Mustafa Uzan

Traumatic Intracranial Carotid Tree Aneurysms

OBJECTIVE This study was designed to elucidate the requirements for angiographic evaluation in blunt head injuries, the timing of angiography, and the selection of appropriate therapeutic approaches. METHODS Twelve cases of traumatic aneurysms (TAs) in the intracranial carotid tree were analyzed in this study. Neurological examination results, computed tomographic scans, pre- and postembolization cerebral angiograms, and follow-up data were included. RESULTS In 11 of 12 cases, TAs were of cranial base origin; in 1 case, the aneurysm was located in the distal anterior cerebral artery. In seven of the cases with cranial base lesions, aneurysms were located in the intracavernous segment of the internal carotid artery; all of the computed tomographic scans for these cases demonstrated sphenoid sinus wall fractures and hematoma in the sphenoid sinus. In two cases, although the initial angiograms revealed no lesions, a second study performed 2 weeks later demonstrated the presence of aneurysms. Nine of the aneurysms were treated with endovascular techniques, two were managed conservatively, and the remaining one patient died with massive epistaxis while awaiting surgical treatment. No morbidity or additional permanent neurological deficits occurred in the endovascularly treated patient group. CONCLUSION Patients with head trauma who present with sphenoid sinus fractures and massive epistaxis should be evaluated for the development of TAs as soon as possible. If the patients exhibit fractures without epistaxis, angiography should be deferred for 2 to 3 weeks; if the first angiographic evaluation reveals normal findings, repeated epistaxis should prompt a second angiographic evaluation. Current treatment of TAs involves occlusion of the main artery through the use of endovascular techniques. Cases involving internal carotid artery TAs of cranial base origin and patients who do not tolerate test occlusion require extracranial-to-intracranial bypass surgery.

Thalamic proton magnetic resonance spectroscopy in vegetative state induced by traumatic brain injury

Objectives: To determine whether proton magnetic resonance spectroscopy (MRS), a newer radiographic technology, would be useful in the evaluation of the thalamus of patients in vegetative states resulting from traumatic brain injury. Methods: 14 victims of severe traumatic brain injury who were in the vegetative state and whose magnetic resonance images of the thalamus were normal underwent bilateral thalamic proton (MRS) studies. The N-acetyl aspartate to creatine (NAA:Cr) and choline to creatine (Cho:Cr) ratios were obtained for each patient. The proton thalamic MRS findings of patients who were in a persistent vegetative state (n = 8) and in patients who had regained awareness after being in the vegetative state (n = 6) were compared with proton thalamic MRS findings in five healthy volunteers. Results: While conventional magnetic resonance imaging suggested that each patient had a normal thalamus, proton MRS indicated that the thalamus of each patient in the series was damaged. The NAA:Cr ratio was significantly lower in the thalami of both the patients who remained in a persistent vegetative state for the duration of the study and in those who regained awareness after being in the vegetative state (p < 0.001). In addition, NAA:Cr ratios were lower in the group of patients who remained in a persistent vegetative state than in the group of patients who regained awareness after being in the vegetative state (p < 0.001). Conclusions: Results suggest that the NAA:Cr ratio within the thalamus is significant and that thalamic MRS may be helpful when attempting to determine the degree of severity of neuronal and axonal injury in patients in the vegetative state.

Surgical outcome of patients with mesial temporal lobe epilepsy related to hippocampal sclerosis

Seizure outcome in mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE‐HS) that was evaluated according to a noninvasive protocol was assessed in 165 patients and reported using both Engels and ILAE classifications. The mean postoperative follow‐up was 5.0 ± 2.7 years. At the end of first year, 77.1% of patients were in Engel‐I, and 52.7% were in ILAE‐I. Antiepileptic drugs (AEDs) were discontinued in 41 patients (42.7%), all remained seizure‐free for >2 years that could be accepted as “cure.” Thirty‐six patients had recurrences, 19 had running‐down phenomena. Anterior temporal lobectomy (ATL) was performed in 27 patients with a better outcome when compared to patients operated by selective anterior hippocampectomy. Clinical risk factors for better and worse outcome, which show some similarity in different reports, seem to veil the main reason, which is the accurate delineation of epileptogenic zone considering the presence of different subgroups and underlying developmental pathologies.

Glioma risk associates with polymorphisms of DNA repair genes, XRCC1 and PARP1

Cancer develops through interactions between polygenic and environmental factors, and changes in DNA repair pathway can increase susceptibility to tumours. XRCC1 and PARP1 are two proteins that act cooperatively in base excision repair (BER) of DNA. The polymorphisms of genes coding these proteins may effect their action in BER pathway. In this study, we aimed to investigate the associations between glioma risk and XRCC1 Arg399Gln and PARP1 Val762Ala polymorphisms per se and in combination. XRCC1 Arg399Gln and PARP1 Val726Ala polymorphisms were investigated by PCR–RFLP method in 119 glioma patients and 180 cancer-free control subjects. The results were statistically analysed by calculating the odds ratios (OR) and their 95% confidence intervals (95% CI) using the χ2-tests. Glioma patients in this study had significantly higher frequencies of XRCC1 Arg399Gln polymorphism both in homozygote (GG) and heterozygote (AG) status (31% and 56%, respectively) (p < 0.001), and also increased frequency of 399Gln (G) allele (59%) (p < 0.001). Val/Ala (VA) genotype of PARP1 Val762Ala polymorphism was significantly more in the control group (p = 0.02). The combined genotypes of XRCC1 AG or GG with PARP1 VA or AA, and XRCC1 AG or GG with PARP1 VV were more represented in the glioma patients (p = 0.001 and 0.003, respectively). We conclude that XRCC1 Arg399Gln polymorphism is a significant risk factor, and 399Gln (G) allele carries a 3.5 times greater risk for glioma, while PARP1 Val/Ala genotype may be protective against it. We also suspect that in the presence of a polymorphic (G) allele of XRCC1, the plausible protective effect of PARP1 VA genotype may be greatly suppressed.

Statistical analysis of the factors affecting the outcome of extradural haematomas: 115 cases.

Summary115 traumatic extradural haematoma cases who were treated surgically at Cerrahpasa Medical Faculty Neurosurgery Department between 1987 and 1992 are evaluated.When factors affecting the outcome were examined, a strong correlation was found between the result andGlasgow coma scale (GCS) (p<0.00001). The existence of a fracture, the interval between onset of haematoma symptoms and intervention and the existence of an intracerebral haematoma together with contusion accompanying intradural haematoma, affect the outcome in a negative direction. There was no statistical correlation between the outcome and the age of patient, localization of the haematoma and aetiology.

Acute ethanol intoxication in a model of traumatic brain injury: the protective role of moderate doses demonstrated by immunoreactivity of synaptophysin in hippocampal neurons.

Abstract Although ethanol intoxication is reported to be a complicating factor in traumatic brain injury, some recent studies are indicating its possible protective role especially at lower doses. Ethanol inhibition of NMDA-mediated excitotoxicity which predominates at lower doses is believed to be responsible for this protection. The aim of this study was to demonstrate this neuroprotective role of alcohol using immunoreactivity for synaptophysin as an indirect marker for severity of injury. Acute ethanol intoxication at moderate doses was performed 2 h prior to trauma. Severe traumatic brain injury was administrated using an impact acceleration model in Sprague–Dawley rats. At post-traumatic 48th hour, immunorectivity for synapthophysin in the rat hippocampi was evaluated under light microscopy. According to our results there were slight increases in immunoreactivity for synaptophysin in the stratum oriens and striatum radiatum of CA1 subfield of hippocampus when ethanol was administered prior to trauma comparing to moderate increase in the trauma-only group. On the other hand vacuolar degeneration and red neuron formation was more prominent in the pyramidal cell layer of CA1 and CA3 when ethanol was not administered. Ethanol may have a neuroprotective role when administered at moderate doses prior to traumatic brain injury. This effect of ethanol may primarily be due to inhibition of NMDA receptors.

Expression and cellular distribution of multidrug resistance-related proteins in patients with focal cortical dysplasia

Recent arouse of interest indicated that drug resistant proteins are markedly over-expressed in the epileptogenic tissue and they may be responsible for the one-third of the epileptic patients who were refractory to anti-epileptic drugs (AEDs). Since several AEDs may act as substrates for these drug resistant proteins, the enhanced function of such proteins may increase drug extrusion, resulting in inadequate response to drug therapy in patients with epilepsy. We studied expression of the multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 1 (MRP1) in the epileptic tissues resected surgically in 28 patients with focal cortical dysplasia (FCD) by immunohistochemistry. The results were compared with 10 normal necropsy brain tissues. Normal brain showed no MDR1 expression in neurons and astrocytes, while MRP1 expression was very weak, which were encountered in a few samples. MDR1 expression was mainly localized on the vascular endothelial cells. In contrast to normal brain, we found intense MDR1 and MRP1 expression in both neurons and reactive astrocytes in the vast majority of dysplastic tissues. The majority of the dysplastic neurons demonstrated moderate to strong MRP1 immunoreactivity. Endothelial cells showed both MDR1 and MRP1 expression in the majority of the specimens studied. Multidrug transporters are over-expressed in the epileptogenic zone in patients with FCD. These results are concordant with previous studies, in which over-expression of multidrug proteins were shown in epileptogenic brain tissue in patients with FCD, that the over-expression of drug transport proteins in tissue from patients with refractory epilepsy may explain one possible mechanism for drug resistant in these pathologies.

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.

Visual field defects in selective amygdalohippocampectomy for hippocampal sclerosis: the fate of Meyer's loop during the transsylvian approach to the temporal horn.

OBJECTIVEMeyers loop, the most vulnerable part of the optic radiations during approaches to the temporomedial region, extends to the tip of the temporal horn and is often encountered in epilepsy surgery. The risk of damaging Meyers loop during transsylvian selective amygdalohippocampectomy peaks while accessing the temporal horn through its roof by opening the inferior limiting sulcus of the insula. In this prospective study, we sought to evaluate and identify the incidence of visual field deficits in a homogeneous group of patients who had temporal lobe epilepsy with hippocampal sclerosis and who underwent transsylvian selective amygdalohippocampectomy. METHODSWe studied 30 patients who were referred for epilepsy surgery for intractable complex partial and/or secondary generalized seizures and evaluated according to a noninvasive protocol. All patients underwent selective amygdalohippocampectomy for temporal lobe epilepsy with hippocampal sclerosis using the standard transsylvian approach. Visual field deficits were examined preoperatively in 30 patients, by either a confrontation method (n = 18) or standard Goldmann perimetry (n = 12) and postoperatively in all patients using standard Humphrey digital perimetry. RESULTSVisual field examination was normal in all patients before surgery. Humphrey perimetric measurement revealed visual field deficits in 11 patients (36.6%) after surgery. CONCLUSIONWe have shown that there is a considerable risk of having visual field deficits after standard transsylvian selective amygdalohippocampectomy owing to the interruption of the anterior bundle of the optic radiation fibers, which most likely occurs while opening the temporal horn through the inferior limiting sulcus of the insula.