Mikinobu Takeuchi

Activation of JAK-STAT3 signaling pathway in chronic subdural hematoma outer membranes

Chronic subdural hematoma (CSDH) is an inflammatory disease, the mechanism of which still remains to be elucidated. Interleukin-6 (IL-6), one of the inflammatory cytokines regulating janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, is expressed in human CSDH fluid. The status of this signaling pathway in human CSDH outer membranes was examined in the present study using outer membranes obtained during trepanation surgery. Concentrations of IL-6 in human CSDH fluids were measured using an enzyme immuno-assay kit. Expression patterns of JAK1, STAT1, phosphorylated (p)-STAT1 at Tyr(701) and at Ser(727), STAT3, p-STAT3 at Tyr(705) and at Ser(727) and actin in outer membranes were examined by Western blot analysis and immunohistochemistry. IL-6 is significantly expressed in human CSDH fluids compared with control cerebrospinal fluid. JAK1, STAT1 and STAT3 were detected in all cases. The expression of p-STAT3 at Tyr(705) is more significant compared with that of p-STAT1 at Tyr(701). In some cases, p-STAT3 at Ser(727) could also be detected, while p-STAT1 at Ser(727) could not. The localizations of STAT1 and STAT3 were revealed to be present in fibroblasts in human CSDH outer membranes, especially when p-STAT3 at Tyr(705) was in the nuclei of fibroblasts. These findings suggest that JAK1-STAT3 signaling is dominantly activated in fibroblasts of human CSDH outer membranes compared with STAT1 and indicate the possibility that this JAK1-STAT3 pathway might be activated by IL-6 and play a critical role in progression of human CSDH.

Variance of cervical vertebral artery measured by CT angiography and its influence on C7 pedicle anatomy.

Study Design. Observational study using a retrospective single-institute database. Objective. To investigate the variance of the vertebral artery (VA) V2 segment and the anatomical features of the C7 pedicle with or without VA entry based on computed tomographic (CT) angiography in 919 consecutive Japanese subjects. Summary of Background Data. Generally, the level of the VA entrance into the transverse foramen is assumed to be C6. Therefore, surgeons tend to pay less attention to VA injury when inserting a C7 pedicle screw. However, anomalies at C7 surely exist and are considered to be 1 of the major risk factors for VA injury during posterior instrumentation. Methods. Subjects who underwent contrast-enhanced CT or CT angiography from November 2011 to October 2012 were eligible. The entrance into the transverse foramen was reviewed. In addition, anatomical features of C7 with or without VA entrance were measured. Results. A total of 919 subjects with a mean age of 56.1 years were surveyed. From among 1838 VA courses, VA entered the C6 transverse foramen in 95.6% of specimens (1757 of 1838 VA courses). Sixty-seven of 919 subjects (7.3%) had a unilateral anomaly and 7 (0.8%) had a bilateral anomaly. An abnormal level of entrance was observed in 8.1% of subjects (74 of 919 patients), and 4.4% of specimens (81 of 1838 VA courses), with a level of entrance into the C4, C5, or C7 transverse foramen in 0.5% (n = 10), 3.1% (n = 57), and 0.8% (n = 14) of all specimens, respectively. C7 transverse foramen with a VA entrance was wider in those without a VA entrance, and abnormal cases frequently showed an uneven transverse foramen. Therefore, the C7 pedicle diameter with abnormal VA entrance was significantly narrower in those without VA entrance (P < 0.01; t test). Conclusion. CT angiography is recommended in cases with an uneven transverse foramen for confirming vascular anomaly. Level of Evidence: 2

Expression of the JAK/STAT3/SOCS3 signaling pathway in herniated lumbar discs

The inflammatory cytokine interleukin-6 (IL-6) plays an important role in causing symptoms of lumbar disk herniation. The present study clarifies the expression of the signaling pathway of IL-6 in herniated discs. Homogenates prepared from lumbar herniated discs from 10 patients were assessed. The expression of janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), phosphorylated (p)-STAT3 at Tyr(705), suppressor of cytokine signaling 3 (SOCS3) and actin was examined by Western blot analysis. The expression of JAK1, STAT3, and p-STAT3 at Tyr(705) was also examined by immunostaining. JAK1, STAT3, p-STAT3 at Tyr(705) and SOCS3 were detected in almost all cases. Immunoreactivity against JAK1 and STAT3 was observed mainly in chondrocytes, whereas immunoreactivity against p-STAT3 at Tyr(705) was observed in the nuclei of chondrocytes. The JAK/STAT signaling pathway might be activated by IL-6 and transmit messages from the cell surface to the nucleus, and the pathway is negatively regulated by SOCS3. These JAK1, STAT3 and SOCS3 molecules might tightly regulate and play a role in the degeneration of chondrocytes within herniated discs.

Risks for Vascular Injury During Anterior Cervical Spine Surgery: Prevalence of a Medial Loop of Vertebral Artery and Internal Carotid Artery.

Study Design. Observational study using a retrospective single-institute database. Objective. To investigate the prevalence of a medial loop (ML) of the vertebral artery (VA) and internal carotid artery (ICA), which might be an anatomical risk factor for arterial injury in anterior cervical surgeries. Summary of Background Data. Anterior cervical spine surgeries are generally considered to be safe and effective. VA injury is one of the most serious complications during anterior procedures. Several articles have reported this complication, which might be because of the anomalous course of VA at V2 segment. The prevalence and anatomical features of those high-risk cases were, however, not investigated. Methods. Consecutive Japanese subjects, who underwent contrast-enhanced computed tomography (CT) or computed tomographic angiography (CTA) for reasons other than evaluation of cervical artery disease from November 2011 to October 2012 in our institution, were reviewed. Exclusion criteria included poor images, past surgery, and endovascular intervention of cervical spine and its vessels. The definition of ML was set as the course of VA and ICA extended medially inside the uncovertebral joint. We also investigated whether those anomalous courses were detectable by plain CT. Results. A total of 1251 subjects with age ranging from 14 to 93 years with a mean of 56.1 years were surveyed. Among them, 1054 subjects were eligible and the others were excluded. A total of 421 subjects were male, and 633 were female. There were 10 cases (1%) with an ML of the VA, and 2 (0.2%) cases with a medial loop of internal carotid artery. Five of the 10 cases with a medial loop of vertebral artery were aberrant into the vertebral body, which were detectable by plain CT. Importantly, the other five cases could not be seen on the CT. Conclusion. One percent of all subjects showed higher anatomical risk for VA and ICA injury during anterior surgery, half of which were undetectable by plain CT. Preoperative evaluation for vascular anatomy may be necessary for safer surgical treatment. Level of Evidence: 4

A Simple, 10-minute Procedure for Transforaminal Injection under Ultrasonic Guidance to Effect Cervical Selective Nerve Root Block

The aim is to provide a detailed procedure of a simple and 10-minute cervical nerve root block (CNRB) under ultrasonic guidance, and to report the clinical outcomes, disorders, and complications. Records of patients who had undergone CNRB, were reviewed under ultrasonic guidance at the hospital from 2010 through 2012. The procedure is described in detail. Arm and shoulder pain was evaluated by use of the visual analogue scale (VAS). Forty-three patients agreed to undergo CNRB under ultrasonic guidance. Nerve roots from C5 to C8 were affected in 41, and these nerve roots were readily distinguished. Two of the 43 participants did not receive injections because impediments in visualizing the affected nerve root. Of the 41 who received injections, radicular pain immediately disappeared in 39, who continued to feel pain relief 1 month later. However, pain recurred in 15 patients (38%), of whom 11 underwent cervical spine surgery. The rest of 24 patients felt sustained pain relief longer than 3 months after the injection, significantly. Although one patient had recurrent radicular pain 10 months later, the pain could be controlled by medication. At the final follow-up periods, 17.2 (10–24 months), the median VAS score of the patients, 23 (0 to 71 mm), was significantly improvement (P = 0.001) in comparison to before injection 88 (range; 56–100). No complications occurred. The cervical nerve root block under ultrasonic guidance simply, safely, and efficaciously decreased radicular pain for 17.2 months in 62% patients with intolerable radicular pain.

A large retro-odontoid cystic mass caused by transverse ligament degeneration with atlantoaxial subluxation leading to granuloma formation and chronic recurrent microbleeding case report

BACKGROUND CONTEXT Noninfectious nontumorous retro-odontoid masses are rare, and masses have not been reported to extensively compress the spinal cord. We encountered a case of a large retro-odontoid lesion that extensively compressed the spinal cord. CASE REPORT A 76-year-old-man reported experiencing a sudden onset of neck pain, hand and foot paresthesia, dysarthria, and dysphagia. When symptoms had not eased by 10 days of treatment with external stabilization and bed rest, he was referred to our hospital. Dynamic radiographs of the cervical spine showed that the atlantodental interval widened from 2 mm on extension to 7 mm on flexion. Computed tomography did not reveal abnormality of the odontoid process or the presence of a high-density area that could suggest calcification in or near the cystic mass. Fluid-attenuated inversion recovery axial magnetic resonance image showed a mass that was 3.0-cm wide, 2.7-cm high, and 2.5-cm thick that severely compressed the lower brain stem. T2-weighted magnetic resonance imaging showed that the mass contained a solid part posterior to the C2 dense area, extending rostrally, compatible with the presence of degenerated and hypertrophic ligaments. We performed surgical decompression of the lesion combined with atlantoaxial fixation. The partly cystic mass, which was located extradurally, had xanthochromic content, indicating microbleeding. Dysarthria and dysphagia immediately disappeared, and neurologic symptoms disappeared by 1 month. At 1-year follow-up, the patient remained symptom free, and computed tomography scans did not show recurrence of the mass. The pathologic diagnosis of degenerative ligament tissue with chronic recurrent microbleeding and associated granulation was made. DISCUSSION A possible explanation why the cyst grew to an exceptionally large size is that the transverse ligament of axis became degenerated and hypertrophic because of chronic mechanical stress by atlantoaxial subluxation. Then, a part of the ligament developed reactive granulation with small vessel formation. Finally, rupture of these small vessels caused repeated episodes of microbleeding, resulting in formation of a large cyst. The observation of degenerative ligament tissue, granulation formation, and microbleeding differentiated it from a synovial cyst or a ganglion cyst. The presence of hemosiderin deposits suggested chronic recurrent microbleeding. Taking all our findings together, we believe that our case of retro-odontoid cystic mass is different from the others that have been reported. Atlantoaxial instability may cause a large mass, such as we described here, so that careful observation is important.

Surgical Intervention for Instability of the Craniovertebral Junction

Surgical approaches for stabilizing the craniovertebral junction (CVJ) are classified as either anterior or posterior approaches. Among the anterior approaches, the established method is anterior odontoid screw fixation. Posterior approaches are classified as either atlanto-axial fixation or occipito-cervical (O-C) fixation. Spinal instrumentation using anchor screws and rods has become a popular method for posterior cervical fixation. Because this method achieves greater stability and higher success rates for fusion without the risk of sublaminar wiring, it has become a substitute for previous methods that used bone grafting and wiring. Several types of anchor screws are available, including C1/2 transarticular, C1 lateral mass, C2 pedicle, and translaminar screws. Appropriate anchor screws should be selected according to characteristics such as technical feasibility, safety, and strength. With these stronger anchor screws, shorter fixation has become possible. The present review discusses the current status of surgical interventions for stabilizing the CVJ.

Prevalence of C7 level anomalies at the C7 level: an important landmark for cervical nerve ultrasonography.

Background Recently, various examination and intervention techniques using cervical nerve ultrasonography have been developed. The specific shapes of the C7 transverse process and vertebral artery in front of the C7 transverse process have become landmarks. Purpose To determine the prevalence of anomalies and anomalous vertebral artery entrances at the C7 transverse process. Material and Methods The records of patients who underwent plain or contrast-enhanced neck or cervical spine computed tomography (CT) were reviewed. The examinations were scored for the anomalous presence of anterior tubercles or cervical ribs as well as vertebral artery entrances in the C7 transverse process. The prevalence of anomalies was compared based on patient sex and age. Results Evaluating the examinations from 2067 patients (1046 men; 1021 women), 1% of patients exhibited an anomalous presence of anterior tubercles, and 0.3% of patients displayed cervical ribs at the C7 transverse process. The prevalence of anomalies process was significantly higher in men aged less than 40 years than in older men (P < 0.001), whereas the prevalence was not higher in women aged less than 40 years than in older women. The prevalence of vertebral artery entry into the C7 transverse foramen was 0.6%. Conclusion Although an anomalous vertebral artery entry into the C7 transverse foramen was rare, the prevalence of an anomaly at the C7 transverse process was higher in men aged less than 40 years. Therefore, we recommend performing CT in younger men before cervical nerve ultrasonographic intervention to avoid misinterpretations at the cervical level.

Pathomorphological description of the shunted portion of a filum terminale arteriovenous fistula

BACKGROUND CONTEXT The clinical morphology of a filum terminale arteriovenous fistula (f-AVF) is well known; however, pathological details of the fistulized portion are unknown. Herein, we report the pathological findings of the f-AVF. STUDY DESIGN Case report and literature review. PURPOSE To present a detailed pathological examination of the fistulized portion of the f-AVF. METHODS A 71-year-old man presented with gradually worsening bilateral foot paresthesias and anal dysesthesia. T2-weighted magnetic resonance imaging showed flow voids surrounding an edematous conus medullaris and cauda equina with spinal stenosis at L3-L4 and L4-L5. Spinal digital subtraction angiography demonstrated an f-AVF fed by the left T9 intercostal artery. RESULTS We performed laminotomies of L3 and L4 to open the dura mater and found a hypertrophic filum terminale. It was resected, leaving a length of 2 cm between the abnormal proximal end and normal distal end. The f-AVF completely disappeared after the surgery. On pathological examination, the filum terminale included two vessels at the proximal end and one at the distal end. At the proximal end, immunostaining showed one vessel that was definitively an artery with both an internal elastic membrane (IEM) and smooth muscle. The other was a vein and lacked an IEM. On the distal side, the collagen fibers gradually increased, the IEM partially disappeared from the arterial wall, and the vein became arterialized with a thin IEM. At the distal end the two vessels joined. Therefore, we speculated that the fistulized portion of the f-AVF was not a fistula point but had some lengths where the artery had characteristics of a vein and there was venous arterialization. CONCLUSIONS The filum arteriovenous shunting occurred at the portion where there was venous arterialization and the artery had the characteristics of a vein. Therefore, resecting the filum terminale requires more proximal from the normal distal end.

Radiographic measurements of C-2 in patients with atlas assimilation.

OBJECT The object of this study was to evaluate the radiographic characteristics of C-2 using multiplanar CT measurements for anchor screw placement in patients with C-1 assimilation (C1A). Insertion of a C-2 pedicle screw in the setting of C1A is relatively difficult and technically demanding, and there has been no report about the optimal sizes of the pedicles and laminae of C-2 for screw placement in C1A. METHODS An institutional database was searched for all patients who had undergone cervical CT scanning and cervical spine surgery between April 2006 and December 2012. Two neurosurgeons reviewed the CT scans from 462 patients who met these criteria, looking for C1A and other anomalies of the craniocervical junction such as high-riding vertebral artery (VA), basilar invagination, and VA anomaly. The routine axial images were reloaded on a workstation, and reconstruction CT images were used to measure parameters: the minimum width of bilateral pedicles and laminae and the length of bilateral laminae of the atlas. RESULTS Seven patients with C1A were identified, and 14 sex-matched patients without C1A were randomly selected from the same database as a control group. The mean minimum pedicle width was 5.21 mm in patients with C1A and 7.17 mm in those without. The mean minimum laminae width was 5.29 mm in patients with C1A and 6.53 mm in controls. The mean minimum pedicle and laminae widths were statistically significantly smaller in the patients with C1A (p < 0.05). CONCLUSIONS In patients with C1A, the C-2 bony structures are significantly smaller than normal, making C-2 pedicle screw or translaminar screw placement more difficult.