Preservation Of Neurological Function Research Articles

Restoration of Thoracolumbar Spine Stability and Alignment in Elderly Patients Using Minimally Invasive Spine Surgery (MISS). A Safe and Feasible Option in Degenerative and Traumatic Spine Diseases.

Minimally invasive spine surgery (MISS), including percutaneous pedicle-screw fixation (PPSF), mini-open transforaminal lumbar interbody fusion (m-open TLIF), vertebroplasty, and stentoplasty, allows the preservation of neurological function and the restoration of spine stability, while reducing associated risks and complications. This study aimed to analyze the safety and efficacy of MISS in elderly patients suffering from degenerative or traumatic thoracolumbar diseases. Forty-five patients (28 females), with a mean age of 73 years (range 65-89), suffering from osteoporotic vertebral fractures (24), degenerative spondylolisthesis (15), and lumbar canal stenosis with instability and/or de novo scoliosis (6) were included.Twenty-one patients underwent PPSF and m-open TLIF. The remaining patients received PPSF without interbody fusion, and in six of these fenestrated screws were used for vertebral body cement augmentation.Functional evaluation was obtained with a visual analog scale (VAS) and the Oswestry Disability Index (ODI) pre- and postoperatively. Preoperative imaging included X-rays, computed tomography (CT), and magnetic resonance imaging (MRI). Patients were followed-up with X-rays, and a CT scan was also obtained at the last follow-up. Follow-up ranged from 6 to 59 months (mean 28 months). Follow-up CT scan documented intersomatic fusion in only 14 % of patients treated with m-open TLIF. Despite the high incidence of non-union, mean VAS and ODI scores showed a significant improvement, with a reduction of mean VAS from 9 to 4 and a reduction of mean ODI from 76.33 to 38.15 %. Only three patients developed postoperative complications. No patients showed neurological deficits.Minimally invasive spine surgery for degenerative and traumatic spinal diseases is a safe and effective treatment also in elderly patients.

Robustness of the neurological prognostic score in brain metastasis patients treated with Gamma Knife radiosurgery.

OBJECTIVE The neurological prognostic score (NPS) was recently proposed as a means for predicting neurological outcomes, such as the preservation of neurological function and the prevention of neurological death, in brain metastasis patients treated with Gamma Knife radiosurgery (GKRS). NPS consists of 2 groups: Group A patients were expected to have better neurological outcomes, and Group B patients were expected to have poorer outcomes. NPS robustness was tested in various situations. METHODS In total, 3040 patients with brain metastases that were treated with GKRS were analyzed. The cumulative incidence of the loss of neurological function independence (i.e., neurological deterioration) was estimated using competing risk analysis, and NPS was compared between Groups A and B by employing Gray's model. NPS was tested to determine if it can be applied to 5 cancer categories-non-small cell lung cancer, small cell lung cancer, gastrointestinal tract cancer, breast cancer, and other cancers-as well as if it can be incorporated into the 5 major grading systems: recursive partitioning analysis (RPA), score index for stereotactic radiosurgery (SIR), basic score for brain metastases (BSBM), graded prognostic assessment (GPA), and modified-RPA (M-RPA). RESULTS There were 2263 patients in NPS Group A and 777 patients in Group B. Neurological deterioration was observed in 586 patients (19.2%). The cumulative incidences of neurological deterioration were 9.5% versus 21.0%, 14.1% versus 25.4%, and 17.6% versus 27.8% in NPS Groups A and B at 1, 2, and 5 years, respectively. Significant differences were detected between the NPS groups in all cancer categories. There were significant differences between NPS Groups A and B for all classes in terms of the BSBM, GPA, and M-RPA systems, but the differences failed to reach statistical significance in terms of RPA Class I and SIR Class 0 to 3. CONCLUSIONS The NPS was verified as being highly applicable to all cancer categories and almost all classes for the 5 grading systems in terms of neurological function independence. This NPS system appears to be quite robust in various situations for brain metastasis patients treated with GKRS.

Summary and consensus in 7th International Conference on acoustic neuroma: An update for the management of sporadic acoustic neuromas.

Sporadic vestibular schwannoma (acoustic neuroma) is a benign tumor arising from cochleovestibular nerve. Nowadays, various specialties and medical centers are treating this disease, and the multidisciplinary collaboration is the trend. In an effort to promote a uniform standard for reporting clinical results, even for treatment indications, the mainly controversies were posed and discussed during the 7th International Conference on acoustic neuroma, and the agreement was summarized by the Committee of this conference. The main symptoms grading and tumor stage should note its name of classification for making them comparable. The goal of the modern managements for vestibular schwannoma is to improve the quality of life with lower mortality, lower morbidity and better neurological function preservation. The experience of surgical team and their preference might be a major factor for the outcome. Because of lacking of long-term follow-up large data after radiotherapy, and with the development of microsurgery, radiotherapy is now less recommended except for recurrent cases or elderly patients.

Reducing kyphotic deformity by posterior vertebral column resection with 360° osteosynthesis in metastatic epidural spinal cord compression (MESCC).

Metastatic epidural spinal cord compression (MESCC) often requires anterior-posterior decompression and stabilization. To reduce approach-related complications, single-stage posterolateral vertebrectomy and 360° fusion is often performed. However, a sufficient reduction of kyphotic deformity through this approach has not been reported. The purpose of this study is to investigate the efficacy of kyphotic deformity reduction by this approach in MESCC. A retrospective analysis and chart review was performed for 14 consecutive patients who underwent a vertebrectomy and decompression from a posterolateral approach. Anterior mesh stabilization of the ventral column is used as hypomochlion for the posterior compression manoeuvre, which leads to reduction of the kyphotic deformity. Pre-operative back pain was 7.2 on a visual analogue scale. Back pain was reduced to 4.4 at discharge and 2.0 at the latest follow-up with a mean follow-up of 12months (p<0.001). The Frankel score remains constant or improved from D to E. Radiological segmental kyphosis was corrected from a mean of 16° to 4° (p<0.001) post-operatively with a loss of 3° at the final follow-up, but still with significant corrections compared with the pre-operative measurements (p<0.003). Single-stage posterolateral vertebrectomy and reconstruction is a safe and less invasive approach that allows a sufficient reduction of hyperkyphosis and preservation of neurological function in patients with MESCC. This approach is an efficient alternative to anterior-posterior fusion with good pain reduction and improved sagittal profile.

Posterior approaches for symptomatic metastatic spinal cord compression.

Surgical interventions for spinal metastasis are commonly performed for mechanical stabilization, pain relief, preservation of neurological function, and local tumor reduction. Although multiple surgical approaches can be used for the treatment of metastatic spinal lesions, posterior approaches are commonly performed. In this study, the role of posterior surgical procedures in the treatment of spinal metastases was reviewed, including posterior laminectomy with and without instrumentation for stabilization, transpedicular corpectomy, and costotransversectomy. A review of the literature from 1980 to 2015 was performed using Medline, as was a review of the bibliographies of articles meeting preset inclusion criteria, to identify studies on the role of these posterior approaches among adults with spinal metastasis. Thirty-four articles were ultimately analyzed, including 1 randomized controlled trial, 6 prospective cohort studies, and 27 retrospective case reports and/or series. Some of the reviewed articles had Level II evidence indicating that laminectomy with stabilization can be recommended for improvement in neurological outcome and reduction of pain in selected patients. However, the use of laminectomy alone should be carefully considered. Additionally, transpedicular corpectomy and costotransversectomy can be recommended with the expectation of improving neurological outcomes and reducing pain in properly selected patients with spinal metastases. With improvements in the treatment paradigms for patients with spinal metastasis, as well as survival, surgical therapy will continue to play an important role in the management of spinal metastasis. While this review presents a window into determining the utility of posterior approaches, future prospective studies will provide essential data to better define the roles of the various options now available to surgeons in treating spinal metastases.

Erratum to: Monitoring effectiveness and safety of Tafamidis in transthyretin amyloidosis in Italy: a longitudinal multicenter study in a non-endemic area.

Tafamidis is a transthyretin (TTR) stabilizer able to prevent TTR tetramer dissociation. There have been a few encouraging studies on Tafamidis efficacy in early-onset inherited transthyretin amyloidosis (ATTR) due to Val30Met mutation. However, less is known about its efficacy in later disease stages and in non-Val30Met mutations. We performed a multi-center observational study on symptomatic ATTR patients prescribed to receive Tafamidis. We followed up patients according to a standardized protocol including general medical, cardiological and neurological assessments at baseline and every 6 months up to 3 years. Sixty-one (42 males) patients were recruited. Only 28 % of enrolled subjects had the common Val30Met mutation, mean age of onset was remarkably late (59 years) and 18 % was in advanced disease stage at study entry. Tafamidis proved safe and well-tolerated. One-third of patients did not show significant progression along 36 months, independently from mutation type and disease stage. Neurological function worsened particularly in the first 6 months but progression slowed significantly thereafter. Autonomic function remained stable in 33 %, worsened in 56 % and improved in 10 %. Fifteen percent of patients showed cardiac disease progression and 30 % new onset of cardiomyopathy. Overall, Tafamidis was not able to prevent functional progression of the disease in 23 (43 %) subjects, including 16 patients who worsened in their walking ability and 12 patients who reached a higher NYHA score during the follow-up period. A higher mBMI at baseline was associated with better preservation of neurological function. In conclusion, neuropathy and cardiomyopathy progressed in a significant proportion of patients despite treatment. However, worsening of neurological function slowed after the first 6 months and also subjects with more advanced neuropathy, as well as patients with non-Val30Met mutation, benefited from treatment. Body weight preservation is an important favorable prognostic factor.

Monitoring effectiveness and safety of Tafamidis in transthyretin amyloidosis in Italy: a longitudinal multicenter study in a non-endemic area.

Tafamidis is a transthyretin (TTR) stabilizer able to prevent TTR tetramer dissociation. There have been a few encouraging studies on Tafamidis efficacy in early-onset inherited transthyretin amyloidosis (ATTR) due to Val30Met mutation. However, less is known about its efficacy in later disease stages and in non-Val30Met mutations. We performed amulti-center observational study on symptomatic ATTR patients prescribed to receive Tafamidis. We followed up patients according to a standardized protocol including general medical, cardiological and neurological assessments at baseline and every 6months up to 3years. Sixty-one (42 males) patients were recruited. Only 28% of enrolled subjects had the common Val30Met mutation, mean age of onset was remarkably late (59years) and 18% was in advanced disease stage at study entry. Tafamidis proved safe and well-tolerated. One-third of patients did not show significant progression along 36months, independently from mutation type and disease stage. Neurological function worsened particularly in the first 6months but progression slowed significantly thereafter. Autonomic function remained stable in 33%, worsened in 56% and improved in 10%. Fifteen percent of patients showed cardiac disease progression and 30% new onset of cardiomyopathy. Overall, Tafamidis was not able to prevent functional progression of the disease in 23 (43%) subjects, including 16 patients who worsened in their walking ability and 12 patients who reached a higher NYHA score during the follow-up period. A higher mBMI at baseline was associated with better preservation of neurological function. In conclusion, neuropathyand cardiomyopathy progressed in a significant proportion of patients despite treatment. However, worsening of neurological function slowed after the first 6months and also subjects with more advanced neuropathy, as well as patients with non-Val30Met mutation, benefited from treatment. Body weight preservation is an important favorable prognostic factor.

Spine Surgery in Patients with Metastatic Breast Cancer: A Retrospective Analysis

Pathologic or iatrogenic symptomatic spinal lesions are common in metastatic breast cancer. Given the longer duration of overall survival provided by modern oncologic therapies, a prompt and effective treatment of such lesions may have a significant impact on patient's quality of life, improving pain and preventing deterioration of neurologic functions. A retrospective review was conducted on patients with breast cancer operated to the spine between 2005 and 2013. The series includes 41 patients and 57 vertebral levels treated (4 cervical, 35 dorsal, and 18 lumbar). There were 28 patients who received palliative surgery and 13 who received excisional surgery, according to their clinical conditions, Spinal Instability Neoplastic Score, and Tokuhashi scores. Of the 41 patients, 38 presented with a median survival of 50 months (95% confidence interval [CI], 39-61), still preserving a Karnofsky Performance Status Scale score ≥60 and a retained ability to ambulate independently. The median overall survival after the first spine surgery was also 50 months (95% CI, 35-65), suggesting that in this cohort of patients, a reasonable quality of life was preserved almost to the end of their clinical history. In patients treated with palliative surgery, the median survival was 37 months (95% CI, 26-48). In those treated with complex surgery, it was 57 months (95% CI, 41-73; P= 0.03). Major excisional surgery, albeit associated with an increased length of hospital stay, allowed in our series a prolonged survival compared with less aggressive types of surgery. However, percutaneous or open balloon kyphoplasty techniques have expanded indications for palliative surgery and even patients with lower Tokuhashi scores may benefit from rapid and sustained pain relief, preservation of neurologic function, and early mobilization.

Attenuated traumatic axonal injury and improved functional outcome after traumatic brain injury in mice lacking Sarm1.

Axonal degeneration is a critical, early event in many acute and chronic neurological disorders. It has been consistently observed after traumatic brain injury, but whether axon degeneration is a driver of traumatic brain injury remains unclear. Molecular pathways underlying the pathology of traumatic brain injury have not been defined, and there is no efficacious treatment for traumatic brain injury. Here we show that mice lacking the mouse Toll receptor adaptor Sarm1 (sterile α/Armadillo/Toll-Interleukin receptor homology domain protein) gene, a key mediator of Wallerian degeneration, demonstrate multiple improved traumatic brain injury-associated phenotypes after injury in a closed-head mild traumatic brain injury model. Sarm1(-/-) mice developed fewer β-amyloid precursor protein aggregates in axons of the corpus callosum after traumatic brain injury as compared to Sarm1(+/+) mice. Furthermore, mice lacking Sarm1 had reduced plasma concentrations of the phophorylated axonal neurofilament subunit H, indicating that axonal integrity is maintained after traumatic brain injury. Strikingly, whereas wild-type mice exibited a number of behavioural deficits after traumatic brain injury, we observed a strong, early preservation of neurological function in Sarm1(-/-) animals. Finally, using in vivo proton magnetic resonance spectroscopy we found tissue signatures consistent with substantially preserved neuronal energy metabolism in Sarm1(-/-) mice compared to controls immediately following traumatic brain injury. Our results indicate that the SARM1-mediated prodegenerative pathway promotes pathogenesis in traumatic brain injury and suggest that anti-SARM1 therapeutics are a viable approach for preserving neurological function after traumatic brain injury.

Awake Surgery for Brain Tumors in Eloquent Zones: First Cases in Croatia

Introduction Awake brain surgery has been approved as a safe and efficacious operative procedure with the goal of maximal tumor resection and preservation of neurological function. This study presents first cases of full awake primary brain tumor surgical procedures performed in Croatia.

Long-Term Functional and Recurrence Outcomes of Surgically Treated Jugular Foramen Schwannomas: A 20-Year Experience

To investigate the outcomes of jugular foramen schwannomas (JFSs) and to evaluate the risk factors for tumor recurrence and poor final outcomes. Between 1993 and 2013, 133 patients (68 female patients) with JFSs were surgically treated. Clinical charts were reviewed, and scheduled follow-up examinations were performed. The average preoperative Karnofsky Performance Scale (KPS) score was 79.6. The JFSs were classified as follows: 65 cases, type A; 15 cases, type B; 5 cases, type C; and 48 cases, type D. Gross total resection was achieved in 107 (80.5%) patients. Transient and permanent morbidities affecting cranial nerves IX and X were 19.8% and 11.5%, respectively. After a mean follow-up duration of 108.0 months, 13 (9.9%) patients experienced recurrence. The most recent KPS scores averaged 83.7. Compared with the preoperative KPS score, the most recent KPS score was improved in 87 (65.4%) patients and stabilized in 29 (21.8%) patients. The presence of a solid tumor (hazard ratio [HR] = 5.815, P = 0.010), nontotal resection (HR = 4.613, P = 0.007), and pathologic mitoses (HR = 11.018, P < 0.001) were independent risk factors for tumor recurrence. Decreased preoperative KPS score (per 10 points) (odds ratio [OR] = 2.483, P = 0.027), a less soft tumor consistency (OR = 2.257, P = 0.039), and a solid tumor (OR = 3.755, P = 0.041) were risk factors for poor long-term outcomes. Quality of life and preservation of neurologic function are the goals of surgical treatment of JFSs. Favorable long-term surgical outcomes for JFSs can be achieved. Morbidity of cranial nerves IX and X is significant, and patients with nontotal resection or pathologic mitosis should be followed closely.

Intramedullary spinal cord metastases: an increasingly common diagnosis.

OBJECT Intramedullary spinal cord metastases (ISCM) represent a small proportion of intramedullary tumors. However, with the lifespans of patients with malignant tumors increasing, incidents of ISCM are on the rise. Due to threateningly severe disabilities in patients, accompanied by limited life expectancy, every attempt should be made to treat these tumors the same way as metastases elsewhere in the CNS, with the goal of complete removal of the ISCM and preservation of neurological functions. The object of this study is to retrospectively analyze the experiences of 22 patients who were surgically treated for ISCM over a 22-year period. METHODS Hospital charts of 22 patients, who were surgically treated for ISCM between 1992 and 2014, were reviewed retrospectively. Demographic data, histopathological diagnoses of primary cancer, chronological sequence of the disease, and neurological status using the simplified McCormick functional classification were collected and reanalyzed. RESULTS The most frequent histology was metastasis of lung cancer, followed by brain and breast cancers. The time span from primary cancer diagnosis to the development of symptomatic spinal metastases ranged from 0 to 285 months, with a mean interval of 38 months. The leading presenting sign was dysesthesia (77% of the population), followed by paresis (68%). Only 5 patients (23%) showed urinary retention. Initial performance status represented by the McCormick Scale was on average 2.47. Total or near-total removal was achieved in 87% of cases. Compared with the clinical status 1-2 days after surgery, there was an improvement in the McCormick Scale grade at the last follow-up from 2.47 to 2.12 (p = 0.009). Likewise, an improvement was detected when comparing the preoperative status with the last follow-up (from 2.45 to 2.12; p = 0.029). The mean survival time after surgery was 11.6 months. CONCLUSIONS These results suggest that surgery for intramedullary metastases-with all of the challenges of a rare and potentially risky procedure-can be beneficial to patients with advanced stages of cancer. Surgery can be performed with minimal new morbidity and results in maintaining neurological performance status.

Use of Actuator-Driven Pulsed Water Jet in Brain and Spinal Cord Cavernous Malformations Resection.

A piezo actuator-driven pulsed water jet (ADPJ) system is a novel surgical instrument that enables dissection of tissue without thermal damage. It can potentially resect intra-axial lesions while preserving neurological function. To report our first experience of applying an ADPJ system to brain and spinal cord cavernous malformations. Four patients (2 women and 2 men, mean age 44.5 years) with brain (n = 3) and spinal cord (n = 1) cavernous malformations were enrolled in the study. All surgeries were performed with the aid of the ADPJ system. Postoperative neurological function and radiological findings were evaluated. The ADPJ system was useful in dissecting boundaries between the lesion and surrounding brain/spinal cord tissues. The pulsed water jet provided a clear surgical view and helped surgeons follow the margins. Water jet dissection peeled off the brain and spinal cord tissues from the lesion wall. Surrounding gliotic tissue was preserved. As a consequence, the cavernous malformations were successfully removed. Postoperative magnetic resonance imaging confirmed total removal of lesions in all cases. Preoperative neurological symptoms completely resolved in 2 patients. The others experienced partial recovery. No patients developed new postoperative neurological deficits; facial palsy temporarily worsened in 1 patient who underwent a suprafacial colliculus approach for the brainstem lesion. The ADPJ provided a clear surgical field and enabled surgeons to dissect boundaries between lesions and surrounding brain and spinal cord gliotic tissue. The ADPJ system is a feasible option for cavernous malformation surgery, enabling successful tumor removal and preservation of neurological function.

Neurological Impairment Linked with Cortico-Subcortical Infiltration of Diffuse Low-Grade Gliomas at Initial Diagnosis Supports Early Brain Plasticity.

Diffuse low-grade gliomas (DLGG) are slow-growing brain tumors that in spite of an indolent behavior at onset show a continuous expansion over time and inevitably transform into malignant gliomas. Extensive tumor resections may be performed with preservation of neurological function due to neuroplasticity that is induced by the slow tumor growth. However, DLGG prefer to migrate along subcortical pathways, and white matter plasticity is considerably more limited than gray matter plasticity. Whether signs of functional decompensating white matter that may be found as early as at disease presentation has not been systematically studied. Here, we examined 52 patients who presented with a DLGG at the time of radiological diagnosis. We found a significant correlation between neurological impairment and eloquent cortico-subcortical tumor localization, but not between neurological function and tumor volume. These results suggest that even small tumors invading white matter pathways may lack compensatory mechanisms for functional reorganization already at disease presentation.

Reduction of inflammation and preservation of neurological function by anti-CD52 therapy in murine experimental autoimmune encephalomyelitis

Alemtuzumab, a monoclonal antibody directed against human CD52, is used in the treatment of MS. To characterize the impact of anti-CD52 administration, a monoclonal antibody to mouse CD52 (anti-muCD52) was generated and evaluated in EAE mouse models of MS. A single course of anti-muCD52 provided a therapeutic benefit accompanied by a reduction in the frequency of autoreactive T lymphocytes and production of pro-inflammatory cytokines. Examination of the CNS revealed a decrease in infiltrating lymphocytes, demyelination and axonal loss. Electrophysiological assessment showed preservation of axonal conductance in the spinal cord. These findings suggest that anti-CD52 therapy may help preserve CNS integrity.

Clinical and Radiologic Outcome of Gamma Knife Radiosurgery on Nonfunctioning Pituitary Adenomas.

Objective To elucidate the role of Gamma Knife radiosurgery (GKRS) in the management of nonfunctioning pituitary adenomas (NFAs). Materials and Methods A retrospective review of 57 consecutive patients spanning 2000 to 2013 with NFAs was performed. Of 57 patients, 53 patients had recurrent or residual tumors after microsurgical resection. The study population was evaluated clinically and radiographically after GKRS treatment. The median follow-up time was 45.57 months. Results GKRS in pituitary adenomas showed significant variations in tumor growth control (decreased in 32 patients [56.1%], arrested growth in 21 patients [36.1%], and increased tumor size in 4 patients [7%]). Progression-free survival after GKRS at 3, 7, and 10 years was 100%, 98%, and 90%, respectively. The neurologic signs and symptoms were significantly improved after GKRS (14% versus 107%) compared with pretreated signs and symptoms (p < 0.0001). Five patients (8.8%) required additional treatment. Conclusion Recent follow-up revealed that GKRS offers a high rate of tumor control and preservation of neurologic functions in both new and recurrent patients with NFAs. Thus GKRS is an effective treatment option for recurrent and residual as well as newly diagnosed patients with NFAs.

Long-term Surgical Outcomes of Spinal Schwannomas: Retrospective Analysis of 49 Consecutive Cases.

Spinal schwannomas (SS) represent the most common intradural extramedullary lesions, accounting for approximately 24% of all nerve sheath tumors in adults. Schwannomas have infrequent, but existent possibility of malignancy. In this study, long-term outcomes of 49 consecutive SS have been presented. Medical records were retrospectively reviewed in 371 cases of spinal tumors who underwent surgery between the years 2005 and 2014. Cases confirmed as schwannoma histopathologically were included in this study. Patients" complaints, localizations, recurrence rate and complications were evaluated. Forty-nine cases were detected in 47 (26 female, 21 male) patients. The mean age was 45.8±13.7 years. The mean follow-up period was 61.4±21.5 months. The most common complaint was local pain. Eleven were cervical, ten thoracic, twentyfour lumbar, and four in the sacral spine. Thirty-three cases were intradural-extramedullary, fifteen cases were the extradural type, and one case was the extra-intradural type. Recurrence rate was 4.08%. Gross-total resection (GTR) was achieved in forty-seven patients. The most common complications were surgical site infection and intraoperative instability that were seen in three patients each. Posterior instrumentation was performed in two patients. SS is mostly benign and intradural-extramedullary. To treat patients with SS, there is no need for adjuvant treatments; GTR with preservation of neurological functions is the best treatment to relieve patients" complaints and to reduce the recurrence rate of SS. To avoid serious complications, we recommend intraoperative neurophysiological monitoring and laminoplasty, especially in young patients. Dumbbell SS may require extensive bone resection. Posterior instrumentation can be used if instability occurs.

Preservation of neurological functions during the extended middle fossa approach operation of small cerebellopontine angle tumors

Preservation of neurological functions during the extended middle fossa approach operation of small cerebellopontine angle tumors

A new grading system focusing on neurological outcomes for brain metastases treated with stereotactic radiosurgery: the modified Basic Score for Brain Metastases.

The Basic Score for Brain Metastases (BSBM) proposed by Lorenzoni and colleagues is one of the best grading systems for predicting survival periods after stereotactic radiosurgery (SRS) for brain metastases. However, it includes no brain factors and cannot predict neurological outcomes, such as preservation of neurological function and prevention of neurological death. Herein, the authors propose a modified BSBM, adding 4 brain factors to the original BSBM, enabling prediction of neurological outcomes, as well as of overall survival, in patients undergoing SRS. To serve as neurological prognostic scores (NPSs), the authors scored 4 significant brain factors for both preservation of neurological function (qualitative survival) and prevention of neurological death (neurological survival) as 0 or 1 as described in the following: > 10 brain tumors = 0 or ≤ 10 = 1, total tumor volume > 15 cm(3) = 0 or ≤ 15 cm(3) = 1, MRI findings of localized meningeal dissemination (yes = 0 or no = 1), and neurological symptoms (yes = 0 or no = 1). According to the sum of NPSs, patients were classified into 2 subgroups: Subgroup A with a total NPS of 3 or 4 and Subgroup B with an NPS of 0, 1, or 2. The authors defined the modified BSBM according to the NPS subgroup classification applied to the original BSBM groups. The validity of this modified BSBM in 2838 consecutive patients with brain metastases treated with SRS was verified. Patients included 1868 with cancer of the lung (including 1604 with non-small cell lung cancer), 355 of the gastrointestinal tract, 305 of the breast, 176 of the urogenital tract, and 134 with other cancers. Subgroup A had 2089 patients and Subgroup B 749. Median overall survival times were 2.6 months in BSBM 0 (382 patients), 5.7 in BSBM 1 (1143), 11.4 in BSBM 2 (1011) and 21.7 in BSBM 3 (302), and pairwise differences between the BSBM groups were statistically significant (all p < 0.0001). One-year qualitative survival rates were 64.6% (modified BSBM 0A, 204 patients), 45.0% (0B, 178), 82.5% (1A, 825), 63.3% (1B, 318), 86.4% (2A, 792), 73.7% (2B, 219), 91.4% (3A, 268), and 73.5% (3B, 34). One-year neurological survival rates were 82.6% (0A), 52.4% (0B), 90.5% (1A), 78.1% (1B), 91.1% (2A), 83.2% (2B), 93.9% (3A), and 76.3% (3B), where A and B identify the subgroup. Statistically significant differences in both qualitative and neurological survivals between Subgroups A and B were detected in all BSBM groups. The authors' new index, the modified BSBM, was found to be excellent for predicting neurological outcomes, independently of life expectancy, in SRS-treated patients with brain metastases.

Inhibition of Src phosphorylation reduces damage to the blood-brain barrier following transient focal cerebral ischemia in rats.

The disruption of the blood-brain barrier (BBB) caused by cerebral ischemia determines the extent of injury and patient prognosis. Inhibitors of Src can markedly minimize the infarct size and preserve neurological function. The Src protein tyrosine kinase (PTK) inhibitor, PP2, protects the rat brain against ischemic injury, possibly through the reduction of vascular endothelial growth factor A (VEGFA) expression and the upregulation of claudin-5 expression, which preserves the integrity of the BBB. In this study, the expression levels of phosphorylated (p)-Src, VEGFA and claudin-5 were determined to investigate the changes occurring in the levels of these proteins and to determine the benefits of PP2 treatment following cerebral ischemia/reperfusion (I/R). Our study included a sham-operated group, an I/R group, a vehicle-treated group (V) and a PP2-treated group (PP2). We found that the rats in the PP2 group exhibited greater preservation of neurological function and reduced VEGFA and p-Src protein expression compared with the rats in the I/R and V groups. Moreover, the mRNA and protein levels of claudin-5 were markedly higher in the PP2 group than in the I/R group or the V group after 3 days of reperfusion. Immunofluorescence staining revealed that the co-localized immunostaining of fibrinogen and claudin-5 was reduced in the PP2 group, which suggests that the exudation of fibrinogen in this group was less than that in the I/R and V groups. Furthermore, the reduced co-localization of immunostaining of glial fibrillary acidic protein (GFAP) and claudin-5 indicated that the rats in the PP2 group had only a slight disruption of the BBB. These findings suggested that PP2 treatment attenuated the disruption of the BBB following ischemia and minimized the neurological deficit; these effects were associated with a decreased VEGFA expression and an increased claudin-5 expression. Members of the Src PTK family may be critical targets for the protection of the BBB following cerebral ischemia.