Multidrug chemotherapy, whole-brain radiation and cytarabine therapy for primary central nervous system lymphoma in elderly patients with dose modification based on geriatric assessment: study protocol for a phase II, multicentre, non-randomised study.

INTRODUCTION: Multidrug chemoimmunotherapy with rituximab, high-dose methotrexate, procarbazine and vincristine (R-MPV) is a standard therapy for younger patients with primary central nervous system lymphoma (PCNSL); however, prospective data regarding its use in elderly patients are lacking. This multi-institutional, non-randomised, phase II trial will assess the efficacy and safety of R-MPV and high-dose cytarabine (HD-AraC) for geriatric patients with newly diagnosed PCNSL. METHODS AND ANALYSIS: Forty-five elderly patients will be included. If R-MPV does not achieve complete response, the patients will undergo reduced-dose, whole-brain radiotherapy comprising 23.4 Gy/13 fractions, followed by local boost radiotherapy comprising 21.6 Gy/12 fractions. After achieving complete response using R-MPV with or without radiotherapy, the patients will undergo two courses of HD-AraC. All patients will undergo baseline geriatric 8 (G8) assessment before HD-AraC and after three, five and seven R-MPV courses. Patients with screening scores of ≥14 points that decrease to <14 points during subsequent treatment, or those with screening scores <14 points that decrease from the baseline during subsequent treatment are considered unfit for R-MPV/HD-AraC. The primary endpoint is overall survival, and the secondary endpoints are progression-free survival, treatment failure-free survival and frequency of adverse events. The results will guide a later phase III trial and provide information about the utility of a geriatric assessment for defining chemotherapy ineligibility. ETHICS AND DISSEMINATION: This study complies with the latest Declaration of Helsinki. Written informed consent will be obtained. All participants can quit the study without penalty or impact on treatment. The protocol for the study, statistical analysis plan and informed consent form have been approved by the Certified Review Board at Hiroshima University (CRB6180006) (approval number: CRB2018-0011). The study is ongoing within nine tertiary and two secondary hospitals in Japan. The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications. TRIAL REGISTRATION: jRCTs061180093.

Successful treatment of a case of tentorial dural arteriovenous fistula causing subarachnoid hemorrhage with invagination of the brainstem by huge and multiple venous pouches.

BACKGROUND: We present a case of tentorial dural arteriovenous fistula (TDAVF) causing subarachnoid hemorrhage with mass effect of large venous pouches, which was struggling to diagnosis and management due to complex vasculature and severe general condition. CASE DESCRIPTION: A 43-year-old man was transferred to our hospital due to sudden consciousness disturbance. A neurological examination revealed tetraparesis and pupil dilatation with no light reflex. Imaging findings showed a large lesion in the brainstem with subarachnoid and intraventricular hemorrhage. Since there were multiple feeding arteries and large and multiple venous pouches on vascular imaging, we diagnosed the patient with TDAVF. Because of a high-flow arteriovenous shunt and the presence of large venous pouches, it appeared to be very difficult to approach the shunting point by direct surgery. Therefore, we first performed transarterial endovascular treatment with 25% n-butyl-2-cyanoacrylate to shrink the venous pouches and to reduce the pressure of the posterior fossa, followed by direct radical interruption of the shunting point using the craniotomy maneuver. Postoperative vascular imaging revealed disappearance of abnormal feeding arteries, draining veins, and venous pouches. The patient was discharged and transferred to a rehabilitation hospital with a modified Rankin Scale Score of 3. Accurate interpretation of the detailed vasculature preoperatively and an appropriate treatment strategy using endovascular and direct surgical technique are required to achieve a satisfactory outcome for difficult-to-treat dural arteriovenous fistulas. CONCLUSIONS: This combined maneuver with endovascular embolism as complementary pretreatment for radical surgery is useful for a case with high-flow shunting and large venous pouches.

A surgical strategy using a fusion image constructed from 11C-methionine PET, 18F-FDG-PET and MRI for glioma with no or minimum contrast enhancement.

The objective of this study was to investigate the distribution of 11C-methionine (MET) and F-18 fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET) imaging and the hyperintense area in T2 weighted imaging (T2WI) in glioma with no or poor gadolinium enhancement in magnetic resonance imaging (GdMRI). Cases were also analyzed pathologically. We prospectively investigated 16 patients with non- or minimally enhancing (< 10% volume) glioma. All patients underwent MET-PET and FDG-PET scans preoperatively. After delineating the tumor based on MET uptake, integrated 3D images from FDG-PET and MRI (GdMRI, T2WI or FLAIR) were generated and the final resection plane was planned. This resection plane was determined intraoperatively using the navigation-guided fencepost method. The delineation obtained by MET-PET imaging was larger than that with GdMRI in all cases with an enhanced effect. In contrast, the T2WI-abnormal signal area (T2WI+) tended to be larger than the MET uptake area (MET+). Tumor resection was > 95% in the non-eloquent area in 4/5 cases (80%), whereas 10 of 11 cases (90.9%) had partial resection in the eloquent area. In a case including the language area, 92% resection was achieved based on the MET-uptake area, in contrast to T2WI-based partial resection (65%), because the T2WI+/MET- area defined the language area. Pathological findings showed that the T2WI+/MET+ area is glioma, whereas 6 of 9 T2WI+/MET- lesions included normal tissues. Tissue from T2W1+/MET+/FDG+/GdMRI+ lesions gave an accurate diagnosis of grade in six cases. Non- or minimally enhancing gliomas were classified as having a MET uptake area that totally or partially overlapped with the T2WI hyperintense area. Resection planning with or without a metabolically active area in non- or minimally enhancing gliomas may be useful for accurate diagnosis, malignancy grading, and particularly for eloquent area although further study is needed to analyze the T2WI+/MET- area.

Avoidance of ischemic complications after resection of a brain lesion based on intraoperative real-time recognition of the vasculature using laser speckle flow imaging.

OBJECTIVE To avoid ischemic complications, it is important to consider the arteries in resection planning for lesions such as a vascular intraparenchymal tumor and arteriovenous malformation. Here, the clinical application of laser speckle flow imaging (LSFI) as a complementary method for the management of mass lesion-related arteries during surgery was evaluated. METHODS LSFI was performed in 12 patients with mass lesion-related arteries and brain tumor or arteriovenous malformation. The portable LSFI device was centered over the surgical field, and the relative cerebral blood flow (CBF) before and after the temporary interruption of the arteries was measured through continuous recording. CBF fluctuations permitted the classification of 3 kinds of artery-a feeding artery (FA), a "passing through" artery (PA), and a combined FA and PA (FA+PA)-based on decreased relative CBF in the inner resection area and unchanged CBF in the surrounding area (FA), unchanged CBF in the inner area and decreased CBF in the surrounding area (PA), or decreased CBF in both areas (FA+PA). This information allowed the appropriate management of these arteries and avoidance of postoperative ischemic complications. RESULTS Good visualization of CBF in the surgical field and relative CBF measurements in the regions of interest were achieved in real time with excellent spatiotemporal resolution. In 11 patients (92%) and 20 regions of interest, a decline in CBF was observed after temporary interruption of the FA (n = 8), PA (n = 2), and FA+PA (n = 2) types. There was a significant average reduction in CBF of 15.3% ± 29.0%. There were no ischemic complications, and only 1 patient had a postoperative ischemic lesion caused by resection through an artery that could not be viewed by LSFI due to a positional problem. CONCLUSIONS LSFI permits noninvasive and rapid intraoperative real-time recognition of mass lesion-related vasculature. This information can be used to avoid ischemic complications as a procedure complementary to neurophysiological monitoring.

Metastatic cerebellar tumor of papillary thyroid carcinoma mimicking cerebellar hemangioblastoma.

INTRODUCTION: Well-differentiated papillary thyroid carcinoma generally (PTC) have a favorable prognosis. This metastasis is rare in the central nervous system. Brain metastasis has a relatively poor prognosis. We present a rare case of cerebellar metastasis, one that mimics a solid type cerebellar hemangioblastoma and because of which it was very hard to reach accurate preoperative diagnosis. Accurate diagnosis was challenging because of the similar imaging and histopathological findings for these two tumors. CASE DESCRIPTION: A brain lesion was detected by routine medical checkup of the brain with MRI in a 49-year-old woman 2 years after thyroidectomy for well-differentiated PTC. Gadolinium-enhanced MRI showed a homogeneous prominently enhanced lesion with surrounding enhanced dilated vessels in the left cerebellar hemisphere. Digital subtraction angiography showed a strongly stained lesion fed by the peripheral branch of the left posterior inferior cerebellar artery with drainage into the inferior vermian vein, revealing arteriovenous shunting. The most like likely preoperative diagnosis was felt to be that of a solid cerebellar hemangioblastoma. Gross total resection of the tumor was achieved by bilateral suboccipital craniotomy, and intraoperative pathological analysis suggested hemangioblastoma. Histopathological findings showed proliferation of vacuolated sheeted tumor cells with clear and eosinophilic cytoplasm and numerous thin-walled microvessels, consistent with hemangioblastoma. However, the final diagnosis was brain metastasis of the follicular variant of PTC due to a partial thyroid follicle-like pattern including eosinophilic fluid pathologically and positive TTF-1 immunostaining. DISCUSSION AND EVALUATION: Since presented rare case of cerebellar metastasis of PTC was very similar to solid type cerebellar hemangioblastoma on imaging and histopathological findings, accurate diagnosis was challenging. Moreover, it is extremely rare for a cerebellar metastasis to occur as an initial distant metastasis of PTC, and hemangioblastoma is the most common primary cerebellar neoplasm in adults. This epidemiological data was also one of the reason of difficulty to reach preoperative accurate diagnosis. CONCLUSIONS: To the best of our knowledge, there are no other reports of challenging diagnosis case of these two tumors in the literature. Brain metastasis of a well-differentiated PTC could be a relatively poor prognostic factor, and accurate diagnosis and suitable surgical therapy or radiotherapy are needed.

Strategies and Pitfalls of Motor-Evoked Potential Monitoring during Supratentorial Aneurysm Surgery.

BACKGROUND: The aims of this study were to reveal the strategies and pitfalls of motor-evoked potential (MEP) monitoring methods during supratentorial aneurysm surgery, and to discuss the drawbacks and advantages of each method by reviewing our experiences. METHODS: Intraoperative MEP monitoring was performed in 250 patients. Results from 4 monitoring techniques using combinations of 2 stimulation sites and 2 recording sites were analyzed retrospectively. RESULTS: MEP was recorded successfully in 243 patients (97.2%). Direct cortical stimulation (DCS)-spinal recorded MEP (sMEP) was used in 134 patients, DCS-muscle recorded MEP (mMEP) in 97, transcranial electrical stimulation (TES)-mMEP in 11 and TES-sMEP in 1. TES-mMEP during closure of the skull was used in 21 patients. DCS-mMEP was able to detect waveforms from upper and/or lower limb muscles. Alternatively, DCS-sMEP (direct [D]-wave) could accurately estimate amplitude changes. A novel "early warning sign" indicating ischemia was found in 21 patients, which started with a transiently increased amplitude of D-wave and then decreased after proximal interruption of major arteries. False-negative findings in MEP monitoring in 2 patients were caused by a blood insufficiency in the lenticulostriate artery and by a TES-sMEP recording, respectively. CONCLUSIONS: The results of this study suggest that to perform accurate MEP monitoring, DCS-mMEP or DCS-sMEP recording should be used as the situation demands, with combined use of TES-mMEP recording during closure of the skull. DCS-sMEP is recommended for accurate analysis of waveforms. We also propose a novel "early warning sign" of blood insufficiency in the D-wave.

Epithelioid/rhabdoid glioblastoma: a highly aggressive subtype of glioblastoma.

Epithelioid glioblastoma (GBM) and rhabdoid GBM are rare variants that are morphologically similar, but there is no consensus on the characteristics of each disease. These tumors have aggressive features of early recurrence and leptomeningeal dissemination and tend to develop in younger patients compared to typical GBM. The prognosis is normally worse than typical GBM, even with intensive chemoradiotherapy after surgical resection. Thus, accurate diagnosis and effective therapy for epithelioid/rhabdoid GBM are required. Four consecutive patients aged 16-48 years were diagnosed with epithelioid/rhabdoid GBM by pathological and immunohistochemical analysis at Yamaguchi University Hospital from 2006 to 2012. Two of these patients had relatively long-term survival (19 and 23 months after diagnosis). Two cases had a BRAF V600E mutation, whereas no ATRX mutation was present in any cases. All patients suffered leptomeningeal and/or spinal dissemination that worsened their prognosis. These results illustrate the need for a new therapeutic approach, such as molecular targeted drug therapy like BRAF inhibition, in addition to standard chemoradiotherapy for typical GBM.

MRI findings and pathological features in early-stage glioblastoma.

Magnetic resonance imaging (MRI) is an important diagnostic tool for glioblastoma, with almost all cases showing characteristic imaging findings such as a heterogeneous-ring enhanced pattern associated with significant edema. However, MRI findings for early-stage glioblastoma are less clear. In this study, a retrospective review of MRI findings in five patients showed slight T2WI signal changes on initial scans that developed into typical imaging findings of a ring-like or heterogeneously enhanced bulky tumor within 6 months. The diagnoses based on initial MRI were low grade glioma in three cases, venous thrombosis in one case, and uncertain in one case. Four cases were treated with gross total resection, while one case underwent biopsy. Immunohistochemical examinations showed that two cases were p53-positive, and that all cases were IDH1 R132H-negative and had overexpression of EGFR. FISH analysis showed that all cases were 1p19q LOH-negative. De novo glioblastoma was the final diagnosis in all cases. Our results show that initial MRI findings in early-stage glioblastoma of small ill-defined T2WI hyperintense lesions with poor contrast develop to bulky mass lesions with typical findings for glioblastoma in as short a period as 2.5 months. The early MRI findings are difficult to distinguish from those for non-neoplastic conditions, including ischemic, degenerative or demyelinating processes. Thus, there is a need for proactive diagnosis of glioblastoma using short-interval MRI scans over several weeks, other imaging modalities, and biopsy or resection, particularly given the extremely poor prognosis of this disease.

Cognitive dysfunction might be improved in association with recovered neuronal viability after intracranial meningioma resection.

Intracranial meningiomas are the most common types of neoplasms that cause mental disorders. Although higher brain function can be restored and even improved in some patients after tumor resection, the mechanisms remain unclear. We investigated changes in the brains of patients after resection of an intracranial meningioma using (123)I-Iomazenil (IMZ)-single photon emission computed tomography (SPECT). Ten patients underwent IMZ-SPECT within 4 weeks before and 3 months after intracranial meningioma resection. Changes in IMZ accumulation in brain parenchyma were assessed as ratios of counts in the lesion-to-contralateral hemisphere (L/C ratios). Mean Mini-Mental State Examination scores before and after resection of 19.9±11.4 vs. 26.5±3.8, respectively (p=0.03) indicated that the cognitive function of these patients was significantly improved after tumor resection. The average L/C ratios calculated from image counts of IMZ were 0.92±0.05 and 0.98±0.02 before and after surgery, respectively. The L/C ratio of IMZ accumulation was significantly decreased after tumor resection (p=0.0003). In contrast, regional cerebral blood flow calculated from (123)I-Iodoamphetamine-SPECT images did not significantly differ after tumor resection. The recovered binding potential of IMZ in brain parenchyma surrounding the tumor bulk after resection indicates that the viability of central benzodiazepine receptors was reversibly depressed and recoverable after release from compression by the tumor. The recovered neuronal viability revealed by IMZ-SPECT might be responsible for the improved cognitive function after intracranial meningioma resection.

Pathological features of highly invasive glioma stem cells in a mouse xenograft model.

Glioma stem cells (GSCs) may be a source of tumor progression and recurrence after multimodal therapy, because of their high invasive potential. The purpose of this study was to compare the invasive and migratory properties of GSCs and non-GSCs and examine the distribution of these cells in a mouse xenograft model. Three GSC lines, G144, Y02, and Y10, cultured from human glioblastoma, were used in the study. Matrigel-invasion assays of infiltration and time-lapse studies of migration were performed for comparison of the GSCs with the corresponding differentiated non-GSC lines. Cells were also transplanted into mouse brain and the different distribution of GSCs and non-GSCs was examined in the tumor xenograft model. All 3 GSC lines had greater invasion and migration ability than the corresponding non-GSCs. In vivo, GSCs infiltrated more widely than non-GSCs and reached the contralateral hemisphere via the corpus callosum in the early stage of tumorigenesis. GSCs also primarily penetrated the subventricular zone (SVZ). GSCs have high invasive potential and tend to be present in the outer tumor bulk and infiltrate the contralateral hemisphere via the corpus callosum, in addition to penetrating the SVZ.

Fatty acid binding protein 7 as a marker of glioma stem cells.

Glioblastomas are the most aggressive brain tumors. Glioblastoma stem cells (GSCs) are thought to be responsible for the recurrence, chemoresistance, and poor prognosis of glioblastoma. Fatty acid binding protein 7 (FABP7), which is a cellular chaperone for a variety of omega-3 fatty acids, is a known marker for neural stem cells. In this study, using a newly developed anti-FABP7 antibody and patient-derived GSC lines, we evaluated the expression of FABP7 in GSCs. Using immunocytochemistry, Western blotting, and qPCR analyses, FABP7 was found to be highly enriched in GSCs and its localization was found in cytosol and nuclei. FABP7 expression was significantly downregulated in differentiated GSCs induced by the addition of serum. In the glioma surgical specimens, FABP7 was highly expressed in the majority of glioblastoma. Double immunostaining for FABP7 and Sox2 showed that FABP7(+) Sox2(+) tumor cells were significantly increased in glioblastoma (grade IV) compared with diffuse astrocytoma (grade II) and anaplastic astrocytoma (grade III). Our data introduces FABP7 as a marker for GSCs and further highlights its possible significance for glioma diagnosis and treatment.

Characteristics of intraoperative abnormal hemodynamics during resection of an intra-fourth ventricular tumor located on the dorsal medulla oblongata.

Abnormal hemodynamics during extirpation of a para-medulla oblongata (MO) tumor is common and may be associated with direct vagal stimulation of the medullary circuit. However, resection of tumors on the dorsal MO may also induce hemodynamic instability without direct vagal stimulus. The objective of this study was to examine the characteristics of hemodynamic instability unrelated to vagal stimulus during dissection of an intra-fourth ventricular tumor with attachment to the dorsal MO. A retrospective analysis was performed in 13 patients. Abnormal hemodynamics were defined as a > 20% change from the means of the intraoperative mean arterial pressure (MAP) and heart rate (HR). Relationships of intraoperative hemodynamics were evaluated with various parameters, including the volume of the MO. Six patients (46.2%) had intraoperative hypertension during separation of the tumor bulk from the dorsal MO. The maximum MAP and HR in these patients were significantly greater than those in patients with normal hemodynamics (116.0 ± 18.0 mmHg versus 85.6 ± 6.5 mmHg; 124.3 ± 22.8 bpm versus 90.5 ± 14.7 bpm). All six cases with abnormal hemodynamics showed hemodynamic fluctuation during separation of the tumor bulk from the dorsal MO. The preoperative volume of the MO in these patients was 1.11 cc less than that in patients with normal hemodynamics, but the volume after tumor resection was similar in the two groups (5.23 cc and 5.12 cc). This suggests that the MO was compressed by the conglutinate tumor bulk, with resultant fluctuation of hemodynamics. Recognition of and preparation for this phenomenon are important for surgery on a tumor located on the dorsal MO.

Cortical region-specific engraftment of embryonic stem cell-derived neural progenitor cells restores axonal sprouting to a subcortical target and achieves motor functional recovery in a mouse model of neonatal hypoxic-ischemic brain injury.

Hypoxic-ischemic encephalopathy (HIE) at birth could cause cerebral palsy (CP), mental retardation, and epilepsy, which last throughout the individual's lifetime. However, few restorative treatments for ischemic tissue are currently available. Cell replacement therapy offers the potential to rescue brain damage caused by HI and to restore motor function. In the present study, we evaluated the ability of embryonic stem cell-derived neural progenitor cells (ES-NPCs) to become cortical deep layer neurons, to restore the neural network, and to repair brain damage in an HIE mouse model. ES cells stably expressing the reporter gene GFP are induced to a neural precursor state by stromal cell co-culture. Forty-hours after the induction of HIE, animals were grafted with ES-NPCs targeting the deep layer of the motor cortex in the ischemic brain. Motor function was evaluated 3 weeks after transplantation. Immunohistochemistry and neuroanatomical tracing with GFP were used to analyze neuronal differentiation and axonal sprouting. ES-NPCs could differentiate to cortical neurons with pyramidal morphology and expressed the deep layer-specific marker, Ctip2. The graft showed good survival and an appropriate innervation pattern via axonal sprouting from engrafted cells in the ischemic brain. The motor functions of the transplanted HIE mice also improved significantly compared to the sham-transplanted group. These findings suggest that cortical region specific engraftment of preconditioned cortical precursor cells could support motor functional recovery in the HIE model. It is not clear whether this is a direct effect of the engrafted cells or due to neurotrophic factors produced by these cells. These results suggest that cortical region-specific NPC engraftment is a promising therapeutic approach for brain repair.

The effect of hypothermia therapy on cortical laminar disruption following ischemic injury in neonatal mice.

Hypothermia has been proposed as a treatment for reducing neuronal damage in the brain induced by hypoxic ischemia. In the developing brain, hypoxic ischemia-induced injury may give rise to cerebral palsy (CP). However, it is unknown whether hypothermia might affect the development of CP. The purpose of this study was to investigate whether hypothermia would have a protective effect on the brains of immature, 3-day old (P3) mice after a challenge of cerebral ischemia. Cerebral ischemia was induced in P3 mice with a right common carotid artery ligation followed by hypoxia (6% O2, 37°C) for 30 min. Immediately after hypoxic ischemia, mice were exposed to hypothermia (32°C) or normothermia (37°C) for 24 h. At 4 weeks of age, mouse motor development was tested in a behavioral test. Mice were sacrificed at P4, P7, and 5 weeks to examine brain morphology. The laminar structure of the cortex was examined with immunohistochemistry (Cux1/Ctip2); the number of neurons was counted; and the expression of myelin basic protein (MBP) was determined. The hypothermia treatment was associated with improved neurological outcomes in the behavioral test. In the normothermia group, histological analyses indicated reduced numbers of neurons, reduced cortical laminar thickness in the deep, ischemic cortical layers, and significant reduction in MBP expression in the ischemic cortex compared to the contralateral cortex. In the hypothermia group, no reductions were noted in deep cortical layer thickness and in MBP expression in the ischemic cortex compared to the contralateral cortex. At 24 h after the hypothermia treatment prevented the neuronal cell death that had predominantly occurred in the ischemic cortical deep layers with normothermia treatment. Our findings may provide a preclinical basis for testing hypothermal therapies in patients with CP induced by hypoxic ischemia in the preterm period.

Yolk sac tumor of the bilateral basal ganglia in a patient with Down syndrome.

We report a case of intracranial yolk sac tumor in a 17-year-old girl with Down syndrome who presented with left slowly progressive hemiparesis. Initial magnetic resonance imaging (MRI) showed a small area of ill-defined abnormal signal intensity without a mass in the bilateral basal ganglia. These findings progressed very slowly for 2 years, but then the lesion rapidly progressed to a huge mass on MRI 4 months after the previous scan. The patient subsequently underwent a blood examination and endoscopic biopsy, and was finally diagnosed with yolk sac tumor. Standard platinum-based chemotherapy and radiotherapy were performed as soon as practicable. The frequency of solid cancer in patients with Down syndrome is generally lower than that in individuals without this disorder. Brain tumor is also rare in Down syndrome, but half of these cases are germ cell tumors. Moreover, slowly progressive non-tumor-like lesions in the basal ganglia may also be germ cell tumors. Therefore, MRI signal abnormalities in the basal ganglia in patients with Down syndrome require careful and frequent follow-up scans based on the possibility of a germ cell tumor that may exhibit rapid growth.

[Insular psammomatous meningioma presenting intractable complex partial seizures].

We describe a 30-year-old female with intractable symptomatic epilepsy caused by an insular calcified mass, which was histologically proved as psammomatous meningioma. Seizures were described as consciousness impairment, motionless stare and automatism. After total removal of the tumor with a neuronavigation system and motor evoked potential (MEP) monitoring, seizures completely disappeared without neurological deficit. We emphasize that insular meningioma presents complex partial seizures which mimic medial temporal lobe epilepsy and seizures are controlled by total resection of the tumor.

Intra-operative monitoring of lower extremity motor-evoked potentials by direct cortical stimulation.

OBJECTIVE: Motor-evoked potentials (MEPs) are commonly recorded from upper-extremity muscles, whereas lower-extremity MEP (LE-MEP) monitoring has not been adequately established. The goal of the study was to develop a MEP monitoring method using direct cortical stimulation (DCS) for predicting motor deficits of lower extremities. METHODS: Intra-operative LE-MEP monitoring was performed in 22 patients. After craniotomy, a subdural electrode was placed on the cortex so that the optimal contact was positioned 2 cm lateral from the midline on the motor cortex. The electrodes for stimulation consisted of a cathode at Fpz and an anode at the optimal contact site on the motor cortex. After stimulation was performed with short trains of five stimuli, LE-MEPs were recorded from the lower-limb muscles. RESULTS: LE-MEPs were consistently recorded in all patients. Disappearance or amplitude reduction of MEP waveforms was observed in five patients, but the MEP waveforms had recovered and remained at the control level by dural closure, and no permanent motor deficit was observed in any patient. CONCLUSIONS: We accomplished LE-MEP recording during supratentorial surgery using monopolar DCS with a subdural electrode placed on the convex side of the motor cortex. SIGNIFICANCE: A useful method of intra-operative LE-MEP recording was described.

Intracranial yolk sac tumor in a patient with Down syndrome.

The authors report a rare case of intracranial yolk sac tumor in a 13-year-old boy with Down syndrome who presented with left hemiparesis. Admission MR imaging revealed a tumor in the right basal ganglia. Serum α-fetoprotein was markedly elevated. Yolk sac tumor was diagnosed radiologically and serologically. The standard therapy for intracranial yolk sac tumor is platinum-based chemotherapy with concomitant radiotherapy. However, the authors used reduced-dose chemotherapy and asynchronized radiotherapy because of the well-known low tolerance of patients with Down syndrome to chemotherapy. This treatment was successful with no complications. Blood cancers are frequently associated with Down syndrome, whereas solid tumors occur less frequently in these patients, and the risk of chemoradiotherapy is unclear. The results indicate that dose-reduction therapy can be effective for treatment of a brain tumor in a patient with Down syndrome.