Contrast-Enhanced FLAIR (Fluid-Attenuated Inversion Recovery) for Evaluating Mild Traumatic Brain Injury

Purpose

To evaluate whether adding a contrast-enhanced fluid-attenuated inversion recovery (FLAIR) sequence to routine magnetic resonance imaging (MRI) can detect additional abnormalities in the brains of symptomatic patients with mild traumatic brain injury.

Materials and Methods

Fifty-four patients with persistent symptoms following mild closed head injury were included in our retrospective study (M∶F = 32∶22, mean age: 59.8±16.4, age range: 26–84 years). All MRI examinations were obtained within 14 days after head trauma (mean: 3.2±4.1 days, range: 0.2–14 days). Two neuroradiologists recorded (1) the presence of traumatic brain lesions on MR images with and without contrast-enhanced FLAIR images and (2) the pattern and location of meningeal enhancement depicted on contrast-enhanced FLAIR images. The number of additional traumatic brain lesions diagnosed with contrast-enhanced FLAIR was recorded. Correlations between meningeal enhancement and clinical findings were also evaluated.

Results

Traumatic brain lesions were detected on routine image sequences in 25 patients. Three additional cases of brain abnormality were detected with the contrast-enhanced FLAIR images. Meningeal enhancement was identified on contrast-enhanced FLAIR images in 9 cases while the other routine image sequences showed no findings of traumatic brain injury. Overall, the additional contrast-enhanced FLAIR images revealed more extensive abnormalities than routine imaging in 37 cases (p<0.001). In multivariate logistic regression analysis, subdural hematoma and posttraumatic loss of consciousness showed a significant association with meningeal enhancement on contrast-enhanced FLAIR images, with odds ratios 13.068 (95% confidence interval 2.037 to 83.852), and 15.487 (95% confidence interval 2.545 to 94.228), respectively.

Conclusion

Meningeal enhancement on contrast-enhanced FLAIR images can help detect traumatic brain lesions as well as additional abnormalities not identified on routine unenhanced MRI. Therefore contrast-enhanced FLAIR MR imaging is recommended when a contrast MR study is indicated in a patient with a symptomatic prior closed mild head injury.     

Changes of Endogenous Antioxidant Enzymes during Ischemic Tolerance Acquisition

The purpose of this study was to investigate the role of superoxide dismutase (SOD) and catalase (CAT) in brain ischemic tolerance induced by ischemic preconditioning. Forebrain cerebral ischemia was induced in rat by four vessel occlusion. The activities of the antioxidant enzymes CuZn-SOD, Mn-SOD and CAT were measured in the hippocampus, striatum and cortex after 5 min of ischemia used as a preconditioning and subsequent reperfusion, by spectrophotometric methods. In all ischemia-reperfusion groups (5 h, 1 and 2 days of reperfusion), CuZn-SOD activities were found to be increased if compared to the sham operated controls. The increase was significant (P < 0.05) in all reperfusion groups, particularly after 5 h of reperfusion (3 times) in all studied brain regions; the largest increase was detected in the more vulnerable hippocampus and striatum. Very similar changes were found in Mn-SOD activity. The activity of CAT was increased too, but reached the peak of postischemic activity 24 h after ischemia. Our attempt to understand the mechanisms of increased SOD and CAT activities by application of protein synthesis inhibitor cycloheximide showed that this increase was caused by de novo synthesis of enzymes during first hours after ischemia. Our findings indicate that both major endogenous antioxidant enzymes SOD and CAT are synthesized as soon as 5 h after ischemia. In spite of significant upregulation of these enzymes a large number of neurons in selectively vulnerable CA1 region of hippocampus undergoes to neurodegeneration within 7 days after ischemia.     

原发全面强直-阵挛型癫痫的体素形态学研究

采用基于体素形态学（voxel- based morphometry,VBM）的方法,分析了全面强直-阵挛型癫痫（epilepsy with generalized tonic clonic seizures,GTCS）患者的大脑结构异常情况。对31例临床诊断为GTCS的患者和31例正常志愿者,采集大脑三维（3-dimensional,3D）T1结构像,进行VBM全脑分析比较。通过GTCS患者组与正常对照组的比较,发现GTCS患者的双侧丘脑、双侧额叶、双侧岛叶、双侧小脑等区域的灰质体积有比较明显的减小,但没发现有意义的灰质体积增高的区域;患者双侧丘脑、左侧中央前回、左侧额内侧回、左侧额中回和其发病频率呈负相关,没有正相关的区域。结果显示,全面强直-阵挛型癫痫患者的大脑结构存在异常,说明大脑灰质体积的异常可能和全面强直-阵挛型癫痫的发病存在一定的关系。     

Region-specific DNA synthesis in brains of F344 rats following a six-day bromodeoxyuridine infusion

Abstract. Prolonged exposure to certain alkylating chemicals induces glial and meningeal tumours in rats, probably resulting from DNA damage to dividing neural cells. The present work evaluated DNA synthesis in the brains of untreated, young adult male F344 rats in order to define a BrdUrd infusion protocol to more adequately assess proliferation in slowly dividing neural cell populations. BrdUrd (2.5 to 160 mg/ml) was administered for 6 days via subcutaneous osmotic pumps. Clinical toxicity was not observed at any dose. The labelling index (LI; % of cells per brain area that incorporated BrdUrd) and unit length labelling index (ULLI; % of cells per meningeal length that incorporated BrdUrd) were calculated for selected regions by counting labelled neural cells in defined areas of the right hemisphere in coronal brain sections. Intensely stained cells were numerous in the cerebral subependymal layer (LI=35.8%); scattered in cerebral white matter tracts (e.g. corpus callosum and internal capsule; LI=6.2%) as well as cerebral (ULLI=4.2%) and cerebellar (ULLI=3.6%) meninges; and rare in the hippocampus (LI>0.1%). Mildy stained cells were dispersed in the pons (LI=2.1%), deep cerebral (LI=1.8%) and cerebellar (LI=1.0%) grey matter, and thalamus (LI=0.3%). Phenotypically, BrdUrd-positive cells in neuropil were glial cell precursors and their progeny, while those associated with meninges were usually located in the superficial subarachnoid space and appeared to be fibrocytes. Using BrdUrd infusion, LI for glial precursors at these sites ranged from two- to 10-fold higher than those reported previously after a brief parenteral pulse dose. These data indicate that continuous BrdUrd infusion for 6 days by subcutaneous osmotic pump is an efficient means of labelling neural cells throughout the brain.     

Free-GABA levels in the cerebrospinal fluid of patients suffering from several neurological diseases Its potential use for the diagnosis of diseases which course with inflammation and tissular necrosis

Summary Free GABA levels were measured in the cerebrospinal fluid (CSF) of 74 neurological patients suffering from cerebral cysticercosis (n = 9), Parkinson's disease (n = 5), multiple sclerosis (n = 6), epilepsy (n = 24), meningeal tuberculosis (n = 6), viral encephalitis (n = 3), cerebrovascular disease (n = 8) and several kinds of dystonia (n = 5). A statistical significant four-fold elevation in free GABA levels was found in patients with cerebral cysticercosis. A non statistical significant two-fold increase in free GABA levels was also encountered in the CSF of patients affected by cerebrovascular disease and viral encephalitis. No changes in CSF free GABA levels were found in patients suffering from any of the other disorders. It is suggested that free GABA levels may be elevated in the CSF of patients suffering from neurological diseases which course with inflammation and tissular necrosis such as cerebral cysticercosis. Much work is needed however to establishd whether CSF free GABA levels can be used as a diagnostic tool in at least some type of these patients.     

Computerized tomography of the head in patients with epilepsy

A detection of structural changes in the brain of epileptic patients is of importance to the choice of therapeutical management. Incidence and character of lesions in CT-scans of the skull were analysed in the random group of epileptic patients. Normal areas in CT-scans were prevailing in young patients. Atrophic lesions to the brain increased with the patients' age and duration of the disease. Normal results were obtained in post-traumatic epilepsy and that of unknown etiology similarly to atrophic lesions whereas localized lesions were found in all patients with cerebral tumors. Partial epilepsy, especially of short duration, was characterized by high incidence of localized lesions. Normal EEG records were rare in patients with localized lesions detected with CT-scans whereas normal CT-scans may be related to abnormal EEG record. Presence of the localized lesions in some patients and atrophic areas did not limit clinical results of monitored therapy. CT-scanning of the skull should be performed in case of all patients with epilepsy even if there are no significant changes in EEG records or clinical status.     

血源性兔VX2肿瘤脑及脑膜转移瘤动物模型的建立及MRI检测

目的：研究MRI对血源性脑及脑膜转移瘤动物模型转移灶的检出效果。方法：18只新西兰大白兔随机分为3组,分别从左颈总动脉内接种VX2瘤细胞,A组：20％甘露醇注入5min后接种VX2瘤细胞：B组：20％甘露醇注入5min后,加入肝素再接种VX2瘤细胞;C组,对照组,单纯注入等量生理盐水。术后2周后行MRI检查。病理取材HE染色光镜下观察。结果：平扫：A组,1只（1／6）发现脑内结节并脑膜结节样增厚,T1WI为等信号,T2WI为稍高信号。B组,2只（2／6）为脑内多发结节,T1WI为等信号,TM为稍高信号。2只（2／6）脑膜结节样增厚。增强扫描：A组,2只（2／6）脑内见强化结节灶;直径在1．5mm-7．0mm之间。4K（4／6）脑膜线样增厚或结节样增厚强化。B组,6只（6／6）脑内见直径在1．5mm-5．0mm的高信号结节,其中5只为脑内多发结节灶;4只（4／6）脑膜线样或结节样增厚强化,左侧为主,其中2只（2／6）为双侧脑膜增厚。增强扫描A、B组问脑内病灶差异有统计学意义（Fisher’s确切概率值为0．04）。C组平扫及增强扫描均未见异常信号。结论：上述方法制成的动物模型可为医学影像学研究提供可靠的动物模型,加入肝素可提高瘤灶的形成几率,并证实血脑屏障对脑转移瘤的形成起重要作用。MRI增强检查是检出脑内及脑膜转移瘤的首选方法。     

Posttraumatic Epilepsy: Hemorrhage,Free Radicals and the Molecular Regulation of Glutamate

Traumatic brain injury causes development of posttraumatic epilepsy. Bleeding within neuropil is followed by hemolysis and deposition of hemoglobin in neocortex. Iron from hemoglobin and transferring is deposited in brains of patients with posttraumatic epilepsy. Iron compounds form reactive free radical oxidants. Microinjection of ferric ions into rodent brain results in chronic recurrent seizures and liberation of glutamate into the neuropil, as is observed in humans with epilepsy. Termination of synaptic effects of glutamate is by removal via transporter proteins. EAAC-1 is within neurons while GLT-1 and GLAST are confined to glia. Persistent down regulation of GLAST production is present in hippocampal regions in chronic seizure models. Down regulation of GLAST may be fundamental to a sequence of free radical reactions initiated by brain injury with hemorrhage. Administration of antioxidants to animals causes interruption of the sequence of brain injury responses induced by hemorrhage, suggesting that such a strategy needs to be evaluated in patients with traumatic brain injury. Special issue article in honor of Dr. Akitane Mori.     

Cerebrospinal fluid cytology diagnosis of meningeal carcinomatosis in patients with small-cell carcinoma of the lung. A study of interobserver and intraobserver variability

The interobserver and intraobserver variation in the cytologic diagnosis of malignancy was determined in 62 cerebrospinal fluid (CSF) specimens from 46 patients with small-cell carcinoma of the lung. In all patients, lumbar puncture was carried out because of suspected central nervous system metastases. Forty CSF specimens from 26 patients with meningeal carcinomatosis and thus with a high probability of a positive CSF cytology were mixed with 22 specimens from 20 patients without meningeal carcinomatosis. The slides were evaluated blindly by two observers, one of whom evaluated all specimens on two separate occasions; only positive, negative and suspicious conclusions were permitted. The consistency of the intraobserver and interobserver conclusions on the initial CSF specimen in each case was 87%. In 13% of the initial CSF specimens in each case, a suspicious conclusion was reached in one of the three evaluations. For all 62 CSFs, the intraobserver and interobserver disagreement was 2% and 3%, respectively. In the first and second evaluations by the one observer and the single evaluation by the other, 17 (65%), 15 (58%) and 12 (46%), respectively, of the 26 "high probability" patients were found to have malignant cells in the CSF. CSF cytology was negative in all 20 patients without meningeal carcinomatosis. Of 10 patients with autopsy-proven meningeal carcinomatosis, 40% were not diagnosed while alive. Multiple CSFs from repeated lumbar punctures increased the number of positive evaluations by 30%. At least 60% of those patients with a suspicious CSF cytology did in fact have meningeal carcinomatosis. On the other hand, 30% of the patients with a positive lumbar puncture had a subsequent negative one.     

Time-dependent changes in superoxide dismutase, catalase, xanthine dehydrogenase and oxidase activities in focal cerebral ischaemia

Time-dependent changes in the activities of antioxidant enzymes and an oxidant enzyme, xanthine oxidase (XO), were detected in primary and peri-ischaemic brain regions during permanent occlusion of the middle cerebral artery (MCAO) in rats. There were no changes in superoxide dismutase (SOD) and catalase (CAT) activities after 3 h of MCAO, whereas antioxidant enzyme activities decreased significantly in ischaemic brain areas following 24 h of ischaemia. After 48 h, the enzyme activities returned to the baseline but then a further increase was observed in ischaemic brain areas by 72 h post-ischaemia. Normally, XO exists as a dehydrogenase (XD), but it is converted to XO which contributes to injury in some ischaemic tissues. The XO activity increased slightly at 3 h after ischaemia, but after 24 h of ischaemia it returned to the baseline and then remained relatively unchanged in ischaemic areas. Pretreatment with allopurinol before ischaemia prevented changes in SOD and CAT activities and attenuated brain oedema during 24 h of ischaemia. Neither XO nor XD activity changed in allopurinol-treated rats at the times of ischaemia. These results indicated that ischaemic brain tissue remained vulnerable to free radical damage for as long as 48 h after ischaemia, and XO was probably not an important source of free radicals in cerebral ischaemia.     

Cerebroprotective activity of Wedelia calendulacea on global cerebral ischemia in rats

The present study was to investigate the effect of W. calendulacea on ischemia and reperfusion-induced cerebral injury. Cerebral ischemia was induced by occluding right and left common carotid arteries (global cerebral ischemia) for 30 min followed by reperfusion for 1 h and 4 h individually. Various biochemical alterations, produced subsequent to the application of bilateral carotid artery occlusion (BCAO) followed by reperfusion viz. increase in lipid peroxidation (LPO), hydrogen peroxide (H2O2), and decrease in reduced glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD), level in the brain tissue, Western blot analysis (Cu-Zn-SOD and CAT) and assessment of cerebral infarct size were measured. All those enzymes are markedly reversed and restored to near normal level in the groups pretreated with W. calendulacea (250 and 500 mg/kg given orally in single and double dose/day for 10 days) in dose-dependent way. The effect of W. calendulacea had increased significantly the protein expression of copper/zinc superoxide dismutase (Cu-Zn-SOD) and CAT in cerebral ischemia. W. claendulacea was markedly decrease cerebral infarct damages but results are not statistically significant. It can be concluded that W. calendulacea possesses a neuroprotective activity against cerebral ischemia in rat.     

胚胎型大脑后动脉与脑白质病之间的关系

目的:探讨胚胎型大脑后动脉(Fetal origin of the posterior cerebral artery,FTP)与脑白质病之间的关系。方法:收集2013年1月~2014年6月在我院住院患者共485例,所有患者均行头颅磁共振平扫及血管成像,观察脑白质病变、急性脑梗死及FTP存在与否,并分为观察组(脑白质病组)和对照组(无脑白质病组),比较FTP的发生率。结果:观察组和对照组分别为232例和253例,观察组共发现53例FTP患者(左侧、右侧、双侧FTP分别为15例、19例、19例),FTP总发生率为22.8%,左侧、右侧、双侧FTP发生率分别为6.5%、8.2%、8.2%;对照组98例FTP患者(左侧、右侧、双侧FTP分别为26例、44例、28例),FTP总发生率为38.7%,左侧、右侧、双侧FTP发生率分别为10.3%、17.4%、11.1%,观察组FTP总发生率及右侧FTP发生率明显低于对照组(P0.001和P0.01)。232例观察组中急性脑梗死患者共156例,无急性脑梗死患者76例,其中急性脑梗死组有28例FTP患者(左侧、右侧、双侧FTP分别为7例、15例、6例),FTP总发生率及左侧、右侧、双侧FTP发生率分别为17.9%、4.5%、9.6%、3.8%;而无急性脑梗死的患者中,有24例FTP患者(左侧、右侧、双侧FTP分别为8例、4例、12例),FTP总发生率及左侧、右侧、双侧FTP发生率分别为31.6%、10.5%、5.3%、15.8%,观察组FTP总发生率及双侧FTP发生率明显低于对照组(P0.05和P0.01)。结论:FTP的存在可能一定程度上降低脑白质病甚至脑梗死的发生。     

脑膜中动脉的形态变异及其在人类进化上的意义

对现代人、直立人、早期智人、晚期智人脑膜中动脉前支和后支压迹的形态的观察和对比发现：从直立人到现代人脑膜中动脉管径从粗到逐渐变细,分枝从简单到逐渐复杂,前支趋向于增大,后支趋向于缩小,呈现出一定的规律性,有地域性差异。作者认为脑膜中动脉的这种分布形式间接地反映了直立人向智人演化及现代人类形成过程中,大脑各部分比例的变化和功能的日益复杂对供血需求的影响。在研究颅骨与大脑之间的关系上及脑演化上,脑膜中动脉有一定的意义。     

Neuropsychology, plasticity and childhood epilepsy

Epilepsy is one of the most frequent childhood disorders. While most cases are well controlled, approximately 30-50% are resistant to medical treatment. In these cases, neurosurgery may be an option. Since 1979, our team at the Sainte-Justine Hospital in Montreal has studied the impact of epilepsy on the psycho-motor and cognitive development of the affected children. The aim of a first series of studies was to explore the extent and limits of cerebral plasticity by investigating the neuropsychological sequelae of early versus late callosotomy and hemispherectomy. In keeping with the plasticity hypothesis, the results revealed that the children who were operated before puberty showed fewer deficits than those operated during adolescence or adulthood. However, the compensatory mechanisms available to them appeared to be limited with respect to the nature and complexity of the information they can process. For instance, young children having undergone section of the corpus callosum resembled individuals born without a corpus callosum (callosal agenesis) in that there did not show the typical disconnection deficits seen in adult 'split-brain' patients. However, they exhibited deficits on tasks requiring interhemispheric integration of motor and visuo-motor information. By the same token, hemispherectomy patients were still able to make visual judgements in their 'blind' visual field but they were found to be impaired on a variety of visual and auditory tasks (localization of a sound sources in space) requiring the participation of both hemispheres. In a second series of studies, carried out in collaboration with a Parisian team, we intended to describe the neuropsychological profile of focal epilepsies, specifically frontal and temporal epilepsy. Contrary to the common belief that childhood epilepsy would result in diffuse impairments, we were able to demonstrate that children manifest the same localized deficits as adult patients. In studies presently underway in our laboratories, we make use of functional neuroimaging techniques such as high density electrophysiology, optical imaging and magnetoencephalography to investigate pre-and postoperative language and memory functions and to study the impact of epilepsy on brain maturation.     

Lysosulfatide (Sulfogalactosylsphingosine) Accumulation in Tissues from Patients with Metachromatic Leukodystrophy

We describe here a sensitive assay method for lysosulfatide (sulfogalactosylsphingosine) in human tissues using HPLC. The method involves extraction of lipids, saponification, isolation using a C18 Sep-Pak column, derivatization with o-phthalaldehyde, and detection of the fluorescent lysosulfatide using HPLC. In control subjects, a small amount of lysosulfatide was detected in the cerebral white matter (9-35 pmol/mg of protein), spinal cord (35 pmol/mg of protein), sciatic nerve (14 pmol/mg of protein), and kidney (approximately 2 pmol/mg of protein) but not in the cerebral gray matter and liver. A marked accumulation of the lipid was noted in tissues from six patients with metachromatic leukodystrophy (MLD). The concentration of lysosulfatide was high in the cerebral white matter, spinal cord, and sciatic nerve (223-1,172 pmol/mg of protein). Even in the cerebral gray matter, kidney, and liver, where lysosulfatide was hardly detected in the control sample, a considerable amount (3-45 pmol/mg of protein) accumulated in MLD patients. The concentration and distribution pattern of lysosulfatide were similar to those of galactosylsphingosine (psychosine) accumulated in patients with Krabbe disease. Therefore, the accumulation of lysosulfatide may explain the demyelination in patients with MLD, as is the case with Krabbe disease.