Clinical Neurophysiology 126 (2015) 2040–2041
Contents lists available at ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
Letter to the Editor Axonal damage in papilledema linked to idiopathic intracranial hypertension as revealed by multifocal visual evoked potentials
Pattern visual evoked potentials are broadly used to assess functional integrity of the visual system. Cortical magnification potentials generated by full-field stimulation (ffVEP) are almost exclusively derived from the area of the visual cortex dedicated to the central few degrees of the visual field. Therefore, it is not suited to reveal visual disturbances of the peripheral visual field. Multifocal visual evoked potentials (mfVEP) in contrast allow for a more precise investigation of the visual field with varying retinal representation. The VisionsearchÒ mfVEP device applies simultaneous multi-focal stimulation of 56 segments of the visual field (24° of eccentricity) via a 68 s pseudorandom sequence and recording a 2-channel visual response using a custom designed occipital cross electrode holder which predetermines the four occipital electrode positions (Klistorner and Graham, 2001). Cross-correlation of the event-related response with the sequence itself allows for recording of evoked potentials in the nanovolt range, which originate from monocular stimulation of distinct areas of the visual field. We present the case of a 25-year old female with a 15 months history of visual blurring of her right eye without any further neurological symptoms. The data in this report were acquired as a part of a clinical study, which was approved by the local ethical committee. Written informed consent was given by the patient prior to enrollment. Bilateral optic nerve head (ONH) edema was diagnosed on formal fundoscopy and optical coherence tomography (OCT, Fig. 1A/B). Visual acuity was 100% on both eyes and there was no relative afferent pupillary deficit. Her body mass index was 27. A custom automated 3D-ONH-segmentation analysis (Kaufhold et al., 2012) of the OCT data revealed an optic disc volume of 4.0 mm3 of the right and 3.9 mm3 of the left eye which was above 2.5 standard deviations of a normative collective of 26 healthy controls (>2.5 mm3). Assessment of the visual field with a Goldmann perimeter and an OctopusÒ device revealed a marked enlargement of the physiological blind spot of the right eye with related temporal scotoma as well as an incomplete centrocecal scotoma of the left eye (Fig. 1C). Abnormalities of the anterior eye segment were excluded via slit lamp examination. Increased cerebrospinal fluid pressure with other than that normal findings (>50 cm H2O) and regular results of cranial MRI excluding cerebral venous sinus thrombosis in venous MR-angiography indicated idiopathic intracranial hypertension. Medication-associated elevated intracranial pressure was ruled out; she was not on regular treatment. While ffVEP generated results within normal limits (Fig. 1D, right eye (OD): P100 latency 103.2 ms, P100/N140
amplitude 5.2 lV; left eye (OS): P100 latency 102.6 ms, P100/N140 amplitude 4.9 lV), assessment with the VisionsearchÒ mfVEP device objectified reduced amplitudes for the temporal quadrant of the right-compared to the left eye but no difference in latency (Fig. 1E and F). While total amplitudes between both eyes differed by only 6.5%, local amplitudes around the blind spot were significantly lower on the symptomatic right eye (Cutoff for significance: 50% asymmetry). This finding suggests a reduced axonal function and shows that mfVEP but not ffVEP are suitable to objectify mild visual impairment due to papilledema, which spare the central visual field. The advantage of the mfVEP approach over the Goldmann perimeter alone is that mfVEPs provide an objective and well quantifiable measure of visual field deficits allowing the differentiation between demyelination and axonal loss. Using the VisionsearchÒ device, the assessments are easy to perform and show a high reproducibility. The disadvantages are that rather long acquisition times of around 30–45 min are needed and that the device is rather costly. Furthermore, while amplitude differences between the two eyes of healthy subjects are generally low and virtually never attain 50%, amplitudes between subjects differ to a much higher degree. Therefore, amplitude comparisons between both eyes represent a much more sensitive measure than the comparison to normative collectives. In line with this, the comparison to a collective of nine age matched healthy controls revealed no significant reductions (>2 standard deviations below the mean) of the VEP amplitudes for any quadrant or sector of either of our patient’s eyes. Our case indicates that intracranial hypertension may lead to axonal damage rather than demyelination. It is however difficult to speculate whether the nature of amplitude reduction reflects conduction block (and therefore, potentially reversible) or is due to permanent axonal loss. Conflict of Interest The authors declare no conflicts of interest or financial disclosures related to this case report except for Alexander U. Brandt who is named as co-inventor on a patent application encompassing the optic nerve head volume algorithm. References Kaufhold F, Kadas EM, Schmidt C, Kunt H, Hoffmann J, Zimmermann H, et al. Optic nerve head quantification in idiopathic intracranial hypertension by spectral domain OCT. PLoS One 2012;7:e36965. Klistorner AI, Graham SL. Electroencephalogram-based scaling of multifocal visual evoked potentials: effect on intersubject amplitude variability. Invest Ophthalmol Vis Sci 2001;42:2145–52.
http://dx.doi.org/10.1016/j.clinph.2014.12.014 1388-2457/Ó 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Letter to the Editor / Clinical Neurophysiology 126 (2015) 2040–2041
left eye
2041
Christian J. Hartmann Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
right eye
A
Alexander I. Klistorner Department of Ophthalmology, Save Sight Institute, University of Sydney, Australia Alexander U. Brandt NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Charité – Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany
B
Katharina Schroeder NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Charité – Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany
C
Robert Kolbe Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
D N75
N140
N75
Eva Cohn Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
N140
Norbert Goebels Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
P100 P100 30 ms/Div
30 ms/Div
E
Rainer Guthoff Department of Ophthalmology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany Orhan Aktas Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
F
Hans-Peter Hartung Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
⇑
Philipp Albrecht Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
Fig. 1. Multimodal assessment of bilateral papilledema of the right eye. (A) Fundoscopy revealed the characteristic swelling of the optic discs. (B) Optic coherence tomography demonstrated a significantly increased volume of the optic disc on both sides. (C) Manual kinetic Goldmann perimetry (isopters III/4e, I/4e, I/ 2e, illustrated in light to dark blue color respectively) and static (stippling of central visual fields with target I/2e and I/1e) indicated an enlargement of the blind spot (illustrated as red area) of the right eye and central skotoma for target I/2e. Green spots represent static perception of target I/2e, red spots represent missing target perception mainly located in the temporal field. In the left eye a centrocecal skotoma of isopter I/2e was revealed. (D) Visual evoked potentials gained from fullfield stimulation provided regular latencies and amplitudes. (E) Multifocal visual evoked potentials in contrast suggested a reduction of amplitudes generated from stimulation of the temporal quadrant of the right eye, which could be confirmed by symmetry analysis of both eyes (F). Segments are visually coded to illustrate the difference of relative amplitudes between the left and the right eye (black: >50%; dark gray: 37.5–50%, medium gray: 25–37.5%, light gray: 12.5–25%, white:
Contents lists available at ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
Letter to the Editor Axonal damage in papilledema linked to idiopathic intracranial hypertension as revealed by multifocal visual evoked potentials
Pattern visual evoked potentials are broadly used to assess functional integrity of the visual system. Cortical magnification potentials generated by full-field stimulation (ffVEP) are almost exclusively derived from the area of the visual cortex dedicated to the central few degrees of the visual field. Therefore, it is not suited to reveal visual disturbances of the peripheral visual field. Multifocal visual evoked potentials (mfVEP) in contrast allow for a more precise investigation of the visual field with varying retinal representation. The VisionsearchÒ mfVEP device applies simultaneous multi-focal stimulation of 56 segments of the visual field (24° of eccentricity) via a 68 s pseudorandom sequence and recording a 2-channel visual response using a custom designed occipital cross electrode holder which predetermines the four occipital electrode positions (Klistorner and Graham, 2001). Cross-correlation of the event-related response with the sequence itself allows for recording of evoked potentials in the nanovolt range, which originate from monocular stimulation of distinct areas of the visual field. We present the case of a 25-year old female with a 15 months history of visual blurring of her right eye without any further neurological symptoms. The data in this report were acquired as a part of a clinical study, which was approved by the local ethical committee. Written informed consent was given by the patient prior to enrollment. Bilateral optic nerve head (ONH) edema was diagnosed on formal fundoscopy and optical coherence tomography (OCT, Fig. 1A/B). Visual acuity was 100% on both eyes and there was no relative afferent pupillary deficit. Her body mass index was 27. A custom automated 3D-ONH-segmentation analysis (Kaufhold et al., 2012) of the OCT data revealed an optic disc volume of 4.0 mm3 of the right and 3.9 mm3 of the left eye which was above 2.5 standard deviations of a normative collective of 26 healthy controls (>2.5 mm3). Assessment of the visual field with a Goldmann perimeter and an OctopusÒ device revealed a marked enlargement of the physiological blind spot of the right eye with related temporal scotoma as well as an incomplete centrocecal scotoma of the left eye (Fig. 1C). Abnormalities of the anterior eye segment were excluded via slit lamp examination. Increased cerebrospinal fluid pressure with other than that normal findings (>50 cm H2O) and regular results of cranial MRI excluding cerebral venous sinus thrombosis in venous MR-angiography indicated idiopathic intracranial hypertension. Medication-associated elevated intracranial pressure was ruled out; she was not on regular treatment. While ffVEP generated results within normal limits (Fig. 1D, right eye (OD): P100 latency 103.2 ms, P100/N140
amplitude 5.2 lV; left eye (OS): P100 latency 102.6 ms, P100/N140 amplitude 4.9 lV), assessment with the VisionsearchÒ mfVEP device objectified reduced amplitudes for the temporal quadrant of the right-compared to the left eye but no difference in latency (Fig. 1E and F). While total amplitudes between both eyes differed by only 6.5%, local amplitudes around the blind spot were significantly lower on the symptomatic right eye (Cutoff for significance: 50% asymmetry). This finding suggests a reduced axonal function and shows that mfVEP but not ffVEP are suitable to objectify mild visual impairment due to papilledema, which spare the central visual field. The advantage of the mfVEP approach over the Goldmann perimeter alone is that mfVEPs provide an objective and well quantifiable measure of visual field deficits allowing the differentiation between demyelination and axonal loss. Using the VisionsearchÒ device, the assessments are easy to perform and show a high reproducibility. The disadvantages are that rather long acquisition times of around 30–45 min are needed and that the device is rather costly. Furthermore, while amplitude differences between the two eyes of healthy subjects are generally low and virtually never attain 50%, amplitudes between subjects differ to a much higher degree. Therefore, amplitude comparisons between both eyes represent a much more sensitive measure than the comparison to normative collectives. In line with this, the comparison to a collective of nine age matched healthy controls revealed no significant reductions (>2 standard deviations below the mean) of the VEP amplitudes for any quadrant or sector of either of our patient’s eyes. Our case indicates that intracranial hypertension may lead to axonal damage rather than demyelination. It is however difficult to speculate whether the nature of amplitude reduction reflects conduction block (and therefore, potentially reversible) or is due to permanent axonal loss. Conflict of Interest The authors declare no conflicts of interest or financial disclosures related to this case report except for Alexander U. Brandt who is named as co-inventor on a patent application encompassing the optic nerve head volume algorithm. References Kaufhold F, Kadas EM, Schmidt C, Kunt H, Hoffmann J, Zimmermann H, et al. Optic nerve head quantification in idiopathic intracranial hypertension by spectral domain OCT. PLoS One 2012;7:e36965. Klistorner AI, Graham SL. Electroencephalogram-based scaling of multifocal visual evoked potentials: effect on intersubject amplitude variability. Invest Ophthalmol Vis Sci 2001;42:2145–52.
http://dx.doi.org/10.1016/j.clinph.2014.12.014 1388-2457/Ó 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Letter to the Editor / Clinical Neurophysiology 126 (2015) 2040–2041
left eye
2041
Christian J. Hartmann Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
right eye
A
Alexander I. Klistorner Department of Ophthalmology, Save Sight Institute, University of Sydney, Australia Alexander U. Brandt NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Charité – Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany
B
Katharina Schroeder NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Charité – Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany
C
Robert Kolbe Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
D N75
N140
N75
Eva Cohn Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
N140
Norbert Goebels Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
P100 P100 30 ms/Div
30 ms/Div
E
Rainer Guthoff Department of Ophthalmology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany Orhan Aktas Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
F
Hans-Peter Hartung Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
⇑
Philipp Albrecht Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
Fig. 1. Multimodal assessment of bilateral papilledema of the right eye. (A) Fundoscopy revealed the characteristic swelling of the optic discs. (B) Optic coherence tomography demonstrated a significantly increased volume of the optic disc on both sides. (C) Manual kinetic Goldmann perimetry (isopters III/4e, I/4e, I/ 2e, illustrated in light to dark blue color respectively) and static (stippling of central visual fields with target I/2e and I/1e) indicated an enlargement of the blind spot (illustrated as red area) of the right eye and central skotoma for target I/2e. Green spots represent static perception of target I/2e, red spots represent missing target perception mainly located in the temporal field. In the left eye a centrocecal skotoma of isopter I/2e was revealed. (D) Visual evoked potentials gained from fullfield stimulation provided regular latencies and amplitudes. (E) Multifocal visual evoked potentials in contrast suggested a reduction of amplitudes generated from stimulation of the temporal quadrant of the right eye, which could be confirmed by symmetry analysis of both eyes (F). Segments are visually coded to illustrate the difference of relative amplitudes between the left and the right eye (black: >50%; dark gray: 37.5–50%, medium gray: 25–37.5%, light gray: 12.5–25%, white:
