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.     

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.     

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)     

Enkephalin mRNA production by cochlear and vestibular efferent neurons in the gerbil brainstem

Summary Preproenkephalin mRNA production by efferent neurons projecting to the gerbil inner ear was assessed using combined in situ hybridization and retrograde labeling with florescent tracers. Virtually all vestibular efferent neurons were positive for preproenkephalin mRNA. Of the cochlear efferents, one-half of the medial olivocochlear neurons were positive for enkephalin. All lateral olivocochlear neurons were negative for enkephalin. The results suggest that there are two, biochemically distinct subpopulations of medial olivocochlear efferents in the gerbil. Offprint requests to: Division of Otolaryngology, ENT, V-112C     

辽宁产东亚钳蝎毒镇痛作用与脑内中枢关系的研究

应用立体定位、核团内注射与电解损毁核团技术及微电极细胞外记录方法，以猫丘脑后核内脏大神经诱发单位放电为内脏痛指标，观察向尾状核、中脑导水管周围灰质及杏仁内侧核内注入东亚钳蝎毒及在电解损毁３个核团前后ＰＯ内脏大神经诱发单位放电的变化。在损毁诸核之前刺激内脏大神经引起单位诱发放电，损毁诸核之后诱发放电减弱或消失，这与辽宁产东亚钳蝎毒注入诸核团中的作用相一致。表明蝎毒的作用部位与上述核团有关，更进一步证明蝎毒作用部位     

Isolated angiitis of the central nervous system: involvement of penetrating vessels at the base of the brain

Summary Isolated angiitis of the central nervous system (IAC) was diagnosed in a 40-year-old Caucasian male by histological examination of a leptomeningeal biopsy specimen, and the exclusion of systemic inflammatory or infective disease. Therapy with prednisone 30 mg/day and cyclophosphamide 100 mg/day resulted in clinical and radiological improvement, which have been maintained for an 8-month follow-up period. Magnetic resonance imaging (MRI) showed lesions implicating involvement of specific penetrating vessels at the base of the brain, an unusual complication of IAC, and allowed an accurate MRI-clinical correlation.     

Pathophysiology of idiopathic dystonia: findings from genetic animal models

Dystonia is a common movement disorder which is thought to represent a disease of the basal ganglia. However, the pathogenesis of the idiopathic dystonias, i.e. the neuroanatomic and neurochemical basis, is still a mystery. Research in dystonia is complicated by the existence of various phenotypic and genotypic subtypes of idiopathic dystonia, probably related to heterogeneous dysfunctions.In neurological diseases in which no obvious neuronal degeneration can be found, such as in idiopathic dystonia, the identification of a primary defect is difficult, because of the large number of chemically distinct, but functionally interrelated, neurotransmitter systems in the brain.The variable response to pharmacological agents in patients with idiopathic dystonia supports the notion that the underlying biochemical dysfunctions vary in the subtypes of idiopathic dystonia. Hence, in basic research it is important to clearly define the involved type of dystonia.Animal models of dystonias were described as limited. However, over the last years, there has been considerable progress in the evaluation of animal models for different types of dystonia.Apart from animal models of symptomatic dystonia, genetic animal models with inherited dystonia which occurs in the absence of pathomorphological alterations in brain and spinal cord are described.This review will focus mainly on genetic animal models of different idiopathic dystonias and pathophysiological findings. In particular, in the case of the mutant dystonic (dt) rat, a model of generalized dystonia, and in the case of the genetically dystonic hamster (dt^sz), a model of paroxysmal dystonic choreoathetosis has been used, as these show great promise in contributing to the identification of underlying mechanisms in idiopathic dystonias, although even a proper animal model will probably never be equivalent to a human disease.Several pathophysiological findings from animal models are in line with clinical observations in dystonic patients, indicating abnormalities not only in the basal ganglia and thalamic nuclei, but also in the cerebellum and brainstem. Through clinical studies and neurochemical data several similarities were found in the genetic animal models, although the current data indicates different defects in dystonic animals which is consistent with the notion that dystonia is a heterogenous disorder.Different supraspinal dysfunctions appear to lead to manifestation of dystonic movements and postures. In addition to increasing our understanding of the pathophysiology of idiopathic dystonia, animal models may help to improve therapeutic strategies for this movement disorder.     

Glutamic acid decarboxylase-like immunoreactivity in brainstem auditory nuclei of the rat

The distribution of GABA-producing neurons in the brainstem auditory nuclei of the rat was investigated immunohistochemically by using an antibody to glutamic acid decarboxylase (GAD). In the cochlear nuclei, GAD immunoreactive neurons are present only in the superficial granular and molecular layers, whereas terminals are found in all subdivisions of the nuclei and are particularly dense surrounding large spherical cells and one type of stellate cell. In the superior olivary complex, GAD immunoreactive neurons are located in the lateral olivary nucleus and throughout the periolivary region. Immunoreactive terminals are distributed along dendrites of principal cells of the medial and lateral olivary nuclei and are clustered around somata of globular neurons of the nucleus of the trapezoid body. An extremely dense band of immunoreactive somata and terminals is present along the ventral edge of the olivary complex. The ventral, intermediate, and dorsal nuclei of the lateral lemniscus contain small fusiform GAD-immunoreactive neurons and a moderately dense plexus of immunoreactive terminals. The inferior colliculus contains a large population of GAD-immunoreactive perikarya and an extremely dense accumulation of immunoreactive terminals in the central, dorsomedial, and external nuclei. These observations indicate that GABA systems are involved in function at all levels of the brainstem auditory pathway.