Injury of the Internal Carotid Artery During Dissection of a Craniopharyngioma via the Pterional Approach: Case Report.

Among the various causes of intraoperative neurosurgical complications, a major arterial injury is one of the most devastating. Herein, the authors present a case of a 76-year-old patient who underwent removal of a craniopharyngioma via the pterional approach and experienced severe damage of her sclerotic left internal carotid artery because it was retracted excessively by a brain spatula, which resulted in complete sacrifice of the vessel. Despite stable parameters on intraoperative monitoring of motor evoked potentials and sufficient collateral blood flow, confirmed by Doppler flowmetry, a large infarct in the left cerebral hemisphere was noted after surgery. Although retraction of movable arteries, veins, and cranial nerves can often be done safely during neurosurgical procedures for effective exposure of the operative field, forced displacement of a sclerotic internal carotid artery in its paraclinoid portion anchored to the fixed distal dural ring should definitely be avoided because it poses a significant risk of major vessel damage.

[Chronic Subdural Hematoma with Middle Cranial Fossa Arachnoid Cyst Concomitant with Bilateral Papilledema:A Case Report].

Arachnoid cysts(AC)are benign cystic lesions often diagnosed in childhood. Although usually asymptomatic, AC can become symptomatic when the lesion size increases or coexists with a subdural hygroma or hematoma. AC patients with signs of increasing intracranial pressure(IICP)or neurological deficits may need surgical intervention; this usually results in a good prognosis. However, whether asymptomatic AC patients should undergo surgical treatment is controversial. Although trivial head trauma, such as that from contact sports, can cause subdural hematoma in AC patients, there are currently no definite criteria regarding sports participation for children with AC. CASE: A 12-year-old boy who belonged to a soccer club visited an ophthalmologist with the chief complaint of having had diplopia for two weeks. He was identified as having bilateral papilledema. Since he had been diagnosed with a right middle cranial fossa AC five years earlier, he was referred to our outpatient clinic. Cranial CT scans showed right chronic subdural hematoma alongside the AC. The patient subsequently underwent burr hole surgery and was discharged after one week. In this case, the patient did not present with the typical signs of IICP, such as headache or vomiting. This experience indicates that care must be taken when encountering patients with atypical symptoms, particularly children. In addition, it is important to carefully consider sports participation for children with AC.

Primary central nervous system malignant melanoma with leptomeningeal melanomatosis: a case report and review of the literature.

Leptomeningeal melanomatosis is an extremely rare variant of primary central nervous system (CNS) melanoma and has a poor prognosis and no standard treatment. Primary CNS melanoma is derived from the melanocytes of the leptomeninges. Here, we describe a case of a 37-year-old male who visited our hospital due to worsening headaches. Characteristic imaging findings of this tumor type include hyper-dense lesions that are enhanced by contrast medium on computed tomography and hyper-intensity on T1-weighted magnetic resonance images and iso- to hypo-intensity on T2-weighted magnetic resonance images. Imaging of the CNS in our patient showed several lesions of this type. Pathological diagnosis and exclusion of systemic melanoma are required to confirm primary CNS malignant melanoma. Partial resection of the mass in the left temporal lobe of this patient was performed, and histological analysis showed pigmentation, melanin black-45 positivity, and BRAF mutation. Because no lesions were found outside the CNS following a thorough whole-body search, he was diagnosed with primary CNS malignant melanoma with leptomeningeal melanomatosis. He was treated with whole-brain radiation and the BRAF kinase inhibitor vemurafenib. His condition worsened, and he was given the anti-programmed cell death-1 antibody nivolumab as second-line therapy. This was also unsuccessful, and he died 5 months after treatment initiation. Further studies are needed to improve treatment and prognosis of this rare but serious disease.

Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas.

Intracranial germ cell tumors (iGCTs) are the second most common brain tumors among children under 14 in Japan. The World Health Organization classification recognizes several subtypes of iGCTs, which are conventionally subclassified into pure germinoma or non-germinomatous GCTs. Recent exhaustive genomic studies showed that mutations of the genes involved in the MAPK and/or PI3K pathways are common in iGCTs; however, the mechanisms of how different subtypes develop, often as a mixed-GCT, are unknown. To elucidate the pathogenesis of iGCTs, we investigated 61 GCTs of various subtypes by genome-wide DNA methylation profiling. We showed that pure germinomas are characterized by global low DNA methylation, a unique epigenetic feature making them distinct from all other iGCTs subtypes. The patterns of methylation strongly resemble that of primordial germ cells (PGC) at the migration phase, possibly indicating the cell of origin for these tumors. Unlike PGC, however, hypomethylation extends to long interspersed nuclear element retrotransposons. Histologically and epigenetically distinct microdissected components of mixed-GCTs shared identical somatic mutations in the MAPK or PI3K pathways, indicating that they developed from a common ancestral cell.

Recurrent neomorphic mutations of MTOR in central nervous system and testicular germ cell tumors may be targeted for therapy.

Germ cell tumors constitute a heterogeneous group that displays a broad spectrum of morphology. They often arise in testes; however, extragonadal occurrence, in particular brain, is not uncommon, and whether they share a common pathogenesis is unknown. We performed whole exome sequencing in 41 pairs of central nervous system germ cell tumors (CNS GCTs) of various histology and their matched normal tissues. We then performed targeted sequencing of 41 selected genes in a total of 124 CNS GCTs, 65 testicular germ cell tumors (tGCTs) and 8 metastatic GCTs to the CNS. The results showed that mutually exclusive mutations of genes involved in the MAPK pathway were most common (48.4 %), typically in KIT (27.4 %), followed by those in the PI3K pathway (12.9 %), particularly in MTOR (6.5 %), among the 124 CNS GCTs. Pure germinomas and non-germinomatous germ cell tumors (NGGCTs), as well as CNS and testicular GCTs, showed similar mutational profiles, suggesting that GCTs share a common molecular pathogenesis. Mutated MTOR identified in CNS GCTs upregulated phosphorylation of the AKT pathway proteins including AKT and 4EBP1 in nutrient-deprived conditions and enhanced soft-agar colony formation; both events were suppressed in a dose-dependent manner by addition of the MTOR inhibitor pp242. Our findings indicate that the dominant genetic drivers of GCTs regardless of the site of origin are activation of the MAPK and/or PI3K pathways by somatic point mutations. Mutated MTOR represents a potential target for novel targeted therapies for refractory GCTs.

Distinct patterns of copy number alterations may predict poor outcome in central nervous system germ cell tumors.

We have previously reported that 12p gain may predict the presence of malignant components and poor prognosis for CNS germ cell tumor (GCT). Recently, 3p25.3 gain was identified as an independent predictor of poor prognosis for testicular GCT. Eighty-one CNS GCTs were analyzed. Copy number was calculated using methylation arrays. Five cases (6.2%) showed 3p25.3 gain, but only among the 40 non-germinomatous GCTs (NGGCTs) (5/40, 12.5%; p = 0.03). Among NGGCTs, those with a yolk sac tumor component showed a significantly higher frequency of 3p25.3 gain (18.2%) than those without (1.5%; p = 0.048). NGGCTs with gain showed significantly shorter progression-free survival (PFS) than those without (p = 0.047). The 3p25.3 gain and 12p gain were independent from each other. The combination of 3p25.3 gain and/or 12p gain was more frequent among NGGCTs with malignant components (69%) than among those without (29%; p = 0.02). Germinomas containing a higher number of copy number alterations showed shorter PFS than those with fewer (p = 0.03). Taken together, a finding of 3p25.3 gain may be a copy number alteration specific to NGGCTs and in combination with 12p gain could serve as a marker of negative prognosis or treatment resistance. Germinoma with frequent chromosomal instability may constitute an unfavorable subgroup.

Expression of RECK in endothelial cells of glioma: comparison with CD34 and VEGF expressions.

Angiogenesis is thought to be involved in the progression of glioma grades, and reversion-inducing cysteine-rich protein with Kazal motifs (RECK) has been said to be involved in maturation of vessels. In this study, we aimed to determine whether high micro-vessel density (MVD) expressed by RECK in glioma tissue is correlated with grades of glioma. We also compared RECK expression with that of the formerly known vessel marker, CD34, and vascular endothelial growth factor (VEGF). RECK, CD34, and VEGF immuno-reactivities of 72 glioma tissues were studied. RECK was seen in microvessels of glioma tissues. CD34 showed a similar pattern to RECK, whereas VEGF showed positive staining in cytoplasm of tumor cells and endothelial cells. Average MVD with RECK was 107.6 microvessels (range 7-290). RECK was positively correlated with grades of glioma. RECK and CD34 also showed a strong correlation (P = 0.001). Higher frequency of VEGF staining was also correlated with higher grade of glioma. This is the first study describing expression of RECK in glioma, and its angiogenesis-related nature may provide a potential therapeutic target for glioma treatment in the future.

Comparison of manual and digital microvascular density counting of RECK expression in glioma.

A microvascular density (MVD) counting method for reversion-inducing cysteine-rich protein with Kazal motifs (RECK) expression, using a digital image analysis tool, has advantages over manual counting by microscope. Thirty glioma cases with RECK staining were photographed at a magnification of 200× high power field and the photographs in RGB images were analyzed, and stained vessels were captured and were counted automatically. MVD with RECK expression using a digital image analysis tool showed comparable results to those of the manual method. RECK intensity expression could show linear correlation with grades of glioma by the digital method, which was superior compared to the manual method. The present method is recommended to researchers undertaking MVD study for glioma.

12p gain is predominantly observed in non-germinomatous germ cell tumors and identifies an unfavorable subgroup of central nervous system germ cell tumors.

BACKGROUND: Central nervous system (CNS) germ cell tumors (GCTs) are neoplasms predominantly arising in pediatric and young adult populations. While germinomas generally respond to chemotherapy and radiation, non-germinomatous GCTs (NGGCTs) require more intensive treatment. This study aimed to determine whether 12p gain could predict the prognosis of CNS GCTs. METHODS: Eighty-two CNS GCTs were included in this study. The 12p gain was defined by an additional 12p in the background of potential polyploidy or polysomy. Cases were analyzed using an Illumina methylation 450K array for copy number investigations and validated by fluorescence in situ hybridization (FISH). RESULTS: A 12p gain was found in 25-out-of-82 cases (30%) and was more frequent in NGGCTs (12% of germinoma cases and 50% of NGGCT cases), particularly in cases with malignant components, such as immature teratoma, yolk sac tumor, choriocarcinoma, and embryonal carcinoma. 12p gain and KIT mutation were mutually exclusive events. The presence of 12p gain correlated with shorter progression-free (PFS) and overall survival (OS) (10-year OS: 59% vs. 94%, with and without 12p gain, respectively, P = 0.0002), even with histology and tumor markers incorporated in the multivariate analysis. Among NGGCTs, 12p gain still had prognostic significance for PFS and OS (10-year OS: 47% vs. 90%, respectively, P = 0.02). The 12p copy number status was shared among histological components in mixed GCTs. CONCLUSIONS: 12p gain may predict the presence of malignant components of NGGCTs, and poor prognosis of the patients. It may be associated with early tumorigenesis of CNS GCT.

Transcriptome and methylome analysis of CNS germ cell tumor finds its cell-of-origin in embryogenesis and reveals shared similarities with testicular counterparts.

BACKGROUND: CNS germ cell tumors (GCTs) predominantly develop in pediatric and young adult patients with variable responses to surgery, radiation, and chemotherapy. This study aimed to examine the complex and largely unknown pathogenesis of CNS GCTs. METHODS: We used a combined transcriptomic and methylomic approach in 84 cases and conducted an integrative analysis of the normal cells undergoing embryogenesis and testicular GCTs. RESULTS: Genome-wide transcriptome analysis in CNS GCTs indicated that germinoma had a transcriptomic profile representative of primitive cells during early embryogenesis with high meiosis/mitosis potentials, while nongerminomatous GCTs (NGGCTs) had differentiated phenotypes oriented toward tissue formation and organogenesis. Co-analysis with the transcriptome of human embryonic cells revealed that germinomas had expression profiles similar to those of primordial germ cells, while the expression profiles of NGGCTs were similar to those of embryonic stem cells. Some germinoma cases were characterized by extensive immune-cell infiltration and high expression of cancer-testis antigens. NGGCTs had significantly higher immune-cell infiltration, characterized by immune-suppression phenotype. CNS and testicular GCTs (TGCTs) had similar mutational profiles; TGCTs showed enhanced copy number alterations. Methylation analysis clustered germinoma/seminoma and nongerminoma/nonseminoma separately. Germinoma and seminoma were co-categorized based on the degree of the tumor microenvironment balance. CONCLUSIONS: These results suggested that the pathophysiology of GCTs was less dependent on their site of origin and more dependent on the state of differentiation as well as on the tumor microenvironment balance. This study revealed distinct biological properties of GCTs, which will hopefully lead to future treatment development.

Reversion-inducing cysteine-rich protein with kazal motifs and matrix metalloproteinase-9 are prognostic markers in skull base chordomas.

Prognosis of chordomas is difficult to predict based solely on histological findings. The purpose of this study was to assess expressions of reversion-inducing cysteine-rich protein with kazal motifs (RECK) and matrix metalloproteinase (MMP)-2, MMP-9 in skull base chordomas and to find out their correlations to outcome. Immunohistochemical study was performed in 19 samples (initial, n = 11; recurrent, n = 8) from 11 patients. The correlations among expression of RECK, MMP-2, MMP-9, and their prognostic values were analyzed. Significant correlation between RECK and MMP-9 was found, but there was no correlation found between MMP-2 and MMP-9. Higher MMP-9 expression significantly influenced outcome. Furthermore, MMP-9/RECK ratio showed significant correlation to outcome, showing their inverse relationship in the disease progress of skull base chordoma. RECK and MMP-9 can be valuable markers to predict prognosis in skull base chordomas.

Urgent open embolectomy for cardioembolic cervical internal carotid artery occlusion.

Acute ischemic stroke attributable to cervical internal carotid artery (ICA) occlusion is frequently associated with severe disability or death and is usually caused by atherosclerosis. By contrast, the cardioembolic cervical ICA occlusion is rare, and feasibility of urgent recanalization remains unclear. We present the first study in the literature that focuses on urgent open embolectomy for the treatment of cardioembolic cervical ICA occlusion. A retrospective review of the charts for patients undergoing open embolectomy was performed. Between April 2006 and September 2007, 640 consecutive patients with acute ischemic stroke were treated. Of them, three patients (0.47%) with the acute complete cardioembolic cervical ICA occlusion underwent urgent open embolectomy. All patients presented with profound neurological deficits and atrial fibrillation. The urgent open embolectomy achieved complete recanalization in all patients without any complications. All emboli in three patients were very large and fibrinous in histological findings. Two of three patients showed rapid improvement in neurological functions after surgical treatments. The cardioembolic occlusion of the cervical ICA is rare, but its possibility should be considered in patients with acute ischemic stroke suffering profound neurological deficits and atrial fibrillation. Urgent open embolectomy may be a treatment option to obtain successful recanalization for cardioembolic cervical ICA occlusion and is recommended because it is technically easier and similar to carotid endarterectomy.

Standard and limitation of intraoperative monitoring of the visual evoked potential.

BACKGROUND: Visual evoked potential (VEP) has been installed as one of the intraoperative visual function monitoring. It remains unclear, however, whether intraoperative VEP monitoring facilitates as a real time visual function monitoring with satisfactory effectiveness and sensitivity. To evaluate this, relationships between VEP waveform changes and postoperative visual function were analysed retrospectively. METHODS: Intraoperative VEP monitoring was carried out for 106 sides (eyes) in 53 surgeries, including two intraorbital, 36 parasellar and 15 cortical lesions in Shinshu University Hospital under total intravenous anaesthesia. Red light flash stimulation was provided to each eye independently. VEP recording and postoperative visual function were analysed. RESULTS: In 103 out of 106 sides (97%), steady VEP monitoring was recorded. Stable VEP was acquired from eyes having corrected visual acuity greater than 0.4. VEP was not recorded in one side with corrected visual acuity of 0.3 and two sides in whom sevoflurane was used incidentally for anaesthesia. Transient VEP decrease was observed in three sides, but visual function was preserved. Permanent VEP decrease was seen in seven sides, which presented visual impairment postoperatively. In one side, visual acuity improved but minor visual field defect was encountered postoperatively, though VEP unchanged throughout the surgery. CONCLUSIONS: Intraoperative monitoring of VEP predicts postoperative visual function: reversible change in VEP means visual function to be preserved. Visual field defect without decrease in the visual acuity may not be predicted by VEP monitoring. Intraoperative VEP monitoring will be mandatory for surgeries harbouring a risk of visual impairment.

[Application of a polyethylene glycol hydrogel sealant system to prevent CSF leakage for lumbar intradural surgery: technical case report].

Postoperative cerebrospinal fluid (CSF) leakage is one of the most important surgical complications in spinal surgery. Particularly in intradural spinal cord tumor surgery, it is very important to prevent CSF leakage postoperatively, as it can lead to postoperative complications such as infection and pseudomeningocele formation. Compared to the intracranial region, as the operative field is narrower and the structure of the dura mater is more fragile in the spinal region, meticulous dural suturing is sometimes impossible after intradural procedures. To prevent CSF leakage, some surgical procedures and materials have been developed in the neurosurgical field, including the recently introduced polyethylene glycol-based hydrogel sealant system. The hydrogel sealant system consists of synthetic absorbable material, which eliminates the risk of viral transmission and reduces the risk of allergic reaction. It proved to have potential for reducing postoperative CSF leakage. We used this material in intradural lumbar lesion surgery, and postoperative CSF leakage did not occur with this surgical procedure. We report our experience with dural plasty using the hydrogel sealant system in the intradural lumbar spinal lesion surgery and discuss the usefulness of this material.

Integrated clinical, histopathological, and molecular data analysis of 190 central nervous system germ cell tumors from the iGCT Consortium.

BACKGROUND: We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management. METHODS: Data from the Intracranial Germ Cell Tumor Genome Analysis (iGCT) Consortium were reviewed. A total of 190 cases were classified as primary germ cell tumors (GCTs) based on central pathological reviews. RESULTS: All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker positive and 6.1% of non-germinomatous GCTs were marker negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better progression-free survival than those at atypical sites (P = 0.03). A molecular clinical association study revealed frequent mitogen-activated protein kinase (MAPK) pathway mutations in males (51.4% vs 14.3%, P = 0.007), and phosphatidylinositol-3 kinase/mammalian target of rapamycin (PI3K/mTOR) pathway mutations in basal ganglia cases (P = 0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance. CONCLUSIONS: The in-depth findings of this study regarding clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.

Emergency embolectomy for treatment of acute middle cerebral artery occlusion.

OBJECT: The authors evaluated the efficacy of emergency embolectomy in patients with acute middle cerebral artery occlusion (MCAO). METHODS: A retrospective review of the charts for patients undergoing embolectomy at the authors' institution was performed. Between October 1997 and May 2004, 12 patients (mean age 70 years) with acute MCAO were treated using embolectomy. Local intraarterial fibrinolysis with urokinase was initially undertaken in eight of 12 patients. Sufficient recanalization was not achieved with fibrinolysis in any patient, and thus embolectomy was performed immediately thereafter. Recanalization by embolectomy was achieved in all patients (mean occlusion time 6 hours, 11 minutes). Each patient's condition was evaluated on discharge. Outcomes in the 12 patients according to the Glasgow Outcome Scale were good recovery in five, moderate disability in two, severe disability in three, vegetative state in one, and death due to a cardiac complication in one. None of the 12 patients had symptomatic hemorrhagic infarction. CONCLUSIONS: Emergency embolectomy can be performed in patients with MCAO with minimal morbidity and death. The procedure can be used to achieve good recovery even in patients in whom fibrinolysis is insufficient after acute MCAO and should be a part of the algorithm for the treatment of MCAO.

Loss of visual evoked potential following temporary occlusion of the superior hypophyseal artery during aneurysm clip placement surgery. Case report.

The authors report a case in which a 62-year-old woman with a history of subarachnoid hemorrhage due to a ruptured aneurysm was found to have a de novo paraclinoid aneurysm in the right internal carotid artery during a routine medical examination. Surgical clip placement was performed via a contralateral pterional approach under visual evoked potential (VEP) monitoring. The superior hypophyseal artery (SHA) was found to originate from the aneurysm body. The artery was temporarily occluded prior to application of the clip to the aneurysm neck. The VEP signal was lost 3 minutes after the SHA was occluded, and the potentials gradually recovered 10 minutes after the artery was released. The disappearance of VEP signal was reproducible with SHA occlusion. The clip was applied to the aneurysm body to preserve the origin of the SHA. The patient did not have any deterioration of vision after surgery. Intraoperative VEP monitoring can be used to help determine whether the SHA can be sacrificed safely.

Analysis of immunohistochemical expression of p53 and the proliferation marker Ki-67 antigen in skull base chordomas: relationships between their expression and prognosis.

The prognosis of chordomas is difficult to predict based solely on histological findings. The purpose of this study was to assess the immunohistochemical expression of the proliferation marker Ki-67 antigen and the expression of p53 in skull base chordomas and to relate their expressions to the outcome. We examined the expression of p53 and the MIB-1 labeling index (LI), assessed by Ki-67 expression, in 19 tumors (initial, n = 11; recurrent, n = 8) from 11 patients. The correlation among the MIB-1 LI, p53 expression, and the clinical outcome was analyzed. The mean MIB-1 LI and p53 expression at the initial surgery were 5.6 +/- 4.6% and 9.0 +/- 9.4%, respectively. At the time of recurrence, the mean MIB-1 LI and p53 expression were 10.2 +/- 7.4% and 16.5 +/- 12.0%. The correlation between the MIB-1 LI and p53 expression at the initial and recurrent surgeries was highly significant (r = 0.948; P < 0.0001). The change in p53 expression from the initial to the recurrent chordomas was significantly greater in patients who died of tumor-related causes than in the surviving patients. In the surviving patients, the values for MIB-1 LI and p53 expression in the recurrent tumors were significantly higher in the disease-ongoing group than in the disease-free group. Our results suggest that determination of the immunohistochemical expression of p53 and Ki-67 antigen is helpful to predict tumor recurrence and prognosis in skull base chordomas.

Retraction suture technique for carotid endarterectomy.

We propose a retraction suture technique as a safe and effective surgical procedure for carotid endarterectomy. Retraction sutures of the skin flap, the carotid sheath and the adventitia of the carotid artery are used to obtain an adequate operative field without the use of retractors or assistants. This technique is useful for carotid endarterectomy.

Atlantoaxial dislocation associated with a mass in the extradural craniovertebral junction unrelated to rheumatoid arthritis. Case report.

A 61-year-old woman without rheumatoid arthritis (RA) was admitted with atlantoaxial dislocation (AAD) and a retroodontoid mass at the craniovertebral junction manifesting as a 1-year history of numbness and mild weakness of the right upper extremity. Computed tomography and magnetic resonance (MR) imaging showed AAD and a mass at the craniovertebral junction. She had no past history of RA or trauma in the head and neck. She underwent surgery to obtain the histological diagnosis of the mass and to improve AAD-induced instability. The lesion was approached through the right transcondylar fossa approach with C-1 laminectomy. Intraoperative pathological examination showed cicatrizing collagen fibers and no obvious tumor cells. After partial removal of the lesion, the AAD was fixed with the posterior approach. The symptoms subsided soon after surgery and the mass decreased on MR images taken 3 months after surgery. If a pseudotumor is suspected based on the preoperative radiological investigation in a non-RA patient with AAD and the symptoms are not progressive, stabilization can be expected to induce spontaneous regression without urgent direct excision of the mass.