Sei Haga

Involvement of the Multidrug Resistance Protein 3 in Drug Sensitivity and Its Expression in Human Glioma

The multidrug resistance protein (MRP) family belongs to the ATP‐binding cassette superfamily (ABC) of transporters, which are involved in ATP‐dependent transport of hydrophobic compounds. One of the MRP family, MRP1, is partially associated with the multidrug resistance phe‐notype in brain tumors. In this study, we asked whether another MRP family gene, MRP3, could affect drug sensitivity to anticancer agents in human glioma cell lines and clinical glioma specimens. We first produced two antisense transfectants by introduction of antisense MRP3 cDNA into the glioma cell line NHG2, which endogenously expresses MRP3. The two MRP3 antisense transfectants showed 2‐ to 5‐fold increases in drug sensitivity to etoposide and cisplatin compared with NHG2 cells, but their sensitivity to vincristine or nitrosourea was not changed. Two MRP3 cDNA sense transfectants of pig kidney cell lines showed 4‐ to 6‐fold drug resistance to etoposide, but only 1.4‐ to 1.5‐fold to cisplatin. We next compared the mRNA levels of four ABC transporters, multi‐drug resistance 1 (MDR1), MRP1, MRP2 and MRP3 in clinical samples, including 34 patients with gliomas, by quantitative RT‐PCR analysis. In some of the clinical samples, increased expression of MRP1 and MRP3 was apparent in malignant gliomas. In situ hybridization revealed that glioma cells were stained with MRP3 probe. MRP3 may modulate drug sensitivity to certain anticancer agents in human gliomas.

Arterial Spin Labeling Perfusion Magnetic Resonance Image with Dual Postlabeling Delay: A Correlative Study with Acetazolamide Loading 123I-Iodoamphetamine Single-Photon Emission Computed Tomography

BACKGROUND Perfusion magnetic resonance image with arterial spin labeling (ASL) provides a completely noninvasive measurement of cerebral blood flow (CBF). However, arterial transient times can have a marked effect on the ASL signal. For example, a single postlabeling delay (PLD) of 1.5 seconds underestimates the slowly streaming collateral pathways that maintain the cerebrovascular reserve (CVR). To overcome this limitation, we developed a dual PLD method. SUBJECTS AND METHODS A dual PLD method of 1.5  and 2.5 seconds was compared with (123)I-iodoamphetamine single-photon emission computed tomography with acetazolamide loading to assess CVR in 10 patients with steno-occlusive cerebrovascular disease. RESULTS In 5 cases (Group A), dual PLD-ASL demonstrated low CBF with 1.5-second PLD in the target area, whereas CBF was improved with 2.5-second PLD. In the other 5 cases (Group B), dual PLD-ASL depicted low CBF with 1.5-second PLD, and no improvement in CBF with 2.5-second PLD in the target area was observed. On single-photon emission computed tomography, CVR was maintained in Group A but decreased in Group B. CONCLUSIONS Although dual PLD methods may not be a completely alternative test for (123)I-iodoamphetamine single-photon emission computed tomography with acetazolamide loading, it is a feasible, simple, noninvasive, and repeatable technique for assessing CVR, even when employed in a routine clinical setting.

Multicentric pleomorphic xanthoastrocytomas: Case report

We report the case of a 22-year-old woman who developed multicentric pleomorphic xanthoastrocytomas (PXAs) in the cerebral hemisphere. She underwent a first operation for a PXA in the right parietal lobe at the age of 7 years and a second operation at the age of 15 years in the right frontal lobe, remote from the previous tumor site. At age 22 years, she was found to have a tumor, which was a newly formed PXA, in the left occipital lobe. There was no recurrent tumor in the right frontal lobe. Clinical and pathological aspects of multicentric PXAs are reviewed and discussed.

Arterial Spin-Labeling Magnetic Resonance Perfusion Imaging with Dual Postlabeling Delay in Internal Carotid Artery Steno-occlusion: Validation with Digital Subtraction Angiography

BACKGROUND Arterial spin-labeling magnetic resonance perfusion imaging (ASL-MRI) allows noninvasive measurement of cerebral blood flow (CBF) but depends on the arterial transit time (ATT). With the commonly used single postlabeling delay (PLD) of 1.5 seconds, slow flow through collateral vessels may be underestimated. We used both 1.5 and 2.5 seconds to overcome this problem. We validated these PLD settings by measuring the ATT and identifying the angiographic circulation using digital subtraction angiography (DSA). METHODS We retrospectively selected 5 patients with unilateral occlusion or stenosis of the internal carotid artery (ICA) in whom ASL-MRI showed low CBF with 1.5-second PLD in the target area and improved CBF with 2.5-second PLD. We then compared the ASL-MRI findings visually with DSA findings at 1.5 and 2.5 seconds after injection of the contrast. When arterial transit artifacts (ATAs), attributed to stagnant intravascular spin-labeled blood, were observed, DSA findings were analyzed visually at 4.5 seconds. RESULTS DSA revealed that the hypovascular area seen at 1.5 seconds was improved via the primary and secondary collaterals and delayed anterograde flow at 2.5 seconds. Serpiginous or round-shaped ATAs, which appeared in nearly the same configuration on dual PLD ASL-MRI, were attributed to stagnant collaterals and flow in the M2 portion of the middle cerebral artery and ICA during the late venous phase. CONCLUSIONS Use of dual PLD times was validated by the DSA findings. ATA detection using the dual PLDs also differentiated well-developed and stagnant collateral vessels from focal hyperperfusion.

Stroke due to a fusiform aneurysm of the cervical vertebral artery: case report

Abstract Aneurysms of the cervical vertebral artery (VA) are uncommon; they are often caused by trauma or spontaneous dissection. A fusiform aneurysm without evidence of atherosclerosis or dissection has not been reported previously. A 46-year-old man presented with a pontine infarct. Imaging revealed a fusiform aneurysm of the left VA at the C5–6 level, with occlusion of the basilar artery. Associated minor anomalies included fusion of the vertebral bodies of C5 and C6, cervical rib and platybasia. The left VA arose directly from the aortic arch and entered the transverse foramen at the C4 level. Hyperextension and left lateral flexion of the neck caused kinking of the VA proximal to the aneurysm. Turbulent flow in the aneurysm lumen was noted on angiography.

Signal changes on magnetic resonance perfusion images with arterial spin labeling after carotid endarterectomy.

Background: Cerebral hyperperfusion after carotid endarterectomy (CEA) is defined as an increase in ipsilateral cerebral blood flow (CBF). Practically, however, prompt and precise assessment of cerebral hyperperfusion is difficult because of limitations in the methodology of CBF measurement during the perioperative period. Arterial spin labeling (ASL) is a completely noninvasive and repeatable magnetic resonance perfusion imaging technique that uses magnetically-labelled blood water as an endogenous tracer. To clarify the usefulness of ASL in the management of cerebral hyperperfusion, we investigated signal changes by ASL with a single 1.5-s post-labeling delay on visual inspection. Methods: Thirty-two consecutive patients who underwent CEA were enrolled in this retrospective study. Results: On postoperative day 1, 22 (68.8%) and 4 (12.5%) patients exhibited increased ASL signals bilaterally (Group A) and on the operated side (Group B), respectively. Follow-up ASL showed improvement in these findings. Six (18.8%) patients showed no change (Group C). There was no apparent correlation between ASL signals on postoperative day 1 and the preoperative hemodynamic state, including the cerebrovascular reserve (P = 0.2062). Three (9.4%) patients developed cerebral hyperperfusion syndrome (two in Group A and one in Group B). Coincidence in the localization of increased ASL signals and electroencephalographic abnormalities was noted in these patients. Conclusion: Visual analysis of ASL with a single post-labeling delay overestimates CBF and cannot identify patients at risk of cerebral hyperperfusion syndrome probably because of the strong effect of the shortened arterial transit time immediately after CEA. However, ASL may be used as for screening.

Sequential changes of arterial spin-labeling perfusion MR images with dual postlabeling delay following reconstructive surgery for giant internal carotid artery aneurysm

Background: Arterial spin-labeling magnetic resonance perfusion imaging (ASL-MRI) allows noninvasive measurement of cerebral blood flow (CBF) but depends on arterial transit time (ATT). To overcome this problem, we developed a simple ASL technique with dual postlabeling delay (PLD) settings. In addition to the routinely used PLD of 1.5 seconds, we selected another PLD of 2.5 seconds to assess slowly streaming blood flow and detect arterial transit artifacts (ATAs) resulting from stagnant intravascular magnetically labeled spins. Case Description: We validated the dual PLD method with digital subtraction angiography (DSA) findings in a patient with an unruptured right giant internal carotid artery (ICA) aneurysm who underwent proximal ligation of the right cervical ICA followed by right superficial temporal artery–middle cerebral artery anastomosis. The giant aneurysm was detected as a strongly hyperintense signal area of ATA using both values of PLD. Decreased signal in the right hemisphere at PLD 1.5 seconds was somewhat improved at PLD 2.5 seconds. DSA revealed that this laterality resulted from the different ATT values between hemispheres due to stagnation of the labeled spin within the aneurysm. Postoperatively, with gradual but complete thrombosis and regression of the aneurysm, the size of the ASL hyperintense signal area decreased markedly. At postoperative 2 years, the aneurysm was not demonstrated as an ATA; furthermore, the decreased signals in the right hemisphere at PLD 1.5 seconds had mostly improved. Conclusion: Serial ASL-MRI with dual PLDs could show dynamic changes of giant aneurysms and the associated hemodynamic state following the surgery.

Various pathophysiological states of acute symptomatic seizures immediately following ischemic stroke, namely “onset seizures”, revealed by complementary use of periictal MRI and EEG

“Onset seizures” are acute symptomatic seizures occurring within 24 h after the onset of ischemic stroke, and their pathophysiological states are unknown. Electroencephalography is commonly used to diagnose epileptic activities; however, it is limited for use with acute stroke. Magnetic resonance imaging, including diffusion‐weighted imaging and perfusion imaging with arterial spin labeling, are applied mainly in an emergency. Ictal hyperperfusion on arterial spin labeling and cortical hyperintensity of cytotoxic edema on diffusion‐weighted imaging, peri‐ictally, can be obtained from an epileptically activated cortex.

[Brain Abscess due to Infection with Dematiaceous Fungi Cladophialophora bantiana Associated with Hypogammaglobulinemia Following Gastrectomy: A Case Report].

Dematiaceous fungi have melanin-like pigment in the cell wall and usually cause a variety of dermal infections in humans. Infections of the central nervous system(cerebral phaeohyphomycosis)are rare but serious, since they commonly occur in immunocompromized patients. A 76-year-old man was admitted with mild motor aphasia and underwent total excision of a mass in the left frontal lobe. With the postoperative diagnosis of brain abscess due to infection with dematiaceous fungi (C. bantiana) associated with hypogammaglobulinemia following gastrectomy, intravenous antifungal drugs including amphotericin B and fluconazole were administered. Regrowth of the abscess with intraventricular rupture was noted at about the 88th day after the initial surgery, and the patient underwent neuroendoscopic aspiration of the pus and placement of a ventricular drain. Following intraventricular administration of miconazole through ventricular drainage or an Ommaya reservoir, neuroradiological findings improved, but general and neurological conditions worsened. Further treatment was discontinued and the patient died 9 months after onset. The poor outcome in this patient is attributed to 1)intractability of dematiaceous fungi, 2)development of ventriculitis and the need for intraventricular administration of antifungal drugs, and 3)untreatable hypogammaglobulinemia following gastrectomy.

Cerebellar abscess due to infection with the anaerobic bacteria fusobacterium nucleatum: A case report

We report a rare case of cerebellar abscess produced by anaerobic bacteria. A 76-year-old man was admitted to our hospital with a history of fever, vomiting, and dizziness lasting 14 days. Computed tomography(CT)scan and magnetic resonance images showed the presence of a multiloculated cerebellar abscess with a right subdural abscess. The patient underwent aspiration of the abscess through a suboccipital craniotomy. Fusobacterium nucleatum, which is an anaerobic bacteria naturally present in the human oral cavity, was detected in cultures of the aspirated abscess. The patient was administered antibiotic treatment combined with hyperbaric oxygen therapy(HBO). The symptoms were briefly relieved but the cerebellar abscess recurred, which required a second aspiration. The combined treatment with antibiotics and HBO was maintained after the second operation. After 6 weeks of treatment, the cerebellar abscess was completely controlled. We conclude that antibiotic treatment combined with HBO is useful for treatment of cerebellar abscesses caused by infection with anaerobic bacteria.