Predictive language comprehension in Parkinson's disease.

Verb and action knowledge deficits are reported in persons with Parkinson's disease (PD), even in the absence of dementia or mild cognitive impairment. However, the impact of these deficits on combinatorial semantic processing is less well understood. Following on previous verb and action knowledge findings, we tested the hypothesis that PD impairs the ability to integrate event-based thematic fit information during online sentence processing. Specifically, we anticipated persons with PD with age-typical cognitive abilities would perform more poorly than healthy controls during a visual world paradigm task requiring participants to predict a target object constrained by the thematic fit of the agent-verb combination. Twenty-four PD and 24 healthy age-matched participants completed comprehensive neuropsychological assessments. We recorded participants' eye movements as they heard predictive sentences (The fisherman rocks the boat) alongside target, agent-related, verb-related, and unrelated images. We tested effects of group (PD/control) on gaze using growth curve models. There were no significant differences between PD and control participants, suggesting that PD participants successfully and rapidly use combinatory thematic fit information to predict upcoming language. Baseline sentences with no predictive information (e.g., Look at the drum) confirmed that groups showed equivalent sentence processing and eye movement patterns. Additionally, we conducted an exploratory analysis contrasting PD and controls' performance on low-motion-content versus high-motion-content verbs. This analysis revealed fewer predictive fixations in high-motion sentences only for healthy older adults. PD participants may adapt to their disease by relying on spared, non-action-simulation-based language processing mechanisms, although this conclusion is speculative, as the analyses of high- vs. low-motion items was highly limited by the study design. These findings provide novel evidence that individuals with PD match healthy adults in their ability to use verb meaning to predict upcoming nouns despite previous findings of verb semantic impairment in PD across a variety of tasks.

A Comparison of Diagnostic Accuracy of Imaging Modalities to Detect Optic Disc Drusen: The Age of Enhanced Depth Imaging Optical Coherence Tomography.

PURPOSE: To identify the most accurate diagnostic imaging modality to detect optic disc drusen (ODD) between B-scan ultrasonography (US), fundus photography, fundus autofluorescence (FAF), and enhanced depth imaging optical coherence tomography (EDI-OCT). DESIGN: Comparative diagnostic analysis. METHODS: Two hundred five eyes of 105 patients referred to 2 tertiary care neuro-ophthalmology clinics for suspected ODD were recruited: 108 eyes had ODD and 97 did not have ODD. All eyes received a full in-person ophthalmic exam with 3D view of the optic nerve and all 4 imaging modalities. Images were independently reviewed by 3 masked neuro-ophthalmologists to determine the presence or absence of ODD. Final interpretation was made through consensus. The reference standard was defined as the attending ophthalmologist's clinical judgement based on open chart review, with access to all image modalities and clinical information, including disease course. Main outcome measures were sensitivity, specificity, accuracy, and precision for each imaging modality. Examiner confidence was quantified as the proportion of eyes in which the reviewers were certain of their decision. RESULTS: The EDI-OCT had the highest sensitivity and accuracy (95%, 97%) to detect ODD, compared with FAF (84%, 92%), US (74%, 86%), and fundus photography (38%, 66%), respectively. All image modalities had high specificity (> 97%) and precision (> 93%). The EDI-OCT also had highest examiner confidence (96%) compared with all others (88%). CONCLUSIONS: Among all modalities, EDI-OCT was the imaging modality with the highest diagnostic utility for the detection of ODD and should be considered as the preferred initial diagnostic modality.

Volumetric Measurement of Peripapillary Hyperreflective Ovoid Masslike Structures in Patients with Optic Disc Drusen.

Purpose: To develop a method to determine the volume of peripapillary hyperreflective ovoid masslike structures (PHOMS) and to examine the correlation between PHOMS and anatomic optic nerve head characteristics in a large cohort of patients with optic disc drusen (ODD). Design: Retrospective, observational study of patients with ODD. Participants: Patients with ODD seen in a 3-year period. Methods: We determined the prevalence of PHOMS. We then developed a method to calculate the volume of PHOMS and measured this in all patients where radial scans on OCT were available. We analyzed the correlation between PHOMS volume and patient age, size of Bruch's membrane opening (BMO), ODD visibility, and anatomic location of ODD in the optic nerve. Main Outcome Measures: Prevalence and characteristics of PHOMS in patients with ODD. Results: In 247 (77%) eyes with ODD, PHOMS were found. Among these, 80% were in the first decade of life, 87% were in the second decade, 89% were in the third decade, 85% were in the fourth decade, 74% were in the fifth decade, 73% were in the sixth decade, 58% were in the seventh decade, 40% were in the eighth decade, and 0% were in the ninth decade. The ophthalmoscopic visibility of ODD increased with age. The volume of PHOMS decreased with age, but with no correlation to the size of BMO. The median volume of PHOMS was 0.27 mm3 (interquartile range [IQR], 0.13-0.49 mm3). Predominantly, PHOMS were observed in the nasal peripapillary area (87.5% nasal, 78.5% superior, 67% inferior, and 63.5% temporal). Conclusions: In patients with ODD, PHOMS are seen frequently, with the highest prevalence in younger individuals. The volume of PHOMS decreases with age, and PHOMS are seen more frequently in patients with superficial ODD.

Peripapillary Hyper-reflective Ovoid Mass-like Structure (PHOMS): An Optical Coherence Tomography Marker of Axoplasmic Stasis in the Optic Nerve Head.

BACKGROUND: With the development and widespread adoption of spectral-domain optical coherence tomography (OCT), peripapillary hyper-reflective ovoid mass-like structures (PHOMS) have become a frequent OCT finding in neuro-ophthalmic practice. Although originally assumed to represent a form of buried optic disc drusen (ODD), PHOMS differ from ODD in many important ways. The histopathological underpinnings of PHOMS are now becoming more clearly understood. EVIDENCE ACQUISITION: Review of literature. RESULTS: PHOMS can be broadly classified as disk edema-associated PHOMS, ODD-associated PHOMS, or anomalous disk-associated PHOMS. PHOMS are seen in many conditions, including papilledema, nonarteritic anterior ischemic optic neuropathy, central retinal vein occlusion, acute demyelinating optic neuritis, ODD, and tilted disks (myopic obliquely inserted disks) and in many cases resolve along with the underlying condition. The histopathological study of these diverse entities reveals the common feature of a bulge of optic nerve fibers herniating centrifugally over Bruch membrane opening into the peripapillary space, correlating exactly with the location, shape, and space-occupying nature of PHOMS on OCT. Because of the radial symmetry of these herniating optic nerve fibers, PHOMS are best thought of as a complete or partial torus (i.e., donut) in 3 dimensions. CONCLUSIONS: PHOMS are a common but nonspecific OCT marker of axoplasmic stasis in the optic nerve head. They are not themselves ODD or ODD precursors, although they can be seen in association with ODD and a wide spectrum of other conditions. They do not exclude papilledema and often accompany it. The circumferential extent and characteristic 3D toroidal nature of a PHOMS are best appreciated by scrolling through consecutive OCT images.

Prevalence of Optic Disc Drusen in Young Patients With Nonarteritic Anterior Ischemic Optic Neuropathy: A 10-Year Retrospective Study.

BACKGROUND: Nonarteritic anterior ischemic optic neuropathy (NAION) in young patients (age ≤50) accounts for a minority of all cases of NAION and is more highly associated with crowding of the optic nerves and bilateral involvement than NAION in older patients. Optic disc drusen (ODD) are likewise associated with crowded optic nerves and are located in the prelaminar optic nerve head where they could contribute to NAION pathogenesis. The purpose of this study was to determine the prevalence of ODD in the eyes of young NAION patients using modern imaging methods and to compare it to the baseline 1.8%-2.0% prevalence of ODD in the general population. METHODS: In this retrospective study, all young NAION patients (ages 18-50 years, inclusive) seen in 2 tertiary care neuro-ophthalmology clinics (in London, Canada and Copenhagen, Denmark) in the ten-year interval between April 1, 2009, and March 31, 2019, were identified and their medical charts reviewed. Patients were included in the study if ODD were diagnosed by any method (including ophthalmoscopy, ultrasound [US], fundus autofluorescence [FAF], computed tomography [CT], or any optical coherence tomography [OCT] method), or if ODD were excluded by enhanced-depth imaging OCT (EDI-OCT) using the ODD Studies (ODDS) Consortium protocol. The presence or absence of ODD was recorded for each eye. RESULTS: There were 37 eligible patients (74 eyes). Mean age of NAION onset was 38.5 ± 10.0 years, and 23 patients (62%) were men. Patients had undergone the following methods of ODD detection: ophthalmoscopy (37 patients), EDI-OCT (36 patients), FAF (31 patients), US (9 patients), and CT orbits (8 patients). We found a prevalence of ODD of 56.7% in NAION-affected patients and 53.3% in NAION-affected eyes. Only 35.9% of ODD were visible on ophthalmoscopy. Twenty of 21 ODD patients (95.2%) had bilateral ODD. Age of onset and sex did not differ significantly between the ODD-positive group and the ODD-negative group. EDI-OCT outperformed any combination of ophthalmoscopy, US, FAF, and CT at detecting ODD. CONCLUSION: ODD were found with much higher prevalence in young patients with NAION than in the general population and were usually bilateral and buried. ODD may contribute to NAION pathogenesis by exacerbating an underlying compartment syndrome in the crowded "disc at risk." EDI-OCT may be the best imaging modality for ODD detection in future studies.

Young Adults With Anterior Ischemic Optic Neuropathy: A Multicenter Optic Disc Drusen Study.

PURPOSE: Optic disc drusen (ODD), present in 2% of the general population, have occasionally been reported in patients with nonarteritic anterior ischemic optic neuropathy (NA-AION). The purpose of this study was to examine the prevalence of ODD in young patients with NA-AION. DESIGN: Retrospective, cross-sectional multicenter study. METHODS: All patients with NA-AION 50 years old or younger, seen in neuro-ophthalmology clinics of the international ODDS (Optic Disc Drusen Studies) Consortium between April 1, 2017, and March 31, 2019, were identified. Patients were included if ODD were diagnosed by any method, or if ODD were excluded by enhanced-depth imaging optical coherence tomography (EDI-OCT) using ODDS Consortium guidelines. NA-AION eyes with ODD were termed "ODD-AION"; those without were termed "NODD-AION". RESULTS: A total of 65 patients (127 eyes) with NA-AION were included (mean 41 years old). Of the 74 eyes with NA-AION, 51% had ODD-AION, whereas 43% of fellow eyes without NA-AION had ODD (P = .36). No significant differences were found between ODD-AION and NODD-AION eyes in terms of Snellen best-corrected VA or perimetric mean deviation. According to EDI-OCT results, 28% of eyes with NODD-AION had peripapillary hyperreflective ovoid mass-like structures (PHOMS); 7% had hyperreflective lines, whereas 54% with ODD-AION had PHOMS; and 66% had hyperreflective lines (P = .006 and P < .001, respectively). CONCLUSIONS: Most of these young NA-AION patients had ODD. This indicates that ODD may be an independent risk factor for the development of NA-AION, at least in younger patients. This study suggests ODD-AION be recognized as a novel diagnosis.