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Relapsing White Matter Disease and Subclinical Optic Neuropathy: From the National Multiple Sclerosis Society Case Conference Proceedings

O'Neill, Kimberly A; Dugue, Andrew; Abreu, Nicolas J; Balcer, Laura J; Branche, Marc; Galetta, Steven; Graves, Jennifer; Kister, Ilya; Magro, Cynthia; Miller, Claire; Newsome, Scott D; Pappas, John; Rucker, Janet; Steigerwald, Connolly; William, Christopher M; Zamvil, Scott S; Grossman, Scott N; Krupp, Lauren B
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.
PMID: 38181317
ISSN: 2332-7812
CID: 5628442

A Comparison of Patients' and Neurologists' Assessments of their Teleneurology Encounter: A Cross-Sectional Analysis

Thawani, Sujata P; Minen, Mia T; Grossman, Scott N; Friedman, Steven; Bhatt, Jaydeep M; Foo, Farng-Yang A; Torres, Daniel M; Weinberg, Harold J; Kim, Nina H; Levitan, Valeriya; Cardiel, Myrna I; Zakin, Elina; Conway, Jenna M; Kurzweil, Arielle M; Hasanaj, Lisena; Stainman, Rebecca S; Seixas, Azizi; Galetta, Steven L; Balcer, Laura J; Busis, Neil A
PMID: 37624656
ISSN: 1556-3669
CID: 5599032

Peering further into the mind's eye: combining visual evoked potential and optical coherence tomography measures enhances insight into the variance in cognitive functioning in multiple sclerosis

Covey, Thomas J; Golan, Daniel; Sergott, Robert; Wilken, Jeffrey; Zarif, Myassar; Bumstead, Barbara; Buhse, MariJean; Kaczmarek, Olivia; Doniger, Glen M; Penner, Iris-Katharina; Hancock, Laura M; Bogaardt, Hans; Barrera, Marissa A; Morrow, Sarah A; Galetta, Steve; Gudesblatt, Mark
BACKGROUND:Spectral Optical Coherence Tomography (OCT) and Visual Evoked Potentials (VEPs) have both emerged as potentially useful biomarkers of cognitive decline in people with multiple sclerosis (PwMS). Their combined use may provide additional predictive value for identifying disease impact, progression, and remyelination capacity above-and-beyond what is captured using either approach alone. OBJECTIVE:We examined the relationship between OCT/VEP measures and cognitive functioning in 205 PwMS. OCT measures included Retinal Nerve Fiber Layer Volume (RNFLV), Papillo-Macular Bundle Volume (PBMV), and Macular Volume (MV). VEP measures included latency of the P100, and inter-ocular latency. Cognitive performance was evaluated across seven separate domains of performance, and for overall cognition, using the NeuroTrax computerized testing battery. RESULTS:Both OCT and VEP measures were significantly correlated with cognitive performance across several domains. Linear regression models that controlled for the influence of visual acuity revealed (1) that reduced MV was significantly predictive of poorer visual-spatial functioning, and (2) that delayed VEP latency was significantly predictive of performance in global cognitive functioning and visual-spatial functioning, after controlling for multiple comparisons. Among PwMS with normal visual acuity, PwMS with a combination of both relatively low MV and delayed VEP latency tended to have poorer performance in the domains of global, executive, and visual-spatial functioning compared to PwMS with both high MV and normal VEP latency. CONCLUSION/CONCLUSIONS:Approaches that combine the use of OCT and VEP measures can enhance insight into underlying factors that contribute to variance in cognitive functioning in PwMS.
PMID: 38091086
ISSN: 1432-1459
CID: 5589302

Assignment Completed: The Optic Nerve Should Graduate to Be the Fifth Lesion Site for the Diagnosis of Multiple Sclerosis [Editorial]

Galetta, Steven; Brownlee, Wallace
Optic neuritis has long been considered a characteristic finding of multiple sclerosis and the initial manifestation of the disorder in about 25% of patients. Approximately 70% of patients will experience optic nerve dysfunction during their disease course.1.
PMID: 38165384
ISSN: 1526-632x
CID: 5625982

Occipital Nocardia Abscess Presenting With Positive Visual Phenomenon and Quadrantanopsia

Fein, Alexander S; Kelly, Sean M; Louie, Eddie; Young, Matthew G; Jain, Rajan; William, Christopher M; Galetta, Steven L; Grossman, Scott N
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.
PMID: 37440372
ISSN: 1536-5166
CID: 5537712

Vision as a piece of the head trauma puzzle [Comment]

Bell, Carter A; Grossman, Scott N; Balcer, Laura J; Galetta, Steven L
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.
PMID: 36801966
ISSN: 1476-5454
CID: 5592092

Corrigendum to "Longitudinal stability of inter-eye differences in optical coherence tomography measures for identifying unilateral optic nerve lesions in multiple sclerosis" [Journal of the Neurological Sciences 449C (2023) Start page-End page/JOTNS D-23-00048R2]

Patil, Sachi A; Joseph, Binu; Tagliani, Paula; Sastre-Garriga, Jaume; Montalban, Xavier; Vidal-Jordana, Angela; Galetta, Steven L; Balcer, Laura J; Kenney, Rachel C
PMID: 37468371
ISSN: 1878-5883
CID: 5535862

Neuro-Ophthalmologic Variability in Presentation of Genetically Confirmed Wolfram Syndrome: A Case Series and Review [Case Report]

Jauregui, Ruben; Abreu, Nicolas J; Golan, Shani; Panarelli, Joseph F; Sigireddi, Meenakshi; Nayak, Gopi K; Gold, Doria M; Rucker, Janet C; Galetta, Steven L; Grossman, Scott N
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.
PMCID:10376978
PMID: 37508961
ISSN: 2076-3425
CID: 5593192

Longitudinal stability of inter-eye differences in optical coherence tomography measures for identifying unilateral optic nerve lesions in multiple sclerosis

Patil, Sachi A; Joseph, Binu; Tagliani, Paula; Sastre-Garriga, Jaume; Montalban, Xavier; Vidal-Jordana, Angela; Galetta, Steven L; Balcer, Laura J; Kenney, Rachel C
INTRODUCTION:Optical coherence tomography (OCT)-derived peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell+inner plexiform layer (GCIPL) thickness inter-eye differences (IEDs) are robust measurements for identifying clinical history acute ON in people with MS (PwMS). This study investigated the utility and durability of these measures as longitudinal markers to identify optic nerve lesions. METHODS:Prospective, multi-center international study of PwMS (with/without clinical history of ON) and healthy controls. Data from two sites in the International MS Visual System Consortium (IMSVISUAL) were analyzed. Mixed-effects models were used to compare inter-eye differences based on MS and acute ON history. RESULTS:Average age of those with MS (n = 210) was 39.1 ± 10.8 and 190 (91%) were relapsing-remitting. Fifty-nine (28.1%) had a history of acute unilateral ON, while 9/210 (4.3%) had >1 IB episode. Median follow-up between OCT scans was 9 months. By mixed-effects modeling, IEDs were stable between first and last visits within groups for GCIPL for controls (p = 0.18), all PwMS (p = 0.74), PwMs without ON (p = 0.22), and PwMS with ON (p = 0.48). For pRNFL, IEDs were within controls (p = 0.10), all PwMS (p = 0.53), PwMS without ON history (p = 0.98), and PwMS with history of ON (p = 0.81). CONCLUSION:We demonstrated longitudinal stability of pRNFL and GCIPL IEDs as markers for optic nerve lesions in PwMS, thus reinforcing the role for OCT in demonstrating optic nerve lesions.
PMID: 37167654
ISSN: 1878-5883
CID: 5503382

Optical coherence tomography angiography measurements in multiple sclerosis: a systematic review and meta-analysis

Mohammadi, Soheil; Gouravani, Mahdi; Salehi, Mohammad Amin; Arevalo, J Fernando; Galetta, Steven L; Harandi, Hamid; Frohman, Elliot M; Frohman, Teresa C; Saidha, Shiv; Sattarnezhad, Neda; Paul, Friedemann
BACKGROUND AND OBJECTIVES/OBJECTIVE:Recent literature on multiple sclerosis (MS) demonstrates the growing implementation of optical coherence tomography-angiography (OCT-A) to discover potential qualitative and quantitative changes in the retina and optic nerve. In this review, we analyze OCT-A studies in patients with MS and examine its utility as a surrogate or precursor to changes in central nervous system tissue. METHODS:PubMed and EMBASE were systematically searched to identify articles that applied OCT-A to evaluate the retinal microvasculature measurements in patients with MS. Quantitative data synthesis was performed on all measurements which were evaluated in at least two unique studies with the same OCT-A devices, software, and study population compared to controls. A fixed-effects or random-effects model was applied for the meta-analysis based on the heterogeneity level. RESULTS:The study selection process yielded the inclusion of 18 studies with a total of 1552 evaluated eyes in 673 MS-associated optic neuritis (MSON) eyes, 741 MS without optic neuritis (MSNON eyes), and 138 eyes without specification for the presence of optic neuritis (ON) in addition to 1107 healthy control (HC) eyes. Results indicated that MS cases had significantly decreased whole image superficial capillary plexus (SCP) vessel density when compared to healthy control subjects in the analyses conducted on Optovue and Topcon studies (both P < 0.0001). Likewise, the whole image vessel densities of deep capillary plexus (DCP) and radial peripapillary capillary (RPC) were significantly lower in MS cases compared to HC (all P < 0.05). Regarding optic disc area quadrants, MSON eyes had significantly decreased mean RPC vessel density compared to MSNON eyes in all quadrants except for the inferior (all P < 0.05). Results of the analysis of studies that used prototype Axsun machine revealed that MSON and MSNON eyes both had significantly lower ONH flow index compared to HC (both P < 0.0001). CONCLUSIONS:This systematic review and meta-analysis of the studies reporting OCT-A measurements of people with MS confirmed the tendency of MS eyes to exhibit reduced vessel density in the macular and optic disc areas, mainly in SCP, DCP, and RPC vessel densities.
PMCID:10041805
PMID: 36973708
ISSN: 1742-2094
CID: 5463142