Clinical Characteristics and Long-term Outcomes of Spinal Pilocytic Astrocytomas: A Multicenter Retrospective Study by the Neurospinal Society of Japan.

OBJECTIVE: The characteristics, imaging features, long-term surgical outcomes, and recurrence rates of primary spinal pilocytic astrocytomas (PAs) have not been clarified owing to their rarity and limited reports. Thus, this study aimed to analyze the clinical presentation, radiological features, pathological findings, and long-term outcomes of spinal PAs. METHODS: Eighteen patients with spinal PAs who were surgically treated between 2009 and 2020 at 58 institutions were included in this retrospective multicenter study. Patient data, including demographics, radiographic features, treatment modalities, and long-term outcomes, were evaluated. RESULTS: Among the 18 consecutive patients identified, 11 were women and 7 were men; the mean age at presentation was 31 years (3-73 years). Most PAs were located eccentrically, were solid or heterogeneous in appearance (cystic and solid), and had unclear margins. Gross total resection (GTR), subtotal resection (STR), partial resection (PR), and biopsy were performed in 28%, 33%, 33%, and 5% of cases, respectively. During a follow-up period of 65 ± 49 months, 4 patients developed a recurrence; however, the recurrence-free survival did not differ significantly between the GTR and non-GTR (STR, PR, and biopsy) groups. CONCLUSION: Primary spinal PAs are rare and present as eccentric and intermixed cystic and solid intramedullary cervical tumors. The imaging features of spinal PAs are nonspecific, and a definitive diagnosis requires pathological support. Surgical resection with prevention of neurological deterioration can serve as the first-line treatment; however, the resection rate does not affect recurrence-free survival. Investigation of relevant molecular biomarkers is required to elucidate the regrowth risk and prognostic factors.

Bone wax technique for full-endoscopic lumbar laminotomy.

Hemostatic procedures in endoscopic spine surgery have not yet been established, especially in full-endoscopic spine surgery (FESS) performed under continuous irrigation, which has been a major concern for surgeons. Chu et al. had previously reported a technique to convey bone wax during full-endoscopic cervical spine surgery via intracorporeal route by using ball tip of the drill in 2018. However, to the best of our knowledge, there has been no report by surgeons to adopt bone wax as a hemostatic material in full-endoscopic lumbar surgery to date, probably because of difficulty in handling bone wax under continuous irrigation and through a narrow and long working channel in endoscope. We have renewed the bone wax technique (BWT) for hemostasis in FESS, improving its handling by introducing a nozzle applicator, without which the bone wax would stick to the working channel of the endoscope on the way to the bleeding target. This would result in significant loss of bone wax and repeated bone-wax contact would cause dirt build-up on the endoscope lens, which would then be pushed out from the wall of the working channel, thereby disturbing the laminectomy procedure and obfuscating the visual field. Technical details using nozzle-loaded bone wax have been demonstrated.

Utility of intraoperative real-time near-infrared fluorescence surgery for spinal schwannoma.

The authors report the first cases of fluorescence-guided spinal surgery of schwannomas using near-infrared fluorescence imaging with the delayed window indocyanine (ICG) green (DWIG) technique for accurate real-time intraoperative tumor visualization. Patients with intradural spinal schwannomas received 0.5 mg/kg ICG at the beginning of surgery. After 1 hour, using the DWIG technique, near-infrared spectroscopy (NIRS) detected the spinal schwannomas, showing the exact tumor location and boundaries. DWIG with NIRS microscopy confirmed the exact location of spinal schwannomas before and after opening of the dura mater, thereby facilitating successful tumor dissection from the surrounding tissues, tumor resection, and confirmation of tumor removal. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21158.

Usefulness of three-dimensional computed tomography venography differentiating calvarium subperiosteal hematoma crossing the suture lines due to hair pulling from subgaleal hematoma: case report and review of the literature.

This case showed a 13-year-old boy presented with calvarium subperiosteal hematoma crossing the suture lines caused by hair pulling, and 3D-CTV can differentiate calvarium subperiosteal hematoma crossing the suture lines from subgaleal hematoma. He was treated successfully.

Intraoperative real-time near-infrared optical imaging for the identification of metastatic brain tumors via microscope and exoscope.

OBJECTIVE: As chemotherapy and radiotherapy have developed, the role of a neurosurgeon in the treatment of metastatic brain tumors is gradually changing. Real-time intraoperative visualization of brain tumors by near-infrared spectroscopy (NIRS) is feasible. The authors aimed to perform real-time intraoperative visualization of the metastatic tumor in brain surgery using second-window indocyanine green (SWIG) with microscope and exoscope systems. METHODS: Ten patients with intraparenchymal brain metastatic tumors were administered 5 mg/kg indocyanine green (ICG) 1 day before the surgery. In some patients, a microscope was used to help identify the metastases, whereas in the others, an exoscope was used. RESULTS: NIRS with the exoscope and microscope revealed the tumor location from the brain surface and the tumor itself in all 10 patients. The NIR signal could be detected though the normal brain parenchyma up to 20 mm. While the mean signal-to-background ratio (SBR) from the brain surface was 1.82 ± 1.30, it was 3.35 ± 1.76 from the tumor. The SBR of the tumor (p = 0.030) and the ratio of Gd-enhanced T1 tumor signal to normal brain (T1BR) (p = 0.0040) were significantly correlated with the tumor diameter. The SBR of the tumor was also correlated with the T1BR (p = 0.0020). The tumor was completely removed in 9 of the 10 patients, as confirmed by postoperative Gd-enhanced MRI. This was concomitant with the absence of NIR fluorescence at the end of surgery. CONCLUSIONS: SWIG reveals the metastatic tumor location from the brain surface with both the microscope and exoscope systems. The Gd-enhanced T1 tumor signal may predict the NIR signal of the metastatic tumor, thus facilitating tumor resection.

Growing skull fracture with an atypical mechanism: a case report.

Growing skull fractures (GSFs) are well-known but rare causes of pediatric head trauma. They generally occur several months after a head injury, and the main lesion is located under the periosteum. We herein report a case involving a 3-month-old boy with GSF that developed by a different mechanism than previously considered. It developed 18 days after the head injury. A large mass containing cerebrospinal fluid and brain tissue was present within the periosteum. A good outcome was obtained with early strategic surgery. Injury to the inner layer of the periosteum and sudden increase in intracranial pressure might be related to GSF in this case.

Efficacy of Endovascular Proximal Occlusion before Direct Reposition Surgery of Blunt Cervical Fracture with Unilateral Vertebral Injury.

Cerebral infarction related to traumatic vertebral artery (VA) injuries is not common. However, if VA injuries cause ischemic and/or hemorrhage stroke, these subsequent problems can result in severe residual impairment and mortality. Herein, we present five patients with cervical vertebra fractures due to blunt cervical trauma who underwent preoperative endovascular therapy. Between June 2010 and April 2018 in our hospital, five patients with traumatic occlusion of a unilateral VA underwent coil embolization to prevent post-surgical stroke due to reperfusion in the VA. Because of cervical instability or subluxation, all of the patients received endovascular therapy before surgery for their cervical fracture. None of the patients presented with stroke after presurgical embolization and direct surgery. When stagnated blood, including thrombi, in the occluded VA is released during cervical surgery, brain embolism may occur. Therefore, early cerebrovascular vessel assessment and presurgical endovascular treatment must be considered to prevent stroke after direct surgery.

Endovascular Embolization of Sinus Pericranii Using Plastic Cup During Glue Injection.

BACKGROUND: Sinus pericranii (SP) is a rare abnormal connection between the intracranial and extracranial venous drainage pathways through the osseous channels. Herein we present the case of a patient with growing SP, which was successfully treated using endovascular transvenous embolization through external compression with a plastic cup for preventing glue migration into subcutaneous veins. CASE DESCRIPTION: A 9-month-old boy presented with a gradually growing mass on the midline cranial vertex after his birth, for which transvenous embolization was performed. A microcatheter was successfully navigated into the SP from the superior sagittal sinus. Because the subcutaneous drainages were confirmed to be multidirectional, we compressed the drainages through the skin using a plastic cup during the glue injection step for preventing glue migration. Subsequently, the SP was completely obliterated. The postoperative course was uneventful. CONCLUSIONS: Manual compression using a plastic cup was useful not only for embolization but also for reducing the physician's exposure to radiation as compared with that in the finger compression method. When a direct puncture is required, a plastic cylinder can also be used.

Reliability of an Intraoperative Radiographic Anteroposterior View of the Spinal Midline for Detection of Pedicle Screws Breaching the Medial Pedicle Wall in the Thoracic, Lumbar, and Sacral Spine.

OBJECTIVE: The purpose of this study was to determine the sensitivity and specificity of using the spinal midline (M line) on a radiographic anteroposterior (AP) view for detecting pedicle screws (PSs) breaching the medial pedicle wall. METHODS: We retrospectively reviewed 145 patients who underwent fusion surgery using PSs between January 2006 and May 2017. We defined the M line as a line that connected the upper and lower spinous processes through the fixed vertebrae. The M line was positive if the tip of the PS crossed the M line. The reference standard was a computed tomography scan. The reliability of the M line was examined. RESULTS: The subjects included 145 patients (70 men and 75 women; mean age, 63.4 years). A total of 599 PSs were examined. Most cases were because of spondylolisthesis (66.9%). Most screws were inserted at a lower lumber level (77.6%). Analysis of the diagnostic accuracy of the M line yielded a sensitivity of 74.1% and a specificity of 95.3%. In addition, the positive predictive value of the M line was 42.6%, and the negative predictive value of the M line was 98.7%. CONCLUSIONS: Assessment of the M line via an intraoperative radiographic AP view is a simple, readily available, complementary method for detecting PSs that have breached the medial pedicle wall in the thoracic, lumbar, and sacral spine. In particular, the M line has a strong negative predictive value, which is much more meaningful.

Pseudoprogression successfully treated with bevacizumab in a child with spinal pilocytic astrocytoma.

CLINICAL CASE: We report on a 7-year-old female with spinal pilocytic astrocytoma complicated by pseudoprogression 1 month after completion of radiation therapy. Although she was initially treated with high-dose steroids, her clinical symptoms did not completely resolve, and magnetic resonance imaging (MRI) revealed extension of the lesions into the medulla oblongata. Treatment with bevacizumab was commenced, followed by rapid resolution of the clinical symptoms and improvements in the MRI findings. CONCLUSION: This case highlights the efficacy and tolerability of bevacizumab for the treatment of pseudoprogression in children with spinal low-grade gliomas.

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.

Duration of the horizontal decubitus position for prevention of cerebrospinal fluid leakage following transection of a tight filum terminale.

OBJECT: The untethering of a tethered spinal cord in patients with a tight filum terminale is a relatively simple procedure that can prevent or improve neurological symptoms. Postoperatively, patients are usually kept in the horizontal decubitus position to prevent a CSF leak. However, the optimal period for keeping patients flat has not been determined yet. The authors compared 2 cohorts with different periods of horizontal decubitus; one with 72 hours and the other with 8 days. METHODS: The authors retrospectively analyzed surgical results in 2 cohorts of pediatric patients who had tethered spinal cord with a tight filum terminale. One cohort was maintained flat for 8 days and the other cohort for 72 hours postoperatively. The patients' charts were reviewed for demographic data, clinical presentation, surgical therapy, and clinical course. RESULTS: Three hundred fifty-four patients underwent sectioning of a tight filum terminale. Of those, 238 were kept lying flat for 8 days postoperatively, and 116 were maintained flat for 72 hours. Magnetic resonance imaging was performed 1 to 2 weeks after the surgery. None of the patients in either cohort developed a CSF leak. Pseudomeningocele, which was confirmed by MRI, developed in 1 patient who had been kept flat for 8 days. The occurrence rates of a CSF leak and pseudomeningocele were not significantly different in either cohort. CONCLUSIONS: Keeping patients flat for longer than 72 hours did not change the rate of postoperative CSF leakage or pseudomeningocele. Seventy-two hours or less would be an appropriate period for maintaining patients flat after transection of a tight filum terminale.

Lumbar extraforaminal entrapment: performance characteristics of detecting the foraminal spinal angle using oblique coronal MRI. A multicenter study.

BACKGROUND CONTEXT: Previous conventional magnetic resonance imaging reports on extraforaminal entrapment (e-FE) on L5-S1 have been problematic because of their complexity or lack of sensitivity and specificity. In this study, we propose a simple diagnostic method for e-FE. PURPOSE: The purpose of this study was to determine the sensitivity and specificity of using the difference in the foraminal spinal nerve (FSN) angle of the L5 nerve, as determined by oblique coronal T2-weighted imaging (OC-T2WI), for diagnosing L5-S1 unilateral e-FE. STUDY DESIGN: The study design involves diagnostic accuracy with retrospective case-control study. PATIENT SAMPLE: Seventy consecutive patients with unilateral L5 radiculopathy who underwent unilateral L5-S1 extraspinal canal decompression for e-FE or 4/5 intraspinal canal decompression for lumbar spinal canal stenosis between 2009 and 2013 were included. OUTCOME MEASURES: The Japanese Orthopedic Association score, Visual Analog Scale score for leg pain, and OC-T2WI for the FSN angle of the L5 nerve were examined. METHODS: The 70 patients were divided into two groups: Group A (n=21) with unilateral L5-S1 e-FE and Group B (n=49) with intraspinal canal L4-L5. Group C (n=44) comprised the control group, which included only patients with back pain without leg radiculopathy. All patients underwent OC-T2WI, and the differences in the FSN angle of the fifth lumbar spinal nerve between the symptomatic and asymptomatic sides (ΔFSN angle) were examined and compared among the groups. RESULTS: There were no significant differences in the patient characteristics among the three groups. The ΔFSN angle was 17° in Group A, 4.8° in Group B, and 6.4° in Group C, and the laterality was significantly larger in Group A than in the other two groups. A receiver-operating characteristic curve showed areas under the curve between groups A and B and between groups A and C of 0.93 and 0.97, respectively. In addition, the cutoff value of the ΔFSN angle (10°) indicated diagnostic accuracies of 94% and 91% (sensitivity and specificity) and of 93% and 95%, respectively. CONCLUSIONS: Determining differences in the FSN angle between the symptomatic and asymptomatic sides of greater than 10° via OC-T2WI represented a simple, readily available, and complementary diagnostic method for lumbar e-FE.

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.

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.

Different modifications of phosphorylated Smad3C and Smad3L through TGF-ß after spinal cord injury in mice.

Transforming growth factor-ß (TGF-ß) is an anti-inflammatory cytokine and is expressed in the injured spinal cord. TGF-ß signals through receptors to activate Smad proteins, which translocate into the nucleus. In the present study, we investigated the chronological alterations and cellular locations of the TGF-ß/Smad signaling pathway following spinal cord injury (SCI) in mice. ELISA analysis showed that the concentration of interleukin-6 (IL-6) in injured spinal cords significantly increases immediately after SCI, while the concentration of TGF-ß gradually increased after SCI, peaked at 2 days, and then gradually decreased. Immunohistochemical studies revealed that Smad3 was mainly expressed in neurons of the spinal cord. Phosphorylated Smad3 at the C-terminus (p-Smad3C) was stained within the motor neurons in the anterior horn, while phosphorylated Smad3 at the linker regions (p-Smad3L) was expressed in astrocytes within gray matter. These findings suggest that SCI induces gradual increases in TGF-ß and induces different activation of p-Smad3C and p-Smad3L. Phosphorylated Smad3C might be involved in neuronal degeneration after SCI, and p-Smad3L may play a role in glial scar formation by astrocytes.

Duration of horizontal decubitus after section of a tight filum terminale as a means to prevent cerebrospinal fluid leakage.

OBJECT: The untethering of a tethered spinal cord by transecting a tight filum terminale is a relatively simple surgical procedure that can prevent or ameliorate neurological symptoms. Postoperatively patients are usually kept flat in order to prevent a cerebrospinal fluid (CSF) leak. However, the optimal period of maintaining patients flat has not been determined yet. The authors present their experience, compare with ones of previous reports, and try to determine the optimal period. METHODS: We retrospectively analyzed surgical results of pediatric patients with tethered spinal cord by a tight filum terminale. The patients' charts were reviewed for demographic data, clinical presentation, surgical therapy, and clinical course. RESULTS: One hundred-sixty-one patients underwent sectioning of a tight filum terminale. They all were kept lying flat for 8 days. Magnetic resonance imaging (MRI) was performed 10 to 14 days after the surgery. None of the patients developed a CSF leak. Pseudomeningocele, which was confirmed by MRI, developed in one patient (0.6%). The occurrence rate of a CSF leak was significantly lower in our series than that of previous reports in which patients maintained flat less than 72 hours (P = 0.0069). CONCLUSION: To keep patients flat for a longer time after transection of a tight filum terminale seems to lower the rate of CSF leakage and psuedomeningocele.

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.

Endoscopic fenestrations for suprasellar arachnoid cysts.

OBJECT: The endoscopic treatment of a suprasellar arachnoid cyst (SAC) consists mainly of ventriculocystostomy (VC) and ventriculocystocisternostomy (VCC). However, the most appropriate treatment for these cysts has not been fully determined yet. The authors report on the effectiveness of endoscopic VC for SACs communicating with the basal cisterns, which is demonstrated by preoperative CT cisternography. METHODS: The authors retrospectively analyzed the surgical results of patients with an SAC treated using endoscopic fenestration. The patient charts were reviewed for demographic data, clinical presentations, surgical therapies, and clinical outcomes. RESULTS: Six consecutive patients with SAC were surgically treated using endoscopic fenestration (VC or VCC) between March 2004 and February 2011. The mean age was 18.5 months (range 5 days to 37 months). Five patients were previously untreated, and 1 patient had previously undergone ventriculoperitoneal shunt placement. Five patients underwent preoperative CT cisternography, and communication between the SAC and the basal cisterns was demonstrated in 3 patients, very slight communication in 1, and no communication in 1. Four patients, including the 3 with communication between the SAC and basal cisterns, underwent VC. Two patients with very slight or no communication underwent VCC. In all patients the SAC decreased in size and hydrocephalus improved postoperatively. Five patients (3 treated with VC and 2 with VCC [83%]) have been stable without reoperation (mean follow-up 32.7 months). All 3 patients with an SAC communicating with the basal cisterns have been stable without reoperation following VC. CONCLUSIONS: Preoperative cisternography may be useful for selecting the optimal endoscopic treatment method for SAC. If an SAC communicates with the basal cisterns, a VC could be an effective, safe, and simpler treatment option.