An uncovered risk factor of sonothrombolysis: Substantial fluctuation of ultrasound transmittance through the human skull.

Sonothrombolysis is one of the most feasible methods for enhancing clot lysis with a recombinant tissue plasminogen activator (rt-PA) in cases of acute ischemic strokes. For safe and efficient clinical practices of sonothrombolysis, accurate estimation of ultrasound transmittance through the human skull is critical. Previously, we reported substantial and periodic fluctuation of ultrasound transmittance through a bone-phantom plate following changes to ultrasound frequency, the thickness of the bone-phantom plate, and the distance between a transducer and the bone-phantom plate. In the present study, we clarify the transmittance behavior of medium-frequency ultrasound (from 400kHz to 600kHz) through the human skull, and examine reduction of the transmittance fluctuation. For the study, we measured transmittance of sinusoidal ultrasound waves at 400kHz, 500kHz, and 600kHz at 13 temple spots on 3 human skulls by changing the distance between a transducer and the skull bone, and found substantial and periodic fluctuation in the transmittance behaviors for these sinusoidal voltage excitations. Degrees of the fluctuation varied depending on the measurement spots. A fluctuation ratio between the maximum transmittance and the minimum transmittance reached 3 in some spots. This large transmittance fluctuation is considered to be a risk factor for sonothrombolysis therapies. We examined a modulated ultrasound wave to reduce the fluctuation, and succeeded in obtaining considerable reduction. The average fluctuation ratios for 400-kHz, 500-kHz, and 600-kHz waves were 2.38, 2.38, and 2.07, respectively. We successfully reduced the ratio to 1.72 by using a periodic selection of random frequency (PSRF)-type of modulation wave. The thus obtained results indicate that attention to the fluctuation in ultrasound transmittance through the skull is necessary for safe and effective sonothrombolysis therapies, and that modulated ultrasound waves constitute a powerful method for reducing the risk of fluctuation.

An In Vitro Assay for Sonothrombolysis Based on the Spectrophotometric Measurement of Clot Thickness.

OBJECTIVES: For improved thrombolysis therapy based on ultrasound irradiation, researchers and practitioners would strongly benefit from an easy and efficient in vitro assay system of thrombolysis activity involving irradiated ultrasound. For the present study, we designed a new in vitro sonothrombolysis assay system using a sheet-type clot. METHODS: We designed a cell for clot assay, and we confirmed that this clot cell did not significantly intervene in the acoustic field. Using human plasma, we made a sheet-type clot in the cell. Clot thicknesses at 100 points along 4 directions were measured photometrically at a rate of approximately 4 points/s. RESULTS: The sonothrombolysis effects at 13 levels of ultrasonic intensity were obtained with only one sheet-type clot. With this method, we used a clinically oriented probe at 0.7 and 0.3 W/cm2 to confirm that sonothrombolysis took place. CONCLUSIONS: We successfully established a new, easy, and efficient method for conducting in vitro sonothrombolysis assays. This method involves little intervention of either ultrasound reflection or standing waves in the clot cell. We believe that this new assay method is very useful for fundamental analyses of ultrasound's thrombolysis effects.

Early initiation of steroid pulse therapy for neuromyelitis optica in an emergency room setting.

Case: A 40-year-old man presented to the emergency room with visual impairment, dysesthesia of lower legs, and urinary retention. Two days before admission, he was consulted to the neurology department due to bilateral optic neuritis and scheduled the magnetic resonance imaging of spine. However, the urinary retention deteriorated acutely and he came to the emergency room. On arrival, the plain magnetic resonance image of his spine showed diffuse hyperintensity signals of the spinal cord in T2-weighted images. He was diagnosed with neuromyelitis optica and steroid pulse therapy was initiated. Outcome: We began treatment immediately in the emergency room, cooperating with the neurology team. After admission, plasmapheresis was added for his fluctuating symptoms. On hospital day 7, he was discharged without complication. Conclusion: It is important to understand the various clinical manifestations of neuromyelitis optica. In emergency settings, immediate steroid therapy is necessary for better outcomes.

Substantial fluctuation of acoustic intensity transmittance through a bone-phantom plate and its equalization by modulation of ultrasound frequency.

For safe and efficient sonothrombolysis therapies, accurate estimation of ultrasound transmittance through the human skull is essential. The present study clarifies uncertainty surrounding this transmittance and experimentally verifies the equalization of transmittance through the modulation of ultrasound frequency. By changing three factors (ultrasound frequency, the thickness of a bone-phantom plate, and the distance between a transducer and a bone-phantom plate), we measured the intensity of ultrasound passing through the plate. Two activating methods, sinusoidal waves at 500 kHz and modulated waves, were compared. When we changed (1) the distance between a transducer and a bone-phantom plate and (2) the thickness of the bone-phantom plate, ultrasound transmittance through the plates substantially fluctuated. The substantial fluctuation in transmittance was observed also for a cut piece of human temporal skull bone. This fluctuation significantly declined for the modulated wave. In conclusion, modulation of ultrasound frequency can equalize the transmittance with an approximately 30-65% fluctuation drop and an approximately 40% fluctuation drop for a bone-phantom plate and for a cut piece of skull bone, respectively. By using modulated waves, we can develop safer and more effective sonothrombolysis therapies.

Combined surgical and endovascular treatment of complex cerebrovascular diseases in the hybrid operating room.

BACKGROUND: Although most neurovascular diseases can be treated either by microsurgical or endovascular means, a subset of patients may require a combined approach. Patient transfer from the operating room (OR) to the angiosuite has been a fundamental drawback of this type of approach. OBJECTIVE: The purpose of this study is to report our clinical experience performing combined surgical and endovascular procedures for neurovascular diseases in the hybrid OR. METHODS: 29 patients with neurovascular diseases underwent combined endovascular and surgical procedures in a single session: 16 were scheduled combined treatment and 13 were emergency combined procedures. Of the emergency cases, three were rescue surgeries after endovascular complications. Three patients had ruptured intracranial aneurysms, eight had unruptured intracranial aneurysms, eight had arteriovenous malformations and eight had arteriovenous fistulae; two patients had either a spinal tumor or dural arteriovenous fistulae. RESULTS: All combined procedures were performed in a single session without changing the patient's surgical position. In cases of ruptured arteriovenous malformations or aneurysms with hematoma, an emergency embolization was performed to assist the surgical procedure. Combined superficial temporal artery-middle cerebral artery (STA-MCA) bypass followed by endovascular parent artery trapping were successfully performed for complex large or giant aneurysms. There were two periprocedural ischemic complications. Of the three patients who underwent surgical rescue after endovascular complications, two remained intact and one died despite immediate surgical procedures. CONCLUSION: A combined endovascular and surgical approach conducted in a hybrid OR provides a new strategy for the treatment of complex neurovascular diseases.

[Current clinical trends in brain trauma--Japan Neurotrauma Databank].

Traumatic brain injury is one of the subjects that always arouse intense attention from emergency medicine. In the latter half of the 1960s, death by traffic accidents had drastically increased in Japan and, this period was called "the age of traffic war". Traumatic brain injury was considered to be one of the major causes of traffic death, and the need for neurosurgeons was widely recognized. It should be kept in mind that such a social condition acted as a trigger for the foundation of the Japan Society of Neurotraumatology (JSNT) in 1978. The 1970s were also remarkable because CT scan brought about radical changes in the diagnosis and management of brain diseases. Since the 1970s, CT scan has been rapidly and constantly advancing and is now considered an essential and reliable diagnostic technique, even in emergency medicine. In 1998, the Japan Neurotrauma Data Bank Committee (JNTDB) was established as a part of the JSNT. The aim of this committee is to conduct an epidemiologic research on the epidemiology of traumatic brain injuries in Japan. After conducting a pilot study in 1997, a nationwide investigation was conducted for 3 years from 1998 to 2001, at 10 emergency medical centers. The investigation is now referred to as "Project 1998". Subsequently, Project 2004 was performed over a period of 2 years, from 2004 to 2006, at 19 emergency medical centers. In April 2009, we initiated another investigation called Project 2009 at 23 emergency medical centers and it is planned to be completed in 2011. In 2000, JNST released the first version of the Guideline for Severe Brain Injury and aroused social attention widely. In 2006, the revised version was issued as the Guideline for Severe Brain Injury 2nd version. Since that we have been reviewing the guideline and are currently preparing for the 3rd version. This time, we report on actual incidences of traumatic brain injury in Japan. We have compared 1,002 cases from Project 1998 with other 1,101 cases from Project 2004. We think that it is essential for neurosurgeons engaging in emergency medicine to make a continuous effort to wards accumulating data regarding traumatic brain injury and improving the guideline.

Age-associated increases in poor outcomes after traumatic brain injury: a report from the Japan Neurotrauma Data Bank.

Age is an important factor influencing outcome after severe traumatic brain injury (TBI). In general, the older the victim, the higher the probability of a poor outcome. To investigate the mechanism underlying the link between age and outcome, the data for 797 patients enrolled in the Japan Neurotrauma Data Bank (JNTDB), aged 6 years or older, with Glasgow Coma Scale (GCS) scores of 8 or less on admission or deterioration to that level within 48 h of impact were analyzed. Thirty-eight percent of the patients were between the ages of 40 and 69 years, and 24% of the patients were older than 69 years. Older patients had higher rates of mortality and lower rates of favorable outcome. The frequency of mass lesions which were associated with poorer outcomes significantly increased with age, but regardless of the intracranial lesion type, older patients had poorer outcomes. The GCS score and the occurrence of systemic complications did not differ significantly according to age. Multiple systemic injury was less frequent in older patients. The varied occurrence of intracranial lesion types according to age is likely caused by the disparity between the young and aged brain in the progression of secondary brain injury. Alteration in the pathophysiological response, which is related to the development of secondary brain injury in the aging brain, probably contributes to more severe and irreversible brain damage in older patients, and is thus associated with poor outcomes.

[Mechanism of injury in acute subdural hematoma and diffuse brain injury: analysis of 587 cases in the Japan Neurotrauma Data Bank].

OBJECTIVE: The aim of this study was to analyze and compare the epidemiology of injury mechanisms in acute subdural hematoma (ASDH) with those of diffuse brain injury (DBI) in the Japan Neurotrauma Data Bank. METHODS: Data in the Japan Neurotrauma Data Bank were reviewed for 1,002 patients with severe head injury treated at hospitals between 1998 and 2001 (ASDH, n=246; DBI, n=341). Clinical variables including mechanisms of injury were evaluated. RESULTS: Patients with DBI were significantly younger, with higher incidence of skull fracture, lower Glasgow coma scale score and higher injury severity score than patients with ASDH. Different mechanisms of injury were involved, with ASDH occurring much more commonly in non-vehicular injuries, particularly falls (47.2%), while DBI resulted almost exclusively from vehicular injuries (79.7%). Impact sites on the head with ASDH were more commonly occipital or temporal, while those for DBI were frontal, temporal or facial. Alcohol use was involved in 13.8% of drivers with ASDH and 33.6% of drivers with DBI. CONCLUSION: The principal mechanical damage in DBI was to the brain itself, while primary damage in ASDH occurred to surface blood vessels. ASDH and DBI remain the two worst and most-important types of traumatic brain injury, although the pathogenesis differs with age and mechanism injury.

[Acute subdural hematoma associated with diffuse brain injury: analysis of 526 cases in Japan neurotrauma data bank].

OBJECTIVE: Traumatic acute subdural hematomas (ASDH) in Japan Neurotrauma Data Bank were categorized into focal brain injury (FBI) group and diffuse brain injury (DBI) group, and were analyzed to clarify the pathophysiological and therapeutic aspects of these injuries. METHODS: Data in Japan Neurotrauma Data Bank were reviewed for 1,002 severely head-injured patients treated at hospitals between 1998 and 2001; 526 of these patients had ASDH. ASDH in this data bank were categorized into FBI group and DBI group on the findings of CT scan. The clinical variables in these injuries were evaluated. RESULTS: Of 526 patients with ASDH, 246 (46.8%) were categorized into FBI group, 280, (53.2%) were DBI group. The patients with DBI group were younger, injured in traffic accident, lower Glasgow Coma Scale (GCS), higher Injury Severity Score, poorer outcome, compared to those with FBI group. The patients in DBI group, who underwent decompressive craniectomy and craniotomy, had a significantly better outcome than those who underwent hematoma evacuation via burr hole. There were no relationship between the time from injury to operation and outcome in the patients with DBI group, whereas patients with early surgery in FBI group showed significantly poorer outcome. Hypothermia and the placement of intracranial pressure monitor improved outcome only in patients of DBI group. CONCLUSION: It seems that the pathophysiological and therapeutic aspects of ASDH associated with DBI might differ from that with FBI alone.

Final report of the Japan Neurotrauma Data Bank project 1998-2001: 1,002 cases of traumatic brain injury.

A 4-year study (Japan Neurotrauma Data Bank) of the medical treatment of 1002 cases of traumatic brain injuries in Japan was conducted from 1998 to 2001 at 10 emergency medical centers. Patients with severe head injury were eligible for entry with a Glasgow Coma Scale score of 8 or less at admission. Patients who underwent craniotomy were also included. Children under 5 years old were excluded. An original data sheet with 392 items from multi-focal viewpoints, such as etiology of injury, pre-hospital care, initial treatment including neuro-intensive care unit, and surgical treatment, was created. The results show that the patient's age and mechanism of injury are the most important factors in the outcome.

Endovascular operating suite: future directions for treating neurovascular disease.

OBJECT: The purpose of this study was to evaluate initial experiences in a surgical operating room (OR) with a multipurpose angiography unit, which offers integrated neurosurgical and radiological capabilities. METHODS: A specially designed biplane digital subtraction (DS) angiography system was installed in the neurosurgery OR. The new suite, which allows three-dimensional DS angiography with C-arm for computerized tomography and microsurgery capabilities, allows the neurosurgeon to perform a wide range of neurosurgical and endovascular procedures. Three hundred thirty-two procedures were performed in the endovascular OR between November 2003 and March 2005. Patients arriving in the emergency department were transferred to the endovascular OR without delay. The neurovascular team performed diagnostic angiography followed by endovascular interventional procedures or surgery. CONCLUSIONS: The newly designed endovascular OR facilitates safe and systemic treatment of neurovascular disease.