Synergistic effects of GFAP and Aß42: Implications for white matter integrity and verbal memory across the cognitive spectrum.

Background: Plasma glial fibrillary acidic protein (GFAP), an astrocytic biomarker, has previously been linked with Alzheimer's disease (AD) status, amyloid levels, and memory performance in older adults. The neuroanatomical pathways by which astrogliosis/astrocyte reactivity might impact cognitive outcomes remains unclear. We evaluated whether plasma GFAP and amyloid levels had a synergistic effect on fornix structure, which is critically involved in AD-associated cholinergic pathways. We also examined whether fornix structure mediates associations between GFAP and verbal memory. Methods: In a cohort of both asymptomatic and symptomatic older adults (total n = 99), we assessed plasma GFAP, amyloid-ß42 (Aß42), other AD-related proteins, and vascular markers, and we conducted comprehensive memory testing. Tractography-based methods were used to assess fornix structure with whole brain diffusion metrics to control for diffuse alterations in brain white matter. Results: In individuals in the low plasma amyloid-ß42 (Aß42) group, higher plasma GFAP was associated with lower fractional anisotropy (FA; p = 0.007), higher mean diffusivity (MD; p < 0.001), higher radial diffusivity (RD; p < 0.001), and higher axial diffusivity (DA; p = 0.001) in the left fornix. These associations were independent of APOE gene status, plasma levels of total tau and neurofilament light, plasma vascular biomarkers, and whole brain diffusion metrics. In a sub-analysis of participants in the low plasma Aß42 group (n = 33), fornix structure mediated the association between higher plasma GFAP levels and lower verbal memory performance. Discussion: Higher plasma GFAP was associated with altered fornix microstructure in the setting of greater amyloid deposition. We also expanded on our prior GFAP-verbal memory findings by demonstrating that in the low plasma Aß42 group, left fornix integrity may be a primary white matter conduit for the negative associations between GFAP and verbal memory performance. Overall, these findings suggest that astrogliosis/astrocyte reactivity may play an early, pivotal role in AD pathogenesis, and further demonstrate that high GFAP and low Aß42 in plasma may reflect a particularly detrimental synergistic role in forniceal-memory pathways.

Promoting Growth in Behavioral Neurology: A Path Forward.

Behavioral neurology & neuropsychiatry (BNNP) is a field that seeks to understand brain-behavior relationships, including fundamental brain organization principles and the many ways that brain structures and connectivity can be disrupted, leading to abnormalities of behavior, cognition, emotion, perception, and social cognition. In North America, BNNP has existed as an integrated subspecialty through the United Council for Neurologic Subspecialties since 2006. Nonetheless, the number of behavioral neurologists across academic medical centers and community settings is not keeping pace with increasing clinical and research demand. In this commentary, we provide a brief history of BNNP followed by an outline of the current challenges and opportunities for BNNP from the behavioral neurologist's perspective across clinical, research, and educational spheres. We provide a practical guide for promoting BNNP and addressing the shortage of behavioral neurologists to facilitate the continued growth and development of the subspecialty. We also urge a greater commitment to recruit trainees from diverse backgrounds so as to dismantle persistent obstacles that hinder inclusivity in BNNP-efforts that will further enhance the growth and impact of the subspecialty. With rapidly expanding diagnostic and therapeutic approaches across a range of conditions at the intersection of neurology and psychiatry, BNNP is well positioned to attract new trainees and expand its reach across clinical, research, and educational activities.

Lobar Microbleeds in the Posterior Cortical Atrophy Syndrome: A Comparison to Typical Alzheimer's Disease.

PURPOSE OF THE STUDY: Posterior cortical atrophy is a clinico-radiographical syndrome that presents with higher-order visual dysfunction and is most commonly due to Alzheimer's disease. Understanding factors associated with atypical presentations of Alzheimer's disease, such as posterior cortical atrophy (PCA), holds promise to shape our understanding of AD pathophysiology. Thus, we aimed to compare MRI evidence of lobar microbleeds (LMBs) in posterior cortical atrophy (PCA) syndrome to typical AD (tAD) and to assess and compare MRI evidence of cerebral amyloid angiopathy (CAA) in each group. FINDINGS: We retrospectively collected clinical and MRI data from participants with PCA (n = 26), identified from an institutional PCA registry, and participants with tAD (n = 46) identified from electronic health records from a single institution. LMBs were identified on susceptibility-weighted imaging (SWI); the Fazekas grade of white matter disease was assessed using FLAIR images, and Boston criteria version 2.0 for cerebral amyloid angiopathy were applied to all data. The proportion of participants with PCA and LMB (7.7%) was lower than for tAD (47.8%) (p = 0.005). The frequency of "probable" CAA was similar in both groups, while "possible" CAA was more frequent in tAD (30.4%) than PCA (0%) (p = 0.001). The Fazekas grades were not different between groups. Lobar microbleeds on SWI were not more common in PCA than in typical AD. Clinicopathological investigations are necessary to confirm these findings. The factors that contribute to the posterior cortical atrophy phenotype are unknown.

Demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy: an international cohort study and individual participant data meta-analysis.

BACKGROUND: Posterior cortical atrophy is a rare syndrome characterised by early, prominent, and progressive impairment in visuoperceptual and visuospatial processing. The disorder has been associated with underlying neuropathological features of Alzheimer's disease, but large-scale biomarker and neuropathological studies are scarce. We aimed to describe demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy in a large international cohort. METHODS: We searched PubMed between database inception and Aug 1, 2021, for all published research studies on posterior cortical atrophy and related terms. We identified research centres from these studies and requested deidentified, individual participant data (published and unpublished) that had been obtained at the first diagnostic visit from the corresponding authors of the studies or heads of the research centres. Inclusion criteria were a clinical diagnosis of posterior cortical atrophy as defined by the local centre and availability of Alzheimer's disease biomarkers (PET or CSF), or a diagnosis made at autopsy. Not all individuals with posterior cortical atrophy fulfilled consensus criteria, being diagnosed using centre-specific procedures or before development of consensus criteria. We obtained demographic, clinical, biofluid, neuroimaging, and neuropathological data. Mean values for continuous variables were combined using the inverse variance meta-analysis method; only research centres with more than one participant for a variable were included. Pooled proportions were calculated for binary variables using a restricted maximum likelihood model. Heterogeneity was quantified using I2. FINDINGS: We identified 55 research centres from 1353 papers, with 29 centres responding to our request. An additional seven centres were recruited by advertising via the Alzheimer's Association. We obtained data for 1092 individuals who were evaluated at 36 research centres in 16 countries, the other sites having not responded to our initial invitation to participate to the study. Mean age at symptom onset was 59·4 years (95% CI 58·9-59·8; I2=77%), 60% (56-64; I2=35%) were women, and 80% (72-89; I2=98%) presented with posterior cortical atrophy pure syndrome. Amyloid ß in CSF (536 participants from 28 centres) was positive in 81% (95% CI 75-87; I2=78%), whereas phosphorylated tau in CSF (503 participants from 29 centres) was positive in 65% (56-75; I2=87%). Amyloid-PET (299 participants from 24 centres) was positive in 94% (95% CI 90-97; I2=15%), whereas tau-PET (170 participants from 13 centres) was positive in 97% (93-100; I2=12%). At autopsy (145 participants from 13 centres), the most frequent neuropathological diagnosis was Alzheimer's disease (94%, 95% CI 90-97; I2=0%), with common co-pathologies of cerebral amyloid angiopathy (71%, 54-88; I2=89%), Lewy body disease (44%, 25-62; I2=77%), and cerebrovascular injury (42%, 24-60; I2=88%). INTERPRETATION: These data indicate that posterior cortical atrophy typically presents as a pure, young-onset dementia syndrome that is highly specific for underlying Alzheimer's disease pathology. Further work is needed to understand what drives cognitive vulnerability and progression rates by investigating the contribution of sex, genetics, premorbid cognitive strengths and weaknesses, and brain network integrity. FUNDING: None.

Cataract Phacoemulsification in People with Dementia: Characterization and Outcomes.

PURPOSE: To characterize cataract surgery in people with dementia (PWD) using a cataract surgery outcomes database. METHODS: Demographics, medical and ocular history, surgical characteristics, and postoperative measures were analyzed for differences between PWD and non-PWD cohorts. Patient-level data were analyzed with Fisher's Exact Test, and eye-level data were analyzed with logistic regression using generalized estimating equations to account for correlation of eyes from the same individual. RESULTS: 507 eyes from 296 PWD were identified using appropriate ICD codes and cross-referenced to a cataract surgery outcomes database containing 12,949 eyes from 7,853 patients who underwent cataract phacoemulsification at a single center between January 2014 and October 2019. PWD were older (p < .001), had shorter duration cataract surgeries (p = .006), and were more likely to have mature cataract (p = .017). The rate of general anesthesia was higher in PWD (p = .005). There were no differences in complication rates between PWD and non-PWD cohorts. Both preoperative best corrected LogMAR distance visual acuity (CDVA) (p < .001) and postoperative CDVA (p < .001) were worse in PWD. CDVA significantly improved in both groups (p < .001); however, the average magnitude of improvement in CDVA was not significantly different between groups (p = .169). CONCLUSIONS: PWD present for cataract surgery at a later age and were more likely to have mature cataracts and general anesthesia, but did not have higher rates of complication, and showed significant improvement in CDVA following surgery. These findings should be encouraging to PWD undergoing counseling for cataract surgery, and for the potential for improved function in PWD.

Astrogliosis, neuritic microstructure, and sex effects: GFAP is an indicator of neuritic orientation in women.

BACKGROUND: Data from human studies suggest that immune dysregulation is associated with Alzheimer's disease (AD) pathology and cognitive decline and that neurites may be affected early in the disease trajectory. Data from animal studies further indicate that dysfunction in astrocytes and inflammation may have a pivotal role in facilitating dendritic damage, which has been linked with negative cognitive outcomes. To elucidate these relationships further, we have examined the relationship between astrocyte and immune dysregulation, AD-related pathology, and neuritic microstructure in AD-vulnerable regions in late life. METHODS: We evaluated panels of immune, vascular, and AD-related protein markers in blood and conducted in vivo multi-shell neuroimaging using Neurite Orientation Dispersion and Density Imaging (NODDI) to assess indices of neuritic density (NDI) and dispersion (ODI) in brain regions vulnerable to AD in a cohort of older adults (n = 109). RESULTS: When examining all markers in tandem, higher plasma GFAP levels were strongly related to lower neurite dispersion (ODI) in grey matter. No biomarker associations were found with higher neuritic density. Associations between GFAP and neuritic microstructure were not significantly impacted by symptom status, APOE status, or plasma Aß42/40 ratio; however, there was a large sex effect observed for neurite dispersion, wherein negative associations between GFAP and ODI were only observed in females. DISCUSSION: This study provides a comprehensive, concurrent appraisal of immune, vascular, and AD-related biomarkers in the context of advanced grey matter neurite orientation and dispersion methodology. Sex may be an important modifier of the complex associations between astrogliosis, immune dysregulation, and brain microstructure in older adults.

Posterior white matter integrity and self-reported posterior cortical symptoms using the Colorado Posterior Cortical Questionnaire.

Background: The Colorado Posterior Cortical Questionnaire (CPC-Q) is a self-report, 15-item screening questionnaire for posterior cortical symptoms, including visuospatial and visuoperceptual difficulties. Changes in white matter connectivity may precede obvious gray matter atrophy in neurodegenerative conditions, especially posterior cortical atrophy. Integration of CPC-Q scores and measures of white matter integrity could contribute to earlier detection of posterior cortical syndromes. Methods: We investigated the relationships between posterior cortical symptoms as captured by the CPC-Q and diffusion tensor imaging fractional anisotropy (DTI FA) of white matter regions of interest localized to posterior brain regions (posterior thalamic radiations, splenium of corpus callosum, tapetum). Comparisons were also made by diagnostic group [healthy older adult (n = 31), amnestic Alzheimer's disease (AD, n = 18), and posterior cortical atrophy (PCA, n = 9)] and by SENAS battery visuospatial composite score quartile. Exploratory comparisons of all available individual white matter region DTI FA to CPC-Q, as well as comparisons of DTI FA between diagnostic groups and visuospatial quartiles, were also made. Results: CPC-Q score was correlated with the average DTI FA for the averaged posterior white matter regions of interest (r = -0.31, p = 0.02). Posterior thalamic radiation DTI FA was most strongly associated with CPC-Q (r = -0.34, p = 0.01) and visuospatial composite (r = 0.58, p < 0.01) scores and differed between the PCA and AD groups and the lower and higher visuospatial quartiles. The DTI FA of body and splenium of the corpus callosum also demonstrated this pattern but not the DTI FA of the tapetum. Conclusion: The integrity of posterior white matter tracts is associated with scores on the CPC-Q, adding to the validation evidence for this new questionnaire. White matter regions that may be related to posterior cortical symptoms detected by the CPC-Q, and distinct from those affected in amnestic syndromes, include the posterior thalamic radiations and body and splenium of the corpus callosum. These findings are in line with previous neuroimaging studies of PCA and support continued research on white matter in posterior cortical dysfunction.

Are cognitive researchers ignoring their senses? The problem of sensory deficit in cognitive aging research.

Sensory impairments are common in older adult populations and have notable impacts on aging outcomes. Relationships between sensory and cognitive functions have been clearly established, though the mechanisms underlying those relationships are not fully understood. Given the growing burden of dementia, older adults with sensory deficits are an important and growing population to study in cognitive aging research. Yet, cognitive research sometimes excludes those with uncorrected significant/severe sensory deficits and often poorly or inconsistently assesses those deficits. Observational and interventional studies that exclude participants with sensory deficits will be limited in their generalizability to the narrower subset of the older adult population without vision or hearing impairment and may be missing an opportunity to study a growing population of older adults at higher risk of cognitive impairment. Strategies exist for adapting cognitive testing instruments, and inroads could be made into collecting normative data to inform ongoing research. Bringing together psychometricians with researchers who specialize in vision and hearing impairments could launch highly innovative research on both measurement methods and cognitive disease etiology, as sensory organs provide readily accessible neuronal and vascular beds that may show pathology earlier and elucidate innovative screening opportunities for early signs of cognitive disease.

Consensus recommendations for clinical assessment tools for the diagnosis of posterior cortical atrophy syndrome from the Atypical AD PIA of ISTAART.

INTRODUCTION: Delay in diagnosis of posterior cortical atrophy (PCA) syndrome is common, and the lack of familiarity with assessment tools for identifying visual cortical dysfunction is a contributing factor. We propose recommendations for the approach to the evaluation of PCA clinical features during the office visit, the neuropsychological evaluation, and the research setting. A recommended screening battery for eye clinics is also proposed. METHODS: Recommendations were developed using results from a web-based survey of members of Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) Atypical Alzheimer's Disease Professional Interest Area (PIA), literature review, and consensus by the PCA assessment working party of the Atypical Alzheimer's Disease PIA. RESULTS: Survey results revealed robust agreement for assessment tool preferences for PCA features, and many respondents indicated that they reserve assessment tools for use only when PCA is suspected. For some PCA features, curated tools were preferred over validated battery tools, particularly for the office visit. Consensus recommendations superseded survey preferences for two core cognitive features within the 2017 PCA diagnostic criteria. DISCUSSION: These consensus recommendations provide an evaluation framework for PCA clinical features and can facilitate timely and accurate recognition and diagnosis of PCA. Broader use of these tools should be sought, and development and validation of novel PCA clinical outcome assessments are needed to improve our understanding of atypical AD and other dementias and support the inclusion of those with PCA in treatment trials.

Perspectives and a Systematic Scoping Review on Longitudinal Profiles of Posterior Cortical Atrophy Syndrome.

PURPOSE OF REVIEW: To provide perspectives on the importance of understanding longitudinal profiles of posterior cortical atrophy (PCA) and report results of a scoping review to identify data and knowledge gaps related to PCA survival and longitudinal clinical and biomarker outcomes. RECENT FINDINGS: Thirteen longitudinal studies were identified; all but two had fewer than 30 participants with PCA. Relatively few longitudinal data exist, particularly for survival. In PCA, posterior cortical dysfunction and atrophy progress at faster rates compared to non-posterior regions, potentially up to a decade after symptom onset. Unlike typical AD, PCA phenotype-defined cognitive dysfunction and atrophy remain relatively more severe compared to other regions throughout the PCA course. Select cognitive tests hold promise as PCA outcome measures and for staging. Further longitudinal investigations are critically needed to enable PCA inclusion in treatment trials and to provide appropriate care to patients and enhance our understanding of the pathophysiology of dementing diseases.

Development of the Colorado posterior cortical questionnaire within an Alzheimer's disease study cohort.

INTRODUCTION: Non-amnestic presentations of neurodegenerative dementias, including posterior- and visual-predominant cognitive forms, are under-recognized. Specific screening measures for posterior cortical symptoms could allow for earlier, more accurate diagnosis and directed treatment. METHODS: Based on clinical experience with posterior cortical atrophy evaluations, high-yield screening questions were collected and organized into a 15-item self-report questionnaire, titled the Colorado Posterior Cortical Questionnaire (CPC-Q). The CPC-Q was then piloted within a longitudinal cohort of cognitive aging, including 63 older adults, including healthy older adults (n = 33) and adults with either amnestic Alzheimer's disease (n = 21) or posterior cortical atrophy (PCA, n = 9). RESULTS: The CPC-Q demonstrated acceptable psychometric properties (internal consistency, α = 0.89; mean item-total correlation = 0.62), correlated strongly with visuospatial measures on cognitive testing (p < 0.001), and could distinguish PCA from non-PCA groups (p < 0.001; AUC 0.95 (95% CI 0.88, 1.0)). CONCLUSIONS: The CPC-Q captured posterior cortical symptoms in older adults, using a gold standard of expert consensus PCA diagnosis. Future studies will validate the CPC-Q in a larger cohort, with recruitment of additional PCA participants, to evaluate its convergent and discriminant validity more thoroughly. As a short, self-report tool, the CPC-Q demonstrates potential to improve detection of non-amnestic neurodegenerative dementias in the clinical setting.

Corrigendum: Editorial: Visual Snow: Old Problem, New Understanding.

[This corrects the article DOI: 10.3389/fneur.2022.884752.].

An Exploratory Study to Investigate the Utility of Clinical Screening for Neurodegenerative Disease in Age-Related Eye Disease Research.

BACKGROUND: Unrecognized neurodegenerative diseases (NDD) in age-related eye disease research studies have the potential to confound vision-specific quality of life and retinal optical coherence tomography (OCT) outcome measures. The aim of this exploratory study was to investigate relationships between NDD screening tools and visual outcome measures in a small cohort of controls from the Colorado Age-Related Macular Degeneration Registry (CO-AMD), to consider the utility of future studies. METHODS: Twenty-nine controls from the CO-AMD were screened using the Montreal Cognitive Assessment (MoCA), a Colorado Parkinsonian Checklist, and the Lewy Body Composite Risk Score. Univariate and multivariable linear regression modeling was used to assess associations between screening tools and the National Eye Institute Visual Function Questionnaire-25 (VFQ-25) and macular OCT outcome measures, and t tests were used to evaluate outcome measure differences between those with normal vs abnormal MoCA scores. RESULTS: One patient withdrew. The average age was 72.8 years, and 68% were female patients. Ten participants (36%) had abnormal MoCA scores, and their VFQ-25 scores were only 1 point less and not statistically different than those with normal MoCA scores. Macular OCT volumes and thicknesses for retinal nerve fiber layer (RNFL) and retinal ganglion cell layer were consistently and moderately lower for those with abnormal MoCA scores, and a positive association between MoCA and macular RNFL volume was observed, although differences and regression were not significant. Parkinson screening tests were abnormal for only 4 participants and were not associated with OCT or VFQ-25 measures by regression modeling. CONCLUSIONS: Given the degree and direction of observed differences, further investigation is warranted regarding the relationship between cognitive screening tools and macular OCT measures in age-related eye disease research, but future investigations regarding the relationship between NDD screening tools and VFQ-25 seem unwarranted.

The clinical approach to the identification of higher-order visual dysfunction in neurodegenerative disease.

PURPOSE OF REVIEW: This review is intended to assist the reader in gaining the knowledge and skills necessary for the recognition and assessment of higher-order visual dysfunction due to neurodegenerative diseases including Alzheimer's disease, dementia with Lewy bodies, Parkinson's dementia, corticobasal degeneration, Creutzfeldt-Jakob disease, and the posterior cortical atrophy syndrome. Clinical problem-solving and pattern recognition must be developed and practiced to accurately diagnosis disturbances of higher-order visual function, and knowledge of higher-order visual brain regions and their visual syndromes forms the foundation for deciphering symptoms presented by patients and/or their care partners. Tests of higher-order visual dysfunction must be assembled by the clinician and assessment can take time and effort. The use of screening tests, follow-up visits, and formal neuropsychological referrals are critical components for accurate diagnosis and these principles are reviewed here. RECENT FINDINGS: A recent survey of neuro-ophthalmologists revealed that over half of the respondents report that 5-10% of their new patient referrals carry a diagnosis of neurodegenerative disease and many patients were referred for visual symptoms of unknown cause. Despite over a century of discovery related to higher-order visual functions of the human brain, translation of discovery to the clinical assessment of patients has been slow or absent. As with the approach to translational medicine in general, to see meaningful progress, an interdisciplinary approach is indispensable. The first step involves the application of discoveries from the field visual neuroscience by clinicians from the fields of ophthalmology, neurology, and neuropsychology, and from the disciplines of neuro-ophthalmology and behavioral neurology. The unmet need for recognition, assessment, and management of higher-order visual dysfunction in neurodegeneration is evident and clinicians can contribute to closing the gap by using the approach and the tools outlined in the review.

Network Localization of Unconscious Visual Perception in Blindsight.

OBJECTIVE: Blindsight is a disorder where brain injury causes loss of conscious but not unconscious visual perception. Prior studies have produced conflicting results regarding the neuroanatomical pathways involved in this unconscious perception. METHODS: We performed a systematic literature search to identify lesion locations causing visual field loss in patients with blindsight (n = 34) and patients without blindsight (n = 35). Resting state functional connectivity between each lesion location and all other brain voxels was computed using a large connectome database (n = 1,000). Connections significantly associated with blindsight (vs no blindsight) were identified. RESULTS: Functional connectivity between lesion locations and the ipsilesional medial pulvinar was significantly associated with blindsight (family wise error p = 0.029). No significant connectivity differences were found to other brain regions previously implicated in blindsight. This finding was independent of methods (eg, flipping lesions to the left or right) and stimulus type (moving vs static). INTERPRETATION: Connectivity to the ipsilesional medial pulvinar best differentiates lesion locations associated with blindsight versus those without blindsight. Our results align with recent data from animal models and provide insight into the neuroanatomical substrate of unconscious visual abilities in patients. ANN NEUROL 2022;91:217-224.

A Study Protocol for an Open-Label Feasibility Treatment Trial of Visual Snow Syndrome With Transcranial Magnetic Stimulation.

Background: Visual Snow (VS) syndrome is believed to be due to aberrant central visual processing. Positron Emission Tomography (PET) brain imaging and visual evoked potential studies provide evidence for excessive neuronal activity in the medial temporal lobe, specifically the lingual gyrus, and suggest the VS syndrome is a hyperexcitability syndrome. These data provide the basis for consideration of repetitive transcranial magnetic stimulation (rTMS) as a potential treatment for the VS syndrome. Objective: To publish the study protocol for a pilot study underway at the University of Colorado School of Medicine to investigate the use of rTMS intervention to improve symptoms and visual dysfunction associated with VS. The study aims to determine the adverse events and drop-out rate, evaluate performance of outcome measures, including a novel VS symptom scale, and describe changes in outcomes associated with treatment. Methods and Design: Up to 10 participants meeting criteria for VS syndrome, age 19-65 years, will undergo an open-label intervention consisting of 10 rTMS sessions, occurring 5 days a week over a 2-week period. Participants will complete pre-treatment and post-treatment assessments that include: the Colorado Visual Snow Scale (CVSS), the National Eye Institute Visual Functional Questionnaire-25 (VFQ-25), the General Anxiety Disorder-7 scale (GAD-7), and three psychophysical visual processing tasks. Discussion: Knowledge gained from this pilot study will inform future study planning and provide valuable lessons for future investigation of rTMS for the VS syndrome. An overview of study proceedings thus far demonstrates recruitment challenges associated with the COVID-19 pandemic, and additional challenges that are unique to the VS syndrome and to treatment schedules associated with TMS. Registration: This study has been approved by the Colorado Multiple Institutional Review Board. ClinicalTrials.gov Identifier: NCT04925232.

Persistent visual dysfunction following posterior reversible encephalopathy syndrome due to COVID-19: Case series and literature review.

BACKGROUND AND PURPOSE: The full spectrum of neurological sequelae in COVID-19 is beginning to emerge. SARS-CoV-2 has the potential to cause both direct and indirect brain vascular endothelial damage through infection and inflammation that may result in long-term neurological signs and symptoms. We sought to illuminate persistent neuro-ophthalmological deficits that may be seen following posterior reversible encephalopathy syndrome (PRES) due to COVID-19. METHODS: We identified three individuals with PRES due to COVID-19 in our hospital system. One patient was identified on presentation to our neuro-ophthalmology clinic. The other patients were identified through internal records search. These cases were compared to published reports of PRES in COVID-19 identified through systematic literature search of PubMed/LitCOVID. RESULTS: All three patients were hospitalized with severe COVID-19 and developed altered mental status with new onset seizures that led to the recognition of PRES through diagnostic imaging. During recovery, two patients had persistent visual dysfunction including visual field deficits. One patient also experienced hallucinatory palinopsia and visual hallucinations. Literature search identified 32 other cases of PRES in the context of COVID-19. Visual disturbances were described in 14 cases (40%), with only seven cases (50%) reporting full recovery by the time of publication. CONCLUSIONS: As we learn about enduring neurological complications of COVID-19, it is possible that complications may be underrecognized and underreported. Understanding the range of complications can help in postcare evaluation and management changes in the critical care setting to potentially allow intervention before persistent deficits occur due to COVID-19.

A Shortage of Neurologists We Must Act Now: A Report From the AAN 2019 Transforming Leaders Program.

In nearly every US state today, a large mismatch exists between the need for neurologists and neurological services and the availability of neurologists to provide these services. Patients with neurologic disorders are rising in prevalence and require access to high level care to reduce disability. The current neurology mismatch reduces access to care, worsens patient outcomes, and erodes career satisfaction and quality of life for neurologists as they face increasingly insurmountable demands. As a community, we must address this mismatch in the demand and supply of neurological care in an aggressive and sustained manner to ensure the future health of our patients and our specialty. The American Academy of Neurology has multiple ongoing initiatives to help reduce and resolve the existing mismatch. With the intent of raising awareness and widening the debate nationally, we present a strategic plan that the Academy could implement to coordinate and expand existing efforts. We characterize the suggested strategies as: shaping the demand, enhancing the workforce, and advocating for neurologist value The proposed framework is based on available data and expert opinion when data were lacking. Prioritization of strategies will vary by geography, practice setting, and local resources. We believe the time to act is now, to allow concerted effort and targeted interventions to avert this looming public health crisis.