Faculty Bibliography

BACKGROUND/PURPOSE/UNASSIGNED:Downbeat nystagmus (DBN) is an uncommon finding in comatose patients, especially as a manifestation of epileptiform activity. We report a 59-year-old man who developed DBN in the context of myoclonic status epilepticus following anoxic brain injury secondary to cardiac arrest. The DBN was phase-locked with generalized periodic epileptiform discharges (GPDs) on electroencephalography (EEG) and resolved with pharmacologic burst suppression. CONCLUSION/UNASSIGNED:This case suggests a potential link between DBN and cortical epileptiform activity, which we hypothesize may be due to bilateral cortical hyperexcitability and cerebellar disinhibition. The presence of DBN in this setting may indicate a poor prognosis.

A 58-year-old woman presented with painless progressive bilateral blurred vision, worse in the right eye, over several days. Two months prior, she developed a diffuse pruritic rash that spared her face. On examination, she was found to have reduced visual acuity bilaterally, optic nerve edema, anterior uveitis, and scattered intraretinal and peripapillary nerve fiber layer hemorrhages. Diagnostic evaluation demonstrated optic nerve head enhancement on MRI. Her serum workup showed positive antibodies for Borrelia burgdorferi with a negative Lyme disease Western blot and positive Treponema pallidum antibodies with an rapid plasma reagin titer of 1:1,024. CSF showed normal protein, a slight elevation in nucleated cells with lymphocytic predominance, and a negative Venereal Disease Research Laboratory. We examine the differential diagnosis for bilateral optic nerve edema and uveitis and explore challenges around interpreting diagnostic testing for a neuro-ophthalmic pathology of ongoing public health interest.

The gene SPG7 codes for the protein paraplegin, a subunit of the m-AAA protease in the inner mitochondrial membrane involved in protein quality control. SPG7 was initially identified as causing autosomal recessive hereditary spastic paraplegia (HSP), with a pure (insidiously progressive bilateral leg weakness and spasticity) and complex (with additional neurologic features including cerebellar signs and optic atrophy) forms. Now identified as one of the most common causes of HSP, SPG7-associated disease has been linked to additional neuro-ophthalmologic features, including isolated dominant optic atrophy, cerebellar eye signs (various forms of nystagmus, dysmetric saccades), progressive external ophthalmoplegia (PEO), and supranuclear vertical palsy. This review describes in detail the various neuro-ophthalmologic presentations of SPG7-associated disease, illustrating the role of mitochondrial dysfunction in the pathophysiology of these different entities. Knowledge of the different manifestations of SPG7-associated disease is crucial for both neurologists and ophthalmologists, and SPG7 should be considered in the work-up of patients presenting with entities such as optic atrophy, PEO, and cerebellar eye signs.

PURPOSE/OBJECTIVE:Many studies estimate that more than 50% of non-hospitalized patients with long-COVID develop moderate to severe autonomic dysfunction. However, the specific impact of autonomic dysfunction as it relates to quality of life in long-COVID is not fully understood. The aim of the current study is to assess autonomic symptoms and quality-of-life in patients with Post-Acute Sequelae of COVID-19 (PASC) recruited from a neurology department outpatient setting. METHODOLOGY/METHODS:In a two-year follow-up study of a baseline cohort of 93 non-hospitalized SARS-CoV-2 laboratory-positive patients evaluated for PASC between November 2020-August 2021, 44 participants completed follow-up telephone questionnaires examining quality-of-life as well as neurologic and autonomic symptoms. RESULTS:Among 93 participants, 44 (47 %) completed the two-year follow-up evaluation and 27 (61 %) were female with a median age of 55 years (IQR = 24-88). Most participants (95 %, 42/44) were vaccinated against COVID-19 and 43 % (19/44) had a pre-existing neurological disorder. Median time from index COVID-19 infection to follow-up was 26 months (IQR = 23-17), with a median of 15 months (IQR = 15-16) between visits. Fatigue, word finding difficulty, and changes in memory were the most commonly reported PASC symptoms. Sixty-six percent (29/44) of individuals met criteria for autonomic dysfunction as defined by the Composite Autonomic Symptom Score-31 (COMPASS-31) scale. Secretomotor and gastrointestinal subdomains demonstrated significant associations with Neuro-QoL metrics for Anxiety, Depression, and Fatigue. For every 1 additional PASC symptom reported at a follow-up study visit, there was an average increase of 1.5 points on the COMPASS-31 composite score. In addition, visual disturbances and sleep impairment were both associated with increased autonomic dysfunction. CONCLUSION/CONCLUSIONS:The strong association between autonomic dysfunction and reduced QoL in PASC and the relation to insomnia, visual dysfunction, and functional impairment are valuable findings, reinforcing the clinical impact of these symptoms longitudinally after index COVID-19 infection.

BACKGROUND AND OBJECTIVES/OBJECTIVE:While reductions in optical coherence tomography (OCT) pRNFL and ganglion cell-inner plexiform layer thicknesses have been shown to be associated with brain atrophy in adult-onset MS (AOMS) cohorts, the relationship between OCT and brain MRI measures is less established in pediatric-onset MS (POMS). Our aim was to examine the associations of OCT measures with volumetric MRI in a cohort of patients with POMS to determine whether OCT measures reflect CNS neurodegeneration in this patient population, as is seen in AOMS cohorts. METHODS:This was a cross-sectional study with retrospective ascertainment of patients with POMS evaluated at a single center with expertise in POMS and neuro-ophthalmology. As part of routine clinical care, patients with POMS are evaluated by a POMS expert and undergo volumetric brain MRI, including whole-brain (WB), subregional, and gray matter (GM) volume analyses. Patients with POMS are routinely referred to neuro-ophthalmology for evaluation that includes high-contrast visual acuity, color vision testing, and OCT. Generalized estimating equation (GEE) models, accounting for within-patient, intereye correlations (both eyes of each patient were included), MS disease duration, and disease-modifying therapy efficacy, were used to determine the relationship between visual pathway structure and function and volumetric MRI measures. RESULTS:= 0.015, respectively). DISCUSSION/CONCLUSIONS:Our results demonstrate that changes in visual pathway structures are associated with reductions in overall brain volume and GM volumes, as well as greater lesion and black hole burden. Collectively, our results emphasize the importance of visual assessment in POMS and suggest that OCT reflects overall CNS neurodegeneration in this cohort.