Neuroprotection by marine-derived compound, 11-dehydrosinulariolide, in an in vitro Parkinson's model: a promising candidate for the treatment of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by tremor, rigidity, bradykinesia, and gait impairment. So far, very few pharmacological agents have been isolated or developed that effectively inhibit the progression of PD. However, several studies have demonstrated that inflammatory processes play critical roles in PD. Therefore, anti-inflammatory agents may suppress disease progression in PD. 11-Dehydrosinulariolide was isolated from cultured soft corals. The anti-inflammatory effect of this molecule has been observed through suppression of the expression of two main pro-inflammatory proteins: inducible nitric oxide synthase and cyclooxygenase-2, in lipopolysaccharide-stimulated macrophage cells. We also found that 11-dehydrosinulariolide significantly reduced 6-hydroxydopamine (6-OHDA)-induced cytotoxicity and apoptosis in a human neuroblastoma cell line (SH-SY5Y). The pharmacological activity of this compound has been studied, and it is associated with the inhibition of 6-OHDA-induced activation of caspase-3 and translocation of nuclear factor kappa B. 11-Dehydrosinulariolide increased the activation of survival-signaling phospho-Akt but not phospho-ERK. The neuroprotective effect of 11-dehydrosinulariolide was assessed here using 6-OHDA-treated SH-SY5Y cells, wherein neuroprotection is mediated through regulation of phosphatidylinositol 3-kinase (PI3K). Furthermore, 11-dehydrosinulariolide caused a significant decrease in caspase-3/7 activity in comparison to the 6-OHDA-treated group, indicating that 11-dehydrosinulariolide has neuroprotective properties. We conclude that 11-dehydrosinulariolide is a promising candidate for the treatment of Parkinson's disease through its anti-apoptotic and anti-inflammatory action via PI3K signaling.

Multiple cerebral aneurysms and brain metastasis from primary cardiac myxosarcoma: a case report and literature review.

Primary neoplasms of the heart are rare. Malignant cardiac myxoma, or so-called myxosarcoma, accounts for about 6% of primary malignant cardiac tumors. Cerebral metastasis of malignant cardiac myxoma is extremely rare; only three cases have been reported and two of them included an autopsy study. The case described herein is the first reported brain metastasis combined with multiple cerebral aneurysms originating from primary cardiac myxosarcoma. The true incidence of cerebral myxomatous aneurysm is unknown and the pathogenesis of myxomatous aneurysm formation has not been fully defined. The current hypothesis favors that tumor materials from cardiac myxomas embolize into the vasa vasorum of the peripheral arteries and subsequently prolifere in the vessel wall. This then leads to a weakening of subintimal tissue, such as the internal elastic lamina, with subsequent aneurysm formation. The prognosis of cardiac myxosarcoma is very poor. Although malignancies most likely develop from the mesenchymal cells, they are difficult to treat with any modality (operation, chemotherapy, radiotherapy or transplantation) because these tumors have usually undergone extensive spread by the time the diagnosis is made.

Predictors and outcome of acute symptomatic cerebral infarctions following aneurysmal subarachnoid hemorrhage.

The leading cause of unfavorable outcomes following aneurysmal subarachnoid hemorrhage (SAH) is cerebral infarction. In this 3-year retrospective study, we have retrospectively evaluated 172 hospitalized patients with aneurysmal SAH, and compared those who developed a complicated cerebral infarction with those who did not. In this study, acute symptomatic cerebral infarctions accounted for 22.6% (39/172) of all episodes. Significant statistical analysis between the two patient groups included age at onset, hypertension as the underlying disease, presence of symptomatic vasospasm, mean hospitalization days and Glasgow Outcome Score at the time of discharge. After a minimum 1.5-year follow-up period, the median (interquantile range) Barthel index score was 75 (6-85) for those patients who had cerebral infarctions, and 80 (0-90) for those who had no cerebral infarctions. Multiple logistic regression analysis demonstrated that the presence of symptomatic vasospasm was independently associated with the presence of acute symptomatic cerebral infarctions. The presence of symptomatic vasospasm implies the danger of acute symptomatic cerebral events after aneurysmal SAH. Although our study demonstrates a worse short-term outcome and longer duration of hospitalization in this special group of patients, the functional outcome for patients with cerebral infarction was not inferior to those patients without cerebral infarction after a follow-up of at least 1.5-years.

Systemic and local reactions of a water-soluble copolymer bone on a bony defect of rabbit model.

BACKGROUND: Ostene, a synthetic water-soluble bone hemostatic agent, is commercially available. In the current study, we evaluated the systemic and local effects of this copolymer in a rabbit model. METHODS: Eighteen rabbits underwent creation of a bony defect at right iliac crest. These rabbits were then evenly divided into 3 groups. In group 1, the defect surfaces were treated with bone wax; in group 2, the defect surfaces were treated with Ostene; in group 3, the defect surfaces were not treated with anything. Then, the animals underwent blood examinations, including WBC count, CRP, and ESR at 0, 1, 3, and 6 weeks, and were killed at 6 weeks for histologic examination. Another 6 rabbits (group 4) underwent the same surgical treatment of group 2 animals but had blood examinations of BUN and creatinine. RESULTS: The blood examinations showed that the WBC count, CRP, and ESR of all the animals in the first 3 groups were within normal limits in the postoperative periods. Microscopic examinations demonstrated residual bone wax and fibrotic tissue at the defect surfaces in group 1 animals. However, there was no Ostene at the defect surfaces in group 2 animals. The groups 2 and 3 animals showed no fibrotic tissue at the defect surfaces. The group 4 animals showed normal serum levels of BUN and creatinine in the postoperative periods. CONCLUSION: Ostene is absorbable and induces no systemic inflammation (including acute renal damage) and local inflammation in animal bodies.

Acute thrombosis and recanalization of a ruptured anterior communicating artery aneurysm.

A 35-year-old man sustained a subarachnoid hemorrhage due to the rupture of an anterior communicating artery aneurysm. A second angiogram taken 8 hours later demonstrated that the ruptured aneurysm had thrombosed spontaneously with a small residual aneurysm stump at the neck. CT scans and conventional angiograms taken 2 days later demonstrated recanalization of the aneurysm, which was successfully treated by endovascular coiling. This case differs from previous reports of spontaneously thrombosed ruptured aneurysms because the aneurysm recanalized within 2 days. Thus a thrombosed ruptured aneurysm has the potential for recanalization, and should be considered at risk of further hemorrhage.

Concurrent chemoradiotherapy for primary cervical spinal cord germinoma.

We report a rare case of primary intramedullary germinoma in the cervical spine of a 39-year-old woman without evidence of intracranial or disseminated disease. The germinoma was treated by a biopsy and follow-up concurrent chemoradiotherapy. This is the only reported case of primary spinal cord germinoma for which concurrent chemoradiotherapy was given. Furthermore, this is only the second reported case of histologically documented primary intramedullary cervical spinal cord germinoma. The patient was disease-free and there was near-complete resolution of the pre-operative neurological deficits at the 20-month follow-up examination.

Contralateral acute epidural hematoma after decompressive surgery of acute subdural hematoma: clinical features and outcome.

BACKGROUND: Delayed contralateral epidural hematoma (EDH) after decompressive surgery for acute subdural hematoma (SDH) is uncommon. If unrecognized, this delayed hematoma can cause devastating consequences. We present our experience with this group of patients and discuss the diagnosis and management of this dangerous condition. METHODS: This study included 12 traumatic patients with acute SDH who developed delayed contralateral EDH after acute SDH evacuation. Clinical and radiographic information was obtained through a retrospective review of the medical records and the radiographs. RESULTS: There were seven males and five females. Nine patients had severe head injury (Glasgow Coma Scale {GCS} score < or = 8). Ten patients underwent acute SDH evacuation within 4 hours after the trauma. Intraoperative brain swelling during SDH evacuation was noted in 10 patients. A skull fracture at the site of the EDH on computed tomography (CT) was noted only in 10 patients. However, a skull fracture overlying the EDH was found during EDH evacuation in all patients. Only three patients with less severe head injury (GCS > 8) had good recovery. Other patients with severe head injury (GCS < or = 8) had poor outcome. CONCLUSIONS: Severe head injury, a skull fracture contralateral to the original hematoma, intraoperative brain protrusion, and a poor outcome are typical clinical findings in this disorder. In patients with acute SDH and a contralateral skull fracture, immediate postoperative CT scan is indicated to evaluate this rare but potentially lethal complication. According to the findings of the postoperative CT scan, the neurosurgeon can make an appropriate strategy of treatment promptly. Early detection and prompt treatment may improve the poor outcome in this group of patients.

Multiloculated pyogenic brain abscess: experience in 25 patients.

OBJECTIVE: To report our experience in treating multiloculated pyogenic brain abscess and determine whether there are differences in the bacteriology, predisposing factors, treatment choices, and outcomes between multiloculated and uniloculated brain abscesses. METHODS: We studied clinical data collected during a 16-year period from 124 patients with pyogenic brain abscess, including 25 cases of multiloculated abscess. RESULTS: The incidence of multiloculated brain abscess was 20%. In these 25 patients, hematogenous spread from a remote infectious focus was the most common cause of infection, as it was for the cases of uniloculated abscess. Headache and hemiparesis were the most common symptoms in patients with multiloculated abscess. In patients with uniloculated abscess, fever was the most common symptom. Viridans streptococci were the most commonly isolated pathogens. Bacteroides fragilis was the most common anaerobe in multiloculated abscess, and aerobic gram-negative bacilli were the most common pathogens in patients with uniloculated abscess. Of the patients with multiloculated abscess, 21 were treated surgically and 4 were treated with antibiotics only. Overall, eight patients (38%) needed another operation because of abscess recurrence after the initial operation. In uniloculated abscess, the rate of abscess recurrence after initial surgery was 13.1%. Mortality was 16% in multiloculated abscess and 17.1% in uniloculated abscess. CONCLUSION: Multiloculated abscesses accounted for 20% of our patients with pyogenic brain abscess. Excision seems to be the more appropriate surgical choice in multiloculated abscess. Prognosis for patients with multiloculated abscess can be as good as that for patients with uniloculated abscess. However, clinicians must carefully monitor these patients because the possibility of recurrence after surgery is significantly higher in patients with multiloculated abscess than in those with uniloculated abscess.

Clinical features and predictive factors of intraventricular rupture in patients who have bacterial brain abscesses.

BACKGROUND: Intraventricular rupture of brain abscesses (IVRBA) remains a catastrophic and fatal complication of bacterial brain abscess (BBA). However, no information has been reported about the risk factors that are predictive of intraventricular rupture. METHODS: This study was undertaken to determine the potential risk factors that are predictive of intraventricular ruptures in patients with BBA but without intraventricular rupture when arriving at the hospital. A comparison is also made between patients who already have IVRBA at the time of admission (initial IVRBA) and those who have the episode during hospitalisation (subsequent IVRBA). RESULTS: 62 patients, including 45 who had initial IVRBA and 17 who had subsequent IVRBA, were examined. Stepwise logistic regression analysis showed that the adjusted risk of intraventricular rupture during hospitalisation for patients with multiloculated brain abscesses had an odds ratio (OR) of 4.2 (95% confidence interval (CI) 1.24 to 14.3; p = 0.02) compared with those without multiloculated brain abscesses (referent); a reduction of 1 mm in the distance between the ventricle and brain abscesses would increase the rupture rate by 10% (p = 0.006, OR 0.9, 95% CI 0.83 to 0.97). CONCLUSION: This study shows that if the abscess is deep seated, multiloculated and close to the ventricle wall, a reduction of 1 mm in the distance between the ventricle and brain abscesses will increase the rupture rate by 10%. Despite aggressive medical and surgical management shown in this series, many patients continue to progress poorly.

Lumbosacral spinal subdural hematoma following burr hole craniotomy: case report and literature review.

Spinal subdural hematoma is a rare complication of cranial surgery. This study reports a case of postcraniotomy lumbosacral spinal subdural hematoma in the absence of predisposing factors. A review of the literature is also presented.

The effect of acute smoking on spinal fusion: an experimental study among rabbits.

BACKGROUND: The establishment of an environment to force animals to inspire cigarette smoke is mandatory to study the true effects of smoking. This model has been used to study long-bone healing but has not yet been used to study spinal fusion. METHODS: Forty male rabbits were divided into four equal groups. All the animals underwent bilateral intertransverse-process fusion at L5-L6 using the 1995 fusion model of Boden et al. The first (C8-week) group did not undergo cigarette smoke inhalation and individual rabbits were killed at 8 weeks; the second (S8-week) group underwent intermittent cigarette smoke inhalation and individual rabbits were killed at 8 weeks; the third (C6-week) group did not undergo cigarette smoke inhalation, and animals were killed at 6 weeks; and the fourth (S6-week) group underwent intermittent smoke inhalation and group-included rabbits were killed at 6 weeks. Subsequent to the animals having been killed, the fusion masses were harvested for a series of studies including manual palpation, biomechanical testing, radiographic examination, and histologic analysis. RESULTS: Six rabbits died shortly after the operation. Of the remaining 34 rabbits, the lumbar spine specimen was harvested for study. Manual palpation, radiographic examination, and histologic analysis of the fusion masses revealed no statistically significant difference in fusion results between the control and the corresponding smoking group killed at either 8 weeks or 6 weeks. Biomechanical testing of the fusion masses also revealed no statistically significant difference in fusion results between the control and the smoking group killed at 8 weeks, although it did indicate that smoking resulted in a 44% decrease in mean flexion stiffness and a 32% decrease in mean extension stiffness among the animals killed at 6 weeks. The former (decrease in flexion stiffness) was statistically significant (p < 0.05). CONCLUSION: The results of the biomechanical testing conducted as a part of the current study demonstrate that acute cigarette smoke inhalation delays but does not prevent the spinal fusion process for rabbits.

Post-neurosurgical nosocomial bacterial meningitis in adults: microbiology, clinical features, and outcomes.

The clinical data of 62 adult patients who suffered post-neurosurgical nosocomial bacterial meningitis, retrospectively collected over a 16-year period, were studied. Cases were divided into two groups based on the date of presentation, the first period being 1986-1993 and the second 1994-2001. Fever and progressive consciousness disturbance were the most consistent clinical features - signs that may also be attributed to other postoperative neurosurgical problems. The common pathogens included Staphylococcus aureus, coagulase negative Staphylococcus, Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii. An increase in polymicrobial infections and multi-antibiotic resistance during the second period was identified. In the first half of the study, mortality was 22%, and in the second half 36%. Adult post-neurosurgical nosocomial bacterial meningitis has become an important clinical problem. The choice of appropriate empirical antibiotics is challenging and must be guided by an awareness of the relative frequency of various pathogens and the increasing incidence of resistant strains. Although high mortality rates may, in part, be related to the primary brain pathology, early diagnosis and the timely use of antibiotics based on antimicrobial susceptibility testing are essential for survival.

Percutaneous vertebroplasty improves pain and physical functioning in elderly osteoporotic vertebral compression fracture patients.

BACKGROUND: Osteoporotic vertebral compression fractures are being recognized increasingly often in the elderly. They frequently cause severe and prolonged back pain and physical decline. Bed rest, narcotic analgesia, and external bracing were the only therapeutic modalities available in the past and had limited success. OBJECTIVE: The purpose of our study was to determine the efficacy of percutaneous vertebroplasty in treating osteoporotic vertebral compression fractures in the elderly. METHODS: Twenty-two vertebroplasties were performed in 16 elderly patients. Pain relief, medication requirements, and physical functioning were evaluated before and 24 h and 6 months after vertebroplasty. RESULTS: There was 81% improvement in pain intensity 24 h after operation, and 94% improvement was noted at the 6-month follow-up checkup. Physical functioning improved 69% 24 h after vertebroplasty and 63% 6 months later. Medication requirements also decreased in 75% of the patients. CONCLUSION: Percutaneous vertebroplasty for osteoporotic vertebral compression fractures is safe and effective and should not be withheld from the elderly.

Single versus separate registration for computer-assisted lumbar pedicle screw placement.

STUDY DESIGN: This is a retrospective study conducted to evaluate the efficacy of single versus separate registration in assessing the pedicle screw accuracy in the computer-assisted lumbar spinal instrumentation. OBJECTIVES: To see if separate registration reduced lumbar pedicle screw misplacement. SUMMARY OF BACKGROUND DATA: Computer-assisted spinal instrumentation has been shown to improve pedicle screw installation accuracy, but 2.7% to 8% of screws still perforate the pedicular cortex. Suspected causes include differences in lumbar lordosis between preoperative CT scans and surgery. METHODS: Postoperative radiographs and CT scans were used to assess the accuracy of pedicle screw placement in 47 adult patients following computer-assisted lumbar spinal instrumentation. Twenty-two patients underwent single registration at one level, while the other 25 underwent registration at each level. RESULTS: The time required for a registration procedure on one level was 6 to 8 minutes, while the time required for application of a pedicle screw using computer-assisted techniques was an additional 6 to 10 minutes. The total number of screw placements was 118 in the single registration group and 130 in the separate registration group. In the former group, 85 (72%) pedicle screw placements were categorized as good, 28 (24%) were fair, and 5 (4%) were poor. All five poorly placed screws were placed in the lower lumbar or upper sacral spine with high mobility, and at levels without registration, with one causing root injury. In the latter group, 117 (90%) pedicle screw placements were good and 13 (10%) were fair. The difference in placement was found to be statistically significant (chi2, P = 0.0003). CONCLUSION.: Before the intraoperative real-time CT imaging is widely used, separate registration at each instrumented level during traditional computer-assisted lumbar spinal instrumentation is necessary to enhance the accuracy of screw placement.

Infection of cerebrospinal fluid shunts: causative pathogens, clinical features, and outcomes.

This retrospective chart review describes the clinical features, pathogens, and outcomes of 46 patients with cerebrospinal fluid (CSF) shunt infections collected over 16 years. The overall CSF shunt infection rate was 2.1%, broken down into 1.7 and 9.3% in adult and pediatric groups, respectively. Fever and progressive consciousness disturbance were the most clinical features in the adult patient group, whereas disturbance of consciousness and abdominal symptoms and signs were the two most common clinical features in the pediatric patient group. The most frequently isolated microorganisms were of the Staphylococcus spp., including Staphylococcus aureus and coagulase negative Staphylococcus, which accounted for 47% of the episodes. Furthermore, increases in polymicrobial and Gram-negative bacilli infections were observed in our study. Due to the high proportion of oxacillin-resistant Staphylococcus spp. and polymicrobial infections, we recommend initial empirical antibiotics with both vancomycin and a third-generation cephalosporin for cases in which the causative bacteria has not been identified or for which the results of antimicrobial susceptibility tests are not available. For patients who develop smoldering fevers, progressive disturbed consciousness, seizures, or abdominal fullness after ventriculoperitoneal shunt procedures, CSF shunt infections should be suspected. Although some infections have been managed successfully with antimicrobial therapy alone, the timely use of appropriate antibiotics according to antimicrobial susceptibility testing and the removal of the shunt apparatus are essential for successful treatment.

Shunt surgery for hydrocephalus complicating cryptococcal meningitis in human immunodeficiency virus-negative patients.

From 1988 through 2001, 27 patients with cryptococcal meningitis who had hydrocephalus were identified and were treated by placement of ventriculoperitoneal (VP) shunts. To assess the predictive value of the response to VP shunts in terms of outcome in these patients, univariate analysis for variables was performed. Poor outcome was associated with a Glasgow Coma Scale score of 48 h (P=.02). Use of VP shunts did not result in a good response or outcome in comatose patients. Thus, any delay in the diagnosis or treatment of patients with hydrocephalus could cause a deterioration of consciousness and is associated with poor outcome.

Multiloculated pyogenic brain abscess: experience in 25 patients.

OBJECTIVE: To report our experience in treating multiloculated pyogenic brain abscess and determine whether there are differences in the bacteriology, predisposing factors, treatment choices, and outcomes between multiloculated and uniloculated brain abscesses. METHODS: We studied clinical data collected during a 16-year period from 124 patients with pyogenic brain abscess, including 25 cases of multiloculated abscess. RESULTS: The incidence of multiloculated brain abscess was 20%. In these 25 patients, hematogenous spread from a remote infectious focus was the most common cause of infection, as it was for the cases of uniloculated abscess. Headache and hemiparesis were the most common symptoms in patients with multiloculated abscess. In patients with uniloculated abscess, fever was the most common symptom. Viridans streptococci were the most commonly isolated pathogens. Bacteroides fragilis was the most common anaerobe in multiloculated abscess, and aerobic gram-negative bacilli were the most common pathogens in patients with uniloculated abscess. Of the patients with multiloculated abscess, 21 were treated surgically and 4 were treated with antibiotics only. Overall, eight patients (38%) needed another operation because of abscess recurrence after the initial operation. In uniloculated abscess, the rate of abscess recurrence after initial surgery was 13.1%. Mortality was 16% in multiloculated abscess and 17.1% in uniloculated abscess. CONCLUSION: Multiloculated abscesses accounted for 20% of our patients with pyogenic brain abscess. Excision seems to be the more appropriate surgical choice in multiloculated abscess. Prognosis for patients with multiloculated abscess can be as good as that for patients with uniloculated abscess. However, clinicians must carefully monitor these patients because the possibility of recurrence after surgery is significantly higher in patients with multiloculated abscess than in those with uniloculated abscess.

Intracranial suppuration: a clinical comparison of subdural empyemas and epidural abscesses.

BACKGROUND: We compared the clinical features and therapeutic outcomes of intracranial suppurations (IEs) caused by sub-dural empyema (SDEs) and epidural abscesses (EAs). METHODS: Twenty-four patients with IE were retrospectively identified at our institution over a period of 14 years. Therapeutic outcomes at 6 months were determined using the Glasgow Outcome Scale. RESULTS: Among them, 15 had SDE and nine had EA with or without SDE. The three most frequently encountered clinical features Included fever (79%), disturbed consciousness(58%), and seizures (54%). Postneurosurgical or posttraumatic states (42%) and complication after meningitis (38%) were the two most common modes of infection. The overall mortality rate was 8% (2/24). However, if mortality and severe neurologic sequelae were included in the poor outcome group, then 29% (7/24) of our patients would be considered treatment failures. CONCLUSION: In this study, SDE commonly arose following bacterial meningitis with a more fulminant course, but no deaths occurred. In contrast, EA commonly has a more Indolent course and is postoperatively or post-traumatically related, and therefore may have a higher mortality rate based on primary brain pathophysiology alone. Inpatients with meningitis or who undergo postneurosurgical procedures and develop fever, progressive disturbed consciousness, seizures, and focal neurologic signs, immediate neuroimaging studies should be per-formed to determine whether IE is present. Early surgical drainage and aggressive antimicrobial therapy are necessary.

Brain abscess caused by aerobic Gram-negative bacilli: clinical features and therapeutic outcomes.

Thirty-three patients (24 males and nine females) with brain abscesses resulting from infection by aerobic Gram-negative bacilli were identified at Kaohsiung Chang Gung Memorial Hospital over a period of 14 years. Of these, 23 cases developed spontaneously, with the remaining ten postneurosurgery. The organisms most frequently involved were Klebsiella (K.) pneumoniae, Pseudomonas aeruginosa, Escherichia coli and Proteus species and included some rare pathogens, such as Salmonella and Enterobacter species, K. oxytoca, Vibrio and Morganella morganii. Apart from one exception, the locations of the abscess were supratentorial. Twenty-four patients presented with a single abscess, while nine revealed multiple abscesses, with 26 treated surgically and seven with antibiotics exclusively. In total, seven patients died, representing an overall mortality rate of 21%. This study demonstrates that brain abscesses associated with neurosurgical procedures are not rare, accounting for 30% of cases in this study, with K. pneumoniae, Proteus and Enterobacter species the most prevalent of the revealed pathogens. Further, Proteus species were the most prevalent pathogens demonstrated for cases of both otogenic and polymicrobial infections. If brain abscesses are diagnosed for diabetic patients or have a gas-forming appearance, a diagnosis of K. pneumoniae infection should be considered, with particular attention paid to detection of other metastatic septic abscesses. In light of the high mortality rate, early treatment is essential to maximize the chances of survival.