentation failure associated with loss of correction, three cases of correction loss (> 10 degrees), and one case of deep wound infection. CONCLUSIONS: Solid posterior fusion without secondary dislodgment of hardware was demonstrated in 95% of the cases. The incidence of complications associated with cervical PSF was not high. Postoperative CT scanning showed that 17 (4.0%) of 419 screws perforated the pedicle. It appears that fluoroscopy performed using pedicle axis views improves the accuracy and safety of cervical PS insertion.

Measurement of the cervical spinal cord volume on MRI.

BACKGROUND: There are some reports about the relationships between the clinical manifestations and the spine morphology or spinal cord morphology in patients with myelopathy. It has also been reported that there are interindividual variations in the cross-sectional area of the spinal cord. In most of these reports, the cross-sectional area, compression ratio, and anteroposterior diameter were used as morphologic parameters of the spinal cord, but no reports have been published on the use of spinal cord volume. OBJECTIVES: To measure the cervical spinal cord volume of healthy people and to evaluate the relationships between this volume and each of height, body weight, age, and gender, in a morphologic study of cervical spinal cord on magnetic resonance imaging (MRI). METHODS: The cervical spinal cord volume of 90 healthy people (47 males, 43 females) was measured on MRI, and the relationships between this volume and each of gender, height, body weight, and age were evaluated. In addition, the cervical spinal cord volume ratio was evaluated. RESULTS: Our study showed that in healthy people, the cervical spinal cord volume depended on the gender, age, height, and body weight and that the cervical spinal cord volume was larger in the males than in the females, decreased with age, and increased with height and body weight. However, the cervical spinal cord volume ratio was not affected by gender, age, height, or body weight. CONCLUSIONS: We consider that the cervical spinal cord volume ratio can be used to evaluate cervical spinal cord atrophy in patients with cervical myelopathy and can be important information in looking for clinically critical points. The cervical spinal cord volume was larger in males than in the females, decreased with age, and increased with height and body weight. The cervical spinal cord volume ratio was not affected by gender, age, height, or body weight.

Destructive spondyloarthropathy in hemodialysis patients: comparison between patients with and those without destructive spondyloarthropathy.

OBJECTIVE: Destructive spondyloarthropathy (DSA) is a serious complication of hemodialysis. The authors' objective was to define the incidence of DSA at their hospital and to search for risk factors for DSA. METHODS: The authors examined 616 patients undergoing hemodialysis. Patients were separated into two groups: those with DSA and those without DSA when hemodialysis was begun. Other variables explored were the etiology of renal failure, total duration of hemodialysis, documentation of osteoporosis (including bone mineral density and serum beta2-microglobulin level), the spinal location of DSA lesions, and the presence of amyloidosis outside the spine. RESULTS: DSA lesions were detected in 123 patients (20.0%). The mean period of hemodialysis was statistically longer in patients with DSA. Statistically, the incidence of osteoporosis was higher and bone mineral density was lower in the patients with DSA. CONCLUSION: On multivariate analysis, risk factors for DSA were found to be the patient's age at the start of hemodialysis and the duration of hemodialysis.

Effects of MPSS and a potent iNOS inhibitor on traumatic spinal cord injury.

ONO-1714, a selective inhibitor of inducible nitric oxide synthetase (iNOS) attenuated the increase of apoptosis and improved the functional outcome of urinary bladder after traumatic spinal cord injury. These findings suggest that iNOS plays a role in the process of SCI. Early treatment with 30 mg/kg methylprednisolone sodium succinate (MPSS) could also inhibit the expression of iNOS gene, apoptosis and the loss of urinary bladder function. We confirmed that early MPSS treatment may prevent injury associated with apoptosis and urinary bladder disability by reducing iNOS mRNA. However, delayed single MPSS treatment 8 h after spinal cord injury was not effective. Early repeated MPSS treatment might allow greater recovery from acute spinal cord injury.

Cervical myelopathy due to OPLL: clinical evaluation by MRI and intraoperative spinal sonography.

BACKGROUND: Concerning the relationship between morphology and clinical outcome, there have been many reports using computed tomography/myelography but not so many using axial magnetic resonance imaging (MRI) of the spinal cord. This is the first report to correlate axial cord image, intensity changes in MRI, and cord expansion pattern using intraoperative ultrasonography. OBJECTIVE: The objectives were to correlate MRI studies, axial cord images/expansion, and changes in MRI intensity to see if there is a direct prognostic significance to these changes and to determine whether preoperative axial MRI images of the spinal cord predict recovery from compressive myelopathy. METHODS: Posterior cervical decompressions with laminoplasty were performed in 44 patients with cervical myelopathy due to ossification of the posterior longitudinal ligament. On T2-weighted MR images, the cross-sectional shape of the cord at the level of maximal compression was categorized as boomerang, teardrop, or triangle. Additionally, with use of intraoperative ultrasonography, the expansion pattern of the cord that occurred intraoperatively was contrasted with that seen on postoperative MR images. RESULTS: Clinical recovery rates were the worst for those with triangular, intermediate for those with boomerang, and the best for those with teardrop shape. Preoperative low T1 and high T2 signals were found in most cases with triangular cord configurations. Triangular cord configurations showed the least expansion among the three categorized spinal cords. CONCLUSION: Patients with triangular deformity of the cord have atrophy as confirmed on MR studies where there is a low T1 and high T2 signal in the cord. Poor postoperative clinical recovery correlates with the lack of postoperative cord expansion on either MR or ultrasound evaluations. Those with either teardrop or boomerang deformities demonstrate a relatively good recovery rate.