Ali Metin Kafadar

Evaluation of apoptosis in cerebrospinal fluid of patients with severe head injury

SummaryObjective. To determine whether sFas, caspase-3, proteins which propagate apoptosis, and bcl-2, a protein which inhibits apoptosis, would be increased in cerebrospinal fluid (CSF) in patients with severe traumatic brain injury (TBI) and to examine the correlation of sFas, caspase-3, and bcl-2 with each other and with clinical variables. Methods. sFas, caspase-3, and bcl-2 were measured in CSF of 14 patients with severe TBI on days 1, 2, 3, 5, 7, and 10 post-trauma. The results were compared with CSF samples from control patients who had no brain and spinal pathology and had undergone spinal anesthesia for some other reason. Soluble Fas and bcl-2 were measured by ELISA while caspase-3 was measured enzymatically. Results. No sFas, caspase-3, and bcl-2 activities were found in CSF of controls, but activities significantly increased in CSF of patients at all time points post-trauma (p < 0.01). Caspase-3 significantly correlated to intracranial pressure (p = 0.01) and cerebral perfusion pressure (p = 0.04). Soluble Fas and caspase-3 peaks coincided on day 5 post-trauma and there was significant association between sFas and caspase-3 increase (p = 0.01). Conclusion. This study indicates a prolonged activation of pro-apoptotic (sFas, caspase-3) and anti-apoptotic (bcl-2) proteins after severe TBI in humans. The degree of activation of particularly caspase-3 may be related to the severity of the injury. Parallel increases of these three molecules may indicate a pivotal role of apoptosis in the pathophysiology of post-traumatic brain oedema, secondary cell destruction and chronic cell loss following severe TBI and may open new targets for post-traumatic therapeutic interventions.

Association between interleukin-1 beta (IL-1β) gene polymorphism and outcome after head injury: an early report

SummaryBackground. Recent studies focusing on the genetic influences on outcome after head injury (HI) have suggested that different alleles of certain genes are associated with different outcomes. Interleukin-1 beta (IL-1β) gene, especially β2 polymorphism, is frequently observed in Alzheimer’s disease, a remarkable degenerative state in which HI is among the known risk factors. Therefore, the aim of this paper was to search for the possible association between the outcome and IL-1β gene polymorphism in human HI.Methods. The study group was composed of the 69 patients admitted to the neurosurgery department after HI. The severity of the initial injury was evaluated by means of the Glasgow Coma Scale and outcome six months later was assessed by means of the Glasgow Outcome Scale. IL-1β genotypes were determined from blood samples by standard methods.Findings. Fourteen of 25 (56%) patients with IL-1β +3953 allele 2 had an unfavourable outcome (dead, vegetative state or severe disability) compared with eight of 44 (18.1%) patients without IL-1β +3953 (p = 0.0004). Similarly, 20 of 28 (71.4%) patients with IL-1β −511 allele 2 had an unfavourable outcome compared with two of 41 (4.8%) patients without IL-1β −511 (p = 0.005). Patients who had a composite of IL-1β 2/2 or 1/2 genotype from both −511 and +3953 region of the chromosome 2 were more prone to have bad prognosis.Conclusion. Results of our study demonstrated that there might be a significant association between IL-1β gene polymorphism and outcome after HI, supporting the hypothesis of a genetically determined influence.

Duraplasty Using Autologous Fascia Lata Reenforced by On-site Pedicled Muscle Flap: Technical Note

Objective Postoperative cerebrospinal fluid (CSF) leak is a common complication in the practice of neurosurgery, and various surgical techniques were described to overcome and manage this problem. Besides not applying watertight closure of the duraplasty, the inviability and the poor vascularization of the graft and/or the dura (eg, reoperations, multiple operations, or cranial radiotherapy) may lead to delayed healing of the suture site and resultant persistent CSF leaks. We present a simple technique that uses on-site muscle flap with pedicle to supply and vascularize the autologous fascia lata, preserving the viability of the graft and reenforcing its healing ability. Methods We applied this technique in 6 patients with postoperative CSF leaks. After harvesting a fascia lata graft with appropriate size from the patients, the graft was sutured to dural defect in watertight fashion. The suboccipital, temporal, and temporal muscles in 4 patients who had posterior fossa duraplasty, in 1 patient who had pterional craniotomy, and in 1 patient who had subtemporal craniotomy, respectively, were dissected, stretched, and sutured to the fascia graft covering the dura graft suture site and then reinforced by Tisseel fibrin glue (Baxter Healthcare Corporation, Deerfield, IL). Postoperatively, CSF lumbar drain was kept open for 72 hours with pressure wound dressing. The technical nuances are illustrated. Results Cerebrospinal fluid leaks were controlled successfully in 5 patients without recurrence. One patient with posterior fossa duraplasty had recurrence of CSF leak that required reexploration 21 days after the first surgery and a second dural repair in a site distant from the fascia lata attachment. During reexploration intraoperatively, the fascia lata graft was inspected and studied, which has shown the healing of the dura graft site and the graft neovascularization. Conclusions Duraplasty using autologous fascia lata reenforced by on-site pedicled muscle flap is an effective technique to control CSF leak, especially when dura is poorly vascularized and less viable. The unfortunate recurrence of CSF leak and reexploration in the seventh patient helped us to observe the effectively healed dural defect with profound early postoperative vascularization of the graft, supporting our idea about the effectiveness of this technique.

Use of Cortoss as an alternative material in calvarial defects: the first clinical results in cranioplasty.

A clinical series of 13 patients who underwent cranioplasty using a new quick setting material, namely Cortoss™ was done over 3-year period. Thus, the primary objective of this study is to evaluate the role of Cortoss™ in the treatment calvarial defects which were mainly due to trauma (4 patients), tumor or tumor-like lesions (5 patients), middle cerebral infarction (3 patients), and gun shot wound (1 patient). The surgical technique was found to be simple and effective. Long-term follow-up (mean 24.3 months) demonstrated satisfactory results in terms of surgical (functional) and cosmetic outcomes. None of the patients developed complications including infections, foreign body reactions or material leakage. The results led us to suggest that the use of Cortoss™ in the case of calvarial defects seems to be safe, effective, quick, and a feasible method for cranioplasty. We conclude that the mechanical, immunologic, and technical-grafting properties of Cortoss™, together with its superior esthetic and psychological effects, probably will make it the best material for cranioplasty.

Lack of association between IL-1β/α gene polymorphisms and temporal lobe epilepsy with hippocampal sclerosis

Summary Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is one of the most common medically intractable epilepsy syndromes and the pathogenesis of HS remains highly obscure. Recent studies demonstrated controversial results about the relationship between interleukin (IL) gene polymorphism and epilepsy in different ethnic groups. This correlation was investigated in Turkish patients with MTLE-HS. The allele distribution of IL-1α and IL-1β in 47 patients of Turkish ancestry was determined and compared with 99 ethnically matched control subjects. Analysis of genotype frequencies between patients and controls showed no statistically significant difference ( p >0.05). Our data suggest that IL-1α and IL-1β gene polymorphisms do not act as a strong susceptibility factor for MTLE-HS in individuals of Turkish ancestry.

Cyclin D1 Gene G870A Variants and Primary Brain Tumors

Alterations of cyclin D1, one of the main regulators of the cell cycle, are known to be involved in various cancers. The CCDN1 G870A polymorphism causes production of a truncated variant with a shorter half-life and thus thought to impact the regulatory effect of CCDN1. The aim of the present study was to contribute to existing results to help to determine the prognostic value of this specific gene variant and evaluate the role of CCDN1 G870A polymorphism in brain cancer susceptibility. A Turkish study group including 99 patients with primary brain tumors and 155 healthy controls were examined. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. The CCDN1 genotype frequencies in meningioma, glioma and control cases were not significantly different (p>0.05). No significant association was detected according to clinical parameters or tumor characteristics; however, a higher frequency of AG genotype was recorded within patients with astrocytic or oligoastrocytic tumors. A significant association between AG genotype and gliobilastoma multiforme (GBM) was recorded within the patients with glial tumors (p value=0.048 OR: 1.87 CI% 1.010-3.463). According to tumor characteristics, no statistically significant difference was detected within astrocytic, oligoasltrocytic tumors and oligodentrioglias. However, patients with astrocytic astrocytic or oligoastrocytic tumors showed a higher frequency of AG genotype (50%) when compared to those with oligodendrioglial tumors (27.3%). Our results indicate a possible relation between GBM formation and CCDN1 genotype.

Intracranial migration of bone dust after intraventricular neuroendoscopy complicating acute hydrocephalus and removal of bone dust: case report.

OBJECTIVETo present the first case of neuroendoscopic removal of migrated intraventricular bone dust and gel foam after intraventricular endoscopic surgery. CLINICAL PRESENTATIONA 37-year-old man was admitted with a 2-year history of headache. Brain computed tomography (CT) scan and magnetic resonance imaging revealed a cavum vergae cyst. The patient was operated on by stereotactically guided endoscopic cyst fenestration with no intraoperative complications. Postoperative CT scan demonstrated regression of the cyst with no other pathological findings. Because of a postoperative fever, a lumbar puncture was performed after the brain CT scan to eliminate meningitis as a differential diagnosis. After the lumbar puncture, the patient complained of severe headache and vomiting followed by depression of consciousness. The follow-up CT scan showed the migration of bone dust from the burr hole site to the ventricular system and acute hydrocephalus. It is thought that the negative pressure gradient generated after the lumbar puncture might have been transmitted through the cerebrospinal fluid pathway, resulting in a suction effect and migration of the bone dust from the burr hole to the ventricle. INTERVENTIONAn urgent reexplorative endoscopic procedure was performed, and most of the bone dust and gel foam were removed. The patient recovered with complete resolution of the previous symptoms. CONCLUSIONWe propose not using autologous bone dust for closure of the burr holes after endoscopic intraventricular procedures; instead, alloplastic materials designed especially for burr hole closure may be used. However, our main recommendation is to use an external ventricular drainage, which is maintained closed but can be opened if necessary. In addition, lumbar puncture should be avoided in cases in which bone dust is used for the burr hole reconstruction without dural closure.

Surgical morbidity of invasive monitoring in epilepsy surgery: an experience from a single institution.

AIM This paper aimed to provide information related to surgical and neurological complications encountered following intracranial electrode placements in patients with medically intractable epilepsy. MATERIAL AND METHODS Retrospective review of 70 patients with either subdural grid/strip or depth electrode implanted between 2004 and 2009 at the Epilepsy Unit in Cerrahpasa Medical Faculty. RESULTS A total of 276 electrode implantations were performed in 70 patients. There were no deaths related to implantation. The occurrence of infection and intracranial hematoma were found to be 1.4 and 1.4%, respectively. A total of 1 patient (1.4%) showed transient neurological complications. The rate of overall morbidity including neurological complications was found to be 4.2% (n=3). CONCLUSION Based on our experience, intracranial electrode implantation is an effective and safe method with extremely low morbidity rate, especially in experienced hands.

The effect of duration of compression on lipid peroxidation after experimental spinal cord injury

The present study was performed to evaluate the effect of duration of acute spinal cord compression on tissue lipid peroxidation in rats. A clip compression method (1) was used to produce acute spinal cord injury. Rats were divided into 3 groups, each consisting of 10. At 1 hour after trauma all rats were sacrificed, and MDA content of the injured spinal cord segment was measured. The tissue MDA contents were 3.922 μmolMDA/gww in group 1 (control), 10.192 μmol MDA/gww in group 2 (30 seconds compression), and 12.147 μmolMDA/gww in group 3 (60 seconds compression). These results demonstrate that the length of duration of compression significantly enhances lipid peroxidation. Our study supported the view that persisting compression may cause progression of secondary mechanisms which may irreversibly eliminate any potential for recovery.

Surgical treatment of trigonocephaly: technique and long-term results in 48 cases.

OBJECT The authors present their experience in the surgical treatment of metopic synostosis by orbital bandeau remodeling and frontal bone rotation. The pitfalls and advantages of the surgical technique are discussed, along with the long-term clinical results in 48 consecutive cases. METHODS Forty-eight consecutive patients in whom trigonocephaly was diagnosed between 1990 and 2009 were treated with frontal bone rotation and frontoorbital bandeau remodeling. Of these patients, 38 (79%) were boys and 10 (21%) were girls. The age at the time of surgical treatment ranged between 4 and 42 months (mean ± SD 11.4 ± 8.7 months). The average follow-up period was 5.5 ± 4.2 years (range 5 months-19 years). The preoperative and latest postoperative photographs of the patients were evaluated for the following features: 1) shape of the forehead; 2) hypotelorism; and 3) temporal depression. Scores of 0, 1, or 2 were assigned for each item: 0 was normal, 1 meant moderate deformity, and 2 denoted severe deformity. RESULTS In the early postoperative period, no complications were documented. The average hospitalization period was 4 days. Follow-up radiographs or 3D CT scans were obtained at regular intervals. The mean preoperative scores for the evaluated items were 1.38 ± 0.49 for the shape of the forehead, 1.33 ± 0.48 for hypotelorism, and 1.7 ± 0.46 for the temporal depression. The mean postoperative scores were 0.06 ± 0.24 for the shape of the forehead, 0.21 ± 0.4 for hypotelorism, and 0.67 ± 0.48 for the temporal depression. Overall, the total preoperative score dropped from 4.4 to 0.93 postoperatively (p < 0.05). All the patients were contented with the cosmetic results. CONCLUSIONS Early detection and treatment of metopic suture synostosis has a significant, favorable influence on the outcomes. Good understanding of the structural abnormality and the pathophysiological mechanisms of the possible complications is very important for performing proper surgical reconstruction.