Treatment of high numbers of brain metastases with Gamma Knife radiosurgery: a review.

Effectiveness of stereotactic radiosurgery (SRS) has been shown in patients with one to four brain metastases. Work has been done to evaluate the role of SRS alone treatment without whole-brain radiation therapy in patients with more than four metastases. A recent multiinstitutional JLGK 0901 prospective study revealed the class-2 evidence that SRS without whole-brain radiation therapy is an effective treatment for patients up to 10 metastatic lesions. Several retrospective studies exist to show the efficacy and safety of SRS for patients with even more than 10 lesions. However, patient selection is very critical for SRS alone treatment. The PubMed database was searched using combinations of search terms and synonyms for multiple brain metastases, Gamma Knife and SRS published between January 1, 2005 and January 1, 2015 in order to address the effectiveness of Gamma Knife for patients with multiple brain metastases. Good performance status, controlled primary disease, total treated tumor volume of 15 cm(3) or less have been found to be significant predictors for survival among patients with two or more brain lesions. The data suggest that SRS can be used and whole brain radiation therapy can be withheld in selected patients with multiple lesions to avoid acute or chronic adverse effects, especially neurocognitive decline, without causing survival disadvantage. In this review, we assessed the evidence for SRS treatment of patients with multiple brain metastases.

Comparison of two surgical techniques in Chiari Malformation Type 1 Patients: Duraplasty alone vs duraplasty with arachnoid dissection.

OBJECT: Optimal surgical technique to restore the cerebrospinal fluid flow through the foramen magnum remains to be debated in Chiari malformation type 1 (CM-1) patients. METHOD: This study included 46 patients with CM-1 who underwent surgical treatment by one of two methods: posterior fossa bone decompression (BD) with arachnoid preserving duraplasty (Group 1) and BD with duraplasty and arachnoid dissection (Group 2). Complaints of the patient population and neurological findings were assessed with Neck Disability Index (NDI) and Europe Quality of Life 5 Dimensions (EQ-5D) in pre- and postoperative periods. RESULTS: NDI and EQ-5D scores improved in overall patient population and in each individual surgical group. Both groups showed a significant decrease in size of syringomyelia cavity. Complications resulting in recurrent treatments and re-operations occurred in 15% of patients (n = 7); six of them were from Group 2. CONCLUSION: CM-1 patients benefit significantly from surgical treatment. Duraplasty should be included to surgical technique. Avoiding arachnoid dissection may lead to better results regarding complication rates.

Anatomic basis of anterior and posterior instrumentation of the spine: morphometric study.

STUDY DESIGN: A morphometric study of the linear and angular parameters of the spinal vertebra was conducted by computerized tomographic scans and comparison with previous studies in literature. OBJECTIVES: Detailed knowledge of the spinal vertebral morphometry is important for proper instrumentation. The morphologic measurements vary among races. Morphometric studies have been conducted in white populations. This study aims to suggest dimensions for anterior and posterior spinal implants and to improve the instrumentation techniques. MATERIALS AND METHODS: The vertebral pedicles, bodies and intervertebral disc spaces of the subaxial cervical, thoracic and lumbar spine were studied in 48 healthy individuals by computerized tomographic scan methods. The following parameters were studied: pedicle length, pedicle width, transverse pedicle angle (TPA), sagittal pedicle angle, anterior corpus height, posterior corpus height, anterior disc height, middle disc height and posterior disc height. RESULTS: Our results were slightly different compared to previous studies. Individual differences were found in the same subgroups. The transverse pedicle diameter was largest at L5 (14.95 mm) and smallest at C3 (5.1 mm). The pedicle was longest at L5 (19.9 mm) and shortest at T10 (15.7).The TPA was largest at C3 (47.6 degrees ) and smallest at T6 (11.3 degrees ). The vertebral body was largest at L5 (34.9 mm) and smallest at C3 and C5 (15.6 mm). The vertebral body width was largest at L5 (46.6 mm) and smallest at C4 (22 mm). The intervertebral disc space height was largest at L2-3 (10 mm) and smallest at T1-2 (2.85 mm). There were no significant differences between the left and right sides. CONCLUSIONS: In our morphometric study of the spinal vertebrae, we found differences compared to a number of previous morphometric studies performed mainly on a white population. Also, we documented the individual morphometric differences of the same parameters in the same subgroups. These results emphasize the importance of preoperative computed tomography and conventional radiography of each patient in planning a surgical procedure and selecting the appropriate size of the instruments, thus avoiding possible postoperative complication related to implants.

Reconstruction of growing skull fracture with in situ galeal graft duraplasty and porous polyethylene sheet.

OBJECTIVE: In growing skull fractures with large calvarial defects, it is difficult to use autografts for reconstruction and it requires alternative materials for cranioplasty. In this report, the authors describe their experience and introduce reconstruction of the growing skull fractures' defects with a porous polyethylene sheet (Medpor) and with a novel technique of duraplasty with in situ galeal graft, which avoid the potentially risky dissection and exposure of brain tissue. The goal of this study was to clarify effective surgical methods and to provide the rationale for these techniques. METHODS: We performed this technique on 8 patients with large calvarial defects resulting from growing skull fractures. The skin flap was retracted, leaving the galeal plane adherent to the underlying defect. After removing the bony edges and exposing the underlying retracted dural margins, duraplasty was performed by suturing the galeal tissue left in situ on the defect of the dural margins. Bone reconstruction was performed by placing porous polyethylene sheet (Medpor). CONCLUSIONS: Duraplasty with in situ galeal tissue is a simple, safe, and effective technique to reconstruct dural defects in growing skull fracture, which avoids the risky dissection of the brain tissue. Also, by using Medpor, growing skull fractures can be effectively reconstructed with good cosmetic results.

Thymoquinone Enhances the Effect of Gamma Knife in B16-F10 Melanoma Through Inhibition of Phosphorylated STAT3.

BACKGROUND: Patients with brain metastasis from melanoma have a dismal prognosis with poor survival time. Gamma Knife (GK) is an effective treatment to control brain metastasis from melanoma. Thymoquinone (TQ) has emerged as a potential therapeutic option due to its antiproliferative effects on various cancers. The purpose of the study was to assess the effect of GK on B16-F10 melanoma cells in vitro and intracerebral melanoma in vivo, and its synergistic effect in combination with TQ. METHODS: The effects of GK and combination treatment of GK and TQ were studied on B16-F10 melanoma cells by evaluating cytotoxicity with an adenosine triphosphate assay, apoptosis by acridine orange staining, and genotoxicity by comet assay. Western blot analysis was performed to investigate the expression of STAT3, p-STAT3 (Tyr705), JAK2, p-JAK2, caspase-3, Bax, Bcl-2, survivin, and ß-actin. Expression of inflammatory cytokines was assessed by enzyme-linked immunosorbent assay. GK alone and in combination with TQ was assessed in an established intracerebral melanoma tumor in mice. RESULTS: The effects of GK on cytotoxicity, genotoxicity, and apoptosis were enhanced by TQ in B16-F10 melanoma cells. GK induced apoptosis through inhibition of p-STAT3 expression, which in turn regulated pro- and antiapoptotic proteins such as caspase-3, Bax, Bcl-2, and survivin. Adding TQ to GK irradiation further enhanced this apoptotic effect of GK irradiation. GK was shown to reduce the levels of tumor-related inflammatory cytokines in B16-F10 melanoma cells. This effect was more pronounced when TQ was added to GK irradiation. GK with 15 Gy increased the survival of mice with intracerebral melanoma compared with untreated mice. However, despite the additive effect of TQ in addition to GK irradiation on B16-F10 melanoma cells in vitro, TQ did not add any significant survival benefit to GK treatment in mice with intracerebral melanoma. CONCLUSIONS: Our findings suggest that TQ would be a potential therapeutic agent in addition to GK to enhance the antitumor effect of irradiation. Further studies are required to support our findings.

Glioblastoma Stem Cells and Comparison of Isolation Methods.

BACKGROUND: Glioblastoma (GBM) is the most aggressive and the most common primary brain tumor. Over the last few years, studies have identified many genetical and phenotypical molecular situations for developing new treatment modalities in patients with GBM. Nevertheless, main problem for the GBM is radio-chemotherapy resistance and relapse after the surgery. The identification of glioma stem cells and microenvironmental influences has created a paradigm shift in targets of therapy. Current studies have shown that glioma stem cell is responsible for aggressiveness, recurrence and resistance to therapy of GBM. GBM stem cell isolated from human GBM multiforme fresh tissue samples is important both for curative therapeutic options and personalized targeted therapy. The purpose of this study was to determine the most suitable isolation method of GBM stem cells (GSCs). METHODS: Tumor tissue sample was obtained during the surgical resection of lesion in patients with the diagnosis of GBM. Tumor stem cell isolation from tissue was performed in three different ways: 1) GBM cell isolation with trypsin; 2) GBM cell isolation with brain tumor dissociation Kit (BTD Kit); and 3) GBM cell isolation with tumor dissociation enzyme (TDE). RESULTS: We showed that GSCs were isolated from tumor specimen using flow cytometry and immunofluorescence staining. Our study showed that isolation with BTD Kit is the most suitable method to isolate GBM tissue-derived glial tumor stem cells. CONCLUSIONS: The development of alternative personalized therapies targeting brain tumor stem cell is urgently needed. It is important to understand the fundamental mechanisms of driving stem cells. If their life cycle mechanisms can be identified, we can control the growth of GBM.

Combined Spinal Arteriovenous Malformation and Spinal Dysraphism.

BACKGROUND: Spinal vascular malformations as a group are rare, and coexistence of a spinal arteriovenous malformation (AVM) in or around the spinal dysraphism is extremely rare. We report 2 cases of combined spinal dysraphism and vascular malformations of the spinal cord. CASE DESCRIPTION: The first case was an AVM located in a filum terminale lipoma fed by the artery of the filum terminale. This case was managed by multiple endovascular embolizations followed by surgery. The second case was an AVM located in a lumbar lipomyelocele managed by endovascular embolization. These cases illustrate the imaging findings of a rare entity and present the diagnostic and therapeutic challenges. CONCLUSIONS: Endovascular embolization combined with surgical resection is the most commonly used treatment for spinal dysraphism with spinal cord AVM. Careful analysis of spinal angiography is necessary owing to the distorted vascular and surgical anatomy of the region affected by spinal dysraphism.

Thymoquinone Induces Apoptosis in B16-F10 Melanoma Cell Through Inhibition of p-STAT3 and Inhibits Tumor Growth in a Murine Intracerebral Melanoma Model.

BACKGROUND: Prognosis of patients with melanoma brain metastasis is poor despite various chemotherapeutic agents. Researchers focus on finding effective treatment with a low risk of toxicity. Thymoquinone (TQ) has been found to be effective on different types of cancer. However, no data exist regarding the effect of TQ in intracerebral melanoma. The purpose of this study was to assess the effect of TQ in B16-F10 melanoma cell in vitro and intracerebral melanoma in vivo. METHODS: The mechanisms of efficacy were investigated using adenosine triphosphate assay for cytotoxicity, flow cytometry, and acridine orange staining for apoptosis, comet assay for genotoxicity, CM-H2DCF-DA (2,7-dichlorodihydrofluorescein) for intracellular reactive oxygen species (ROS) generation and ELISA methods for inflammatory cytokines. Western blotting was performed to assess the expressions of p-JAK2, p-STAT3, caspase-3, Bax, Bcl-2, and survivin. In addition, the effect of TQ was investigated in a model system of intracerebral melanoma in syngeneic mice. RESULTS: The median survival was improved by TQ in mice with intracerebral melanoma compared with the control group (16 days vs 9 days; P = 0.008). Cytotoxicity was enhanced by TQ in B16-F10 cells in a dose-dependent manner. TQ also induced apoptosis, DNA damage, and increased intracellular ROS. TQ inhibited p-STAT3, resulting in apoptosis through regulation of proapoptotic and antiapoptotic proteins. CONCLUSIONS: Our findings suggest that TQ would be an effective treatment in intracerebral metastatic lesions. This warrants further investigation.

Guidewire Breakage During Cavernous Sinus Sampling: A Rare Complication and Its Treatment.

BACKGROUND: Venous sampling methods are valuable tools for the diagnosis of pituitary adenomas. However, these interventions also have complications, which may complicate the treatment process. CASE DESCRIPTION: A 49-year-old female pituitary adenoma patient with preliminary diagnosis of Cushing disease underwent cavernous sinus sampling (CSS) to delineate the adenoma. The microguidewire broke during the procedure, and the distal part of the microguidewire had to be left within the right cavernous sinus. Eventually, the broken part of the guidewire was removed after the removal of the tumor through an endoscopic endonasal approach. CONCLUSIONS: Current surgical experience on endoscopic skull base surgery allows management of diagnostic complications related to the cavernous sinus, such as safe access to materials which were inadvertently left during CSS, without the necessity for further interventions.

Intracerebral Whipple disease: unusual location and bone destruction. Case report.

Whipple disease is a rare systemic bacterial infection characterized by migratory polyarthralgia and chronic diarrhea. In 5 to 20% of patients with Whipple disease, the infection may present initially with or eventually develop symptoms related to the central nervous system (CNS). Although CNS involvement is a known feature of systemic Whipple disease, intracerebral mass lesions are uncommon. Mass lesions in these cases are typically deep seated and multifocal. Corticosubcortical regions are unusual sites of CNS involvement in cases of Whipple disease. In the present paper, the authors describe the first case of Whipple disease to feature a single corticosubcortical solid frontoparietal mass lesion that displayed homogeneous contrast enhancement on neuroimaging and was associated with bone destruction of the calvaria. Although CNS involvement has been observed in the form of deep-seated mass lesions in cases of systemic Whipple disease, unusual manifestations should be kept in mind during diagnosis and follow-up review in these patients.

Nitric oxide levels in rat cortex, hippocampus, cerebellum, and brainstem after impact acceleration head injury.

Nitric oxide (NO) is a potential mediator of secondary brain injury in the settings of cerebral ischemia and inflammation. Traumatic brain injury (TBI) alters the levels of stable end products of NO metabolism. We investigated these changes and attempted to identify brain regions that were unique with regard to NO production in the period immediately after TBI. The experiment involved assaying nitrite-nitrate concentrations in the rat cortex, cerebellum, hippocampus, and brainstem after impact-acceleration head injury. Five rats comprised the sham-operated (control) group, five sustained mild head injury (MHI), and five sustained severe head injury (SHI). There was a uniform decline in the tissue concentrations of NO metabolites in all four brain regions in both injured groups. There were no significant differences in the concentrations of NO metabolites among the various sites tested in the MHI group; however, there appeared to be a relationship between degree of decline in NO levels and amount of trauma sustained by a given region in the SHI group. In these rats, NO dropped to the lowest levels in the brain region where the direct trauma was most severe. The results suggest that nitrite-nitrate levels in these four brain regions fall below normal in the first 5 min after impact trauma. This decrease may, in part, be related to reduced activity of all nitric oxide synthase isoforms, which would cause a drop in the levels of NO metabolites. We believe that this decline may be linked to, and may even cause, the global decrease in cerebral blood flow that occurs in the initial stages of TBI.

Surgical treatment of intracranial epidermoid tumors.

Intracranial epidermoid tumors are rare, potentially curable, benign lesions that are sometimes associated with perioperative complications, and tend to recur if not completely removed. Histologically benign epidermoid tumors may also develop into highly malignant tumors. This study evaluated on 28 cases of intracranial epidermoid tumor treated over a 13-year period by radical resection with microneurosurgical techniques. The majority of patients underwent computed tomography and/or magnetic resonance imaging within the first 24 hours postoperatively to confirm the results of surgery. Radical surgical resection was achieved in 21 of the 28 cases, and there was no operative mortality. The most common postoperative complication was transient paresis of various cranial nerves. During a mean follow up of 6 years, only one tumor became malignant. Radical surgical resection should be the goal in treating these benign lesions, but if not possible, every effort should be made to minimize the amount of tumor tissue that remains.

Microsurgical anatomy of the cisternal anterior choroidal artery with special emphasis on the preoptic and postoptic subdivisions.

OBJECT: The object of this study was to delineate the microsurgical anatomy of the cisternal segment of the anterior choroidal artery (AChA). The authors also propose a new classification of this segment on the basis of its complicated course within the carotid and crural cisterns in relation to important neurovascular structures, and the site of origin, course, and areas of supply of perforating arteries. METHODS: Thirty cadaveric cerebral hemispheres injected with colored latex were dissected under surgical magnification to view the cisternal segment of the AChA and its perforators. Fiber dissections using the Klingler technique were performed in two additional latex injected hemispheres to follow the penetration points, courses, and terminal areas of supply of perforating branches that arise from the cisternal segment of the AChA. RESULTS: The cisternal segment of the AChA was divided into pre- and postoptic parts that meet at the artery's genu, the most medial extension point of the cisternal segment where the artery makes an abrupt turn after passing under the optic tract. The preoptic part of the AChA extended from its origin at the inferomedial side of the internal carotid artery to the artery's genu, which is commonly located just inferomedial to the initial part of the optic tract. The postoptic part coursed within the crural cistern and extended from the genu to the inferior choroidal point. The genu of the AChA was 8 mm medial to the artery's origin and was located medial to the optic tract in 13% of the hemispheres. The postoptic part was longer than the preoptic part in all hemispheres and had more perforating arteries supplying critical deep structures (preoptic 3.4 per hemisphere vs postoptic 4.6 per hemisphere), and these results were statistically significant (p = 0.01). At the preoptic part, perforating arteries arose from the superolateral portion of the artery and coursed laterally; at the postoptic part, perforators arose from the inferomedial portion of the artery and coursed medially. Perforating arteries from both segments passed most commonly to the optic tract, followed by the anterior segment and apex of uncus in the preoptic part and the cerebral peduncle in the postoptic part. CONCLUSIONS: Both parts of the cisternal segment of the AChA come into surgical view during surgeries for different pathologies in and around the perimesencephalic cisterns. However, attending to the artery's genu and defining pre- and postoptic parts during surgery may help the surgeon locate the origin and eventual course of these perforators, and even estimate the terminal areas of supply of most of the perforating arteries. The proposed classification system can prove helpful in planning any operative procedure along the crural cistern and may reduce the probability of inadvertent injury to perforating branches of the cisternal segment.

Decompressive craniectomy in patients with cerebral infarction due to malignant vasospasm after aneurysmal subarachnoid hemorrhage.

AIM: The authors present their experience and the clinical results in decompressive craniectomy (DC) in patients with vasospasm after aneurysmal subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: Between 2002 and 2010, six patients underwent DC due to cerebral infarct and edema secondary to vasospasm after aneurysmal SAH. Four patients were male, and two were female. The age of patients ranged between 33 and 60 (mean: 47,6 ± 11,4). The follow up period ranged between 12 to 104 months (mean: 47,6 ± 36,6). The SAH grading according World Federation of Neurosurgeons (WFNS) score ranged between 3 to 5. RESULTS: Last documented modified Rankin Score (mRS) ranged between 2 to 6. One patient died in the following year after decompression due to pneumonia and sepsis. Two patients had moderate disability (mRS of 4) and three patients continue their life with minimal deficit and no major dependency (mRS score 2 and 3). CONCLUSION: DC can be a life-saving procedure which provides a better outcome in patients with cerebral infarction secondary to vasospasm and SAH. However, the small number of the patients in this study is the main limitation of the accuracy of the results, and more studies with larger numbers are required to evaluate the efficiency of DC in this group of patients.

Electrical skin resistance and thermal findings in patients with lumbar disc herniation.

The purpose of this study is to analyze two methods, skin temperature and electrical skin resistance, to evaluate the sympathetic dysfunction in patients with lumbar disc herniation, aiming to determine their accuracy and clinical correlation. Fifteen voluntary patients with lumbar disc herniation were included in this study. Affected dermatome was determined, and skin temperature and electrical skin resistance were recorded from this dermatome and the symmetric healthy dermatome. Results were documented and statistically analyzed. The mean skin temperature of the affected and symmetric healthy dermatome was found to be 32.13 degrees C (+/-1.93) and 32.68 degrees C (+/-1.67), respectively. The difference was found not to be significant (P > 0.05). However, the mean electrical skin resistance recorded from the affected and the symmetric healthy dermatome was found to be 163.39 (+/-8) and 147.05 (+/-9) kOmega, respectively. The difference between these values was found to be statistically significant (P < 0.05). Electrical skin resistance is more sensitive and early in detecting sympathetic dysfunction in patients with lumbar disc herniation than skin temperature. Also, this test is cheap, easy for both the patient and the physician to be performed, and helpful in the follow-up of patients with lumbar disc herniation, after physical therapy and/or surgery.

Correlation between 1H MRS and memory before and after surgery in mesial temporal lobe epilepsy with hippocampal sclerosis.

PURPOSE: Proton magnetic resonance spectroscopy (1H MRS), which can demonstrate neuronal loss and gliosis, may be used as a sensitive tool for lateralization of temporal lobe epilepsy (TLE). Although the correlation between the memory functions and 1H MRS has been investigated, its predictive value after surgery has not been studied previously. This study evaluated memory and 1H MRS values of medically intractable patients with mesial TLE and hippocampal sclerosis (MTLE-HS) before and after selective amygdalohippocampectomy (SAH). METHODS: Twenty-two patients underwent memory tests and 1H MRS investigation before and 6 months after SAH and were compared with nine control subjects. RESULTS: The 1H MRS scores were found to be significantly low on the pathological side of the patients. Both right-sided 1H MRS of right TLE and left-sided 1H MRS values of left TLE patients were correlated only with verbal memory scores. Statistical analysis did not reveal any significance for nonverbal memory scores for both TLE groups on either side, which showed no significant correlation between material specificity and 1H MRS findings. Conversely, regression analyses demonstrated that high right- and low left-sided 1H MRS values obtained before surgery may predict a decline in verbal learning scores after surgery. CONCLUSIONS: 1H MRS can be considered as a useful tool to determine the lateralization in patients with MTLE-HS before the surgery. Although only a weak relation exists between the MRS values and memory scores, presurgical MRS scores may be predictive for a possible deterioration in verbal memory after surgery. However, further studies with higher numbers of cases are needed for confirmation of the results.