Computed Tomography Study of the Retrosigmoid Craniotomy Keyhole Approach Using Surface Landmarks.

Background: Due to a lack of accessibility and individual differences in surgical procedures, many previous studies on keyholes are not practical. Objective: To study the surface landmarks for optimal keyhole placement in the retrosigmoid approach. Methods: The three-dimensional (3D) skull images of 79 patients were reconstructed using workstations, with a total of 149 hemiskull base 3D images then analyzed. Skull-surface landmarks were marked, the lateral-skull surface was observed, and the positional relationships between the asterion and the extension line of the posterior margin of the mastoid process were measured. The position of the superior curvature of the sigmoid sinus groove was located before it was projected onto the lateral surface of the skull and defined as the keypoint. The positional relationship between the keypoint and the skull-surface landmarks was observed in an established coordinate system using spatial proportion relationships. Results: The asterion was located around the extension line of the posterior margin of the mastoid process, and the vertical distance from the extension line was <15 mm. It was found that 93.29% (139/149) of the keypoints were located in a 7 mm radius circle, with the center at (-0.41, -3.01) in the coordinate system in the 3D computed tomography images. Conclusion: When using this method, the spatial proportion relationship of the anatomical marks can accurately locate keyholes, therefore providing technical support when employing the retrosigmoid approach.

Microvascular decompression for a patient with oculomotor palsy caused by posterior cerebral artery compression: A case report and literature review.

BACKGROUND: Aneurysm compression, diabetes, and traumatic brain injury are well-known causative factors of oculomotor nerve palsy (ONP), while cases of ONP induced by neurovascular conflicts have rarely been reported in the medical community. Here, we report a typical case of ONP caused by right posterior cerebral artery (PCA) compression to increase neurosurgeons' awareness of the disease and reduce misdiagnosis and recurrence. CASE SUMMARY: A 54-year-old man without a known medical history presented with right ONP for the past 5 years. The patient presented to the hospital with right ptosis, diplopia, anisocoria (rt 5 mm, lt 2.5 mm), loss of duction in all directions, abduction, and light impaired pupillary reflexes. Magnetic resonance angiography and computed tomography venography examinations showed no phlebangioma, aneurysm, or intracranial lesion. After conducting oral glucose tolerance and prostigmin tests, diabetes and myasthenia gravis were excluded. Cranial nerve magnetic resonance imaging showed that the right PCA loop was in direct contact with the cisternal segment of the right oculomotor nerve (ON). Microvascular decompression (MVD) of the culprit vessel from the ON through a right subtemporal craniotomy was carried out, and the ONP symptoms were significantly relieved after 3 mo. CONCLUSION: Vascular compression of the ON is a rare pathogeny of ONP that may be refractory to drug therapy and ophthalmic strabismus surgery. MVD is an effective treatment for ONP induced by neurovascular compression.

The different role of YKL-40 in glioblastoma is a function of MGMT promoter methylation status.

Inter- and intratumoral heterogeneity is a hallmark of glioblastoma (GBM) that facilitates recurrence, treatment resistance, and worse prognosis. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is a significant prognostic marker for Temozolomide (TMZ) resistance in GBM patients. YKL-40 is a molecular marker for the mesenchymal subtype of GBMs and is responsible for TMZ resistance. However, underlying mechanisms by which MGMT epigenetics impacts patient outcomes and the function of YKL-40 are not fully determined. Herein, we performed in vitro and in vivo experiments, six human IDH1/2 wild-type glioblastoma stem-like cells (GSCs) were established and studied to further determine a potential interaction of YKL-40 and MGMT promoter methylation. We demonstrated that YKL-40 functioned differently in human IDH1/2 wild-type GSCs. In MGMT promoter-methylated (MGMT-m) GSCs, it acted as a tumor suppressor gene. On the other hand, in MGMT promoter-unmethylated (MGMT-um) GSCs, it promoted tumorigenesis. Notably, the reason that YKL-40 played different roles in GSCs could not be interpreted by the molecular classification of each GSCs, but is a function of MGMT promoter methylation status and involves the RAS-MEK-ERK pathway. YKL-40 mediated TMZ sensitivity by activating DNA damage responses (DDRs) in MGMT-m GSCs, and it mediated resistance to TMZ by inhibiting DDRs in MGMT-um GSCs. Our report demonstrated that MGMT promoter methylation status might influence a gene's function in human cancer. Moreover, our data also highlight the point that gene function should be investigated not only according to the molecular tumor classification, but also the epigenetic signature.

Delayed Facial Palsy After Microvascular Decompression for Hemifacial Spasm.

OBJECTIVE: We explored the risk factors for the occurrence of delayed facial paralysis (DFP) after microvascular decompression (MVD) for hemifacial spasm (HFS). METHODS: A retrospective study was conducted of 636 patients who had undergone MVD for HFS by the same neurosurgery department of China-Japan Friendship Hospital from January 2006 to May 2016. Of the 636 patients, 50 (7.9%) had presented with DFP, which had developed from 2 to 60 days postoperatively (average, 12.9 ± 10.0005 days). All 50 patients with DFP had recovered completely within 10-300 days (average, 88.7 ± 61.389 days) after the onset of DFP. We randomly selected 100 patients from the 586 patients without DFP as the control group. Univariate and multivariate logistic analyses were used to analyze the risk factors involved in the occurrence of DFP. RESULTS: Univariate analysis showed that the disease course was the only factor associated with the development of DFP (P = 0.003). Furthermore, on multivariate logistic analysis, the course of HFS was the only risk factor associated with the development of DFP (P = 0.01). Additionally, the Spearman test revealed a positive correlation between the onset of DFP and the duration of the DFP symptoms (rs = 0.682; P < 0.001). CONCLUSION: Although DFP frequently occurred after MVD, it can recover spontaneously. The longer the course of HFS, the more frequently DFP will occur after MVD. The earlier that DFP develops, the shorter will be the time to recovery.

Danhong Injection Alleviates Mechanical Allodynia via Inhibiting ERK1/2 Activation and Elevates BDNF Level in Sciatic Nerve in Diabetic Rat.

Danhong injection (DHI) has been widely used in China for cardiocerebrovascular diseases treatments. And in this study, we demonstrated the therapeutic effect of DHI on experimental diabetic neuropathy for the first time. Methods. Streptozotocin- (STZ-) induced SD rats were used. In experiment 1, 4-week treatment with DHI or saline started 4 weeks after STZ injection; mechanical allodynia was measured before and every 2 weeks after STZ injection. In experiment 2, chronic intrathecal infusion of U0126 was conducted during the 8th week of diabetes. Phosphorylated and total ERK1/2 in spinal cord were analyzed by western blot. BDNF level in sciatic nerve was evaluated by ELISA. Results. DHI treatment significantly alleviated mechanical allodynia at the end of the study and downregulated the expression of phosphorylated ERK1/2 in spinal cord. In addition, DHI treatment also elevated brain-derived neurotrophic factor (BDNF) level in sciatic nerve of DPN rat. In experiment 2, inhibition of ERK1/2 activation was confirmed to result in the alleviation of mechanical allodynia. Conclusions. We demonstrated that DHI was able to alleviate mechanical allodynia in diabetic neuropathy rat through inhibiting the activation of ERK1/2. The reduction of BDNF content in sciatic nerve was also partially reversed by DHI treatment.

Tanshinone IIA Improves Painful Diabetic Neuropathy by Suppressing the Expression and Activity of Voltage-Gated Sodium Channel in Rat Dorsal Root Ganglia.

Painful diabetic neuropathy (PDN) is one of the intractable complications of diabetes mellitus, which manifest as exaggerated pain perception. Previous studies showed that Tanshinone IIA (TIIA), one of the major bioactive extracts of Salvia miltiorrhiza Bunge, have obvious analgesic effect on different types of pain process, and the underlying analgesic mechanisms are not fully understood. The present study combined the behavioral, electrophysiological and biochemical methods to elucidate the analgesic mechanism of TIIA, using streptozotocin (STZ)-induced PDN rat models. Intraperitoneal injection (i.p.) of TIIA for 3 weeks in PDN rats significantly improved mechanical allodynia and thermal hyperalgesia. Patch clamp recordings showed that the excitability of dorsal root ganglion (DRG) nociceptive neuron was increased in diabetic state, and TIIA treatment effectively recovered the subnormality, which was achieved by preventing augments of both Tetrodotoxin-sensitive (TTX-resistant) and Tetrodotoxin-sensitive (TTX-S) sodium currents. Further, the protein expressions of voltage-gated sodium channels (VGSCs) α-subunits Nav1.3, Nav1.7 and Nav1.9 increased in DRG of diabetic rats and were normalized by TIIA application. In conclusion, this study provides evidence that the TIIA attenuated PDN by effecting VGSCs activities and expressions, indicating that the TIIA could be a promising agent for PDN treatment.

Two-Point Discrimination Predicts Pain Relief after Lower Limb Nerve Decompression for Painful Diabetic Peripheral Neuropathy.

BACKGROUND: Peripheral nerve decompression surgery has been reported to be effective for pain reduction in patients with painful diabetic peripheral neuropathy. The aim of this study was to characterize which patients may have more pain relief benefits in the lower limbs after nerve decompression surgery. METHODS: A retrospective study was conducted. Pain levels were measured with the Numerical Rating Scale. Treatment effects were classified by either substantial relief (at least 50 percent reduction in Numerical Rating Scale score compared with preoperative Numerical Rating Scale score) or nonsubstantial relief (<50 percent reduction or worse in Numerical Rating Scale score) at 12 months based on established criteria. Sex, age, body mass index, duration of diabetes mellitus, duration of diabetic peripheral neuropathy pain, preoperative Numerical Rating Scale score, and two-point discrimination were evaluated using univariate and logistic regression analysis. RESULTS: The mean preoperative Numerical Rating Scale score (8.65 ± 1.29) decreased significantly 6 days (3.56 ± 2.22; p < 0.01), 6 months (3.03 ± 2.11; p < 0.01), and 12 months (3.44 ± 2.36; p < 0.01) after surgery; 64.7 percent of patients had substantial pain relief at 12 months. According to univariate and logistic regression analysis, better two-point discrimination was associated with substantial pain relief (OR, 3.700; p = 0.046, logistic regression analysis). CONCLUSIONS: Nerve decompression surgery was able to alleviate pain in patients with painful diabetic peripheral neuropathy. Two-point discrimination may be a predictive factor for the prognosis of painful diabetic peripheral neuropathy after nerve decompression surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Long-Term Outcome of Repeat Microvascular Decompression for Hemifacial Spasm.

OBJECTIVE: Although repeat microvascular decompression (MVD) for hemifacial spasm (HFS) in patients with failed prior MVD is potentially curative, little is known about the long-term results of repeat MVD. We aimed to evaluate the long-term outcomes and complications after repeat MVD for HFS. METHODS: We performed repeat MVD on 78 consecutive patients who had undergone a prior MVD >1 year previously. Follow-up data were available for 58 patients, with a median follow-up period of 8.6 years (range, 6.9-10.2 years). The patients were assessed for intraoperative findings, relief results, and complications at discharge and at follow-up, as well as the associations between the preoperative characteristics and outcomes. RESULTS: At discharge, of 78 patients with repeat MVD, 72 (92.3%) achieved complete spasm resolution and 1 (2.6%) had significantly improved spasm resolution. Of all patients, 9% (7 of 78) presented short-term complications, including partial hearing loss, hemifacial paresis, and cerebrospinal fluid leak. At follow-up, 45 of 58 (77.6%) patients had complete relief and 10 of 58 (17.2%) had improved relief. Permanent complications occurred in 14 patients (24.1%), with partial hearing loss and mild hemifacial paresis being the most common. Despite the complications, 51 of 58 patients (91.4%) reported an excellent life quality. No significant correlation was found between preoperative characteristics, such as age, interval to prior MVD, or interval to recurrence, and outcomes including short-term or long-term relief results and complications. CONCLUSIONS: Repeat MVD provides lasting relief for most patients with persistent or recurrent HFS, albeit with a relatively high complication rate.

[Effect of Tongmai Jiangtang Capsule on Experimental Diabetic Peripheral Neuropathy Rats].

OBJECTIVE: To observe the effect of Tongmai Jiangtang Capsule (TJC) on experimental diabetic peripheral neuropathy (DPN) rats. METHODS: Forty Wistar rats were divided into the TJC group, the mecobalamin treatment group, the model group, and the normal group according to random digit table, 10 in each group. Except rats in the normal group, DPN rat model was prepared using intraperitoneally in- jecting streptozotocin (STZ) in the rest rats. One rat in the model group died during the modeling. Different drugs were administered by gastrogavage to rats in corresponding groups from the 8th week after successful modeling. TJC (0.23 g crude drugs/mL, 10 mL/kg) was administered to rats in the TJC group by gastrogavage. Suspension of mecobalamin and normal saline (10 mL/kg, 0.05 mg/mL) was administered by gastrogavage to rats in the mecobalamin treatment group to the end of the 12th week. Meanwhile, equal volume of distilled water was administered by gastrogavage to rats in the model group and the normal group. Peripheral nerve conduction velocity was detected in each group. Gait analysis was performed. Changes of intraepidermal nerve fiber were observed by immunohistochemical assay. Pathological changes of tibial nerve tissue were observed using HE staining. RESULTS: (1) Compared with the normal group, the nerve conduction velocity was slowed down; print length (PL), intermediary toe spread (ITS), and toe spread (TS) were added in the model group, with statistical difference (P <0. 01). Compared with the mod- el group, nerve conduction velocity was speeded; PL and ITS decreased in the TJC group and the mecobal- amin treatment group, with statistical difference (P <0. 01). Besides, the nerve conduction velocity was superior in the TJC group than in the mecobalamin treatment group, with statistical difference (P <0. 05). (2) Immunohistochemical results showed, the staining of intraepidermal nerve fiber was not clear and dispersedly distributed in the model group, with no nerve fiber staining in local regions. Nerve fibers were not regular in lesser amount and shallow stained in the mecobalamin treatment group, with no nerve fiber staining in local regions. Nerve fibers were not regular in lesser amount and dispersedly distributed in the TJC group. (3) HE staining showed that tibial nerve tissue was severely swollen with swollen myelin sheath in the mod- el group. It was difficult to identity myelin sheath. Vaculole degenerated in local regions. Swollen axon could be seen. Partial axons were separated and degenerated. In the mecobalamin treatment group tibial nerve tissue was edematous with swollen myelin sheath. It was difficult to identity myelin sheath. Axons were locally separated. In the JMC group tibial nerve tissue was swollen with unclear myelin sheath and swollen axons. CONCLUSION: TJC could improve peripheral neuropathy of diabetic rats.

Microvascular decompression for atypical hemifacial spasm: lessons learned from a retrospective study of 12 cases.

OBJECTIVE: Typical hemifacial spasm (HFS) commonly initiates from the orbicularis oculi muscle to the orbicularis oris muscle. Atypical HFS (AHFS) is different from typical HFS, in which the spasm of muscular orbicularis oris is the primary presenting symptom. The objective of this study was to analyze the sites of compression and the effectiveness of microvascular decompression (MVD) for AHFS. METHODS: The authors retrospectively analyzed the clinical data for 12 consecutive patients who underwent MVD for AHFS between July 2008 and July 2013. RESULTS: Postoperatively, complete remission of facial spasm was found in 10 of the 12 patients, which gradually disappeared after 2 months in 2 patients. No recurrence of spasm was observed during follow-up. Immediate postoperative facial paralysis accompanied by hearing loss occurred in 1 patient and temporary hearing loss with tinnitus in 2. All 3 patients with complications had gradual improvement during the follow-up period. CONCLUSIONS: The authors conclude that most cases of AHFS were caused by neurovascular compression on the posterior/rostral side of the facial nerve distal to the root entry zones. MVD is a safe treatment for AHFS, but the incidence of postoperative complications, such as facial paralysis and decrease in hearing, remains high.

[Complications of selective posterior rhizotomy for lower limb spasticity of cerebral palsy].

OBJECTIVE: To investigate the complications of spastic cerebral palsy with selective posterior rhizotomy (SPR). METHODS: In the study, 2 593 patients who had undergone SPR from January 2000 to September 2012 were followed-up for at least one year. The complications were classified. RESULTS: Peri-operative complications: pulmonary system complications including bronchial spasm (5 cases, 0.19%) and aspiration pneumonia (4 cases, 0.15%); digestive system complications including abdominal bloating (145 cases, 5.6%) and colic (80 cases, 3.1%); urinary system complications including temporary bladder dysfunction (54 cases, 2.1%) and urinary tract infection (6 cases, 0.23%); peripheral nervous system complications including lower extremity weakness (327 cases, 12.6%) and lower extremity sensory disturbances (140 cases, 5.4%); central nervous system complications including headache (112 cases, 4.3%) and epileptic seizures (4 cases, 0.15%). None spinal or intracranial infection, intraspinal hematoma or intracranial hemorrhage were identified. General surgery complications including back pain (1 382 cases, 53.3%), delay wound healing caused by infection (5 cases, 0.19%) and cerebrospinal fluid leakage (8 cases, 0.31%). Long-term follow-up complications including lower limb decreased exercise capacity (incidence: 7.33%) and lower extremity sensory disturbance (incidence: 5.59%). Urination occurred in only one case and defecation function disturbance with no sexual dysfunction was identified. The incidences of scoliosis, thoracic kyphosis, spondylolisthesis and long-term back pain were 7.23% (31/429), 4.2% (18/429), 10.49% (45/429) and 9.72% respectively. CONCLUSION: SPR is one of the effective and safe surgical treatments for spastic cerebral palsy. Valid methods should be applied to reduce the incidence of postoperative complications, such as choosing the appropriate patients, meticulously operating in the surgery, assistance of electrophysiological guidance, reinforcing perioperative management and regular rehabilitation training after operation.

Overexpression of EpCAM and Trop2 in pituitary adenomas.

We sought to investigate the expression of EpCAM and Trop2 in Pituitary adenomas (PAs) and study the correlation of protein expression with invasiveness, proliferation, clinical functioning, recurrence/progression, and some other factors. We investigated the expression of EpCAM and Trop2 in 74 samples of PAs by immunohistochemistry and made correlative analysis of protein overexpression with clinicopathological parameters. Follow-up data was analyzed for recurrence/progression with Kaplan-Meier method and Multivariate Cox regression analysis. Immunohistochemistry results showed that overexpression rates of EpCAM and Trop2 were 51/74 (68.9%) and 43/74 (58.1%), respectively. For both EpCAM and Trop2, PAs with invasiveness showed a higher overexpression rate than PAs without invasiveness (PEpCAM = 0.001; PTrop2 = 0.006). Nonfunctional Pituitary adenomas (NFPAs) demonstrated a higher EpCAM overexpression than functional Pituitary adenomas (FPAs) (P = 0.026). Both EpCAM and Trop2 overexpression correlated significantly with expression of proliferation factor Ki-67 (PEpCAM = 0.011; PTrop2 = 0.000), but not with gender and age. Follow-up analysis revealed that Trop2 overexpression was a significantly predictive factor for recurrence/progression by means of Kaplan-Meier method d (P = 0.028) and Multivariate Cox regression analysis (P = 0.025). This study reveals that both EpCAM and Trop2 overexpression in PAs correlate significantly with invasiveness and proliferation. EpCAM presents a potential target for differential diagnosis and immunotherapy for NFPAs. Follow-up analysis shows that Trop2 is a predictive factor for recurrence/progression for PAs.

20-Hydroxyecdysone protects against oxidative stress-induced neuronal injury by scavenging free radicals and modulating NF-κB and JNK pathways.

Oxidative stress plays an important role in the pathological processes of ischemic brain damage. Many antioxidants have been shown to protect against cerebral ischemia injury by inhibiting oxidative stress both in vitro and in vivo. 20-Hydroxyecdysone (20E), an ecdysteroid hormone, exhibits antioxidative effects. For the work described in this paper, we used an in vitro oxidative damage model and an in vivo ischemic model of middle cerebral artery occlusion (MCAO) to investigate the neuroprotective effects of 20E and the mechanisms related to these effects. Treatment of cells with H(2)O(2) led to neuronal injury, intracellular ROS/RNS generation, mitochondrial membrane potential dissipation, cellular antioxidant potential descent, an increase in malondialdehyde (MDA) and an elevation of intracellular [Ca(2+)], all of which were markedly attenuated by 20E. Inhibition of the activation of the ASK1-MKK4/7-JNK stress signaling pathway and cleaved caspase-3 induced by oxidative stress were involved in the neuroprotection afforded by 20E. In addition, 20E reduced the expression of iNOS protein by inhibition of NF-κB activation. The neuroprotective effect of 20E was also confirmed in vivo. 20E significantly decreased infarct volume and the neurological deficit score, restored antioxidant potential and inhibited the increase in MDA and TUNEL-positive and cleaved caspase-3-positive cells in the cerebral cortex in MCAO rats. Together, these results support that 20E protects against cerebral ischemia injury by inhibiting ROS/RNS production and modulating oxidative stress-induced signal transduction pathways.

[Causes of ineffectiveness of microvascular decompression for hemifacial spasm].

OBJECTIVE: To study causes of ineffectiveness of microvascular decompression (MVD) in treatment of hemifacial spasm (HFS). METHODS: Reoperative MVD was performed in 23 HFS patients with previous ineffective MVD. In the patients, the main causes of ineffectiveness included misjudgment of compressing vessels (7 patients), improper insertion of decompressing grafts (9), improper selection of grafts (5) and small grafts (2). RESULTS: Symptoms of HFS disappeared immediately after the second MVD in 21 patients and delayed in 2 patients (after 2 weeks, 6 weeks). No recurrence of HFS was noted during the follow-up period of 1.0 - 6.0 years (mean 3.4 years). CONCLUSIONS: MVD is an effective microsurgical method for treating HFS. Accurate judgement of compressing vessels and proper decompression are the key to surgical effectiveness.