Shirley G. Diamond

Ocular counterrolling as an indicator of vestibular otolith function

Sixteen normal subjects, 8 patients with unilateral vestibular nerve section, and 11 patients with acoustic neuromas underwent dynamic ocular counterrolling (OCR) testing. Both eyes were photographed at every 10° as the subject was tilted about the naso-occipital axis at a constant velocity of 3°/sec. Normal subjects differed from patients in four characteristics: (1) The binocular OCR patterns of normal subjects were consistent from one trial to the next. (2) The two eyes were mostly conjugate in movement. (3) The patterns were smooth. (4) OCR was approximately symmetric to right and left tilts. In the patients, patterns were abnormal when tilted to the side opposite the lesion. In quantified measures of the four characteristics, differences between the normal group and the group of patients with unilateral vestibular nerve sections were significant in consistency and total scores. In the patients with acoustic neuromas, OCR abnormalities corresponded to the size and location of the tumors and the extent to which they impinged on the utricular nerve and brainstem.

Parkinson's disease: sensory and motor problems in arms and hands.

Fifteen undemented patients with Parkinsons disease (PD) and 15 age-matched controls were given a battery of tests to assess sensorimotor integration in the arms. PD patients made more errors (p < 0.01) than controls, particularly in tests of proprioception. Age was not related to errors. Compared with controls, two-point discrimination thresholds were significantly higher (p <0.02) on the index finger of PD patients, but not on the forearm. Results confirm the sensorimotor deficits found earlier in an orofacial study, and imply that PD involves a generalized dysfunction of sensorimotor integration and proprioception, probably a result of impaired basal ganglia function in processing and integrating sensory input to organize and guide movement.

An examination of male‐female differences in progression and mortality of Parkinson's disease

We conducted disability and mortality studies to determine if the male preponderance usually found in Parkinsons disease (PD) was reflected in different courses of the disease in the 2 sexes. We analyzed longitudinal disability score in 47 men and 23 women with PD followed for 6 years at UCLA. We found no significant differences between the sexes in mean disability scores in any of the 6 years. Mean dopa dosage was significantly higher in men, possibly reflecting their generally larger body mass. Choreoathetosis, dementia, or other side effects did not differ between the 2 groups. We obtained observed to expected mortality ratios in 239 men and 132 women followed for 3,831 person-years from records of 4 medical centers. Using the sex-specific US Life Tables to calculate expected mortality, we found the observed to expected ratio for the men was 1.7457 and for the women 2.4740, a significantly greater excess in female mortality. Analyses of mortality using tables which are not sex-specific will fail to uncover the decreased longevity in women with PD. We conclude that, despite the male preponderance in PD, men and women acquire it at the same age, have the same progression and duration of disease, and die at the same age; whereas, in the general population, women have a longer life expectancy than men. It is not known what factors protect women from incurring PD and what lowers their life expectancy to that of men when they do have the disease.

Effect of age at onset on progression and mortality in Parkinson's disease

We examined longitudinal disability scores in 54 patients with Parkinsons disease followed for 6 years at UCLA. We sorted data into 3 groups based on age at onset of symptoms: group A, onset under 50 years; group B, 50 to 59 years; group C, 60 years or older. There were no significant differences between groups initially. All 3 groups improved dramatically when levodopa was given, but group A showed significantly less disability in years 4, 5, and 6 than did group C. The groups did not differ with respect to side effects. To determine if age at onset affected mortality, we sorted records from 4 geographically diverse centers into the same 3 groups. Results on 359 patients followed for 3,314 person-years, covering a period of 17 years after onset of symptoms, showed that group A had the most favorable observed-to-expected mortality ratio, 1.82, compared with 2.17 and 2.20 for groups B and C respectively, but the difference was not statistically significant. Results from the disability analyses indicate that patients with onset of Parkinsons disease under 50 years of age may have a more favorable prognosis than those whose symptoms begin in later years.

Evidence to support early levodopa therapy in Parkinson disease

To see whether duration of disease or of levodopa treatment was responsible for gradual worsening of parkinsonian patients, 58 persons treated with levodopa were classified into three groups based on predopa disease duration. Data over 6 years of treatment showed that disease duration was the determining factor. Patients matched for disease duration had similar disability scores regardless of duration of therapy. Matched for therapy duration, patients with longer disease duration had consistently higher disability scores. Side effects showed no differences between groups and did not increase over time. In sum, delaying therapy fails to improve disability in the early years of disease and does not confer any benefit in later years.

Binocular counterrolling in humans during dynamic rotation

Seven subjects 18 to 66 years old underwent 360 degrees rotation at a constant velocity of 3 degrees/sec, in 27 trials beginning randomly right ear down or left ear down. A camera on the rotating chair photographed both eyes every 10 degrees. Dual projectors measured counterrolling, the image from one projector being aligned and rotated until it was superimposed on the image from the other. Right and left eyes were measured independently. The group reached maximum counterrolling at about 70 degrees and 270 degrees in rotations to the right, with values of about -6 degrees and 4 degrees respectively. Rotations to the left reached maximum at 50 degrees and 270 degrees with about 4.5 degrees and -5.25 degrees respectively. Individual subjects showed ranges of counterrolling varying from 4.03 degrees to 17.44 degrees, mean 11.30 degrees. More counterrolling was observed when subjects were tilted to right than to left. The downward eye counterrolled more than the upward. Amount of counterrolling was inversely correlated with age.

Double‐blind trial of pergolide for Parkinson's disease

Pergolide mesylate, a dopamine agonist, was studied as adjunctive therapy in ia 6-month double-blind trial in 20 patients with Parkinsons disease who were achieving less than optimal response from Sinemet. As pergolide or placebo was administered in increasing dosage, Sinemet was reduced if side effects developed. Both the pergolide and placebo groups improved significantly (p < 0.05). The pergolide group improved 30% at the end of 24 weeks, and the placebo group 23%. There was no significant difference between drug and placebo groups, possibly due to a fortuitous support group and the side effects that may have burdened the pergolide group. Nevertheless, pergolide had a definite antiparkinsonian effect.

Binocular counterrolling in humans with unilateral labyrinthectomy and in normal controls.

Ocular counterrolling (OCRJ is the reflex torsion of the eyes about their visual axes in the direction opposite to the head as it is rolled about its naso-occipital axis. Considered to be mediated by the otolith receptors in the utricle,’ OCR is an observable behavior that invites inferences on the complex functions of the inner ear. More than 75 years of effort have been devoted to the seemingly simple task of comparing OCR in persons with known unilateral lesions to that of normal persons, focusing on the amplitude of OCR under static tilt. The contradictory results of the several studies, as reviewed below, suggest that this measure is not a productive parameter in detecting unilateral otolith dysfunction. B5rAny is credited with first introducing OCR to the clinic in 1906.4*5 He examined the response in normals and in deaf-mutes, and felt that OCR was regulated by the semicircular canals. In 1925, Kompanejetz examined OCR in 48 deaf-mutes, tilting their heads 30” to the right and looking at both eyes “simultaneously” (actually ~equentially).~ He separated his patients into two groups, one having some response to caloric or rotatory stimulation, and the other group having none. He found the presence and absence of OCR in both groups and therefore concluded that OCR was innervated from a point independent of the semicircular canals. He further observed that OCR may be different in the two eyes, suggesting that “in an asymmetrically injured otolith apparatus, a disturbance of the associated eye movements may occur, manifesting itself in different angles for the two eyes in ~ounterrolling.”~ A few years later, Kompanejetz looked at 100 normal subjects to see i f hoth eyes performed equally.6 He observed that there was more OCR in the right eye when the head was inclined to the right and more in the left eye when the head was inclined to the left. He also found that both eyes showed more OCR on tilt to the right than on tilt to the left. He considered it normal to find differences of 5’ in a given eye when tilted to either side, or of 3-4” between the two eyes when the head was tilted to one side. Unfortunately, this study differed in design and followed his work in the deaf-mute patients, so he was unable to make comparatile observations in persons with labyrinthine defects. He wrote, “It is regrettable that up to now we have not succeeded in commanding such methods [for the otolith apparatus] as may be used for examining the functions of the semicircular canals.”fi Today, more than 50 years later, we may say the same. Many investigators over the years have studied OCR in a variety of experimental designs. In 1936, Gollas studied seven patients with unilateral labyrinthine and cochlear de~truction.~ He held them at 20, 40, 60, and 90” positions on both sides and examined OCR in both eyes. He found that tipping to the side of the lesion resulted in normal OCR, but that tipping to the contralateral side produced much less OCR. He found no difference in the two eyes. In 1963, Miller and Graybiel compared OCR in 9 normal persons to 10

Evaluating the evaluations: Or how to weigh the scales of parkinsonian disability

We used four disability scales to evaluate eight patients with Parkinsons disease who were treated with pergolide mesylate for 1 year. Disability was rated on all four scales by the same neurologist at each of 11 visits. Prior ratings were not available to the examiner, who did not know that the scales themselves were an object of study. Disability scores, converted to percentage improvement relative to baseline, varied considerably between scales; for instance, at 5 months, one showed 13% improvement and another 58%. At 9 months, one showed worsening of 6% and another showed improvement of 34%. The four disability scales clearly measure different aspects of parkinsonism, and comparing results of different studies may not be valid if the disability scales are not the same.

Binocular Counterrolling during Sustained Body Tilt in Normal Humans and in a Patient with Unilateral Vestibular Nerve Section

Two normal persons and a patient with unilateral vestibular nerve section were held motionless for ten minutes in the upright position, at 60° tilt right ear down, and at 60° tilt left ear down. In addition, one normal subject was held for ten minutes at each of 30, 60, and 90° tilt left ear down. Photographs were taken of both eyes every ten seconds. Measurements of ocular counterrolling during these trials revealed torsional eye movements in all positions, including the upright, even though the head and body were stationary. Variations in torsion in the upright position ranged up to 2.75°. At the tilt positions, variations ranged up to 4°. Disconjugate movements were seen in all subjects in all positions. There were no significant differences in measurements of ocular counterrolling during static tilt between the normal subjects and the patient with the vestibular nerve section, in contrast to measures obtained during slow velocity dynamic testing.