Comparison of endoscopic third ventriculostomy versus cerebrospinal fluid shunt procedures for the treatment of pediatric hydrocephalus in Taiwan.

PURPOSE: Pediatric hydrocephalus is the most common cause of surgically treatable neurological disease in children. Controversies exist whether endoscopic third ventriculostomy (ETV) or cerebrospinal fluid (CSF) shunt placement is the most appropriate treatment for pediatric hydrocephalus. This study aimed to compare the risk of re-operation and death between the two procedures. METHODS: We performed a retrospective population-based cohort study and included patients younger than 20-years-old who underwent CSF shunt or ETV for hydrocephalus from the Taiwan National Health Insurance Research Database. RESULTS: A total of 3,555 pediatric patients from 2004 to 2017 were selected, including 2,340 (65.8%) patients that received CSF shunt placement and 1215 (34.2%) patients that underwent ETV. The incidence of all-cause death was 3.31 per 100 person-year for CSF shunt group and 2.52 per 100 person-year for ETV group, with an adjusted hazard ratio (HR) of 0.79 (95% confidence interval [CI] = 0.66-0.94, p = 0.009). The cumulative incidence competing risk for reoperation was 31.2% for the CSF shunt group and 26.4% for the ETV group, with an adjusted subdistribution HR of 0.82 (95% CI = 0.70-0.96, p = 0.015). Subgroup analysis showed that ETV was beneficial for hydrocephalus coexisting with brain or spinal tumor, central nervous system infection, and intracranial hemorrhage. CONCLUSION: Our data indicates ETV is a better operative procedure for pediatric hydrocephalus when advanced surgical techniques and instruments are available.

Roles of microRNA-1 in hypoxia-induced apoptotic insults to neuronal cells.

Hypoxia is a common occurrence in brain tumors and traumatic brain injury. microRNA (miR)-1 participates in the regulation of brain development and neuronal function. Interestingly, miR-1 can mediate ischemia-induced injury to cardiomyocytes. This study was designed to evaluate the roles of miR-1 in hypoxia-induced insults to neurons and the possible mechanisms. Exposure of neuro-2a cells to oxygen/glucose deprivation (OGD) or cobalt chloride decreased cell viability and induced cell apoptosis in time-dependent manners. In parallel, OGD caused augmentation of cellular Bax and cytochrome c levels, a reduction in the mitochondrial membrane potential (MMP), activation of caspase-3, and fragmentation of DNA. miR-1 was induced in neuro-2a cells by OGD. Knocking down miR-1 expression using specific antisense inhibitors significantly alleviated OGD-induced neuronal death. Administration of OGD to neuro-2a cells induced heat-shock protein (HSP)-70 messenger (m)RNA and protein expressions. A bioinformatic search revealed that miR-1-specific binding elements exist in the 3'-untranslated region of HSP-70 mRNA. Overexpression of miR-1 simultaneously attenuated OGD-induced HSP-70 mRNA and protein expressions. In comparison, knocking down miR-1 expression synergistically enhanced OGD-induced HSP-70 mRNA. As to the mechanism, reducing miR-1 expression lowered OGD-induced alterations in the MMP, caspase-3 activation, DNA fragmentation, and cell apoptosis. Taken together, this study shows that miR-1 can target HSP-70 expression and consequently mediate hypoxia-induced apoptotic insults to neuro-2a cells via an intrinsic Bax-mitochondrion-caspase protease pathway.

Sensory axonal dysfunction in cervical radiculopathy.

OBJECTIVE: The aim of this study was to evaluate changes in sensory axonal excitability in the distal nerve in patients with cervical radiculopathy. METHODS: The patients were classified by the findings of cervical MRI into two subgroups: 22 patients with C6/7 root compression and 25 patients with cervical cord and root compression above/at C6/7. Patients were investigated using conventional nerve conduction studies (NCS) and nerve excitability testing. Sensory nerve excitability testing was undertaken with stimulation at the wrist and recording from digit II (dermatome C6/7). The results were compared with healthy controls. Both preoperative and postoperative tests were performed if the patient underwent surgery. RESULTS: Sensory axonal excitability was significantly different in both cohorts compared with healthy controls, including prolonged strength-duration time constant, reduced S2 accommodation, increased threshold electrotonus hyperpolarisation (TEh (90-100 ms)), and increased superexcitability. The changes in these excitability indices are compatible with axonal membrane hyperpolarisation. In five patients who underwent surgery, the postoperative sensory excitability was tested after 1 week, and showed significant changes in TE (TEh (90-100 ms) and TEh slope, p<0.05) between presurgery and postsurgery. CONCLUSIONS: The present study demonstrated distal nerve axonal hyperpolarisation in patients with cervical radiculopathy. These findings suggest that the hyperpolarised pattern might be due to Na(+)-K(+) ATPase overactivation induced by proximal ischaemia, or could reflect the remyelinating process. Distal sensory axons were hyperpolarised even though there were no changes in NCS, suggesting that nerve excitability testing may be more sensitive to clinical symptoms than NCS in patients with cervical radiculopathy.

Solitary intracranial osteoma with attachment to the falx: a case report.

BACKGROUND: Intracranial osteomas are uncommon lesions that usually arise from the inner table of the cranium. There are few reports in the literature of intracranial osteomas with meninges attachment and without direct relation with the skull bone; these osteomas were mostly attached with dura. We report a rare osteoma with falx attachment. CASE: A 64-year-old woman presented with a 3-month history of intermittent tinnitus and dizziness. The scout film of petrous bone computed tomography scan revealed a high-density lesion in the frontal area. Magnetic resonance imaging showed a 2.5-cm mass attached to the surface of the falx in the right frontal parasagittal area. The patient underwent right frontal craniotomy, and a bony hard mass was found located in the right frontal parasagittal region extra-axially, with its medial surface attached to the falx. It could not be broken down by the cavitron ultrasonic surgical aspirator or even the cutting loop and was detached from the falx and removed in one piece. Histopathological examination showed a nodule with bony trabeculae and bone marrow tissue, compatible with osteoma. The postoperative course was uneventful, and the patient was discharged from the hospital with no neurological deficits one week after operation. CONCLUSIONS: This is the first case report in the English literature of an intracranial osteoma arising from the falx. Because of their slow growth and their locations in silent brain areas, intracranial osteomas are usually diagnosed incidentally. Surgical resection is the primary treatment choice.

MicroRNA-495 inhibits proliferation of glioblastoma multiforme cells by downregulating cyclin-dependent kinase 6.

BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive type of glioma and carries the poorest chances of survival. There is therefore an urgent need to understand the mechanisms of glioma tumorigenesis and develop or improve therapeutics. The aim of this study was to assess the possible prognostic value of cyclin-dependent kinase 6 (CDK6) and the effects of microRNA-495 (miR-495) manipulation on CDK6 expression and cell survival in glioma cells. METHODS: Analyses of clinical specimens from GBM patients were used. Expression of CDK6 was analyzed by real-time polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry. Expression of CDK6 was also analyzed after over-expression of miR-495 in T98 cells; both cell proliferation and RB phosphorylation were examined. Cell proliferation, cell cycle distribution, and RB phosphorylation were also examined after knockdown of CDK6 in U87-MG and T98 cells. RESULTS: Analyses of clinical specimens from GBM patients identified that CDK6 is significantly expressed in gliomas. CDK6 antigen expression was higher in tumor cores and margins than in adjacent normal brain tissues, and higher levels of CDK6 expression in the tumor margin correlated with decreased survival. Over-expression of miR-495 in T98 cells downregulated the expression of CDK6 and inhibited retinoblastoma phosphorylation, and knockdown of CDK6 in U87-MG and T98 cells by siRNAs resulted in cell cycle arrest at the G1/S transition and inhibition of cell proliferation. CONCLUSIONS: This study revealed miR-495 is down-regulated in glioma tissues. Furthermore, miR-495 regulated CDK6 expression and involved in glioma cell growth inhibition, which indicated the possible role of miR-495 in tumor progression.

The clinical experience of medulloblastoma treatment and the significance of time sequence for development of leptomeningeal metastasis.

OBJECTS: Among patients with medulloblastoma, an unrare aggressive central nervous system (CNS) tumor found mostly in the posterior fossa, drop metastasis from primary location to anatomically lower sites including whole spinal cord is known as a potential way for tumor to spread. There were already lots of extensive discussions regarding diagnosis and treatment for such common neurologic complication in systemic cancer; however, fewer were found about medulloblastoma. This study aimed to reexamine the possible known prognostic factors, especially drop metastasis, and defined the influence of them. MATERIALS AND METHODS: We retrospectively review a series of 36 patients who suffered from posterior fossa medulloblastoma and found leptomeningeal metastasis in 12 of them. Incidence, diagnosis, prognostic factors, and treatments for this common complication are discussed. The magnetic resonance images (MRI) of these patients were reviewed. The time sequence between primary surgical procedure and development of MRI evidences of drop metastasis was used for subgrouping. Log-rank test was used for survival analysis. CONCLUSIONS: By survival analysis, patients with late drop metastasis, defined as new radiologic evidence of leptomeningeal involvement after primary CNS procedures, were found to have significant survival difference to those with early metastasis defined as drop metastasis found at the time of diagnosis (log-rank test, p = 0.0047). Further stratification of patients within this group may help in evaluation of prognosis and development of different treatment strategies.

Multivariate survival analysis of children with medulloblastoma--a single-center experience.

The authors sought to evaluate the treatment outcome of children with medulloblastoma at a single institution. Forty-two children were analyzed. Eighty-six percent of the children who received chemotherapy were treated with cisplatin-based chemotherapy. No factors were found to affect outcome significantly. Compared with children treated before 1994 at the same institution, the median survival time was significantly longer (40 vs. 25 months, p = .0003). The authors conclude that some improvement of treatment outcome for children with medulloblastoma seemed to be achieved.

Targeting inhibitors of apoptosis proteins suppresses medulloblastoma cell proliferation via G2/M phase arrest and attenuated neddylation of p21.

Medulloblastoma (MB) is the most common type of malignant childhood brain tumor. We previously showed that inhibitors of apoptosis proteins (IAP) small-molecule inhibitors (LCL161 or LBW242) combined with chemotherapy have synergistic antiproliferative effects on MB cells. The synergistic antitumor effects of combination treatments happen through induction of autophagy and caspase-3/7-activated apoptosis. Here, we investigated the effects of IAP inhibitors or silencing IAP on cell cycle regulation. We discovered that treatment with IAP inhibitors or their combination with conventional chemotherapy (vincristine or cisplatin), as well as RNAi knockdown of cIAP1/2 or XIAP arrested MB cells in the G2/M phase through downregulation of cyclin B1-CDK1 and cyclin A-CDK1/2. Among these three IAPs, only silencing cIAP1 expression enhanced p21 dependent-G2/M phase accumulation. IAP inhibitors reduced cIAP1 expression and increased p21 expression in time course experiments. Furthermore, cIAP1 can govern p21 proteasomal degradation via neddylation in lieu of ubiquitination. Inhibition of IAPs significantly abrogated cIAP1-mediated p21 degradation. We also observed an inverse correlation between nuclear cIAP1 and nuclear p21 expressions in MB tumor tissues. These findings provide new mechanistic evidence of the influence of IAP inhibitors on MB cell proliferation through disruption of the cell cycle.

Endodermal cyst presenting as a prenatally diagnosed large intracranial cyst. Case report and review of the literature.

Endodermal cysts of the central nervous system are unusual lesions. Most reported cysts develop in the spinal canal, whereas others, which occur intracranially, are usually located in the posterior fossa. Although endodermal cysts are considered congenital, a prenatal diagnosis has not been reported. In this report the authors present an extremely rare case of a large intracranial endodermal cyst detected prenatally and treated successfully after birth.

Spinal intramedullary abscess with an epidermoid secondary to a dermal sinus.

Congenital dermal sinuses are relatively uncommon, and result from abnormal neurulation. A lack of awareness about this problem causes these patients to manifest significant mortality and morbidity. Spinal intramedullary abscesses are rare and potentially devastating lesions. Intraspinal epidermoids are also unusual lesions. We report on a boy, aged 1 year and 5 months, who had a lower-back hairy hemangioma at birth without further evaluation, and dermal sinus tract without surgical intervention at age 7 months. He also manifested rapidly progressive paraplegia with urine and stool retention, and was found to have a spinal intramedullary abscess with an epidermoid as the result of a dermal sinus. This patient illustrates the importance of the recognition and evaluation of skin markers, and of an awareness and complete neurological assessment of all patients with a congenital dermal sinus, because of the potential for intradural extension and a frequent association with other dysraphic abnormalities. Prophylactic surgery is indicated to prevent dangerous and recurrent infections of the central nervous system.

Hypertension-induced cerebellar encephalopathy and hydrocephalus in a male.

Hypertensive encephalopathy is believed to be caused by an abrupt elevation in systemic blood pressure. It rarely occurs in children and can be neurologically devastating if it is not recognized and treated immediately. This report describes an 11-year-old male who presented with edema and a cerebellar lesion, with acute obstructive hydrocephalus resulting from hypertensive encephalopathy. A shunt was inserted to relieve pressure in the acute stage. The patient's hydrocephalus and cerebellar swelling subsided when his blood pressure was controlled. The cerebellar lesion had been initially diagnosed as a glioma. In children, a cerebellar lesion occurring with acute obstructive hydrocephalus and hypertensive encephalopathy is rare but reversible. Clinicians should be aware of this condition because it might be misdiagnosed as a tumor of the posterior fossa.

Unilateral traumatic posterior fossa subdural effusion in an infant.

Supratentorial subdural effusion is common after infection and trauma, but rarely occurs in the posterior fossa, and is even less commonly unilateral. The authors report a rare case of unilateral traumatic posterior fossa subdural effusion with secondary hydrocephalus. A 6-month-old female infant presented with lethargy, poor appetite, and persistent vomiting after head trauma 2 weeks previously. A non-enhanced brain CT scan revealed a right posterior fossa subdural fluid collection that displaced the fourth ventricle and brainstem and dilated lateral ventricles. While monitoring the intracranial pressure, the baby was treated with temporary external subdural drainage, followed by a permanent subdural peritoneal shunt. The treatment and likely physiopathology of this unique case are discussed.

Risk of death in patients with post-traumatic cerebrospinal fluid leakage--analysis of 1773 cases.

BACKGROUND: Post-traumatic cerebrospinal fluid (CSF) leakage is one of the most troublesome conditions associated with head trauma. CSF fistulae, meningitis/central nervous infection, or even death may accompany it. Few studies have discussed post-traumatic CSF leakage as a risk factor in mortality following head trauma. We conducted this cohort study to examine the issue. METHODS: We reviewed the records in the Taiwan Traumatic Brain Injury (TBI) Registry System between 1993 and 2008. The study group included patients with acute TBI and post-traumatic CSF leakage, and the control group included cases with TBI but without CSF leakage, selected randomly at a 5:1 ratio with respect to the study group. The demographic data, Glasgow Coma Scale, brain computerized tomography, association of skull fractures and intracranial lesions, and 1-year mortality rates between these two cohorts were reviewed meticulously and analyzed statistically. RESULTS: Of 174,236 cases, 1773 with post-traumatic CSF leakage were included in the study group, and 8865 cases in the control group. Of the total 10,638 sampled cases, 406 (3.8%) died during the 1-year follow-up period, 159 (9.0%) cases in the CSF leakages group, and 247 (2.8%) in the control group. The patients with CSF leakage had a significantly higher mortality rate within 1 year (adjusted hazard ratio = 1.44, p < 0.001) than those without. We divided the CSF leakage group into three subgroups: otorrhea (n = 568), rhinorrhea (n = 302), and tension pneumocephalus (n = 903). The mortality rates were 8.5% (48/568) in the otorrhea subgroup, 10.9% (33/302) in the rhinorrhea subgroup, and 8.6% (78/903) in the tension pneumocephalus subgroup. The cases with CSF rhinorrhea had a significantly higher mortality rate than the other two subgroups (p < 0.05). All three subgroups had significantly higher mortality rates than the control group during the 1-year follow-up period (adjusted hazard ratios = 2.29, 1.35, and 1.32 in the rhinorrhea, tension pneumocephalus, and otorrhea subgroups, respectively). CONCLUSION: Post-traumatic CSF leakages had higher mortality rates than those without CSF leakages in TBI cases, and the cases with CSF rhinorrhea had worse outcomes compared with CSF leakages with pneumocephalus or otorrhea.

Blockade of Inhibitors of Apoptosis Proteins in Combination with Conventional Chemotherapy Leads to Synergistic Antitumor Activity in Medulloblastoma and Cancer Stem-Like Cells.

BACKGROUND: Medulloblastoma (MB) is the most common pediatric primary malignant brain tumor. Approximately one-third of MB patients succumb to treatment failure and some survivors suffer detrimental side effects. Hence, the purpose of this study is to explore new therapeutic regimens to overcome chemotherapeutic agent resistance or reduce chemotherapy-induced toxicity. METHODS: We detected the expression of inhibitors of apoptosis proteins (IAPs) in MB and CD133+ MB cell lines and MB tissues using immunoblotting and immunohistochemical staining. The antitumor effects of inhibitors against IAPs on MB or CD133+ MB cells were evaluated by MTT assay, Annexin V/PI analysis, and caspase-3/7 activity. Autophagy was assessed by the conversion of light chain (LC) 3-I to LC3-II and Cyto-ID autophagy detection kit. RESULTS: MB cells showed higher expression of IAPs compared to normal astrocytes and normal brain tissues. Conventional chemotherapeutic agents combined with small-molecule IAP inhibitors (LCL161 or LBW242) showed a synergistic effect in MB cells. Combined treatments triggered apoptosis in MB cells through activation of caspase-3/7 and autophagic flux simultaneously. In addition, we found that CD133+ MB cells with features of cancer stem cells displayed higher levels of X-linked inhibitor of apoptosis (XIAP) and cellular inhibitor of apoptosis 1/2 (cIAP1/2), and were hypersensitive to treatment with IAP inhibitors. CONCLUSIONS: These results shed light on the biological effects of combination therapy on MB cells and illustrate that IAP inhibitors are more effective for CD133+ stem-like MB cells.

Spinal cord injury without radiological abnormality in preschool-aged children: correlation of magnetic resonance imaging findings with neurological outcomes.

OBJECT: Spinal cord injury without radiological abnormality (SCIWORA) was defined in the era when magnetic resonance (MR) images were not popularly used as diagnostic tools. Although it is generally accepted that MR imaging can effectively illustrate the level and severity of spinal cord injury in the acute phase of trauma, only a few reports of MR imaging studies of SCIWORA have been published. The authors retrospectively reviewed nine preschool-aged patients with SCIWORA to study the correlation between MR imaging findings and the outcomes of neurological deficits, with an elimination of the bias for age. METHODS: Clinical manifestations, radiological images, surgical records, and MR imaging studies were reviewed. The pre- and postoperative neurological statuses of the patients were reappraised using American Spinal Injury Association scores and Nurick grades. Nonparametric tests were used to analyze the correlations among the variables of patient characteristics, MR imaging appearances of the injured spinal cord, and neurological outcome. CONCLUSIONS: Among the patients with SCIWORA younger than 8 years old, the different patterns of the injured spinal cords could be identified using MR imaging as transection, contusive hemorrhage, traumatic edema, and concussion. The MR imaging patterns of SCIWORA had significant prognostic correlations with the neurological outcomes of these patients; that is, a normal spinal cord appearance was prognostic of a complete recovery of neurological deficits, and intramedullary lesions correlated with permanent deficits with functional disability.

Comparison between botulinum toxin type A injection and selective posterior rhizotomy in improving gait performance in children with cerebral palsy.

OBJECT: Both botulinum toxin type A (BTA) injection and selective posterior rhizotomy (SPR) are well-recognized treatments for children with spastic cerebral palsy (CP); however, there has been no study in which the long-term effectiveness of these two approaches has been compared. METHODS: The study population comprised 62 ambulatory children with spastic diplegic CP who were participating in the same rehabilitation program and 19 healthy volunteers. The children with CP were divided into the following three groups: BTA (22 cases), SPR (20 cases), and no treatment (20 cases); the healthy volunteers served as the control group. A computer-assisted gait analysis system was used to assess gait performance. Gait was assessed in the three groups of children at 1 week before treatment, and 3, 6, 12, and 20 months after treatment. Based on the analysis of walking velocity, cadence, and step length, the BTA group demonstrated rapid improvement posttreatment but the improvement became insignificant after 12 months even with repeated BTA injections at 4-month intervals. In contrast, the SPR group displayed initial deterioration of gait parameters during the first 3 months posttreatment and then improved continuously from 6 to 20 months. The control group did not display a significant change in gait. CONCLUSIONS: The findings suggest that the effectiveness of BTA injection is more short-lived and SPR initially decreases gait performance but is expected to improve gait performance at between 6 and 20 months after the procedure.

Posterior Cerebral Artery Pseudoaneurysm, a Rare Complication of Pituitary Tumor Transsphenoidal Surgery: Case Report and Literature Review.

Endoscopic endonasal transsphenoidal surgery for pituitary tumors has been the standard therapy for decades. This approach offers surgeons an effective, safe, and wide exposure to the pituitary gland, with a relatively low mortality rate and acceptable complication rates. However, severe complications, including cerebrospinal fistula, meningitis, neural component injury, and vascular injury, may occur. One of the most common and severe complications is carotid artery injury; however, only 2 posterior cerebral artery injuries with pseudoaneurysm formation have been reported previously. One of them received bypass surgery and recovered well, but the other received endovascular treatment and died of intracranial hypertension. Herein, we report a rare case of iatrogenic pseudoaneurysm formation with hemorrhage after transsphenoidal surgery, in which tumor traction-related adjacent vessel injury was most likely. Aneurysm clipping, vascular bypass, and embolization are considered reasonable choices depending on the patient's condition for iatrogenic aneurysm formation. In our case, no surgical or endovascular intervention was performed, and the aneurysm healed spontaneously 3 weeks later.

Comparison of percutaneous endoscopic lumbar discectomy and open lumbar surgery for adjacent segment degeneration and recurrent disc herniation.

Objective. The goal of the present study was to examine the clinical results of percutaneous endoscopic lumbar discectomy (PELD) and open lumbar surgery for patients with adjacent segment degeneration (ASD) and recurrence of disc herniation. Methods. From December 2011 to November 2013, we collected forty-three patients who underwent repeated lumbar surgery. These patients, either received PELD (18 patients) or repeated open lumbar surgery (25 patients), due to ASD or recurrence of disc herniation at L3-4, L4-5, or L5-S1 level, were assigned to different groups according to the surgical approaches. Clinical data were assessed and compared. Results. Mean blood loss was significantly less in the PELD group as compared to the open lumbar surgery group (P < 0.0001). Hospital stay and mean operating time were shorter significantly in the PELD group as compared to the open lumbar surgery group (P < 0.0001). Immediate postoperative pain improvement in VAS was 3.5 in the PELD group and -0.56 in the open lumbar surgery group (P < 0.0001). Conclusion. For ASD and recurrent lumbar disc herniation, PELD had more advantages over open lumbar surgery in terms of reduced blood loss, shorter hospital stay, operating time, fewer complications, and less postoperative discomfort.