Vertical Saccades Research Articles

EVALUATION OF VERTICAL AND HORIZONTAL SACCADES USING THE DEVELOPMENTAL EYE MOVEMENT TEST COMPARED TO THE KING-DEVICK TEST

Oculomotor function is impaired when an individual has a concussion and as such, it is important to identify tests that are able to assess oculomotor impairment. The King-Devick (K-D) test assesses horizontal saccadic eye movement and attention. The Developmental Eye Movement (DEM) test is designed to identify oculomotor dysfunction in children. It measures both horizontal and vertical saccades. The K-D test shows promise as a concussion-screening tool and part of a multifactorial assessment. The DEM has not been tested as a concussion assessment tool, but the neuroanatomical control of horizontal and vertical saccades originates from different areas of the brain, so one might expect to see differences in performance on the K-D and DEM tests when administered to concussed patients. First, it is important to determine if performance on the DEM and K-D tests, particularly with respect to the measurement of vertical and horizontal saccades, is similar in a healthy population.Hypothesis/Purpose: The primary purpose was to evaluate the relationship between horizontal and vertical saccade tests over repeated trials in normal, healthy subjects. A secondary purpose of this study was to determine the number of trials needed to reach a performance plateau for both the DEM and K-D tests.Study Design: This study used a prospective cohort research design. Forty-two healthy non-concussed participants (22 males, 20 females; mean age, 24.2 ± 2.92 years) completed six repeated trials of both the DEM, and then six trials of the K-D test in a single testing session. Trials within each test were performed in random order and participants were offered short rest breaks as needed between test administrations. Results indicated strong correlations, r=.67, or greater, between measurements of horizontal and vertical saccades. Performance plateaued on the K-D at trial three and on the DEM at trial two for both horizontal and vertical saccades. It appears that the DEM and K-D tests measure similar constructs in healthy individuals and that no additional information is provided by assessment of vertical saccades. Additional studies are required to investigate the usefulness of the DEM in concussed individuals. 3: Laboratory study with repeated measures.

A new MR imaging index for differentiation of progressive supranuclear palsy-parkinsonism from Parkinson's disease

IntroductionDifferentiating clinically progressive supranuclear palsy-parkinsonism (PSP-P) from Parkinson's disease (PD) may be challenging, especially in the absence of vertical supranuclear gaze palsy (VSGP). The Magnetic Resonance Parkinsonism Index (MRPI) has been reported to accurately distinguish between PSP and PD, yet few data exist on the usefulness of this biomarker for the differentiation of PSP-P from PD. MethodsThirty-four patients with PSP-P, 46 with PSP-Richardson's syndrome (PSP-RS), 53 with PD, and 53 controls were enrolled. New consensus criteria for the clinical diagnosis of PSP were used as the reference standard. The MRPI, and a new index termed MRPI 2.0 including the measurement of the third ventricle width (MRPI multiplied by third ventricle width/frontal horns width ratio), were calculated on T1-weighted MR images. ResultsThe MRPI differentiated patients with PSP-P from those with PD with sensitivity and specificity of 73.5% and 98.1%, respectively, while the MRPI 2.0 showed higher sensitivity (100%) and similar specificity (94.3%) in differentiating between these two groups. Both biomarkers showed excellent performance in differentiating PSP-P patients with VSGP from those with PD, but the MRPI 2.0 was much more accurate (95.8%) than MRPI in differentiating PSP-P patients with slowness of vertical saccades from PD patients. ConclusionThe MRPI 2.0 accurately differentiated PSP-P patients from those with PD. This new index was more powerful than MRPI in differentiating PSP patients in the early stage of the disease with slowness of vertical saccades from patients with PD, thus helping clinicians to consolidate the diagnosis based on clinical features, in vivo.

P22. Long-term course of progression of clinical ocular motor signs in progressive supranuclear palsy

Aim To investigate the natural course of progression of ocular motor signs in patients with progressive supranuclear palsy (PSP). Methods 114 patients with a possible or probable PSP following NINDS-SPSP criteria seen at the Department of Neurology and the German Center for Vertigo and Balance Disorders (LMU, Munich) were included in this retrospective study. All patients underwent a structured neuro-ophthalmological testing by a orthoptist at initial diagnostic evaluation, 35 patients several times during their course of disease. The following ocular motor signs were extracted from the charts: Saccadic slowing (with normal range of movement) and saccadic paresis (loss of saccade initiation or severe saccadic hypometria) in vertical and horizontal direction, range of up- and downward as well as horizontal ocular motility during smooth pursuit in mm, presence of square wave jerks, function of the vestibulo-ocular reflex on head impulse testing. Clinical ocular motor signs were analysed in all patients in relation to the duration of disease at the time of examination (based on the medical history of the first sign indicative for PSP) or longitudinally during the course of disease in a subgroup of 35 patients. Results In the whole group of PSP patients saccadic abnormalities showed the following distribution over time: at 1 year of disease duration 10% showed only saccadic slowing on upgaze, 40% on up- and downgaze, 21% saccadic paresis on upgaze and 29% complete vertical saccade paresis; at 2 years the proportion of vertical saccade paresis was 32%, at 3 years 65% and at 4 years 82%. Progression of horizontal saccade paresis was slower (year 1: 6%, year 2: 9%, year 3: 21%, year 4: 41%). The subgroup of patients with longitudinal follow up showed a similar tendency. Ocular motility in this group decrease by a mean of 1.5 mm/a on upgaze, 1.6 mm/a on downgaze and 1.4 mm/a on horizontal gaze. The degree of motility loss on up- and downgaze over time showed a good correlation (R2 = 0.71). Conclusion Ocular motor examination can be used as a robust marker of disease progression. Variability between patients however is considerable. Prospective clinical and apparative quantification of ocular motor markers in well-characterized cohorts of PSP patients is needed.

The Influence of Caffeine on Rotary Chair and Oculomotor Testing.

When patients are given instructions before vestibular function testing, they are often asked to refrain from ingesting caffeine 24 h before testing. However, research regarding the effects of caffeine on the outcome of vestibular function testing is limited. To evaluate whether the results from rotational chair tests are influenced by caffeine. Participants were tested after consuming a caffeinated beverage (i.e., coffee containing ∼300 mg of caffeine), as well as after abstaining from caffeinated beverages. The participants underwent oculomotor testing, sinusoidal harmonic acceleration testing, optokinetic testing, visual enhancement/suppression testing, subjective visual vertical/horizontal testing, trapezoidal step testing, and unilateral utricular centrifugation testing. Thirty healthy young controls aged 18-40 yr (mean = 23.28 yr; 9 males, 21 females) participated in the study. Rotational chair tests were completed with the Neuro Kinetics rotary chair (Pittsburgh, PA). VEST 7.0 software was used to collect and analyze the participants' eye movements (I-Portal VOG; Neuro Kinetics). IBM SPSS was used to statistically analyze the results. Statistically significant differences were found for the results from several oculomotor tests (i.e., vertical saccades [SCs], horizontal SCs, and optokinetics), whereas the remaining rotational chair tests did not reveal any statistically significant differences between sessions. If a statistically significant difference was found, the participants were then stratified based on the amount of caffeine they consumed on a daily basis. This stratification was accomplished based on the guidelines from the International Coffee Organization. When the data were analyzed based on the stratified groups, statistically significant results remained in the no/low caffeine intake group, whereas no statistically significant results remained in the moderate/high caffeine intake group. Clinically speaking, the largest effect was seen in those individuals who did not typically ingest large amounts of caffeine, whereas the results were not found to be significantly different in those individuals who were typical caffeine consumers. This strengthens the argument that it is not necessary to require that individuals refrain from consuming caffeinated beverages before oculomotor/rotary chair testing as the results from typical caffeine consumers are not significantly affected. Although statistically significant results were found for a number of the oculomotor function tests, the ingestion of caffeine had little influence on the clinical interpretation of the responses. Therefore, the results from the present study indicate that it is not necessary to require that healthy young individuals abstain from caffeine before undergoing rotary chair/oculomotor testing. Further research is necessary to determine whether there is also a limited effect of caffeine on rotary chair/oculomotor test results from older individuals, as well as individuals diagnosed with a vestibular impairment.

Instruction-based clinical eye-tracking study on the visual interpretation of divergence: How do students look at vector field plots?

Relating mathematical concepts to graphical representations is a challenging task for students. In this paper, we introduce two visual strategies to qualitatively interpret the divergence of graphical vector field representations. One strategy is based on the graphical interpretation of partial derivatives, while the other is based on the flux concept. We test the effectiveness of both strategies in an instruction-based eye-tracking study with N = 41 physics majors. We found that students’ performance improved when both strategies were introduced (74% correct) instead of only one strategy (64% correct), and students performed best when they were free to choose between the two strategies (88% correct). This finding supports the idea of introducing multiple representations of a physical concept to foster student understanding.Relevant eye-tracking measures demonstrate that both strategies imply different visual processing of the vector field plots, therefore reflecting conceptual differences between the strategies. Advanced analysis methods further reveal significant differences in eye movements between the best and worst performing students. For instance, the best students performed predominantly horizontal and vertical saccades, indicating correct interpretation of partial derivatives. They also focused on smaller regions when they balanced positive and negative flux. This mixed method research leads to new insights into student visual processing of vector field representations, highlights the advantages and limitations of eye-tracking methodologies in this context, and discusses implications for teaching and for future research. The introduction of saccadic direction analysis expands traditional methods, and shows the potential to discover new insights into student understanding and learning difficulties.

Vestibular Test Patterns in the NICoE Intensive Outpatient Program Patient Population.

The National Intrepid Center of Excellence (NICoE), on the campus of Walter Reed National Military Medical Center, was developed to help improve the lives of active duty service members (SMs) with traumatic brain injury (TBI) and comorbid behavioral health (BH) conditions. During the NICoE intensive outpatient program, SM who have all been identified as having some degree of TBI, undergo extensive interdisciplinary evaluations, including comprehensive vestibular assessment. These SMs sometimes present with vestibular symptoms ranging from lightheadedness to vertigo associated with the dual TBI/BH diagnoses, and vestibular testing results reported elsewhere have varied among this population. The study's purpose was to collate the vestibular test results obtained from a sample of the NICoE patients to determine if specific tests have a tendency to be abnormal in these SMs. Results indicate that oculomotor tests, particularly pursuit and saccade, were most often abnormal. The vertical subtests of the pursuit and saccade tests were abnormal more frequently than the horizontal subtests, suggesting that the vertical subtests should be utilized when evaluating the TBI population. Overall, oculomotor tests of vertical pursuit and saccades, as well as tests of central vestibular function, appear useful for detecting neurologic changes in active duty SMs with chronic symptoms after TBI.

Recent advances in head impulse test findings in central vestibular disorders.

The head impulse test (HIT) is used to evaluate the vestibulo-ocular reflex (VOR) during a high-velocity head rotation. Corrective catch-up saccades that occur during or after the HITs usually indicate peripheral vestibular hypofunction, whereas in acute vestibular syndrome, normal clinical (bedside) HITs should prompt a search for a central lesion. However, recent quantitative studies that evaluated HITs using magnetic search coils or video-based techniques have demonstrated that specific patterns of HIT abnormalities are associated with central vestibular disorders. While normal clinical HITs are typical of central lesions, discrepancies have been observed between clinical and quantitative HITs. The horizontal head impulse VOR gains can be significantly reduced unilaterally or bilaterally (positive HITs) in lesions involving the vestibular nucleus, nucleus prepositus hypoglossi, or flocculus. In diffuse cerebellar lesions, the VOR gain during horizontal head impulses may increase (hyperactive) with corrective saccades directed the opposite way. The presence of cross-coupled vertical corrective saccades during horizontal HITs is also suggestive of diffuse cerebellar lesions. Lesions involving the vestibular nucleus, medial longitudinal fasciculus, and cerebellum may show decreased or increased gains of the VOR during vertical HITs. Defining the differences in patterns observed during abnormal HITs may help practitioners localize the responsible lesions in both central and peripheral vestibulopathy.

Distractor displacements during saccades are reflected in the time-course of saccade curvature

Every time we make a saccade we form a prediction about where objects are going to be when the eye lands. This is crucial since the oculomotor system is retinotopically organized and every saccade drastically changes the projection of objects on the retina. We investigated how quickly the oculomotor system accommodates new spatial information when a distractor is displaced during a saccade. Participants performed sequences of horizontal and vertical saccades and oculomotor competition was induced by presenting a task-irrelevant distractor before the first saccade. On half of the trials the distractor remained in the same location after the first saccade and on the other half the distractor moved during the first saccade. Curvature of the second saccade was used to track target-distractor competition. At short intersaccadic intervals, saccades curved away from the original distractor location, confirming that in the oculomotor system spatiotopic representations emerge rapidly and automatically. Approximately 190 ms after the first saccade, second saccades curved away from the new distractor location. These results show that after a saccade the oculomotor system is initially driven by the spatial prediction made before the saccade, but it is able to quickly update these spatial predictions based on new visual information.

Oculomotor and Vestibular Findings in Gaucher Disease Type 3 and Their Correlation with Neurological Findings

To evaluate the function of the oculomotor and vestibular systems and to correlate these findings with the clinical status of patients with Gaucher disease type 3 (GD3). The goal of this cross-sectional and longitudinal study was to find oculomotor biomarkers for future clinical trials. Twenty-six patients with GD3 were assessed for eligibility and 21 were able to perform at least one task. Horizontal and vertical reflexive saccades, smooth pursuit, gaze-holding, optokinetic nystagmus, and horizontal vestibulo-ocular reflex (VOR) were examined by video-oculography/video-head impulse test and compared concurrently with 33 healthy controls. The Scale for the Assessment and Rating of Ataxia (SARA), the modified Severity Scoring Tool (mSST), and Grooved Pegboard Test (GPT) were administered to assess overall neurological function. Eleven patients were also re-assessed after 1 year. Nine out of 17 patients exhibited gaze-holding deficits. One patient had upbeat nystagmus. Three patients presented with bilateral abducens palsy in combination with central oculomotor disorders, suggesting a bilateral involvement of the abducens nucleus. Horizontal angular VOR gain was reduced in all patients (0.66 ± 0.37) compared with controls (1.1 ± 0.11, p < 0.001). Most strongly correlated with clinical rating scales were peak velocity of downward saccades (SARA: ρ = -0.752, p < 0.0005; mSST: ρ = -0.611, p = 0.003; GPT: ρ = -0.649, p = 0.005) and duration of vertical saccades (SARA: ρ = 0.806, p < 0.001; mSST: ρ = 0.700, p < 0.0005; GPT: ρ = 0.558, p = 0.02) together with the VOR gain (SARA: ρ = -0.63, p = 0.016; mSST: ρ = -0.725, p = 0.003; GPT: ρ = -0.666, p = 0.004). Vertical smooth pursuit gain decreased significantly at follow-up. This study shows neuronal degeneration of the brainstem and cerebellum with combined involvement of both supranuclear and nuclear oculomotor structures and the vestibular system in GD3. We also identified oculomotor parameters that correlate with the neurological status and can be used as biomarkers in future clinical trials.

Screening for Niemann-Pick Type C Disease in a Memory Clinic Cohort.

Niemann-Pick type C disease (NPC) is a neurovisceral lysosomal storage disorder with a heterogeneous phenotype including ataxia, cognitive impairment, impairment of vertical saccades, and psychiatric symptoms, among many others. Based on clinical, genetic, and biomarker findings, recent guidelines put forward a screening for atypical and oligosymptomatic forms of NPC in clinical niches with an increased risk. Here, we report methods and results of a negative screening study in the niche of a memory clinic. We retrospectively and prospectively identified 83 patients with unclassified cognitive impairment (15 dementia, 46 mild cognitive impairment, and 22 progressive subjective cognitive decline) before 60years of age (82 patients between 41 and 60years). We explored the prevalence of clinical features compatible with NPC and measured plasma levels of chitotriosidase and cholestantriol. The NPC suspicion index indicated high probability for NPC in 3 and moderate probability in 16 patients. Prevalent (>5%) neurological and psychiatric features were depression, seizures, ataxia, dysarthria, and psychotic symptoms. Vertical gaze palsy without parkinsonism was observed in one patient. Cholestantriol levels were only abnormal in one patient. Chitotriosidase levels were susceptible to slight elevations that were reproducible in only two of five patients. Our study does not exclude NPC among memory clinic patients. Instead, we suggest conducting prospective screening studies in younger cohorts that include a focused neurological examination. Excluding minor cognitive impairment and discarding depression as an independent disease symptom probably further improve screening effectivity but may delay or miss therapeutic options in early or mild disease.

Oculomotor abnormalities in children with Niemann-Pick type C.

Niemann-Pick type C (NP-C) is a rare recessive disorder associated with progressive supranuclear gaze palsy. Degeneration occurs initially for vertical saccades and later for horizontal saccades. There are studies of oculomotor degeneration in adult NP-C patients [1, 2] but no comparable studies in children. We used high-resolution video-based eye tracking to record monocular vertical and horizontal eye movements in 2 neurological NP-C patients (children with clinically observable oculomotor abnormalities) and 3 pre-neurological NP-C patients (children without clinically observable oculomotor abnormalities). Saccade onset latency, saccade peak velocity and saccade curvature were compared to healthy controls (N=77). NP-C patients had selective impairments of vertical saccade peak velocity and vertical saccade curvature, with slower peak velocities and greater curvature. Changes were more pronounced in neurological than pre-neurological patients, showing that these measures are sensitive to disease progress, but abnormal curvature and slowed downward saccades were present in both groups, showing that eye-tracking can register disease-related changes before these are evident in a clinical exam. Both slowing, curvature and the detailed characteristics of the curvature we observed are predicted by the detailed characteristics of RIMLF population codes. Onset latencies were not different from healthy controls. High-resolution video-based eye tracking is a promising sensitive and objective method to measure NP-C disease severity and neurological onset. It may also help evaluate responses to therapeutic interventions.

Saccadic eye movements in hereditary spinocerebellar degeneration – horizontal and vertical saccades

Background: The cerebellum is implicated in the control of saccade movement but it is unknown how it differs for vertical and horizontal saccades, since vertical saccades has been rarely studied.

P2-71. Saccadic eye movements in Spinocerebellar Degeneration – study of saccades in eight directions

Objectives The cerebellum is implicated in the control of saccadic eye movement but it is unknown how it differs for vertical and horizontal saccades, since vertical saccades have been rarely studied. To clarify the role of the cerebellum we studied saccades in hereditary spinocerebellar degeneration in two dimensional directions. Methods We compared saccade performance in 16 patients (SCA31 and SCA6) with that in 19 normal age-matched controls. We used the visual guided (VGS) and memory guided tasks (MGS) in which targets were presented in eight directions with 45 degrees separation, and recorded saccades with a video-based eye tracker. Results In SCA patients, latency of VGS was significantly delayed compared with normal subjects in vertical and oblique directions, which correlated with SARA scores. MGS latency was significantly delayed only in the oblique direction. Hypermetria was prominently detected in the vertical and oblique directions, but less in the horizontal directions. Conclusion Abnormal latency and dysmetria are easily detected for directions having vertical component. The cerebellum may be more involved in vertical than in horizontal saccade system, or vertical saccade system may be more susceptible to diseases than horizontal saccades. Further study of other diseases will be helpful to differentiate between these possibilities.

Saccades in progressive supranuclear palsy - maladapted, irregular, curved, and slow.

Slowed and curved rapid eye movements, saccades, are the well-known features of progressive supranuclear palsy (PSP). We hypothesized that the saccades in PSP are not only slow and curved, but they are also irregular and have timing deficits. We tested this hypothesis in 12 patients with PSP by measuring vertical and horizontal visually guided saccades using a limbus tracker. Both, horizontal and vertical saccades were slow and had irregular trajectory and velocity profiles, but deficits were much more robust in vertical saccades. The irregularity in the saccade velocity was due to premature interruptions that either completely stopped the eyes, or moved the eyes at much slower velocity along or in the opposite direction of the ongoing saccade. The direction of the eyes' trajectory was often changed after the interruption. We simulated a conductance based single-compartment model of the burst neurons embedded in local feedback circuit for saccade generation. This model mimicked anatomical and physiological realism, while allowing the liberty to selectively change the activation of individual burst neurons or the pause neurons. The PSP saccades were comparable to the simulations during reduced activity of the inhibitory and excitatory burst neurons. PSP saccades are due to the paucity in burst generation at the excitatory and imprecise timing signal from the inhibitory burst neurons. Premature discharge of the inhibitory burst neuron further leads to breaks in the saccade trajectory, and maladaptive superior colliculus activity leading to aberrant saccades changing the intended trajectory of the ongoing saccade.

Saccadic Impairments in Patients with the Norrbottnian Form of Gaucher's Disease Type 3.

Chronic neuronopathic Gaucher's disease type 3 (GD3) is relatively frequent in northern Sweden. Besides multiple other neurological symptoms, horizontal gaze palsy or oculomotor apraxia is common in GD3. To characterize the saccades in patients with Norrbottnian GD3 with respect to their neurological and cognitive status using a computer-based eye-tracking technique. Horizontal and vertical reflexive saccades as well as antisaccades of nine GD3 patients [4M/5F; 41.1 ± 11.0 years; modified severity scoring tool (mSST): 9.3 ± 5.4; Montreal Cognitive Assessment (MoCA): 24.0 ± 4.2] and age-matched controls were analyzed using EyeBrain T2, a head-mounted binocular eye tracker. Systematic clinical assessment included the mSST, a valid tool for monitoring the neurological progression in GD3 and MoCA. In Norrbottnian GD3 patients, gain, peak, and average velocity (107.5°/s ± 41.8 vs. 283.9°/s ± 17.0; p = 0.0009) of horizontal saccades were reduced compared to healthy controls (HCs). Regarding vertical saccades, only the average velocity of downward saccades was decreased (128.6°/s ± 63.4 vs. 244.1°/s ± 50.8; p = 0.004). Vertical and horizontal saccadic latencies were increased (294.3 ms ± 37.0 vs. 236.5 ms ± 22.4; p = 0.005) and the latency of horizontal reflexive saccades was correlated with the mSST score (R2 = 0.80; p = 0.003). The latency of antisaccades showed association to MoCA score (R2 = 0.70; p = 0.009). GD3 patients made more errors in the antisaccade task (41.5 ± 27.6% vs. 5.2 ± 5.8%; p = 0.005), and the error rate tended to correlate with the cognitive function measured in MoCA score (p = 0.06). The mean age of 41 years of our GD3 cohort reflects the increased life expectancy of patients in the Norrbottnian area compared to other GD3 cohorts. Marked impairment of horizontal saccades was evident in all patients, whereas vertical saccades showed distinct impairment of downward velocity. Latency of reflexive saccades was associated with the severity of neurological symptoms. Increased latency and error rate in the antisaccade task were linked to cognitive impairment. The assessment of saccades provides markers for neurological and neuropsychological involvement in Norrbottnian GD3.

Novel PNKP mutation in siblings with ataxia-oculomotor apraxia type 4

The phenotypic and genetic spectrum of ataxia with oculomotor apraxia (AOA) disorders is rapidly evolving and new technologies such as genetic mapping using whole exome sequencing reveal subtle distinctions among the various subtypes. We report a novel PNKP mutation in two siblings with progressive ataxia, abnormal saccades, sensorimotor neuropathy and dystonia consistent with the AOA type 4 phenotype. Laboratory evaluation revealed hypoalbuminemia, hypercholesterolemia with elevated LDL, elevated IgE levels and normal α fetoprotein levels. Eye movement examination demonstrated a marked saccade initiation defect with profound hypometric horizontal saccades. Vertical saccades were also affected but less so. Also present were conspicuous thrusting head movements when attempting to change gaze, but rather than an apraxia these were an adaptive strategy to take advantage of an intact vestibulo-ocular reflex to carry the eyes to a new target of interest. This is demonstrated in accompanying videos.

Trajectories of social vision: Eye contact increases saccadic curvature

ABSTRACTSaccades are known to deviate away from distractors, and the amplitude of this deviation seems to reflect the salience of these stimuli, as in the case of human faces. Here, we investigated whether eye contact can modulate attention allocation by examining saccadic curvature when faces with closed vs. open eyes act as distractors. In two experiments, participants were asked to perform a vertical saccade towards a symbolic target. At the same time, task-irrelevant faces with open or closed eyes (Experiments 1 and 2) and scrambled faces (Experiment 2) could appear leftwards or rightwards with respect to the ideal trajectory towards the target. Overall, a greater saccadic curvature was observed in response to faces with open eyes, as compared to the other two conditions. These results confirm that eye contact plays an important role in shaping attentional mechanisms and provide further evidence concerning the link between social vision and eye movements.

頭位性めまいを主訴とした脊髄小脳失調症6型 (SCA6) 例の ENG 検討

A 57-year-old woman presented at our outpatient clinic with the recent and frequent experience of paroxysmal positional vertical vertigo similar to the sensation of a somersault, especially changing position from sitting to lying supine, accompanied with spells of nausea and blackout. On examination, we observed prominent downbeat nystagmus in the primary eye position and lateral gaze. MRI disclosed prominent cerebellar cortical atrophy, especially in the vermal regions. The patient had a family history of spinocerebellar ataxia type 6 (SCA6) and had herself received a definitive diagnosis of the same phenotype disease from genetic studies. The points of the ENG findings were as follows: (1) downbeat nystagmus was prominent in the primary eye position and was combined with gaze nystagmus in the lateral gaze; (2) both horizontal & vertical rebound nystagmus were noted; and (3) impairment of both horizontal & vertical smooth pursuit were seen. In horizontal and upward pursuit, catch-up saccades (lower gain) were intermingled. In contrast, backup-saccades (higher gain) were intermingled in downward pursuit. Furthermore, (4) Horizontal saccades were hypometric, though vertical saccades were hypermetric (overshoot); (5) In both horizontal and vertical OKN, the slow phase of OKN was severely impaired. Finally, (6) vestibular caloric nystagmus was well induced bilaterally. Both sides of visual suppression of caloric nystagmus were severely impaired. Most of present results are well explainable with the pure cerebellar cortical atrophy as the typical pathological finding of SCA6. However, two important findings should be mainly discussed and stressed here. One, the gain of the horizontal smooth pursuit was lower, while the gain of the downward pursuit was higher. It seemed to be inconsistent that a single part of the cerebellum would simultaneously modulate decreasing gain of the horizontal and increasing gain of vertical smooth pursuit systems. Therefore, this finding suggested that several parts, not a single part, of the cerebellum would be simultaneously engaged in the gain modulation of the smooth pursuit system. Second, the severe impairments of both horizontal and vertical OKN implied disturbances of both the pursuit and the velocity storage systems. In Cohen & Raphan's model, the slow phase of OKN is composed of the “direct pathway” and the “indirect pathway.” The “direct pathway” utilizes the ocular pursuit system in the flocculus/paraflocculus, while the “indirect pathway” is mediated through the velocity storage system in the medial vestibular nuclei/prepositus hypoglossi nuclei or the interstitial nuclei of Cajal in the brainstem. Consequently, the present results of OKN strongly suggested that the neural circuits related to the velocity storage integrator in the brainstem would also be perturbed, together with the disturbance of the ocular pursuit system in the cerebellum.

Cortical control of vertical and horizontal saccades in progressive supranuclear palsy: An exploratory fMRI study

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder showing predominant brainstem involvement, characterized by marked slowing of rapid eye movements (saccades), particularly along the vertical plane. While the contribution of the brainstem damage for the saccadic disturbance in PSP has been extensively studied, much less is known about its cortical and subcortical pathomechanisms. We measured reflexive (prosaccades) and voluntary (antisaccades) saccades in the vertical and horizontal plane in PSP patients (n=8) and controls (n=10) in an eye tracking study, followed by the measurement of blood oxygenation-level dependent (BOLD) activation (PSP, n=6; controls, n=10) during similar saccade paradigms. Behaviorally, PSP patients evidenced slower and lower amplitude prosaccades (horizontal and vertical) and lower amplitude antisaccades (vertical) than controls. Functionally, patients showed decreased frontostriatal BOLD activation during prosaccades (horizontal and vertical) and antisaccades (vertical), relative to controls. Additionally, PSP patients showed less default mode network (DMN) deactivation than controls for all types of saccades. Within groups, controls showed no BOLD differences between horizontal and vertical prosaccades while PSP patients demonstrated greater DMN deactivation during vertical prosaccades. Both groups evidenced greater DMN deactivation during vertical antisaccades when compared to their horizontal counterpart and patients further showed relative frontostriatal BOLD hypoactivity during vertical antisaccades. We found fMRI evidence of frontostriatal hypoactivity in PSP patients relative to controls, especially during vertical saccades. These new findings highlight the impact of cortical impairment in saccadic disturbance of PSP.

Understanding falls in progressive supranuclear palsy

IntroductionProgressive supranuclear palsy (PSP) is characterized by frequent falls which worsen with disease progression, causing substantial morbidity and mortality. Few studies have investigated which factors contribute to falls in PSP, and all have involved few participants, thus lacking necessary statistical power. The aim of this study was to identify clinical parameters most significantly associated with increasing falls in PSP, using the largest sample of patients to date. MethodsComprehensive clinical data were collected from 339 not demented PSP patients meeting the NINDS-SPSP criteria, who were divided into two groups – Infrequent Fallers (IF; n = 118) with rare falls, and Frequent Fallers (FF; n = 221) who fell occasionally to multiple times a day. Of 198 clinical parameters, we hypothesized 38 to be correlated with an increasing risk of falls. These 38 parameters were analyzed via univariate regression analysis to determine the strength of their association with fall frequency. Unit odds ratios identified the magnitude with which each parameter resulted in an increasing risk of falls. ResultsTwenty-five of 38 parameters analyzed were significantly associated with fall frequency based on univariate analysis. Symptom duration, clinical measures of disease severity, and several motoric and oculomotor clinical parameters were associated with FF. Examined cognitive parameters and slowing of vertical saccades were not. ConclusionsThe clinical parameters identified as associated with increased frequency of falls improve our understanding of why they occur and may help identify not demented PSP patients at risk for increasing falls.