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Xavier T. J. Hsu, Chih-Hsiang Liao, Chun-Fu Lin and Sanford P. C. Hsu

A 57-year-old man presented with acute changes in mental status. Brain CT showed a high-density lesion at the pons. Brain MRA revealed a very slow-flow vascular lesion at the right aspect of the pons, about 3.9 ⋅ 3.0 ⋅ 3.0 cm3, compatible with a pontine cavernous malformation (CM). Gross-total removal was achieved. In this approach, a wider surgical corridor was obtained by opening the Meckel’s cave and cutting the tentorium. For a midline attack point on the pons, additional removal of the posterior clinoid process can meet the goal. In the authors’ opinion, this approach is safe and effective in selected ventrolateral pontine CMs.

The video can be found here: https://youtu.be/moHqEkp5eCA.

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Chih-Hsiang Liao, Chun-Fu Lin, Sanford PC. Hsu, Min-Hsiung Chen and Yang-Hsin Shih

Symptomatic intracavernous aneurysm is rare. Cranial nerves in the cavernous sinus are subjected to the mass effect of an expanding aneurysm. Microsurgical clipping is the treatment of choice to relieve compressive cranial neuropathy. In this video, the authors present a case of intracavernous aneurysm causing diplopia, ptosis, and facial numbness. The patient was operated on via a pretemporal transclinoid-transcavernous approach. The aneurysm was completely obliterated through direct clipping. There were no new-onset neurologic deficits and complications after the operation. Complete recovery of the diplopia, ptosis, and facial numbness was observed at the 6-month postoperative follow up.

The video can be found here: http://youtu.be/4w5QUoNIAQM.

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Cheng-Shyuan Rau, Chun-Chung Lui, Cheng-Loong Liang, Han-Jung Chen, Yeh-Lin Kuo and Wu-Fu Chen

✓ There is a wide variety of disorders associated with thrombosis of the superior sagittal sinus (SSS), including infectious disease, noninfectious conditions such as vasculitis and hypercoagulable states, and complications arising from pregnancy or use of oral contraceptive medications. Despite these well-defined associations, approximately 25% of the cases remain idiopathic. In this article the authors describe a patient who was found to have SSS thrombosis while experiencing a thyrotoxic phase of Graves disease. The patient presented with intracerebral hemorrhage, subarachnoid hemorrhage, seizure, coma, a raised fibrinogen concentration, low protein C activity, and atrial fibrillations. Thrombolysis was successfully performed despite the coexistence of thrombosis and intracranial hemorrhage. Patients with thyrotoxicosis and a diffuse goiter may be predisposed to the development of SSS thrombosis, as a result of hypercoagulation and stasis of local venous blood flow. In the present case, a patient in whom thrombosis coexisted with intracranial hemorrhage was successfully treated using thrombolytic therapy.

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Chien-Yi Chiang, Meei-Ling Sheu, Fu-Chou Cheng, Chun-Jung Chen, Hong-Lin Su, Jason Sheehan and Hung-Chuan Pan

Object

Neuropathic pain is debilitating, and when chronic, it significantly affects the patient physically, psychologically, and socially. The neurobehavior of animals used as a model for chronic constriction injury seems analogous to the neurobehavior of humans with neuropathic pain. However, no data depicting the severity of histomorphological alterations of the nervous system associated with graded changes in neurobehavior are available. To determine the severity of histomorphological alteration related to neurobehavior, the authors created a model of chronic constrictive injury of varying intensity in rats and used the CatWalk XT system to evaluate neurobehavior.

Methods

A total of 60 Sprague-Dawley rats, weighing 250–300 g each, were randomly assigned to 1 of 5 groups that would receive sham surgery or 1, 2, 3, or 4 ligatures of 3-0 chromic gut loosely ligated around the left sciatic nerve. Neurobehavior was assessed by CatWalk XT, thermal hyperalgesia, and mechanic allodynia before injury and periodically after injury. The nerve tissue from skin to dorsal spinal cord was obtained for histomorphological analysis 1 week after injury, and brain evoked potentials were analyzed 4 weeks after injury.

Results.

Significant differences in expression of nerve growth factor existed in skin, and the differences were associated with the intensity of nerve injury. After injury, expression of cluster of differentiation 68 and tumor necrosis factor–α was increased, and expression of S100 protein in the middle of the injured nerve was decreased. Increased expression of synaptophysin in the dorsal root ganglion and dorsal spinal cord correlated with the intensity of injury. The amplitude of sensory evoked potential increased with greater severity of nerve damage. Mechanical allodynia and thermal hyperalgesia did not differ significantly among treatment groups at various time points. CatWalk XT gait analysis indicated significant differences for print areas, maximum contact maximum intensity, stand phase, swing phase, single stance, and regular index, with sham and/or intragroup comparisons.

Conclusions.

Histomorphological and electrophysiological alterations were associated with severity of nerve damage. Subtle neurobehavioral differences were detected by the CatWalk XT system but not by mechanical allodynia or thermal hyperalgesia. Thus, the CatWalk XT system should be a useful tool for monitoring changes in neuropathic pain, especially subtle alterations.

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Chih-Hsiang Liao, Jui-To Wang, Chun-Fu Lin, Shao-Ching Chen, Chung-Jung Lin, Sanford P. C. Hsu and Min-Hsiung Chen

OBJECTIVE

Despite the advances in skull base techniques, large petroclival meningiomas (PCMs) still pose a challenge to neurosurgeons. The authors’ objective of this study was to describe a pretemporal trans–Meckel’s cave transtentorial approach for large PCMs and to report the surgical outcomes.

METHODS

From 2014 to 2017, patients harboring large PCMs (> 3 cm) and undergoing their first resection via this procedure at the authors’ institute were included. In combination with pretemporal transcavernous and anterior transpetrosal approaches, the trans–Meckel’s cave transtentorial route was created. Surgical details are described and a video demonstrating the procedure is included. Retrospective review of the medical records and imaging studies was performed.

RESULTS

A total of 18 patients (6 men and 12 women) were included in this study, with mean age of 53 years. The mean sizes of the preoperative and postoperative PCMs were 4.36 cm × 4.09 cm × 4.13 cm (length × width × height) and 0.83 cm × 1.08 cm × 0.75 cm, respectively. Gross-total removal was performed in 7 patients, near-total removal (> 95%) in 7 patients, and subtotal removal in 4 patients (> 90% in 3 patients and > 85% in 1 patient). There were no surgical deaths or patients with postoperative hemiplegia. Surgical complications included transient cranial nerve (CN) III palsy (all patients, resolved in 3 months), transient CN VI palsy (2 patients), CN IV palsy (3 patients, partial recovery), hydrocephalus (3 patients), and CSF otorrhea (1 patient). Temporal lobe retraction–related neurological deficits were not observed.

CONCLUSIONS

A pretemporal trans–Meckel’s cave transtentorial approach offers large surgical exposure and multiple trajectories to the suprasellar, interpeduncular, prepontine, and upper-half clival regions without overt traction, which is mandatory to remove large PCMs. To unlock Meckel’s cave where a large PCM lies abutting the cave, pretemporal transcavernous and anterior transpetrosal approaches are prerequisites to create adequate exposure for the final trans–Meckel’s cave step.

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Chih-Hsiang Liao, Chung-Jung Lin, Chun-Fu Lin, Hsin-Yi Huang, Min-Hsiung Chen, Sanford P. C. Hsu and Yang-Hsin Shih

OBJECTIVE

The treatment of paraclinoid aneurysms remains challenging. It is important to determine the exact location of the paraclinoid aneurysm when considering treatment options. The authors herein evaluated the effectiveness of using the optic strut (OS) and tuberculum sellae (TS) as radiographic landmarks for distinguishing between intradural and extradural paraclinoid aneurysms on source images from CT angiography (CTA).

METHODS

Between January 2010 and September 2013, a total of 49 surgical patients with the preoperative diagnoses of paraclinoid aneurysm and 1 symptomatic cavernous-clinoid aneurysm were retrospectively identified. With the source images from CTA, the OS and the TS were used as landmarks to predict the location of the paraclinoid aneurysm and its relation to the distal dural ring (DDR). The operative findings were examined to confirm the definitive location of the paraclinoid aneurysm. Statistical analysis was performed to determine the diagnostic effectiveness of the landmarks.

RESULTS

Nineteen patients without preoperative CTA were excluded. The remaining 30 patients comprised the current study. The intraoperative findings confirmed 12 intradural, 12 transitional, and 6 extradural paraclinoid aneurysms, the diagnoses of which were significantly related to the type of aneurysm (p < 0.05) but not factors like sex, age, laterality of aneurysm, or relation of the aneurysm to the ophthalmic artery on digital subtraction angiography. To measure agreement with the correct diagnosis, the OS as a reference point was far superior to the TS (Cohen's kappa coefficients 0.462 and 0.138 for the OS and the TS, respectively). For paraclinoid aneurysms of the medial or posterior type, using the base of the OS as a reference point tended to overestimate intradural paraclinoid aneurysms. The receiver operating characteristic curve indicated that if the aneurysmal neck traverses the axial plane 2 mm above the base of the OS, the aneurysm is most likely to grow across the DDR and present as a transitional aneurysm (sensitivity 0.806; specificity 0.792).

CONCLUSIONS

High-resolution thin-cut CTA is a fast and crucial tool for diagnosing paraclinoid aneurysms. The OS serves as an effective landmark in CTA source images for distinguishing between intradural and extradural paraclinoid aneurysms. The DDR is supposed to be located 2 mm above the base of the OS in axial planes.

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Fu-Chou Cheng, Meei-Ling Sheu, Hong-Lin Su, Ying-Ju Chen, Chun-Jung Chen, Wen-Ta Chiu, Jason Sheehan and Hung-Chuan Pan

Object

Mobilization of hematopoietic progenitor cells (HPCs) from bone marrow involved in the process of peripheral nerve regeneration occurs mostly through deposits of CD34+ cells. Treadmill exercise, with either differing intensity or duration, has been shown to increase axon regeneration and sprouting, but the effect of mobilization of HPCs on peripheral nerve regeneration due to treadmill exercise has not yet been elucidated.

Methods

Peripheral nerve injury was induced in Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The animals were categorized into 2 groups: those with and without treadmill exercise (20 m/min for 60 minutes per day for 7 days). Cytospin and flow cytometry were used to determine bone marrow progenitor cell density and distribution. Neurobehavioral analysis, electrophysiological study, and regeneration marker expression were investigated at 1 and 3 weeks after exercise. The accumulation of HPCs, immune cells, and angiogenesis factors in injured nerves was determined. A separate chimeric mice study was conducted to assess CD34+ cell distribution according to treadmill exercise group.

Results

Treadmill exercise significantly promoted nerve regeneration. Increased Schwann cell proliferation, increased neurofilament expression, and decreased Schwann cell apoptosis were observed 7 days after treadmill exercise. Elevated expression of S100 and Luxol fast blue, as well as decreased numbers of vacuoles, were identified in the crushed nerve 3 weeks after treadmill exercise. Significantly increased numbers of mononuclear cells, particularly CD34+ cells, were induced in bone marrow after treadmill exercise. The deposition of CD34+ cells was abolished by bone marrow irradiation. In addition, deposits of CD34+ cells in crushed nerves paralleled the elevated expressions of von Willebrand factor, isolectin B4, and vascular endothelial growth factor.

Conclusions

Bone marrow HPCs, especially CD34+ cells, were able to be mobilized by low-intensity treadmill exercise, and this effect paralleled the significant expression of angiogenesis factors. Treadmill exercise stimulation of HPC mobilization during peripheral nerve regeneration could be used as a therapy in human beings.

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Meei-Ling Sheu, Fu-Chou Cheng, Hong-Lin Su, Ying-Ju Chen, Chun-Jung Chen, Chih-Ming Chiang, Wen-Ta Chiu, Jason Sheehan and Hung-Chuan Pan

Object

Increased integration of CD34+ cells in injured nerve significantly promotes nerve regeneration, but this effect can be counteracted by limited migration and short survival of CD34+ cells. SDF-1α and its receptor mediate the recruitment of CD34+ cells involved in the repair mechanism of several neurological diseases. In this study, the authors investigate the potentiation of CD34+ cell recruitment triggered by SDF-1α and the involvement of CD34+ cells in peripheral nerve regeneration.

Methods

Peripheral nerve injury was induced in 147 Sprague-Dawley rats by crushing the left sciatic nerve with a vessel clamp. The animals were allocated to 3 groups: Group 1, crush injury (controls); Group 2, crush injury and local application of SDF-1α recombinant proteins; and Group 3, crush injury and local application of SDF-1α antibody. Electrophysiological studies and assessment of regeneration markers were conducted at 4 weeks after injury; neurobehavioral studies were conducted at 1, 2, 3, and 4 weeks after injury. The expression of SDF-1α, accumulation of CD34+ cells, immune cells, and angiogenesis factors in injured nerves were evaluated at 1, 3, 7, 10, 14, 21, and 28 days after injury.

Results

Application of SDF-1α increased the migration of CD34+ cells in vitro, and this effect was dose dependent. Crush injury induced the expression of SDF-1α, with a peak of 10–14 days postinjury, and this increased expression of SDF-1α paralleled the deposition of CD34+ cells, expression of VEGF, and expression of neurofilament. These effects were further enhanced by the administration of SDF-1α recombinant protein and abolished by administration of SDF-1α antibody. Furthermore, these effects were consistent with improvement in measures of neurological function such as sciatic function index, electrophysiological parameters, muscle weight, and myelination of regenerative nerve.

Conclusions

Expression of SDF-1α facilitates recruitment of CD34+ cells in peripheral nerve injury. The increased deposition of CD34+ cells paralleled significant expression of angiogenesis factors and was consistent with improvement of neurological function. Utilization of SDF-1α for enhancing the recruitment of CD34+ cells involved in peripheral nerve regeneration may be considered as an alternative treatment strategy in peripheral nerve disorders.

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Dar-Yu Yang, Meei-Ling Sheu, Hong-Lin Su, Fu-Chou Cheng, Ying-Ju Chen, Chun-Jung Chen, Wen-Ta Chiu, Jia-Jean Yiin, Jason Sheehan and Hung-Chuan Pan

Object

Human amniotic fluid–derived mesenchymal stem cells (AFMSCs) have been shown to promote peripheral nerve regeneration. The expression of stromal cell–derived factor-1α (SDF-1α) in the injured nerve exerts a trophic effect by recruiting progenitor cells that promote nerve regeneration. In this study, the authors investigated the feasibility of intravenous administration of AFMSCs according to SDF-1α expression time profiles to facilitate neural regeneration in a sciatic nerve crush injury model.

Methods

Peripheral nerve injury was induced in 63 Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The animals were randomized into 1 of 3 groups: Group I, crush injury as the control; Group II, crush injury and intravenous administration of AFMSCs (5 × 106 cells for 3 days) immediately after injury (early administration); and Group III, crush injury and intravenous administration of AFMSCs (5 × 106 cells for 3 days) 7 days after injury (late administration). Evaluation of neurobehavior, electrophysiological study, and assessment of regeneration markers were conducted every week after injury. The expression of SDF-1α and neurotrophic factors and the distribution of AFMSCs in various time profiles were also assessed.

Results

Stromal cell–derived factor-1α increased the migration and wound healing of AFMSCs in vitro, and the migration ability was dose dependent. Crush injury induced the expression of SDF-1α at a peak of 10–14 days either in nerve or muscle, and this increased expression paralleled the expression of its receptor, chemokine receptor type-4 (CXCR-4). Most AFMSCs were distributed to the lung during early or late administration. Significant deposition of AFMSCs in nerve and muscle only occurred in the late administration group. Significantly enhanced neurobehavior, electrophysiological function, nerve myelination, and expression of neurotrophic factors and acetylcholine receptor were demonstrated in the late administration group.

Conclusions

Amniotic fluid–derived mesenchymal stem cells can be recruited by expression of SDF-1α in muscle and nerve after nerve crush injury. The increased deposition of AFMSCs paralleled the expression profiles of SDF-1α and its receptor CXCR-4 in either muscle or nerve. Administration of AFMSCs led to improvements in neurobehavior and expression of regeneration markers. Intravenous administration of AFMSCs may be a promising alternative treatment strategy in peripheral nerve disorder.

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Fu-Chou Cheng, Ming-Hong Tai, Meei-Ling Sheu, Chun-Jung Chen, Dar-Yu Yang, Hong-Lin Su, Shu-Peng Ho, Shu-Zhen Lai and Hung-Chuan Pan

Object

Human amniotic fluid–derived mesenchymal stem cells (AFMSCs) have been shown to promote peripheral nerve regeneration, and the local delivery of neurotrophic factors may additionally enhance nerve regeneration capacity. The present study evaluates whether the transplantation of glia cell line–derived neurotrophic factor (GDNF)–modified human AFMSCs may enhance regeneration of sciatic nerve after a crush injury.

Methods

Peripheral nerve injury was produced in Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. Either GDNF-modified human AFMSCs or human AFMSCs were embedded in Matrigel and delivered to the injured nerve. Motor function and electrophysiological studies were conducted after 1 and 4 weeks. Early or later nerve regeneration markers were used to evaluate nerve regeneration. The expression of GDNF in the transplanted human AFMSCs and GDNF-modified human AFMSCs was monitored at 7-day intervals.

Results

Human AFMSCs were successfully transfected with adenovirus, and a significant amount of GDNF was detected in human AFMSCs or the culture medium supernatant. Increases in the sciatic nerve function index, the compound muscle action potential ratio, conduction latency, and muscle weight were found in the groups treated with human AFMSCs or GDNF-modified human AFMSCs. Importantly, the GDNF-modified human AFMSCs induced the greatest improvement. Expression of markers of early nerve regeneration, such as increased expression of neurofilament and BrdU and reduced Schwann cell apoptosis, as well as late regeneration markers, consisting of reduced vacuole counts, increased expression of Luxol fast blue and S100 protein, paralleled the results of motor function. The expression of GDNF in GDNF-modified human AFMSCs was demonstrated up to 4 weeks; however, the expression decreased over time.

Conclusions

The GDNF-modified human AFMSCs appeared to promote nerve regeneration. The consecutive expression of GDNF was demonstrated in GDNF-modified human AFMSCs up to 4 weeks. These findings support a nerve regeneration scenario involving cell transplantation with additional neurotrophic factor secretion.