Original Paper - Travail original ■Originalarbeit
Ophthalmologies 1992:205:194-203
Benedetto Falsinia Ciro TamburrelliJ Vittorio Porciattib Carmelo Anilec Giovanni Porrelloa Nunzio MangiohP
Pattern Electroretinograms and Visual Evoked Potentials in Idiopathic Intracranial Hypertension
Key Words
Abstract
Pattern electrorctinogram Pattern visual evoked potentials Spatial frequency Idiopathic intracranial hypertension Papilledema
A subclinical visual dysfunction can be detected by psycho physical methods in early-stage papilledema associated with idiopathic intracranial hypertension (11H). We recorded stea dy-state pattern electroretinograms (PERGs) and visual evoked potentials (VEPs) to sinusoidal gratings of variable spatial frequency [0.6,1.0,1.4,2.2and4.8cycles/degree(cpd)] in 18 patients with IIH and early papilledema and in 21 agematched controls. Spatial frequency selective reductions in the mean PERG (at 1-4.8 cpd) and VEP (at 4.8 cpd) amplitudes were found in patients in comparison with controls. The re sponse functions of amplitude versus spatial frequency of pa tients' PERG and VEP displayed a low-pass shape, whereas in normal subjects PERG and VEP functions showed a band pass and a high-pass shape, respectively. PERG and VEP ab normalities were found in 14 (77.7%) and 10 (55.5%) out of 18 patients, respectively. Most of these abnormalities involved only selected spatial frequencies (1.4-4.8 cpd). These results indicate spatial-frequency-dependent functional losses on both PERG and VEP in early papilledema, and suggest a po tential value of these responses for detecting subtle visual ab normalities in IIH.
Presented in pari at the Annual M eeting of the Association for Research in Vision and O phthalmology Sarasota. Fla.. USA. April 28-M ay 3. 1991.
Received: July H». 1992 Accepted: July 14. 1992
Benedetto Falsini. MD Eye Clinic. Catholic University Lgo F. Vito I 1-00168 Rome (Italy)
■ 1992 S. Karger AG. Basel 0030-3755AJ2/ 2054- 0194 S 2.75/0
Downloaded by: Lund University Libraries 130.235.66.10 - 7/2/2017 3:50:06 AM
Eye Clinic. Catholic University. Rome, Institute of Neurophysiology, CN R. Pisa. Institute of Neurosurgery, Catholic University. Rome. Italy
In this study, we simultaneously recorded PERGs and VEPs as a function of the stimulus spatial frequency in 1IH patients with uncom plicated papilledema (i.e. no or minimal vi sual abnormalities with standard clinical ex amination) as well as in age-matched normal subjects. The results showed spatial-frequen cy-dependent losses in both PERGs and VEPs associated with early stages of IIH.
Materials and Methods Patients
Eighteen patients (4 males. 14 females: mean age: 39.2 years: SD: 11.2: range: 22-94) with IIH and un complicated papilledema participated in this study. Criteria for IIH diagnosis [18] included: (1) initial lumbar cerebrospinal fluid (CSF) pressure >200 m m H ;0 ;) (2) normal or small ventricles without evi dence of a space-occupying lesion (determined by CT scan): (3) normal neurological examination (except for nerve VI weakness), and (4) normal CSF analysis. All patients underwent complete neuro-ophthalmological examination and were selected on the basis of their having normal corrected visual acuity (20/20 or better; refractive errors, when present, were comprised be tween ± 3 sp h . and ±1 cvl. and fully corrected for the PERG and VEP recordings), no or minimal visual field defects by Goldmann perimetry, no afferent pupillary defect and early optic disk edema. Visual field defects, determined with kinetic and static techniques, were graded according to the criteria proposed by Wall and George |2| (grade 0: normal field, to grade 5: blinding field loss), and all patients were of grade 0 or 1 (slight isopter constriction or relative paracentral scotomas that do not involve fixation). Optic disk edema was evaluated according to the staging scheme proposed by Frisen [19| (stage 0: normal disk, to stage 5: marked disk swelling with anterior expansion of the nerve head), and allcases were of stage 1(blurring of the nasal border of the disk) or 2 (blurring of the nasal and tem poral border). Intraocular pressures, measured by ap planation tonometry, ranged from 15 to 18 mm Hg. All patients were tested before starting any treatment. Clinical data of individual patients are reported in ta ble 1. All patients had typical ocular and neurological symptoms of IIH [20]. The median of the duration of symptoms was 14 months (range: 3-90). No concom itant ocular diseases were clinically evident. Concom-
195
Downloaded by: Lund University Libraries 130.235.66.10 - 7/2/2017 3:50:06 AM
Visual sensory abnormalities can be de tected in early stages of idiopathic intracranial hypertension (IlH) [1,2] by means of contrast sensitivity testing [2-6] and automated thresh old perimetry [2. 7. 8]. Abnormalities in con trast sensitivity have been reported to nonuniformly affect the spatial frequency spectrum, being more marked at low [6] and medium [2, 4, 5] than at higher spatial frequencies (i.e. sensitivity is more altered for coarse-medium than for fine patterns). Early perimetric de fects commonly include constriction, inferonasal loss and arcuate scotomas [2], Visual loss in 11H is associated with a swell ing of the optic nerve head (i.e. papilledema) due to raised intracranial pressure. Studies in monkeys with experimentally induced papil ledema [9.10] have demonstrated that edema involves swelling of ganglion cell axons ante rior to the lamina cribrosa. Axonal swelling may be secondary to compression-induced is chemia [11], or may reflect a stasis of the ax oplasmic flow in the optic nerve head [12]. Early visual loss in 11H patients with papille dema has been related to a dysfunction of reti nal ganglion cells, owing to ischemic and/or mechanical damage [2. 6]. The combined assessment of electroretinograms and visually evoked potentials in re sponse to contrast-reversing patterns (PERGs and VEPs, respectively) has proven to be use ful in the diagnosis of optic nerve disease [13— 15], The PERG. unlike the flash ERG. is thought to originate in inner retinal layers, and has been reported to be correlated with ganglion cell activity [16. 17]. A combined PERG and VEP assessment may help to dis tinguish. at least in part, inner retina from postretina dysfunctions. Furthermore. PERG and VEP recordings for stimuli of different spatial frequencies may help to detect selec tive functional losses which can be found in the early stages of some optic nerve diseases [ 14].
Table 1. Clinical data of ÎIH patients Patient
Sex
i 2 3 4 5 6 7
F F F F VI M F
8
Age
Symptoms ocular
neurological
Duration of symptoms months
64 36 28 54 32 50 44
TVO TVO BV BV TV O .BV TVO TVO. BV. photopsi a
headache headache headache headache headache headache headache
42 24 6 24 10 9 25
1 II 1) 0 0 1 1
I 0 0 0 0 1 1
1 1 1 1 1 2 2
-)
ES
hyper tension. obesitv
F
35
BV. TVO
12
1
1
2
2
ES
—
9
M
22
TV O .BV
36
1
1
2
2
10
F
46
BV
35
1
1
1
i
ES
11 12
F F
55 26
TVO. BV TV O .BV
36 36
1 1
1 1
2 2
2 2
ES
13 14
F F
41 35
9 14
1
1 0
2 1
2 0
-
-
0
ES
—
15 16
F F
40 33
—
17 18
M F
35 29
TVO TVO. BV. photopsia TVO TVO. diplopia TVO
headache diplopia headache. tinnitus. paraesthesiae headache. diplopia headache headache. tinnitus headache headache
OD
OS
OD
OS
1 1 1 1 1
Radiologic findings
Systemic diseases
ES
—
-
ES -
-
headache headache
6 90
0
0 0
1 1
1 1
-
0
headache headache
12 3
1 0
1
2
0
1
2 1
ES ES
ES
obesih -
obesitx anémia
-
TVO = Transient visual obscurations: BV = blurred vision: ES = empty sella. Goldmann perimetry: grade 0 or I according to the classification proposed by Wall and George. 1991 [2], Grade l or 2. according to the papilledema staging scheme proposed by Frisen, I982 119].
itant systemicdieseases, such asobesitv. arterial hyper tension and anemia, were present in some cases. Twelve patients had evidence on CT and/or magnetic resonance imaging of an empty sella. Twenty-one control subjects (6 males. 15 females: mean age: 38.4 years: SD: 12: range: 22-65), with nor mal general and neuro-ophthalmological examination, were also tested. Informed consent was obtained from each subject or patient after the nature of the technique and the aim of our research were fully explained to them.
loo
Optic disk
Methods Visual stimuli were vertical sinusoidal gratings of variable spatial frequency (0.6.1.0.1.4.2.2and4.8cpd), electronically generated on a high-resolution (Mangoni. Pisa-I) TV monitor (85 cd/nr mean luminance. 56% contrast) and square-wave modulated in counterphase at 8 Hz (16 rps). Subjects fixated monocularly, with natural pupils, on the center of the stimulator from a distance of 57 cm (stimulation field size: 24°x 14°). Pu pil sizes were measured, and no differences were ob served between patients and controls. PERGs were
Falsini/Tamburrelli/Porciatti/Anile/ Porrello/Mangiola
Pattern ERGs and VEPs in Early Papilledema
Downloaded by: Lund University Libraries 130.235.66.10 - 7/2/2017 3:50:06 AM
'
-
Visual field1
Results
In figure la and b, representative examples of steady-state PERGs and VEPs obtained in response to 1 cpd sinusoidal gratings from a control subject and from a patient with IIH are shown. It can be noted that both responses display an approximately sinusoidal wave form with a temporal period of 62.5 ms, corre sponding to the reversal frequency. In the same figure, the second harmonic compo nents of PERG and VEP responses, isolated by a discrete Fourier series, are also presented on polar plots. Each point of the plots repre sents a vector whose length and orientation indicate the component (peak-to-peak) am plitude and phase angle, respectively. Figure 2 shows the mean (±SEM ) PERG amplitude and phase values plotted as a func tion of spatial frequency for normal subjects and patients. In normal subjects, the mean amplitude showed a peak at 1.4 cpd and atten uation at higher and lower spatial frequencies. In IIH patients, the mean PERG amplitude was reduced, compared to that of controls, at intermediate and high spatial frequencies (14.8 cpd). At the lowest spatial frequency (0.6cpd), mean amplitudes of both groups were similar. A two-way Anova indicated a significant main effect for group [F(l, 37) = 9.02, p
Ophthalmologies 1992:205:194-203
Benedetto Falsinia Ciro TamburrelliJ Vittorio Porciattib Carmelo Anilec Giovanni Porrelloa Nunzio MangiohP
Pattern Electroretinograms and Visual Evoked Potentials in Idiopathic Intracranial Hypertension
Key Words
Abstract
Pattern electrorctinogram Pattern visual evoked potentials Spatial frequency Idiopathic intracranial hypertension Papilledema
A subclinical visual dysfunction can be detected by psycho physical methods in early-stage papilledema associated with idiopathic intracranial hypertension (11H). We recorded stea dy-state pattern electroretinograms (PERGs) and visual evoked potentials (VEPs) to sinusoidal gratings of variable spatial frequency [0.6,1.0,1.4,2.2and4.8cycles/degree(cpd)] in 18 patients with IIH and early papilledema and in 21 agematched controls. Spatial frequency selective reductions in the mean PERG (at 1-4.8 cpd) and VEP (at 4.8 cpd) amplitudes were found in patients in comparison with controls. The re sponse functions of amplitude versus spatial frequency of pa tients' PERG and VEP displayed a low-pass shape, whereas in normal subjects PERG and VEP functions showed a band pass and a high-pass shape, respectively. PERG and VEP ab normalities were found in 14 (77.7%) and 10 (55.5%) out of 18 patients, respectively. Most of these abnormalities involved only selected spatial frequencies (1.4-4.8 cpd). These results indicate spatial-frequency-dependent functional losses on both PERG and VEP in early papilledema, and suggest a po tential value of these responses for detecting subtle visual ab normalities in IIH.
Presented in pari at the Annual M eeting of the Association for Research in Vision and O phthalmology Sarasota. Fla.. USA. April 28-M ay 3. 1991.
Received: July H». 1992 Accepted: July 14. 1992
Benedetto Falsini. MD Eye Clinic. Catholic University Lgo F. Vito I 1-00168 Rome (Italy)
■ 1992 S. Karger AG. Basel 0030-3755AJ2/ 2054- 0194 S 2.75/0
Downloaded by: Lund University Libraries 130.235.66.10 - 7/2/2017 3:50:06 AM
Eye Clinic. Catholic University. Rome, Institute of Neurophysiology, CN R. Pisa. Institute of Neurosurgery, Catholic University. Rome. Italy
In this study, we simultaneously recorded PERGs and VEPs as a function of the stimulus spatial frequency in 1IH patients with uncom plicated papilledema (i.e. no or minimal vi sual abnormalities with standard clinical ex amination) as well as in age-matched normal subjects. The results showed spatial-frequen cy-dependent losses in both PERGs and VEPs associated with early stages of IIH.
Materials and Methods Patients
Eighteen patients (4 males. 14 females: mean age: 39.2 years: SD: 11.2: range: 22-94) with IIH and un complicated papilledema participated in this study. Criteria for IIH diagnosis [18] included: (1) initial lumbar cerebrospinal fluid (CSF) pressure >200 m m H ;0 ;) (2) normal or small ventricles without evi dence of a space-occupying lesion (determined by CT scan): (3) normal neurological examination (except for nerve VI weakness), and (4) normal CSF analysis. All patients underwent complete neuro-ophthalmological examination and were selected on the basis of their having normal corrected visual acuity (20/20 or better; refractive errors, when present, were comprised be tween ± 3 sp h . and ±1 cvl. and fully corrected for the PERG and VEP recordings), no or minimal visual field defects by Goldmann perimetry, no afferent pupillary defect and early optic disk edema. Visual field defects, determined with kinetic and static techniques, were graded according to the criteria proposed by Wall and George |2| (grade 0: normal field, to grade 5: blinding field loss), and all patients were of grade 0 or 1 (slight isopter constriction or relative paracentral scotomas that do not involve fixation). Optic disk edema was evaluated according to the staging scheme proposed by Frisen [19| (stage 0: normal disk, to stage 5: marked disk swelling with anterior expansion of the nerve head), and allcases were of stage 1(blurring of the nasal border of the disk) or 2 (blurring of the nasal and tem poral border). Intraocular pressures, measured by ap planation tonometry, ranged from 15 to 18 mm Hg. All patients were tested before starting any treatment. Clinical data of individual patients are reported in ta ble 1. All patients had typical ocular and neurological symptoms of IIH [20]. The median of the duration of symptoms was 14 months (range: 3-90). No concom itant ocular diseases were clinically evident. Concom-
195
Downloaded by: Lund University Libraries 130.235.66.10 - 7/2/2017 3:50:06 AM
Visual sensory abnormalities can be de tected in early stages of idiopathic intracranial hypertension (IlH) [1,2] by means of contrast sensitivity testing [2-6] and automated thresh old perimetry [2. 7. 8]. Abnormalities in con trast sensitivity have been reported to nonuniformly affect the spatial frequency spectrum, being more marked at low [6] and medium [2, 4, 5] than at higher spatial frequencies (i.e. sensitivity is more altered for coarse-medium than for fine patterns). Early perimetric de fects commonly include constriction, inferonasal loss and arcuate scotomas [2], Visual loss in 11H is associated with a swell ing of the optic nerve head (i.e. papilledema) due to raised intracranial pressure. Studies in monkeys with experimentally induced papil ledema [9.10] have demonstrated that edema involves swelling of ganglion cell axons ante rior to the lamina cribrosa. Axonal swelling may be secondary to compression-induced is chemia [11], or may reflect a stasis of the ax oplasmic flow in the optic nerve head [12]. Early visual loss in 11H patients with papille dema has been related to a dysfunction of reti nal ganglion cells, owing to ischemic and/or mechanical damage [2. 6]. The combined assessment of electroretinograms and visually evoked potentials in re sponse to contrast-reversing patterns (PERGs and VEPs, respectively) has proven to be use ful in the diagnosis of optic nerve disease [13— 15], The PERG. unlike the flash ERG. is thought to originate in inner retinal layers, and has been reported to be correlated with ganglion cell activity [16. 17]. A combined PERG and VEP assessment may help to dis tinguish. at least in part, inner retina from postretina dysfunctions. Furthermore. PERG and VEP recordings for stimuli of different spatial frequencies may help to detect selec tive functional losses which can be found in the early stages of some optic nerve diseases [ 14].
Table 1. Clinical data of ÎIH patients Patient
Sex
i 2 3 4 5 6 7
F F F F VI M F
8
Age
Symptoms ocular
neurological
Duration of symptoms months
64 36 28 54 32 50 44
TVO TVO BV BV TV O .BV TVO TVO. BV. photopsi a
headache headache headache headache headache headache headache
42 24 6 24 10 9 25
1 II 1) 0 0 1 1
I 0 0 0 0 1 1
1 1 1 1 1 2 2
-)
ES
hyper tension. obesitv
F
35
BV. TVO
12
1
1
2
2
ES
—
9
M
22
TV O .BV
36
1
1
2
2
10
F
46
BV
35
1
1
1
i
ES
11 12
F F
55 26
TVO. BV TV O .BV
36 36
1 1
1 1
2 2
2 2
ES
13 14
F F
41 35
9 14
1
1 0
2 1
2 0
-
-
0
ES
—
15 16
F F
40 33
—
17 18
M F
35 29
TVO TVO. BV. photopsia TVO TVO. diplopia TVO
headache diplopia headache. tinnitus. paraesthesiae headache. diplopia headache headache. tinnitus headache headache
OD
OS
OD
OS
1 1 1 1 1
Radiologic findings
Systemic diseases
ES
—
-
ES -
-
headache headache
6 90
0
0 0
1 1
1 1
-
0
headache headache
12 3
1 0
1
2
0
1
2 1
ES ES
ES
obesih -
obesitx anémia
-
TVO = Transient visual obscurations: BV = blurred vision: ES = empty sella. Goldmann perimetry: grade 0 or I according to the classification proposed by Wall and George. 1991 [2], Grade l or 2. according to the papilledema staging scheme proposed by Frisen, I982 119].
itant systemicdieseases, such asobesitv. arterial hyper tension and anemia, were present in some cases. Twelve patients had evidence on CT and/or magnetic resonance imaging of an empty sella. Twenty-one control subjects (6 males. 15 females: mean age: 38.4 years: SD: 12: range: 22-65), with nor mal general and neuro-ophthalmological examination, were also tested. Informed consent was obtained from each subject or patient after the nature of the technique and the aim of our research were fully explained to them.
loo
Optic disk
Methods Visual stimuli were vertical sinusoidal gratings of variable spatial frequency (0.6.1.0.1.4.2.2and4.8cpd), electronically generated on a high-resolution (Mangoni. Pisa-I) TV monitor (85 cd/nr mean luminance. 56% contrast) and square-wave modulated in counterphase at 8 Hz (16 rps). Subjects fixated monocularly, with natural pupils, on the center of the stimulator from a distance of 57 cm (stimulation field size: 24°x 14°). Pu pil sizes were measured, and no differences were ob served between patients and controls. PERGs were
Falsini/Tamburrelli/Porciatti/Anile/ Porrello/Mangiola
Pattern ERGs and VEPs in Early Papilledema
Downloaded by: Lund University Libraries 130.235.66.10 - 7/2/2017 3:50:06 AM
'
-
Visual field1
Results
In figure la and b, representative examples of steady-state PERGs and VEPs obtained in response to 1 cpd sinusoidal gratings from a control subject and from a patient with IIH are shown. It can be noted that both responses display an approximately sinusoidal wave form with a temporal period of 62.5 ms, corre sponding to the reversal frequency. In the same figure, the second harmonic compo nents of PERG and VEP responses, isolated by a discrete Fourier series, are also presented on polar plots. Each point of the plots repre sents a vector whose length and orientation indicate the component (peak-to-peak) am plitude and phase angle, respectively. Figure 2 shows the mean (±SEM ) PERG amplitude and phase values plotted as a func tion of spatial frequency for normal subjects and patients. In normal subjects, the mean amplitude showed a peak at 1.4 cpd and atten uation at higher and lower spatial frequencies. In IIH patients, the mean PERG amplitude was reduced, compared to that of controls, at intermediate and high spatial frequencies (14.8 cpd). At the lowest spatial frequency (0.6cpd), mean amplitudes of both groups were similar. A two-way Anova indicated a significant main effect for group [F(l, 37) = 9.02, p
