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  • Author or Editor: Gentian Toshkezi x
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Gentian Toshkezi, Michele Kyle, Sharon L. Longo, Lawrence S. Chin and Li-Ru Zhao

OBJECTIVE

Traumatic brain injury (TBI) is a major cause of long-term disability and death in young adults. The lack of pharmaceutical therapy for post–acute TBI recovery remains a crucial medical challenge. Stem cell factor (SCF) and granulocyte colony–stimulating factor (G-CSF), which are 2 key hematopoietic growth factors, have shown neuroprotective and neurorestorative effects in experimental stroke. The objective of this study was to determine the therapeutic efficacy of combined treatment (SCF + G-CSF) in subacute TBI.

METHODS

Young-adult male C57BL mice were subject to TBI in the cortex of the right hemisphere. After TBI induction, mice were randomly divided into 2 groups: a vehicle control group and an SCF + G-CSF treatment group. Mice without TBI served as sham operative controls. Treatment was initiated 2 weeks after TBI induction. SCF (200 μg/kg) and G-CSF (50 μg/kg) or an equal volume of vehicle solution was subcutaneously injected daily for 7 days. A battery of neurobehavioral tests for evaluation of memory and cognitive function (water maze and novel object recognition tests), anxiety (elevated plus maze test), and motor function (Rota-Rod test) was performed during the period of 2–9 weeks after treatment. Neurodegeneration and dendritic density in both hemispheres were determined through histochemistry and immunohistochemistry at 11 weeks posttreatment.

RESULTS

Water maze testing showed that TBI-impaired spatial learning and memory was restored by SCF + G-CSF treatment. The findings from the elevated plus maze tests revealed that SCF + G-CSF treatment recovered TBI-caused anxiety and risk-taking behavior. There were no significant differences between the treated and nontreated TBI mice in both the Rota-Rod test and novel object recognition test. In the brain sections, the authors observed that widespread degenerating neurons were significantly increased in both hemispheres in the TBI-vehicle control mice. TBI-induced increases in neurodegeneration were significantly reduced by SCF + G-CSF treatment in the contralateral hemisphere, making it no different from that of the sham controls. Dendritic density in the frontal cortex of the contralateral hemisphere was significantly reduced in the TBI-vehicle control mice, whereas SCF + G-CSF–treated TBI mice showed significant increases of the dendritic density in the same brain region. SCF + G-CSF–treated TBI mice also showed a trend toward increasing dendritic density in the contralateral hippocampus.

CONCLUSIONS

SCF + G-CSF treatment in the subacute phase of TBI restored TBI-impaired spatial learning and memory, prevented posttraumatic anxiety and risk-taking behavior, inhibited TBI-induced neurodegeneration, and enhanced neural network remodeling. These findings suggest the therapeutic potential of hematopoietic growth factors for brain repair in the subacute phase of TBI.

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Gentian Toshkezi, John Dejesus, Joe F. Jabre, Anna Hohler and Keith Davies

Long thoracic nerve palsy has been reported to have traumatic, iatrogenic, and idiopathic causes. The authors describe the case of a 62-year-old man who presented with progressively worsening right shoulder pain, winging of the scapula, and Horner syndrome. A chest CT scan revealed an apical pulmonary mass. To the authors' knowledge, this is the first report of a long thoracic nerve palsy caused by an apical pulmonary tumor.

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Amit Singla, Eric M. Deshaies, Vlad Melnyk, Gentian Toshkezi, Amar Swarnkar, Hoon Choi and Lawrence S. Chin

The role of preoperative embolization in meningioma management remains controversial, even though 4 decades have passed since it was first described. It has been shown to offer benefits such as decreased blood loss and “softening of the tumor” during subsequent resection. However, the actual benefits remain unclear, and the potential harm of an additional procedure along with the cost of embolization have limited its use to a small proportion of the meningiomas treated.

In this article the authors retrospectively reviewed their experience with preoperative embolization of meningiomas over the previous 6 years (March 2007–March 2013). In addition, they performed a MEDLINE search using a combination of the terms “meningioma,” “preoperative,” and “embolization” to analyze the indications, embolizing agents, timing, and complications reported during preoperative embolization of meningiomas. In this retrospective review, 18 cases (female/male ratio 12:6) were identified in which endovascular embolization was used prior to resection of an intracranial meningioma. Craniotomy for tumor resection was performed within 4 days after endovascular embolization in all cases, with an average time to surgery of 1.9 days. The average duration of surgery was 4 hours and 18 minutes, and the average blood loss was 574 ml, with a range of 300–1000 ml. Complications following endovascular therapy were identified in 3 (16.7%) of 18 cases, including one each of transient hemiparesis, permanent hemiparesis, and tumor swelling.

The literature review returned 15 articles consisting of a study population greater than 25 patients. No randomized controlled study was found. The use of small polyvinyl alcohol particles (45–150 μm) is more effective in preoperative devascularization than larger particles (150–250 μm), but is criticized due to the higher risk of complications such as cranial nerve palsies and postprocedural hemorrhage. Time to surgery after embolization is inconsistently reported across the articles, and conclusions on the appropriate timing of surgery could not be drawn. The overall complication rate reported after treatment with preoperative meningioma embolization ranges from as high as 21% in some of the older literature to approximately 6% in recent literature describing treatment with newer embolization techniques. The evidence in the literature supporting the use of preoperative meningioma embolization is mainly from case series, and represents Level III evidence. Due to the lack of randomized controlled clinical trials, it is difficult to draw any significant conclusions on the overall usefulness of preoperative embolization during the management of meningiomas to consider it a standard practice.