Unique yellow shifts for small and brief stimuli in the central retina.

The spectral locus of unique yellow was determined for flashes of different sizes (<11 arcmin) and durations (<500 ms) presented in and near the fovea. An adaptive optics scanning laser ophthalmoscope was used to minimize the effects of higher-order aberrations during simultaneous stimulus delivery and retinal imaging. In certain subjects, parafoveal cones were classified as L, M, or S, which permitted the comparison of unique yellow measurements with variations in local L/M ratios within and between observers. Unique yellow shifted to longer wavelengths as stimulus size or duration was reduced. This effect is most pronounced for changes in size and more apparent in the fovea than in the parafovea. The observed variations in unique yellow are not entirely predicted from variations in L/M ratio and therefore implicate neural processes beyond photoreception.

Guillain-Barré Syndrome with Rapid Onset and Autonomic Dysfunction Following First Dose of Pfizer-BioNTech COVID-19 Vaccine: A Case Report.

Guillain-Barre syndrome (GBS) is an immune-mediated, often post-infectious illness manifesting as an acute, characteristically monophasic, polyradiculoneuropathy. We present a case of GBS with autonomic involvement following an mRNA-based vaccine against SARS-COV2 (Pfizer/BioNTech mRNA-BNT162b2). A 58-year-old woman presented with fatigue, distal extremity paresthesias, and severe back pain within 3 days after receiving her first vaccine dose. She developed worsening back pain and paresthesias in distal extremities which prompted her initial presentation to the hospital. By the third week post-vaccine, she developed increasing gait unsteadiness, progression of paresthesias, and new autonomic symptoms including presyncopal episodes and constipation. Neurological exam showed bilateral distal predominant lower extremity weakness, decreased sensation in a length-dependent pattern, and areflexia. EMG/NCS showed a diffuse sensorimotor polyneuropathy with mixed demyelinating and axonal features consistent with GBS. She was treated with 2 g/kg of IVIG over 3 days and also received prednisone 60 mg daily for 3 days for severe back pain, with improvement of symptoms. This possible association with mRNA-based vaccination expands the potential triggers for an autoimmune-based attack on the peripheral nervous system.

Acquired Hemicerebral Atrophy Secondary to Chronic Internal Carotid Steno-Occlusive Disease: A Case Series.

Cerebral atrophy is a common finding in elderly patients; however, cerebrovascular disease causing progressive focal cerebral atrophy and dysfunction is unusual. In this report, we present 3 cases of hemicerebral atrophy due to ipsilateral internal carotid artery (ICA) stenosis or occlusion mimicking neurodegenerative conditions. Patient 1 had a frontal dysexecutive syndrome potentially consistent with a diagnosis of behavioral variant frontotemporal dementia; however, neuroimaging revealed a chronically occluded left ICA and a pattern of atrophy restricted to the left middle cerebral artery territory, suggestive of a vascular etiology. Patient 2 presented with progressively worsening seizures and right-sided weakness consistent with left hemispheric dysfunction, with radiographic evidence of left hemicerebral atrophy. Angiography revealed a chronic dissection of the left ICA leading to left cerebral hypoperfusion. Patient 3 had asymmetric parkinsonism, alien limb, and cognitive impairment consistent with a diagnosis of corticobasal syndrome. His imaging, however, revealed atrophy and encephalomalacia within the anterior circulation watershed territories with chronic, severe stenosis of the left ICA suggestive of a chronic hypoperfused state. In this case series, we report 3 examples of hemicerebral atrophy secondary to chronic ipsilateral ICA vascular disease with diverse progressive clinical symptoms mimicking primary neurodegenerative conditions. This case series highlights the importance of considering chronic hypoperfusion and large-vessel severe stenosis or occlusion in patients with cognitive impairment and evidence of asymmetric brain atrophy. In addition to symptomatic treatment, the management of vascular risk factors including treatment with antiplatelet agents, statins, and revascularization procedures can be considered.

Improving the antibody-based evaluation of autoimmune encephalitis.

OBJECTIVE: We tested whether antibody screening samples of patients with suspected autoimmune encephalitis with additional research assays would improve the detection of autoimmune encephalitis compared with standard clinical testing alone. METHODS: We examined 731 samples (333 CSF, 182 sera, and 108 pairs) from a cohort of 623 patients who were tested for CNS autoantibodies by the University of Pennsylvania clinical laboratory over a 24-month period with cell-based assays (CBAs) on commercially obtained slides of fixed cells for antibodies to NMDA receptor (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), γ-aminobutyric acid-B receptor (GABABR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (Caspr2), and glutamic acid decarboxylase (GAD65). In parallel, our research laboratory screened all samples for reactivity to brain sections and for anti-NMDAR using in-house CBAs. Samples with brain reactivity or positive clinical studies were examined with CBAs for a larger panel of antibodies. RESULTS: The clinical laboratory reported positive findings for NMDAR (80 samples), GAD65 (8), LGI1 (5), Caspr2 (2), and GABABR (4). Sixty-five serum samples and 32 CSF samples were indeterminate for one or more antibodies. In our research laboratory, all but 4 positive results were confirmed, 88 of 97 indeterminate results were resolved, and 15 additional samples were found positive (10 NMDAR, 1 AMPAR, 3 LGI1, and 1 Caspr2). Clinical information supported these diagnoses. Overall, informative autoantibodies were detected in 15.5% of cases. CONCLUSIONS: Standard clinical laboratory kits were specific, but some tests were insensitive and prone to indeterminate results. Screening with immunohistochemistry for reactivity to brain sections, followed by additional CBAs for cases with brain reactivity, improves the diagnostic accuracy of testing for autoimmune encephalitis.

Delta/Notch-Like EGF-Related Receptor (DNER) Is Not a Notch Ligand.

Delta/Notch-like EGF-related receptor (DNER) has been reported to act as a Notch ligand, despite lacking a Delta/Serrate/Lag (DSL) binding domain common to all other known ligands. The established Notch ligand Delta-like 1 (DLL1), but not DNER, activated Notch1 in a luciferase assay, prevented the differentiation of myoblasts through Notch signaling, and bound Notch-fc in a cell-based assay. DNER is not a Notch ligand and its true function remains unknown.

Antibodies to Delta/notch-like epidermal growth factor-related receptor in patients with anti-Tr, paraneoplastic cerebellar degeneration, and Hodgkin lymphoma.

IMPORTANCE: The anti-Tr immune response is associated with paraneoplastic cerebellar degeneration and Hodgkin lymphoma (HL). One case series has reported that the Delta/notch-like epidermal growth factor-related receptor (DNER) is the actual target for anti-Tr antibodies, but this result has not been replicated. OBJECTIVE: To describe a patient with anti-Tr and confirm that DNER is the autoantigen for a series of patients with anti-Tr. DESIGN, SETTING, AND PARTICIPANTS: Observational study and analysis of biological samples for antibodies to DNER at the hospital of the University of Pennsylvania. We examined a cerebrospinal fluid sample from 1 patient with anti-Tr and serum and/or cerebrospinal fluid samples from 5 other patients with anti-Tr. EXPOSURE: Transfection of HEK293T and Hela cells to express DNER coupled to an enhanced green fluorescent protein tag using a plasmid previously used to detect human DNER antibodies. RESULTS: A man in his 30s with paraneoplastic cerebellar degeneration and anti-Tr underwent treatment with corticosteroids and intravenous immunoglobulin, resulting in clinical improvement before chemotherapy. Despite close oncologic follow-up, a biopsy, positron emission tomography, and computed tomography, he was not diagnosed as having HL until 6 months after symptom onset. The cerebrospinal fluid sample from this patient reacted with cells transfected to express DNER, as did cerebrospinal fluid and/or serum samples from 5 other patients with paraneoplastic cerebellar degeneration, HL, and anti-Tr. Only 4 of the 5 serum samples reacted to permeabilized cells enough to be distinguished from background, but all 5 serum samples convincingly labeled live cells, which had considerably less background. All 6 control serum samples and 1 serum sample from a patient previously diagnosed as having anti-Tr (but without HL or cerebellitis) did not recognize DNER. CONCLUSIONS AND RELEVANCE: This case demonstrates the importance of testing for the anti-Tr immune response in patients with cerebellar degeneration. The strong association of anti-Tr with HL requires careful surveillance for this tumor. We also confirm that DNER is the target antigen of the anti-Tr immune response. Screening for DNER antibodies against living transfected cells may offer an improved signal-to-noise characteristic compared with immunostaining of fixed, permeabilized cells.

Influences of lobar gray matter and white matter lesion load on cognition and mood.

Depressed mood is a frequent co-morbidity of dementia suggesting that they might share a common neuropathological substrate. Gray matter (GM) atrophy and white matter lesions (WML) have been described in both conditions. Our aims were to determine the relationship of GM and WML with cognition and depressed mood in the same population. Structural brain images were obtained from 42 controls, 20 Alzheimer's disease (AD) patients and 32 subjects with cognitive impairment/dementia due to subcortical cerebrovascular disease (vascCIND/IVD). Images were segmented to obtain lobar GM, white matter and WML volumes. Lobar WML had a negative effect on GM in all lobes in controls, on frontal, parietal and occipital GM in AD and on frontal GM in vascCIND/IVD. Frontal, temporal and hippocampal GM were associated with cognitive functions and frontal WML load with depressed mood. Cognitive function is associated with GM atrophy and depressed mood is associated with frontal WML. This indicates that although both often occur together, depressed mood and cognitive impairment have different pathological correlates.