Hideki Shimazu

Functional anatomy of the basal ganglia in X-linked recessive dystonia-parkinsonism.

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

Bilateral deep brain stimulation of the globus pallidus internus in tardive dystonia

Tardive dystonia is a disabling movement disorder as a consequence of exposure to neuroleptic drugs. We followed 6 patients with medically refractory tardive dystonia treated by bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) for 21 ± 18 months. At last follow‐up, the Burke‐Fahn‐Marsden Dystonia Rating Scale (BFMDRS) motor score improved by 86% ± 14%, and the BFMDRS disability score improved by 80% ± 12%. Bilateral GPi‐DBS is a beneficial therapeutic option for the long‐term relief of tardive dystonia.

Pre-movement gating of short-latency somatosensory evoked potentials.

Somatosensory evoked potentials (SEPs) are reduced in amplitude during movement (gating). The mechanism involves central gating of afferent input and competition from other afferents activated by the movement. We distinguished these two by giving 11 normal subjects a warning sound followed 1 s later by an electric stimulus to the right median nerve at the wrist. The latter served both as a cue to start a finger movement and as stimulation to evoke SEPs. Gating effects were widespread in frontal (N30) and central (N60) areas, but were also seen, albeit to a lesser extent, in the recordings at P3 (P30). Since finger movement began after the stimulus, such gating must have been purely central in origin, presumably reflecting motor preparation.

Subthalamic nucleus deep brain stimulation for camptocormia associated with Parkinson's disease

Camptocormia becomes increasingly recognized as a disabling symptom associated with Parkinsons disease (PD). We here report six patients with advanced PD in whom continuous bilateral stimulation of the subthalamic nucleus produced substantial (mean 78% ± 9.1% of the thoracolumbar angle) improvement of camptocormia along with other motor symptoms.

Theta Oscillations in Primate Prefrontal and Anterior Cingulate Cortices in Forewarned Reaction Time Tasks

Previously, we introduced a monkey model for human frontal midline theta oscillations as a possible neural correlate of attention. It was based on homologous theta oscillations found in the monkeys prefrontal and anterior cingulate cortices (areas 9 and 32) in a self-initiated hand-movement task. However, it has not been confirmed whether theta activity in the monkey model consistently appears in other situations demanding attention. Here, we examined the detailed properties of theta oscillations in four variations of forewarned reaction time tasks with warning (S1) and imperative (S2) stimuli. We characterized the theta oscillations generated exclusively in areas 9 and 32, as follows: 1) in the S1-S2 interval where movement preparation and reward expectation were presumably involved, the theta power was higher than in the pre-S1 period; 2) in the no-go trials of go/no-go tasks instructed by S1, the theta power in the S1-S2 interval was lower than in the pre-S1 period in an asymmetrical reward condition, whereas it was moderately higher in a symmetrical condition; 3) the theta power after reward delivery was higher than in the unrewarded trials; 4) the theta power in the pre-S1 period was higher than in the resting condition; and 5) when the monkey had to guess the S1-S2 duration internally without seeing S2, the theta power in the pre-S1 period was higher than in the original S1-S2 experiment. These findings suggest that attentional loads associated with different causes can induce the same theta activity, thereby supporting the consistency of attention-dependent theta oscillations in our model.

DYT1 mutation in Japanese patients with primary torsion dystonia.

A GAG deletion at position 946 in the DYT1 gene has been identified as one of the gene mutations responsible for autosomal dominant primary torsion dystonia. We examined 178 Japanese patients with various forms of dystonia, and found the mutation in six patients (3.4%) from three families. Five of them had early clinical onset (before age 12) with initial involvement of a limb. To our knowledge, this is the first report of the frequency and the clinical features of DYT1 mutation in oriental patients, and the clinical presentation of the mutation in these patients was similar to that of Jewish or non-Jewish Caucasian patients.

Comparison of monophasic versus biphasic stimulation in rTMS over premotor cortex: SEP and SPECT studies

OBJECTIVE To optimize the clinical uses of repetitive transcranial magnetic stimulation (rTMS), we compared the effects of rTMS on somatosensory-evoked potentials (SEPs) and regional cerebral blood flow (rCBF) using different phases (monophasic vs. biphasic) or frequencies (0.2Hz vs. 0.8Hz) of stimulation. METHODS In the first experiment, different phases were compared (0.2Hz monophasic vs. 0.2Hz biphasic). Biphasic 1Hz or sham condition served as controls. The second experiment was to explore the effect of frequencies (0.2Hz vs. 0.8Hz) using the monophasic stimulation. Substhreshold TMS was applied 250 times over the left premotor cortex. Single photon emission computed tomography (SPECT) was performed before and after monophasic 0.2Hz or biphasic 1Hz rTMS. RESULTS Monophasic rTMS of both 0.2 and 0.8Hz significantly increased the ratio of N30 amplitudes as compared with sham rTMS, whereas biphasic stimulation showed no significant effects. SPECT showed increased rCBF in motor cortices after monophasic 0.2Hz rTMS, but not after biphasic 1Hz stimulation. CONCLUSIONS Monophasic rTMS exerted more profound effects on SEPs and rCBF than biphasic rTMS over the premotor cortex. SIGNIFICANCE Monophasic rTMS over the premotor cortex could be clinically more useful than biphasic rTMS.

Abnormal sensory gating in basal ganglia disorders

Basal ganglia encompass four to five distinct loops to allow parallel processing of information. Among them, the most intensively studied is the motor loop, which includes two distinct direct and indirect pathways. The direct pathway exerts facilitatory influence upon the motor cortex, whereas the indirect pathway exerts an inhibitory effect. Overall, this dual system provides a center(excitatory)-surround-(inhibitory) mechanism to focus its effect on selected cortical neurons, and several lines of evidence suggest that this center-surround mechanism is used to focus the output on a specific group of muscles required for performing a specific task. This operation is made possible through opening the sensory channel for the expected sensory feed-back afferents during movement. Thus, one of the important functions of basal ganglia seems to be the gating of sensory input for motor control. Dystonia may be caused by a mismatch between sensory input versus motor output, and parkinsonism may be viewed as a disorder of gain control of this sensorimotor integration.

High-frequency SEP components generated in the somatosensory cortex of the monkey.

To investigate the origin of high-frequency somatosensory evoked potential (SEP) components, we recorded median nerve SEPs from the scalp and the depth in six monkeys. Laminar field potentials were analyzed in area 3b (N10; corresponding to human N20) and area 1 (P12; corresponding to human P25). After digital filtering (300–900 Hz), 4–6 components were identified, and the 1st to 4th peaks in area 3b (7–11 ms in latency) and the 3rd to 5th in area 1 (9–13 ms) showed clear polarity reversals between the surface and the depth of the cortex. These results provide direct evidence for intracortical origin of early high-frequency components in area 3b and of late ones in area 1.

THALAMIC VO-COMPLEX VS PALLIDAL DEEP BRAIN STIMULATION FOR FOCAL HAND DYSTONIA

Focal hand dystonia (FHD) is a primary dystonia produced by the excessive co-contraction of antagonistic muscles of the hand and forearm.1,2 Although deep brain stimulation (DBS) is now recognized as a beneficial option to treat a wide spectrum of dystonias,3 little is known regarding its effects on FHD. This is a report of DBS of the thalamic Vo-complex nucleus or the globus pallidus internus (GPi) effecting the complete, sustained relief of medically intractable FHD. The term Vo-complex refers to the combination of the ventralis oralis anterior nucleus (Voa) and ventralis oralis posterior nucleus (Vop) of the thalamus. ### Case report. A 34-year-old right-handed man without a notable medical history experienced gradual onset of writers cramp of the right hand beginning at age 31. At age 32 he also noted progressively worsening stiffness of the fingers and wrist of his left hand. As the focal injection of botulinum toxin and sequential pharmacologic trials that included clonazepam, baclofen, and etizolam produced unsatisfactory results, they were discontinued. On admission, his physical and mental condition was normal. Brain MRI and laboratory studies revealed no abnormal findings. The causes of secondary dystonia were excluded as far as possible. There were no neurologic abnormalities except for …