Satoshi Tomura

Anti–high mobility group box-1 antibody therapy for traumatic brain injury

High mobility group box‐1 (HMGB1) plays an important role in triggering inflammatory responses in many types of diseases. In this study, we examined the involvement of HMGB1 in traumatic brain injury (TBI) and evaluated the ability of intravenously administered neutralizing anti‐HMGB1 monoclonal antibody (mAb) to attenuate brain injury.

Effect of Decompressive Craniectomy on Aquaporin-4 Expression after Lateral Fluid Percussion Injury in Rats

Decompressive craniectomy is one therapeutic option for severe traumatic brain injury (TBI), and it has long been used for the treatment of patients with malignant post-traumatic brain edema. A lack of definitive evidence, however, prevents physicians from drawing any conclusions about the effects of decompressive craniectomy for the treatment of TBI. Therefore, the aim of the present study was to investigate the influence of decompressive craniectomy on post-traumatic brain edema formation. The aquaporin-4 (AQP4) water channel is predominantly expressed in astrocytes, and it plays an important role in the regulation of brain water homeostasis. In the present study, we investigated the time course of AQP4 expression and the water content of traumatized cortex following decompressive craniectomy after TBI. Adult male Sprague-Dawley rats (300-400 g) were subjected to lateral fluid percussion injury using the Dragonfly device. The effect of decompressive craniectomy was studied in traumatized rats without craniectomy (closed skull, DC-), and in rats craniectomized immediately after trauma (DC+). AQP4 expression was investigated with a Western blot analysis and immunohistochemistry. Brain edema was measured using the wet weight/dry weight method. At 48 h after TBI, AQP4 expression of the DC- group was significantly increased compared with the DC+ group (p < 0.01). In addition, the cortical water content of the DC- group was significantly increased compared to the DC+ group at the same time point (p < 0.05). The present results suggest that decompressive craniectomy may affect AQP4 expression and reduce brain edema formation after TBI.

Pathophysiology and diagnosis of spontaneous intracranial hypotension.

BACKGROUND Spontaneous intracranial hypotension (SIH) has become a well-recognized syndrome. However, diagnosis of SIH is still challenging. The problem with SIH is that the precise mechanism of cerebrospinal fluid (CSF) leakage remains largely unknown and there is no definite diagnostic criterion in the imaging. METHODS The clinical findings of our ten cases and 301 literature reports on SIH were investigated in a retrospective analysis to clarify the pathophysiology of CSF leakage, correlate the findings of imaging studies and determine the most adequate diagnostic criteria. RESULTS The events precede symptoms of SIH were categorized as traumatic, secondary and strictly spontaneous (62%). The location of the spinal CSF leak remains undetectable in approximately 50% of cases reported. In 93% of patients, the CSF leakage sites were detected at the cervical or thoracic level of the spine. On recent MRI studies, 88% of patients showed spinal epidural fluid collections that most likely represent CSF leakage. MR myelography using heavily T2-weighted fast-spin-echo sequence can clearly demonstrate the site of CSF leakage. Although numerous treatment options are available, none of the treatments have been evaluated by randomized clinical trials. In 48% of papers, autologous epidural blood patch (EBP) was the treatment of choice in patients who have failed initial conservative management. Forty-nine percent of patients showed relief of symptoms after up to three repeated EBPs. CONCLUSION We propose new diagnostic criteria of SIH to avoid misdiagnosis.

Effects of intravenous infusion of hydrogen-rich fluid combined with intra-cisternal infusion of magnesium sulfate in severe aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial

BackgroundThe failures of recent studies intended to prevent cerebral vasospasm have moved the focus of research into delayed cerebral ischemia away from cerebral artery constriction towards other mechanisms. Recent accumulating evidence has suggested that early brain injury is also involved in the development of delayed cerebral ischemia, and that hydrogen can prevent early brain injury. Therefore, we have established a combination therapy of intravenous hydrogen infusion and intra-cisternal magnesium sulfate infusion for the treatment of both early brain injury and cerebral vasospasm. The present randomized controlled clinical trial is designed to investigate the effects of this novel therapeutic strategy on the occurrence of cerebral vasospasm, delayed cerebral ischemia, and clinical outcomes after high-grade subarachnoid hemorrhage.MethodsThis study is a randomized, double-blind, placebo-controlled design to be conducted in two hospitals. A total of 450 patients with high-grade subarachnoid hemorrhage will be randomized to one of three arms: (i) Mg + H2 group, (ii) Mg group, and (iii) control group. Patients who are assigned to the Mg + H2 group will receive intra-cisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days and intravenous hydrogen-rich fluid infusion (200 mL) twice a day for 14 days. Patients who are assigned to the Mg group will receive intra-cisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days and intravenous normal glucose-electrolyte solution (200 mL) without added hydrogen twice a day for 14 days. Patients who are assigned to the control group will receive intra-cisternal Ringer solution without magnesium sulfate at 20 mL/h for 14 days and intravenous normal glucose-electrolyte solution (200 mL) without added hydrogen twice a day for 14 days. Primary outcome measures will be occurrence of delayed cerebral ischemia and cerebral vasospasm. Secondary outcome measures will be modified Rankin scale score at 3, 6, and 12 months and biochemical markers.DiscussionThe present protocol for a randomized, placebo-controlled study of intravenous hydrogen therapy with intra-cisternal magnesium infusion is expected to establish the efficacy and safety of this therapeutic strategy.Trial registrationUMIN-CTR: UMIN000014696

Retrograde Suction Decompression Through Direct Puncture of the Common Carotid Artery for Paraclinoid Aneurysm.

BACKGROUND Surgical clipping of paraclinoid aneurysm can be very difficult because strong adhesions may hinder the dissection of the perforators and surrounding anatomical structures from the aneurysm dome. We describe our experience with using retrograde suction decompression during the clipping of paraclinoid aneurysms and discuss the relative advantages and pitfalls. MATERIALS AND METHODS This study included 23 patients with large and giant paraclinoid aneurysms who underwent surgical treatment consisting of direct clipping with suction decompression between March 2004 and August 2014. Direct puncture of the common carotid artery (CCA) was performed with a 20-gauge needle. The aneurysm was temporarily trapped by clamping of the CCA and external carotid artery (ECA), followed by temporary clipping of the intracranial internal carotid artery (ICA) distal to the aneurysm neck. Blood was then gently aspirated through a catheter introduced into the cervical ICA, resulting in collapse of the aneurysm. Therefore, safe aneurysm dissection was feasible during interruption of the blood flow, which could be maintained for up to 5 min. This procedure was repeated until dissection and clipping of the aneurysm were completed. RESULTS Seven patients were admitted with SAH, 11 with asymptomatic unruptured aneurysm, and 5 with symptomatic unruptured aneurysm. The aneurysms were located on the paraclinoidal segment of the ICA in 15 cases, on the ICA-posterior communicating artery (PComA) in 6, at the ICA bifurcation in 1, and on the anterior wall of the ICA in 1. None of them suffered complications related to the CCA puncture. Surgical outcome was good recovery in 13 patients, moderate disability in 4, severe disability in 4, and vegetative state in 1. CONCLUSION Retrograde suction decompression through direct puncture of the common carotid artery is a useful adjunct technique for the clipping of paraclinoid ICA aneurysms.

Reverse bypass using a naturally formed "bonnet" superficial temporal artery in symptomatic common carotid artery occlusion: a case report.

We herein describe a patient with symptomatic common carotid artery occlusion who underwent a reverse superficial temporal artery (STA)-middle cerebral artery (MCA) single bypass using a naturally formed “bonnet” STA. The surgical procedure was performed without difficulty, and no further neurological deterioration was observed after surgery. In practice, this case highlights that the reverse STA-MCA bypass can be achieved safely and less invasively using a naturally formed “bonnet” STA.

Long-Term Neurological and Radiological Results of Consecutive 63 Unruptured Anterior Communicating Artery Aneurysms Clipped via Lateral Supraorbital Keyhole Minicraniotomy

BACKGROUND Treatments for unruptured anterior communicating artery (AcomA) aneurysm have relatively high morbidity. OBJECTIVE To assess the lateral supraorbital keyhole approach for safe and complete clipping of unruptured AcomA aneurysm and evaluate the long-term clinical and radiological outcomes, including cognitive and depressive status. METHODS A total of 63 patients (aged 41-79 yr, mean 64 yr) with relatively small AcomA aneurysms clipped via the lateral supraorbital approach were retrospectively analyzed among the 105 AcomA aneurysms treated by clipping from 2005 to 2014. Neurological and cognitive functions were examined by several scales, including the modified Rankin Scale (mRS) and Mini-Mental Status Examination. The depressive state was assessed using the Beck Depression Inventory and Hamilton Depression Scale. The state of clipping was assessed 1 yr and then every few years after the operation by 3-dimensional computed tomography angiography. RESULTS Complete neck clipping was confirmed in 62 aneurysms (98.4%). Perioperative complications occurred in 5 patients (5/63; mild frontalis muscle weakness in 3, anosmia in 1, and meningitis in 1). The mean clinical follow-up period was 5.2 ± 2.1 yr. No patient showed an mRS score more than 2 and all were completely independent in daily life. The depression scores were significantly improved after surgery. The overall mortality was 0% and overall morbidity (mRS score > 2 or Mini-Mental Status Examination score < 24) was 1.6%. All completely clipped aneurysms did not show any recurrence during the mean follow-up period of 4.9 ± 2.1 yr. CONCLUSION Lateral supraorbital keyhole approach to clip relatively small unruptured AcomA aneurysm promises less invasive and durable treatment.

The Relationship between Functional Outcome and Prehospital Time Interval in Patients with Cerebral Infarction

BACKGROUND When symptoms of cerebral infarction are recognized in a patient, he or she should be transported to a hospital and should be started on the appropriate treatments. The effectiveness of delayed treatment of cerebral infarction with respect to the initial diagnosis or perception of the disease is still unclear. METHODS We retrospectively investigated whether the functional outcomes would improve if patients with cerebral infarction were transported to the hospital with minimum delay. One-hundred twenty-two patients who were transported to Mishuku Hospital from January 2012 to August 2015 were included. We conducted multiple regression analyses. The criterion variable included the BI at discharge, and the explanatory variables were age, sex, days of hospital stay, the Barthel Index (BI) on admission, time from symptom onset to hospital arrival, time from emergency medical service perception to hospital arrival, recombinant tissue plasminogen activator (rt-PA) treatment, and the occluded artery type. RESULTS In all 122 cases, the BI at the time of discharge was not related to onset time (P = .453) but was significantly related to perception time (P = .026). BI scores at discharge were high for young patients (P = .002) and for patients with short hospital stays (P <.001). In the rt-PA group (52 cases), BI scores at discharge were also high when the perception time was short (P = .036). CONCLUSIONS A short interval between perception and hospital arrival improves the functional outcomes for patients with cerebral infarction. Thus, patients with cerebral infarctions must be treated with minimal delay after diagnosis of the condition.

Usefulness of Extradural Optic Nerve Decompression via Trans–Superior Orbital Fissure Approach for Treatment of Traumatic Optic Nerve Injury: Surgical Procedures and Techniques from Experience with 8 Consecutive Patients

OBJECTIVE To describe our experience of extradural optic nerve decompression via the trans-superior orbital fissure approach for traumatic optic neuropathy (TON) and retrospectively analyze its advantages and pitfalls. METHODS Between September 2009 and August 2014, 8 consecutive patients with TON underwent extradural optic canal decompression via the trans-superior orbital fissure approach. We retrospectively reviewed medical charts, radiologic findings, surgical techniques, complications, and final surgical results. RESULTS All 8 patients presented with visual disturbance caused by head injury; 2 patients had no light perception, 6 had light perception, and 2 had ophthalmoplegia. All patients underwent extradural optic canal decompression and high-dose steroid administration within 24 hours after injury. Postoperative visual acuity on discharge was improved in 6 patients and unchanged in 2. The 2 patients with ophthalmoplegia gradually recovered by 3 months after operation. The postoperative outcome was good recovery in 7 patients and moderate disability in 1 patient. There were no complications related to the surgical procedure. CONCLUSIONS Emergent optic canal release has been recommended in patients with TON. The advantage of the extradural optic canal decompression via the trans-superior orbital fissure approach is easy identification of the optic canal after partial removal of the anterior clinoid process, resulting in fewer surgical complications. In addition, this procedure can achieve intraorbital decompression if necessary. We recommend this modified approach with mini-peeling as a safe and reliable procedure in patients with TON.

Validation of effectiveness of keyhole clipping in nonfrail elderly patients with unruptured intracranial aneurysms.

OBJECTIVE Advanced age is known to be associated with a poor prognosis after surgical clipping of unruptured intracranial aneurysms (UIAs). Keyhole clipping techniques have been introduced for less invasive treatment of UIAs. In this study, the authors compared the complications and clinical and radiological outcomes after keyhole clipping between nonfrail elderly patients (≥ 70 years) and nonelderly patients. METHODS Keyhole clipping (either supraorbital or pterional) was performed to treat 260 cases of relatively small (≤ 10 mm) anterior circulation UIAs. There were 62 cases in the nonfrail elderly group (mean age 72.9 ± 2.6 years [± SD]) and 198 cases in the nonelderly group (mean age 59.5 ± 7.6 years). The authors evaluated mortality and morbidity (modified Rankin Scale score > 2 or Mini-Mental State Examination [MMSE] score < 24) at 3 months and 1 year after the operation, the general cognitive function by MMSE at 3 months and 1 year, anxiety and depression by the Beck Depression Inventory (BDI) and Hamilton Rating Scale for Depression (HAM-D) at 3 months, and radiological abnormalities and recurrence at 1 year. RESULTS Basic characteristics including comorbidities, frailty, and BDI and HAM-D scores were not significantly different between the 2 groups, whereas the MMSE score was slightly but significantly lower in the elderly group. Aneurysm location, largest diameter, type of keyhole surgery, neck clipping rate, and hospitalization period were not significantly different between the 2 groups. The incidence of chronic subdural hematoma was not significantly higher in the elderly group than in the nonelderly group (8.1% vs 4.5%, p = 0.332); rates of other complications including stroke and epilepsy were not significantly different. Lacunar infarction occurred in 3.2% of the elderly group and 3.0% of the nonelderly group. No patient in the elderly group required re-treatment or demonstrated recurrence of clipped aneurysms. The MMSE score at 3 months significantly improved in the nonelderly group but did not change in the elderly group. The BDI and HAM-D scores at 3 months were significantly improved in both groups. No patient died in either group. The morbidity at 3 months and 1 year in the elderly group (1.6% and 4.8%, respectively) was not significantly different from that in the nonelderly group (2.0% and 1.5%, respectively). CONCLUSIONS Keyhole clipping for nonfrail elderly patients with relatively small anterior circulation UIAs did not significantly increase the complication, mortality, or morbidity rate; hospitalization period; or aneurysm recurrence compared with nonelderly patients, and it was associated with improvement in anxiety and depression. Keyhole clipping to treat UIAs in the nonfrail elderly is an effective and long-lasting treatment.