Faculty Bibliography

A 16-year-old adolescent boy presented with recurrent episodes of weakness and numbness. Brain MRI demonstrated subcortical, juxtacortical, and periventricular white matter T2 hyperintensities with gadolinium enhancement. CSF was positive for oligoclonal bands that were not present in serum. Despite treatment with steroids, IV immunoglobulins, plasmapheresis, and rituximab, he continued to have episodes of weakness and numbness and new areas of T2 hyperintensity on imaging. Neuro-ophthalmologic examination revealed a subclinical optic neuropathy with predominant involvement of the papillomacular bundle. Genetic evaluation and brain biopsy led to an unexpected diagnosis.

BACKGROUND:Hereditary optic neuropathies comprise a group of clinically and genetically heterogeneous disorders. Optic neuropathy has been previously reported in families with spastic paraplegia type 7 (SPG7) gene mutations. However, the typical time course and clinical presentation of SPG7-associated optic neuropathy is poorly understood. We report a series of 5 patients harboring pathogenic SPG7 mutations who originally presented to a neuro-ophthalmology clinic with symptoms of optic neuropathy. METHODS:Retrospective case series of 5 patients with pathogenic SPG7 mutations and optic atrophy from 3 neuro-ophthalmology clinics. Demographic, clinical, diagnostic, and treatment data were collected and reported by the clinician authors. RESULTS:Five patients ranging in age from 8 to 48 years were evaluated in the neuro-ophthalmology clinic. Although there were variable clinical presentations for each subject, all noted progressive vision loss, typically bilateral, and several also had previous diagnoses of peripheral neuropathy (e.g., Guillain-Barré Syndrome). Patients underwent neuro-ophthalmic examinations and testing with visual fields and optic coherence tomography of the retinal nerve fiber layer. Genetic testing revealed pathogenic variants in the SPG7 gene. CONCLUSIONS:Five patients presented to the neuro-ophthalmology clinic with progressive vision loss and were diagnosed with optic atrophy. Although each patient harbored an SPG7 mutation, this cohort was phenotypically and genotypically heterogeneous. Three patients carried the Ala510Val variant. The patients demonstrated varying degrees of visual acuity and visual field loss, although evaluations were completed during different stages of disease progression. Four patients had a previous diagnosis of peripheral neuropathy. This raises the prospect that a single pathogenic variant of SPG7 may be associated with peripheral neuropathy in addition to optic neuropathy. These results support the consideration of SPG7 testing in patients with high suspicion for genetic optic neuropathy, as manifested by symmetric papillomacular bundle damage without clear etiology on initial workup. Applied judiciously, genetic testing, including for SPG7, may help clarify the cause of unexplained progressive optic neuropathies.

PURPOSE OF REVIEW/OBJECTIVE:Opsoclonus and ocular flutter are saccadic intrusions characterized by spontaneous, back-to-back, fast eye movements (saccades) that oscillate about the midline of central visual fixation without intervening inter-saccadic intervals. When this type of movement occurs exclusively in the horizontal plane, it is called ocular flutter. When it occurs in multiple planes (i.e. horizontal, vertical, and torsional) it is called opsoclonus. The most common etiologic categories are parainfectious and paraneoplastic diseases. Less common are toxic-metabolic, traumatic, or idiopathic origins. The mechanism of these movements relates to dysfunction of brainstem and cerebellar machinery involved in the generation of saccades. In this review, we discuss the characteristics of opsoclonus and ocular flutter, describe approaches to clinical evaluation and management of the patient with opsoclonus and ocular flutter, and review approaches to therapeutic intervention. RECENT FINDINGS/RESULTS:Recent publications demonstrated eye position-dependent opsoclonus present only in left gaze, which may be related to dysfunction of frontal eye fields or structures in the cerebellar vermis. SUMMARY/CONCLUSIONS:Opsoclonus and ocular flutter originate from a broad array of neuropathologies and have value from both a neuroanatomic and etiologic perspective.

Mitigating the substantial public health impact of concussion is a particularly difficult challenge. This is partly because concussion is a highly prevalent condition, and diagnosis is predominantly symptom-based. Much of contemporary concussion management relies on symptom interpretation and accurate reporting by patients. These types of reports may be influenced by a variety of factors for each individual, such as preexisting mental health conditions, headache disorders, and sleep conditions, among other factors. This can all be contributory to non-specific and potentially misleading clinical manifestations in the aftermath of a concussion. This review aimed to conduct an examination of the existing literature on emerging approaches for objectively evaluating potential concussion, as well as to highlight current gaps in understanding where further research is necessary. Objective assessments of visual and ocular motor concussion symptoms, specialized imaging techniques, and tissue-based concentrations of specific biomarkers have all shown promise for specifically characterizing diffuse brain injuries, and will be important to the future of concussion diagnosis and management. The consolidation of these approaches into a comprehensive examination progression will be the next horizon for increased precision in concussion diagnosis and treatment.

A 74-year-old man with chronic obstructive pulmonary disease, glaucoma, and Stage IIIB squamous cell lung cancer experienced several minutes of flashing lights in his right visual hemifield, followed by onset of a right visual field defect. On examination, the patient had a right homonymous hemianopsia that was most dense inferiorly by confrontation testing. Emergent CT scan of the head revealed a 2.5 × 3 cm hypodensity in the left occipital lobe, which was interpreted as an acute stroke. Continuous EEG monitoring captured left posterior quadrant seizures that were temporally correlated to the positive visual phenomena. Subsequent MRI of the brain with and without contrast revealed a conglomerate of centrally necrotic and peripherally enhancing mass lesions. On biopsy, a thick purulent material was drained and Gram stain of the sample revealed gram-positive beaded rods, which speciated to Nocardia farcinica. The patient was treated with a six-week course of intravenous meropenem and a one-year course of oral trimethroprim-sulfamethoxazole. On follow-up, the patient experienced resolution of the right visual field deficit.

Approximately half of the brain's circuits are involved in vision and control of eye movements. Therefore, visual dysfunction is a common symptom of concussion, the mildest form of traumatic brain injury (TBI). Photosensitivity, vergence dysfunction, saccadic abnormalities, and distortions in visual perception have been reported as vision-related symptoms following concussion. Impaired visual function has also been reported in populations with a lifetime history of TBI. Consequently, vision-based tools have been developed to detect and diagnose concussion in the acute setting, and characterize visual and cognitive function in those with a lifetime history of TBI. Rapid automatized naming (RAN) tasks have provided widely accessible and quantitative measures of visual-cognitive function. Laboratory-based eye tracking approaches demonstrate promise in measuring visual function and validating results from RAN tasks in patients with concussion. Optical coherence tomography (OCT) has detected neurodegeneration in patients with Alzheimer's disease and multiple sclerosis and may provide critical insight into chronic conditions related to TBI, such as traumatic encephalopathy syndrome. Here, we review the literature and discuss the future directions of vision-based assessments of concussion and conditions related to TBI.

Wolfram syndrome is a neurodegenerative disorder caused by pathogenic variants in the genes WFS1 or CISD2. Clinically, the classic phenotype is composed of optic atrophy, diabetes mellitus type 1, diabetes insipidus, and deafness. Wolfram syndrome, however, is phenotypically heterogenous with variable clinical manifestations and age of onset. We describe four cases of genetically confirmed Wolfram syndrome with variable presentations, including acute-on-chronic vision loss, dyschromatopsia, and tonic pupils. All patients had optic atrophy, only three had diabetes, and none exhibited the classic Wolfram phenotype. MRI revealed a varying degree of the classical features associated with the syndrome, including optic nerve, cerebellar, and brainstem atrophy. The cohort's genotype and presentation supported the reported phenotype-genotype correlations for Wolfram, where missense variants lead to milder, later-onset presentation of the Wolfram syndrome spectrum. When early onset optic atrophy and/or diabetes mellitus are present in a patient, a diagnosis of Wolfram syndrome should be considered, as early diagnosis is crucial for the appropriate referrals and management of the associated conditions. Nevertheless, the condition should also be considered in otherwise unexplained, later-onset optic atrophy, given the phenotypic spectrum.

There are multiple treatment alternatives for cavernous dAVFs, with transvenous routes being most common. Among these routes, occluded inferior petrosal sinus is well-described, and, apart from being imaginative and elegant, it is also safe and effective. Herein we describe the application of this method to reach the fistulous pouch of a cavernous dAVF via an occluded superior petrosal sinus.

OBJECTIVE:The primary objective was to determine the effect of the COVID-19 pandemic on volume, demographics, and mechanisms of injury (MOI) for patients seen at an urban multidisciplinary concussion center. During the first phase of the pandemic in the United States, stay-at-home orders led to decreased group activities and required cancellation of outpatient appointments or initiation of telemedicine visits. METHODS:This study was a retrospective chart review of 3500 patient electronic medical records (EMR). Patients aged 1-99 years were eligible if they had been seen at New York University Langone Health Concussion Center during March 1-December 31, 2019 (control/pre-pandemic period) or during the same period in 2020 (pandemic period). Injury date, appointment date, age, sex, and MOI were captured; statistical analyses were performed using Stata17 (StataCorp, College Station, TX). RESULTS:There were 48% fewer visits during the COVID-19 pandemic period compared to the 2019 control period. There was a decreased proportion of pediatric patients (15% control, 6% pandemic; p = 0.007, chi-square test). Fewer concussions were related to team sports (21% control, 5% pandemic; p < 0.001), and a greater proportion were caused by bicycle accidents (4% control, 8% pandemic; p = 0.037) and assault/domestic violence (3% control, 9% pandemic; p < 0.001). CONCLUSION/CONCLUSIONS:The relative proportions of concussion MOI, age distributions, and visit volumes were significantly associated with pre-pandemic vs. pandemic periods, suggesting that COVID-19 changed concussion epidemiology during the pandemic period. This study demonstrates how epidemiologic data may inform future resource allocation during public health emergencies.