Faculty Bibliography

BACKGROUND: Benign multiple sclerosis (MS), traditionally defined as Expanded Disability Status Scale (EDSS) score /=15-year disease duration, is thought to follow a milder clinical course. We determined the extent of visual pathway axonal loss by optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness in a benign MS cohort and examined the relation to vision and quality of life (QOL). METHODS: In this longitudinal study of vision in MS at 3 academic centers, a subset of patients with EDSS, visual function, OCT, and QOL assessments was analyzed. Low- and high-contrast letter acuity was performed to assess visual function. RNFL thickness was determined using time-domain OCT. QOL scales included the 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) and Short Form-36 Health Survey. RESULTS: Among 68 patients (135 eyes) studied longitudinally, 13 (26 eyes) had benign MS using criteria of EDSS score /=15-year disease duration. Benign MS eyes had as much RNFL thinning (-3.6 mum, P = 0.0008 vs baseline, paired t test) as typical MS eyes (-3.3 mum, P < 0.0001). Both groups had significant low-contrast acuity loss. History of optic neuritis (ON) was more frequent in benign MS (69% vs 33% of eyes). History of ON distinguished benign vs typical MS (P = 0.002) and correlated with RNFL thickness at baseline (P = 0.002) and disease duration (P = 0.03) but not EDSS (P = 0.32, logistic regression). NEI-VFQ-25 scores were also worse for benign MS, accounting for age (75 +/- 21 vs 88 +/- 11, P = 0.005). CONCLUSION: Patients with benign MS have RNFL axonal loss that is as marked as that of typical MS and have reduced vision and QOL. While overall neurologic impairment is mild, visual dysfunction, not well captured by the EDSS, accounts for a substantial degree of disability in benign MS.

OBJECTIVE: Ocular motility abnormalities may be a marker of neuro-degeneration beyond motor neurons in amyotrophic lateral sclerosis (ALS). We formally compared clinical neuro-ophthalmic abnormalities in ALS patients and a control population. METHODS: Patients attending a multidisciplinary ALS clinic (n=63, age 60.8+/-16.4 years) and their caregivers serving as controls (n=37, ages 55.0+/-12.7 years) participated in this cross-sectional study. Visual acuity was assessed. Video recordings of a standardized ocular motility exam including gaze fixation, voluntary saccades, reflex saccades, smooth pursuit, eyelid opening and Bell's phenomenon were rated by two senior neuro-ophthalmologists who were masked to subject group. RESULTS: Visual acuity was lower in ALS patients versus control subjects (OR 0.81 (0.71-0.93), p=0.003, logistic regression). Inter- and intra-rater reliability for ocular motility examination ratings were good (Cohen's Kappa>0.6). Findings observed only in ALS subjects included gaze impersistence (14%, p=0.01), moderately or severely restricted voluntary upgaze (13%, p=0.01), and moderate or severe eyelid opening apraxia (27%, p=0.0002). Accounting for age, moderately or severely saccadic horizontal smooth pursuits distinguished ALS from control subjects (OR 3.6 (1.2-10.9), p=0.02, logistic regression). CONCLUSIONS: Clinical findings of decreased visual acuity, gaze impersistence, voluntary upgaze restriction, eyelid opening apraxia, and saccadic horizontal smooth pursuits are more frequent in patients with ALS than in similar-aged controls. These findings are potential clinical markers of neurodegeneration beyond upper and lower motor neuron disease in ALS. Further study is warranted regarding their application to disease categorization and outcomes assessment.

For 40 years, visual evoked cortical potentials (VEPs) have been used to aid in the diagnosis of demyelinating optic neuropathy.(1) Early studies demonstrated an increased latency of the positive peak normally seen at about 100 msec-the P100-in patients with optic neuritis.(1) Since the P100 often remains prolonged following recovery from the acute episode, the VEP is useful to detect optic nerve involvement in patients with suspected multiple sclerosis (MS).(2) One might posit that the VEP would be useful in the identification of subclinical optic neuropathy, in which the demyelination is so mild as to give no abnormal physical examination findings.(3).

ABSTRACT:: Crohn disease (CD) is primarily considered an inflammatory condition of the small and large intestine although associated extraintestinal inflammation is relatively common. Ocular manifestations are generally localized to the anterior chamber and ocular surface but rarely can involve the posterior pole, orbit, and optic nerve. We report a case of an otherwise healthy 42-year-old man who was diagnosed with CD after presenting with acute vision loss from optic perineuritis.

Orbital apex and skull base masses often present with neuro-ophthalmic signs and symptoms. Though the localization of these syndromes and visualization of the responsible lesion on imaging is typically straightforward, definitive diagnosis usually relies on biopsy. Immunohistochemistry is important for categorization and treatment planning. IgG4-related disease is emerging as a pathologically defined inflammatory process that can occur in multiple organ systems. We present two patients with extensive inflammatory mass lesions of the central nervous system with immunohistochemistry positive for IgG4 and negative for ALK-1 as examples of meningeal based IgG4-related inflammatory pseudotumors. In both patients, there was treatment response to mycophenolate mofetil.

The incidence of neurologic complications from bariatric surgery is rising with the prevalence of obesity and the increasing number of bariatric surgeries. We report a 25-year-old woman who developed subacute progressive weakness and areflexia followed by confusion, ophthalmoplegia, and nystagmus following bariatric surgery. While the differential of generalized weakness with altered mental status is broad, vitamin deficiency should be routinely suspected after bariatric surgery to prevent permanent neurological injury. Multifocal neurological dysfunction in our patient represented beriberi and Wernicke's encephalopathy related to vitamin B1 deficiency.

Patients with neuro-ophthalmologic findings and diseases commonly present in the emergency room. This article reviews the approach to acute visual loss, the abnormal optic disc, double vision, and the neuro-ophthalmologic signs of neurologic emergencies, including hydrocephalus, herniation syndromes, vascular lesions, and trauma.

Standard clinical endpoints in multiple sclerosis (MS) studies, such as disability progression defined by the expanded disability status scale (EDSS) and annualized relapse rate, may not fully reflect all aspects of therapeutic benefit experienced by patients. Pivotal studies showed that natalizumab is effective both as monotherapy (AFFIRM study) and in combination with interferon beta-1a (IFNbeta-1a) (SENTINEL study) in patients with relapsing MS. We present AFFIRM and SENTINEL data demonstrating the efficacy of natalizumab on prespecified tertiary endpoints, including extent of confirmed change in EDSS score from baseline, time to sustained progression to EDSS milestone scores, hospitalizations, corticosteroid use, and time to confirmed progression of cognitive deficits. Natalizumab significantly reduced changes in EDSS scores (P < 0.001) and proportion of patients progressing to an EDSS score >/=4.0 (P < 0.001) and >/=6.0 (P = 0.002) compared with placebo. Natalizumab + IFNbeta-1a significantly reduced changes in EDSS scores compared with placebo + IFNbeta-1a (P = 0.011). Based on 0.5 standard deviation change in paced auditory serial addition test-3 score, natalizumab treatment reduced the risk of confirmed progression of cognitive deficits by 43% compared with placebo (HR 0.57 [95% CI 0.37, 0.89], P = 0.013); however, no significant difference between groups was seen in SENTINEL. Natalizumab, both as monotherapy and in combination with IFNbeta-1a, significantly reduced the annualized rate of MS-related hospitalizations (by 64 and 61%, respectively) and the annualized rate of relapses severe enough to require steroid treatment (by 69 and 61%, respectively) compared with placebo and placebo + IFNbeta-1a (P < 0.001). These analyses underline beneficial effects of natalizumab therapy in relapsing MS patients.

BACKGROUND: In the setting of head trauma, progressive bradycardia may raise suspicion for intracranial hypertension, especially when accompanied by pupillary abnormalities or systemic hypertension. METHODS: We describe the case of a patient with concomitant cerebral and ocular trauma who presented with a fixed and dilated pupil and progressive bradycardia due to an oculocardiac reflex. RESULTS: The oculocardiac reflex is an unusual cause of bradycardia due to stimulation of the ophthalmic division of the trigeminal nerve and has been described in a variety of clinical settings. CONCLUSIONS: Clinicians should be aware that the oculocardiac reflex might mimic signs of intracranial hypertension in patients with combined facial and cerebral trauma.