A 69-year-old woman with Parkinson's disease and levodopa-induced dyskinesias had a deep brain stimulation (DBS) electrode inserted into the right globus pallidus internus (GPi). During the operation, the GPi was mapped with dual microelectrode recordings. Stimulation through one microelectrode in GPi inhibited the firing of GPi neurons recorded with another microelectrode 600--1,000 microm distant. The inhibition could be obtained with pulse widths of 150 micros and intensities as low as 10 microA. Single stimuli inhibited GPi neurons for approximately 50 ms. Trains of 300 Hz stimuli inhibited GPi neuron firing almost completely. Postoperatively, stimulation through macroelectrode contacts located in the posterior ventral pallidum controlled the patient's dyskinesias. The effect could be obtained with pulse widths of 50 micros and frequencies as low as 70--80 Hz. We postulate stimulation of the ventral pallidum controls dyskinesias by activating large axons which inhibit GPi neurons.
We tested the hypotheses that orthostatic tremor is generated by a central oscillator and that the tremor is expressed through spinal Ib interneurons. Six patients with orthostatic tremor were examined. The tremor was reset by electrical stimulation over the posterior fossa at intensities that were below the threshold for a motor evoked potential (MEP) but was not reset by transcranial magnetic stimulation over the motor cortex that did produce an MEP. It is argued that the oscillator involves the cerebellum or brainstem. The inhibition of voluntary EMG produced by stimulation over tendons, which has been attributed to effects from Golgi tendon organs (GTO), was not modulated in synchrony with the tremor. We were unable to demonstrate, therefore, that the tremor is expressed through GTO interneurons with this method.
Endoplasmic reticulum (ER) chaperone heat shock 70 kDa protein 5 (HSPA5/GRP78) is known to be involved in the metabolism of amyloid precursor protein and neuronal death in Alzheimer's disease (AD) could arise from dysfunction of the ER. Through a case-control study and an expression assay, we investigated the association of HSPA5 -415 G/A (rs391957), -370 C/T (rs17840761) and -180 del/G (rs3216733) polymorphisms with Taiwanese AD. The overall genotype and allele frequency distribution at the completely linked -415 G/A and -180 del/G sites showed significant difference between AD cases and controls (P = 0.020 and 0.009, respectively). A decrease in risk of developing AD was demonstrated for -415 AA/-180 GG genotype [OR = 0.38, 95% confidence interval (CI) = 0.18-0.75, P = 0.007] and -415 A/-180 G allele (OR = 0.69, 95% CI = 0.51-0.91, P = 0.009). The HSPA5 transcriptional activity of the -415 A/-180 G allele was significantly lower than that of the -415 G/-180 del alleles, whereas induction of HSPA5 expression after ER stress was markedly increased in the cells with the -415 A/-180 G allele. Therefore, our preliminary results may suggest a protective role of the HSPA5 -415 A/-180 G allele in Taiwanese AD susceptibility.
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