Ocular counterrolling differs in dynamic and static stimulation.

In the past, the majority of ocular counterrolling (OCR) studies were performed with subjects tilted and held statically. Studies in our laboratory have focused on dynamic rotation below the threshold of the semicircular canals. The present study compares OCR in both static and dynamic modes. Ten normal subjects, mean age 50.9 years (SD 16.2 years), underwent rotation about their naso-occipital axis to 90 degrees to the right and left, at a constant velocity of 3 degrees/s and an acceleration of 0.2 degree/s2. Subsequently, they were tilted at the same acceleration and velocity to 30 degrees, 60 degrees, 90 degrees, 60 degrees, 30 degrees and 0 degree to both sides and held in each position for 1 min. The results showed that OCR varied substantially in the two protocols. The most dramatic difference was disconjugacy in the static mode, with the two eyes differing by as much as 4 degrees, in contrast to the generally conjugate OCR in the dynamic mode. Amplitudes also tended to differ, some subjects having greater and others lesser OCR in one mode vis-à-vis the other. Possible explanations for these differences may be found in the work of Hudspeth and colleagues, who found that mechanical deflection of the bullfrog saccula resulted in gradated responses in the underlying hair cells. Further, hair cells in the process of active bending led to different responses than those in a fixed position. Possibly in humans, too, the otoconia do not maintain a fixed relation to the underlying hair cells. Additionally, this study confirms our earlier finding of independent control in the two eyes.

Parabolic flight reveals independent binocular control of otolith-induced eye torsion.

To examine otolith-governed ocular torsion in hyper- and hypogravity, eight subjects, including two astronauts, underwent parabolic flight while seated upright with head fixed. A mask fitted with two video cameras provided synchronized images of both eyes at a rate of 25/sec during 15 parabolas, the individual parabolas separated by a few minutes of level 1 G flight. Three main findings emerged: 1) After the first parabola, most subjects showed differential torsional offset of the two eyes in the 1 G portions between parabolas, compared to the conjugate baseline position of the eyes prior to the first parabola. 2) Changes in binocular torsion in the 0 G and 1.8 G portions of parabolic flight revealed in most subjects systematic reversal of direction. The reversal was consistent within, but not across subjects. 3) Disconjugacy defined as the moment-to-moment difference in the movements of the two eyes, and evaluated without the contribution of the differential offset, found two subjects with relatively high disconjugacy scores, and the remaining six with low scores. On the basis of prior studies (9, 20), we would predict the first two would be subject to SMS, the remainder not. The two astronauts, who did not have SMS on their space missions, fell into the low scoring group. We propose that the disconjugacies may be due to intrinsic asymmetries in the otolith receptors on the two sides of the head, which appear to be independently linked to the extraocular muscles of the two eyes, a phenomenon masked in normal 1 G states by adaptation. The apparently independent control of the two sides cannot be detected by the simpler and more common monocular studies.

MRI evaluation of brain iron in earlier- and later-onset Parkinson's disease and normal subjects.

Tissue iron levels in the extrapyramidal system of earlier- and later-onset Parkinson's disease (PD) subjects were evaluated in vivo using a magnetic resonance imaging (MRI) method. The method involves scanning subjects in both high- and low-field MRI instruments, measuring tissue relaxation rate (R2), and calculating the field-dependent R2 increase (FDRI) which is the difference between the R2 measured with the two MRI instruments. In tissue, only ferritin iron is known to increase R2 in a field-dependent manner and the FDRI measure is a specific measure of this tissue iron pool. Two groups of male subjects with PD and two age-matched groups of normal control males were studied. The two groups of six subjects with PD consisted of subjects with earlier- or later-onset (before or after age 60) PD. FDRI was measured in five subcortical structures: the substantia nigra reticulata (SNR), substantia nigra compacta (SNC), globus pallidus, putamen, and caudate nucleus, and in one comparison region; the frontal white matter. Earlier-onset PD subjects had significant (p < 0.05) increases in FDRI in the SNR, SNC, putamen, and globus pallidus, while later-onset PD subjects had significantly decreased FDRI in the SNR when compared to their respective age-matched controls. Controlling for illness duration or structure size did not meaningfully alter the results. Published post-mortem studies on SN iron levels indicate decreased ferritin levels and increased free iron levels in the SN of older PD subjects, consistent with the decreased FDRI observed in our later-onset PD sample, which was closely matched in age to the post-mortem PD samples. The FDRI results suggest that disregulation of iron metabolism occurs in PD and that this disregulation may differ in earlier- versus later-onset PD.

The effect of space missions on gravity-responsive torsional eye movements.

Three astronauts underwent preflight, inflight, and postflight testing of spontaneous ocular torsion and of ocular counterrolling (OCR), reflexes governed by the gravity-responsive otolith organs in the inner ear. One astronaut, A, had a 30-day space mission on Euromir '94 and was examined monocularly with SensoMotoric Instruments video-oculography (VOG). The other two astronauts, B and C, were studied with a binocular VOG and flew an 180-day mission on Euromir '95. In space, spontaneous eye torsion in the upright position was found to be substantially offset from baseline Earth-based recordings in all three subjects for the duration of the flights. In addition, the binocular studies showed a marked torsional disconjugacy. On return to Earth, offset and torsional disconjugacy persisted for many days. OCR in response to 30 degrees right and left tilt was examined preflight and postflight. Compared to preflight, Astronaut A showed reduced OCR immediately postflight, which increased over the next few days. Both Astronauts B and C had increased OCR postflight, which gradually approached but did not achieve the preflight values over 13 days postflight. The adaptation of ocular torsion in space in one astronaut and not in the other two, and slow adaptation postflight, may reflect the lack of visual feed-back and the open loop nature of the otolith-ocular torsion reflex.

Changes in gravitational state cause changes in ocular torsion.

NASA: Gravity-responsive eye torsion was studied simultaneously in both eyes during parabolic flight to determine the effects of weightlessness. Observed effects were that torsional position of eyes in the 1G states between parabolas was offset from the baseline positions obtained prior to the onset of parabolas, responses to hyper- and hypogravity were seen in most subjects, and responses were consistent within subjects but varied between subjects.^ieng

Neural transplantation of cells expressing the anti-apoptotic gene bcl-2.

Long-term survival of grafted neural cells is a major goal of neural transplantation, but typical survival rates of grafted fetal neurons are in the range of 5-10%. Whether the death of transplanted neural cells is apoptotic or necrotic is unknown. The expression of the proto-oncogene bcl-2 inhibits both apoptotic and necrotic neural cell death. In a 6-OHDA induced rat model of Parkinson's disease, Hoechst 33258 prelabelled conditionally immortalized nigral cells engineered to express bcl-2 were stereotactically transplanted into the striatum ipsilaterally to the lesioned nigrostriatal pathway. Sixteen rats received bcl-2 transfected cells, 15 received cells transfected with vector alone, and 12 received either a nondopaminergic cell line or were sham transplanted as controls. Four wk following transplantation, the rats with grafts containing bcl-2 expressing cells showed an approximately 43% decrease in apomorphine-induced rotational behavior. In contrast, 12% improvement occurred in the rats with transplanted cells transfected with vector alone (p < 0.05), and no improvement occurred in sham-operated animals (p < 0.05). Histological examination showed no tumor formation. Despite the difference in behavioral effect, no clear difference in Hoechst fluorescent staining or staining for TH, GFAP was noted; therefore, it is unknown at present whether the observed effect was due to a difference in survival or to increased efficacy per surviving transplanted neural cell, or both.

Four-year follow-up of adrenal-to-brain transplants in Parkinson's disease.

OBJECTIVE: Evaluate long-term efficacy of autologous adrenal-to-caudate transplants in idiopathic Parkinson's disease refractory to medical treatment. DESIGN: Subjects underwent evaluations several times preoperatively on the University of California-Los Angeles Parkinson's Disease Disability Scale and the Hoehn and Yahr stage of disease. Postoperatively, they were also repeatedly rated on the Unified Parkinson's Disease Rating Scale. SETTING: Clinical visits and surgery took place at the University of California-Los Angeles Center for the Health Sciences. PATIENTS: Three men and one woman, ages 44 to 55 years, were followed up for several years preoperatively. At surgery, disease durations ranged from 7 to 16 years. Originally, all patients had a good response to levodopa, but for several years preoperatively, they had had fluctuating responses and a short duration of drug action. INTERVENTION: Right adrenalectomy was performed through a midline abdominal incision. Open craniotomy exposed the head of the right caudate into which pieces of adrenal medulla, 1 to 2 mm in size, were implanted. MAIN OUTCOME MEASURES: Scores on the three major scales (see "Design") were augmented with the number of hours "off" per day and severity of abnormal involuntary movements. Disease progression of each patient was compared with his own preoperative course and with those of a cohort of patients with Parkinson's disease followed up for 14 years who had received medical treatment without transplant surgery. RESULTS: After 4 years, transplants continued to be beneficial to three patients and had been of brief transient benefit to the fourth. The course of disease was more benign postoperatively than preoperatively and was more slowly progressive than that in the cohort. CONCLUSION: Improvement was not sufficient to justify adrenal transplants as routine therapy but does point the way to the use of other dopamine tissue transplantation.

MR imaging findings after transplant surgery for Parkinson disease.

The authors describe the magnetic resonance (MR) imaging appearance of the head of the right caudate nucleus in patients who have undergone adrenal medullary transplant surgery for Parkinson disease. All four patients examined showed some clinical improvement after surgery. The MR images acquired 4-6 months postoperatively showed no evidence of caudate atrophy. Three of the four patients showed some increase in size of the operated caudate head relative to preoperative studies. Neither cavitation nor high signal intensity on T2-weighted images was evident within the caudate head. The one patient studied after administration of gadopentetate dimeglumine showed no abnormal enhancement. These images provided a description of the transplant site and also suggested that the clinical improvement seen was not due to simple ablation of caudate tissue or to postoperative inflammation. The increase in size of the caudate head also suggested that some implanted tissue may have remained in these patients at the time the MR images were acquired.

A predictive test for space motion sickness.

Eye torsion was examined in 13 astronaut subjects, tested during repeated episodes of 0 G and 1.8 G in parabolic flight aboard NASA's KC-135. Four findings are included. 1) A strong relationship between previous history of SMS and ocular torsional disconjugacy in novel gravitational states. 2) Responses were unchanged in 4 subjects retested a year later. 3) Ocular torsional disconjugacy scores increased as exposure to 0 and 1.8 G increased. This was particularly evident in subjects who had had SMS. 4) Torsional studies during 10 to 20 parabolas are required to accurately predict SMS. The hypothesis of otolith asymmetry, compensated in 1 G but becoming unmasked in novel gravitational states, is proposed to explain the torsional disconjugacy and ensuing SMS.

Ocular torsion as a test of the asymmetry hypothesis of space motion sickness.

Disconjugate eye torsion induced by 0 G and 1.8 G during parabolic flight was studied in nine former astronauts in 1990 and eight in 1991, four of whom were included in the previous experiment. The astronauts could be divided into two statistically significant groups on the basis of low and high scores of disconjugacy. When their histories of space motion sickness (SMS) were later revealed, all of the low scorers had not been sick on previous space flights; all the high scorers had had SMS. These data give support to the hypothesis that SMS in one-half or two-thirds of astronauts is due to an otolith, probably utricular, asymmetry in those persons.

The dystonias.

The various dystonias have been found in at least five different hereditary backgrounds. The gene responsible for one of the dystonias, idiopathic torsion dystonia (ITD), lies on chromosome 9q32-34, with flanking markers now 1-2 cM apart. Magnetic resonance imaging and computerized tomography (CT) abnormalities in the basal ganglia, especially in the putamen, are found in many secondary dystonias. Botulinum toxin therapy is proving very useful in the treatment of focal dystonias.

Transplantation of human neuroblastoma cells, catecholaminergic and non-catecholaminergic: effects on rotational behavior in Parkinson's rat model.

Cultured human catecholaminergic and non-catecholaminergic donor cells were used in neural transplantation experiments in a rat model of Parkinson's disease. Using two different human catecholaminergic neuroblastoma cell lines, one control non-catecholaminergic neuroblastoma cell line, and one sham control (tissue culture medium), transplants were made into the striatum using a modified Ungerstedt hemiparkinsonian rat model. Significant decreases in apomorphine-induced rotational behavior were produced by two of three catecholaminergic cell lines. Grafted cells staining positively for tyrosine hydroxylase (TH) and catecholamine fluorescence indicated viable catecholamine activity in the two cell lines which produced reductions in rotational behavior. Catecholamine fluorescence was not detected in either of the two controls. These data suggest a link between catecholamine secretion by transplanted cells and motor improvement using a rat rotational behavior model.

Further evidence to support disconjugate eye torsion as a predictor of space motion sickness.

Disconjugate eye torsion in hypo- and hypergravity of parabolic flight was examined in four former astronauts and four previously tested ex-astronauts to replicate an earlier study and to further test the asymmetry hypothesis of otolith function. Results in the new subjects supported the asymmetry hypothesis and confirmed previous findings that those with low scores of torsional disconjugacy on the KC-135 did not suffer space motion sickness in their prior Shuttle missions while those with high scores did. Tilting subjects with high disconjugacy scores slightly to one side and the other failed to find a position that decreased disconjugacy in hypergravity, leading to the conclusion that a simple planar asymmetry about the y-axis was probably not the cause of the observed torsional differences in the two eyes. Disconjugacy increased at 0 G with increasing parabolas, much more so in subjects who had suffered SMS. Because of this, 10 to 20 parabolas were deemed to be a more certain discriminator than a fewer number.

Ventral intermediate thalamotomy for posttraumatic hemiballismus.

An unusual case of hemiballismus following closed head injury is presented. The abnormal movement persisted for 16 years despite medical treatment. Preoperative studies did not reveal a specific lesion within the subthalamic nucleus or within the basal ganglia. A stereotactic ventral intermediate thalamotomy was performed producing a complete resolution of the ballistic movement which persisted for the length of our 12-month follow-up.