The Relationship Between Quantitative MRI and Neuropsychological Functioning in Temporal Lobe Epilepsy

Summary: Purpose: Quantitative MRI techniques provide an unparalleled opportunity to examine in vivo the relationship between the extent and laterality of hippocampal pathology and associated neuropsychological deficits. The purpose of this study was to examine the nature of the relationship between quantitative measures of hippocampal pathology and neuropsychological measures, using a multivariate approach. Methods: We examined the relationship between two MRI measures of hippocampal structure; hippocampal volumes (HCvol) and T2 relaxation times (HCT2), and memory performance, in 80 presurgical temporal lobe epilepsy patients. Results: As a group, patients with left hippocampal sclerosis (LHS) performed more poorly that those with right hippocampal sclerosis (RHS) on immediate and delayed prose recall. In the group as a whole, right hippocampal volume was significantly correlated with the delayed recall of a complex figure. None of the verbal memory test scores were significantly correlated with the right or left HCvol or HCT2 measures. However, stepwise multiple regression analyses indicated that up to a third of the variation in specific test scores could be explained by the quantitative MRI hippocampal measures in conjunction with chronological age, and age at onset of habitual epilepsy. Left hippocampal measures explained 24% of the variance in the story-recall tasks, while right hippocampal measures explained 18% of the variance in a design-learning task and 32% of the variance in a figure-recall task. Conclusions: Our results provide some support for the lateralised model of material specific memory deficits, but suggest that a number of demographic and epilepsy-related factors may interact with the extent and laterality of hippocampal pathology in shaping the nature of the associated neuropsychological deficit.     

The influx of Ca and the release of noradrenaline evoked by the stimulation of presynaptic nicotinic receptors of chick sympathetic neurons in culture are not mediated via L-, N-, or P-type calcium channels

We have shown earlier that nicotinic agonists induce the release of noradrenaline from chick sympathetic neurons in culture in two ways: (a) by activating the postsynaptic nicotinic receptors on nerve cell bodies, giving rise to spreading electrical activity and opening of voltage operated calcium channels in neuronal processes; (b) by activating the presynaptic nicotinic receptors on neuronal processes. In the present work, we investigated the contribution of various pathways to the observed Ca²⁺ influx and subsequent noradrenaline release. Sympathetic neurons in culture were stimulated either by the nicotinic agonist dimethylphenylpiperazinium or electrically, in the presence or absence of tetrodotoxin and of specific blockers of calcium or nicotinic channels, and the effects on [Ca²⁺]_i in the area of neuronal processes and on noradrenaline release were measured. Under control conditions, the N-type channel blocker ω-conotoxin (0.1 μmol/1) diminished the release of noradrenaline and the increase of intraterminal Ca²⁺ by 48% and 55%, respectively, whereas the L-type channel blocker (+)Bay k 8644 (1 μmol/1) diminished the release of noradrenaline by 25% and the increase of [Ca²⁺]_i by 39%. The P-type channel blocker ω-agatoxin (0.3 μmol/1) had no effect. The effects of the L-type channel ligands were complex and could only be explained on the assumption that, at high concentrations, these drugs also act as nicotinic antagonists. Tetrodotoxin blocked the Ca²⁺ response evoked by electrical stimulation whereas DMPP applied in the presence of tetrodotoxin still evoked an increase of [Ca²⁺]_i and the release of noradrenaline (27% and 30% of control without tetrodotoxin, respectively). These residual responses were not blocked by any of the calcium channel blockers used or by their combination. Apparently, a substantial part of the influx of Ca²⁺ induced by the activation of presynaptic nicotinic receptors is not carried by the N-, L- or P-type channels and probably occurs directly via the open channels of nicotinic receptors.     

Temporal lobe epilepsy with varying severity: MRI study of 222 patients

MRI was performed in 222 consecutive adult patients with temporal lobe epilepsy of varying severity from January 1991 to May 1993. The diagnosis of hippocampal sclerosis was established visually by three independent observers. The accuracy of visual assessment of hippocampal asymmetry was compared with volumetric measurements. Neuropathological correlations were obtained in 63 patients with refractory seizures. Temporal lobe abnormalities were observed in 180 patients (81 %) as follows: hippocampal sclerosis in 122 (55 %); developmental abnormalities in 16 (7.2 %); tumours in 15 (6.8 %); scars in 11 (5 %); cavernous angiomas in 10 (4.5 %); miscellaneous lesions in 6. MRI was normal or showed unrelated changes in 42 patients (19 %). Visual assessment correctly lateralised hippocampal sclerosis in 79 of the 84 patients measured (94 %). Temporal lobectomy confirmed the MRI data (side and aetiology) in all 63 operated patients. Patients with normal MRI had an older age of seizure onset and were more often drug-responsive than patients with hippocampal sclerosis. MRI showed temporal lobe abnormalities in 81 % of epileptic patients with varying severity with good neuropathological correlation. Patients with normal MRI had a less severe form of the disease. Received: 19 August 1996 Accepted: 13 November 1996     

THE CONTROL OF HUMAN MOTOR UNITS

1. The motor unit, consisting of a single motor neuron and the skeletal muscle fibres that it innervates, is the final output pathway of the motor system. 2. Much is now known about the way that human motor neurons are recruited and controlled during voluntary and reflex movements. This review briefly summarizes some of the recent experimental data that has contributed to our present understanding. The review is largely limited to data obtained in human experiments. While much of what we know about the organization of the nervous system has come from studies of the anatomy and physiology of experimental animals, there are some questions that cannot be addressed in reduced animal preparations. The development of new techniques has made it possible to investigate the human nervous system at a level of detail that has not hitherto been possible.     

Topographic organization of descending projection neurons to the spinal cord of the goldfish, Carassius auratus

Several neurons from different nuclei give rise to descending spinal tracts and project to various levels in the spinal cord of goldfish, Carassius auratus. These were visualized by retrograde transport of horseradish peroxidase (HRP) administered to the bilaterally transected spinal cord at 6 levels, corresponding to 1st, 5th, 10th, 15th, 20th and 25gh segments of the vertebral column. As many as 16 brain nuclei or neuronal aggregations and the Mauthner cells project posteriorly up to the 20th spinal segment. Restricted neurons of the dorsolateral area in the nucleus preopticus magnocellularis and those of the ventromedial nucleus of the thalamus projected up to the 20th and 25th segments respectively. In the mesencephalon, the nucleus ruber and the nucleus of the medial longitudinal fasciculus revealed retrogradely labeled somata; the former extended up to the 20th segment, while the latter projected up to the 25th segment. The remaining descending projected neurons of the brain belonged to the rhombencephalon. The nucleus of the lateral lemniscus; anterior, magnocellular, descending and posterior divisions of the octaval nucleus: raphe nucleus; Mauthner cell and the neurons located adjacent to the trigeminal tract and those in the vicinity of the secondary gustatory tract sent their processes up to 20th segmental level. However, somata of the superior, medial and inferior divisions of the reticular nucleus and restricted neurons of the facial lobe extended up to 25th segmental level. The pattern of neuronal projections into the spinal cord suggests a topographic organization.     

Effect of KB-2796, a new diphenylpiperazine Ca antagonist, on voltage-dependent Ca currents and oxidative metabolism in dissociated mammalian CNS neurons

The effects of KB-2796, 1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine-2HCl, on the low- and high-voltage activated Ca²⁺ currents (LVA and HVA I_Ca, respectively) and on oxidative metabolism were studied in neurons freshly dissociated from rat brain. KB-2796 reduced the peak amplitude of LVA I_Ca in a concentration-dependent manner with a threshold concentration of 10⁻⁷ M when the LVA I_Ca was elicited every 30 s in the external solution with 10 mM Ca²⁺. The concentration for half-maximum inhibition (IC₅₀) was 1.9 × 10⁻⁶M. At 10⁻⁵ M or more of KB-2796, a complete suppression of the LVA I_Ca was observed in the majority of neurons tested. There was no apparent effect on the current-voltage (I-V) relationship and the current kinetics. KB-2796 delayed the reactivation and enhanced the inactivation of the Ca²⁺ channel for LVA I_Ca voltage- and time-dependently, suggesting that KB-2796 preferentially binds to the inactivated Ca²⁺ channel. KB-2796 at a concentration of3.0 × 10⁻⁶M also decreased the peak amplitude of the HVA I_Ca without shifting the I-V relationship. In addition, KB-2796 reduced the oxidative metabolism (the formation of reactive oxygen species) of the neuron in a concentration-dependent manner with a threshold concentration of3 × 10⁻⁶M. It is suggested that the inhibitory action of KB-2796 on the neuronal Ca²⁺ influx and the oxidative metabolism, in combination with a cerebral vasodilatory action, may reduce ischemic brain damage.     

近交系胎鼠中脑多巴胺能神经元体外定向分化的初步研究

目的体外培养近交系大鼠胚胎腹侧中脑前体细胞(VMP)并诱导其分化为多巴胺能神经元(DN),为研究DN定向分化的分子机制提供细胞模型。方法取材胎龄11d的近交系大鼠胚胎VMP,体外用碱性成纤维细胞生长因子(bFGF)增殖培养7d后换用L-抗坏血酸-2-磷酸酯倍半镁盐(AA-2P)诱导分化为DN,随后进行免疫荧光染色鉴定。结果细胞总数扩增49.76倍,免疫荧光染色显示β-TubulinⅢ阳性的神经元中(71.33±20.42)%为TH阳性的DN,后者占细胞总数的(24.85±12.85)%。结论近交系大鼠VMP经体外原代培养能够得到较高比例的DN,可作为深入研究DN定向分化分子机制的细胞模型。     

神经保护剂鸡尾酒疗法对海马神经元氧糖剥离（OGD）后神经元凋亡及抗凋亡蛋白Bcl一2表达的影响

目的：探讨不同类型神经保护剂联合应用即鸡尾酒（cocktail）疗法是否较单一神经保护剂对海马神经元培养氧糖剥离（OGD）后有更好的保护作用。方法：采用海马神经元培养氧糖剥离（OGD）模型，分为1，6-二磷酸果糖（FDP）组、MK-801组、N-乙酰半胱氨酸（NAC）组、cocktail组和对照组，观察神经元凋亡及抗凋亡蛋白Bcl-2表达情况。结果：cocktail组神经元凋亡减少，Bcl-2表达增多，与单-用药各组相比有显著性差异（P＜0．05）。结论：神经保护剂cocktail疗法对神经元缺血保护作用较单一用药明显增强。     

大鼠大脑皮质向脊髓与红核投射的比较

目的 比较大脑皮质向脊髓与红核发出投射的区域并探讨是否有分支投射存在。方法 将。TB及NY分别注入大白鼠的脊髓与红核内，在大脑皮质观察比较标记细胞出现的部位。结果 FB标记细胞出现在24，10，8，6，4，3，1，2，23，29b，29c，18，7，13，39区。NY标记细胞出现于6，4，3，1区，10区的尾侧部及7，18区的颅饲部亦有少量存在。无发现双标记细胞。结论 大脑皮质向脊髓发出投射的区域非常广泛，向红核发出投射的区域全部重叠于皮质脊髓神经元分布的区域内，皮质脊髓神经元无分支投射到红核。