Faculty Bibliography

PURPOSE: To determine the relationships among age, unilateral versus bilateral simultaneous presentation, magnetic resonance imaging (MRI) lesions, and the risk of multiple sclerosis (MS) in children with optic neuritis. METHODS: A systematic literature review and meta-analysis were performed by the use of a MEDLINE search to identify published studies containing individual patient data for children with optic neuritis. Age, laterality (unilateral vs bilateral simultaneous optic neuritis), presence of brain MRI abnormalities, and development of MS were recorded. Logistic regression was used to determine the relationships among these parameters. RESULTS: Fourteen studies met inclusion criteria. Data for 223 patients (age range 2-17.8 years) were analyzed. Unilateral optic neuritis occurred more frequently in older children but was not associated with an increased risk of MS, after adjusting for age (odds ratio [OR] = 1.9, P = 0.11; 95% confidence interval [CI], 0.9-4.3). For every 1-year increase in age, the odds of developing MS increased by 32% (OR = 1.3, P = 0.005; 95% CI, 1.1-1.6, adjusted for the presence of MRI lesions). The risk of MS was greater in children with abnormal brain MRI scans at presentation compared with normal MRIs (OR = 28.0, P < 0.001, 95% CI, 6.3-125.1, adjusted for age). CONCLUSIONS: The relationship between unilateral and bilateral optic neuritis and the development of MS is dependent on age. Older children and those with brain MRI abnormalities at presentation, are at greater risk for MS. Long-term follow-up of children with optic neuritis is needed to establish the true risk for the development of MS.

BACKGROUND: Neuronal loss in the retina has been demonstrated pathologically in eyes of patients with multiple sclerosis (MS). In vivo, MS eyes have reduced total macular volumes by optical coherence tomography (OCT). Using a high-resolution spectral-domain OCT, this pilot study used a manual method to measure ganglion cell layer (GCL) volumes and to determine the relation of these volumes to visual function in MS eyes. METHODS: Sixteen eyes of 8 patients with MS and 8 eyes of 5 disease-free control participants were studied using fast macular OCT scans performed with Spectralis OCT (Heidelberg Engineering). Visual function tests of low-contrast letter acuity and high-contrast visual acuity were administered. RESULTS: MS patient eyes had significantly lower GCL volumes than the control eyes (P < 0.001 vs controls, generalized estimating equation regression models accounting for age and within-patient intereye correlations). Within the MS group, eyes with a history of optic neuritis (ON, n = 4) had significantly lower GCL volumes than MS eyes with no ON history (P < 0.001). In contrast to measures of high-contrast visual acuity (P = 0.14), decreased GCL volumes were associated with worse performance on low-contrast letter acuity testing (P = 0.003). CONCLUSIONS: This pilot study has characterized thinning of the GCL in MS patient eyes, particularly in those with a history of acute ON, which corresponded to a reduced performance on low-contrast letter acuity testing. Studies utilizing computerized segmentation algorithms will continue to facilitate the detection of GCL loss on a larger scale and provide important information in vivo on the role and timing of neuronal vs axonal loss in MS eyes.

PURPOSE: To determine the magnitudes of binocular summation for low- and high-contrast letter acuity in a multiple sclerosis (MS) cohort, and to characterize the roles that MS disease, age, interocular difference in acuity, and a history of optic neuritis have on binocular summation. The relation between binocular summation and monocular acuities and vision-specific quality of life (QoL) was also examined. DESIGN: Cross-sectional observational study. METHODS: Low-contrast acuity (2.5% and 1.25% contrast) and high-contrast visual acuity (VA) were assessed binocularly and monocularly in patients and disease-free controls at 3 academic centers. Binocular summation was calculated as the difference between the binocular and better eye scores. QoL was measured using the 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) and the 10-item neuro-ophthalmic supplement. The relation of the degree of binocular summation to monocular acuity, clinical history of acute optic neuritis, age, interocular acuity difference, and QoL was determined. RESULTS: Binocular summation was demonstrated at all contrast levels, and was greatest at the lowest level (1.25%). Increasing age (P < .0001), greater interocular differences in acuity (P < .0001), and prior history of optic neuritis (P = .015) were associated with lower magnitudes of binocular summation; binocular inhibition was seen in some of these patients. Higher magnitudes of summation for 2.5% low-contrast acuity were associated with better scores for the NEI VFQ-25 (P = .02) and neuro-ophthalmic supplement (P = .03). CONCLUSION: Binocular summation of acuity occurs in MS but is reduced by optic neuritis, which may lead to binocular inhibition. Binocular summation and inhibition are important factors in the QoL and visual experience of MS patients, and may explain why some prefer to patch or close 1 eye in the absence of diplopia or ocular misalignment.

BACKGROUND: Based upon scarce clinical data in humans and experimental findings in animal studies, it has been postulated that the ascending gustatory projection from the nucleus tractus solitarii courses ipsilaterally through the pons and midbrain to the ipsilateral ventral posteromedial nucleus. Thus, it has been assumed that ischemic lesions affecting the secondary projection gustatory fibers would cause ipsilateral taste disorders. DESCRIPTION OF CASE: We report a case of bilateral ageusia following an acute right midbrain and thalamic infarction affecting the ipsilateral central trigeminal tract and ventral posteromedial nucleus in a right-handed man. CONCLUSION: The present case indicates that, in contrast to animal data, some secondary projection gustatory fibers may cross in humans and consequently unilateral right-sided posterior circulation ischemic lesions can cause bilateral gustatory deficits.

OBJECTIVE: To determine whether weight gain is associated with recurrence in idiopathic intracranial hypertension (IIH). METHODS: Medical records of adult patients with IIH seen between 1993 and 2009 at 2 university hospitals were reviewed to identify those with and without recurrence. Patients with documented height and weight at presentation and at subsequent visits were studied. The Wilcoxon rank sum test was used to compare mean body mass index (BMI) and percent weight change between the groups of patients with recurrence and without recurrence. The signed-rank test was used for comparing BMI within groups at the various time points. RESULTS: Fifty women with IIH were included in the analyses: 26 had IIH recurrence and 24 did not. Patients with recurrence had greater BMI at the time of recurrence compared to BMI at diagnosis (p = 0.02, signed-rank test). They also demonstrated a greater degree of weight gain between initial resolution and recurrence (BMI change +2.0 kg/m(2) [-1.5 to 10.8]) compared to patients without recurrence (-0.75 kg/m(2) [-35 to 3.6], p = 0.0009, Wilcoxon rank sum test). Patients without recurrence demonstrated stable weights (0%[95% CI -9.6 to 10.1%]), while patients with recurrence demonstrated a 6% weight gain ([-3.5 to 40.2%], p = 0.005), with an average rate of BMI gain of 1.3 kg/m(2)/year vs -0.96 kg/m(2)/year in those without recurrence. CONCLUSION: Patients with IIH recurrence had significant increases in BMI compared to patients without recurrence in this cohort. Patients with resolved IIH should be advised that weight gain may be a risk factor for IIH recurrence.

OBJECTIVE: Sports-related concussion has received increasing attention as a cause of short- and long-term neurologic symptoms among athletes. The King-Devick (K-D) test is based on measurement of the speed of rapid number naming (reading aloud single-digit numbers from 3 test cards), and captures impairment of eye movements, attention, language, and other correlates of suboptimal brain function. We investigated the K-D test as a potential rapid sideline screening for concussion in a cohort of boxers and mixed martial arts fighters. METHODS: The K-D test was administered prefight and postfight. The Military Acute Concussion Evaluation (MACE) was administered as a more comprehensive but longer test for concussion. Differences in postfight K-D scores and changes in scores from prefight to postfight were compared for athletes with head trauma during the fight vs those without. RESULTS: Postfight K-D scores (n = 39 participants) were significantly higher (worse) for those with head trauma during the match (59.1 +/- 7.4 vs 41.0 +/- 6.7 seconds, p < 0.0001, Wilcoxon rank sum test). Those with loss of consciousness showed the greatest worsening from prefight to postfight. Worse postfight K-D scores (r(s) = -0.79, p = 0.0001) and greater worsening of scores (r(s) = 0.90, p < 0.0001) correlated well with postfight MACE scores. Worsening of K-D scores by >/=5 seconds was a distinguishing characteristic noted only among participants with head trauma. High levels of test-retest reliability were observed (intraclass correlation coefficient 0.97 [95% confidence interval 0.90-1.0]). CONCLUSIONS: The K-D test is an accurate and reliable method for identifying athletes with head trauma, and is a strong candidate rapid sideline screening test for concussion.

A 56-year-old man developed a pupil-involving left third nerve palsy. Imaging studies of the brain and intracranial vessels were normal. Neurological examination demonstrated a sensory polyneuropathy and mild distal weakness. Nerve conduction studies showed prolonged distal motor latencies. An enzyme-linked immunosorbent assay test detected high titers of anti-myelin-associated glycoprotein (MAG) antibodies. The patient improved with prednisone and rituximab treatment. Anti-MAG neuropathy should be considered when evaluating a patient with an undiagnosed cranial neuropathy, especially in the setting of a sensory neuropathy.

OBJECTIVE: To report the first histopathologic description of optic nerve demyelination from tacrolimus (FK 506) toxicity in the absence of toxic levels of tacrolimus in a patient presenting with asymmetric bilateral visual loss after 5 years of tacrolimus therapy. PATIENTS: We report a patient status post cardiac and renal transplantation who developed severe, progressive and asynchronous bilateral visual loss after prolonged treatment with tacrolimus. Orbital MRI showed an enlarged left optic nerve that enhanced with gadolinium. CONCLUSION: After extensive negative work up, biopsy of one optic nerve was performed. Microscopic analysis showed extensive demyelination in the absence of vasculitis, neoplastic or infectious etiologies. Our patient illustrates that demyelination of the optic nerve causing asynchronous vision loss can be associated with tacrolimus toxicity in the absence of toxic drug levels.

The efficient organization of the human afferent visual system meets enormous computational challenges. Once visual information is received by the eye, the signal is relayed by the retina, optic nerve, chiasm, tracts, lateral geniculate nucleus, and optic radiations to the striate cortex and extrastriate association cortices for final visual processing. At each stage, the functional organization of these circuits is derived from their anatomical and structural relationships. In the retina, photoreceptors convert photons of light to an electrochemical signal that is relayed to retinal ganglion cells. Ganglion cell axons course through the optic nerve, and their partial decussation in the chiasm brings together corresponding inputs from each eye. Some inputs follow pathways to mediate pupil light reflexes and circadian rhythms. However, the majority of inputs arrive at the lateral geniculate nucleus, which relays visual information via second-order neurons that course through the optic radiations to arrive in striate cortex. Feedback mechanisms from higher cortical areas shape the neuronal responses in early visual areas, supporting coherent visual perception. Detailed knowledge of the anatomy of the afferent visual system, in combination with skilled examination, allows precise localization of neuropathological processes and guides effective diagnosis and management of neuro-ophthalmic disorders.