Bilateral focused ultrasound medial thalamotomies for trigeminal neuropathic pain: a randomized controlled study.

OBJECTIVE: Medial thalamotomy has been shown to benefit patients with neuropathic pain, but widespread adoption of this procedure has been limited by reporting of clinical outcomes in studies without a control group. This study aimed to minimize confounders associated with medial thalamotomy for treating chronic pain by using modern MRI-guided stereotactic lesioning and a rigorous clinical design. METHODS: This prospective, double-blinded, randomized controlled trial in 10 patients with trigeminal neuropathic pain used sham procedures as controls. Participants underwent assessments by a pain psychologist and pain management clinician, including use of the following measures: the Numeric Pain Rating Scale (NPRS); patient-reported outcome measures; and patient's impression of improvement at baseline, 1 day, 1 week, 1 month, and 3 months postprocedure. Patients in the treated group underwent bilateral focused ultrasound (FUS) medial thalamotomy targeting the central lateral nucleus. Patients in the control group underwent sham procedures with energy output disabled. The primary efficacy outcome measure was between-group differences in pain intensity (using the NPRS) at baseline and at 3 months postprocedure. Adverse events were measured for safety and included MRI analysis. Exploratory measures of connectivity and metabolism were analyzed using diffusion tensor imaging, functional MRI, and PET, respectively. RESULTS: There were no serious complications from the FUS procedures. MRI confirmed bilateral medial thalamic ablations. There was no significant improvement in pain intensity from baseline to 3 months, either for patients undergoing FUS medial thalamotomy or for sham controls; and the between-group change in NPRS score as the primary efficacy outcome measure was not significantly different. Patient-reported outcome assessments demonstrated improvement (i.e., a decrease) only in pain interference with enjoyment of life at 3 months. There was a perception of benefit at 1 week, but only for patients treated with FUS and not for the sham cohort. Advanced neuroimaging showed that these medial thalamic lesions altered structural connectivity with the postcentral gyrus and demonstrated a trend toward hypometabolism in the insula and amygdala. CONCLUSIONS: This randomized controlled trial of bilateral FUS medial thalamotomy did not reduce the intensity of trigeminal neuropathic pain, although it should be noted that the ability to estimate the magnitude of treatment effects is limited by the small cohort.

Automatic processing of gaze movements to quantify gaze scanning behaviors in a driving simulator.

Eye and head movements are used to scan the environment when driving. In particular, when approaching an intersection, large gaze scans to the left and right, comprising head and multiple eye movements, are made. We detail an algorithm called the gaze scan algorithm that automatically quantifies the magnitude, duration, and composition of such large lateral gaze scans. The algorithm works by first detecting lateral saccades, then merging these lateral saccades into gaze scans, with the start and end points of each gaze scan marked in time and eccentricity. We evaluated the algorithm by comparing gaze scans generated by the algorithm to manually marked "consensus ground truth" gaze scans taken from gaze data collected in a high-fidelity driving simulator. We found that the gaze scan algorithm successfully marked 96% of gaze scans and produced magnitudes and durations close to ground truth. Furthermore, the differences between the algorithm and ground truth were similar to the differences found between expert coders. Therefore, the algorithm may be used in lieu of manual marking of gaze data, significantly accelerating the time-consuming marking of gaze movement data in driving simulator studies. The algorithm also complements existing eye tracking and mobility research by quantifying the number, direction, magnitude, and timing of gaze scans and can be used to better understand how individuals scan their environment.

Substantial Elevation of Liver Enzymes During Ketamine Infusion: A Case Report.

Intravenous infusion of a subanesthetic dose of ketamine has been shown to improve neuropathic pain. However, ketamine-induced liver injury can occur. Reported here are 2 cases with substantial liver enzyme elevations less than 2 days after initiation of repeat ketamine infusion at least 7 months after the last infusion. Although their liver enzymes normalized within a few weeks, it is unclear what the long-term consequences are. Furthermore, drug-induced liver injury can cause acute liver failure. Therefore, we recommend close monitoring of liver enzymes every 1 to 2 days during ketamine infusions.

The Effects of Age and Central Field Loss on Head Scanning and Detection at Intersections.

PURPOSE: Using a driving simulator, we quantified the effects of age and central field loss (CFL) on head scanning when approaching an intersection and investigated the role of inadequate head scanning in detection failures. METHODS: Participants with CFL (n = 20) and with normal vision (NV; n = 29), middle-aged (36-60 years) or older (67-87 years), drove along city routes with multiple intersections while head movements were recorded. The effects of age and CFL on scanning were analyzed at 32 intersections with stop/yield signs. The relationships between age, CFL, scanning, and detection were examined at four additional intersections with a pedestrian appearing on the far left. RESULTS: Older NV participants made fewer total scans than middle-aged NV participants and had smaller maximum scan magnitudes. Head scanning of older CFL and NV participants did not differ, but middle-aged CFL participants made fewer head scans, had higher rates of failing to scan, and made smaller head scans than middle-aged NV participants. For the older NV and both CFL groups, detection failures were high (≥58%); head scan magnitudes were 15° smaller when the pedestrian was not detected than when it was detected. CONCLUSIONS: Both older NV and CFL participants exhibited head scanning deficits relative to middle-aged NV participants. Unexpectedly, however, it was the middle-aged CFL group that performed least well when scanning, a finding that warrants further investigation. TRANSLATIONAL RELEVANCE: Failing to head scan sufficiently far at intersections may place older drivers and drivers with vision impairment at a higher risk for causing collisions.

Low-Dose Intrathecal Ziconotide for Spasticity From Primary Lateral Sclerosis: A Case Report.

Spasticity can be very debilitating and painful. We present a case of severe spasticity from primary lateral sclerosis refractory to intrathecal baclofen in doses up to 1100 µg/d. Baclofen was weaned down and switched to intrathecal ziconotide at 0.6 µg/d. The dose was then titrated up to 3 µg/d with excellent control of spasticity. This case suggests that low-dose intrathecal ziconotide should be considered in patients with lower extremity spasticity refractory to intrathecal baclofen.

Driving With Hemianopia VI: Peripheral Prisms and Perceptual-Motor Training Improve Detection in a Driving Simulator.

PURPOSE: Drivers with homonymous hemianopia (HH) were previously found to have impaired detection of blind-side hazards, yet in many jurisdictions they may obtain a license. We evaluated whether oblique 57Δ peripheral prisms (p-prisms) and perceptual-motor training improved blind-side detection rates. METHODS: Patients with HH (n = 11) wore p-prisms for 2 weeks and then received perceptual-motor training (six visits) detecting and touching stimuli in the prism-expanded vision. In a driving simulator, patients drove and pressed the horn upon detection of pedestrians who ran toward the roadway (26 from each side): (1) without p-prisms at baseline; (2) with p-prisms after 2 weeks acclimation but before training; (3) with p-prisms after training; and (4) 3 months later. RESULTS: P-prisms improved blind-side detection from 42% to 56%, which further improved after training to 72% (all P < 0.001). Blind-side timely responses (adequate time to have stopped) improved from 31% without to 44% with p-prisms (P < 0.001) and further improved with training to 55% (P = 0.02). At the 3-month follow-up, improvements from training were maintained for detection (65%; P = 0.02) but not timely responses (P = 0.725). There was wide between-subject variability in baseline detection performance and response to p-prisms. There were no negative effects of p-prisms on vehicle control or seeing-side performance. CONCLUSIONS: P-prisms improved detection with no negative effects, and training may provide additional benefit. TRANSLATIONAL RELEVANCE: In jurisdictions where people with HH are legally driving, these data aid in clinical decision making by providing evidence that p-prisms improve performance without negative effects.

Driving with Hemianopia V: Do Individuals with Hemianopia Spontaneously Adapt Their Gaze Scanning to Differing Hazard Detection Demands?

PURPOSE: We investigated whether people with homonymous hemianopia (HH) were able to spontaneously (without training or instructions) adapt their blind-side scan magnitudes in response to differing scanning requirements for detection of pedestrians in a driving simulator when differing cues about pedestrian eccentricities and movement behaviors were available in the seeing hemifield. METHODS: Twelve HH participants completed two sessions in a driving simulator pressing the horn when they detected a pedestrian. Stationary pedestrians outside the driving lane were presented in one session and approaching pedestrians on a collision course in the other. Gaze data were analyzed for pedestrians initially appearing at approximately 14° in the blind hemifield. No instructions were given regarding scanning. RESULTS: After appearing, the stationary pedestrians' eccentricity increased rapidly to a median of 31° after 2.5 seconds, requiring increasingly larger blind-side gaze scans for detection, while the approaching pedestrians' eccentricity remained constant at approximately 14°, requiring a more moderate scan (∼14°) for detection. Although median scan magnitudes did not differ between the two conditions (approaching: 14° [IQR 9°-15°]; stationary: 13° [IQR 9°-20°]; P = 0.43), three participants showed evidence of adapting (increasing) their blind-side scan magnitudes in the stationary condition. CONCLUSIONS: Three participants (25%) appeared to be able to apply voluntary cognitive control to modify their blind-side gaze scanning in response to the differing scanning requirements of the two conditions without explicit training. TRANSLATIONAL RELEVANCE: Our results suggest that only a minority of people with hemianopia are likely to be able to spontaneously adapt their blind-side scanning in response to rapidly changing and unpredictable situations in on-road driving.

The risk of pedestrian collisions with peripheral visual field loss.

Patients with peripheral field loss complain of colliding with other pedestrians in open-space environments such as shopping malls. Field expansion devices (e.g., prisms) can create artificial peripheral islands of vision. We investigated the visual angle at which these islands can be most effective for avoiding pedestrian collisions, by modeling the collision risk density as a function of bearing angle of pedestrians relative to the patient. Pedestrians at all possible locations were assumed to be moving in all directions with equal probability within a reasonable range of walking speeds. The risk density was found to be highly anisotropic. It peaked at ≈45° eccentricity. Increasing pedestrian speed range shifted the risk to higher eccentricities. The risk density is independent of time to collision. The model results were compared to the binocular residual peripheral island locations of 42 patients with forms of retinitis pigmentosa. The natural residual island prevalence also peaked nasally at about 45° but temporally at about 75°. This asymmetry resulted in a complementary coverage of the binocular field of view. Natural residual binocular island eccentricities seem well matched to the collision-risk density function, optimizing detection of other walking pedestrians (nasally) and of faster hazards (temporally). Field expansion prism devices will be most effective if they can create artificial peripheral islands at about 45° eccentricities. The collision risk and residual island findings raise interesting questions about normal visual development.

A Pilot Study of Perceptual-Motor Training for Peripheral Prisms.

PURPOSE: Peripheral prisms (p-prisms) shift peripheral portions of the visual field of one eye, providing visual field expansion for patients with hemianopia. However, patients rarely show adaption to the shift, incorrectly localizing objects viewed within the p-prisms. A pilot evaluation of a novel computerized perceptual-motor training program aiming to promote p-prism adaption was conducted. METHODS: Thirteen patients with hemianopia fitted with 57Δ oblique p-prisms completed the training protocol. They attended six 1-hour visits reaching and touching peripheral checkerboard stimuli presented over videos of driving scenes while fixating a central target. Performance was measured at each visit and after 3 months. RESULTS: There was a significant reduction in touch error (P = 0.01) for p-prism zone stimuli from pretraining median of 16.6° (IQR 12.1°-19.6°) to 2.7° ( IQR 1.0°-8.5°) at the end of training. P-prism zone reaction times did not change significantly with training (P > 0.05). P-prism zone detection improved significantly (P = 0.01) from a pretraining median 70% (IQR 50%-88%) to 95% at the end of training (IQR 73%-98%). Three months after training improvements had regressed but performance was still better than pretraining. CONCLUSIONS: Improved pointing accuracy for stimuli detected in prism-expanded vision of patients with hemianopia wearing 57Δ oblique p-prisms is possible and training appears to further improve detection. TRANSLATIONAL RELEVANCE: This is the first use of this novel software to train adaptation of visual direction in patients with hemianopia wearing peripheral prisms.

Asymmetry in the Collision Judgments of People With Homonymous Field Defects and Left Hemispatial Neglect.

PURPOSE: Although the impact of homonymous visual field defects (HFDs) on mobility has been investigated previously, the emphasis has been on obstacle detection. Relatively little is known about HFD patients' ability to judge collisions once an obstacle is detected. We investigated this using a walking simulator. METHODS: Patients with HFDs (n = 29) and subjects with normal vision (NV; n = 21) were seated in front of a large screen on which a visual simulation of walking was displayed. They made collision judgments for a human figure that appeared for 1 second at lateral offsets from the virtual walking path. A perceived-collision threshold was calculated for right and left sides. RESULTS: Symmetrical collision thresholds (same on left and right sides) were measured for participants with NV (n = 21), and right (n = 9) and left (n = 7) HFD without hemispatial neglect. Participants with left neglect (n = 10) showed significant asymmetry with thresholds smaller (compared to the NV group and other HFD groups) on the blind (P < 0.001) and larger on the seeing (P = 0.05) sides. Despite the asymmetry, the overall width of the zone of perceived collision risk was not different, suggesting a relatively uniform rightward deviation in judgments of the left neglect group. CONCLUSIONS: Left neglect was associated with rightward asymmetry in collision judgments, which may cause collisions on the left side even when an obstacle is detected. These behaviors may represent the spatial misperceptions in body midline described previously in patients with left neglect.

Driving with hemianopia: IV. Head scanning and detection at intersections in a simulator.

PURPOSE: Using a driving simulator, we examined the effects of homonymous hemianopia (HH) on head scanning behaviors at intersections and evaluated the role of inadequate head scanning in detection failures. METHODS: Fourteen people with complete HH and without cognitive decline or visual neglect and 12 normally sighted (NV) current drivers participated. They drove in an urban environment following predetermined routes, which included multiple intersections. Head scanning behaviors were quantified at T-intersections (n = 32) with a stop or yield sign. Participants also performed a pedestrian detection task. The relationship between head scanning and detection was examined at 10 intersections. RESULTS: For HH drivers, the first scan was more likely to be toward the blind than the seeing hemifield. They also made a greater proportion of head scans overall to the blind side than did the NV drivers to the corresponding side (P = 0.003). However, head scan magnitudes of HH drivers were smaller than those of the NV group (P < 0.001). Drivers with HH had impaired detection of blind-side pedestrians due either to not scanning in the direction of the pedestrian or to an insufficient scan magnitude (left HH detected only 46% and right HH 8% at the extreme left and right of the intersection, respectively). CONCLUSIONS: Drivers with HH demonstrated compensatory head scan patterns, but not scan magnitudes. Inadequate scanning resulted in blind-side detection failures, which might place HH drivers at increased risk for collisions at intersections. Scanning training tailored to specific problem areas identified in this study might be beneficial.

Psychophysical contrast calibration.

Electronic displays and computer systems offer numerous advantages for clinical vision testing. Laboratory and clinical measurements of various functions and in particular of (letter) contrast sensitivity require accurately calibrated display contrast. In the laboratory this is achieved using expensive light meters. We developed and evaluated a novel method that uses only psychophysical responses of a person with normal vision to calibrate the luminance contrast of displays for experimental and clinical applications. Our method combines psychophysical techniques (1) for detection (and thus elimination or reduction) of display saturating non-linearities; (2) for luminance (gamma function) estimation and linearization without use of a photometer; and (3) to measure without a photometer the luminance ratios of the display's three color channels that are used in a bit-stealing procedure to expand the luminance resolution of the display. Using a photometer we verified that the calibration achieved with this procedure is accurate for both LCD and CRT displays enabling testing of letter contrast sensitivity to 0.5%. Our visual calibration procedure enables clinical, internet and home implementation and calibration verification of electronic contrast testing.

Hazard Detection by Drivers with Paracentral Homonymous Field Loss: A Small Case Series.

INTRODUCTION: Stroke frequently causes homonymous visual field loss. We previously found in a driving simulator that patients with complete homonymous hemianopia had difficulty detecting potential hazards on the side of the field loss. Here we measured the effects of limited paracentral homonymous field loss on detection performance. METHODS: Three patients with paracentral homonymous scotomas, yet meeting vision requirements for driving in the United States, performed a pedestrian detection task while driving in a simulator. Pedestrians appeared in a variety of potentially hazardous situations on both sides of the road. Three age- and gender-matched control participants with normal vision participated for comparison purposes. RESULTS: Pedestrians appearing in the scotomatous side of the visual field were less likely to be detected, and when they were, reaction times were longer, frequently too late to respond safely. CONCLUSIONS: Although legally permitted to drive in the U.S.A., and possibly in other countries, patients with paracentral homonymous field loss may have impaired hazard detection and may benefit from education about their deficit and a fitness-to-drive evaluation.

Driving with hemianopia, II: lane position and steering in a driving simulator.

PURPOSE: The hypothesis that drivers with homonymous hemianopia (HH) would take a lane position that increased the safety margin on their blind side was tested with a driving simulator. METHODS: Twelve participants with HH (six right HH and six left; nine men; mean age, 50 years; range 31-72), and 12 matched current drivers with normal vision (NV) each completed approximately 120 minutes of simulator driving. Lane position and steering stability were evaluated for specific road segment types (straight segments, curves, and turns) in city and rural undivided highway driving. RESULTS: The drivers with right HH held a lane position significantly (P = 0.001) to the left of NV drivers on the straight road segments and to a lesser extent on the curves. The drivers with left HH had a lane position similar to that of the NV drivers on straights and curves, but followed a significantly (P = 0.005) more rightward path on the left turns. CONCLUSIONS: The results support the hypothesis that drivers with HH take a lane position that increases the safety margin on their blind side; however, absolute lane position varies as the steering maneuver and location of the risk from oncoming traffic change with road segment type.

Driving with hemianopia, I: Detection performance in a driving simulator.

PURPOSE: This study was designed to examine the effect of homonymous hemianopia (HH) on detection of pedestrian figures in multiple realistic and hazardous situations within the controlled environment of a driving simulator. METHODS: Twelve people with complete HH and without visual neglect or cognitive decline and 12 matched (age, sex, and years of driving experience) normally sighted (NV) drivers participated. They drove predetermined city and rural highway routes (total, 120 minutes) during which pedestrian figures appeared at random intervals along the roadway (R-Peds; n = 144) and at intersections (I-Peds; n = 10). Detection rates and response times were derived from participant horn presses. RESULTS: Drivers with HH exhibited significantly (P < 0.001) lower R-Ped detection rates on the blind side than did NV drivers (range, 6%-100%). Detection of I-Peds on the blind side was also poor (8%-55%). Age and blind-side detection rates correlated negatively (Spearman r = -0.71, P = 0.009). Although blind-side response times of drivers with HH were significantly (P < 0.001) longer than those of NV drivers, most were within a commonly used 2.5-second guideline. CONCLUSIONS: Most participants with HH had blind-side detection rates that seem incompatible with safe driving; however, the relationship of our simulator detection performance measures to on-road performance has yet to be established. In determining fitness to drive for people with HH, the results underscore the importance of individualized assessments including evaluations of blind-side hazard detection.

Successful medication withdrawal after cognitive-behavioral therapy in a treatment-resistant preadolescent male with obsessive-compulsive disorder.

There are no reports of a child taking a selective serotonin reuptake inhibitor and an atypical anti-psychotic being successfully tapered from these medications after completion of cognitive-behavioral therapy (CBT) for obsessive-compulsive disorder. With this in mind, we report the case of an 8.5-year-old male who was taking risperidone 0.5 mg bid, sertraline 100 mg, and atomoxetine 25 mg at presentation. After a successful course of CBT, we describe how medications were systematically withdrawn. Implications of this case on practice parameters (e.g., CBT may be an effective augmenting agent for those non-responsive to initial pharmacological treatments) are highlighted.

The impact of a video intervention on the use of low vision assistive devices.

PURPOSE: An image-enhanced educational and motivational video was developed for patients with low vision and their caretakers. Impact on knowledge, self-efficacy, and attitudes was assessed. METHODS: The video incorporated cognitive restructuring to change emotional response; a "virtual home"; a veridical simulation of vision with age-related macular degeneration and contrast enhancement of the video. Subjects (median age 77.5) were randomized into control (n=79) and intervention (n=75) groups. Telephone interviews were at baseline, 2 weeks and 3 months. Main outcome measures were: knowledge (eight questions), self-efficacy score (seven questions), adaptive behaviors (10 questions), willingness to use devices, and emotional response (4-point scales). RESULTS: The intervention group showed a statistically significant improvement in knowledge, (difference of 1.1 out of eight questions, p<0.001). Change in use of books-on-tape was more for the intervention group than for controls (p=0.005). The intervention group increased use of books-on-tape from 28 to 51% whereas the control group did not (34% at both times). However, there was no significant change in the use of other assistive devices, including magnifiers. Both groups increased adaptive behaviors. There was no significant difference in change of self-efficacy score or in emotional affect between the two groups. CONCLUSIONS: The video had a small, but statistically significant impact on knowledge and willingness to use assistive devices. There was little impact on adaptive behaviors and emotional affect. The minimal changes in outcome were disappointing, but this does not minimize the importance of patient education; it just emphasizes how hard it is to effect change.

Where people look when watching movies: do all viewers look at the same place?

Magnification around the most important point of a movie scene (center of interest-COI) might aid people with visual impairments that cause resolution loss. This will be effective only if most people look at the same place when watching a movie. We recorded the eye movements of 20 normally sighted subjects as each watched six movie clips, totaling 37.5 min. More than half of the time the distribution of subject gaze points fell within an area statistic that was less than 12% of the movie scene. Male and older subjects were more likely to look in the same place than female and younger subjects, respectively. We conclude that the between-subject agreement is sufficient to make the approach practical.

Wideband enhancement of television images for people with visual impairments.

Wideband enhancement was implemented by detecting visually relevant edge and bar features in an image to produce a bipolar contour map. The addition of these contours to the original image resulted in increased local contrast of these features and an increase in the spatial bandwidth of the image. Testing with static television images revealed that visually impaired patients (n = 35) could distinguish the enhanced images and preferred them over the original images (and degraded images). Most patients preferred a moderate level of wideband enhancement, since they preferred natural-looking images and rejected visible artifacts of the enhancement. Comparison of the enhanced images with the originals revealed that the improvement in the perceived image quality was significant for only 22% of the patients. Possible reasons for the limited increase in perceived image quality are discussed, and improvements are suggested.