Tetsu Satow

The Basic Helix-Loop-Helix Gene hesr2 Promotes Gliogenesis in Mouse Retina

Members of a subclass of hairy/Enhancer of split [E(spl)] homologs, calledhesr genes, are structurally related to another subclass of hairy/E(spl) homologs,Hes genes, which play an important role in neural development. To characterize the roles of hesr genes in neural development, we used the retina as a model system. In situ hybridization analysis indicated that allhesr genes are expressed in the developing retina, but only hesr2 expression is associated spatially with gliogenesis. Each member was then misexpressed with retrovirus in the retinal explant cultures prepared from mouse embryos or neonates, which well mimic in vivo retinal development. Interestingly,hesr2 but not hesr1 orhesr3 promoted gliogenesis while inhibiting rod genesis without affecting cell proliferation or death, suggesting that the cells that normally differentiate into rods adopted the glial fate by misexpression of hesr2. The gliogenic activity ofhesr2 was more profound when it was misexpressed postnatally than prenatally. In addition, double mutation of the neuronal determination genes Mash1 andMath3, which increases Müller glia at the expense of bipolar cells, upregulated hesr2 expression. These results indicate that, among structurally related hesrgenes, only hesr2 promotes glial versus neuronal cell fate specification in the retina and that antagonistic regulation between hesr2 and Mash1–Math3 may determine the ratios of neurons and glia.

Intracarotid propofol test for speech and memory dominance in man

Objective: To evaluate the usefulness of propofol as an alternative drug to amobarbital for the Wada test. Methods: The authors analyzed 67 right-handed patients out of 123 patients who were candidates for neurosurgical therapy and thus underwent the Wada test as a preoperative evaluation. Twelve were tested with propofol and 55 were tested with amobarbital. Test conditions of the Wada test, recovery time of muscle power to manual muscle testing (MMT) Grade 3 (T3/5) and Grade 5 (T5/5), onset time of the first verbal response (Tverb) after injection and that of the first nonverbal response (Tnon-verb), were compared between the two groups. Power spectrum analysis of EEG background activity during the Wada test was performed and the time and spatial distribution of polymorphic slow activities were also compared in three cases. Results: With propofol injection, lateralities of language and memory function were identified in 12 and 9 of 12 patients in comparison to amobarbital (52 and 41 of 55 patients detection in language and memory function). No complications with direct intracarotid injection of propofol were observed. T3/5 and T5/5 with propofol injection were shorter while Tverb and Tnon-verb were longer compared to amobarbital. Absolute power of polymorphic slow EEG waves gradually increased and then rapidly decreased with propofol, which was in contrast to amobarbital injection. Conclusions: With direct intracarotid propofol injection, the Wada test was satisfactorily performed in all 12 patients and 2 more patients with left-handedness or with different injection dose for each side without any complications. Clinical usefulness of propofol as an alternative drug to amobarbital for the Wada test was indicated.

Short-lasting impairment of tactile perception by 0.9Hz-rTMS of the sensorimotor cortex

To test whether low-frequency repetitive transcranial magnetic stimulation (rTMS) of sensorimotor cortex (SM1) has prolonged effects on somatosensory function, eight subjects were given 900 TMS pulses over the left hand SM1 (0.9Hz, 90% of the resting motor threshold) or at sites 3 cm anterior or posterior to it. Tactile threshold of the right hand was increased for a short duration after rTMS over SM1, but two-point discrimination and median nerve SEPs were unaffected after rTMS at any sites.

Periventricular and deep white matter leukoaraiosis have a closer association with cerebral microbleeds than age

Background:  Taking an advantage of the high sensitivity of 3D T2*‐weighted gradient‐recalled‐echo (GRE) imaging to cerebral microbleeds, we investigated the relationship between cerebral microbleeds and leukoaraiosis.

Growth potential and response to multimodality treatment of partially thrombosed large or giant aneurysms in the posterior circulation

OBJECTIVEThis study examined the growth potential and response to multimodality treatment of partially thrombosed large or giant aneurysms in the posterior circulation. METHODSThe 17 aneurysms arose from nonbranching sites of the vertebral artery (VA) in 6 patients and from branching sites in 11 patients (the VA-posteroinferior cerebellar artery [PICA], 3 cases; basilar artery [BA] fenestration, 1 case; BA-superior cerebellar artery [SCA], 5 cases; and BA tip, 2 cases). RESULTSEndovascular trapping was performed in 5 VA aneurysms at nonbranching sites, 2 VA-PICA cases with or without revascularization of the PICA, and 1 BA fenestration case. Endosaccular embolization was performed in 2 BA-SCA aneurysms as the sole treatment or after superficial temporal artery-SCA bypass for a broad-necked lesion. Surgical proximal occlusion (PO) with or without revascularization of the PICA was performed in 2 VA cases. Endovascular treatment failed to prevent growth in 1 VA-PICA case and the broad-necked BA-SCA case. Simple flow alteration by PO of 3 BA aneurysms, with gadolinium enhancement on T1-weighted images, did not prevent growth. Maximum flow reduction by various combinations of bypass (superficial temporal artery-posterior cerebral artery or superficial temporal artery-SCA) and BA PO, aimed at reducing hemodynamic stress on the neck, was tailored to 5 cases, including those refractory to PO; it achieved marked shrinkage in 2 cases and stabilization of the aneurysms in 3 cases. The aneurysms harboring neither gadolinium enhancement nor hyperintensity on fluid-attenuated inversion recovery images showed significantly lower growth potential before treatment and a lesser degree of shrinkage after tailored treatment than the remaining cases (P = 0.03 and P = 0.01, respectively). Overall, marked shrinkage was achieved in 27%, moderate shrinkage in 20%, stabilization in 47%, enlargement in 7%, and favorable outcome in 71%. Maximum flow reduction strategy for BA aneurysms tended to show higher shrinking efficacy than endovascular trapping for VA and BA aneurysms (P = 0.08). CONCLUSIONFor aneurysms at nonbranching sites, endovascular trapping may be effective, although its shrinking efficacy may be moderate. For the most formidable BA aneurysms at branching sites, maximum flow reduction may cause marked shrinkage, even of aggressive lesions.

Mirth and laughter arising from human temporal cortex

Laughter and mirth are essential in our enjoyment of daily life and in facilitating communication. Various studies have been done relating to the emotional processing that takes place in the human cerebral cortex, but few have explored the cerebral origins of mirth. Some reports on pathological laughter have implicated the hypothalamus, brain stem, and temporal lobe.1–3 As part of the presurgical evaluation of patients with epilepsy, electric cortical stimulation is used to delineate the functional cortical areas, and sometimes this elicits various emotional responses.4 However, only two stimulation studies2,5 have been conducted with a focus on mirth and laughter. Arroyo et al suggested that the motor act of laughter and the processing of its emotional content were separately represented in, respectively, the anterior cingulate area and the basal temporal area (the fusiform gyrus or parahippocampal gyrus, or both).2 Fried et al suggested not only that laughter and mirth were represented in the presupplementary motor area, but also that there was close linkage between the motor, affective, and cognitive components of laughter.5 We report a patient in whom electric cortical stimulation applied to the inferior temporal gyrus produced mirth alone or laughter preceded by mirth, depending on the intensity of the stimulation. A 24 year old right handed …

Histopathologic Analysis of Retrieved Thrombi Associated With Successful Reperfusion After Acute Stroke Thrombectomy

Background and Purpose— Histopathologic evaluation of occlusive thrombi retrieved from cerebral arteries using endovascular therapy is possible. We investigated the relationship between successful reperfusion after thrombectomy and histopathologic characteristics of retrieved thrombi. Methods— Among consecutive patients with acute ischemic stroke treated with endovascular therapy at our institute from December 2010 to July 2015, we retrospectively reviewed those with acute major arterial occlusion from which retrieved thrombi were evaluated histopathologically. Obtained thrombi were assessed for the existence of atheromatous gruel, organization, and the ratios of erythrocyte and fibrin/platelet components. Successful reperfusion was defined as the modified Treatment in Cerebral Ischemia grade of 2b to 3. Results— Of 83 patients studied, 58 (70%) underwent successful reperfusion. Atheromatous gruel was less frequently identified (3% versus 20%; P=0.024), and the proportion of erythrocyte components was higher (57±23% versus 47±24%; P=0.042) in thrombi retrieved from the reperfused than the unreperfused group. On multivariate logistic regression analysis, atheromatous gruel was inversely related (odds ratio, 0.062; 95% confidence interval, 0.002–0.864), and >64% erythrocyte components (cutoff obtained from receiver operating characteristic curve) were positively related (odds ratio, 4.352; 95% confidence interval, 1.185–19.363) to successful reperfusion. Conclusions— Successful reperfusion could be associated with the histopathology of occlusive thrombi, including the existence of atheromatous gruel and proportion of erythrocyte components. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT02251665.

Efficacy of FLOW 800 with Indocyanine Green Videoangiography for the Quantitative Assessment of Flow Dynamics in Cerebral Arteriovenous Malformation Surgery

OBJECTIVE To evaluate the quantitative assessment of flow dynamics during surgery for arteriovenous malformations (AVMs) with FLOW 800 with indocyanine green videoangiography. METHODS Changes in flow dynamics in the superficial AVM components (feeder, nidus, and drainer), the adjacent cortical artery, and the cortical vein surrounding AVM were evaluated. Analysis was performed at predissection, postclipping of the feeders, and postresection of the nidus with the use of quantitative values of the maximum fluorescence intensity, time to half-maximum fluorescence intensity (T1/2 FI), and the fluorescence intensity rate at T1/2 FI semiautomatically obtained with the use of FLOW 800 software. RESULTS FLOW 800 assessments were performed in 7 cases. The time difference between the T1/2 FI, defined as transit time, in the cortical artery and the drainer was prolonged from 0.08 ± 0.65 seconds to 2.63 ± 1.79 seconds (P < 0.0001) at postfeeder clipping phase. The transit time between the cortical artery and the cortical vein was reduced to 3.76 ± 1.37 seconds at post feeder clipping phase (P = 0.024) and 2.63 ± 0.80 seconds at final phase (P = 0.005) compared with 4.56 ± 1.47 seconds at predissection phase. The maximum intensity and the fluorescence intensity rate at T1/2 FI were not significantly different at these phases, excluding the maximum intensity of the drainer decreasing from 533 ± 271 to 399 ± 217 (P = 0.006) at post feeder clipping phase. CONCLUSION FLOW 800 analysis with indocyanine green videoangiography provides the real-time hemodynamic status of the AVMs and adjacent brain at various stages of resection. This technique is feasible to resect AVMs more safely and convincingly.

Superselective Shunt Occlusion for the Treatment of Cavernous Sinus Dural Arteriovenous Fistulae

BACKGROUND: In treating cavernous sinus dural arteriovenous fistulae (CSdAVFs), transvenous embolization of the whole affected sinus is usually performed, which may result in the disturbance of normal venous drainage or permanent cranial nerve palsy. OBJECTIVE: To describe superselective shunt occlusion of CSdAVFs. METHODS: Between July 2005 and August 2011, we had 20 consecutive cases of CSdAVFs. In 14 cases (70%), we could detect the restricted locus of arteriovenous shunts by 3-dimensional rotational angiography and/or superselective arteriography. After navigating the microcatheter to the shunt segment, consecutive superselective arteriovenography was performed to confirm the location of the microcatheter at the proper position. RESULTS: In 12 of 14 cases (85.7%) in which the shunt was restricted, coiling only in the small venous pouch or compartment, which was just downstream of the shunt point, led to complete disappearance of the shunt without obliterating the entire sinus. No recurrence or permanent cranial nerve palsy was observed during the follow-up period with a mean of 46 months (range, 3-69 months) in 12 cases treated by superselective shunt occlusion. CONCLUSION: This technique, which enables complete extirpation of shunts by small amounts of coils, is a feasible way to treat CSdAVFs with excellent mid- to long-term results. Understanding of the angioarchitecture by 3-dimensional rotational angiography and consecutive superselective arteriovenography was useful. This method should be considered before sinus packing or mere obliteration of dangerous venous outlets. ABBREVIATIONS: AVF, arteriovenous fistula CNP, cranial nerve palsy CS, cavernous sinus CSdAVF, cavernous sinus dural arteriovenous fistula ECA, external carotid artery 3-D RA, 3-dimensional rotational angiography SSSO, superselective shunt occlusion

Hybrid operating room for the treatment of complex neurovascular and brachiocephalic lesions

BACKGROUND We examine the impact of the installation of integrated hybrid operating rooms (ORs) that allow both surgical and endovascular procedures and are designed for less invasive and 1-stage treatment of complex neurovascular lesions. METHODS We retrospectively analyzed our experience in the treatment of complex neurovascular lesions in a hybrid OR. RESULTS Three patients with distal middle cerebral artery (MCA) aneurysms underwent a proximal clip occlusion or endovascular trapping with a superficial temporal artery-MCA bypass after correct localization of the recipient branch distal to the aneurysm using superselective intra-arterial infusion of indocyanine green under an operating microscope. Two patients with innominate artery stenosis were treated with retrograde stenting from the common carotid artery (CCA) with distal protection of the internal carotid artery (ICA) alone, and with antegrade stenting with dual protection of the ipsilateral ICA and the vertebral artery. Two patients with tandem stenosis of the proximal CCA and carotid bifurcation underwent 1-stage retrograde stenting combined with a carotid endarterectomy. A patient with the innominate artery and the proximal CCA stenosis underwent staged percutaneous antegrade angioplasty of the innominate artery followed by retrograde stenting of both lesions. A patient with tandem stenosis of the subclavian and innominate arteries underwent 1-stage retrograde stenting. In 2 patients with carotid stenosis that was difficult to access via the endovascular route, carotid stenting was performed by direct puncture of the proximal CCA. No patients suffered from new postoperative neurologic deficits. CONCLUSIONS The integration of a high-end hybrid OR enables combined endovascular and surgical procedures for complex neurovascular and brachiocephalic lesions in a 1-stage treatment.