Mitogen-activated protein kinase in gliosis and pilocytic astrocytoma.

Pilocytic astrocytoma (PA), featuring activation of the mitogen-activated protein kinase (MAPK) pathway, is the most common tumor of the pediatric central nervous system. However, it remains unknown whether MAPK activation is present in the reactive gliosis of non-neoplastic lesions. Therefore, we investigated the expression of MAPK in reactive gliosis associated with cavernous angiomas. Immunohistochemical expression and the extent of BRAF, ERK, p38, and JNK were investigated in 10 patients with gliosis surrounding cavernous angiomas (GS group) and 10 patients with PA (PA group). Evaluation of these parameters was scored as 0, none; 1, scarce; 2, moderate; 3, global. In the GS group, histopathologic features of PA (piloid cells, Rosenthal fibers, microcysts with eosinophilic granular bodies) were identified. Expression of ERK, and p38 was shown in all patients in the GS and PA group. Expression of BRAF was identified in 5 patients (50%) in the GS group and in 8 (80%) in the PA group. The mean score of BRAF expression in the PA group was significantly higher than that in the GS group (p = 0.019). Reactive gliosis may resemble PA in histological findings and MAPK activation. Therefore, PA could be indistinguishable from reactive gliosis with classic histopathologic and/or immunohistochemical methods.
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Precise Evaluation of Striatal Oxidative Stress Corrected for Severity of Dopaminergic Neuronal Degeneration in Patients with Parkinson's Disease: A Study with 62Cu-ATSM PET and 123I-FP-CIT SPECT.

BACKGROUND: This study sought to precisely evaluate striatal oxidative stress and its relationship with the disease severity in Parkinson's disease (PD) using double brain imaging, 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) (62Cu-ATSM) PET and 123I-FP-CIT SPECT. METHODS: Nine PD patients were studied with brain 62Cu-ATSM PET for oxidative stress and 123I-FP-CIT SPECT for the density of striatal dopamine transporter. Standardized uptake values (SUVs) were obtained from the delayed phase of dynamic 62Cu-ATSM PET, and striatum-to-cerebellum SUV ratio (SUVR) was calculated. To correct the effect of neuronal loss in the striatum, 62Cu-ATSM SUVR was corrected for striatal specific binding ratio (SBR) values of 123I-FP-CIT (SUVR/SBR). RESULTS: 62Cu-ATSM SUVR without correction was not significantly correlated with disease severity estimated by the Unified Parkinson's Disease Rating Scale (UPDRS) scores or 123I-FP-CIT SBR. In contrast, the SUVR/SBR showed significant correlations with the UPDRS total and motor scores, and 123I-FP-CIT SBR. CONCLUSION: Oxidative stress in the remaining striatal dopaminergic neurons estimated by SUVR/SBR was increased with disease severity in PD patients, suggesting that oxidative stress based on mitochondrial dysfunction contributes to promoting dopaminergic neuronal degeneration in PD. 62Cu-ATSM PET with 123I-FP-CIT SPECT correction would be a promising tool to evaluate dopaminergic neuronal oxidative stress in PD.

Lobar Hemorrhage Induced by Acquired Factor XIII Deficiency in a Patient with Cerebral Amyloid Angiopathy.

A 68-year-old man presented with intracranial hemorrhage in the right frontal lobe, which rapidly increased the day after admission. We performed hematoma removal with a biopsy of the cortex around the hematoma. The day after the operation, a subcutaneous hematoma over the craniotomy appeared, and the computed tomography showed a recurrent hemorrhage with an acute subdural hematoma. We were aware of a bleeding tendency, and a detailed hematologic examination by hematologists revealed autoimmune acquired factor XIII deficiency due to an antifactor XIII antibody. Specimens taken around the hematomas were pathologically diagnosed as cerebral amyloid angiopathy (CAA) on immunohistochemical examination. We considered that acquired factor XIII deficiency had induced lobar hemorrhage in the frontal lobe affected with CAA, and the coagulation disorder induced postoperative rebleeding. The patient died from repeated lobar hemorrhage 3 years after the surgery. There is no routine screening coagulation test including the active partial thromboplastin time and the prothrombin time for factor XIII deficiency. It is important for neurologists and neurosurgeons to be aware of this rare disease in patients with a bleeding tendency.

Occipital cephalocele with neural crest remnants? Radiological and pathological findings in a newborn boy.

PURPOSE: A cephalocele is a congenital anomaly involving the herniation of intracranial tissue from a skull defect. The sac containing the central nervous system (CNS) with the ventricle system is called the encephalocystocele. An atretic cephalocele is thought to be an abortive form of cephalocele, and the essential nature is still controversial. CASE REPORT: Here, we report the case of a newborn boy with an occipital cephalocele containing a small cystic component which was composed of ependymal cells and the immature CNS tissue. A newborn boy was admitted to our hospital because of an occipital mass, which was about 2.5 cm in diameter, located at the posterior midline, and covered with alopetic skin without CSF leakage. He had a cleft palate. Magnetic resonance imaging (MRI) clearly showed an occipital cephalocele with a tiny cystic component connecting to the subarachnoid space. MRI also showed mild hydrocephalus, hypoplasia of the corpus callosum and tentorium cerebelli, dropping down of the bilateral occipital lobes and vermicular agenesis. We performed the extirpation of the subscalp module under general anesthesia and histologically examined the resected mass. On immunohistopathological examination, most part of the subscalp module was fibrous tissue with numerous vessels and meningeal origin cells. In a small part of the innermost layer, we found a small island consisting of CNS tissue and a tiny cyst lined with a single layer of ependymal cells. CONCLUSION: Based on radiological and immunohistopathological findings, we speculate that the cystic component at the base of the nodule seems to correspond to neural crest remnants but not to true herniation of the brain and cerebral ventricles.

Predictive Factors for the Occurrence of Visual and Ischemic Complications After Open Surgery for Paraclinoid Aneurysms of the Internal Carotid Artery.

OBJECTIVE: To investigate the predictive factors for visual and ischemic complications after open surgery for paraclinoid aneurysms of the internal carotid artery (ICA). MATERIALS AND METHODS: Thirty-eight consecutive patients with unruptured paraclinoid aneurysms of ICA operated on between 2009 and 2013 were included in this study. The male:female ratio was 6:32 and the ages ranged from 33 to 81 (mean: 60 ± 2). Twenty cases were asymptomatic and 18 had ophthalmological symptoms. The sizes of the aneurysms ranged from 2 to 35 mm (mean: 10.6 ± 9 mm). Twenty-three patients were treated by clipping and 15 by trapping with bypass (high-flow bypass in 11, and low-flow in 4). Twenty-four patients underwent removal of the anterior clinoid process. Among them, 8 underwent en bloc anterior clinoidectomy with a high-speed drill, and 16 had piecemeal excision with a microrongeur or ultrasonic bone curette. Intraoperative monitoring was performed using motor-evoked potentials (MEP) and visual-evoked potentials (VEP) in 27 and 15 cases, respectively. RESULTS: Complete obliteration of the aneurysm was achieved in 37 cases (97.4 %). The patency rate of bypass was 100 %. Postoperative worsening of visual acuity, including one case of blindness, was observed in six cases (11 %). Worsening of visual field defects occurred in 14 cases (38 %), but 10 of them were transient. Transient oculomotor nerve palsy occurred in six cases (15 %). Postoperative stroke was detected by diffusion-weighted imaging (DWI) in five cases (13 %), four of which were symptomatic. Statistical analysis showed that piecemeal anterior clinoidectomy was significantly safer than en bloc removal in preserving visual function. Trapping with high-flow bypass had a significantly greater risk of postoperative stroke than direct clipping. CONCLUSIONS: Intraoperative VEP monitoring might be useful for preventing postoperative worsening of visual function. Two-stage treatment with bypass and endovascular trapping might be safer than single-stage trapping alone.

Cerebral amyloid angiopathy causing large contralateral hemorrhage during surgery for lobar hemorrhage: a case report.

We report a rare case of cerebral amyloid angiopathy (CAA) causing large contralateral hemorrhage during surgery for lobar hemorrhage. A 62-year-old woman presented with lobar hemorrhage in the left frontal and parietal lobes recurring over the previous 1 month. Because we could not detect the origin of the lobar hemorrhage, we performed a biopsy around the lobar hemorrhage site with the removal of a hematoma. During the surgery, we identified acute brain swelling without bleeding from the operative field. Intraoperative computed tomography demonstrated new large lobar hemorrhage of the right parietal lobe, which we could promptly remove. Specimens around hematomas on both sides were pathologically diagnosed as CAA on immunohistochemical examination. After the surgery, she suffered from lobar hemorrhage three times in the space of only 3 months. To the best of our knowledge, there has been no reported case of CAA causing intracranial hemorrhage of another lesion during surgery. Neurosurgeons should know a possibility of intraoperative hemorrhage in surgeries for lobar hemorrhage caused by CAA.

Thin-film electroencephalographic electrodes using multi-walled carbon nanotubes are effective for neurosurgery.

BACKGROUND: Intraoperative morphological and functional monitoring is essential for safe neurosurgery. Functional monitoring is based on electroencephalography (EEG), which uses silver electrodes. However, these electrodes generate metal artifacts as silver blocks X-rays, creating white radial lines on computed tomography (CT) images during surgery. Thick electrodes interfere with surgical procedures. Thus, thinner and lighter electrodes are ideal for intraoperative use. METHODS: The authors developed thin brain electrodes using carbon nanotubes that were formed into thin sheets and connected to electrical wires. RESULTS: The nanotube sheets were soft and fitted the curve of the head very well. When attached to the head using paste, the impedance of the newly developed electrodes was 5 kΩ or lower, which was similar to that of conventional metal electrodes. These electrodes can be used in combination with intraoperative CT, magnetic resonance imaging (MRI), or cerebral angiography. Somatosensory-evoked potentials, auditory brainstem responses, and visually evoked potentials were clearly identified in ten volunteers. The electrodes, without any artifacts that distort images, did not interfere with X-rays, CT, or MR images. They also did not cause skin damage. CONCLUSIONS: Carbon nanotube electrodes may be ideal for neurosurgery.

[Determining the tumor-cell density required for macroscopic observation of 5-ALA-induced fluorescence of protoporphyrin IX in cultured glioma cells and clinical cases].

We investigated the association between the cell density and intensity of 5-aminolevulinic acid-induced fluorescence of protoporphyrin IX in 3-dimensionally cultured C6 glioma cells. The ratio between 636-nm red fluorescence excited by a 405-nm laser and 513-nm green autofluorescence of the tissue was measured as the fluorescence intensity. A ratio exceeding 0.68 was macroscopically judged as fluorescence-positive by observers, and the cell density at this fluorescence intensity was 1×107< cells/mL. In clinical surgical fields, the fluorescence ratio was about 0.65 in cases judged as fluorescence-positive, similarly to that in cultured cells. Neurosurgeons and pathologists should recognize that tumor cells are present in fluorescence-negative regions. It is necessary to develop a device which measures fluorescence more simply than macroscopic observation for cutting-edge brain surgery.

[Detection of oculomotor nerve compression by 3D-FIESTA MRI in a patient with pituitary apoplexy and diabetes mellitus].

We report the usefulness of 3D-FIESTA magnetic resonance imaging(MRI)for the detection of oculomotor nerve palsy in a case of pituitary apoplexy. A 69-year-old man with diabetes mellitus presented with complete left-side blepharoptosis. Computed tomography of the brain showed an intrasellar mass with hemorrhage. MRI demonstrated a pituitary adenoma with a cyst toward the left cavernous sinus, which was diagnosed as pituitary apoplexy. 3D-FIESTA revealed that the left oculomotor nerve was compressed by the cyst. He underwent trans-sphenoid tumor resection at 5 days after his hospitalization. Post-operative 3D-FIESTA MRI revealed decrease in compression of the left oculomotor nerve by the cyst. His left oculomotor palsy recovered completely within a few months. Oculomotor nerve palsy can occur due to various diseases, and 3D-FIESTA MRI is useful for detection of oculomotor nerve compression, especially in the field of parasellar lesions.

Relationship between gait parameters and MR imaging in idiopathic normal pressure hydrocephalus patients after shunt surgery.

BACKGROUND: A few previous studies have reported a change in gait motion in idiopathic normal pressure hydrocephalus (iNPH) patients after shunt surgery compared with before shunt surgery; however, there has been no detailed quantitative investigation of gait, including kinetic and kinematic parameters. Furthermore, the relationship between gait parameters and magnetic resonance (MR) imaging has not been confirmed. RESEARCH QUESTION: We investigated the gait motion in patients with iNPH, and evaluated the relationship between kinetic gait parameters and MR imaging before and after shunt surgery. METHODS: The subjects were 12 patients with iNPH who could walk 10 m without aids. A three-dimensional motion analysis system was used to obtain the spatiotemporal, kinetic, and kinematic parameters before and after surgery. Relationships between each gait parameter and MR imaging were assessed. RESULTS: The post-shunt walking speed and step length were increased compared with pre-shunt values. The post-shunt evaluation showed increased range of motion of the hip, knee, and ankle joints in the sagittal plane during the gait cycle. The peak flexion moment of the hip during the stance phase was greater after shunt surgery. The improvement rate of the Evans index was significantly correlated with the improvement rate of walking speed, and the total ranges of motion of the hip and ankle joints in the sagittal plane. SIGNIFICANCE: The propulsive force of the hip and ankle joints was regained after shunt surgery. Normalization of the Evans index could predict improvement in propulsive force after shunt surgery in iNPH.

Pathological examination of cerebral amyloid angiopathy in patients who underwent removal of lobar hemorrhages.

Cerebral amyloid angiopathy (CAA) is a degenerative disorder characterized by amyloid-ß (Aß) deposition in the brain microvessels. CAA is also known to contribute not only to cortical microbleeds but also lobar hemorrhages. This retrospective study examined CAA pathologically in patients who underwent direct surgeries for lobar hemorrhage. Thirty-three patients with lobar hemorrhage underwent open surgery with biopsy from 2007 to 2016 in our hospital. Cortical tissues over hematomas obtained surgically were pathologically examined using hematoxylin, eosin stain, and anti-Aß antibody to diagnose CAA. We also investigated the advanced degree of CAA and clinical features of each patient with lobar hemorrhage. In the 33 patients, 4 yielded specimens that were insufficient to evaluate CAA pathologically. Twenty-four of the remaining 29 patients (82.8%) were pathologically diagnosed with CAA. The majority of CAA-positive patients had moderate or severe CAA based on a grading scale to estimate the advanced degree of CAA. About half of the CAA-positive patients had hypertension, and four took anticoagulant or antiplatelet agents. In five patients who were not pathologically diagnosed with CAA, one had severe liver function disorder, three had uncontrollable hypertension, and one had no obvious risk factor. Our pathological findings suggest that severe CAA with vasculopathic change markedly contributes to lobar hemorrhage. The coexistence of severe CAA and risk factors such as hypertension, anticoagulants or antiplatelets may readily induce lobar hemorrhage.

Super-selective Balloon Test Occlusion of the Posterior Communicating Artery in the Treatment of a Posterior Cerebral Artery Fusiform Aneurysm: a Case Report.

We report the case of a 49-year-old man with underlying hypertension who developed diplopia lasting 2 months. Magnetic resonance imaging and digital subtraction angiography showed multi-lobular unruptured aneurysms in the P2 portion of the posterior cerebral artery (PCA) migrating into the interpeduncular cistern of the midbrain. Because the shapes of the aneurysms were serpentine fusiform and the posterior communicating artery (PCoA) was the fetal type, we planned anastomosis of the occipital artery to the P4 portion of the PCA followed by endovascular obliteration of the parent artery including the aneurysms. Endovascular treatment was performed via a femoral approach one week after the anastomosis. Super-selective balloon test occlusion (BTO) of the PCoA was performed by using an occlusion balloon microcatheter before endovascular treatment. Occlusion of the proximal segment of the PCoA induced disturbance of consciousness of the patient. Occlusion of the distal segment other than the first point of the PCoA did not induce any neurological symptoms. The information from this super-selective BTO helped us to perform precise endovascular obliteration. The aneurysm was successfully obliterated, and the diplopia almost disappeared in a few months. Super-selective BTO of the PCoA might be a useful method for preventing ischemic complications due to occlusion of invisible perforators.

Measurement and cellular sources of the soluble interleukin-2 receptor in primary central nervous system lymphoma.

The aims of this study were to determine the diagnostic utility of the serum levels of the soluble interleukin 2 receptor (sIL-2R) as a tumor marker of primary central nervous system lymphoma (PCNSL) and to investigate the cellular source of sIL-2R using immunohistochemical staining. The serum sIL-2R levels of 37 samples from suspected PCNSL patients were measured. There were 13 patients with PCNSL and 24 patients with other diseases such as glioma, metastatic tumor, inflammation, or cerebrovascular disease. The serum sIL-2R levels of the PCNSL cases and other brain diseases were 629.5 ± 586.0 U/ml (mean ± SD; range 189-2220 U/ml) and 408.5 ± 250.7 U/ml (160-837 U/ml), respectively. The serum sIL-2R levels of the two groups overlapped, and hence the difference between them was not significant. sIL-2R is the α subunit of IL-2R. It is also known as CD25, and is cleaved from its position in the cell membrane and released into the blood. CD25 expression was immunohistochemically detected in 7 of 11 PCNSL samples. Confocal laser microscopy revealed that CD25 signals were present in atypical cells and mononuclear cells. We concluded that both lymphoma cells and infiltrating T cells express CD25, which is one of the cellular sources of sIL-2R.

Glioblastoma with oligodendroglial components: glioblastoma or anaplastic oligodendroglial tumors.

There have been some recent reports about glioblastoma with oligodendroglial (OG) components and malignant glioma with primitive neuroectodermal tumor (PNET)-like components. We investigated whether the presence and extent of OG components and PNET-like components influenced the prognosis in patients with glioblastoma. Eighty-six patients with glioblastoma were divided into an OG group (28 %), which revealed areas with a honeycomb appearance, and a non-OG group (72 %) without a honeycomb appearance. Patients with glioblastoma were also divided into a PNET group (27 %), which revealed areas with PNET-like features defined as neoplastic cells with high N/C ratios and hyperchromatic oval-carrot-shaped nuclei, and lacked the typical honeycomb appearance, and a non-PNET group (73 %) without PNET features. There were no significant differences in overall survival among the OG, the non-OG, the PNET, and the non-PNET groups. Two patients who survived longer than 36 months had both OG and PNET components with 1p or 19q loss of heterozygosity. Perinuclear halo, which is a characteristic feature of oligodendrogliomas, is an artifact of tissue fixation. Therefore, we should not readily use the term glioblastoma with OG components. PNET-like components, which are considered rare in malignant gliomas, may be frequently identified in glioblastomas.

Clinicopathological features in the recurrence of oligodendroglioma and diffuse astrocytoma.

To investigate whether grade II oligodendroglioma was transformed to glioblastoma or not, histopathological evaluation of recurrent oligodendrogliomal tumors (OG) and diffuse astrocytomas (DA) was performed. The OG group was composed of ten patients with OG, including seven oligodendrogliomas and three oligoastrocytomas. The DA group was composed of ten patients with DA, including eight fibrillary astrocytomas and two gemistocytic astrocytomas. The histopathological parameters of glioblastoma including nuclear atypia, multinucleated giant cells, glomeruloid tufts (GT) as a marker of microvascular proliferation, necrosis, and the Ki-67 staining index were investigated. Evaluation of these parameters was scored as follows: 0, none; 1, sporadic; 2, partial; 3, extensive. There were no cases of transformation to glioblastoma in the OG group. There were five cases of transformation to secondary glioblastoma in the DA group. In recurrent tumors, scores of GT and necrosis in the OG group were significantly lower than those in the DA group (p < 0.005). Nuclear atypia and high proliferative activity (Ki-67 index) were identified in recurrent tumors of the OG group. Our study suggested that the extent of GT and necrosis in recurrent OG was less than that in recurrent DA, and transformation to glioblastoma from oligodendroglial tumor was exceptional.