Repair of chronic and large rotator cuff tears using extra-synovial autografts: An experimental study in rabbits.

Purpose: To investigate whether and how extra-synovial autografts can enhance the reconstruction of chronic and large rotator cuff tears in a rabbit subscapularis model. Methods: Twenty rabbits were used to create a large subscapularis tear bilaterally. Six weeks later, the right shoulder of each rabbit was operated to repair the tear with an extra-synovial autograft, whereas the left shoulder did not undergo any surgery. At 6 and 12 weeks after the second procedure, the specimens underwent biomechanical and histological evaluation. Six more rabbits were used only as a normal reference. Results: Biomechanical evaluation demonstrated that the ultimate load to failure of the Graft group (184.1 ± 35.7 N) was significantly higher (p = 0.04) than that of the Defect group (144.5 ± 32.2 N) at 12 weeks after repair, rising to 76% of the normal subscapularis tendon tensile strength. Histological analysis revealed an enhanced healing environment with neoangiogenesis and decreased inflammatory response at the repair site. Moreover, the tendon maturing score of the Graft group increased substantially from 6 (15.8 ± 0.9) to 12 (23.1 ± 0.6) weeks after repair (p = 0.01). Conclusion: In vivo data support the efficacy of extra-synovial autograft interposition in repairing chronic and large rotator cuff tears in a rabbit subscapularis model. The autografts were capable of enhancing the biomechanical properties of the repaired tendons, as evidenced by increased tensile strength, and forming new connective tissue simulating a fibrocartilage zone, as revealed by histological evaluation. Level of Evidence: N/A.

Functional Magnetic Resonance Imaging and Diffusion Tensor Imaging-Tractography in Resective Brain Surgery: Lesion Coverage Strategies and Patient Outcomes.

Diffusion tensor imaging (DTI)-tractography and functional magnetic resonance imaging (fMRI) have dynamically entered the presurgical evaluation context of brain surgery during the past decades, providing novel perspectives in surgical planning and lesion access approaches. However, their application in the presurgical setting requires significant time and effort and increased costs, thereby raising questions regarding efficiency and best use. In this work, we set out to evaluate DTI-tractography and combined fMRI/DTI-tractography during intra-operative neuronavigation in resective brain surgery using lesion-related preoperative neurological deficit (PND) outcomes as metrics. We retrospectively reviewed medical records of 252 consecutive patients admitted for brain surgery. Standard anatomical neuroimaging protocols were performed in 127 patients, 69 patients had additional DTI-tractography, and 56 had combined DTI-tractography/fMRI. fMRI procedures involved language, motor, somatic sensory, sensorimotor and visual mapping. DTI-tractography involved fiber tracking of the motor, sensory, language and visual pathways. At 1 month postoperatively, DTI-tractography patients were more likely to present either improvement or preservation of PNDs (p = 0.004 and p = 0.007, respectively). At 6 months, combined DTI-tractography/fMRI patients were more likely to experience complete PND resolution (p < 0.001). Low-grade lesion patients (N = 102) with combined DTI-tractography/fMRI were more likely to experience complete resolution of PNDs at 1 and 6 months (p = 0.001 and p < 0.001, respectively). High-grade lesion patients (N = 140) with combined DTI-tractography/fMRI were more likely to have PNDs resolved at 6 months (p = 0.005). Patients with motor symptoms (N = 80) were more likely to experience complete remission of PNDs at 6 months with DTI-tractography or combined DTI-tractography/fMRI (p = 0.008 and p = 0.004, respectively), without significant difference between the two imaging protocols (p = 1). Patients with sensory symptoms (N = 44) were more likely to experience complete PND remission at 6 months with combined DTI-tractography/fMRI (p = 0.004). The intraoperative neuroimaging modality did not have a significant effect in patients with preoperative seizures (N = 47). Lack of PND worsening was observed at 6 month follow-up in patients with combined DTI-tractography/fMRI. Our results strongly support the combined use of DTI-tractography and fMRI in patients undergoing resective brain surgery for improving their postoperative clinical profile.

Independent component analysis: a reliable alternative to general linear model for task-based fMRI.

Background: Functional magnetic resonance imaging (fMRI) is a valuable tool for the presurgical evaluation of patients undergoing neurosurgeries. Although many pre-processing steps have been modified according to advances in recent years, statistical analysis has remained largely the same since the first days of fMRI. In this study, we examined the ability of Independent Component Analysis (ICA) to separate the activation of a language task in fMRI, and we compared it with the results of the General Lineal Model (GLM). Methods: Sixty patients undergoing evaluation for brain surgery due to various brain lesions and/or epilepsy and 20 control subjects completed an fMRI language mapping protocol that included three tasks, resulting in 259 fMRI scans. Depending on brain lesion characteristics, patients were allocated to (1) static/chronic not-expanding lesions (Group 1) and (2) progressive/expanding lesions (Group 2). GLM and ICA statistical maps were evaluated by fMRI experts to assess the performance of each technique. Results: In the control group, ICA and GLM maps were similar without any superiority of either technique. In Group 1 and Group 2, ICA performed statistically better than GLM, with a p-value of < 0.01801 and < 0.0237, respectively. This indicated that ICA performs as well as GLM when the subjects are able to cooperate well (less movement, good task performance), but ICA could outperform GLM in the patient groups. When both techniques were combined, 240 out of 259 scans produced reliable results, showing that the sensitivity of task-based fMRI can be increased when both techniques are integrated with the clinical setup. Conclusion: ICA may be slightly more advantageous, compared to GLM, in patients with brain lesions, across the range of pathologies included in our population and independent of symptoms chronicity. Our findings suggest that GLM analysis may be more susceptible to brain activity perturbations induced by a variety of lesions or scanner-induced artifacts due to motion or other factors. In our research, we demonstrated that ICA is able to provide fMRI results that can be used in surgery, taking into account patient and task-wise aspects that differ from those when fMRI is used in research.

N-Acetylcysteine Administration Attenuates Sensorimotor Impairments Following Neonatal Hypoxic-Ischemic Brain Injury in Rats.

Hypoxic ischemic (HI) brain injury that occurs during neonatal period has been correlated with severe neuronal damage, behavioral deficits and infant mortality. Previous evidence indicates that N-acetylcysteine (NAC), a compound with antioxidant action, exerts a potential neuroprotective effect in various neurological disorders including injury induced by brain ischemia. The aim of the present study was to investigate the role of NAC as a potential therapeutic agent in a rat model of neonatal HI brain injury and explore its long-term behavioral effects. To this end, NAC (50 mg/kg/dose, i.p.) was administered prior to and instantly after HI, in order to evaluate hippocampal and cerebral cortex damage as well as long-term functional outcome. Immunohistochemistry was used to detect inducible nitric oxide synthase (iNOS) expression. The results revealed that NAC significantly alleviated sensorimotor deficits and this effect was maintained up to adulthood. These improvements in functional outcome were associated with a significant decrease in the severity of brain damage. Moreover, NAC decreased the short-term expression of iNOS, a finding implying that iNOS activity may be suppressed and that through this action NAC may exert its therapeutic action against neonatal HI brain injury.

Delayed intracranial hemorrhage of patients with mild traumatic brain injury under antithrombotics on routine repeat CT scan: a systematic review and meta-analysis.

BACKGROUND: Patients on antithrombotics experiencing mild traumatic brain injury (mTBI) may benefit from a routine repeat CT scan to detect delayed intracranial hemorrhage (dICH). OBJECTIVES: The primary outcome was the incidence of dICH on routine repeat CT scans of mTBI patients on antithrombotics within an intra-hospital observation period of up to 48 hours. The secondary outcomes were potential risk factors, readmissions, neurosurgical interventions, and mortality. METHODS: A systematic review and a meta-analysis of single proportions were performed according to the PRISMA and PRESS guidelines. The risk of bias was assessed using Newcastle-Ottawa Scale. RESULTS: Eighteen studies with 4613 patients were included. The pooled incidence of dICH was 2% [95% CI 1-2%] with similar rates between different antithrombotic regimens, even in combination. Of the 67 patients with dICH reported (1.45%), eleven required surgery (0.24%), while six died (0.13%). Loss of consciousness was a risk factor of dICH (risk ratio 3.04 [95%CI 0.96; 9.58]). A total of 48 patients were reported for readmission without associated death or surgical intervention. CONCLUSION: The contribution of this routine repeat CT scan should be questioned due to the low incidence, the limited clinical significance, and the unsubstantiated clinical benefit of early or systematic detection of dICH.

Chronic massive rotator cuff tear in rats: in vivo evaluation of muscle force and three-dimensional histologic analysis.

BACKGROUND: Massive rotator cuff tear repair is frequently complicated by unsatisfactory clinical results due to possible tendon retraction, muscle atrophy, and fatty degeneration. The objective of this study was the development of a chronic massive tear in a rat model and the evaluation of the muscle force in vivo and of the histologic changes in a 3- dimensional manner. METHODS: To simulate massive rotator cuff tears, both the supraspinatus (SS) and the infraspinatus (IS) tendons were surgically detached from the right humerus of 15 male adult Sprague-Dawley rats. Twelve weeks postoperatively, all animals underwent isometric tension recordings of both the SS and IS muscles. Histologic analysis and image deconvolution processing were performed to estimate the presence and the distribution of atrophy in 3 dimensions. RESULTS: An overall 30% and 35% reduction in muscle force of the SS and IS muscles, respectively, was observed compared with the left uninjured shoulder (P < .005). Histologic analysis revealed that the degeneration and the fatty infiltration were more evident near the tendon and at the dorsal side in both muscle groups. CONCLUSIONS: These results show that functional impairment of SS and IS muscles after chronic massive tendon tears could be attributed to the decrease in muscle force production during their repair on the greater tuberosity and, second, to the comparatively greater degeneration of their dorsal part.

Volumetric and MGMT parameters in glioblastoma patients: survival analysis.

BACKGROUND: In this study several tumor-related volumes were assessed by means of a computer-based application and a survival analysis was conducted to evaluate the prognostic significance of pre- and postoperative volumetric data in patients harboring glioblastomas. In addition, MGMT (O6-methylguanine methyltransferase) related parameters were compared with those of volumetry in order to observe possible relevance of this molecule in tumor development. METHODS: We prospectively analyzed 65 patients suffering from glioblastoma (GBM) who underwent radiotherapy with concomitant adjuvant temozolomide. For the purpose of volumetry T1 and T2-weighted magnetic resonance (MR) sequences were used, acquired both pre- and postoperatively (pre-radiochemotherapy). The volumes measured on preoperative MR images were necrosis, enhancing tumor and edema (including the tumor) and on postoperative ones, net-enhancing tumor. Age, sex, performance status (PS) and type of operation were also included in the multivariate analysis. MGMT was assessed for promoter methylation with Multiplex Ligation-dependent Probe Amplification (MLPA), for RNA expression with real time PCR, and for protein expression with immunohistochemistry in a total of 44 cases with available histologic material. RESULTS: In the multivariate analysis a negative impact was shown for pre-radiochemotherapy net-enhancing tumor on the overall survival (OS) (p = 0.023) and for preoperative necrosis on progression-free survival (PFS) (p = 0.030). Furthermore, the multivariate analysis confirmed the importance of PS in PFS and OS of patients. MGMT promoter methylation was observed in 13/23 (43.5%) evaluable tumors; complete methylation was observed in 3/13 methylated tumors only. High rate of MGMT protein positivity (> 20% positive neoplastic nuclei) was inversely associated with pre-operative tumor necrosis (p = 0.021). CONCLUSIONS: Our findings implicate that volumetric parameters may have a significant role in the prognosis of GBM patients. Furthermore, volumetry could help not only to improve the prediction of outcome but also the outcome itself by identifying patients at high risk of treatment failure and, thus, seek alternative treatment for these patients. In this small series, MGMT protein was associated with less aggressive tumor characteristics.

The importance of tumor volume in the prognosis of patients with glioblastoma: comparison of computerized volumetry and geometric models.

BACKGROUND AND PURPOSE: The importance of tumor volume as a prognostic factor in high-grade gliomas is highly controversial and there are numerous methods estimating this parameter. In this study, a computer-based application was used in order to assess tumor volume from hard copies and a survival analysis was conducted in order to evaluate the prognostic significance of preoperative volumetric data in patients harboring glioblastomas. PATIENTS AND METHODS: 50 patients suffering from glioblastoma were analyzed retrospectively. Tumor volume was determined by the various geometric models as well as by an own specialized software (Volumio). Age, performance status, type of excision, and tumor location were also included in the multivariate analysis. RESULTS: The spheroid and rectangular models overestimated tumor volume, while the ellipsoid model offered the best approximation. Volume failed to attain any statistical significance in prognosis, while age and performance status confirmed their importance in progression-free and overall survival of patients. CONCLUSION: Geometric models provide a rough approximation of tumor volume and should not be used, as accurate determination of size is of paramount importance in order to draw safe conclusions in oncology. Although the significance of volumetry was not disclosed, further studies are definitely required.

Demyelinating plaque imitates an intramedullary tumour.

An isolated spinal demyelinating lesion is very rare and almost always associated with multiple sclerosis. There are only a few reports of biopsy or resection of MS-associated lesions. Sometimes the radiological and the histopathological findings can lead to a false diagnosis of a tumour. A 15-year-old girl presented with a progressive spastic tetraparesis and various associated clinical symptoms. Magnetic resonance imaging (MRI) suggested a possible intramedullary tumour extending from C4 to C7 and the need for surgical intervention. There was no previous neurological or other history and the brain MRI was normal. The performing surgeons based their procedures on oncological criteria. The extracted lesion was finally diagnosed as a demyelinating plaque. The postoperative course was uneventful without deterioration of the neurological status and the young patient improved completely after 4-months of rehabilitation. After an 8-year follow-up, the patient remains in remission and free of neurological defects. Apart from the radiological findings, the CSF exam as well as the evoked potentials does not suggest a diagnosis of MS. A demyelinating plaque in the cervical spinal cord can occasionally imitate a cervical intramedullary tumour leading to an operation. Such lesions underscore the sensitivity of present-day lesion detection procedures. An addition of a MS work up could be beneficial in some cases of intramedullary tumours without a typical history, although in the case presented this type of workup was negative.

Delayed persistent hyperthermia after resection of a craniopharyngioma.

OBJECTIVE AND IMPORTANCE: Disorders of thermoregulation are occasionally noticed after operations in the region of the third ventricle. Various factors are usually implicated, but the actual contribution of each of them is rather vague. Apart from the presumed derangement in the functional connections of the hypothalamic region, mechanical reasons of compression should be thoroughly considered. CLINICAL PRESENTATION: An 8.5-year-old patient was subjected to a radical excision of a craniopharyngioma compressing the third ventricle. Three months after the operation, he presented with a febrile syndrome of unknown origin. All usual investigations proved negative. INTERVENTION: A chronic subdural hygroma was evacuated, an encapsulated CSF cyst of the suprachiasmatic cistern was drained and the lamina terminalis incised resulting in a moderate control of pyrexia. The administration of chlorpromazine contributed to the final resolution of hyperthermia. CONCLUSION: Postoperative hyperthermia may result following resection of tumors of the hypothalamic floor. It should not be blindly attributed to hypothalamic dysfunction as surgical causes could be implicated as well. Chlorpromazine could be a useful adjunct to the correction of the disorder.