Deniz Konya

Endovascular treatment increases but gamma knife radiosurgery decreases angiogenic activity of arteriovenous malformations: an in vivo experimental study using a rat cornea model.

OBJECTIVETo compare the angiogenic potentials of embolized, gamma knife–treated or untreated cerebral arteriovenous malformations (AVMs), using a rat cornea angiogenesis model. METHODSTissue samples from cerebral AVM patients who were either untreated or had previously been treated with embolization or gamma knife radiosurgery and who had undergone operations for hemorrhage at the Neurosurgery Department or the Neurological Sciences Institute of Marmara University were used. For the macroscopic evaluation of angiogenesis, tissue samples were inoculated in a micropocket created on the rat eye, and the level of angiogenic activity was graded macroscopically for 15 days, with glioblastoma multiforme and normal brain artery tissues serving as positive and negative controls, respectively. For the other part of the experiment, eyes of another set of rats were inoculated with the study samples only using the same cornea angiogenesis model, in which microvessel count and vascular endothelial growth factor assessment was done at days 3, 7, 11, and 15. RESULTSBased on our macroscopic findings in the cornea angiogenesis model, embolized AVMs exhibited the highest angiogenic activity, followed by untreated AVMs and gamma knife–treated AVMs. Evaluations of vascular endothelial growth factor expression and microvessel counts showed a similar relation among the 3 tissue groups with regard to the level of angiogenic activity, supporting the results of macroscopic examinations. CONCLUSIONThis study, for the first time, provides experimental semiquantitative data to compare the angiogenic potentials of embolized and gamma knife–treated AVM tissues. Embolization may increase angiogenic activity, and gamma knife radiosurgery may decrease it when compared with activity in previously untreated AVMs. These data can be useful to understand why recurrence of AVMs after angiographically demonstrated endovascular occlusion is common but after gamma knife occlusion is rare.

Physical activity-mediated functional recovery after spinal cord injury: potential roles of neural stem cells

As data elucidating the complexity of spinal cord injury pathophysiology emerge, it is increasingly being recognized that successful repair will probably require a multifaceted approach that combines tactics from various biomedical disciplines, including pharmacology, cell transplantation, gene therapy and material sciences. Recently, new evidence highlighting the benefit of physical activity and rehabilitation interventions during the post-injury phase has provided novel possibilities in realizing effective repair after spinal cord injury. However, before a comprehensive therapeutic strategy that optimally utilizes the benefits of each of these disciplines can be designed, the basic mechanisms by which these various interventions act must be thoroughly explored and important synergistic and antagonistic interactions identified. In examining the mechanisms by which physical activity-based functional recovery after spinal cord injury is effected, endogenous neural stem cells, in our opinion, engender a potentially key role. Multipotent neural stem cells possess many faculties that abet recovery, including the ability to assess the local microenvironment and deliver biofactors that promote neuroplasticity and regeneration, as well as the potential to replenish damaged or eradicated cellular elements. Encouragingly, the functional recovery owing to physical activity-based therapies appears relatively robust, even when therapy is initiated in the chronic stage of spinal cord injury. In this article, we review experimental outcomes related to our hypothesis that endogenous neural stem cells mediate the functional recovery noted in spinal cord injury following physical activity-based treatments. Overall, the data advocates the incorporation of increased physical activity as a component of the multidimensional treatment of spinal cord injury and underscores the critical need to employ research-based mechanistic approaches for developing future advances in the rehabilitation of neurological injury and disorders.

Lumbar Disc Herniation in Adolescence

Lumbar disc herniation very rarely occurs in adolescence. The aim of this study was to assess the radiological, clinical and surgical features and case outcomes for adolescents with lumbar disc herniation, and to compare with adult cases. The cases of 17 adolescents (7 girls and 10 boys, age range 13–17 years) who were surgically treated for lumbar disc herniation in our clinic between 1998 and 2003 were retrospectively reviewed. The mean follow-up time for these cases was 60 months. The collected histories revealed that 14 (82%) of the 17 cases involved trauma or intense sports activity. Low back pain was the most common complaint (15 cases, 88%). None of the 17 patients had major symptoms during follow-up, and most were engaged in intense sports or heavy work-related activities during this period. The main features of lumbar disc herniation in adolescents are different from those seen in adults. Careful assessment is vital to avoid misdiagnosis and prevent undesirable results from inappropriate surgery. When surgery is indicated and patients are carefully selected, the results of lumbar discectomy in adolescence can be satisfactory.

Superficial siderosis due to papillary glioneuronal tumor

Superficial siderosis of the central nervous system is a rare, progressive, irreversible and debilitating neurological disease characterized by the deposition of haemosiderin in the leptomeninges and the subpial layers of the brain and spinal cord. The main clinical findings are progressive bilateral sensorineural hearing loss, cerebellar ataxia and pyramidal tract signs. The present report describes a 49-year-old woman who presented with intermittent headache of 5 years duration. The pain had become more severe in the previous 6 months. Neurological examination revealed nothing abnormal. Computed tomography showed a cystic mass with apparent internal haemorrhage in the right frontal lobe and T(2)-weighted magnetic resonance imaging showed material of low signal intensity coating the entire surface of the brain. The mass was completely excised via craniotomy. A histopathological study identified the mass as a papillary glioneuronal tumour. The patient recovered well and is still neurologically normal 1 year later. This is the first documented case of superficial siderosis caused by this type of tumour.

Gamma knife radiosurgery for cranial neurocytomas

Gamma-knife surgery may be an effective alternative for treatment of central neurocytomas owing to its relative safety compared with conventional radiotherapy. In this paper we present results of gamma-knife treatment (GKS) of residual or recurrent neurocytomas. Twenty-two patients (14 female, 8 male) with recurrent or residual neurocytomas who underwent GKS were included. Diagnosis was based on histological findings. The proliferative potential of the tumors was examined by immunostaining with MIB-1 antibody, which is specific for detection of Ki-67 antigen. Tumor volume was determined by using post-gadolinium magnetic resonance images. After GKS treatment, MR imaging was scheduled at three-month intervals in the first year, at six months intervals in the second year, and yearly thereafter. Histopathological diagnoses were: 18 cases of central neurocytomas, two liponeurocytomas, one cerebral neurocytoma and one cerebellar neurocytoma. The MIB1 labeling index (LI) varied from 0 to 5.7%. Marked reduction in tumor volume was seen in 15 patients. In six patients, the tumor volume remained unchanged, and progression was observed for one patient. No complications because of GKS were noted. Shrinking effect on tumor volume increased with increasing duration of follow-up. On the other hand, high MIB labeling index did not seem to have an effect on tumor response to GKS treatment. Findings of this study suggest that GKS is an effective and safe treatment alternative for residual or recurrent neurocytomas. However, its effectiveness should be confirmed with larger studies.

The effects of inflammatory response associated with traumatic spinal cord injury in cutaneous wound healing and on expression of transforming growth factor-beta1 (TGF-β1) and platelet-derived growth factor (PDGF)-A at the wound site in rats

At the cellular level, spinal cord injury (SCI) provokes an inflammatory response that generates substantial secondary damage within the cord, but also may contribute to its repair. The aim of this study was to investigate the effects of inflammatory response associated with SCI in cutaneous wound healing and on expression of transforming growth factor-beta1 (TGF-β1) and platelet-derived growth factor (PDGF)-A at the wound site in rats. At the 14th day analysis, the mean TGF-β1 score in trauma group (I) was significantly lower than that in control group (C) (2.60 ± 0.90 vs. 3.64 ± 0.37, respectively; p < 0.05). The mean score for PDGF-A expression in group I was similar to the corresponding value in group C (2.42 ± 0.74 vs. 2.94 ± 0.72, respectively). Compared to group C, group I had significantly lower mean scores for epidermal and dermal regeneration, but higher mean scores for granulation tissue thickness and similar scores for angiogenesis. The dermal layer contains diffuse deposition of collagen fibers that are not organised as in control rat skin, and intraepidermal and subepidermal vasocongestion is distinct. Based on the results on the parameters evaluated in the study, experimental SCI in rats results in delay in wound healing and low intensity of TGF-β1 in the dorsal wound-tissue specimens.

Effects of parenteral fish-oil emulsion (Omegaven) on cutaneous wound healing in rats treated with dexamethasone

BACKGROUND The aim was to assess wound healing when parenteral fish-oil emulsion is given to rats receiving dexamethasone. METHODS For 5 days after skin wounding, group S (control; n = 7) received saline 1 mL/kg intraperitoneal (IP); group D (n = 7), dexamethasone 0.2 mg/kg IP; and group DO (n = 9), dexamethasone 0.2 mg/kg IP plus 1 mL/kg Omegaven (Fresenius Kabi, Austria). Wound specimens were assessed for hydroxyproline level, wound depth, histology (epidermal/dermal regeneration, granulation tissue thickness, and angiogenesis), and expression of transforming growth factor-beta (TGF-beta) and platelet-derived growth factor-AA (PDGF-AA). RESULTS Compared with D and DO specimens, controls had higher hydroxyproline (p < .01), deeper wounds (p < .05), and better histologic scores (p < .01 angiogenesis; others p < .05). There were no significant differences between the group D and DO means for hydroxyproline level, wound depth, or histologic scores (p > .05 for all). Controls had higher TGF-beta expression scores than the other groups (p < .01 for both) and a higher PDGF-AA expression score than group DO (p < .01). Groups D and DO had statistically similar TGF-beta scores, but group D had a higher PDGF-AA score (2.71 +/- 0.75 vs 1.55 +/- 0.72, respectively; p < .05). CONCLUSIONS According to the parameters we studied, adding parenteral omega-3 and omega-6 fatty acids to the nutrition regimen of rats treated with dexamethasone does not seem to have adverse effects on wound healing, and effects on wound healing may not need to be considered when determining if these agents should be supplemented in nutrition support regimens.

Functional recovery in T13–L1 hemisected rats resulting from peripheral nerve rerouting: role of central neuroplasticity

BACKGROUND Functional improvements after spinal cord injury (SCI) have been reported anecdotally following neurotization, in other words, rerouting nerves proximal to injured cord segments to distal neuromuscular targets, although the underlying mechanisms remain largely unknown. AIM To test our hypothesis that neurotization-mediated recovery is primarily attributable to CNS neuroplasticity that therefore manifests optimal response during particular therapeutic windows, we anastomosed the T12 intercostal nerve to the ipsilateral L3 nerve root 1-4 weeks after T13-L1 midline hemisection in rats. RESULTS While axonal tracing and electromyography revealed limited reinnervation in the target muscles, neurobehavioral function, as assessed by locomotion, extensor postural thrust and sciatic functional index of SCI rats receiving neurotization 7-10 days postinjury (n = 11), recovered to levels close to non-SCI controls with neurotization only (n = 3), beginning 3-5 weeks postanastomosis. Conversely, hindlimb deficits were unchanged in hemisected controls with sham neurotization (n = 7) or 4 weeks-delayed neurotization (n = 3) and in rats that had undergone T13-L1 transection plus bilateral anastomoses (n = 6). CONCLUSION Neurotized SCI animals demonstrated multiparameters of neural reorganization in the distal lumbar cord, including enhanced proliferation of endogenous neural stem cells, increased immunoreactivity of serotonin and synaptophysin, and neurite growth/sprouting, suggesting that anastomosing functional nerves with the nerve stump emerging distal to the hemisection stimulates neuroplasticity in the dysfunctional spinal cord. Our conclusion is validated by the fact that severance of the T13-L1 contralateral cord abolished the postanastomosis functional recovery. Neurotization and its neuroplastic sequelae need to be explored further to optimize clinical strategies of post-SCI functional repair.

Lumbar spinal angiolipoma: case report and review of the literature

Spinal angiolipomas are extremely rare benign tumors composed of mature lipomatous and angiomatous elements. Most are symptomatic due to progressive spinal cord or root compression. This article describes the case of a 60-year-old woman who presented with a 6-month history of low back pain radiating to her right leg. The pain was multisegmental. The condition had worsened with time. Lumbar magnetic resonance imaging revealed a dorsal epidural mass at L5 and erosion of the lamina of the L5 vertebra. Laminectomy was performed, and an extradural tumor was totally excised. Neuropathologic examination identified it as a lumbar spinal angiolipoma. There was no evidence of recurrence in follow-up 12 months later. This rare clinical entity must be considered in the differential diagnosis for any spinal epidural lesion.

Relationship of angiogenic potential with clinical features in cranial meningiomas: a corneal angiogenesis study.

BACKGROUND: Intracranial meningiomas constitute approximately one fourth of all primary intracranial tumors. The invention of cranial angiographic techniques has led to the recognition of the angiogenic potential of meningiomas, which has been the subject of extensive research. OBJECTIVE: To test the relationship between the angiogenetic potential of intracranial meningiomas and clinical/prognostic features such as World Health Organization (WHO) grade, peritumoral edema, tumor border shape, and recurrence using rat corneal angiogenesis assay. METHODS: Fifteen WHO grade I (typical), 10 WHO grade II (atypical), and 5 WHO grade III (malignant) meningioma samples were implanted in the micropockets formed on rat corneas, and the number of developed vessels were counted on days 5, 10, 15, and 20. Normal brain and glioblastoma multiforme tissues served as negative and positive controls, respectively. Patients were evaluated by magnetic resonance imaging preoperatively and every 6 months thereafter. RESULTS: The angiogenic potential of WHO grade II tumors was significantly lower than that of grade III tumors and higher than that of grade I tumors throughout the experiment. Tumors with a smooth border shape and nonrecurrent tumors exhibited significantly lower angiogenic activity compared with the tumors with irregular border shape and recurrent tumors, respectively. No association was found between angiogenic activity and peritumoral edema. However, multivariate analysis identified WHO grade, recurrence, and peritumoral edema as significant predictors of a high angiogenic potential. CONCLUSION: Our findings, based on a dynamic in vivo model to examine angiogenesis, demonstrate that the angiogenic potential of meningiomas is correlated with WHO grade, recurrence, and possibly with tumor border shape and peritumoral edema. Angiogenesis seems to be an important factor in the natural course of meningiomas, suggesting that inhibition of angiogenesis may be an option, particularly in the treatment of meningiomas with an aggressive course.