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Objective: To explore longitudinal changes in brain volumetric measures and retinal layer thicknesses following acute optic neuritis (AON) in people with multiple sclerosis (PwMS), to investigate the process of trans‐synaptic degeneration, and determine its clinical relevance. Methods: PwMS were recruited within 40 days of AON onset (n = 49), and underwent baseline retinal optical coherence tomography and brain magnetic resonance imaging followed by longitudinal tracking for up to 5 years. A comparator cohort of PwMS without a recent episode of AON were similarly tracked (n = 73). Mixed‐effects linear regression models were used. Results: Accelerated atrophy of the occipital gray matter (GM), calcarine GM, and thalamus was seen in the AON cohort, as compared with the non‐AON cohort (−0.76% vs −0.22% per year [p = 0.01] for occipital GM, −1.83% vs −0.32% per year [p = 0.008] for calcarine GM, −1.17% vs −0.67% per year [p = 0.02] for thalamus), whereas rates of whole‐brain, cortical GM, non‐occipital cortical GM atrophy, and T2 lesion accumulation did not differ significantly between the cohorts. In the AON cohort, greater AON‐induced reduction in ganglion cell+inner plexiform layer thickness over the first year was associated with faster rates of whole‐brain (r = 0.32, p = 0.04), white matter (r = 0.32, p = 0.04), and thalamic (r = 0.36, p = 0.02) atrophy over the study period. Significant relationships were identified between faster atrophy of the subcortical GM and thalamus, with worse visual function outcomes after AON. Interpretation: These results provide in‐vivo evidence for anterograde trans‐synaptic degeneration following AON in PwMS, and suggest that trans‐synaptic degeneration may be related to clinically‐relevant visual outcomes. ANN NEUROL 2023;93:76–87 [ABSTRACT FROM AUTHOR]

Background: α‐synuclein aggregates in the form of Lewy bodies and Lewy neurites are the pathological hallmark of Parkinson disease (PD) and dementia with Lewy bodies (DLB). Autopsy studies suggest that α‐synuclein aggregates appear in localized areas of the central nervous system before spreading in a sequential pattern from the brainstem to the cerebral cortex, known as the Braak hypothesis. Increased prevalence of peripheral neuropathy in PD is recognized, with multiple hypothesized mechanisms including α‐synuclein deposition. Method: We describe a patient who developed a peripheral sensory neuropathy at age 60, which progressed insidiously over the following decade. Results: During the patient's eighth decade, the patient developed a fluctuant cognitive disturbance with hallucinations before becoming overtly parkinsonian at age 78 years leading to a diagnosis of DLB. At this point, histology slides from a sural nerve biopsy taken at age 72 were re‐evaluated and immunohistochemistry demonstrated α‐synuclein deposition. Conclusion: This case provides important in vivo clinical correlation for the Braak hypothesis, extending its scope beyond idiopathic PD. A growing body of evidence supports the α‐synuclein spreading hypothesis that posits the pathologic process begins in the peripheral nerves and spreads trans‐synaptically to the CNS in an ascending pattern. [ABSTRACT FROM AUTHOR]

Objective: Therapeutic development in progressive multiple sclerosis (PMS) has been hampered by a lack of reliable biomarkers to monitor neurodegeneration. Optical coherence tomography (OCT)-derived retinal measures have been proposed as promising biomarkers to fulfill this role. However, it is unclear whether retinal atrophy persists in PMS, exceeds normal aging, or can be distinguished from relapsing-remitting multiple sclerosis (RRMS).Methods: 178 RRMS, 186 PMS, and 66 control participants were followed with serial OCT for a median follow-up of 3.7 years.Results: The estimated proportion of peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell + inner plexiform layer (GCIPL) thinning in multiple sclerosis (MS) attributable to normal aging increased from 42.7% and 16.7% respectively at age 25 years, to 83.7% and 81.1% at age 65 years. However, independent of age, PMS was associated with faster pRNFL (-0.34 ± 0.09%/yr, p < 0.001) and GCIPL (-0.27 ± 0.07%/yr, p < 0.001) thinning, as compared to RRMS. In both MS and controls, higher baseline age was associated with faster inner nuclear layer (INL) and outer nuclear layer (ONL) thinning. INL and ONL thinning were independently faster in PMS, as compared to controls (INL:-0.09 ± 0.04%/yr, p = 0.03; ONL:-0.12 ± 0.06%/yr, p = 0.04), and RRMS (INL:-0.10 ± 0.04%/yr, p = 0.01; ONL:-0.13 ± 0.05%/yr, p = 0.01), whereas they were similar in RRMS and controls. Unlike RRMS, disease-modifying therapies (DMTs) did not impact rates of retinal layer atrophy in PMS.Interpretation: PMS is associated with faster retinal atrophy independent of age. INL and ONL measures may be novel biomarkers of neurodegeneration in PMS that appear to be unaffected by conventional DMTs. The effects of aging on rates of retinal layer atrophy should be considered in clinical trials incorporating OCT outcomes. ANN NEUROL 2020;87:885-896. [ABSTRACT FROM AUTHOR]

Aicardi–Goutières syndrome (AGS) is a rare and likely underdiagnosed genetic leukoencephalopathy, typically presenting in infancy with encephalopathy and characteristic neuroimaging features, with residual static neurological deficits. We describe a patient who, following an initial presentation at the age of 12 months in keeping with AGS, exhibited a highly atypical relapsing course of neurological symptoms in adulthood with essentially normal neuroimaging. Whole‐exome sequencing confirmed a pathogenic RNASEH2B gene variant consistent with AGS. This case highlights the expanding phenotypes associated with AGS and the potential role of whole‐exome sequencing in facilitating an increase in the rate of diagnosis. [ABSTRACT FROM AUTHOR]

Background: We describe the clinical and neuropathological features of a patient with T‐cell‐mediated paraneoplastic limbic encephalitis, parkinsonism, hypothermia, and narcolepsy‐like presentation associated with endometrial carcinoma. Objectives: This patient with prominent parkinsonism and narcolepsy broadens the phenotype of known paraneoplastic syndromes and demonstrates the importance of investigation for occult malignancy even in the absence of paraneoplastic antibodies. Methods: This is a case report with diagnosis confirmed at postmortem. Results: Paraneoplastic antibodies were not detected. The initial improvement with immunosuppression was short lived, and postmortem neuropathological examination demonstrated encephalitis with predominant T‐cell infiltration affecting the hypothalamus and extending to the brainstem, suggestive of a paraneoplastic syndrome. Conclusions: Although the possibility of a novel antibody cannot be ruled out, consideration must also be given to recent demonstration of purely T‐cell‐mediated neuronal destruction in the context of paraneoplastic syndromes. [ABSTRACT FROM AUTHOR]

Objective: Optical coherence tomography (OCT)‐derived measures of the retina correlate with disability and cortical gray matter atrophy in multiple sclerosis (MS); however, whether such measures predict long‐term disability is unknown. We evaluated whether a single OCT and visual function assessment predict the disability status 10 years later. Methods: Between 2006 and 2008, 172 people with MS underwent Stratus time domain‐OCT imaging [160 with measurement of total macular volume (TMV)] and high and low‐contrast letter acuity (LCLA) testing (n = 150; 87%). All participants had Expanded Disability Status Scale (EDSS) assessments at baseline and at 10‐year follow‐up. We applied generalized linear regression models to assess associations between baseline TMV, peripapillary retinal nerve fiber layer (pRNFL) thickness, and LCLA with 10‐year EDSS scores (linear) and with clinically significant EDSS worsening (binary), adjusting for age, sex, optic neuritis history, and baseline disability status. Results: In multivariable models, lower baseline TMV was associated with higher 10‐year EDSS scores (mean increase in EDSS of 0.75 per 1 mm3 loss in TMV (mean difference = 0.75; 95% CI: 0.11–1.39; P = 0.02). In analyses using tertiles, individuals in the lowest tertile of baseline TMV had an average 0.86 higher EDSS scores at 10 years (mean difference = 0.86; 95% CI: 0.23–1.48) and had over 3.5‐fold increased odds of clinically significant EDSS worsening relative to those in the highest tertile of baseline TMV (OR: 3.58; 95% CI: 1.30–9.82; Ptrend = 0.008). pRNFL and LCLA predicted the 10‐year EDSS scores only in univariate models. Interpretation: Lower baseline TMV measured by OCT significantly predicts higher disability at 10 years, even after accounting for baseline disability status. [ABSTRACT FROM AUTHOR]

The article presents a case study involving a 69-year-old male presented with a 2-week history of severe right periorbital swelling, erythema, and blistering lesions over the right forehead and scalp without associated pain. He reportedly suffered from sharp pain without relief from analgesia. Doctors reportedly suspected acute herpes zoster given the clinical picture and the patient was admitted to the lung transplant unit with consultation from neurology services.