Shigeyuki Nishikawa

Bilateral pallidal stimulation for idiopathic segmental axial dystonia advanced from meige syndrome refractory to bilateral thalamotomy

Meige syndrome is an adult‐onset dystonic movement disorder that predominantly involves facial muscles, while some patients with this syndrome develop spasmodic dysphonia and dystonia of the neck, trunk, arms, and legs. We report that all dystonic symptoms that had been refractory to both pharmacotherapy and bilateral thalamotomy were markedly alleviated by bilateral pallidal stimulation in a patient with segmental axial dystonia advanced from Meige syndrome.

Lack of Reelin causes malpositioning of nigral dopaminergic neurons: Evidence from comparison of normal and Relnrl mutant mice

The reeler gene (Relnrl, formerly rl) product Reelin controls neuronal migration and positioning and thereby plays a key role in brain development. Mutation of Reln leads to widespread disruption of laminar cortical regions and ectopia in some brainstem nuclei. In the embryonic striatum of normal mice, a substantial expression of reelin mRNA has been documented; however, the anomalous positioning of neurons in the basal ganglia of reeler mice remains to be studied. We provide first evidence for a potential role of Reelin in the developmental formation of the substantia nigra. In reeler mutant mice lacking Reelin, dopaminergic neurons destined for the substantia nigra fail to migrate laterally and become anomalously clustered just lateral to the ventral tegmental area. Their axons appear to project to striatal patches forming “dopamine islands.” Results from the normal mice show that, at the midembryonic stage, Reelin identified with CR‐50 is highly concentrated in the ventral mesencephalon, where nigral dopaminergic neurons are in progress to migrate laterally to their eventual position of the adult brain. A combination of CR‐50 labeling and anterograde axonal tracing provided evidence that embryonic striatal neurons may supply the ventral portion of the mesencephalon with Reelin through their axonal projections. We hypothesize that Reelin plays a role in the positioning of nigral dopaminergic neurons and that it can act as an environmental cue at a remote site far from its birthplace via a transaxonal delivery system. J. Comp. Neurol. 461:166–173, 2003.

Neuronal cell migration for the developmental formation of the mammalian striatum

The mammalian striatum is the largest receptive component of the basal ganglia circuit. It is involved in the control of various aspects of motor, cognitive, and emotional functions. In the telencephalon, the striatum has a unique histological property totally different from the cortical area and its ontogenesis remains largely unknown. In this review, we introduce recent advances in the understanding of neuronal cell migration, one of the most critical processes in the early phase of histogenesis that occurs in the embryonic striatum. It appears that there are three major modes of neuronal cell migration in the developmental formation of the striatum. They are (radial) outward, tangential, and inward migration, supplying the striatum with projection neurons, interneurons, and early-generated transient neurons that originate in the preplate, respectively. We challenge the classical concept that the striatum is solely derived from the restricted germinal area located in the basal telencephalon by providing evidence that striatal development requires the intermixture of different types of neurons originating from distinct regions of the telencephalon.

Apraxia of lid opening is alleviated by pallidal stimulation in a patient with Parkinson’s disease

Apraxia of lid opening (ALO) is a syndrome characterized by a non‐paralytic inability to open the eyes at will in the absence of visible contraction of the orbicularis oculi muscle. Here we report that globus pallidus internus deep brain stimulation on the right side markedly alleviates ALO as well as gait freezing in a patient with Parkinson’s disease.

Abolition of postapoplectic hemichorea by Vo-complex thalamotomy: Long-term follow-up study

We report a patient with hemichorea following subthalamic hemorrhage. Vo‐complex thalamotomy abolished the choreic movements for over 4 years of follow‐up.

Expression of four mutant human ornithine transcarbamylase genes in cultured Cos 1 cells relates to clinical phenotypes

Ornithine transcarbamylase (OTC) deficiency is an X-linked disease with a heterogeneous phenotype, even in affected males. To detect mutations in the OTC gene using genomic DNA, we have developed a method in which all exons and adjacent introns are amplified and sequenced. Although this approach detected mutations in many cases, the relationship between a mutation and the OTC phenotype was not firmly established. Therefore, we investigated the issue by expression analysis of mutant OTC cDNA in cultured cells. Four mutant OTC cDNAs were constructed, based on the reported cases, using our newly developed method. The normal (wild-type) human OTC cDNA was reproducibly expressed at high levels in these Cos 1 cells. Predicted OTC activities of mutant OTC cDNAs ranged from 0% to 8.9% of the normal level together with variable amounts of the enzyme protein. The predicted enzyme activities account for the clinical phenotype of the disease. Our observations confirm that these mutations are responsible for OTC deficiency in these patients.

Temporal sequence of response to unilateral GPi pallidotomy of motor symptoms in Parkinson's disease

The present study was performed to determine the temporal sequence of the response to unilateral MRI/microelectrode-guided pallidotomy of each cardinal symptom in Parkinson’s disease (PD). For this purpose, we performed a quantitative assessment of motor functions in 19 patients with PD at several time points up to 6 months following surgery. We here report that although all the motor signs were significantly improved 6 months after pallidotomy, the temporal sequence of tremor response was different from those of other symptoms.

Impact of Posterior GPi Pallidotomy on Leg Tremor in Parkinson’s Disease

Although stereotactic thalamotomy is the mainstay in the surgical treatment of tremor in patients with Parkinson’s disease (PD), this surgery is not favored and is even a matter of potential concern in the treatment of leg tremor since it carries a significant risk of injury to the internal capsule. In this study we have carried out a quantitative assessment of leg tremor alleviation in 12 patients with PD after MRI-/microelectrode-guided stereotactic ablation of the posterior part of the globus pallidus internus (GPi). The results showed that posterior GPi pallidotomy combined with drug therapy is a satisfactorily effective therapeutic strategy to treat parkinsonian leg tremor.