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OBJECT The authors’ goal in this paper is to provide the first clinical, radiological, and genetic studies of panventriculomegaly (PaVM) defined by a wide foramen of Magendie and large cisterna magna. METHODS Clinical and brain imaging data from 28 PaVM patients (including 10 patients from 5 families) were retrospectively studied. Five children were included. In adult patients, the age at onset was 56.0 ± 16.7 years. Tetraventricular dilation, aqueductal opening with flow void on T2-weighted images, and a wide foramen of Magendie and large cisterna magna (wide cerebrospinal fluid space at the fourth ventricle outlet) were essential MRI findings for PaVM diagnosis. 3D fast asymmetrical spin echo sequences were used for visualization of cistern membranes. Time-spatial labeling inversion pulse examination was performed to analyze cerebrospinal fluid movement. Copy number variations were determined using high-resolution microarray and were validated by quantitative polymerase chain reaction with breakpoint sequencing. RESULTS Adult patients showed gait disturbance, urinary dysfunction, and cognitive dysfunction. Five infant patients exhibited macrocranium. Patients were divided into 2 subcategories, those with or without downward bulging third ventricular floors and membranous structures in the prepontine cistern. Patients with bulging floors were successfully treated with endoscopic third ventriculostomy. Genetic analysis revealed a deletion in DNAH14 that encodes a dynein heavy chain protein associated with motile cilia function, and which co-segregated with patients in a family without a downward bulging third ventricular floor. CONCLUSIONS Panventriculomegaly with a wide foramen of Magendie and a large cisterna magna may belong to a subtype of congenital hydrocephalus with familial accumulation, younger age at onset, and symptoms of normal pressure hydrocephalus. In addition, a family with PaVM has a gene mutation associated with dysfunction of motile cilia.

A 56-year-old man complained of gait disturbance and confused thinking. Magnetic resonance imaging(MRI)revealed an arteriovenous malformation(AVM)of the cerebellar vermis(Spetzler-Martin grade IV)causing hydrocephalus. One dilated precentral cerebellar vein was compressing the aqueduct. After feeder embolization over 3 sessions using N-butyl cyanoacrylate(NBCA), the nidus was reduced to one-third in size. However, symptoms remained unimproved, and endoscopic third ventriculostomy(ETV)was performed. The third ventricle showed thinning of the floor, with a fenestration in part of the floor. Radiological findings and clinical symptoms improved, and the patient returned home after rehabilitation. The condition of the patient remained stable as of six months later. On angiography, the draining vein showed a pressure of 20 mmHg with no change in the residual AVM. Embolization alone achieved a reduction in nidus volume, but could not reduce venous pressure, and combination therapy including ETV proved necessary. Cases with hydrocephalus due to aqueductal stenosis by AVM are extremely rare. This pathology is discussed with reference to the literature.

Aquaporin (AQP) water channels play an important role in water movement in the central nervous system. The authors used an animal model to examine the relationship between AQP4 expression and spontaneously arrested hydrocephalus.. Congenitally hydrocephalic H-Tx (hH-Tx) rats and nonhydrocephalic H-Tx (nH-Tx) rats were used in the study. Brain tissue sections were obtained from animals in both groups at 1 day, 1 week, 4 weeks, and 8 weeks of age. Sections were immunostained using AQP4 antibodies, and AQP4 expression was assessed. In the nH-Tx group, no AQP4 expression was seen in 1-day-old rats, and AQP4 expression was found in astrocytes around capillaries of the cerebral cortex and in ependymal cells lining the ventricles in 1-week-old rats. In the 4- and 8-week-old nH-Tx animals, AQP4 expression was seen in subpial zones of the cortex, on foot processes of pericapillary astrocytes, and in periventricular regions. A marked increase in cerebral cortical expression of AQP4 was observed at 8 weeks in the hH-Tx rats but not in the nH-Tx rats.The authors hypothesize that the differences in cerebral AQP4 expression in the 1-day-old and 1-week-old nH-Tx rats compared with the 4- and 8-week-old nH-Tx rats may be related to the fact that the cerebrospinal fluid (CSF) circulation of newborns and infants differs from that of adults. It is also possible that the increased expression of AQP4 seen in the 8-week-old hH-Tx animals was related to the development of alternative pathways of CSF circulation, which also may occur in instances of spontaneously arrested hydrocephalus.

Background. The pathogenesis of idiopathic normal pressure hydrocephalus (INPH) is unknown, and the syndrome of INPH remains a diagnostic and therapeutic challenge. The present study investigated the disease-specific proteins that aid in the diagnosis and treatment of INPH and thus to study their role in the disease process. Methods. A comparative proteomic analysis was used for clinical screening of cerebrospinal fluid (CSF) proteins in 15 patients with INPH and compared with 12 normal subjects. Furthermore, enzyme linked immunosorbent assay (ELISA) was performed for comparison with CSF proteins between individual INPH patients and controls. Results. Seven proteins and their isoforms, including leucine-rich α-2-glycoprotein (LRG), α1-antichymotrypsin, apolipoprotein D, apolipoprotein J, haptoglobin α1, serum albumin, and α-1-microglobulin/bikunin precursor showed significant changes in CSF of INPH patients compared with controls by proteomic analysis. And significant higher CSF levels of LRG in INPH patients compared with controls were found by ELISA. Conclusions. These results indicate that there are significant differences in the expression of certain proteins in the CSF of patients with INPH and normal subjects. In particular, the CSF level assay of LRG suggests that LRG is a specific biomarker for INPH and has potential use in the diagnosis and indication for CSF shunting.

The H-Tx rat is a polygenic inherited model of hydrocephalus. In order to identify disease-specific biomarkers associated with congenital hydrocephalus, comparative proteomic analysis was used to screen cerebellum proteins in H-Tx rats at 1 day after birth. Seven proteins showed significant changes in hydrocephalic H-Tx rats compared with Sprague-Dawley and normal H-Tx rats, including HMG-1, CDCrel-1A, mitochondrial ATP synthase, ERp29, NADP+-ICDH, CCT beta and gamma. This indicates that the hydro-cephalus in H-Tx rats may be the result of a panel of proteins. In particular, the presence of HMG-1 and lack of CDCrel-1 in hydrocephalic H-Tx rats suggests that the use of two protein markers will provide further insight with respect to congenital hydrocephalus.

Peripheral primitive neuroectodermal tumor (PNET) occurring as an extra-axial lesion within the intracranial space and extending to the subarachnoid space is extremely rare.An 18-month-old girl presented with an intracranial peripheral PNET manifesting as abducens nerve palsy. Magnetic resonance imaging on admission revealed a lesion affecting the trigeminal and abducens nerves. The tumor was partially removed via the subtemporal approach. Histological examination showed a high-grade, undifferentiated neoplasm of small cell type with positive immunostaining for MIC2. The histological diagnosis was peripheral PNET.Craniospinal radiotherapy reduced the tumor size, but adjuvant chemotherapy designed for Ewing's sarcomas and PNETs was not effective. She died 1 month after the last chemotherapy, despite whole craniospinal irradiation (total dose 53.2 Gy) and chemotherapy.

Cerebral cavernous malformation (CCM) is a hamartomatous vascular disease affecting the central nervous system. A fraction of CCM are thought to arise in association with genomic mutations in the cerebral cavernous malformation 1 (CCM1) (KRIT1), CCM2 (MGC4607), and CCM3 (PDCD10) genes. In the present study, 18 Japanese patients with multiple CCM (10 with familial type and eight with sporadic type), underwent genomic analysis for CCM1, CCM2 and CCM3 mutations with blood samples and surgical specimens. MRI showed CCM in the cerebral hemisphere in 17 patients, the cerebellum in 10, the brainstem in 10 and the spinal cord in eight. CCM2 mutations were the most prominent, followed by CCM1 and CCM3. CCM1, CCM2 and CCM3 mutations were not identified in seven patients. Among the 10 patients with familial CCM, CCM1, CCM2 and CCM3 mutations were found in two, three and one patient, respectively, whereas four patients lacked these mutations. Among the eight patients with sporadic CCM, these mutations were found in one, three, and one patients, respectively, whereas three patients lacked these mutations. Most of the patients had a stable course during the follow-up period. Genomic mutations other than CCM1, CCM2 and CCM3 may be frequent in patients with multiple CCM in the Japanese population.

Transforming growth factor-β (TGF-β) is an important cytokine with modulatory actions in the nervous system. The development of hydrocephalus in mouse models resulting from the overexpression of TGF-β1 has previously been described, but the mechanism by which this occurs remains obscure. In order to evaluate the role of TGF-β in hydrocephalus, we used SYBR Green I-based real-time quantitative RT-PCR method and Western blot analysis to analyze the TGF-β2 and TGF-β3 mRNA and protein expressions in the cerebral cortex of the H-Tx rat, a model of congenital hydrocephalus. The hydrocephalic H-Tx rat expressed significantly higher TGF-β3 levels than their normal siblings (p

The accurate diagnosis and treatment of posterior plagiocephaly have been a source of controversy. The unilateral lambdoid synostosis that is characterized by flattening of ipsilateral occipital bone is a rare type of craniosynostosis. An 8-month-old infant with unilateral lambdoid synostosis is reported. The patient exhibited right occipital flattening, mastoid bulge, and right frontal bone prominence, with the right auricle displaced anteroinferiorly on gross examination. A Towne projection radiograph of the skull and three-dimensional computed tomography scans revealed that the right lambdoid suture was prematurely fused. Correction of the cranial shape was performed using distraction osteogenesis combined with a barrel stave osteotomy. Significant improvement in the skull was observed 1 year after surgery.

A 30-year-old female complained of sudden onset of severe proptosis, chemosis, diplopia, and bruit. Right carotid angiography showed a high-flow direct carotid-cavernous fistula (CCF) draining into the engorged superior ophthalmic vein, inferior petrosal sinus, and pterygoid plexus. The patient experienced retroperitoneal bleeding from a ruptured right renal artery after undergoing cerebral angiography. We suspected Ehlers-Danlos syndrome (EDS) type IV, which was confirmed by showing cultured fibroblasts failed to secrete procollagen type III. Endovascular surgery cannot be considered the treatment method of choice in view of the fragility of the arteries and veins in patients with EDS type IV. We treated our patient with extracranial internal carotid artery ligation. Currently, there is no ideal treatment for CCF in patients with EDS type IV. Since CCF is rarely life-threatening, the investigative approach and course of treatment must consider the associated vascular fragility.

A Sylvian fissure arachnoid cyst (SAC) is a well-recognized location for an intracranial arachnoid cyst in the pediatric population. For those cysts, which can rupture and be accompanied by a subdural hygroma or hematoma, several treatment modalities have been reported. We report clinical and radiological outcome of fenestration of these cysts by either endoscopy or microsurgery.A retrospective review of the database of operative procedures revealed 24 procedures (20 endoscopic and 4 microsurgical procedures) to fenestrate a SAC at university hospitals in Berlin, Germany and Tokyo, Japan.With the applied technique, a reduction of SAC volume of more than 10% was achieved in 83.3% of all patients. The median volume of SACs (n = 24) was significantly reduced from 83.5 mL (range 21-509 mL) preoperatively to 45.5 mL (range 8.4-261 mL; P0.01) after 3.5 months and to 29.0 mL (range 0-266 mL; P0.01) after 15 months. In children (n = 8) with a ruptured SAC the combined extraaxial volume of a SAC and accompanying hygroma/hematoma was reduced from 166 mL (range 111-291 mL) before surgery to 127 mL (range 87-329 mL) after 2 months and to 77 mL (range 25-140 mL; P0.05) after 11 months. Acute clinical symptoms were generally resolved postoperatively; headaches were resolved or improved in 75%. A significant association of resolution or improvement of headaches and volume reduction was demonstrated.The study demonstrated efficacy in a predominantly endoscopically treated patient cohort with Sylvian fissure arachnoid cysts, as indicated by improvement of clinical symptoms and diminished radiological SAC volume after treatment.

Two glycan isoforms of transferrin (Tf), Tf-1 and Tf-2, were found in cerebrospinal fluid (CSF). Tf-1 concentration in CSF was reduced in idiopathic normal pressure hydrocephalus (iNPH), an elderly dementia caused by abnormal metabolism of CSF, whereas Tf-2 concentration was not. The reduction of Tf-1 concentration was not found in Alzheimer’s disease, indicating that Tf-1 can distinguish iNPH from Alzheimer’s disease. Glycan analysis revealed that Tf-1 has unique biantennary asialoand agalacto-complex N-glycans, which carry bisecting b1,4-GlcNAc and core a1,6-fucose. In contrast, Tf-2 has a2,6-sialylglycan like serum Tf, suggesting that Tf-2 is derived from serum. Tf-1, a glycoform unique to CSF, is speculated to be produced in brain tissue. Immunohistochemistry using anti-Tf antibody on brain tissues revealed that the choroid plexus, which produces CSF, was strongly stained by anti-Tf antibody. These results suggest that Tf-1 is secreted from the choroid plexus and its secretion is reduced by abnormal metabolism of CSF in iNPH.

Purpose Previous studies suggest that compression and stretching of the corticospinal tract (CST) potentially cause treatable gait disturbance in patients with idiopathic normal pressure hydrocephalus (iNPH). Measurement of axon diameter with diffusion MRI has recently been used to investigate microstructural alterations in neurological diseases. In this study, we investigated alterations in the axon diameter and intra-axonal fraction of the CST in iNPH by q-space imaging (QSI) analysis. Methods Nineteen patients with iNPH and 10 age-matched controls were recruited. QSI data were obtained with a 3-T system by using a single-shot echo planar imaging sequence with the diffusion gradient applied parallel to the antero-posterior axis. By using a two-component low-q fit model, the root mean square displacements of intra-axonal space ( = axon diameter) and intra-axonal volume fraction of the CST were calculated at the levels of the internal capsule and body of the lateral ventricle, respectively. Results Wilcoxon's rank-sum test revealed a significant increase in CST intra-axonal volume fraction at the paraventricular level in patients (p

The surgical experience of 120 patients with lumbosacral lipomas is described. 47 of 120 patients were preoperatively found to be neurologically intact, the remaining 73 patients presented with various neurological signs including reflex changes, sensory disturbances, muscle weakness and sphincter problems. Neuro-imagings allowed a classification of lumbosacral lipomas into five types: (1) dorsal type; (2) caudal type; (3) combined type; (4) filar type; and (5) lipomyelomeningocele. Although all 120 patients underwent untethering of the spinal cord, the nerve roots passing through the lipoma itself and the neural tissues protruding externally to the spinal canal, respectively, tended to prevent satisfactory surgical removal of the lipoma in combined type lipomas and lipomyelomeningoceles. During 8.96 years of a mean postoperative follow-up period, there was no significant deterioration in most of the patients and some patients even improved in function. However, two patients with combined type lipomas developed neurological deterioration just after surgery, and five (two dorsal, two caudal and one combined type lipomas) did in the fashion of a late-onset. There are two different patient groups of lumbosacral lipomas; one group (caudal and filar type lipomas, and most of dorsal type lipomas) in whom the surgical anatomy is simple and satisfactory untethering surgery could be done without risk, and another (combined type lipomas and lipomyelomeningocele) in whom surgery would be accompanied with some risk and sometimes complete untethering could not be achieved because of the complicated anatomy of the lesion. Surgical difficulty of the latter group can be correlated with the increased frequency of neurological deterioration occurring just after the operation, but not of delayed one. Concerning prophylactic surgery for asymptomatic patients, the former group of patients are obviously good candidates, but the latter group is not.

Objective. A series of 21 patients with tuberculum sellae meningioma who received surgical treatment is reported. Patients and Methods. All 9 females and 12 males (mean age 49 years) presented visual disturbances of varying degrees in either one or both eyes. Eighteen of the tumours were less than 3 cm in size, and 3 were larger. Tumour resection of uniform surgical technique was performed in all cases. Following a bicoronal scalp incision, bifrontal craniotomy combined with removal of the orbital rim bilaterally was performed. The frontal dura was opened bilaterally, and the most anterior portion of the superior sagittal sinus was transected. Bifrontal retraction and arachnoid dissection along the proximal olfactory tracts brought the tumour into view. Additional dissection of the interhemispheric fissure extended the operative field to the anterior communicating artery. The anterior skull base was drilled out to resect the basal part of the tumour. In all cases, the optic canal and sphenoid sinus, and additionally in some cases the ethmoid sinus were opened. The tumour uniformly extended inferomedially to the optic nerve, and direct visualization of this portion of the tumour was possible with our approach. The opened paranasal sinuses were reconstructed with adipose tissue harvested from the patient's abdomen and the pericranial flap. Results. In all patients, total or almost total resection of the tumour was accomplished. Postoperatively, visual function was improved in 11 patients, was unchanged in 8, and worsened in 2. There were no operative deaths. Cerebrospinal fluid leakage was occurred in two patients but could be conservatively managed. In a mean 3-year follow-up, tumour recurrence was observed in only one patient who presented a malignant histology. Conclusions. We are confident that our surgical approach has great clinical value in surgical resection of tuberculum sellae meningioma. The good accessibility to a tumour extending inferomedially to the optic nerve should, in particular, be stressed.

The authors describe early experience in the use of bioabsorbable fixation devices for cranial reconstruction of paediatric craniosynostosis patients.Three patients, individually respectively presenting sagittal synostosis, metopic synostosis, and clover leaf skull deformity, underwent cranial reconstruction using poly L-lactic acid (PLLA) plates and screws. The patients ranged in age from 2 to 10 months at the time of surgery. The postoperative clinical follow-up ranged from 16 to 18 months. All patients showed satisfactory wound healing without signs of infection or local inflammation. The plates provided satisfactory fixation and were not palpable through the skin after 16 to 18 postoperative months.Our experience demonstrated the efficacy of PLLA bioabsorbable plates and screws for cranial reconstruction in cases of infant craniosynostosis. Prospective studies and longer follow-up of a larger number of patients is desirable for confirmation of these findings.

A girl aged 2 years 10 months suddenly went into a deep coma and demonstrated left hemiplegia. At birth, she had exhibited a left-sided facial port-wine stain typical of Sturge-Weber syndrome (SWS) and involving the V1 and V2 distributions of the trigeminal nerve. Computed tomography showed a right thalamic hemorrhage with acute hydrocephalus. Magnetic resonance imaging with Gd enhancement 8 months before the hemorrhage had shown a patent superior sagittal sinus (SSS) and deep venous system. Magnetic resonance imaging and MR angiography studies 2 months before the hemorrhage had revealed obstruction of the SSS and right internal cerebral vein (ICV). Given that a digital subtraction angiography study obtained after the hemorrhage did not show the SSS or right ICV, the authors assumed that impaired drainage was present in the deep venous system at that stage. The authors speculated that the patient's venous drainage pattern underwent compensatory changes because of the occluded SSS and deep venous collectors, shifting outflow through other cortical venous channels to nonoccluded dural sinuses. Sudden congestion (nearly total to total obstruction) of the ICV may have caused the thalamic hemorrhage in this case, which is the first reported instance of pediatric SWS with intracerebral hemorrhage and no other vascular lesion. Findings suggested that the appearance of major venous sinus occlusion in a child with SWS could be a warning sign of hemorrhage.

We developed a high-throughput Enzyme-linked immunosorbent assay (ELISA) for measuring α2,6-sialylated transferrin (Tf), based on inhibition of anti-Tf antibody binding to α2,6-sialylated Tf by a lectin, Sambucus sieboldiana Agglutinin (SSA). The inhibition was not observed with other glycoforms, such as periodate-treated, sialidase-treated and sialidase/galactosidase-treated Tf, suggesting that the assay was glycoform specific. This finding was applied to an automated latex-agglutination immunoassay, using SSA lectin as an inhibitor (SSA-ALI). The concentration of α2,6-sialylated Tf measured by SSA-ALI in human cerebrospinal fluid was correlated with that of ELISA (r2 = 0.8554), previously developed for measuring α2,6-sialylated Tf.

Myelomeningocele is one of the major congenital malformations involving the central nervous system. It is caused by a disruption of the neural tube closure, which is completed at 3–4 weeks of gestation. Multidisciplinary approach is necessary to treat and support this malformation which is a huge burden to the patient, family, and the society. This is a characteristic anomaly that it is known that taking folic acid during the periconceptional period, it is possible to reduce the risk of having a neural tube defect (NTD). Although folate fortification had dramatically reduced the incidence, it was not possible to diminish the risk. To date, many studies have been conducted focusing on candidate genes related to folate and glucose metabolism. We will describe a brief review of genetic etiology of candidate genes of metabolic pathways of folate and glucose, animal models of NTDs, and finally recent studies of microRNA.

Leucine-rich α2-glycoprotein (LRG) is a protein induced by inflammation. It contains a leucine-rich repeat (LRR) structure and easily binds with other molecules. However, the function of LRG in the brain during aging and neurodegenerative diseases has not been investigated. Here, we measured human LRG (hLRG) concentration in the cerebrospinal fluid (CSF) and observed hLRG expression in post-mortem human cerebral cortex. We then generated transgenic (Tg) mice that over-expressed mouse LRG (mLRG) in the brain to examine the effects of mLRG accumulation. Finally, we examined protein-protein interactions using a protein microarray method to screen proteins with a high affinity for hLRG. The CSF concentration of hLRG increases with age and is significantly higher in patients with Parkinson's disease with dementia (PDD) and progressive supranuclear palsy (PSP) than in healthy elderly people, idiopathic normal pressure hydrocephalus (iNPH) patients, and individuals with Alzheimer's disease (AD). Tg mice exhibited neuronal degeneration and neuronal decline. Accumulation of LRG in the brains of PDD and PSP patients is not a primary etiological factor, but it is thought to be one of the causes of neurodegeneration. It is anticipated that hLRG CSF levels will be a useful biomarker for the early diagnosis of PDD and PSP.

The forebrain cholinergic system is correlated with learning ability and memory function. Here changes in choline acetyltransferase (ChAT) activities, nerve growth factor (NGF) concentrations and expression of IL-1 beta and IL-6 genes were determined in the basal forebrain, parieto-occipital cortex and hippocampus of hydrocephalic and nonhydrocephalic HTX rats. ChAT activity was remarkably decreased in the parieto-occipital cortex of hydrocephalic animals compared to the other two regions. On the other hand, the NGF concentration in the parieto-occipital cortex was markedly increased during the progression of hydrocephalus compared to the basal forebrain and hippocampus. IL-1 beta and IL-6 m-RNA were detectable only in hydrocephalic HTX rats. The disturbance of uptake and transport of NGF in the affected cerebral cortex is partly related to the psychomotor maldevelopment of congenital hydrocephalic children.

Among the various disorders manifesting dementia, gait disturbance, and urinary incontinence in the elderly population, idiopathic normal pressure hydrocephalus (iNPH) is becoming of great importance. After the publication of the first edition of the Guidelines for Management of Idiopathic Normal Pressure Hydrocephalus in 2004 (the English version was published in 2008), clinical awareness of iNPH has risen dramatically, and the number of shunt surgeries has increased rapidly across Japan. Clinical and basic research on iNPH has increased significantly, and more high-level evidence has since been generated. The second edition of the Japanese Guidelines was thus published in July 2011, to provide a series of timely evidence-based recommendations related to iNPH. The revision of the Guidelines has been undertaken by a multidisciplinary expert working group of the Japanese Society of Normal Pressure Hydrocephalus in conjunction with the Japanese Ministry of Health, Labour and Welfare research project on "Studies on the epidemiology, pathophysiology, and treatment of normal pressure hydrocephalus." This English version of the second edition of the Guidelines was made to share these ideas with the international community and to promote international research on iNPH.

An otherwise healthy, developmentally normal 3-week-old male infant presented with complex multisuture craniosynostosis involving the metopic suture and bilateral coronal sutures with frontal prominence and hypotelorism. Frontal craniectomy and bilateral frontoorbital advancement remodeling were performed at the age of 5 months. The postoperative course was uneventful. The child's development was normal up to 8 months after the operation. His father and grandfather had similar specific deformities of the cranium, but no anomaly of the extremities was found, and conversation suggested that their intelligence was normal, excluding the possibility of syndromic craniosynostosis. A DNA analysis revealed large-scale copy number polymorphism of chromosome 4 in the patient and his family, which may include the phenotype of the cranium. Neither FGFR mutation nor absence of a TWIST1 mutation in the sequence from 291 to 1087, which includes DNA binding, Helix1, Loop, and Helix2, was identified. The patient apparently had a rare case of familial nonsyndromic craniosynostosis. The authors plan further genomic analysis of this family and long-term observation of the craniofacial deformity of this patient.

BACKGROUND Craniosynostosis is a relatively rare disease. Recently, several studies have investigated the etiology of craniosynostosis using animal models; however, the etiology remains unknown. In this study, we examined transforming growth factor (TGF) βs immunostaining from coronal sutures in patients with plagiocephaly. MATERIALS The examined materials were obtained from 3 patients who had undergone surgery for plagiocephaly. The sections were obtained from the normal patent side and the abnormal fused side of the coronal suture. The subjects included 2 girls and 1 boy with ages ranging from 1 to 4 years. Osteoblasts and connective tissue were observed with hematoxylin and eosin stain. Immunohistochemistry of the TGF-β isoforms was performed to investigate the difference between the patent and fused sutures. RESULTS No connective tissue was observed in the fused suture. The osteoblasts in the patent suture were activated, whereas the osteoblasts in the fused suture were inactivated. The osteoblasts were positive for TGF-β1, -β2, and -β3. The periosteum tended to be positive for TGF-β2 and negative for TGF-β1 and -β3. There was no distinct difference between the patent and fused sutures in this study. DISCUSSION In this study, all sutures had fused completely, and therefore, we may have missed the period when there are differences in protein manifestation. The modulation of the growth factor profile at the suture site may have a potential therapeutic value.

A 2-year-old girl who had previously been treated for stage IV intra-abdominal neuroblastoma presented with headache and vomiting. Computed tomography (CT) showed hematoma in the right temporal lobe. Two months previously, she had suffered a generalized seizure but brain CT was unremarkable. The hematoma was removed completely without evidence of vascular anomaly or tumor. Four weeks after surgery, magnetic resonance imaging with gadolinium showed a developing mass lesion in the hematoma bed. A second operation for tumor removal confirmed the rare diagnosis of intraparenchymal metastasis. Metastatic neuroblastoma to the central nervous system (CNS) occasionally can cause massive hemorrhage. Therefore, early detection of CNS metastasis can be important. The related factors in this patient with abdominal neuroblastoma included elevated serum lactate dehydrogenase, N-myc gene amplification, and coexisting orbital metastasis, which all occurred within 22 months from initial diagnosis. The median interval from diagnosis of the primary tumor to diagnosis of CNS metastasis in neuroblastoma is 12-22 months, which indicates relatively late metastasis presentation. The initial presentation of this late metastasis is hemorrhage that can have sudden detrimental consequences, so a patient with neuroblastoma must be followed up carefully, particularly if elevated serum lactate dehydrogenase, orbital metastasis, N-myc gene amplification, or clinical symptoms are present, even if brain CT is unremarkable. The understanding that intraparenchymal hematoma can occur prior to detectable CNS metastasis may be important for early detection of this life-threatening condition.

High mobility group box-1 protein (HMGB-1), a protein expressed highly in developing neurons, is involved in the development and differentiation of neurons. At the same time, it functions as a transcriptional regulator of particular genes and as a cytokine: HMGB-1 released from a defective cell has been reported to induce damage to the adjacent cells.With a view to examine the relationship between neuronal damage caused by hydrocephalus and HMGB-1, we analyzed the expression of HMGB-1 in the cerebellum, cerebrum, and hippocampus of 1-day-old congenitally hydrocephalic H-Tx rats.As opposed to nonhydrocephalic H-Tx rats, the hydrocephalic H-Tx rats were observed to show stronger expression of HMGB-1 in the cerebellum, cerebrum, and hippocampus. Consequently, the protein was presumed to influence the development of neurons from an early postnatal stage not only in the cerebral cortex and hippocampus but also in the cerebellum, which is less susceptible to the direct effects of hydrocephalus. We expect that, in the future, regulating the expression or functions of HMGB-1 will lead to the possibility of impeding the progress of neuronal damage caused by hydrocephalus.

Neuroendoscopic surgery is distinct from usual craniotomy as it is performed in water. We have previously reported that the use of artificial cerebrospinal fluid (CSF) as perfusate in third ventriculostomy is more efficacious in minimizing severe host reaction than normal saline or lactated Ringer's solution. In this study, we investigated the effects of different perfusion solutions in human cultured astrocytes. We cultured human astrocytes in growth medium. Then each of them was further cultured for 6 h in artificial CSF, lactated Ringer's solution, or normal saline. Using DNA microarray, RNAs were extracted from each of the cells and were comprehensively analyzed to identify differences in patterns of gene manifestation. Compared to the use of artificial CSF, in cases where lactated Ringer's solution or normal saline was used, there was little difference in the pattern of gene manifestation, but there was an increase in gene manifestation related to apoptosis and inflammatory reaction. For neuroendoscopic surgery, the use of artificial CSF as a perfusate is considered effective in maintaining brain homeostasis compared to the use of normal saline or lactated Ringer's solution.

High mobility group box-1 protein (HMGB-1), a protein expressed highly in developing neurons, is involved in the development and differentiation of neurons. At the same time, it functions as a transcriptional regulator of particular genes and as a cytokine: HMGB-1 released from a defective cell has been reported to induce damage to the adjacent cells.

Neuroendoscopic surgery is distinct from usual craniotomy as it is performed in water. We have previously reported that the use of artificial cerebrospinal fluid (CSF) as perfusate in third ventriculostomy is more efficacious in minimizing severe host reaction than normal saline or lactated Ringer's solution. In this study, we investigated the effects of different perfusion solutions in human cultured astrocytes. We cultured human astrocytes in growth medium. Then each of them was further cultured for 6 h in artificial CSF, lactated Ringer's solution, or normal saline. Using DNA microarray, RNAs were extracted from each of the cells and were comprehensively analyzed to identify differences in patterns of gene manifestation. Compared to the use of artificial CSF, in cases where lactated Ringer's solution or normal saline was used, there was little difference in the pattern of gene manifestation, but there was an increase in gene manifestation related to apoptosis and inflammatory reaction. For neuroendoscopic surgery, the use of artificial CSF as a perfusate is considered effective in maintaining brain homeostasis compared to the use of normal saline or lactated Ringer's solution.

Objectives: We have previously reported that the level of leucine-rich alpha-2-glycoprotein (LRG) expression is specifically increased in cerebrospinal fluid (CSF) of idiopathic normal pressure hydrocephalus (INPH). The objective of this study is to examine the localization of LRG – the cerebral areas where it is expressed.

The authors report their investigation on the current status of neuroendoscopic biopsy for ventricular and paraventricular tumors as well as treatment for associated hydrocephalus in Japan.Patients who had undergone therapeutic neuroendoscopy between 2005 and 2009 were included in this study. The main items examined were age; sex; localization of tumor; pathological diagnosis using biopsy; the presence, treatment, and efficacy of treatment of associated hydrocephalus; perioperative complications; activities of daily living (ADL) before and after therapeutic neuroendoscopy; and the presence of dissemination during the postoperative course.Seven hundred fourteen patients from 123 sites (462 male and 252 female patients, mean age 33.3 years) were enrolled. Localization of the tumor was mainly classified into the lateral ventricle in 91 patients, the third ventricle in 339, the fourth ventricle in 18, the suprasellar region in 75, and other paraventricular areas in 191 patients. The most commonly observed tumors were germ cell tumors in the third ventricle (177 cases [39%]), cystic lesions in the suprasellar region (56 cases [75%]), and astrocytic tumors in the thalamus-basal ganglia (71 cases [38%]). Although 641 (92.8%) of 691 patients could receive neuroendoscopic diagnosis using biopsy, the diagnosis obtained with endoscopic biopsy differed from the final diagnosis based on subsequent craniotomy in 18 patients and clinical course in 3 patients. Of these 21 patients, 7 had astrocytic tumors, 4 had pineal tumors, 6 had germ cell tumors, and 4 had other tumors. The final diagnostic accuracy rate was 89.7%. Associated hydrocephalus was observed in 517 patients (72.4%), of whom 316 and 39 underwent third ventriculostomy and fenestration of the septum, respectively. The response rates were 96.2% and 89.7%, respectively. Third ventriculostomy was required for recurrence of hydrocephalus in 41 patients (13.0%), and the long-term response rate was therefore 83.2% (263 of 316 patients). Perioperative complications other than fever, such as new onset of or progressive hydrocephalus, infection due to CSF leakage, and bleeding in the ventricle or tumor, were found in 81 patients (11.3%). The median Karnofsky Performance Scale score before endoscopic surgery was 80, but it increased to 90 after surgery. The score was thus significantly increased after surgery (p0.0001, Mann-Whitney U-test). Activities of daily living after surgery decreased due to perioperative complications in 15 patients (2.1%). The incidence of new dissemination after endoscopic biopsy was 6.8% and not high compared with routine surgical treatment.The authors concluded that neuroendoscopic diagnosis using biopsy for ventricular and paraventricular tumors is adequately accurate and safe. It was demonstrated that endoscopic procedures play important roles not only in the treatment of hydrocephalus associated with intra- and paraventricular tumors but also in significantly improving ADL. Furthermore, the long-term outcome of endoscopic third ventriculostomy was clearly favorable.

Background In cases of surgery for syndromic craniosynostosis with posterior flattering, it is not possible to achieve sufficient expansion of the skull through fronto-orbital advancement alone. Although it is necessary to expand the occipital region, the surgery is risky and highly invasive. We applied the distraction osteogenesis technique for skull expansion and performed occipital expansion and fronto-orbital advancement in succession. Methods Three patients with syndromic craniosynostosis (2 with Crouzon syndrome, 1 with Pfeiffer syndrome) were treated in Juntendo University Hospital between 2002 and 2007. Using the distraction osteogenesis technique, we performed occipital advancement followed immediately by fronto-orbital advancement for 2 cases of Crouzon syndrome and performed fronto-orbital advancement followed by occipital advancement for a case of Pfeiffer syndrome. Results In all of the cases, we were able to perform bone extension of 25 mm or more and achieve sufficient skull expansion for both of the frontal and occipital regions. Within 1 year after the surgery, in all of the cases, favorable osteogenesis was observed in the distraction gap, and there were no bone defects. Discussion By using the distraction osteogenesis technique, the difficult procedure of occipital advancement can be performed relatively safely. In addition, as active expansion of the cranium is possible after the surgery, sufficient expansion of the cranium can be successfully performed to a degree that cannot be achieved through conventional methods. New bone is formed in the distraction gap, and there are no bone defects. The present method is extremely useful for skull formation in cases of syndromic craniosynostosis with posterior flattering.

We have established high-throughput lectin-antibody ELISAs to measure different glycans on transferrin (Tf) in cerebrospinal fluid (CSF) using lectins and an anti-transferrin antibody (TfAb). Lectin blot and precipitation analysis of CSF revealed that PVL (Psathyrella velutinalectin) bound an unique N-acetylglucosamine-terminated N-glycans on “CSF-type” Tf whereas SSA (Sambucus sieboldianaagglutinin) boundα2,6-N-acetylneuraminic acid-terminated N-glycans on “serum-type” Tf. PVL-TfAb ELISA of 0.5 μL CSF samples detected “CSF-type” Tf but not “serum-type” Tf whereas SSA-TfAb ELISA detected “serum-type” Tf but not “CSF-type” Tf, demonstrating the specificity of the lectin-TfAb ELISAs. In idiopathic normal pressure hydrocephalus (iNPH), a senile dementia associated with ventriculomegaly, amounts of the SSA-reactive Tf were significantly higher than in non-iNPH patients, indicating that Tf glycan analysis by the high-throughput lectin-TfAb ELISAs could become practical diagnostic tools for iNPH. The lectin-antibody ELISAs of CSF proteins might be useful for diagnosis of the other neurological diseases.

Objective Cerebrospinal fluid (CSF) shunting can improve symptoms of elderly patients' idiopathic normal pressure hydrocephalus (iNPH). However, adjunctive means for confirming the diagnosis remain unavailable. We have previously reported the specific increase of leucine-rich alpha-2-glycoprotein (LRG) in iNPH CSF, and the present study investigates its potential clinical applications. Methods We performed CSF tap test (TT) on 90 patients (mean age 73.4 years) and shunting in 52 patients (mean age 73.5 years), evaluating symptom improvement and higher cerebral functions—mini-mental state examination (MMSE) and Frontal Assessment Battery (FAB) before and 12 months after shunting. LRG and tau protein concentrations in TT CSF were simultaneously measured using enzyme-linked immunosorbent assay. We then compared the predictive value of these concentrations with TT results regarding successful shunting outcomes. Results Positive combinations of TT and LRG concentrations of 67 ng/ml or higher, gave 81.6% sensitivity and 78.6% specificity. Therefore we used LRG (67 ng/ml) and tau (200 pg/ml) cut-off values, dividing patients into four groups. In group A (LRG ≥ 67 ng/ml and tau

Multiple-suture synostosis is a rare condition among patients with craniosynostosis. Their cranial shapes demonstrate various types depending on the fused sutures, and it tends to be less consistent in comparison to single-suture synostosis. The details regarding surgical intervention for multiple-suture synostosis have rarely been documented. This report presents 4 patients with nonsyndromic multiple-suture synostosis who were incidentally diagnosed as school-aged children. The age at the time of the surgery ranged from 7 to 11 years. All of the patients demonstrated digital printings on radiographs and an increased intracranial pressure. They underwent cranial expansion using the technique of distraction osteogenesis. In 3 patients, a pi osteotomy was performed; however, the osteotomized bone was not detached from the underlying dura. Four distraction devices were applied. In one patient, an occipital osteotomy was performed, and 2 distraction devices were applied. Distraction was completed in all patients, and the results of surgery were satisfactory. Large bony gaps are generally created by the conventional course of skull expansion. In older children, the bone defects are optimally treated by bone grafts. To harvest bone grafts, it is preferable to split the cranial bone. In this series, however, the calvarial bones were so thin that they could not be split. Therefore, the technique of distraction osteogenesis was used. Cranial distraction is a reliable and less invasive modality. In addition, it can allow for skull expansion without bone grafting in school-aged children.

The authors have developed a minimally invasive lumboperitoneal shunt placement procedure conducted after administration of a local anesthetic. The procedure involves placing a guide wire and a peel-away sheath under fluoroscopic and CT guidance. Between June 2004 and August 2006, 40 patients (21 men and 19 women; mean age 72.5 years [range 33-86 years]) underwent surgery. A Codman Hakim programmable valve system (82-3844, CodmanShurtleff, Inc.) was used for the procedure. The mean operating time was 53 minutes, and 7 patients (17.5%) developed shunt dysfunction complications. These complications comprised an infected shunt valve in 2 patients, postoperative lower-limb pain in 1 patient, and shunt obstruction (caused by debris and hemorrhage) at the ventral and lumbar ends in 2 patients each. This procedure is less invasive than conventional lumboperitoneal shunt insertion and could be performed as an outpatient surgery for treatment of idiopathic normal-pressure hydrocephalus.

Within the existing consensus for the best management of pediatric infratentorial ependymomas (PIE), surgery is the most important stage, where complete removal should be the perfect aim, before complementing it with chemo- or radiotherapy. That, however, remains a challenge even for the most skillful surgeons because of the vicinity of important brainstem and cranial nerve structures involved and is particularly difficult in lateral extensions. The paper analyzes the current trends of PIE treatment with emphasis on resection difficulties created by lateral extensions. Anatomical analysis and clinical application of the cerebellomedullary fissure dissection has created specific approaches, providing safe route to the lateral recess and cerebellopontine area by dividing safely tenia and tonsils and biventer lobes retraction. Bilateral and unilateral approaches have been developed. This approach prevents the damage of transvermian access and the resulting cerebellar mutism in some cases. Indications, technique and benefits of transcerebellomedullary fissure types of approaches are discussed.

Some cases of compensatory hydrocephalus have been reported in which cognitive deficiency progresses despite the absence of progressive ventricular dilation. In this study, the differentially expressed genes in compensated hydrocephalic H-Tx rat cortices were determined. A molecular mechanism that induces neuronal death in the cerebral cortex of compensated hydrocephalus is proposed.The cerebral cortices of 8-week-old H-Tx rats with spontaneously arrested hydrocephalus (hH-Tx) and nonhydrocephalic H-Tx (nH-Tx) control rats were subjected to cDNA microarray analysis followed by canonical pathway analysis.In the hH-Tx rats, many genes in the amyloidal processing pathway showed altered expression, including Akt3 and p38 MAPK. These latter genes are involved in tau protein phosphorylation, and their increased expression in hydrocephalus was confirmed by real-time polymerase chain reaction analysis. Immunohistological and immunoblot analysis revealed elevated phosphorylated tau expression in the cerebral cortex neurons of the hH-Tx rats.The accumulation of phosphorylated tau protein in the cerebral cortex may be one of the mechanisms by which later cognitive dysfunction develops in patients with compensated hydrocephalus. More work needs to be done to determine if the accumulation of phosphorylated tau in the cortex can help predict which patients may decompensate thus requiring more aggressive treatment for compensated hydrocephalus.