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
The intracranial dermoid cyst (ICD) can be complicated by rupture and spilling of its contents with potentially dreadful consequences. Head trauma as a predisposing element for this phenomenon is extremely rare. Few reports address the diagnosis and management of trauma-related rupture of ICD. However, there is a pronounced knowledge gap related to the long-term follow-up and the fate of the leaking contents. Here, we present a unique case of traumatic rupture of ICD complicated by continuous fat particle migration within the subarachnoid space with its surgical implications and outcome.A 14-year-old girl had an ICD rupture following a vehicle collision. The cyst was located near the foramen ovale with intra and extradural extensions. Initially, we opted to follow the patient clinically and radiologically as she had no symptoms, and the imaging showed no red flags. Over the next 24 months, the patient remained asymptomatic. However, the sequential brain magnetic resonance imaging revealed significant continuous migration of the fat within the subarachnoid space, with the droplets noticed to increase in the third ventricle. That is considered an alarming sign of potentially serious complications impacting the patient's outcome. Based on the above, the ICD was completely resected through an uncomplicated microsurgical procedure. On follow-up, the patient is well, with no new radiological findings.Trauma-related ruptured ICD may have critical consequences. Persistent migration of dermoid fat can be managed with surgical evacuation as a viable option to prevent those potential complications such as obstructive hydrocephalus, seizures, and meningitis.
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.
Chronic encapsulated intracerebral hematoma (CEIH) is a rare cerebrovascular disease that behaves as a slowly expanding lesion with a gradual onset. It is well established that CEIH is associated with arteriovenous malformations; however, CEIH associated with cavernous malformation (CM) is extremely rare. We herein report a case of CEIH associated with CM, and discuss its pathogenesis. A 12-year-old female was admitted to our hospital because of a one week history of progressive headache and nausea. Brain computed tomography scan and magnetic resonance imaging showed an intracerebral hematoma surrounded by edema in the right frontal lobe. One week later, her headache and nausea worsened, and a brain computed tomography scan revealed the enlargement of hematoma. A right frontal craniotomy was performed. The capsule, mass, and hematoma were totally removed. Histological examination confirmed the diagnosis of CEIH associated with CM. Immunohistochemical analysis revealed increased expression of vascular endothelial growth factor (VEGF) and the VEGF receptor-1 in the endothelium and fibroblasts. Our findings suggest that the activated VEGF pathway might have positively contributed to development of CEIH in the present patient.
Csk (carboxyl-terminalSrc kinase) is a cytoplasmic tyrosine kinase that phosphorylates a critical tyrosine residue in each of the Src family kinases (SFKs) to inhibit their activities. Recently, we identified a transmembrane protein, Cbp (Csk-binding protein), that, when phosphorylated, can recruit Csk to the membrane where the SFKs are located. The Cbp-mediated relocation of Csk to the membrane may play a role in turning off the signaling events initiated by SFKs. To further characterize the Csk-Cbp interaction, we have generated a reconstituted system using soluble, highly purified proteins. Csk and phosphorylated Cbp were co-purified as a large protein complex consisting of at least four Csk·Cbp units. The addition of the phosphorylated, but not nonphosphorylated, Cbp to an in vitro assay stimulated Csk activity toward Src. Csk was also activated by a phosphopeptide containing the tyrosine in Cbp that binds to Csk (Tyr-314). Kinetic analysis revealed that Cbp or the phosphopeptide induced up to a 6-fold reduction in the Km for Src, indicating that the Csk·Cbp complex has a greater affinity for Src than free Csk. These findings suggest that Cbp is involved in the regulation of SFKs not only by relocating Csk to the membrane but also by directly activating Csk. Csk (carboxyl-terminalSrc kinase) is a cytoplasmic tyrosine kinase that phosphorylates a critical tyrosine residue in each of the Src family kinases (SFKs) to inhibit their activities. Recently, we identified a transmembrane protein, Cbp (Csk-binding protein), that, when phosphorylated, can recruit Csk to the membrane where the SFKs are located. The Cbp-mediated relocation of Csk to the membrane may play a role in turning off the signaling events initiated by SFKs. To further characterize the Csk-Cbp interaction, we have generated a reconstituted system using soluble, highly purified proteins. Csk and phosphorylated Cbp were co-purified as a large protein complex consisting of at least four Csk·Cbp units. The addition of the phosphorylated, but not nonphosphorylated, Cbp to an in vitro assay stimulated Csk activity toward Src. Csk was also activated by a phosphopeptide containing the tyrosine in Cbp that binds to Csk (Tyr-314). Kinetic analysis revealed that Cbp or the phosphopeptide induced up to a 6-fold reduction in the Km for Src, indicating that the Csk·Cbp complex has a greater affinity for Src than free Csk. These findings suggest that Cbp is involved in the regulation of SFKs not only by relocating Csk to the membrane but also by directly activating Csk. Src family kinase protein tyrosine kinase polyacrylamide gel electrophoresis glutathione S-transferase Src homology 2/3 carboxyl-terminalSrc kinase Csk-binding protein detergent-insoluble membrane phenylmethylsulfonyl fluoride phosphotyrosine The Src family kinases (SFKs)1 are nonreceptor protein tyrosine kinases (PTKs) that are associated with the inner surface of plasma membrane through their fatty-acylated amino termini (1Brown M.T. Cooper J.A. Biochim. Biophys. Acta. 1996; 1287: 121-149Crossref PubMed Scopus (1079) Google Scholar). SFKs are known to act as molecular switches that regulate a variety of cellular events, including cell growth and division, cell attachment and movement, differentiation, survival, or death (2Thomas S.M. Brugge J.S. Annu. Rev. Cell Dev. Biol. 1997; 13: 513-609Crossref PubMed Scopus (2145) Google Scholar). SFKs are ordinarily present in an inactive state in which the phosphorylated carboxyl-terminal regulatory tyrosine binds to its own SH2 domain (3Xu W. Harrison S.C. Eck M.J. Nature. 1997; 385: 595-602Crossref PubMed Scopus (1242) Google Scholar). In response to an external stimulus, an SFK is activated through dephosphorylation of the carboxyl-terminal tyrosine or through binding to another protein that displaces the intramolecular interaction. The phosphorylation of the regulatory tyrosine of SFK is known to be catalyzed by another PTK, Csk (4Nada S. Okada M. MacAuley A. Cooper J.A. Nakagawa H. Nature. 1991; 351: 69-72Crossref PubMed Scopus (509) Google Scholar, 5Nada S. Yagi T. Takeda H. Tokunaga T. Nakagawa H. Ikawa Y. Okada M. Aizawa S. Cell. 1993; 73: 1125-1135Abstract Full Text PDF PubMed Scopus (360) Google Scholar). In contrast, the phosphatases that activate SFKs have not yet been positively identified, although some candidate molecules have been proposed (6Ponniah S. Wang D.Z. Lim K.L. Pallen C.J. Curr. Biol. 1999; 9: 535-538Abstract Full Text Full Text PDF PubMed Scopus (187) Google Scholar, 7Thomas M.J. Brown E.J. Immunol. Today. 1999; 20: 406-411Abstract Full Text Full Text PDF PubMed Scopus (160) Google Scholar). To understand the regulation of SFKs, it is essential to clarify the regulation mechanism controlling the phosphorylation and dephosphorylation of the critical carboxyl-terminal tyrosine.Csk is a cytoplasmic PTK consisting of an SH3, an SH2, and a kinase domain. Because it lacks an amino-terminal acylation signal and a carboxyl-terminal tyrosine, the regulatory mechanisms of Csk itself have remained unknown. A line of evidence has suggested that the SH2 and/or SH3 domain of Csk is essential for SFK regulation (8Sabe H. Hata A. Okada M. Nakagawa H. Hanafusa H. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 3984-3988Crossref PubMed Scopus (212) Google Scholar, 9Cloutier J.F. Chow L.M. Veillette A. Mol. Cell. Biol. 1995; 15: 5937-5944Crossref PubMed Scopus (56) Google Scholar). The relocation of Csk to the membrane, specifically to regions where SFKs are active, was also observed (10Howell B.W. Cooper J.A. Mol. Cell. Biol. 1994; 14: 5402-5411Crossref PubMed Scopus (123) Google Scholar). In addition, a membrane-targeted form of Csk, containing the myristoylation signal of Src, more actively suppressed SFK functions (11Chow L.M. Fournel M. Davidson D. Veillette A. Nature. 1993; 365: 156-160Crossref PubMed Scopus (236) Google Scholar). These facts suggested the possible existence of a membrane factor that can recruit Csk to the membrane where SFKs are active. The importance of the SH2 domain of Csk further suggested that such a membrane factor might be a tyrosine-phosphorylated protein.To test the hypothesis presented above, we searched for phosphoproteins that can bind tightly to the SH2 domain of Csk and identified a transmembrane phosphoprotein, Cbp (Csk-bindingprotein) (12Kawabuchi M. Satomi Y. Takao T. Shimonishi Y. Nada S. Nagai K. Tarakhovsky A. Okada M. Nature. 2000; 404: 999-1003Crossref PubMed Scopus (458) Google Scholar). Cbp is involved in the membrane localization of Csk as well as in the Csk-mediated inhibition of Src. When phosphorylated on Tyr-314, Cbp can bind to Csk. Within the plasma membrane, Cbp is exclusively localized in the GM1 ganglioside-enriched detergent-insoluble membrane (DIM) domain, which is thought to play an important role in receptor-mediated signaling and where the majority of SFKs are localized (13Simons K. Ikonen E. Nature. 1997; 387: 569-572Crossref PubMed Scopus (8018) Google Scholar, 14Brown D.A. London E. Annu. Rev. Cell Dev. Biol. 1998; 14: 111-136Crossref PubMed Scopus (2542) Google Scholar, 15Anderson R.G. Annu. Rev. Biochem. 1998; 67: 199-225Crossref PubMed Scopus (1715) Google Scholar, 16Xavier R. Brennan T. Li Q. McCormack C. Seed B. Immunity. 1998; 8 (1998): 723-732Abstract Full Text Full Text PDF PubMed Scopus (836) Google Scholar). These findings suggested that Cbp is a novel component of the regulatory mechanism controlling the activity of SFKs. To further evaluate the role of Cbp in the Csk-mediated regulation of SFKs, we examined the effect of Cbp binding on the kinase activity of Csk. The binding of phosphorylated Cbp or a phosphopeptide containing Tyr-314 could substantially elevate the affinity of Csk for Src. The Src family kinases (SFKs)1 are nonreceptor protein tyrosine kinases (PTKs) that are associated with the inner surface of plasma membrane through their fatty-acylated amino termini (1Brown M.T. Cooper J.A. Biochim. Biophys. Acta. 1996; 1287: 121-149Crossref PubMed Scopus (1079) Google Scholar). SFKs are known to act as molecular switches that regulate a variety of cellular events, including cell growth and division, cell attachment and movement, differentiation, survival, or death (2Thomas S.M. Brugge J.S. Annu. Rev. Cell Dev. Biol. 1997; 13: 513-609Crossref PubMed Scopus (2145) Google Scholar). SFKs are ordinarily present in an inactive state in which the phosphorylated carboxyl-terminal regulatory tyrosine binds to its own SH2 domain (3Xu W. Harrison S.C. Eck M.J. Nature. 1997; 385: 595-602Crossref PubMed Scopus (1242) Google Scholar). In response to an external stimulus, an SFK is activated through dephosphorylation of the carboxyl-terminal tyrosine or through binding to another protein that displaces the intramolecular interaction. The phosphorylation of the regulatory tyrosine of SFK is known to be catalyzed by another PTK, Csk (4Nada S. Okada M. MacAuley A. Cooper J.A. Nakagawa H. Nature. 1991; 351: 69-72Crossref PubMed Scopus (509) Google Scholar, 5Nada S. Yagi T. Takeda H. Tokunaga T. Nakagawa H. Ikawa Y. Okada M. Aizawa S. Cell. 1993; 73: 1125-1135Abstract Full Text PDF PubMed Scopus (360) Google Scholar). In contrast, the phosphatases that activate SFKs have not yet been positively identified, although some candidate molecules have been proposed (6Ponniah S. Wang D.Z. Lim K.L. Pallen C.J. Curr. Biol. 1999; 9: 535-538Abstract Full Text Full Text PDF PubMed Scopus (187) Google Scholar, 7Thomas M.J. Brown E.J. Immunol. Today. 1999; 20: 406-411Abstract Full Text Full Text PDF PubMed Scopus (160) Google Scholar). To understand the regulation of SFKs, it is essential to clarify the regulation mechanism controlling the phosphorylation and dephosphorylation of the critical carboxyl-terminal tyrosine. Csk is a cytoplasmic PTK consisting of an SH3, an SH2, and a kinase domain. Because it lacks an amino-terminal acylation signal and a carboxyl-terminal tyrosine, the regulatory mechanisms of Csk itself have remained unknown. A line of evidence has suggested that the SH2 and/or SH3 domain of Csk is essential for SFK regulation (8Sabe H. Hata A. Okada M. Nakagawa H. Hanafusa H. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 3984-3988Crossref PubMed Scopus (212) Google Scholar, 9Cloutier J.F. Chow L.M. Veillette A. Mol. Cell. Biol. 1995; 15: 5937-5944Crossref PubMed Scopus (56) Google Scholar). The relocation of Csk to the membrane, specifically to regions where SFKs are active, was also observed (10Howell B.W. Cooper J.A. Mol. Cell. Biol. 1994; 14: 5402-5411Crossref PubMed Scopus (123) Google Scholar). In addition, a membrane-targeted form of Csk, containing the myristoylation signal of Src, more actively suppressed SFK functions (11Chow L.M. Fournel M. Davidson D. Veillette A. Nature. 1993; 365: 156-160Crossref PubMed Scopus (236) Google Scholar). These facts suggested the possible existence of a membrane factor that can recruit Csk to the membrane where SFKs are active. The importance of the SH2 domain of Csk further suggested that such a membrane factor might be a tyrosine-phosphorylated protein. To test the hypothesis presented above, we searched for phosphoproteins that can bind tightly to the SH2 domain of Csk and identified a transmembrane phosphoprotein, Cbp (Csk-bindingprotein) (12Kawabuchi M. Satomi Y. Takao T. Shimonishi Y. Nada S. Nagai K. Tarakhovsky A. Okada M. Nature. 2000; 404: 999-1003Crossref PubMed Scopus (458) Google Scholar). Cbp is involved in the membrane localization of Csk as well as in the Csk-mediated inhibition of Src. When phosphorylated on Tyr-314, Cbp can bind to Csk. Within the plasma membrane, Cbp is exclusively localized in the GM1 ganglioside-enriched detergent-insoluble membrane (DIM) domain, which is thought to play an important role in receptor-mediated signaling and where the majority of SFKs are localized (13Simons K. Ikonen E. Nature. 1997; 387: 569-572Crossref PubMed Scopus (8018) Google Scholar, 14Brown D.A. London E. Annu. Rev. Cell Dev. Biol. 1998; 14: 111-136Crossref PubMed Scopus (2542) Google Scholar, 15Anderson R.G. Annu. Rev. Biochem. 1998; 67: 199-225Crossref PubMed Scopus (1715) Google Scholar, 16Xavier R. Brennan T. Li Q. McCormack C. Seed B. Immunity. 1998; 8 (1998): 723-732Abstract Full Text Full Text PDF PubMed Scopus (836) Google Scholar). These findings suggested that Cbp is a novel component of the regulatory mechanism controlling the activity of SFKs. To further evaluate the role of Cbp in the Csk-mediated regulation of SFKs, we examined the effect of Cbp binding on the kinase activity of Csk. The binding of phosphorylated Cbp or a phosphopeptide containing Tyr-314 could substantially elevate the affinity of Csk for Src. We thank T. Hirose for production of recombinant Csk in Sf9 cells, S. Aimoto for peptide synthesis, and J. A. Cooper for critical comments.
In this study, we analyzed the causes of problems encountered during aneurysm surgery based on “the study of failure, ” which was originally devised for system engineering. We describe four problematic cases, which were all successfully managed by troubleshooting techniques. The majority of the problems (failures) were caused by the surgeon’s “carelessness and/or decision error”. Large vessel injury during aneurysm dissection is formidable but can be managed by troubleshooting techniques such as micro-suturing or a bypass procedure in the deep operative field. Prompt and secure micro-anastomotic suturing is one of the vital troubleshooting techniques during aneurysm surgery. Personal preparation of micro-suturing instruments and daily off-the-job training are essential to master such troubleshooting procedures.
