Hidehito Kimura

Rev‐erbα gene expression in the mouse brain with special emphasis on its circadian profiles in the suprachiasmatic nucleus

Rev‐erbα is an orphan nuclear receptor that constitutively suppresses gene transcription. In the present study, the expression of Rev‐erbα was investigated in the mouse brain by in situ hybridization using antisense cRNA probe. Positive Rev‐erbα mRNA signals were detected widely in the brain with the highest expression in the suprachiasmatic nucleus (SCN). In the constant dark condition, the circadian expression profiles of Rev‐erbα m RNA in the SCN showed a peak at early daytime (CT4) and a trough at early night time (CT16). The environmental lighting condition (light–dark environmental condition and exposure in the subjective night) did not alter the expression profiles. These findings indicate that Rev‐erbα gene is a transcription factor intimately related to the circadian clock in the SCN.

Endoscopic endonasal translacerum approach to the inferior petrous apex.

OBJECTIVE The surgical approach to lesions involving the inferior petrous apex (IPA) is still challenging. The purpose of this study is to demonstrate the anatomical features of the IPA and to assess the applicability of an endoscopic endonasal approach through the foramen lacerum (translacerum approach) to the IPA. METHODS The surgical simulation of the endoscopic endonasal translacerum approach was conducted in 3 cadaver heads. The same technique was applied in 4 patients harboring tumors involving the IPA (3 chordomas and 1 chondro-sarcoma). RESULTS By removing the fibrocartilaginous component of the foramen lacerum, a triangular space was created between the anterior genu of the petrous portion of the carotid artery and the eustachian tube, through which the IPA could be approached. The range of the surgical maneuver reached laterally up to the internal auditory canal, jugular foramen, and posterior vertical segment of the petrous portion of the carotid artery. In clinical application, the translacerum approach provided sufficient space to handle tumors at the IPA. Gross-total and partial removal was achieved in 3 and 1 cases, respectively, without permanent surgery-related morbidity and mortality. CONCLUSIONS The endoscopic endonasal translacerum approach provides reliable access to the IPA. It is indicated alone for lesions confined to the IPA and in combination with other approaches for more extensive lesions.

Vestibular dysfunction and compensation after removal of acoustic neuroma

OBJECTIVE To evaluate vestibular function after unilateral acoustic neuroma surgery via a retrosigmoid approach. METHODS Thirty-eight patients were tested using caloric irrigation, static posturography, and the Dizziness Handicap Inventory (DHI) before, and one week to nine months after surgery. RESULTS Twenty-six patients were categorized as a response group and 12 as a no-response group on the basis of preoperative caloric irrigation findings. The posturographic parameters and DHI scores at one week after surgery showed significant deterioration in the response group, but not in the no-response group. However, they recovered to the preoperative baseline at 3 months after surgery. The posturographic parameters and DHI scores for older patients tended to be worse than those for younger patients at 6 and 9 months after surgery. CONCLUSION Patients in whom caloric responses are retained preoperatively show a temporary disturbance of balance after removal of acoustic neuroma. Disequilibrium after surgery ameliorates to the preoperative baseline within three months due to vestibular compensation, regardless of preoperative vestibular function. It is possible that poorer vestibular compensation may facilitate incomplete recovery in older patients after surgery.

A very unusual case of fibromuscular dysplasia with multiple aneurysms of the vertebral artery and posterior inferior cerebellar artery

Fibromuscular dysplasia (FMD) is a noninflammatory and nonatheromatous arteriopathy that commonly affects the renal and cervical internal carotid arteries and sometimes the vertebral arteries (VAs). The association of FMD with intracranial aneurysms is widely known. The authors describe a rare case of FMD presenting with subarachnoid hemorrhage due to the rupture of 1 of 10 aneurysms located in the extra- and intracranial vertebral and posterior inferior cerebellar arteries. The FMD was treated successfully using flow reversal therapy, consisting of proximal occlusion of the VA with Guglielmi detachable coils, and was diagnosed histopathologically using a biopsy specimen of the distal superficial temporal artery. Originally FMD may be caused by a fragile arterial wall that may progress to the formation of an aneurysm due to hemodynamic stress. For this reason, FMD may be treatable by reducing this hemodynamic stress.

Cilostazol Administration with Combination Enteral and Parenteral Nutrition Therapy Remarkably Improves Outcome After Subarachnoid Hemorrhage

OBJECTIVE In order to prevent cerebral vasospasm (VS) following aneurysmal subarachnoid hemorrhage (SAH), we introduced combined enteral nutrition (EN) and parenteral nutrition (PN) with oral cilostazol administration to the postoperative patient after SAH and investigated the effect on VS. METHODS After aneurysmal SAH, 130 postoperative patients were enrolled in this study between April 2008 and March 2012. The patients enrolled before April 2010 were treated by conventional therapy (control group). The patients enrolled after April 2010 were administrated cilostazol 200 mg/day and received EN and PN simultaneously (combined group). RESULTS The combined group consisted of 62 patients and the control group of 68 patients. Angiographic VS occurred in 33.9 % (n = 21) of the combined group and in 51.5 % (n = 35) of the control group (p = 0.051, Fisher exact test). The incidence of symptomatic VS was significantly lower in the combined group (p = 0.001). The incidence of new cerebral infarctions was also significantly lower in the combined group (p = 0.0006). Clinical outcome at discharge was also significantly better in the combined group than in control group (p = 0.031). CONCLUSIONS Cilostazol administration with combination EN and PN is remarkably effective in preventing cerebral VS after aneurysmal SAH.

Radiographic occult cerebellar germinoma presenting with progressive ataxia and cranial nerve palsy

BackgroundAlthough the usefulness of susceptibility-weighted imaging (SWI) for detecting basal ganglia germinoma has been reported, the technique is not widely used. We recently encountered an unusual case of primary cerebellar germinoma, presenting with progressive ataxia and cranial nerve palsy, characterized by gradually enlarging low-intensity lesions visible with both T2*-weighted imaging (T2*WI), which were the key to the diagnosis.Case presentationA 30-year-old man was referred to our hospital because of slowly progressive dizziness and mild ataxia. Magnetic resonance imaging (MRI) revealed a small, low-intensity spot in the left cerebellar peduncle on the T2*WI and SWI without enhancement. Cerebral angiography revealed no vascular abnormality. The serum α-fetoprotein value was normal. A steroid-pulse was administered as a therapeutic and diagnostic trial, but the symptoms improved little. The patient was discharged from the hospital but soon developed brainstem dysfunction, characterized by dyspnea or hiccups, and he was readmitted. T2*WI imaging revealed expanded and extended spotty lesions in the cerebellum and brainstem, which had not enhanced with contrast agent previously. Targeted stereotactic biopsy of the newly enhanced cerebellar lesion was performed; histopathological examination of the tissue revealed pure germinoma. Serum and cerebral spinal fluid values of beta-human chorionic gonadotropin were not significantly elevated. Chemotherapy with carboplatin and etoposide was initiated. The enhanced lesion disappeared promptly, but the patient continued to require assisted automatic ventilation because of paralysis of respiratory muscles.ConclusionsWe conclude that enlarging low-intensity lesions on T2*WI and SWI may be a reliable clue to the diagnosis of germinomas, irrespective of their location, even without enhancement. Biopsy of the tumor at an early stage is the only way to make the diagnosis conclusively and enable prompt start of treatment.

Brain expression of apurinic/apyrimidinic endonuclease (APE/Ref-1) multifunctional DNA repair enzyme gene in the mouse with special reference to the suprachiasmatic nucleus

Multifunctional mammalian apurinic/apyrimidinic endonuclease (APE, also known as redox factor-1; Ref-1) repairs baseless sites of damaged DNA caused by oxidative stress and regulates the redox state of various DNA binding proteins. Here, we examined the expression of APE/Ref-1 m-RNA in the mouse brain by in situ hybridization. We detected APE/Ref-1 transcripts throughout the mouse brain particularly in the clock oscillating neurons of the suprachiasmatic nucleus (SCN), hippocampal pyramidal cells, granular cells, and in monoaminergic neurons. In the circadian center SCN, levels of APE/ref-1 mRNA transcripts were constantly high, and were not influenced by either circadian rhythms or by exposure to light.

Long-Term Outcomes of Carotid Endarterectomy and Carotid Artery Stenting for Carotid Artery Stenosis: Real-World Status in Japan

BACKGROUND AND PURPOSE We investigated long-term outcomes of carotid endarterectomy (CEA) and carotid artery stenting (CAS) in our institute to evaluate the outcomes of real-world practice in Japan. METHODS Between August 2006 and July 2013, 203 consecutive carotid revascularizations with either CEA or CAS were performed in our institute. The initial treatment was regarded as the starting point in the cases of the patients who received treatment by bilateral carotid artery stenosis or retreatment. We assessed the long-term outcomes with survival analyses. RESULTS A total of 182 patients (CEA 111, CAS 71), including 86 symptomatic patients, were included in the current study with a mean follow-up period of 42.9 months. The periprocedural stroke/death/myocardial infarction (MI) rate was 3.6% for CEA and 5.6% for CAS groups (P = .71). Estimates of the 4-year event-free rate from the primary end point (the composite of any stroke, death, or MI within 30 days, and any ipsilateral stroke thereafter) using competing risk analysis were 3.6% for CEA and 7.1% for CAS (P = .156). Kaplan-Meier estimates of the 4-year event-free rate from the secondary end point (the composite of any stroke, death, or MI within 30 days, and any stroke or death thereafter) were 13.8% for CEA and 19.1% for CAS (P = .072). Age was the only significant predictor for the primary end point. Both age and CAS were significant predictors for the secondary end point. CONCLUSIONS The current study on real-world practices demonstrated perioperative and long-term outcomes that were comparable to previous major studies of large numbers of patients.

Minimum Transpetrosal Retrolabyrinthine Approach for Revascularization of Posterior Cerebral Artery: Operative Nuance.

BACKGROUND: Revascularization of the posterior cerebral artery (PCA) can be essential for treating complex cerebral aneurysms in the posterior circulation, and it is considered technically challenging. To help decrease the difficulty of this technique, we developed the minimum transpetrosal approach (MTPA). OBJECTIVE: The technical nuances of the MTPA were innovated by cadaver head dissections and an actual clinical case. METHODS: Four sides of the formalin-fixed cadaver heads were used to investigate if the posterior cerebral artery could be exposed with this minimum retraction of the temporal lobe in the subtemporal approach and the MTPA. By using the MTPA, 1 patient harboring a ruptured PCA aneurysm underwent superficial temporal artery-PCA anastomosis followed by isolation of the aneurysm. RESULTS: In the cadaver head dissections, we noticed that the PCAs were difficult to expose with gentle retraction of the temporal lobe in the subtemporal approach. By performing an additional retrolabyrinthine mastoidectomy, performed as the MTPA, all 4 PCAs were easily exposed in the 4 wide surgical fields. The maximum widths of the surgical fields above and below the PCA could be successfully measured in 2 cases, which were 13.3 mm and 11.2 mm, respectively (mean, 12.3 mm). Additionally, in the actual live surgery using MTPA, the PCAs were relative easy to expose with a surgical field wide enough to perform PCA bypass, which was performed without complication. CONCLUSION: The MTPA may be the most favorable approach for PCA bypass that can be performed easily with minimal temporal lobe retraction. ABBREVIATIONS: MTPA, minimum transpetrosal approach PCA, posterior cerebral artery STA, superficial temporal artery

Clear Detection of Thin-Walled Regions in Unruptured Cerebral Aneurysms by Using Computational Fluid Dynamics

OBJECTIVE Thin-walled regions (TIWRs) within cerebral aneurysms have a high risk of rupture during surgical manipulation. Previous reports have demonstrated specific changes in the parameters of computational fluid dynamics in TIWRs; however, they have not been fully evaluated. We identified and investigated a novel parameter, wall shear stress vector cycle variation (WSSVV), with user-friendly software that could predict TIWRs. METHODS Twelve unruptured cerebral aneurysms were analyzed. TIWRs were defined as reddish areas compared with the normal-colored parent artery on intraoperative views. The position and orientation of these clinical images were adjusted to match the WSSVV color maps. TIWRs and thick-walled regions (TKWRs) were marked and compared with the corresponding regions on WSSVV maps. The default images obtained from WSSVV imaging required appropriate maximum color bar value (MCBV) adjustment for predicting TIWRs. Sensitivity and specificity analyses were performed by changing the MCBV from 300 to 700 at intervals of 100. With the optimal MCBV, the WSSVV values were quantitatively compared. RESULTS All of the selected 18 TIWRs and 16 TKWRs corresponded to low- and high-value regions of the WSSVV color maps at the adjusted MCBV, respectively. The mean optimal MCBV was 483.3 ± 167.50 (range, 300-700). According to receiver operating characteristic analysis, the best MCBV for predicting TIWRs was 500 (highest sensitivity, 0.89; specificity, 0.94). Under this condition, the quantitative values of the computational fluid dynamics color maps for TIWRs and TKWRs were significantly different (P < 0.01). CONCLUSIONS Low WSSVV values may indicate TIWRs within cerebral aneurysms.