Akira Gomi

Sensitivity and specificity in transcranial motor-evoked potential monitoring during neurosurgical operations.

Background: Intraoperative transcranial motor-evoked potential (TCMEP) monitoring is widely performed during neurosurgical operations. Sensitivity and specificity in TCMEP during neurosurgical operations were examined according to the type of operation. Methods: TCMEP monitoring was performed during 283 neurosurgical operations for patients without preoperative motor palsy, including 121 spinal operations, 84 cerebral aneurysmal operations, and 31 brain tumor operations. Transcranial stimulation at 100–600 V was applied by screw electrodes placed in the scalp and electromyographic responses were recorded with surface electrodes placed on the affected muscles. To exclude the effects of muscle relaxants on TCMEP, compound muscle action potential (CMAP) by supramaximal stimulation of the peripheral nerve immediately after transcranial stimulation was used for compensation of TCMEP. Results: In spinal operations, with an 80% reduction in amplitude as the threshold for motor palsy, the sensitivity and specificity with CMAP compensation were 100% and 96.4%, respectively. In aneurysmal operations, with a 70% reduction in amplitude as the threshold for motor palsy, the sensitivity and specificity with CMAP compensation were 100% and 94.8%, respectively. Compensation by CMAP was especially useful in aneurysmal operations. In all neurosurgical operations, with a 70% reduction in amplitude as the threshold for motor palsy, the sensitivity and specificity with CMAP compensation were 95.0% and 90.9%, respectively. Conclusions: Intraoperative TCMEP monitoring is a significantly reliable method for preventing postoperative motor palsy in both cranial and spinal surgery. A 70% reduction in the compensated amplitude is considered to be a suitable alarm point in all neurological operations.

An R132H Mutation in Isocitrate Dehydrogenase 1 Enhances p21 Expression and Inhibits Phosphorylation of Retinoblastoma Protein in Glioma Cells

Cytosolic isocitrate dehydrogenase 1 (IDH1) with an R132H mutation in brain tumors loses its enzymatic activity for catalyzing isocitrate to α-ketoglutarate (α-KG) and acquires new activity whereby it converts α-KG to 2-hydroxyglutarate. The IDH1 mutation induces down-regulation of tricarboxylic acid cycle intermediates and up-regulation of lipid metabolism. Sterol regulatory element-binding proteins (SREBPs) regulate not only the synthesis of cholesterol and fatty acids but also acyclin-dependent kinase inhibitor p21 that halts the cell cycle at G1. Here we show that SREBPs were up-regulated in U87 human glioblastoma cells transfected with an IDH1R132H-expression plasmid. Small interfering ribonucleic acid (siRNA) for SREBP1 specifically decreased p21 messenger RNA (mRNA) levels independent of the p53 pathway. In IDH1R132H-expressing U87 cells, phosphorylation of Retinoblastoma (Rb) protein also decreased. We propose that metabolic changes induced by the IDH1 mutation enhance p21 expression via SREBP1 and inhibit phosphorylation of Rb, which slows progressionof the cell cycle and may be associated with non-aggressive features of gliomas with an IDH1 mutation.

Distraction Osteogenesis Update: Introduction of Multidirectional Cranial Distraction Osteogenesis

In this review, we discuss in detail our current procedure for treating craniosynostosis using multidirectional cranial distraction osteogenesis (MCDO). The MCDO method allows all phenotypes of skull deformity to be reshaped by distraction osteogenesis, except in patients who are 5 months of age or younger and patients with posterior cranial vault problems. We report the results of clinical data of 36 children with craniosynostosis who underwent MCDO between 2005 and 2014 in our institute. This method has the following benefits, such as a high flexibility of reshaping, shorter treatment period and less invasive secondary intervention. We also discuss the other distraction osteogenesis techniques that are used to treat craniosynostosis and compare them with MCDO. The preferred procedure for correction of craniosynostosis may depend on the patients age, the extent of deformity, and the extent of correction achievable by surgery. We can arrange the combinations of various methods according to the advantage and disadvantage of each technique.

Multidirectional Cranial Distraction Osteogenesis with Simplified Modifications for Treating Sagittal Synostosis

Background: Multidirectional cranial distraction osteogenesis (MCDO) is a procedure of ours developed earlier for treating craniosynostosis. However, the numerous bone flaps led to prolonged operative time and occasional bone detachment from dura. We have since simplified the osteotomy design. In treating sagittal synostosis, required bone flaps have been reduced to 11 (from ~20). Methods: In a 2-year period (2014–2015), 5 boys with sagittal synostosis underwent MCDO using our simplified and fixed-form osteotomy. Mean age at surgery was 9.4 months (range, 8–11 months). Pre- and postoperative cranial morphology was assessed by cephalic index and by mid-sagittal vector analysis. Results: Improved cranial shape was confirmed by 3-dimensional CT scans and by mid-sagittal vector index. Mean preoperative cephalic index (68.7) progressively increased to means of 78.5 immediately after distraction device removal, 75.2 at postoperative month 6, and 75.1 at 1 year postoperatively. There were no major complications, although transient cerebrospinal fluid leakage and loosening of anchor pins occurred in 1 patient. Conclusions: Simplified MCDO has a number of advantages over conventional distraction procedures such as discretionary reshaping/expansion of cranium and predictable osteogenesis and is a valid treatment option for patients with sagittal synostosis.

Embolization for Refractory Subacute Subdural Hematoma in a Child with Severe Hemophilia Type A

Hemophilia is an X-linked hemorrhagic disease due to coagulation factor VIII or IX deficiency with approximately 5–10% incidence of central nervous system bleeding. We present an intriguing case of a refractory subacute subdural hematoma (SDH) controlled with endovascular embolization in a hemophilic patient. A 5-year-old severe hemophilic A boy presented with a life threatening left parietal subcortical hemorrhage, for which he underwent craniotomy and evacuation of the hematoma. Recurrent hemorrhage necessitated a repeat craniotomy. This was followed by three episodes of SDH development at the craniotomy site that were treated surgically, and finally controlled with embolization in the subacute period. This case presents a novel option for treating a refractory SDH in patients with coagulation disorders.

Birth injury after cesarean section at 24 weeks of gestation: a large scalp laceration

Cesarean section (CS), compared with vaginal delivery, has a lower incidence of neonatal birth injury. Previously, we reported a femur fracture after term CS in this journal [1]. In a pregnant woman with chronic abruption oligohydramnios sequence, CS was performed at 24 weeks under general anesthesia due to continued oligohydramnios and elevated C-reactive protein level (4.5 mg/dL). The obstetrician had 20 years of experience. Being in head presentation, lower segment transverse incision was made with surgical knife: the incision was stopped before entering the uterine cavity to avoid direct injury to the fetal scalp. The uterine cavity was entered with a finger and the incision was extended laterally by both index fingers (Fig. 1a). Then the doctor recognized something ‘‘white’’ just beneath the fingers. In retrospect, it was the skull bone: the scalp skin may have been lacerated by the fingers, sliding off from the underlying skull bone (Fig. 1b). This was well reconstructed. Bleeding from the laceration was slight, requiring no blood transfusion. Extra-or-subdural hematoma or intra-ventricular hemorrhage was absent. The infant, weighing 544 g with Apgar score 4/7 (1/5 min), died the next day due to prematurity. Autopsy was not performed. The scalp laceration itself was not considered to have influenced the outcome. Another similar experience: a scalp laceration in an infant after 23 weeks’ CS. Oligohydramnios due to premature rupture of the membranes and signs of intrauterine infection required CS. The fetal head was deeply engaged and thus the hand was put deeply into the uterine cavity, pulling out the fetal head with the fingers. In retrospect, the scalp, being pushed and possibly scratched by the fingers, was lacerated at the parietal area. The infant died next day due to prematurity. The laceration was not considered to have influenced the outcome. There is a close similarity between the two patients: preterm CS, oligohydramnios, and intrauterine infections. A previous report [2] also showed that ruptured membranes and thus oligohydramnios were the risk factors of fetal scalp laceration, in which, however, infants suffering laceration were almost term infants (average of 38.67 weeks), with the earliest and the lightest being 29 weeks and 825 g of birth weight, respectively. Its context was that obstetricians should avoid direct injury to the fetal scalp with the knife or scalpel [2]. The present significance is different: pushing or scratching the scalp skin with fingers was the considered culprit. Skin and the underlying skull bone, especially at the parietal area, are more loosely connected than skin and other body parts such as the extremities or the trunk. This is more exaggerated in preterm infants. Intra-uterine infection, weakening the skin, may also have caused scalp laceration. Oligohydramnios, pushing the fetal head tightly to the uterine wall, obliged the obstetrician to put fingers into the narrow space between the fetal head and the uterine wall, which may also have caused this injury. The CS procedure was performed gently, considering the infant’s prematurity; however, a much gentler maneuver S. Matsubara (&) R. Usui Department of Obstetrics and Gynecology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan e-mail: matsushi@jichi.ac.jp

A case of unclassified, radiosensitive, malignant neuroepithelial tumor in the temporal lobe of a child

A case of unclassified, pediatric cerebral neuroepithelial tumor in a 10-year-old girl that showed remarkable radiosensitivity is reported. MRI revealed a brain tumor of mixed intensity with heterogeneous enhancement in the medial temporal lobe, extending to the basal ganglia. The tumor was partially removed. On pathology, the main part of the tumor showed immature features: the tumor cells had a chromatin-rich large nucleus and less cytoplasm, and mitoses and fragmentation of the nuclei were frequent. On immunohistochemistry, the tumor cells were negative for glial fibrillary acidic protein (GFAP) and synaptophysin and positive for Olig2. The maximum MIB-1 index was 70%. The part invading into the surrounding brain showed similarities in form to a highly anaplastic astrocytoma. The infiltrating tumor cells were positive for GFAP and less positive for Olig2. After 40 Gy radiation, the residual tumor was markedly reduced. Neuroepithelial tumors rarely show such high radiosensitivity, and the reason for the radiosensitivity in the present case may have been the immaturity of the tumor cells.