Visual evoked potentials findings in non-affected subjects from a large Brazilian pedigree of 11778 Leber’s hereditary optic neuropathy

Sacai, Paula Yuri; Salomão, Solange Rios; Carelli, Valerio; Pereira, Josenilson Martins; Belfort, Rubens; Sadun, Alfredo A.; Berezovsky, Adriana

doi:10.1007/s10633-010-9241-2

Cited by 24 publications

(15 citation statements)

References 22 publications

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“…This extended LHON family has been characterized in a number of clinical studies. [20][21][22][23][24][25][26] One proband, displaying milder neurodegenerative changes in the optic nerves, died at the age of 59 years from acute myocardial infarction. His younger brother, showing more severe neurodegenerative changes in the optic nerves died at the age of 52 years, also from an acute myocardial infarct.…”

Section: Postmortem Control Tissues (Lhon and Controls)mentioning

confidence: 99%

Mathematically Modeling the Involvement of Axons in Leber's Hereditary Optic Neuropathy

Pan

Ross‐Cisneros

Carelli

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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108

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PURPOSE. Leber's hereditary optic neuropathy (LHON), a mitochondrial disease, has clinical manifestations that reflect the initial preferential involvement of the papillomacular bundle (PMB). The present study seeks to predict the order of axonal loss in LHON optic nerves using the Nerve Fiber Layer Stress Index (NFL-S I ), which is a novel mathematical model. METHODS.Optic nerves were obtained postmortem from four molecularly characterized LHON patients with varying degrees of neurodegenerative changes and three age-matched controls. Tissues were cut in cross-section and stained with pphenylenediamine to visualize myelin. Light microscopic images were captured in 32 regions of each optic nerve. Control and LHON tissues were evaluated by measuring axonal dimensions to generate an axonal diameter distribution map. LHON tissues were further evaluated by determining regions of total axonal depletion. RESULTS.A size gradient was evident in the control optic nerves, with average axonal diameter increasing progressively from the temporal to nasal borders. LHON optic nerves showed an orderly loss of axons, starting inferotemporally, progressing centrally, and sparing the superonasal region until the end. Values generated from the NFL-S I equation fit a linear regression curve (R 2 ¼ 0.97; P < 0.001).CONCLUSIONS. The quantitative histopathologic data from this study revealed that the PMB is most susceptible in LHON, supporting clinical findings seen early in the course of disease onset. The present study also showed that the subsequent progression of axonal loss within the optic nerve can be predicted precisely with the NFL-S I equation. The results presented provided further insight into the pathophysiology of LHON. (Invest Ophthalmol Vis Sci. 2012;53:7608-7617)

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Section: Postmortem Control Tissues (Lhon and Controls)mentioning

confidence: 99%

Mathematically Modeling the Involvement of Axons in Leber's Hereditary Optic Neuropathy

Pan

Ross‐Cisneros

Carelli

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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108

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“…to 30´, while it decreases at other angles. A recent study implied that 15´ or 60´ might be optimal for estimating visual acuity [34] . The different results among studies might reflect the selective conflicting of the testing coefficient and age-differences between the test groups.…”

Section: Features Of the Prvep Responding To Visual Acuity P1mentioning

confidence: 99%

Visual acuity evaluated by pattern-reversal visual-evoked potential is affected by check size/visual angle

Chen

Liu

et al. 2012

Neurosci. Bull.

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Objective To systemically explore the range of visual angles that affect visual acuity, and to establish the relationship between the P1 component (peak latency ~100 ms) of the pattern-reversal visual-evoked potential (PRVEP) and the visual acuity at particular visual angles. Methods Two hundred and ten volunteers were divided into seven groups, according to visual acuity as assessed by the standard logarithmic visual acuity chart (SLD-ii). For each group, the PRVEP components were elicited in response to visual angle presentations at 8°, 4°, 2°, 1°/60´, 30´, 15´, and 7.5´, in the whiteblack chess-board reversal mode with a contrast level of 100% at a frequency of 2 Hz. Visual stimuli were presented monocularly, and 200 presentations were averaged for each block of trials. The early and stable component P1 was recorded at the mid-line of the occipital region (oz) and analyzed with SPSS 13.00. Results (1) oz had the maximum P1 amplitude; there was no significant difference between genders or for interocular comparison in normal controls and subjects with optic myopia. (2) The P1 latency decreased slowly below 30´, then increased rapidly. The P1 amplitude initially increased with check size, and was maximal at ~1° and ~30´. (3) The P1 latency in the group with visual acuity ≤0.2 was significantly different at 8°, 15´ and 7.5´, while the amplitude differed at all visual angles, compared with the group with normal vision. Differences in P1 for the groups with 0.5 and 0.6 acuity were only present at visual angles <1°. (4) Regression analysis showed that the P1 latency and amplitude were associated with visual acuity over the full range of visual angles. There was a moderate correlation at visual angles <30´. Regression equations were calculated for the P1 components and visual acuity, based on visual angle. Conclusion (1) Visual angle should be taken into consideration when exploring the function of the visual pathway, especially visual acuity. A visual angle ~60´ might be appropriate when using PRVEP components to evaluate poor vision and to identify malingerers. (2) increased P1 amplitude and decreased P1 latency were associated with increasing visual acuity, and the P1 components displayed a linear correlation with visual acuity, especially in the range of optimal visual angles. Visual acuity can be deduced from P1 based on visual angle.

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“…1,2,15 Optical coherence tomography (OCT) imaging shows thickening of the retinal nerve fiber layer (RNFL) in asymptomatic carriers 23 and during the acute phase of LHON, 22 in relation to the stress and possibly swelling of RGC axons, preceding cell death. OCT has also shown the Asymptomatic carriers also have subclinical color defects, 25 decreased contrast sensitivity, 26 pattern-reversal visual evoked potential (PRVEP) changes, 27 and fundus abnormalities. 15 We hypothesized that NSE may provide earlier risk detection for LHON conversion than structural changes detected on OCT and functional changes detected by PRVEP.…”

Section: Discussionmentioning

confidence: 99%

Neuron-Specific Enolase Is Elevated in Asymptomatic Carriers of Leber's Hereditary Optic Neuropathy

Yee

Ross‐Cisneros

Lee

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Neuron-specific enolase (NSE) is a biomarker for neuronal stress. Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease affecting retinal ganglion cells (RGC). These RGCs and their axons in the retinal nerve fiber layer (RNFL) and optic nerve head may show subclinical pathology in unaffected mutation carriers, or undergo cell death in affected patients. We hypothesize that increased levels of blood NSE may characterize LHON carriers as a biomarker of ongoing RGC stress.METHODS. Serum was obtained from 74 members of a Brazilian pedigree with LHON carrying the homoplasmic 11778/ND4 mitochondrial DNA mutation. Classified by symptoms and psychophysical metrics, 46/74 patients were unaffected mutation ''carriers,'' 14/74 were ''affected,'' and 14/74 were ''off-pedigree'' controls. Serum NSE levels were determined by ELISA specific for the c subunit of NSE.RESULTS. Serum NSE concentrations in carriers (27.17 6 39.82 lg/L) were significantly higher than affected (5.66 6 4.19 lg/ L; P ¼ 0.050) and off-pedigree controls (6.20 6 2.35 lg/L; P ¼ 0.047). Of the 14/46 (30.4 %) carriers with significantly elevated NSE levels (mean ¼ 75.8 6 42.3 lg/L), 9/14 (64.3%) were male. Furthermore, NSE levels were nearly three times greater in asymptomatic male carriers (40.65 6 51.21 lg/L) than in asymptomatic female carriers (15.85 6 22.27 lg/L; P ¼ 0.034).CONCLUSIONS. Serum NSE levels are higher in LHON carriers compared with affected and off-pedigree individuals. A subgroup of mostly male carriers had significantly elevated serum NSE levels. Thus, male carriers are at higher risk for LHON-related neuronal stress. (Invest Ophthalmol Vis Sci.

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Visual evoked potentials findings in non-affected subjects from a large Brazilian pedigree of 11778 Leber’s hereditary optic neuropathy

Cited by 24 publications

References 22 publications

Mathematically Modeling the Involvement of Axons in Leber's Hereditary Optic Neuropathy

Mathematically Modeling the Involvement of Axons in Leber's Hereditary Optic Neuropathy

Visual acuity evaluated by pattern-reversal visual-evoked potential is affected by check size/visual angle

Neuron-Specific Enolase Is Elevated in Asymptomatic Carriers of Leber's Hereditary Optic Neuropathy

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