To the Editor: We read with great interest the article by Bauer et al1 in which the authors reviewed the records of 71 patients who received a ventriculostomy after severe traumatic brain injury. The authors found that 16 patients (22%) needed permanent cerebrospinal fluid (CSF) diversion (mean time between placement of ventriculostomy and CSF diversion, 18.3 days). They found that predisposing factors for permanent CSF diversion included the need for craniotomy within 48 hours of admission and a history of culture-positive CSF. We agree with these findings and would like to add further comment on this issue. First, according to the authors' method, a shunt is placed if the intracranial pressure climbs or if CSF output remains substantial in the setting described by the authors. Therefore, the decision to shunt or to remove the ventriculostomy is not affected by computed tomography (CT) findings. On the other hand, many other investigators have used the Evans ratio or the frontal horn index measured from CT scans to diagnose hydrocephalus after traumatic brain injury.2,3 We consider the method of Bauer et al1 for deciding whether to shunt to be reasonable, whereas the authors' results cannot be applied to patients who are diagnosed as hydrocephalus with a CT scan or neurological examination, as they described in their Discussion. Additional information from CT findings in the authors' study may provide insights into the elucidation of risk factors for posttraumatic hydrocephalus. Second, Poca et al4 reported that, among 33 patients with ventriculomegaly after traumatic brain injury, ventriculomegaly appeared > 2 months after injury in 10 patients (30.3%). On the other hand, Bauer et al1 found that the mean length of stay was 31 days in 55 patients who did not need CSF diversion. These results indicate that, after discharge, posttraumatic ventriculomegaly might appear in some of the patients who did not receive CSF diversion. Long-term follow-up examinations should be performed. Further studies are required to decide the optimal indication and timing for ventricular shunt for posttraumatic hydrocephalus. Satoru Takeuchi Hiroshi Nawashiro Saitama, Japan
Tumor necrosis factor alpha (TNF-alpha) is expressed in the ischemic brain; however, its precise role is not fully understood. We studied the effect of the dimeric form of the type I soluble TNF receptor linked to polyethylene glycol (TNFbp) on focal cerebral ischemia in mice using a permanent middle cerebral arterial occlusion (MCAO) model. TNFbp was applied topically, intravenously, or intraperitoneally. TNFbp binds and inhibits TNF-alpha. The volume of cortical ischemic lesions was measured by means of 2,3,5-triphenyltetrazolium chloride 24 h after MCAO. TNFbp produced a significant reduction in the cortical infarct volume of vehicle-treated animals (p < 0.001). The reduction in the volume of brain damage was 26% in animals that received 3 mg/kg of TNFbp topically. Further analysis of TNF-alpha inhibition following acute brain ischemia is indicated.
We performed simultaneous measurement of light scattering and absorption due to reduction of cytochrome c oxidase as intrinsic optical signals that are related to morphological characteristics and energy metabolism, respectively, for rat brains after oxygen/glucose deprivation by saline infusion. To detect change in light scattering, we determined the wavelength that was the most insensitive to change in light absorption due to the reduction of cytochrome c oxidase on the basis of multiwavelength analysis of diffuse reflectance data set for each rat. Then the relationships between scattering signal and absorption signals related to the reductions of heme aa3 (605 nm) and CuA (830 nm) in cytochrome c oxidase were examined. Measurements showed that after starting saline infusion, the reduction of heme aa3 started first; thereafter triphasic, large scattering change occurred (200-300 s), during which the reduction of CuA started. Despite such complex behaviors of IOSs, almost linear correlations were seen between the scattering signal and the heme aa3-related absorption signal, while a relatively large animal-to-animal variation was observed in the correlation between the scattering signal and CuA-related absorption signal. Transmission electron microscopic observation revealed that dendritic swelling and mitochondrial deformation occurred in the cortical surface tissue after the triphasic scattering change. These results suggest that mitochondrial energy failure accompanies morphological alteration in the brain tissue and results in change in light scattering; light scattering will become an important indicator of tissue viability in brain.
Measurement of intrinsic optical signals (IOSs) is attractive for noninvasive, real-time monitoring of tissue viability in brains. We previously performed measurement of IOSs for a rat global ischemic brain model that was made by rapidly removing blood by saline infusion, and observed that after an induction of ischemia, a unique triphasic change in light scattering occurred. This scattering change preceded the reduction of CuA in cytochrome c oxidase which has been shown to correlate with cerebral ATP decrease. In the present study, we examined whether such triphasic scattering change can be observed in the presence of blood in vivo. Transcranial measurement of diffuse reflectance was performed using a broadband tungsten lamp for a rat brain during hypoxia that was induced by N2 inhalation. The reflectance spectral changes in the visible (500-600 nm) and near-infrared (NIR) (650-850 nm) regions were analyzed to monitor changes in hemodynamics and light scattering, respectively. After starting N2 inhalation, reflectance signals in the visible region showed an increase in deoxy-hemoglobin concentration, and about 80 s after full deoxygenation of hemoglobins, reflectance signals in the NIR region showed a similar triphasic change, which was attributable to change in light scattering. Simultaneous measurement of cerebral EEG showed that neuronal activity ceased about 50 s before this triphasic scattering change. These results show that light scattering will become an important indicator of loss of tissue viability in brain; brain tissue can probably be saved if reoxygenation is achieved before starting this scattering change.
Spontaneous spinal epidural hematomas are rare clinical conditions that are sometimes difficult to diagnose. The severity of preoperative neurologic deficits and the interval between the onset of symptoms and surgical decompression mainly determine therapeutic outcome. Thanks to recent advances in
Most of the results regarding hydrogen (H2) therapy for acute cerebral ischemia are derived from in vitro studies and animal experiments, with only a few obtained from human trials with a limited number of subjects. Thus, there is a paucity of information regarding both the beneficial therapeutic effects as well as the side effects of H2 on acute cerebral ischemia in humans. We designed a pilot study to investigate single dose intravenous H2-administration in combination with edaravone, aiming to provide an initial estimate of the possible risks and benefits in select patients presenting with acute ischemic stroke.An open-label, prospective, non-randomized study of intravenous H2-administration was performed in 38 patients hospitalized for acute ischemic stroke. All patients received an H2-enriched intravenous solution in addition to edaravone immediately after the diagnosis of acute ischemic stroke. Acute stroke patients within 3 h of onset received intravenous tissue plasminogen activator (t-PA) (0.6 mg/kg) treatment, and patients receiving t-PA had to commence the administration of the H2-enriched intravenous solution and edaravone before or at the same time as the t-PA was infused.Complications were observed in 2 patients (5.3%), which consisted of diarrhea in 1 patient (2.6%) and cardiac failure in 1 patient (2.6%). No deterioration in laboratory tests, urinary tests, ECG, or chest X-ray radiograms occurred in any patient in this study. In all patients, the mean National Institutes of Health Stroke Scale (NIHSS) scores at baseline, and 7, 30, and 90 d after admission were 8.2 ± 7.5, 5.6 ± 7.1, 4.9 ± 6.5, and 4.5 ± 6.3, respectively. The early recanalization was identified in 4 of 11 patients (36.4%) who received intravenous t-PA administration. Hemorrhagic transformation was observed in 2 patients (18.2%). None of the patients in this study that were treated with t-PA developed symptomatic intracranial hemorrhage.Data from the current study indicate that an H2-enriched intravenous solution is safe for patients with acute cerebral infarction, including patients treated with t-PA.
We performed the simultaneous measurement of intrinsic optical signals (IOSs) related to metabolic activity and cellular and subcellular morphological characteristics, i.e., light scattering for a rat global ischemic brain model made by rapidly removing blood by saline infusion. The signals were measured on the basis of multiwavelength diffuse reflectances in which 605 and 830 nm were used to detect the IOSs that are thought to be dominantly affected by redox changes of heme aa(3) and CuA in cytochrome c oxidase (CcO), respectively. For measuring the scattering signal, the wavelength that was found to be most insensitive to the absorption changes, e.g., approximately 620 nm, was used. The measurements suggested that an increase in the absorption due to reduction of heme aa(3) occurred soon after blood clearance, and this was followed by a large triphasic change in light scattering, during which time a decrease in the absorption due to reduction of CuA occurred. Through the triphasic scattering change, scattering signals increased by 5.2 +/- 1.5% (n = 5), and the increase in light scattering showed significant correlation with both the reflectance intensity changes at 605 and 830 nm. This suggests that morphological changes in cells correlate with reductions of heme aa(3) and CuA. Histological analysis of tissue after the triphasic scattering change showed no alteration in either the nuclei or the cytoskeleton, but electron microscopic observation revealed deformed, enlarged mitochondria and expanded dendrites. These findings suggest that the simultaneous measurement of absorption signals related to the redox changes in the CcO and the scattering signal is useful for monitoring tissue viability in the brain.
Light scattering signal is a potential indicator of tissue viability in brain because cellular and subcellular structural integrity should be associated with cell viability in brain tissue. We previously performed multiwavelength diffuse reflectance measurement for a rat global ischemic brain model and observed a unique triphasic change in light scattering at a certain time after oxygen and glucose deprivation. This triphasic scattering change (TSC) was shown to precede cerebral ATP exhaustion, suggesting that loss of brain tissue viability can be predicted by detecting scattering signal. In the present study, we examined correlation between light scattering signal and tissue reversibility in rat brain in vivo. We performed transcranial diffuse reflectance measurement for rat brain; under spontaneous respiration, hypoxia was induced for the rat by nitrogen gas inhalation and reoxygenation was started at various time points. We observed a TSC, which started at 140 ± 15 s after starting nitrogen gas inhalation (mean ± SD, n=8). When reoxygenation was started before the TSC, all rats survived (n=7), while no rats survived when reoxygenation was started after the TSC (n=8). When reoxygenation was started during the TSC, rats survived probabilistically (n=31). Disability of motor function was not observed for the survived rats. These results indicate that TSC can be used as an indicator of loss of tissue reversibility in brains, providing useful information on the critical time zone for treatment to rescue the brain.
Hemodynamic responses of the brain to hypoxia or ischemia are one of the major interests in neurosurgery and neuroscience. In this study, we performed real-time transcutaneous PA imaging of the rat brain that was exposed to a hypoxic stress and investigated depth-resolved responses of the brain, including the hippocampus. A linear-array 8ch 10-MHz ultrasonic sensor (measurement length, 10 mm) was placed on the shaved scalp. Nanosecond, 570-nm and 595- nm light pulses were used to excite PA signals indicating cerebral blood volume (CBV) and blood deoxygenation, respectively. Under spontaneous respiration, inhalation gas was switched from air to nitrogen, and then reswitched to oxygen, during which real-time PA imaging was performed continuously. High-contrast PA signals were observed from the depth regions corresponding to the scalp, skull, cortex and hippocampus. After starting hypoxia, PA signals at 595 nm increased immediately in both the cortex and hippocampus for about 1.5 min, showing hemoglobin deoxygenation. On the other hand, PA signals at 570 nm coming from these regions did not increase in the early phase but started to increase at about 1.5 min after starting hypoxia, indicating reactive hyperemia to hypoxia. During hypoxia, PA signals coming from the scalp decreased transiently, which is presumably due to compensatory response in the peripheral tissue to preserve blood perfusion in the brain. The reoxygenation caused a gradual recovery of these PA signals. These findings demonstrate the usefulness of PA imaging for real-time, depth-resolved observation of cerebral hemodynamics.
