Intracranial pressure spikes trigger spreading depolarizations.

Spreading depolarizations are highly prevalent and spatiotemporally punctuated events worsening the outcome of brain injury. Trigger factors are poorly understood but may be linked to sudden worsening in supply-demand mismatch in compromised tissue. Sustained or transient elevations in intracranial pressure are also prevalent in the injured brain. Here, using a mouse model of large hemispheric ischaemic stroke, we show that mild and brief intracranial pressure elevations (20 or 30 mmHg for just 3 min) potently trigger spreading depolarizations in ischaemic penumbra (4-fold increase in spreading depolarization occurrence). We also show that 30 mmHg intracranial pressure spikes as brief as 30 s are equally effective. In contrast, sustained intracranial pressure elevations to the same level for 30 min do not significantly increase the spreading depolarization rate, suggesting that an abrupt disturbance in the steady state equilibrium is required to trigger a spreading depolarization. Laser speckle flowmetry consistently showed a reduction in tissue perfusion, and two-photon pO2 microscopy revealed a drop in venous pO2 during the intracranial pressure spikes suggesting increased oxygen extraction fraction, and therefore, worsening supply-demand mismatch. These haemodynamic changes during intracranial pressure spikes were associated with highly reproducible increases in extracellular potassium levels in penumbra. Consistent with the experimental data, a higher rate of intracranial pressure spikes was associated with spreading depolarization clusters in a retrospective series of patients with aneurysmal subarachnoid haemorrhage with strong temporal correspondence. Altogether, our data show that intracranial pressure spikes, even when mild and brief, are capable of triggering spreading depolarizations. Aggressive prevention of intracranial pressure spikes may help reduce spreading depolarization occurrence and improve outcomes after brain injury.

Association Between Spreading Depolarization and Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: Post Hoc Analysis of a Randomized Trial of the Effect of Cilostazol on Delayed Cerebral Ischemia.

BACKGROUND: Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) remains an important problem with a complex pathophysiology. We used data from a single-center randomized trial to assess the effect of a phosphodiesterase inhibitor, cilostazol, in patients with aneurysmal SAH to explore the relationships of DCI with vasospasm, spreading depolarization (SD) and microcirculatory disturbance. METHODS: A post hoc analysis of a single-center, prospective, randomized trial of the effect of cilostazol on DCI and SD after aneurysmal SAH was performed. From all randomized cohorts, patients who underwent both SD monitoring and digital subtraction angiography (DSA) on day 9 ± 2 from onset were included. Cerebral circulation time (CCT), which was divided into proximal CCT and peripheral CCT (as a measure of microcirculatory disturbance), was obtained from DSA. Logistic regression was conducted to determine factors associated with DCI. RESULTS: Complete data were available for 28 of 50 patients. Of the 28 patients, 8 (28.5%) had DCI during the study period. Multivariate analysis indicated a strong association between the number of SDs on the day DSA was performed (i.e., a delayed time point after SAH onset) and DCI (odds ratio 2.064, 95% confidence interval 1.045-4.075, P = 0.037, area under the curve 0.836), whereas the degree of angiographic vasospasm and peripheral CCT were not significant factors for DCI. CONCLUSIONS: There is a strong association between SD and DCI. Our results suggest that SD is an important therapeutic target and a potentially useful biomarker for DCI.

Hounsfield Unit Value of Interpeduncular Cistern Hematomas Can Predict Symptomatic Vasospasm.

Background and Purpose- Symptomatic vasospasm is an important factor that affects the outcomes of aneurysmal subarachnoid hemorrhage. Subarachnoid blood volume can predict symptomatic vasospasm, and we postulated that the blood clot density would also be an important factor involved in such events. The present study aimed to determine the relationship between the incidence of symptomatic vasospasm and the Hounsfield unit (HU) value of the interpeduncular cistern that reflects the density of hematomas. Methods- Data from 323 patients admitted and treated at a single center between 2008 and 2017 within 24 hours of subarachnoid hemorrhage onset were retrospectively analyzed. Initial HU values of the interpeduncular cistern were measured using CT, then correlations with the incidence of symptomatic vasospasm and HU values as well as other variables were assessed. Results- Symptomatic vasospasm developed in 54 (16.7%) of the 323 patients. The incidence of symptomatic vasospasm was low (1.8%, 2/166) for HU <50, but this incidence increased greatly when the HU value exceeded 50 (23.7%, 22/93 for HU >50 to ≤60, and 45.3%, 29/64 for HU >60). The odds ratio for symptomatic vasospasm was 2.0 (95% CI, 1.6-2.4) per 5 HU increase. Symptomatic vasospasm correlated significantly with intraventricular hemorrhage (P=0.05) and with intracerebral hematoma (P=0.046) but even more significantly with the HU value of the interpeduncular cistern (P<0.0001). Conclusions- The HU value of the interpeduncular cistern on initial CT is an accurate and reliable predictor of symptomatic vasospasm.

Temperature elevation in epileptogenic foci exacerbates epileptic discharge through TRPV4 activation.

Physiological brain temperature is an important determinant of brain function, and it is well established that changes in brain temperature dynamically influence hippocampal neuronal activity. We previously demonstrated that the thermosensor TRPV4 is activated at physiological brain temperature in hippocampal neurons thereby controlling neuronal excitability in vitro. Here, we examined whether TRPV4 regulates neuronal excitability through its activation by brain temperature in vivo. We locally cooled the hippocampus using our novel electrical device and demonstrated constitutive TRPV4 activation in normal mouse brain. We generated a model of partial epilepsy by utilizing kindling stimuli in the ventral hippocampus of wild type (WT) or TRPV4-deficient (TRPV4KO) mice and obtained electroencephalograms (EEG). The frequencies of epileptic EEG in WT mice were significantly larger than those in TRPV4KO mice. These results indicate that TRPV4 activation is involved in disease progression of epilepsy. We expected that disease progression would enhance hyperexcitability and lead to hyperthermia in the epileptogenic foci. To confirm this hypothesis, we developed a new device to measure exact brain temperature only in a restricted local area. From the recording results by the new device, we found that the brain temperatures in epileptogenic zones were dramatically elevated compared with normal regions. Furthermore, we demonstrated that the temperature elevation was critical for disease progression. Based on these results, we speculate that brain cooling treatment at epileptogenic foci would effectively suppress epileptic discharges through inhibition of TRPV4. Notably, the cooling treatment drastically suppressed neuronal discharges dependent on the inactivation of TRPV4.

Cerebral hemodynamics associated with fluid-attenuated inversion recovery hyperintense vessels in patients with extracranial carotid artery stenosis.

PURPOSE: Fluid-attenuated inversion recovery hyperintense vessels (FHVs) are linked to sluggish or disordered blood flow. The purpose of this study is to compare FHVs with digital subtraction angiography (DSA) findings and cerebral hemodynamic changes on acetazolamide challenge SPECT and to determine the clinical and imaging metrics associated with FHVs in patients with extracranial carotid artery stenosis (ECAS). METHODS: The subjects were patients with chronic ECAS who underwent carotid artery stenting in our department between March 2011 and October 2018. Relationships of FHVs with age, sex, medical history, cerebral angiographic findings using DSA, and quantitative values of cerebral blood flow (CBF) were examined. The resting CBF (rCBF) and cerebrovascular reactivity (CVR) in the middle cerebral artery territory were measured quantitatively using SPECT with acetazolamide challenge. We used multivariate logistic regression analysis to identify independent predictors of FHVs. RESULTS: Of 173 patients included, 92 (53.2%) had FHVs. Patients with FHVs had more severe stenosis (P < 0.01) and more leptomeningeal collateral vessels (P < 0.01). FHV-positive cases had significantly reduced CVR compared with FHV-negative cases (P < 0.01), although there was no significant difference in rCBF between FHV-positive and FHV-negative cases. Logistic regression analysis showed that ipsilateral rCBF and ipsilateral CVR were significant predictors for FHVs (P < 0.01). CONCLUSION: In patients with ECAS, cerebral hemodynamic metrics, especially ipsilateral rCBF and ipsilateral CVR, are associated with the presence of FHVs.

Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: Experimental-Clinical Disconnect and the Unmet Need.

BACKGROUND: Delayed cerebral ischemia (DCI) is among the most dreaded complications following aneurysmal subarachnoid hemorrhage (SAH). Despite advances in neurocritical care, DCI remains a significant cause of morbidity and mortality, prolonged intensive care unit and hospital stay, and high healthcare costs. Large artery vasospasm has classically been thought to lead to DCI. However, recent failure of clinical trials targeting vasospasm to improve outcomes has underscored the disconnect between large artery vasospasm and DCI. Therefore, interest has shifted onto other potential mechanisms such as microvascular dysfunction and spreading depolarizations. Animal models can be instrumental in dissecting pathophysiology, but clinical relevance can be difficult to establish. METHODS: Here, we performed a systematic review of the literature on animal models of SAH, focusing specifically on DCI and neurological deficits. RESULTS: We find that dog, rabbit and rodent models do not consistently lead to DCI, although some degree of delayed vascular dysfunction is common. Primate models reliably recapitulate delayed neurological deficits and ischemic brain injury; however, ethical issues and cost limit their translational utility. CONCLUSIONS: To facilitate translation, clinically relevant animal models that reproduce the pathophysiology and cardinal features of DCI after SAH are urgently needed.

[Effect of Antithrombotic Drugs Reversal on Geriatric Traumatic Brain Injury].

BACKGROUND: As the aging rate in the traumatic brain injury population increases, the number of patients taking antithrombotic drugs is also expected to increase among the population with traumatic brain injury; however, the utility or risk of reversal of such drugs is unclear. Therefore, we performed a retrospective cohort study of the effect of reversal of antithrombotic drugs on geriatric traumatic brain injury at our hospital. METHODS: The study subjects included 83 patients(65 years or older)with intracranial traumatic lesions or skull fractures who were admitted to our hospital during 2013-2018. According to the hospital's protocol, we performed platelet transfusion in patients taking antiplatelet drugs, prothrombin complex concentrate(PCC)administration in patients taking warfarin and direct oral anticoagulants except dabigatran: factor IX complex before January 2018 and four-factor PCC after February 2018. We administered idarucizumab in the case of dabigatran. Fresh frozen plasma transfusion was additionally performed in operative cases. RESULTS: Twenty-six patients took antithrombotic drugs. There was no significant difference in the ratio of talk and deteriorate, favorable outcome(Glasgow Outcome Scale: good recovery+moderate disability), and hospitalization period between the non-antithrombotic and antithrombotic administration groups involving reversal. The timing of antithrombotic drug resumption varied, but no major embolic event occurred during the follow-up period. CONCLUSION: This study suggests that reversal of antithrombotic drugs in geriatric traumatic brain injury may contribute to suppression of talk and deteriorate and lead to more favorable outcomes. As there are also contradictory reports about the utility of reversal, additional studies should be performed for confirmation.

Cilostazol decreases duration of spreading depolarization and spreading ischemia after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Traditionally, angiographic vasospasm (aVS) has been thought to cause delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). However, successful treatment of aVS alone does not result in improved neurological outcome. Therefore, there may be other potential causes of poor neurological outcome, including spreading depolarization (SD). A recent study showed beneficial effects of cilostazol on DCI and neurological outcome. The present prospective clinical trial and experimental study focused on effects of cilostazol on SDs. METHODS: Fifty aSAH patients were treated with clip ligation and randomly assigned to a cilostazol (n = 23) or control group (n = 27). Effects of cilostazol on DCI, aVS, and SDs, measured with subdural electrodes, were examined. The effect of cilostazol on SD-induced perfusion deficits (spreading ischemia) was assessed in an aSAH-mimicking model. RESULTS: There was a trend for less DCI in the cilostazol group, but it did not reach our threshold for statistical significance (13.0% vs 40.0%, odds ratio = 0.266, 95% confidence interval [CI] = 0.059-1.192, p = 0.084). However, the total SD-induced depression duration per recording day (22.2 vs 30.2 minutes, ß = -251.905, 95% CI = -488.458 to -15.356, p = 0.043) and the occurrence of isoelectric SDs (0 vs 4 patients, ß = -0.916, 95% CI = -1.746 to -0.085, p = 0.037) were significantly lower in the cilostazol group. In rats, cilostazol significantly shortened SD-induced spreading ischemia compared to vehicle (Student t test, difference = 30.2, 95% CI = 5.3-55.1, p = 0.020). INTERPRETATION: Repair of the neurovascular response to SDs by cilostazol, as demonstrated in the aSAH-mimicking model, may be a promising therapy to control DCI. Ann Neurol 2018;84:873-885.

[Predictive Factors of Intracranial Pressure Elevation in Patients with Severe Acute Subdural Hematoma].

INTRODUCTION: Elevated intracranial pressure(ICP)can cause secondary brain injury after severe traumatic brain injury(TBI), and ICP is the key factor that determines the outcome. Therefore, prediction of elevation of ICP during the course of the injury would allow for more effective care of patients with severe TBI. In this study, we investigated predictive factors for elevation of ICP in patients with severe acute subdural hematoma(ASDH). METHODS: Twenty patients with severe isolated ASDH were admitted to our hospital between January 2009 and April 2016. The patients were divided into two groups with a maximum ICP of ≥20mmHg(elevated ICP group)and <20mmHg(normal ICP group). Age, mechanism of injury, Glasgow Coma Scale score on admission, initial head computed tomography findings, vital signs, serological and blood gas examinations, initial ICP, and clinical outcome were evaluated. RESULTS: The elevated ICP group had significantly higher initial ICP(5.0±3.1 vs. 30±22.4mmHg, p<0.01), arterial oxygen pressure(151.2±68.3 vs. 314.2±197.1mmHg, p<0.05), and activated partial thromboplastin time(APTT;28.17±3.1 vs. 35.96±8.0, p<0.05)at admission, and significantly lower fibrinogen level(273.3±65.1 vs. 188.1±82.4mg/dL, p<0.05)and favorable outcome rate(p<0.01). CONCLUSIONS: Our results show that high initial ICP, APTT, and arterial oxygen and low fibrinogen levels are associated with ICP elevation in patients with severe ASDH. These factors might be useful for the indication of therapeutic methods such as decompressive craniectomy.

Differential temperature sensitivity of synaptic and firing processes in a neural mass model of epileptic discharges explains heterogeneous response of experimental epilepsy to focal brain cooling.

Experiments with drug-induced epilepsy in rat brains and epileptic human brain region reveal that focal cooling can suppress epileptic discharges without affecting the brain's normal neurological function. Findings suggest a viable treatment for intractable epilepsy cases via an implantable cooling device. However, precise mechanisms by which cooling suppresses epileptic discharges are still not clearly understood. Cooling experiments in vitro presented evidence of reduction in neurotransmitter release from presynaptic terminals and loss of dendritic spines at post-synaptic terminals offering a possible synaptic mechanism. We show that termination of epileptic discharges is possible by introducing a homogeneous temperature factor in a neural mass model which attenuates the post-synaptic impulse responses of the neuronal populations. This result however may be expected since such attenuation leads to reduced post-synaptic potential and when the effect on inhibitory interneurons is less than on excitatory interneurons, frequency of firing of pyramidal cells is consequently reduced. While this is observed in cooling experiments in vitro, experiments in vivo exhibit persistent discharges during cooling but suppressed in magnitude. This leads us to conjecture that reduction in the frequency of discharges may be compensated through intrinsic excitability mechanisms. Such compensatory mechanism is modelled using a reciprocal temperature factor in the firing response function in the neural mass model. We demonstrate that the complete model can reproduce attenuation of both magnitude and frequency of epileptic discharges during cooling. The compensatory mechanism suggests that cooling lowers the average and the variance of the distribution of threshold potential of firing across the population. Bifurcation study with respect to the temperature parameters of the model reveals how heterogeneous response of epileptic discharges to cooling (termination or suppression only) is exhibited. Possibility of differential temperature effects on post-synaptic potential generation of different populations is also explored.

Cerebral infarction associated with benign mucin-producing adenomyosis: report of two cases.

BACKGROUND: Cerebral infarction associated with a malignant tumor is widely recognized as Trousseau syndrome. In contrast, few cases of cerebral infarction associated with benign tumors have been reported. We present two cases of embolic stroke that seemed to be caused by mucin-producing adenomyosis. CASE PRESENTATION: The patients were women aged 42 and 50 years old. Both patients developed right hemiparesis and aphasia, and cerebral infarctions were detected in the left cerebral hemisphere. There were no other abnormal findings, except for elevation of CA125 and D-dimer. Trousseau syndrome was suspected in both cases, but whole body examinations did not reveal any malignant tumors. However, uterine adenomyosis was detected in both patients. CONCLUSIONS: From our findings and a review of the literature, both mucin-producing malignant tumors and mucin-producing benign tumors such as adenomyosis may cause hypercoagulability and cerebral infarction. This mechanism should be considered in a case of a young to middle-aged woman with embolic stroke of an undetermined origin.

Idiopathic basal ganglia calcification associated with cerebral micro-infarcts: a case report.

BACKGROUND: Idiopathic basal ganglia calcification (IBGC) is a rare neurodegenerative disorder characterized by symmetric intracranial calcium deposition. We report a patient with IBGC associated with cerebral infarction due to impairment of cerebrovascular reactivity based on single-photon emission computed tomography (SPECT) with acetazolamide challenge. CASE PRESENTATION: A 66-year-old male presented with right conjugate deviation, right hemiparesis and total aphasia due to a convulsive seizure. Brain computed tomography showed symmetric calcifications in the bilateral basal ganglia, thalamus, cerebellar dentate nuclei, which were consistent with IBGC. Diffusion-weighted brain magnetic resonance imaging showed multiple small infarctions in the bilateral cerebral subcortical area. In the search for the cause of cerebral infarction, SPECT with acetazolamide challenge revealed heterogeneous impairment of cerebrovascular reactivity in the whole brain, despite the absence of evidence for steno-occlusive changes in proximal arteries. CONCLUSION: Cerebrovascular insufficiency due to the lack of elasticity caused by microvascular calcification might have been one of the pathophysiological features of IBGC in this case. Thus, vascular calcification may cause cerebrovascular disturbance and could lead to ischemic stroke in patients with IBGC.

A primary extradural malignant rhabdoid tumor at the craniovertebral junction in a 3-year-old boy.

INTRODUCTION: Malignant rhabdoid tumor (MRT) is a highly aggressive childhood neoplasm and mainly presents in kidney and brain. We report the case of a patient with extrarenal extracranial MRT in the craniovertebral junction (CVJ). CASE REPORT: A 3-year-old boy presented with tetraparesis that had rapidly developed for 2 weeks. The tumor was located in the ventral side of the C1 and C2 extradural space and had invaded the lower clivus. The symptom recovered after subtotal resection of the tumor through a lateral approach with removal of bilateral lateral masses at C1 and instrumental occipital-C2 posterior fusion. Definite histological diagnosis of the extradural tumor was difficult; however, a metastatic lesion in the rib showed a proliferation of INI1/SMARCB1-negative spindle and rhabdoid cells, indicating the tumor was MRT. Stereotactic CyberKnife radiotherapy with a marginal dose of 26 Gy contributed to control of local regrowth of the tumor before histopathological confirmation and induction of chemotherapy with ifosfamide, cisplatin, and etoposide. The patient survived for 29 months without local recurrence of the tumor and with independent activity, however then died of multiple metastases. CONCLUSION: Treatment strategies for MRT in the CVJ should include an optimal surgical approach for reduction of tumor volume and stabilization of the spine, followed by high dose chemotherapy. Stereotactic radiotherapy may be useful for local control.

Thrombolysis with rt-PA under Rivaroxaban Anticoagulation in a Hypertensive Rat Model of Intraluminal Middle Cerebral Artery Occlusion.

BACKGROUND: The aim of this study was to assess the risk and the threshold of hemorrhagic transformation (HT) after treatment with recombinant tissue plasminogen activator (rtPA) under the novel oral anticoagulant, rivaroxaban. METHODS: Fifty-three spontaneous hypertensive rats were used in this study. We performed transient middle cerebral artery occlusion for 270 minutes. Placebo, 10 mg/kg or 20 mg/kg rivaroxaban were administered via a stomach tube 180 minutes after induction of ischemia, and rtPA (10 mg/kg) was administered just before reperfusion. Ninety minutes after rivaroxaban administration we measured the rivaroxaban plasma concentration and prothrombin time (PT). HT volume was assessed by hemoglobin spectrophotometry. Additionally, infarct volume, IgG leakage volume, and neurological outcome were assessed. RESULTS: Rivaroxaban plasma concentration and PT increased in a dose dependent manner but were lower than human peak levels after a once-daily dose of 20 mg rivaroxaban. HT volume increased after treatment with 20 mg/kg rivaroxaban compared with placebo treated controls or those treated with 10 mg/kg rivaroxaban (26.5 ± 5.4, 26.8 ± 8.7, and 41.4 ± 12.6 µL in placebo, 10 mg/kg, and 20 mg/kg treated groups, respectively; P < .05). CONCLUSIONS: Our results suggest that even at therapeutic plasma concentrations, rivaroxaban may increase the risk of HT after thrombolysis in some conditions, such as hypertension and/or a prolonged ischemic period.

Effects of focal brain cooling on extracellular concentrations of neurotransmitters in patients with epilepsy.

OBJECTIVE: Brain hypothermia controls epileptic discharge and reduces extracellular concentrations of glutamate (Glu), an excitatory neurotransmitter. We aimed to determine the effects of focal brain cooling (FBC) on levels of γ-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter. The relationship between Glu or GABA concentrations and the severity of epileptic symptoms was also analyzed. METHODS: Patients with intractable epilepsy underwent FBC at lesionectomized (n = 11) or hippocampectomized (n = 8) regions at 15°C for 30 min using custom-made cooling devices. Concentrations of Glu (n = 18) and GABA (n = 12) were measured in extracellular fluid obtained through microdialysis using high-performance liquid chromatography (HPLC). The reduction rate of neurotransmitter levels and its relationship with electrocorticography (ECoG) signal changes in response to FBC were measured. RESULTS: We found no relationship between the concentrations of Glu or GABA and seizure severity. There was a significant decrease in the concentration of Glu to 66.3% of control levels during the cooling period (p = 0.001). This rate of reduction correlated with ECoG power (r2 = 0.68). Cortical and hippocampal GABA levels significantly (p = 0.02) and nonsignificantly decreased to 47.7% and 32.4% of control levels, respectively. However, the rate of this reduction did not correlate with ECoG (r2 = 0.11). SIGNIFICANCE: Although the decrease in hippocampal GABA levels was not significant due to wide variations in its concentration, the levels of cortical GABA and Glu were decreased following FBC. FBC suppresses epileptic discharge and the release of both excitatory and inhibitory neurotransmitters. The reduction in Glu levels further contributes to the reduction in epileptic discharge. However, the reduction in the levels of GABA has no impact on ECoG.

Opening the ventricle during surgery diminishes survival among patients with newly diagnosed glioblastoma treated with carmustine wafers: a multi-center retrospective study.

Carmustine wafers (CW) were approved in Japan for newly diagnosed and recurrent malignant gliomas during 2013. The ventricle is often opened during surgery to achieve maximum resection. While not generally recommended in such situations, CW might be safely achieved by occluding an opened ventricle using gelform or collagen sheets. However, whether CW implantation actually confers a survival benefit for patients who undergo surgery with an open ventricle to treat glioblastoma remains unclear. Clinical, imaging, and survival data were collected in this multicenter retrospective study of 122 consecutive patients with newly diagnosed glioblastoma to determine adverse events and efficacy. Overall, 54 adverse events of all grades developed in 35 (28.6%) patients, with the most common being new seizures (16%). Adverse events did not significantly differ between patients with opened and closed ventricles during surgery. The 10- and 21.7-month, median, progression-free (PFS) and overall survival (OS), respectively did not significantly differ according to resection rates. However, median PFS and OS were significantly longer among patients with closed, than open ventricles (12.8 vs. 7.4 months; p = 0.0039 and 26.9 vs. 18.6 months; p = 0.011, respectively). Implanting CW into the resection cavity during concomitant radiochemotherapy with temozolomide seems to yield better survival rates without increased adverse events. Occlusion of the ventricular opening during surgery might be safe for CW implantation, but less so for treating patients with newly diagnosed glioblastoma.

Safety and Time Course of Drip-and-Ship in Treatment of Acute Ischemic Stroke.

BACKGROUND: The drip-and-ship approach allows intravenous tissue plasminogen activator therapy and adjuvant endovascular treatment in acute ischemic stroke, even in rural areas. Here, we examined the safety and time course of the drip-and-ship approach. METHODS: Fifty consecutive cases treated with the drip-and-ship approach (drip-and-ship group) in June 2009 to March 2016 were retrospectively examined. Changes in mean blood pressure, systemic complications, and neurological complications were compared according to method of transportation. Time courses were compared between drip-and-ship and direct admission groups during the same period. RESULTS: In the drip-and-ship group, 33 and 17 patients were transferred to hospital by ambulance and helicopter, respectively. One patient suffered hemorrhagic infarction during transportation by ambulance. Mean blood pressure change was lower in patients transferred by helicopter than ambulance (<5 mmHg versus 12.2 mmHg, respectively). The mean onset-to-door times in the drip-and-ship and direct admission groups were 71 and 64 minutes, respectively, and mean door-to-needle times were 70 and 47 minutes, respectively (P =.002). Although mean transportation time from the primary stroke hospital to our hospital was 32 minutes, the entry-to-exit time from the primary stroke hospital was 113 minutes. Thereafter, there was an average delay of 100 minutes until reperfusion compared with the direct admission group. CONCLUSIONS: Drip-and-ship was relatively safe in this small series. Transportation by helicopter was less stressful for acute ischemic stroke patients. It is important to reduce door-to-needle time and needle-to-departure time in the primary stroke hospital to minimize the time until treatment in cases of acute ischemic stroke.

[Effect of Platelet Concentrate Transfusion on Prognosis of Patients with Intracerebral Hemorrhage Treated with Anti-Platelet Agents].

BACKGROUND: A recent randomized control study(the PATCH trial)found no beneficial effect of platelet concentrate(PC)transfusion on the prognosis of patients with intracerebral hemorrhage(ICH)treated with anti-platelet agents(APAs). However, the trial excluded surgical cases. In this study, we examined the effect of PC on ICH, including patients who received surgical treatment. METHOD: A retrospective cohort analysis was performed in 23(11 males, 12 females)of 35 patients diagnosed with ICH and treated with APAs between January 2010 and December 2015 at the Department of Neurosurgery, Yamaguchi University Hospital. Twelve patients were excluded due to the use of anticoagulants or replenishment of coagulation factors. RESULTS: PC transfusion was administered in 12 cases(PC group)but not administered in 11(non-PC group). Conservative therapy at admission was used in 7 and 9 cases in the PC and non-PC groups, respectively, and none of these cases showed hematoma enlargement during conservative therapy. Surgical treatment was performed in 6 and 2 patients in the PC and non-PC groups, respectively, and hematoma enlargement occurred postoperatively in one patient in each group. Outcomes at 3 months after onset showed no significant difference between the groups(mRS 0-3:6 vs. 5 cases, p=0.34). Patients who received PC had no serious adverse events during hospitalization. CONCLUSION: In this study, surgery after PC transfusion was performed without any problems. There was no difference in prognosis between patients who did and did not receive PC. These results suggest that surgery can be performed safely after PC transfusion.

Multiple encephalogaleoperiosteal synangiosis for bilateral carotid artery stenosis in a 13-year-old girl: a case report.

INTRODUCTION: Encephalogaleoperiosteal synangiosis (EGS) has been widely used to treat children with moyamoya disease (MMD). We present the first case of successful multiple EGS in a patient with brain ischemic disease who presented with different cerebrovascular findings from MMD. METHODS: A 13-year-old girl had an increased frequency of transient ischemic attacks that affected her right extremities. Digital subtraction angiography showed tapering of the internal carotid artery (ICA). The anterior cerebral artery (ACA) and middle cerebral artery (MCA) were visible on vertebral angiogram, but not on carotid angiogram. The intact circle of Willis and lack of hypervascularity of the lenticulostriate arteries were observed. Decreased regional cerebral blood flow (CBF) in the bilateral ACA and MCA territories quantified by (123)I-N-isopropyl-p-iodoamphetamine-single photon emission computed tomography indicated the need for extracranial-intracranial bypass surgery. Multiple EGS procedures were performed instead of direct anastomosis, which is the standard procedure for intracranial ICA stenosis, because the space for the craniotomy was limited by transdural anastomosis. RESULTS: Despite the fact that the diagnosis of MMD was questionable, the hemispheres were well vascularized, and the neurology and CBF improved postoperatively. CONCLUSION: The preserved circle of Willis and lack of moyamoya vessels were inconsistent with the features of MMD. However, childhood onset, bilateralness, chronic intracranial ICA stenosis, and transdural anastomosis indicated the same underling pathogenicity as MMD. It is hypothesized that ICA stenosis occurred immediately proximal to the posterior communicating artery in this case. This would have produced the atypical finding of the remaining circle of Willis without growth of the basal moyamoya vessels.

Effects of Brain Temperature on Cerebrovascular Autoregulation During the Acute Stage of Severe Traumatic Brain Injury.

The pressure reactivity index (PRx) is calculated as a moving correlation coefficient between intracranial pressure (ICP) and mean arterial blood pressure (MABP), and this analytical value is viewed as reflecting a vasomotor response to MABP variability. At present, the factors influencing the PRx value during the acute stage of traumatic brain injury (TBI) are not known. We observed significant cases where changes in the calculated value of PRx seemed to be influenced by changes in brain temperature during the course of acute stage TBI. In one case, a patient was treated for 72 h with therapeutic brain hypothermia after a decompressive hemicraniectomy. During the hypothermic condition, the mean value of PRx was -0.019; however, after gradual rewarming, the value of PRx increased drastically, and the mean value during the rewarming period, when the brain temperature exceeded 35 °C, was 0.331. Similarly, in another case where the patient underwent therapeutic brain hypothermia, the PRx showed a mean value of -0.038 during the hypothermic condition, and a mean value of 0.052 during the rewarming period. In both cases, a trend toward a negative correlation between ICP and MABP during brain hypothermia shifted to a positive correlation upon rewarming.