Oculomotor function in frontotemporal lobar degeneration, related disorders and Alzheimer's disease

Frontotemporal lobar degeneration (FTLD) often overlaps clinically with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), both of which have prominent eye movement abnormalities. To investigate the ability of oculomotor performance to differentiate between FTLD, Alzheimer's disease, CBS and PSP, saccades and smooth pursuit were measured in three FTLD subtypes, including 24 individuals with frontotemporal dementia (FTD), 19 with semantic dementia (SD) and six with progressive non-fluent aphasia (PA), as compared to 28 individuals with Alzheimer's disease, 15 with CBS, 10 with PSP and 27 control subjects. Different combinations of oculomotor abnormalities were identified in all clinical syndromes except for SD, which had oculomotor performance that was indistinguishable from age-matched controls. Only PSP patients displayed abnormalities in saccade velocity, whereas abnormalities in saccade gain were observed in PSP > CBS > Alzheimer's disease subjects. All patient groups except those with SD were impaired on the anti-saccade task, however only the FTLD subjects and not Alzheimer's disease, CBS or PSP groups, were able to spontaneously self-correct anti-saccade errors as well as controls. Receiver operating characteristic statistics demonstrated that oculomotor findings were superior to neuropsychological tests in differentiating PSP from other disorders, and comparable to neuropsychological tests in differentiating the other patient groups. These data suggest that oculomotor assessment may aid in the diagnosis of FTLD and related disorders

Horizontal and vertical optokinetic nystagmus in normal and abnormal children and adults

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Horizontal and vertical optokinetic nystagmus in normal and abnormal infants and adults

Optokinetic nystagmus (OKN) is a reflexive visual response that can be elicited from humans of all ages. The optokinetic response consists of an alternating sequence of following movements (slow phases) in the direction of stimulus movements, interrupted by fast movements (quick phases) in the opposite direction. This thesis investigates how the slow and the quick phases of both horizontal and vertical OKN may have a role in the assessment of the oculomotor system. In normal adults, the speeds of horizontal OKN quick phases were compared to horizontal saccades. It was found that they had the same main sequence for duration but that the main sequence for peak velocity is sHghtly faster for saccades than OKN quick phases. Also, the speeds of horizontal OKN quick phases in normal infants were considered and found not to be significantly different (p>0.05) to those of adults. Further, the horizontal OKN quick phases in a group of children with neuronopathic Gaucher disease were examined. It was found that horizontal saccades and horizontal OKN quick phases were grossly slow in this condition. It is proposed that examination of OKN quick phases is a simple clinical means for approximating the saccadic main sequence and for identifying patients with brainstem abnormalities. Gaze position during full-field horizontal OKN stimulation was assessed. It was confirmed that the mean position of gaze is shifted in the direction opposite to stimulus movement. This was a robust phenomenon occurring even at very low stimulus speeds (2°/s). An explanation for this behaviour is proposed based on observations from patients with a vestibulocerebellar disorder. In this theory a leaky neural integrator is used to enhance velocity-matching. We also investigated the characteristics of vertical OKN and vertical saccades in normal adult subjects. We found that for amplitudes up to 20° there were no statistical differences between vertical centripetal and centrifugal saccades and no differences m the durations or peak velocities of upward and downward saccades. On the other hand, vertical saccades were significantly slower than horizontal saccades and vertical OKN quick phases were significantly slower than vertical saccades. We found that vertical OKN gain was asymmetrical: upward OKN gain was greater than downward OKN gain by an average of 0.08. Vertical OKN was also studied in adults with strabismus and infants and children with neurological abnormalities. The patients with strabismus often demonstrated a similar asymmetry of vertical OKN as seen in control subjects, with upward OKN stimulus motion eliciting a higher gain, although the gain was usually lower and the responses were very variable. In infants and children, abnormal vertical OKN was found in those who had either a neurometabolic disease or an abnormality of the cortex, brainstem and/or cerebellum. It is concluded that OKN testing has an important role in the assessment of the oculomotor system both as a visual response and as a motor behaviour

Vertical optokinetic nystagmus and saccades in normal human subjects. Invest Ophthalmol Vis Sci.

PURPOSE. Optokinetic stimulation induces nystagmus that can be used to test the saccadic and visual-tracking systems in some patients with voluntary gaze palsies. The purpose of this study was to characterize vertical optokinetic nystagmus (OKN) in normal human subjects, comparing the dynamic properties of the quick phases with voluntary saccades of similar size and measuring the slow-phase responses to visual stimuli with a range of spatial and temporal frequencies. METHODS. Vertical OKN and saccades were recorded in 10 healthy adult subjects (age range, 24 -54 years) using the magnetic search coil technique. The optokinetic (OK) stimulus subtended 72°horizontally and 60°vertically, consisted of black-and-white stripes with a spatial frequency of 0.04, 0.08, or 0.16 cyc/deg, and moved vertically at 10 to 50 deg/s. Vertical and horizontal saccades to visual targets separated by 1°to 10°were also elicited. RESULTS. Over 95% of quick phases were less than 10°in amplitude; voluntary saccades of this amplitude range were slightly faster than quick phases of similar size. The amplitudepeak velocity relationships and amplitude-duration relationships of upward and downward fast movements (saccades or quick phases) were similar. Most vertical slow-phase OK responses showed greater gain for upward stimulus motion. OK gain decreased with increasing stimulus speed and increased spatial frequency, so that there was a general decrease in slow-phase velocity gain with increasing temporal frequency. CONCLUSIONS. In this study, the best OK responses were obtained using stripes with lower spatial frequencies and lower stripe speeds The magnetic search coil allows for accurate recording of vertical eye movements without distortion by concomitant lid movements. Several studies have delineated the range of dynamic properties of vertical saccades in normal subjects. 4 -11 In contrast, there is little or no reliable information that compares the dynamic properties of vertical quick phases and saccades. Moreover, there is no agreement concerning vertical OKN slow-phase properties in normal humans. Some investigators have reported better slow-phase responses to upward than to downward stimulus movement 12-21 whereas other laboratories have reported the converse METHODS Subjects and Recording Methods Ten healthy adult subjects were recorded (five women; age range, 24 -54 years, median 31). None had any known neurologic or visual defects other than refractive anomalies. No subjects wore spectacle correction during the experiments. In addition, to demonstrate the potential clinical applications of our present study, we investigated a 74-year-old woman with impaired ability to make voluntary vertical saccades because of progressive supranuclear palsy (PSP) and, as a control, a 79-year old man with Parkinson's disease (PD) who was able to make voluntary vertical saccades. All subjects and patients gave informed, written consent, in accordance with the Declaration of Helsinki and our institutional review board. From th

Oculomotor function in frontotemporal lobar degeneration, related disorders and Alzheimer's disease.

Frontotemporal lobar degeneration (FTLD) often overlaps clinically with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), both of which have prominent eye movement abnormalities. To investigate the ability of oculomotor performance to differentiate between FTLD, Alzheimer's disease, CBS and PSP, saccades and smooth pursuit were measured in three FTLD subtypes, including 24 individuals with frontotemporal dementia (FTD), 19 with semantic dementia (SD) and six with progressive non-fluent aphasia (PA), as compared to 28 individuals with Alzheimer's disease, 15 with CBS, 10 with PSP and 27 control subjects. Different combinations of oculomotor abnormalities were identified in all clinical syndromes except for SD, which had oculomotor performance that was indistinguishable from age-matched controls. Only PSP patients displayed abnormalities in saccade velocity, whereas abnormalities in saccade gain were observed in PSP > CBS > Alzheimer's disease subjects. All patient groups except those with SD were impaired on the anti-saccade task, however only the FTLD subjects and not Alzheimer's disease, CBS or PSP groups, were able to spontaneously self-correct anti-saccade errors as well as controls. Receiver operating characteristic statistics demonstrated that oculomotor findings were superior to neuropsychological tests in differentiating PSP from other disorders, and comparable to neuropsychological tests in differentiating the other patient groups. These data suggest that oculomotor assessment may aid in the diagnosis of FTLD and related disorders