A new mouse model for the neurodevelopmental ciliopathy Joubert syndrome

Recent recognition of the key role of primary cilia in orchestrating human development and of the dire consequences of their dysfunction on human health has placed this small organelle in the spotlight. While the causal link between mutations in ciliary genes and central nervous system malformations and dysfunction is well established, the mechanisms by which primary cilia dysfunction acts on development and function of the CNS remain partly unknown. The recent article by Bashford and Subramanian in The Journal of Pathology describes a new mouse model for the neurodevelopmental ciliopathy Joubert syndrome, supporting a role for ciliary-mediated Hedgehog signaling on proliferation, survival, and differentiation of cerebellar granule cell progenitors. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Bilateral Implantation of Centromedian‐Parafascicularis Complex and GPi: A New Combination of Unconventional Targets for Deep Brain Stimulation in Severe Parkinson Disease

Objectives. Traditional deep brain stimulation (DBS) at the subthalamic nucleus (STN) has proved to be efficacious on core Parkinsonian symptoms. However, very disabling l ‐dopa–induced abnormal involuntary movements (AIMs) and axial signs are slightly affected, suggesting that we target less conventional targets. Our candidates for DBS were the globus pallidus internus (GPi) plus the intralaminar thalamic complex (Pf or CM), given its extensive functional links with basal ganglia nuclei. Materials and Methods. The routine utilization of our innovative stereotactic apparatus allows us to implant, at the same time, both the CM‐Pf complex together with the GPi in six Parkinson disease patients. Both intraoperative and postoperative neurophysiologic assessments helped us recognize functional subregions while optimizing implantation of electrodes. Unified Parkinson disease rating scale (UPDRS) motor scores, AIMs, and freezing were carefully blindly evaluated for each condition. Results. A significant amelioration of UPDRS scores was achieved by simultaneous activation of both targets. CM‐Pf activation was only slightly effective in reducing rigidity and akinesia, but more efficacious on freezing. Not surprisingly, AIMs were peculiarly decreased by the activation of the permanent electro‐catheter in the posteroventral GPi. Conclusions. These findings confirm that, in selected patients, it is conceivable to target structures other than the conventional STN in order to maximize clinical benefit.     

Histological and biological developmental characterization of the human cerebellar cortex

The aim of this study was to investigate the histological and biological features of the human cerebellar cortex development and differentiation. We analyzed 52 brains of fetal and infant death victims, aged from 17 gestational weeks to 12th postnatal month. In particular, in the cerebellar cortex at different ages we evaluated, besides the structural aspects, the expression of several biomarkers implicated in proliferative processes (c-fos, PCNA and apoptosis). We observed morphological patterns progressively evolving every month, from the indefinite structure of the second gestational trimester to the four-layered structure (external granular layer, molecular layer, Purkinje cell layer, internal granular layer) of the late fetal cortex and subsequently to the three-layered postnatal definitive morphology, due to involution of the external granular layer. The evaluation of the biological features of the cerebellar cortex showed high proliferative activity mainly confined to the transient external granular layer in prenatal life, and high apoptotic index after birth. Thus, the histological examination, better with the support of biomarker investigations, allows with accuracy to describe the dynamic sequence of steps that occur in human cerebellar cortex development and to establish in each case the age, namely the pre- or postnatal month of life. Consequently, we can diagnose delayed or altered processes of differentiation during the development of the human cerebellar cortex.     

良性小脑出血13例分析

笔者对13例良性小脑出血的患者,从起病、临床表现进行了具体分析.总结出中老年良性小脑出血的6个特点,供临床工作者参考.     

Monolateral hypoplasia of the motor vagal nuclei in a case of sudden infant death syndrome

During the development of motor vagal nuclei (MVN), the neuroblasts of the myeloencephalic basal plate migrate in the dorsolateral direction to form the dorsal motor vagal nucleus (DMVN) and ventrolaterally to form the ventral motor vagal nucleus (VMVN). Those neuroblasts that remain close to the median sulcus will form the hypoglossal nucleus. In support of the congenital origin of the alteration of the MVN in sudden infant death syndrome (SIDS), we report the case of an 8‐month‐old female child who was found dead in her cot. The neuropathological assessment revealed that the medullary triangle of the 4th ventricle floor was asymmetric, owing to the presence of three prominences to the left side of the median sulcus. The medial prominence corresponded to the hypoglossal nucleus, which showed a marked increase in the number of large neurons; the intermediate prominence corresponded to the DMVN whose large neurons were reduced and were recognizable mainly at the level of the medial fringe; the lateral prominence corresponded to the solitary nucleus. The left solitary tract showed a reduction of the transverse diameter. Also, the left VMVN showed marked reduction in the number of neurons. Inflammatory and astrocytic reactions were absent. We suggest that in SIDS cases the hypocellularity of the MVN and the increased number of neurons of the hypoglossal nucleus are intimately related, indicating a congenital alteration due to incomplete migration of the vagal neuroblasts with abnormality of the autonomic cardio‐respiratory control.     

小脑后下动脉动脉瘤的诊断和治疗

目的探讨小脑后下动脉动脉瘤的临床特征、诊断、鉴别诊断和治疗。方法回顾性分析12例小脑后下动脉瘤的临床表现、影像学特征、手术效果及诊治过程中存在的相关问题。结果12例中有11例因动脉瘤破裂出血而发病,单纯第四脑室出血4例,全脑室系统出血2例,小脑半球出血3例,小脑蚓部伴第四脑室出血1例,侧脑室伴第三脑室出血1例,以后颅窝占位病变表现1例。8例术前行DSA检查明确诊断,4例术中明确诊断。12例均行后颅窝开颅显微手术治疗,其中动脉瘤颈夹闭9例,孤立切除2例,动脉瘤加固术1例,术后2例因脑积水加重行脑室-腹腔分流术。12例中除1例术后留有轻偏瘫外,其余11例恢复良好。结论小脑后下动脉瘤多以第四脑室出血发病,少数以小脑半球或蚓部出血发病,及早治疗效果满意。手术方式应尽量夹闭动脉瘤颈,对于小脑后下动脉末端动脉瘤,可以采用孤立切除术。     

大鼠前脑和脑干向中央上核的纤维投射

用辣根过氧化物酶(HRP)微电泳技术研究大鼠前脑和脑干向中央上核(CS)的纤维投射。将HRP输入CS后,观察到缰核、脚间核和被盖背核区有较多的标记细胞,斜角带核、下丘脑核和乳头体核有少量标记细胞。在外侧缰核、脚间核和被盖背核区可见丰富的顺行标记终末。结果表明,前脑的缰核和脑干的脚间核和被盖背核区是CS的主要传入来源,它们之间存在往返的纤维联系。     

GABAergic and glycinergic inputs to the rabbit oculomotor nucleus with special emphasis on the medial rectus subdivision

Contradictory results have been reported about the inhibitory input to the medial rectus subdivision of the oculomotor nucleus of the cat. In the present ultrastructural study, we quantified the GABAergic and glycinergic terminals in the various subdivisions of the rabbit oculomotor nucleus with the use of post-embedding immunocytochemistry combined with retrograde tracing of horseradish peroxidase. The density of the GABAergic input to the medial rectus subdivision was as substantial as that to the other subdivisions and the postsynaptic distribution of the GABAergic and glycinergic innervation did not differ among the different oculomotor subdivisions.     

Widespread cortical projections of the ventral tegmental area and of other brain stem structures in the cat

Summary Thirty-three cat brains with injections of horseradish peroxidase in various regions of the cerebral cortex were screened for afferent projections from the ventral tegmental area, the locus ceruleus, and the parabrachial nuclei. All three structures were found to project to rather divergent parts of the cortex, including regions in the posterior half of the hemisphere. These results, especially for the ventral tegmental area and, to a lesser degree, for the parabrachial neurons, disagree with most of the target loci of established cortical afferents in the rat. Though our results might be attributed to species differences in the cortical innervation of brain stem structures, we prefer explanations which emphasize different densities in the distribution of brain stem afferents to the cortex, and/or which suggest different cortical targets of catecholaminergic and noncatecholaminergic neurons.Supported in part by grant Ma 795 from the Deutsche Forschungsgemeinschaft (DFG)