Satoshi Goto

Early‐onset generalized dystonia attributable to a DYT1 gene mutation is a hyperkinetic movement disorder that responds poorly to pharmacotherapy. In this video brief, we show that continuous bilateral stimulation of the globus pallidus internus produced sustained and marked improvements in the motor symptoms and functional disabilities of Japanese patients with DYT1‐generalized dystonia. © 2006 Movement Disorder Society

Dystonia is a neurological syndrome characterized by sustained muscle contractions that produce repetitive twisting movements or abnormal postures. X‐linked recessive dystonia parkinsonism (XDP; DYT3; Lubag) is an adult‐onset disorder that manifests severe and progressive dystonia with a high frequency of generalization. In search for the anatomical basis for dystonia, we performed postmortem analyses of the functional anatomy of the basal ganglia based on the striatal compartments (ie, the striosomes and the matrix compartment) in XDP. Here, we provide anatomopathological evidence that, in the XDP neostriatum, the matrix compartment is relatively spared in a unique fashion, whereas the striosomes are severely depleted. We also document that there is a differential loss of striatal neuron subclasses in XDP. In view of the three‐pathway basal ganglia model, we postulate that the disproportionate involvement of neostriatal compartments and their efferent projections may underlie the manifestation of dystonia in patients with XDP. This study is the first to our knowledge to show specific basal ganglia pathology that could explain the genesis of dystonia in human heredodegenerative movement disorders, suggesting that dystonia may result from an imbalance in the activity between the striosomal and matrix‐based pathways. Ann Neurol 2005

This 53 year old right-handed man with a history of essential hypertension suddenly developed right hemiparesis and cerebellar ataxia in February 2000. He was admitted to a hospital where radiological examinations showed a left upper brainstem haemorrhage (fig 1A). His neurological state gradually improved. However, in October 2001 a coarse, slowly progressive tremor arose in his right upper extremity. It was severely disabling and he could not use his right arm. He was admitted to our hospital in December 2001.

The mammalian cerebral cortex is organized into horizontal and vertical arrays of neurons and their fiber connections that form anatomically and physiologically distinct laminar and columnar compartments. However, the developmental mechanism(s) underlying this dichotomous pattern remains a mystery. We provide anatomical evidence suggesting that reelin, a diffusible protein produced and secreted by Cajal–Retzius cells, is involved in the developmental formation of the vertical cell structures in the mouse presubicular cortex, the unique site where the vertical columnar arrays of cortical plate neurons and their dendritic branches are clearly identified during the early postnatal period. Our results also suggest that reelin plays a role in the formation of these vertical structures by acting as an inhibitory or stop signal for cortical plate neurons and their dendritic extensions. In addition to having perturbed horizontal laminae, reeler mutant mice, lacking reelin, display disruption of these vertical structures. Based on the present findings, we hypothesize that reelin and Cajal–Retzius cells regulate the developmental formation of not only horizontal laminations, but also vertical columnar structures in the cerebral cortex.

We sought to identify optimal paradigms of bilateral globus pallidus internus (GPi) stimulation in 3 subsequent patients with severe cervical dystonia. At low frequency stimulation (50–60 Hz) with wide pulse width (500 µs) and high amplitude (4.5–8.0 V), we observed immediate and consistent improvement of dystonia and dystonia-associated pain. Stimulation of the posteroventral portion of the GPi led to pronounced alleviation of dystonia; stimulation of the anterodorsal portion or at the dorsal border of the GPi resulted in significant worsening of symptoms. The therapeutic benefit obtained by using the optimal stimulation parameters continues and has lasted for at least 1 year in each patient.

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.

The mammalian striatum arises in the basal telencephalon and contains morphologically homogenous neurons that can be divided into two distinct compartments, patches and the matrix. During development, patch neurons are generated first to form a striatal primordium. After a large influx of later-born matrix neurons into this region, the unique mosaic arrangement of these two neuronal phenotypes is established. The massive migration of matrix neurons continues during the embryonic period, and they eventually comprise 80–85% of the mature striatum. To elucidate the cellular mechanism or mechanisms underlying this critical event in striatal histogenesis, we examined the migration characteristics of striatal subventricular zone (SVZ) cells at embryonic day 18 when neurogenesis peaks for matrix neurons. Using gel cultures, we show that netrin-1, one of the diffusible guidance cues expressed in the striatal ventricular zone (VZ), exerts a repulsive action on migrating SVZ cells. This effect is blocked in the presence of antibodies against Deleted in colorectal cancer (DCC), a putative receptor for netrin-1. The expression patterns ofnetrin-1and DCC strongly suggest the involvement of this effect in the outward migration of SVZ cells into the striatal postmitotic region. Our cell tracing study using living brain slices demonstrates that striatal SVZ cells migrate toward and disperse throughout the striatum, in which they differentiate into phenotypes of striatal projection neurons. We suggest that netrin-1 expressed in the striatal VZ serves to guide the large influx of striatal matrix neurons into the striatal primordium and is thereby involved in the initial formation of fundamental striatal structures.

Specialized subsets of early-generated neurons provide the cellular cues that are necessary for the establishment of characteristic cell and fiber interactions in each brain region. During the development of the mammalian cerebral cortex, the early-generated cells line up in the most superficial part of the telencephalic pallium forming the preplate. It has been generally thought that the preplate derivatives are exclusively located in the cortical region and govern the early histogenetic phase of cortical development. However, we here disclose an unexpected evidence that a subset of early-generated neurons of the piriform preplate migrate inward into and disperse within the subcortical structure striatum during the embryonic stage. Their migratory route is unique and its direction is opposite to the ordinary migration of neuronal precursors directed outward from the periventricular germinal zone. After immigrating into the developing striatum, these early-generated cells are closely associated with the intrastriatal fascicules of axons. The majority of these cells are eliminated by apoptotic cell death during the early postnatal stage. Based on these findings, we propose a new concept: the preplate neurons may not only direct cortical histogenesis but also change their location to play a role in the development of subcortical structures.

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.