Correction to: Revision surgery in thoracic disc herniation.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ ), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

Revision surgery in thoracic disc herniation.

PURPOSE: Surgical treatment failures or strategies for the reoperation of residual thoracic disc herniations are sparsely discussed. We investigated factors that led to incomplete disc removal and recommend reoperation strategies. METHODS: As a referral centre for thoracic disc disease, we reviewed retrospectively the clinical records and imaging studies before and after the treatment of patients who were sent to us for revision surgery for thoracic disc herniation from 2013 to 2018. RESULTS: A total of 456 patients were treated from 2013 to 2018 at our institution. Twenty-one patients had undergone previously thoracic discectomy at an outside facility and harboured residual, incompletely excised and symptomatic herniated thoracic discs. In 12 patients (57%), the initial symptoms that led to their primary operation were improved after the first surgery, but recurred after a mean of 2.8 years. In seven patients (33%) they remained stable, and in two cases they were worse. All patients were treated via all dorsal approaches. In all 21 cases, the initial excision was incomplete regarding medullar decompression. All of the discs were removed completely in a single revision procedure. After mean follow-up of 24 months (range 12-57 months), clinical neurological improvement was demonstrated in seven patients, while three patients suffered a worsening and 11 patients remained stable. CONCLUSION: Our data suggest that pure dorsal decompression provides a short relief of the symptoms caused by spinal cord compression. Progressive myelopathy (probably due to mechanical and vascular deficits) and scar formation may cause worsening of symptoms. These slides can be retrieved under Electronic Supplementary Material.

Natural history of intramedullary spinal cord ependymoma in patients preferring nonoperative treatment.

Surgical resection of intramedullary spinal cord ependymoma still remains the standard of care but is challenging and occasionally associated with poor outcome. The aim of this study is therefore to provide additional information regarding the natural history of conservatively treated symptomatic intramedullary spinal cord ependymoma. Retrospective, single center review of all patients with intramedullary spinal cord ependymoma treated conservatively (wait and see) between 1980 and 2016. The neurological outcomes at first presentation, as well as in long-term follow-up, were assessed using the modified McCormick Disability Scale and modified Rankin Scale. Thirteen of 41 patients were managed conservatively and were included in the study. Mean age at the admission was 49 years. There were seven women and six men. All patients were symptomatic at the time of presentation. The mean follow-up from admission to the last neurological examination was 47.9 months. The mean modified McCormick score in conservatively treated patients was 1.3 at admission and 1.6 (p = 0.3) at last follow-up. There was no significant neurological detoriation over time in conservatively managed patients as assessed by the modified Rankin Scale at first presentation and last follow-up (mRS scores of 0-2, 100 vs 92%; p = 0.9). This cohort of conservatively managed patients with symptomatic intramedullary spinal cord ependymoma was clinically stable throughout the follow-up period. Our data provide additional information for counseling patients with intramedullary spinal cord tumors who chose a nonoperative treatment.

Muscular atrophy in severe cases of cubital tunnel syndrome: prognostic factors and outcome after surgical treatment.

BACKGROUND: Cubital tunnel syndrome (CuTS) is a frequent neuropathy, leading to sensor-motoric dysfunction. Many patients even present with muscular atrophy as a sign for severe and long-lasting nerve impairment, usually suggesting unfavourable outcome. We analysed if those patients benefit from surgical treatment on a long-term basis. METHODS: Between January 2010 and March 2015, 42 consecutive cases of CuTS with atrophy of the intrinsic hand muscles were surgically treated in our department. Clinical data of the treatment course and postoperative results were collected. Follow-up was prospectively assessed according to McGowen grading and Bishop outcome score. Mean follow-up time was 39.8 (±17.0) months. RESULTS: All patients were treated with in situ decompression; in 33%, submuscular transposition was performed. Forty-five percent showed improvement of sensory deficits and 57% showed improvement of motor deficits 6 months after the operation. Atrophy improved in 76%. At the time of follow-up, 79% were satisfied with the postoperative result and 77% of patients reached good or excellent outcome according to modified Bishop rating scale. Patients with improvement of atrophy had significantly shorter symptom duration period (7 ± 10 months vs 26 ± 33 months; p < 0.05). In the case of intraoperative pseudoneuroma observation, atrophy improvement was less likely (p < 0.05). CONCLUSIONS: In severe cases of CuTS with atrophy of the intrinsic hand muscles, surgical treatment enables improvement of sensory function, motor function and atrophy even in cases with muscular atrophy. Atrophy improvement was more likely in cases of short symptom duration and less likely in cases with pseudoneuroma.

Intratumoral Concentrations and Effects of Orally Administered Micellar Curcuminoids in Glioblastoma Patients.

BACKGROUND: The oral bioavailability of curcuminoids is low, but can be enhanced by incorporation into micelles. The major curcuminoid curcumin has antitumor effects on glioblastoma cells in vitro and in vivo. We therefore aimed to determine intratumoral concentrations and the clinical tolerance of highly bioavailable micellar curcuminoids in glioblastoma patients. METHODS: Thirteen glioblastoma patients ingested 70 mg micellar curcuminoids [57.4 mg curcumin, 11.2 mg demethoxycurcumin (DMC), and 1.4 mg bis-demethoxycurcumin (BDMC)] three times per day for 4 days (total amount of 689 mg curcumin, 134 mg DMC, and 17 mg BDMC) prior to planned resection of their respective brain tumors. Tumor and blood samples were taken during the surgery and analyzed for total curcuminoid concentrations. (31)P magnetic resonance spectroscopic imaging was performed before and after curcuminoid consumption. RESULTS: Ten patients completed the study. The mean intratumoral concentration of curcumin was 56 pg/mg of tissue (range 9-151), and the mean serum concentration was 253 ng/ml (range 129-364). Inorganic phosphate was significantly increased within the tumor (P = 0.034). The mean ratio of phosphocreatine to inorganic phosphate decreased, and the mean intratumoral pH increased (P = 0.08) after curcuminoid intervention. CONCLUSION: Oral treatment with micellar curcuminoids led to quantifiable concentrations of total curcuminoids in glioblastomas and may alter intratumoral energy metabolism.

Perioperative cerebral ischemia promote infiltrative recurrence in glioblastoma.

BACKGROUND: Hypoxia is a key driver for infiltrative growth in experimental gliomas. It has remained elusive whether tumor hypoxia in glioblastoma patients contributes to distant or diffuse recurrences. We therefore investigated the influence of perioperative cerebral ischemia on patterns of progression in glioblastoma patients. METHODS: We retrospectively screened MRI scans of 245 patients with newly diagnosed glioblastoma undergoing resection for perioperative ischemia near the resection cavity. 46 showed relevant ischemia nearby the resection cavity. A control cohort without perioperative ischemia was generated by a 1:1 matching using an algorithm based on gender, age and adjuvant treatment. Both cohorts were analyzed for patterns of progression by a blinded neuroradiologist. RESULTS: The percentage of diffuse or distant recurrences at first relapse was significantly higher in the cohort with perioperative ischemia (61.1%) compared to the control cohort (19.4%). The results of the control cohort matched well with historical data. The change in patterns of progression was not associated with a difference in survival. CONCLUSIONS: This study reveals an unrecognized association of perioperative cerebral ischemia with distant or diffuse recurrence in glioblastoma. It is the first clinical study supporting the concept that hypoxia is a key driver of infiltrative tumor growth in glioblastoma patients.

Is postoperative imaging mandatory after meningioma removal? Results of a prospective study.

BACKGROUND: Routine postoperative imaging (PI) following surgery for intracranial meningiomas is common practice in most neurosurgical departments. The purpose of this study was to determine the role of routine PI and its impact on clinical decision making after resection of meningioma. METHODS: Patient and tumor characteristics, details of radiographic scans, symptoms and alteration of treatment courses were prospectively collected for patients undergoing removal of a supratentorial meningioma of the convexity, falx, tentorium, or lateral sphenoid wing at the authors' institution between January 1st, 2010 and March 31st, 2012. Patients with infratentorial manifestations or meningiomas of the skull base known to be surgically difficult (e.g. olfactory groove, petroclival, medial sphenoid wing) were not included. Maximum tumor diameter was divided into groups of < 3 cm (small), 3 to 6 cm (medium), and > 6 cm (large). RESULTS: 206 patients with meningiomas were operated between January 2010 and March 2012. Of these, 113 patients met the inclusion criteria and were analyzed in this study. 83 patients (73.5%) did not present new neurological deficits, whereas 30 patients (26.5%) became clinically symptomatic. Symptomatic patients had a change in treatment after PI in 21 cases (70%), while PI was without consequence in 9 patients (30%). PI did not result in a change of treatment in all asymptomatic patients (p<0.001) irrespective of tumor size (p<0.001) or localization (p<0.001). CONCLUSIONS: PI is mandatory for clinically symptomatic patients but it is safe to waive it in clinically asymptomatic patients, even if the meningioma was large in size.

Benefit of tumor resection for recurrent glioblastoma.

In the treatment of glioblastoma (GBM) the impact of radical tumor resection as first line therapy is beyond controversy. The significance of a second resection in case of tumor-recurrence remains unclear and is an issue of debate. Since GBMs always recur, it is important to determine whether or not patients will benefit from repeat surgery. We performed a retrospective analysis of our prospectively collected database and evaluated all re-resected patients with primary GBM who underwent second surgery during a 3 years period. All patients underwent early postoperative magnetic resonance imaging. We determined survival after re-resection with regard to possible prognostic factors using Kaplan-Meier estimates and Cox regression analyses. Forty patients were included in this study. Median age was 58 years and median KPS score was 80. Average tumor volume was 5.5 cm(3). A radiologically confirmed complete resection was achieved in 29 patients (72.5 %). Median follow-up was 18.8 months, and median survival after re-resection was 13.5 months. Only complete removal of contrast enhancing tumor was significantly correlated with survival after re-resection according to multivariate analysis. There was a statistical trend for KPS score influencing survival. In contrast, time between first diagnosis and tumor-recurrence, tumor volume at recurrence, MGMT status and MSM score were not significantly correlated with survival after second surgery. In the event of tumor recurrence, patients in good clinical condition with recurrent GBM amenable to complete resection should thus not be withheld second surgery as a treatment option.

Male sex as a risk factor for the clinical course of skull base chordomas.

OBJECT: Chordomas of the skull base are rare and locally invasive and have a poor prognosis. The aim of this retrospective multicenter study was to evaluate the current pattern of care and clinical course and to identify prognostic factors. METHODS: A total of 47 patients (26 men; mean age 48.5 years) treated in 5 centers were included. Histology was centrally reviewed; additionally, semiquantitative N- and E-cadherin expression analysis was performed. Prognostic factors were obtained from multivariate regression models. For survival analysis the Kaplan-Meier method was used. RESULTS: The median follow-up period was 5.2 years. Complete resection, incomplete resection, and extended biopsy were performed in 14.9%, 80.9%, and 4.3% of patients, respectively. Surgical morbidity was not associated with extent of resection. Adjuvant radiation therapy was performed in 30 (63.8%) of 47 patients. The median progression-free survival (PFS) was 7.3 years. Complete resection prolonged median overall survival (OS) (p = 0.04). Male patients presented with worse PFS (4.8 years vs 9.8 years; p = 0.04) and OS (8.3 years vs not reached; p = 0.03) even though complete resection was exclusively achieved in the male subpopulation. Multivariate analysis confirmed male sex as the most important risk factor for tumor progression (p = 0.04) and death (p = 0.02). Age, duration of symptoms, initial Karnofsky Performance Scale score, brainstem compression, involvement of the petrous bone, infiltration of the dura mater, modality and dose of radiation therapy, and the E- and N-cadherin expression patterns did not gain prognostic relevance. CONCLUSIONS: In skull base chordomas, male patients bear a higher risk of progressive disease and death. Male patients might benefit from more aggressive adjuvant therapy and/or from a closer follow-up schedule.

Retractor-endoscopic nerve decompression in carpal and cubital tunnel syndromes: outcomes in a small series.

OBJECTIVE: To present midterm to long-term results obtained in carpal tunnel release, in situ decompression, and anterior transposition of the ulnar nerve using the retractor integrated endoscope. METHODS: During the period 2000-2010, 145 patients underwent endoscopic carpal tunnel releases (n = 47), endoscopic in situ decompression of the ulnar nerve (n = 55), and endoscopic anterior transposition of the ulnar nerve (n = 52). Bilateral surgery was performed in 9 patients. Independent examinations at 24 months after surgery were used for objective results (Bishop score). Subjective results were procured using a questionnaire. RESULTS: After endoscopic carpal tunnel release, 59.6% of patients showed excellent results, 21.2% showed good results, 12.8% showed fair results, and 6.4% showed poor results according to objective scoring. In 85% of patients, subjective improvement was noted after surgery; symptoms were the same as before surgery in 12.8% of patients and were worse in 2.1% of patients after surgery. After endoscopic in situ decompression, 56.4% of patients showed excellent results on objective scoring, 32.7% showed good results, 9.1% showed fair results, and 1.8% showed poor results. On subjective questioning, 72.7% of patients reported improvement, 20% reported no change in symptoms, and 7.3% reported worse symptoms. After endoscopic anterior transposition of the ulnar nerve, 48.1% of patients showed excellent results on objective scoring, 26.9% showed good results, 23.1% showed fair results, and 1.9% showed poor results. Subjectively, 65.4% of patients reported improvement, 26.9% reported no change in symptoms, and 7.7% reported worse symptoms. Patients with symptom duration of <9 months before surgery showed better results than patients with symptom duration of >9 months. CONCLUSIONS: The retractor-endoscopic technique provides good long-term results after carpal tunnel release, in situ decompression, and anterior subcutaneous transposition of the ulnar nerve. Outcomes showed some correlation to the duration of preoperative symptoms.

A multi-center retrospective analysis of treatment effects and quality of life in adult patients with cranial ependymomas.

Long term quality of life data of adult patients harboring intracranial ependymomas have not been reported. The role of adjuvant radiation therapy in Grade II ependymomas is unclear and differs from study to study. We therefore sought to retrospectively analyze outcome and quality of life of adult patients that were operated on intracranial ependymomas at four different surgical centers in two countries. All patients were attempted to be contacted via telephone to assess quality of life (QoL) at the time of the telephone interview. The standard EORTC QoL Questionnaire C30 (EORTC QLQ-C30) and the EORTC QLQ-Brain Cancer Module (QLQ-BN20) were used. 64 adult patients with intracranial ependymomas were included in the study. The only factor that was associated with increased survival was age <55 years (p < 0.001). Supratentorial location was correlated with shorter progression free survival than infratentorial location (PFS; p = 0.048). In WHO Grade II tumors local irradiation did not lead to increased PFS (p = 0.888) or overall survival (p = 0.801). Even for incompletely resected Grade II tumors local irradiation did not lead to a benefit in PFS (p = 0.911). In a multivariate analysis of QoL, irradiated patients had significantly worse scores in the item "fatigue" (p = 0.037) than non-irradiated patients. Here we present QoL data of adult patients with intracranial ependymomas. Our data show that local radiation therapy may have long-term effects on patients' QoL. Since in the incompletely resected Grade II tumors local irradiation did not lead to a benefit in PFS in this retrospective study, prospective randomized studies are necessary. In addition to age, supratentorial tumor location is associated with a worse prognosis in adult ependymoma patients.

Anti-tissue factor (TF9-10H10) treatment reduces tumor cell invasiveness in a novel migratory glioma model.

In vitro and descriptive studies of human tissue samples revealed the pro-coagulant glycoprotein tissue factor (TF) as a potent player in glioma cell infiltration that is activated by hypoxia and has also been shown to be upregulated by mutations of TP53 or PTEN. Here we present the morphological and genetic characterization of a novel glioblastoma in vivo model and provide evidence that treatment with an antibody targeting TF leads to reduced glioma cell invasiveness. Therefore, we established a murine xenograft treatment model by transplanting the angiogenic and diffusely infiltrating human glioma cell line MZ-18 with endogenous TF expression into nude mice brains and treating these mice with an intracranial osmotic pump system continuously infusing a monoclonal antibody against TF (mAb TF9-10H10). The human MZ-18 cell line harbors two TP53 mutations resulting in a strong nuclear accumulation of p53, thereby facilitating the unambiguous identification of tumor cells in the xenograft model. Intracranial application of TF9-10H10 significantly reduced invasion of MZ-18 cells compared to mock-treated control animals. The extent of activated blood vessels was also reduced upon anti-TF treatment. Thus, targeting the TF pathway might be a promising treatment strategy for future glioblastoma therapies, by affecting both invading tumor cells and tumor vasculature.

Open vs retractor-endoscopic in situ decompression of the ulnar nerve in cubital tunnel syndrome: a retrospective cohort study.

BACKGROUND: Both open ulnar nerve decompression and retractor-endoscopic ulnar nerve decompression have been shown to yield good results. However, a comparative evaluation of the techniques is lacking. OBJECTIVE: To compare the results of open and endoscopic surgery in cubital tunnel syndrome. METHODS: One hundred fourteen patients undergoing open (n = 59) or endoscopic (n = 55) decompression of the ulnar nerve for cubital tunnel syndrome were retrospectively compared. The long- and short-term outcomes were compared with respect to the time until return to full activity and the duration of postoperative pain. Additionally, matched pairs between the 2 groups were chosen for analysis (n = 34). RESULTS: Long-term results in the open vs endoscopic groups were as follows: excellent results, 54.2% vs 56.4%; good results, 23.8% vs 32.7%; fair results, 20.3% vs 9.1%; and poor results, 1.7% vs 1.8%, respectively. For the matched pairs, the results had similar significance levels (P = .84). The times until return to full activity in the open vs the endoscopic groups were as follows: 2 to 7 days, 18.6% vs 76.4%; 7 to 14 days, 55.9% vs 10.9%; and > 14 days, 25.4% vs 12.7% (P < .001 between nonmatched and matched pairs). The durations of postoperative pain in the open vs the endoscopic groups were as follows: 1 to 3 days, 45.8% vs 67.3%; 3 to 10 days, 42.5% vs 25.4%; and > 10 days, 11.7% vs 7.3% (P =.04 for nonmatched and P = .05 for matched pairs). CONCLUSION: There are no significant differences in long-term outcomes after open and retractor-endoscopic in situ decompression of the ulnar nerve in cubital tunnel syndrome. The short-term results are significantly better in endoscopic surgery.

On the value of routine prothrombin time screening in elective neurosurgical procedures.

OBJECT: The authors performed a study to evaluate whether preoperative assessment of prothrombin time (PT) is mandatory in patients undergoing routinely planned neurosurgical procedures. METHODS: The charts of all patients admitted to general wards of the authors' department for routinely planned surgery (excluding trauma and ICU patients) between 2006 and 2010 were retrospectively reviewed. The authors assessed preoperative PT and the clinical courses of all patients, with special consideration for patients receiving coagulation factor substitution. All cases involving hemorrhagic complications were analyzed in detail with regard to pre- and postoperative PT abnormalities. Prothrombin time was expressed as the international normalized ratio, and values greater than 1.28 were regarded as elevated. RESULTS: Clinical courses and PT values of 4310 patients were reviewed. Of these, 33 patients (0.7%) suffered hemorrhagic complications requiring repeat surgery. Thirty-one patients (94%) had a normal PT before the initial operation, while 2 patients had slightly elevated PT values of 1.33 and 1.65, which were anticipated based on the patient's history. In the latter 2 cases, surgery was performed without prior correction of PT. Preoperatively, PT was elevated in 78 patients (1.8%). In 73 (93.6%) of the 78 patients, the PT elevation was expected and explained by each patient's medical history. In only 5 (0.1%) of 4310 patients did we find an unexpected PT elevation (mean 1.53, range 1.37-1.74). All 5 patients underwent surgery without complications, while 2 had received coagulation factor substitution preoperatively, as requested by the surgeon, because of an estimated risk of bleeding complications. None of the 5 patients received coagulation factor substitution postoperatively, and later detailed laboratory studies ruled out single coagulation factor deficiencies. There was no statistically significant association between preoperatively elevated PT levels and the occurrence of hemorrhagic complications (p = 0.12). Before the second procedure but not before the initial operation, 4 (12%) of the 33 patients had elevated PT. CONCLUSIONS: The findings suggest that the value of preoperative PT testing is limited in patients in whom a normal history can be ascertained. Close postoperative PT control is necessary in every neurosurgical patient, and better tests need to be developed to identify patients who are prone to hemorrhagic complications.

Risk of ischemia in glioma surgery: comparison of first and repeat procedures.

The role of repeat resection in the multimodal treatment of gliomas is unclear. Repeat surgery theoretically carries a higher risk of inducing neurological deficits, which might even out any advantage of cytoreduction. We sought to determine whether the occurrence of perioperative infarction is higher for repeat surgery than for first surgery, and sought to identify factors associated with the occurrence of postoperative infarction. Therefore, we searched our database to identify patients who were operated for primary or recurrent glial tumors between October 2007 and October 2010. We analyzed 177 procedures, of which 130 (73.4%) were first surgeries and 47 (26.5%) were repeat. Initial WHO grades, KPS scores, and age were evenly distributed between the groups. Forty-six (26.0%) patients had new DWI lesions on their postoperative MRI scan. Eighteen (10.2%) patients had new lesions greater than 4 cm(3). Among these were 11 (6.2%) patients, for whom the new lesion caused neurologic deficit. There was no difference between first and repeat surgery with regard to the occurrence of new DWI lesions (27.7 vs. 21.3%, P = 0.77) or neurological deficits (10.0 vs. 10.6%, P = 1.0). Tumor location in the insula, operculum, and temporal lobe was found to be significantly associated with the occurrence of new DWI lesions. We conclude that repeat surgery should not be withheld as a treatment option for patients with recurrent gliomas for fear of a higher risk of postoperative infarction or new neurologic deficit than the first surgery.

Management, risk factors and outcome of cranial dural arteriovenous fistulae: a single-center experience.

BACKGROUND: The role of endovascular interventions in managing dural arteriovenous fistulas (DAVFs) is increasing. Furthermore, in patients with aggressive DAVFs, different surgical interventions are required for complete obliteration or disconnection. Our objective was to evaluate the management of patients with intracranial DAVFs treated in our institution to identify the parameters that may help guide the long-term management of these lesions. METHODS: The hospital records of 53 patients with intracranial DAVFs were reviewed. We then conducted a systematic telephone interview to obtain long-term follow-up information. RESULTS: The main presenting symptoms were tinnitus and headache. Nineteen (35%) patients presented with intracranial bleeding, 84% of patients scored between 0 and 2 using a modified Rankin Scale at the last follow-up visit. Twenty-four patients were treated surgically. Overall postoperative complications occurred in seven (29%) surgically treated patients, but only two patients permanently worsened. For patients with Borden type II and III fistulas, the annual incidence of hemorrhage was 30%. Two patients had late recurrences of surgically and endovascularly occluded DAVFs. Long-term follow-up showed that compared with spinal DAVFs, only 50% of intracranial DAVFs showed complete remission of symptoms, 41% partial remission, 6% no remission and 4% deterioration of symptoms that led to treatment of the DAVF. CONCLUSION: In general, intracranial DAVFs can be successfully surgically managed by simple venous disconnection in many cases. However, half of the patients do not show complete remission of symptoms. Age and the occurrence of perioperative complication were the most important determinants of outcome.

The pro-migratory and pro-invasive role of the procoagulant tissue factor in malignant gliomas.

During the infiltration process, glioma cells are known to migrate along preexisting anatomical structures such as blood vessels, axonal fiber tracts and the subependymal space, thereby widely invading surrounding CNS tissue. This phenomenon represents a major obstacle for the clinical treatment of these tumours. Several extracellular key factors and intracellular signaling pathways have been previously linked to the highly aggressive, invasive phenotype observed in malignant gliomas. The glioblastoma (GBM) which is the most malignant form of these tumors, is histologically characterized by areas of tumor necroses and pseudopalisading cells, the latter likely representing tumor cells actively migrating away from the hypoxic-ischemic core of the tumor. It is believed that intravascular thromboses play a major role in the emergence of hypoxia and intratumoral necroses in GBMs. One of the most highly upregulated prothrombotic factor in malignant gliomas is tissue factor (TF), a 47 kDa type I transmembrane protein belonging to the cytokine receptor superfamily. In a recent study, we provided evidence that TF/FVIIa signaling via the protease-activated receptor 2 (PAR-2) promotes cell growth, migration and invasion of glioma cells. In this point of view article we outline the key molecular players involved in migration and invasion of gliomas, highlight the potential role of TF for the pro-migratory and pro-invasive phenotype of these tumors and discuss the underlying mechanisms on the cellular level and in the tumor microenvironment.

Differential recovery of behavioral status and brain function assessed with functional magnetic resonance imaging after mild traumatic brain injury in the rat.

OBJECTIVE: The relationship between cerebral integrity, recovery of brain function, and neurologic status after mild traumatic brain injury is incompletely characterized. DESIGN: Prospective and randomized study in rodents. SETTING: University laboratory. SUBJECTS: Male Wistar rats (290-310 g). INTERVENTIONS: In rats, quantitative diffusion weighted imaging (DWI), perfusion weighted imaging (PWI), T2-weighted imaging (T2WI), and functional magnetic resonance imaging (fMRI) were performed up to 21 days after weight-induced, closed-head, mild traumatic brain injury (MTBI, n = 6) or sham operation (n = 6). Pixel-by-pixel analysis and region of interest analysis were used to evaluate structural (apparent diffusion coefficient [ADC] and basal cerebral blood flow [bCBF]) and functional magnetic resonance signal changes within the brain, respectively. Quantitative fMRI signal changes were correlated with behavioral measures. MEASUREMENTS AND MAIN RESULTS: Despite normal appearing DWI and T2WI findings following MTBI, persistent hypoperfusion developed that was not associated with cytotoxic edema. In contrast, the ADC was significantly increased by approximately 5% at 1 and 7 days post-MTBI. Post-MTBI fMRI responses to hypercapnia and forepaw stimulation were significantly impaired and showed a differential recovery rate between and within investigated region of interests. Significant dysfunction in forepaw placement test persisted up to day 1 and correlated significantly with fMRI signal changes in the primary somatosensory and motor cortices. CONCLUSIONS: MTBI produced distinct changes on multimodal MRI and behavioral variables acutely and chronically. Following MTBI, fMRI and ADC-bCBF pixel-by-pixel analysis identified subtle structural and functional alterations in the brain that appeared completely normal on conventional DWI and T2WI after concussion injury. The former techniques may therefore provide great potential for understanding mild traumatic brain injury, identifying mechanisms underlying recovery, and investigating specific interventions to enhance functional outcome.