Prognostic value of tumour volume in patients with a poor Karnofsky performance status scale - a bicentric retrospective study.

BACKROUND: Median overall survival (OS) after diagnosis of glioblastoma (GBM) remains 15 months amongst patients receiving aggressive surgical resection, chemotherapy and irradiation. Treatment of patients with a poor preoperative Karnofsky Performance Status Scale (KPSS) is still controversial. Therefore, we retrospectively assessed the outcome after surgical treatment in patients with a KPSS of ≤60%. METHODS: We retrospectively included patients with a de-novo glioblastoma WHO °IV and preoperative KPSS ≤60%, who underwent surgery at two neurosurgical centres between September 2006 and March 2016. We recorded pre- and postoperative tumour volume, pre- and postoperative KPSS, OS, age and MGMT promoter status. RESULTS: One hundred twenty-three patients (58 females/65 males, mean age 67.4 ± 13.4 years) met the inclusion criteria. Seventy-five of the 123 patients (61%) underwent surgical resection. 48/123 patients (39%) received a biopsy. The median preoperative and postoperative tumour volume of all patients was 33.0 ± 31.3 cm3 (IR 15.0-56.5cm3) and 3.1 ± 23.8 cm3 (IR 0.2-15.0 cm3), respectively. The median KPSS was 60% (range 20-60%) preoperatively and 50% (range 0-80%) postoperatively. Patients who received a biopsy showed a median OS for patients who received a biopsy only was 3.0 months (95% CI 2.0-4.0 months), compared to patients who had a resection and had a median OS of 8 months (95% CI 3.1-12.9 months). Age (p < 0.001, HR: 1.045 [95% CI 1.022-1.068]), postoperative tumour volume (p = 0.02, HR: 1.016 [95% CI 1.002-1.029]) and MGMT promotor status (p = 0.016, HR: 0.473 [95% CI 0.257-0.871]) were statistically significant in multivariate analysis. In subgroup analyses only age was shown as a significant prognostic factor in multivariate analyses for patients receiving surgery (p < 0.001, HR: 1.046 [95% CI 1.022-1.072]). In the biopsy group no significant prognostic factors were shown in multivariate analysis. CONCLUSION: GBM patients with a preoperative KPSS of ≤60% might profit from surgical reduction of tumour burden.

How I do it: retrosigmoid suprajugular approach to the jugular foramen.

BACKGROUND: The retrosigmoid suprajugular approach provides a less-aggressive approach for a subset of tumors of the jugular foramen. METHOD: We described the retrosigmoid suprajugular approach with its advantages, caveats, and indications. A Samii-B2 glossopharyngeal nerve schwannoma is shown to exemplify the procedure. CONCLUSION: The retrosigmoid suprajugular approach provides an excellent option for tumors with a variable extension into the cerebellopontine cistern and limited extension into the jugular foramen. It is less destructive than the other approaches and allows a good exposure to the posterior part of the jugular foramen.

Correction to: Prognostic Value of Tumor Volume in Glioblastoma Patients: Size Also Matters for Patients with Incomplete Resection.

Due to a metadata tagging error the names of Stephanie E. Combs and Jan S. Kirschke were indexed incorrectly. Stephanie E. is the author's given name, and Jan S. is the author's given name.

Prognostic Value of Tumor Volume in Glioblastoma Patients: Size Also Matters for Patients with Incomplete Resection.

BACKGROUND: Incomplete resection of glioblastoma is discussed controversially in the era of combined radiochemotherapy. OBJECTIVE: The aim of this study was to analyze the benefit of subtotal tumor resection for glioblastoma patients as this was recently questioned in the era of radiochemotherapy. METHODS: Overall, 209 patients undergoing surgery for newly diagnosed WHO grade IV gliomas were retrospectively analyzed, and pre- and postoperative tumor volumes were manually segmented (cm3). Survival analyses were performed, including prognostic factors such as age, Karnofsky performance score (KPS), O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status, and adjuvant treatment regimen. RESULTS: Pre- and postoperative tumor volume is significantly associated with pre- and postoperative KPS, as well as age (p < 0.001). Postoperative tumor volume remained a significant prognostic factor in a multivariate analysis, independent of other prognostic factors (hazard ratio 1.0365, 95% confidence interval 1.0235-1.0497, p < 0.001). CONCLUSIONS: In the era of molecularly-driven radiochemotherapy, glioblastoma surgery remains a major prognostic factor. Even in situations in which a gross total resection cannot be achieved, maximum safe reduction of tumor burden should be attempted.

Re-irradiation after gross total resection of recurrent glioblastoma : Spatial pattern of recurrence and a review of the literature as a basis for target volume definition.

BACKGROUND: Currently, patients with gross total resection (GTR) of recurrent glioblastoma (rGBM) undergo adjuvant chemotherapy or are followed up until progression. Re-irradiation, as one of the most effective treatments in macroscopic rGBM, is withheld in this situation, as uncertainties about the pattern of re-recurrence, the target volume, and also the efficacy of early re-irradiation after GTR exist. METHODS: Imaging and clinical data from 26 consecutive patients with GTR of rGBM were analyzed. The spatial pattern of recurrences was analyzed according to the RANO-HGG criteria ("response assessment in neuro-oncology criteria for high-grade gliomas"). Progression-free (PFS) and overall survival (OS) were analyzed by the Kaplan-Meier method. Furthermore, a systematic review was performed in PubMed. RESULTS: All but 4 patients underwent adjuvant chemotherapy after GTR. Progression was diagnosed in 20 of 26 patients and 70% of recurrent tumors occurred adjacent to the resection cavity. The median extension beyond the edge of the resection cavity was 20 mm. Median PFS was 6 months; OS was 12.8 months. We propose a target volume containing the resection cavity and every contrast enhancing lesion as the gross tumor volume (GTV), a spherical margin of 5-10 mm to generate the clinical target volume (CTV), and a margin of 1-3 mm to generate the planning target volume (PTV). Re-irradiation of this volume is deemed to be safe and likely to prolong PFS. CONCLUSION: Re-irradiation is worth considering also after GTR, as the volumes that need to be treated are limited and re-irradiation has already proven to be a safe treatment option in general. The strategy of early re-irradiation is currently being tested within the GlioCave/NOA 17/Aro 2016/03 trial.

L5 corpectomy-the lumbosacral segmental geometry and clinical outcome-a consecutive series of 14 patients and review of the literature.

PURPOSE: We analyzed the lumbosacral segmental geometry and clinical outcome in patients undergoing L5 corpectomy. METHODS: Fourteen consecutive patients who underwent L5 (n = 12) or L4 + 5 (n = 2) corpectomy at our department between January 2010 and April 2015 were included. All patients underwent a baseline physical and neurologic examination on admission. The diagnostic routine included MRI and CT scans and, if possible, an upright X-ray of the lumbar spine before and after surgery. The local lordosis angle [L4(L3)-S1] was measured. RESULTS: The most common pathology was infection (N = 7), followed by neoplastic disease (n = 3), pseudarthrosis (n = 2) after previous spinal fusion procedures and burst fractures (n = 2) of the L5 vertebral body. We observed seven complications (2 intraoperative; 5 postoperative) in five (36%) patients. Three patients needed revision surgery because of cage subsidence and/or dislodgement (21%). Additional anterior plating was used in two of the revision surgeries to secure the cage. Two spondylodiscitis patients (14%) with complications died of sepsis. Of the 12 remaining patients, 8 were available for follow-up. CONCLUSION: L5 corpectomy is a technically challenging but feasible procedure even though the overall complication rate can be as high as 36%. The radiologic and clinical outcome seems to be better in patients with a small lordosis angle between L4(L3) and S1, since an angle of >50 degrees seems to facilitate cage dislodgement. Anterior plating should be considered in these cases to prevent implant failure.

Treatment strategy for cerebral hypotension caused by spontaneous cerebrospinal fluid leaks.

OBJECTIVE: Spontaneous spinal cerebrospinal fluid (CSF) leaks are rare (5 per 100,000 per year). Treatment generally consists of conservative therapy or interventional therapy with epidural blood patching. Surgical treatment is conducted rarely, usually in cases when conservative or interventional treatment has failed. The aim of our case series was to assess the clinical outcome after surgery. METHODS: Our clinical database was reviewed for patients with spontaneous spinal CSF leaks who underwent surgical exploration between 2010 and 2013. Etiology, symptoms, preoperative imaging, type of required surgical method, intraoperative findings, and clinical outcome were reported. RESULTS: We identified five patients with a mean age of 62 years with spontaneous spinal CSF leaks who were treated surgically. Two patients received surgery after failure of interventional treatment. The origin of the CSF leak could be identified intraoperatively in three cases. Surgical technique in all cases consisted of an interlaminar fenestration or hemilaminectomy and a complete foraminotomy to explore the thecal sack and the exiting nerve roots and identify the CSF leak. After surgery, the preoperative symptoms improved in all patients. In one case, there was a relapse after 4 weeks. CONCLUSIONS: Preoperative identification of a CSF leak with MRI was positive in only one case. In all other cases, a post-myelography CT had to be performed. In all cases, the preoperative symptoms improved after surgery. Surgical treatment is an effective treatment of spontaneous cerebrospinal fluid leaks in cases of refractory symptoms after failed conservative or interventional treatment.

Risks of postoperative paresis in motor eloquently and non-eloquently located brain metastases.

BACKGROUND: When treating cerebral metastases all involved multidisciplinary oncological specialists have to cooperate closely to provide the best care for these patients. For the resection of brain metastasis several studies reported a considerable risk of new postoperative paresis. Pre- and perioperative chemotherapy (Ctx) or radiotherapy (Rtx) alter vasculature and adjacent fiber tracts on the one hand, and many patients already present with paresis prior to surgery on the other hand. As such factors were repeatedly considered risk factors for perioperative complications, we designed this study to also identify risk factors for brain metastases resection. METHODS: Between 2006 and 2011, we resected 206 brain metastases consecutively, 56 in eloquent motor areas and 150 in non-eloquent ones. We evaluated the influences of preoperative paresis, previous Rtx or Ctx as well as recursive partitioning analysis (RPA) class on postoperative outcome. RESULTS: In general, 8.7% of all patients postoperatively developed a new permanent paresis. In contrast to preoperative Ctx, previous Rtx as a single or combined treatment strategy was a significant risk factor for postoperative motor weakness. This risk was even increased in perirolandic and rolandic lesions. Our data show significantly increased risk of new deficits for patients assigned to RPA class 3. Even in non-eloquently located brain metastases the risk of new postoperative paresis has not to be underestimated. Despite the microsurgical approach, our cohort shows a high rate of unexpected residual tumors in postoperative MRI, which supports recent data on brain metastases' infiltrative nature but might also be the result of our strict study protocol. CONCLUSIONS: Surgical resection is a safe treatment of brain metastases. However, preoperative Rtx and RPA score 3 have to be taken into account when surgical resection is considered.

Retrospective distortion correction of diffusion tensor imaging data by semi-elastic image fusion - Evaluation by means of anatomical landmarks.

OBJECTIVE: Diffusion tensor imaging (DTI) based on echo-planar imaging (EPI) can suffer from geometric image distortions in comparison to conventional anatomical magnetic resonance imaging (MRI). Therefore, DTI-derived information, such as fiber tractography (FT) used for treatment planning of brain tumors, might be associated with spatial inaccuracies when linearly projected on anatomical MRI. Hence, a non-linear, semi-elastic image fusion shall be evaluated in this study that aims at correcting for image distortions in DTI. PATIENTS AND METHODS: In a sample of 27 patient datasets, 614 anatomical landmark pairs were retrospectively defined in DTI and T1- or T2-weighted three-dimensional (3D) MRI data. The datasets were processed by a commercial software package (Elements Image Fusion .0; Brainlab AG, Munich, Germany) providing rigid and semi-elastic fusion functionalities, such as DTI distortion correction. To quantify the displacement prior to and after semi-elastic fusion, the Euclidian distances of rigidly and elastically fused landmarks were evaluated by means of descriptive statistics and Bland-Altman plot. RESULTS: For rigid and semi-elastic fusion mean target registration errors of 3.03 ±â€¯2.29 mm and 2.04 ±â€¯1.95 mm were found, respectively, with 91% of the evaluated landmarks moving closer to their position determined in T1- or T2-weighted 3D MRI data after distortion correction. Most efficient correction was achieved for non-superficial landmarks showing distortions up to 1 cm. CONCLUSION: This study indicates that semi-elastic image fusion can be used for retrospective distortion correction of DTI data acquired for image guidance, such as DTI FT as used for a broad range of clinical indications.

Is Eighty the New Sixty? Outcomes and Complications after Lumbar Decompression Surgery in Elderly Patients over 80 Years of Age.

OBJECTIVE: An increasing demographic aging of the general population results in a rising incidence of octogenarians and nonagenarians with spine disease. Patients older than 65 years represent the majority of patients with degenerative lumbar spine disease in our daily clinical routine. Surgical treatment is undertaken reluctantly because of an increased rate of comorbidities. We therefore assessed complication rates of lumbar decompression in regard to neurological outcome and medical conditions in patients age 80 years or older in a retrospective single-center series. METHODS: Data for 244 patients (124 female, 120 male; mean age, 83.1 ± 3 years; age range, 80-95 years) who underwent decompressive surgery for lumbar spinal stenosis or disc herniation between April 2007 and February 2016 were assessed retrospectively. Age at surgery, neurologic deficits (preoperative and postoperative), relevant medical comorbidities and previous lumbar decompression, intraoperative and postoperative complications (e.g., surgery-related, medical), duration of surgery, length of hospital stay, and rate of revision surgeries were recorded. RESULTS: Surgery was performed for lumbar stenosis (184 patients; 75.4%), lumbar disc herniation (13 patients; 5.3%) or both (47 patients; 19.3%). Seventy-six patients (31.3%) patients experienced preoperative neurologic deficits; 48 (63.2%) of these patients improved, 28 (36.8%) of them were unchanged after surgery, and none deteriorated. New transient, postoperative, neurologic deficits occurred in 6 patients (2.5%). All 55 (22.5%) intraoperative complications were mild to moderate, and no severe surgical complications occurred. Two hundred fifteen patients (88%) had relevant medical disorders. Nineteen (7.7%) postoperative medical complications were reported in 17 patients (7%), of which 14 (73.7%) were severe and 5 (26.3%) were mild (4 pulmonary embolisms, 6 pneumonias, 3 myocardial infarctions, 1 postoperative renal failure, 5 urinary tract infections). Medical complications that necessitated intensive care unit treatment and resulted in lethal outcome were seen in 2 patients (0.8%). CONCLUSION: Despite their age, the vast majority of octogenarians and nonagenarians benefited from lumbar decompression surgery. Mild to moderate intraoperative complications were relatively frequent, whereas severe intraoperative complications did not occur. The majority of medical complications was severe, but the incidence was acceptable, and the postoperative outcome was still favorable in most patients.

Retrospective Analysis of Radiological Recurrence Patterns in Glioblastoma, Their Prognostic Value And Association to Postoperative Infarct Volume.

Recent studies suggested that postoperative hypoxia might trigger invasive tumor growth, resulting in diffuse/multifocal recurrence patterns. Aim of this study was to analyze distinct recurrence patterns and their association to postoperative infarct volume and outcome. 526 consecutive glioblastoma patients were analyzed, of which 129 met our inclusion criteria: initial tumor diagnosis, surgery, postoperative diffusion-weighted imaging and tumor recurrence during follow-up. Distinct patterns of contrast-enhancement at initial diagnosis and at first tumor recurrence (multifocal growth/progression, contact to dura/ventricle, ependymal spread, local/distant recurrence) were recorded by two blinded neuroradiologists. The association of radiological patterns to survival and postoperative infarct volume was analyzed by uni-/multivariate survival analyses and binary logistic regression analysis. With increasing postoperative infarct volume, patients were significantly more likely to develop multifocal recurrence, recurrence with contact to ventricle and contact to dura. Patients with multifocal recurrence (Hazard Ratio (HR) 1.99, P = 0.010) had significantly shorter OS, patients with recurrent tumor with contact to ventricle (HR 1.85, P = 0.036), ependymal spread (HR 2.97, P = 0.004) and distant recurrence (HR 1.75, P = 0.019) significantly shorter post-progression survival in multivariate analyses including well-established prognostic factors like age, Karnofsky Performance Score (KPS), therapy, extent of resection and patterns of primary tumors. Postoperative infarct volume might initiate hypoxia-mediated aggressive tumor growth resulting in multifocal and diffuse recurrence patterns and impaired survival.

Risk of cement leakage and pulmonary embolism by bone cement-augmented pedicle screw fixation of the thoracolumbar spine.

BACKGROUND: Cement-augmented pedicle screw instrumentation (CAPSI) of the thoracolumbar spine is indicated in osteoporosis or osteopenia to improve pullout strength and biomechanical stability of pedicle screws (PS). Only a few studies report on the incidence of pulmonary cement embolism or other complications associated with CAPSI. PURPOSE: The aim of this retrospective study was to assess the rate of CAPSI-associated complications. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Patients who underwent CAPSI due to spinal tumors or degenerative spine disease. OUTCOME MEASURES: Cement leakage, pulmonary cement embolism (PCE), mortality rate. METHODS: Our clinical database was reviewed for patients who underwent CAPSI between January 2012 and June 2015. A total of 165 patients (mean age 71±11.2; range: 46 to 93 years; m=62, f=103) were included. Indications were osteoporotic fractures (n=40), spinal metastases (n=57), degenerative (n=49) or infectious spine disease (n=5), and traumatic vertebral fractures (n=14) with an associated osteoporosis. Every patient received between 2 and 21 (mean 8±3.3) cement-augmented pedicle screws in the thoracolumbar and lumbosacral spine. Both intraoperative cement leakage in prevertebral veins, the inferior vena cava, and/or pulmonary arteries, and leakage detected on postoperative imaging were evaluated. We assessed the incidence of clinically symptomatic and asymptomatic events. RESULTS: In 29 of 31 patients with intraoperative suspicion of cement leakage into prevertebral veins or the inferior vena cava on lateral fluoroscopy, which were without hemodynamic relevance, cement extrusion was confirmed on postoperative X-ray or computed tomography (CT) scan. In three of eight patients with suspicion of PCE, PCE was verified on thoracic CT. Four patients experienced life-threatening intraoperative hemodynamic reactions, either due to cement embolism (n=2; 1.2%) or anaphylactic shock (n=2; 1.2%) with need for intraoperative cardiopulmonary resuscitation in three cases. Two patients died due to fulminant PCE. Three patients with dyspnea 1 day after surgery were also confirmed with PCE on chest CT. In five patients, an asymptomatic PCE was found incidentally on postoperative imaging. In addition, 68 patients with cement leakage into prevertebral veins or the ascending cava vein were found incidentally on postoperative spine X-ray or CT. Two of 10 patients with intraspinal epidural cement leakage required revision surgery. One hundred ten of 165 patients (66.7%) had clinically asymptomatic cement leakage. Thirteen patients had PCE (7.9%), of whom five (3.0%) were symptomatic. Two patients experienced intraoperative cement-induced anaphylaxis (1.2%). The overall symptomatic complication rate was 5.5% (n=9). The 30-day mortality rate was 1.8% (n=3). CONCLUSIONS: CAPSI bears a high risk of asymptomatic cement leakage. The risk for associated severe complications was also relatively high and probably underestimated considering the retrospective nature of the present study. A strict indication for cement augmentation, especially in patients with cardiac predisposition, should be the consequence. We doubt that technical aspects of cement application and/or different types of cement are capable of reducing the risk of these complications substantially.

Fractional Anisotropy Correlates with Overall Survival in Glioblastoma.

OBJECTIVE: Glioblastoma (GB) is an infiltrative disease that results in microstructural damage on a cellular level. Fractional anisotropy (FA) is an important estimate of diffusion tensor imaging (DTI) that can be used to assess microstructural integrity. The aim of this study was to examine the correlation between FA values and overall survival (OS) in patients with GB. METHODS: This retrospective single-center study included 122 consecutive patients with GB (50 women; median age, 63 years) with preoperative MRI including fluid attenuated inversion recovery (FLAIR), contrast-enhanced T1-weighted sequences, and DTI. FA and apparent diffusion coefficient (ADC) values in contrast-enhancing lesions (FA-CEL, FA-ADC), nonenhancing lesions, and central tumor regions were correlated to histopathologic and clinical parameters. Univariate and multivariate survival analyses were performed. RESULTS: Patients with low FA-CEL (median <0.31) showed significantly improved OS in univariate analysis (P = 0.028). FA-CEL also showed a positive correlation with Ki-67 proliferation index (P = 0.003). However, in a multivariate survival model, FA values could not be identified as independent prognostic parameters beside established factors such as age and Karnofsky performance scale score. FA values in nonenhancing lesions and central tumor regions and mean ADC values had no distinct influence on OS. CONCLUSIONS: FA values can provide prognostic information regarding OS in patients with GB. There is a correlation between FA-CEL values and Ki-67 proliferation index, a marker for malignancy. Noninvasive identification of more aggressive GB growth patterns might be beneficial for preoperative risk evaluation and estimation of prognosis.

Infarct volume after glioblastoma surgery as an independent prognostic factor.

Postoperative ischemia is associated with reduced functional independence measured by karnofsky performance score (KPS), which correlates well with overall survival. Other studies suggest that postoperative hypoxia might initiate infiltrative tumor growth. Therefore, aim of this study was to analyze the impact of infarct volume on overall survival and progression free survival (PFS) of glioblastoma patients.251 patients with surgery for a newly diagnosed glioblastoma (WHO IV) were retrospectively assessed. Pre- and postoperative KPS, date of death/last follow-up and histopathological markers were recorded. Pre- and postoperative tumor volume and the volume of postoperative infarction were manually segmented.A significant correlation of infarct volume with postoperative KPS decrease (P = 0.001) was observed. Infarct volume showed a significant impact on overall survival (P = 0.014), but not on PFS (P = 0.112) in univariate analysis. This effect increased in the subgroup of patients with near-total tumor resection (> 90%) (overall survival: P = 0.006, PFS: P = 0.066). Infarct volume remained as an independent prognostic factor for overall survival in multivariate analysis (HR 1.013 [1.000-1.026], P = 0.042) including other prognostic factors (age, extent of resection, postoperative KPS).Postoperative infarct volume significantly correlates as an independent factor with overall survival after glioblastoma surgery. Besides the influence of perioperative infarction on postoperative KPS, postoperative hypoxia might also have an effect on tumor biology initiating infiltrative growth and therefore impaired survival.

Postoperative ischemic changes following brain metastasis resection as measured by diffusion-weighted magnetic resonance imaging.

OBJECT: Brain metastases occur in 10% to 40% of patients harboring cancer. In cases of neurosurgical metastasis resection, all postoperative neurological deterioration should be avoided. Reasons for postoperative deficits can be direct tissue damage due to resection, hemorrhage, venous congestive infarcts, or arterial ischemic events leading to tissue infarction. The aim of this study was to evaluate whether postoperative ischemic infarctions occur in surgery for brain metastasis and to determine their influence on new postoperative neurological deficits. METHODS: Patients who underwent resection of brain metastases and had preoperative and early postoperative (within 48 hours) MRI scans, including diffusion-weighted imaging sequences and apparent diffusion coefficient maps, between January 2009 and May 2012 were included in this study. Clinical and histopathological data (histopathological results, pre- and postoperative neurological status, and previous tumor-specific therapy) were recorded. RESULTS: One hundred twenty-two patients (56 male, 66 female) who underwent resection of brain metastases were included. The patients' mean age was 60 years (range 21-89 years). The mean time span from initial tumor diagnosis to resection of brain metastasis was 44 months (range 0-338 months). The mean preoperative Karnofsky Performance Status was 80% (exact mean 76% ± 17% [SD]), and the mean postoperative value was 80% (exact mean 78% ± 17%). Twelve (9.8%) of the 122 patients had postoperative permanent worsening of a neurological deficit or a new permanent neurological deficit; 44 (36.1%) of the 122 patients had postoperative ischemic lesions. When comparing patients with and without previous brain irradiation, 53.8% of patients with previous brain irradiation had ischemic lesions on postoperative imaging compared with 31.3% of patients without previous brain irradiation (p = 0.033). There was a significant association between ischemia and postoperative neurological status deterioration (transient or permanent); 13 (29.5%) of 44 patients with ischemic lesions had deterioration of their neurological status compared with 7 (9%) of the 78 patients who did not have ischemic lesions (p = 0.003). CONCLUSIONS: This study demonstrates a high prevalence of vascular incidents in patients undergoing resection for metastatic brain disease. Patients harboring postoperative ischemic lesions detected by MRI have a higher rate of neurological deficits (transient or permanent). Patients who had previous irradiation therapy are at higher risk of developing postoperative ischemic lesions. A large number of postoperative neurological deficits are caused by ischemic incidents.