83
Detection of Early Abnormalities in the Mucopolysaccharidoses by the Use of Visual and Brainstem Auditory Evoked Potentials By A. Perretti1, A. Petrillo 1, L. Pelosi1, P. Balbi1, G. Parenti2, A. Riemma2 and P. Strisciuglio2 1Department of Clinical
Neurophysiology and the 2Department of Pediatrics, 2nd School of Medicine, University of Naples, ltaly
Patients and methods Abstract
The presence of these abnormalities in most neurologically normal patients suggests that electrophysiological techniques provide a useful tool for detecting early abnormalities.
Keywords Mucopolysaccharidoses - Brainstem auditory evoked potentials - Flash visual evoked potentials
Introduction Mucopolysaccharidoses (MPS) are lysosomal disorders characterized by the storage of mucopolysaccharides in various organs and tissues. They have been classified into different types, according to the clinical presentation and the specific enzyme deficiency. In most types nervous system involvement is responsible for the most devastating effects of the disease. In the past years different authors have investigated individual CNS functions (1, 4), in MPS using electrophysiological techniques, but none of these studies adopted a multimodal approach. The purpose of this study was to explore visual and auditory systems in a group of patients with MPS by flash visual evoked potentials (FVEPs), brainstem auditory evoked potentials (BAEPs), and electroretinography (ERG), in order to detect the presence of early abnormalities and to evaluate the extent of impairment of the systems.
Received lune 27, 1989; accepted August 14, 1989 Neuropediatrics 21 (1990) 83-86 © Hippokrates Verlag Stuttgart
Thirteen patients (1 female and 12 males, mean age 6 years; ·range 3-17 years) with different forms of MPS (3 MPS/IS, 1 MPS IH/S, 6 MPS 11, 3 MPS 111 B, Table 1) were examined. In all patients the diagnosis was based on specific enzyme deficiency. Neurological examination was normal in all patients. One patient affected by the mild form of MPS 11 (Case 5) presented generalized seizures. Mild mental retardation was present in five patients (3 MPS 11 mild form; 2 MPS 111 B) moderate in two (1 MPS WS and 1 MPS 111 B) and severe in two patients affected by the severe form of MPS 11. Visual evoked potentials were obtained in all patients by stimulating each eye in turn with a white light flash. Stimulus frequency was 1 Hz. Cortical responses were recorded via Ag/AgC12 12 mm surface disc electrodes placed 1 cm lateral to 01 and 02 (International 10-20 System) both referred to an electrode located at the vertex (CZ). Two trials of 100 responses with stimulation of each eye, were averaged by an Otebiomedical Neuroaverager (Type 1239). Filter bandpass was 0.5-300 Hz and analysis time 500 ms. The averaged responses were recorded by a Nikon camera. The peak latency to the main positive component (major P) was calculated and amplitude was measured peak-to-peak from this wave to the major N component (3). Patient results were compared with data from 13 age-matched normal subjects examined in our laboratory. Values deviating by more than 2.5 SDs from those controls were considered abnormal. All patients underwent ophthalmological examination which included fundus oculi and ocular anterior chamber examination. Electroretinographic examination (ERG) was performed in 6 patients. Pupils were dilated with 1 % tropicamide and the ERG was recorded monocularly by a Henkes active corneal electrode referred to an Ag/AgC12 disc electrode placed at the external canto palpebralis and a ground electrode on the forehead. Light flashes were generated with a LACE electronics FST 1 photostimulator and a band pass of 1-250 Hz was used. Scotopic, previa retinal adaptation, white and red oscillatory potentials and white and red flicker ERG were performed. The responses were analyzed with a bioaverager (Nicolet CA 1000 system). ERG amplitudes were compared to those of controls. Brainstem auditory evoked potentials were obtained in 11 patients. Alternate clicks (100 IlS in duration) at 60-80 dB above the click hearing threshold were delivered to each ear in turn from a Camel Stereo Earphon GE 505, at a rate of 10/s. Recordings were performed via Ag/AgC12 12 mm disc
Downloaded by: Universite Laval. Copyrighted material.
Flash visual evoked potentials (FVEPs) and brainstem auditory evoked potentials (BAEPs) were performed in 13 children (aged 3-1 7 years) affected by mucopolysaccharidoses (MPSs). FVEPs and BAEPs were abnormal in 6 and 9 patients, respectively.
Neuropediatrics 21 (1990) Table 1
Case
Clinical and electrophysiological findings in 13 patients with MPS.
lAge (years) I 5
2
3 4
A. Perretti et al
5 5 7
IType MPS
I Sex IF I IS M M
M
IS IS I HIS
I VISUAL
Abnormalities (*)
I Co rneaI co I udin g Corneal clouding Corneal clouding Corneal clouding
I ERG
FVEPs Right eye major P AMP LAT
Left eye major P AMP LAT
BAEPs Absolute latencies
I Audiological
IAboa n rm I
o1
I Bilateral
examination
N N
N N
o1
02
02
N
N N
01 02
N N
N N
01 02
N N
01 02
N
N
N
-
01 02
Not performed
01 02
N
N
N
N
01 02
N N
01 02
Normal Normal
N
N N N N
I
1I
1II
?
severe CHL
Al A2
A -
N N
Bilateral mild CHL
Al A2
N
N
N
N
Left mild CHL
Al A2
A N
A N
A N
N
Bilateral severe CHL
Al A2
A A
A
A
ABilateral A severe CHL
Al A2
-
Not performed
Al A2
N
Bilateral mild CHL
Al A2
N N
A A
Not performed
Al A2
N N
N N
Not performed
Al A2
N -
N N
M
11 mild
No corneal clouding
Normal
01 02
N N
6
3
M
11 mild
No corneal clouding
Not performed
01 02
Not performed
11
No corneal clouding
Normal
mild
01 02
N N
N N
01 02
A A
"
mild
No corneal clouding
Not performed
01 02
N N
N N
01 02
-
11 severe
No corneal clouding
Not performed
01 02
Not performed
severe
No corneal clouding
Not performed
01 02
N N
N N
01 02
N N
N N
Not performed
Al A2
Not performed
8
5
M
M
9
6
M
10
13
M
N N
N
11
5
M
111 B
No corneal douding
Not performed
01 02
N N
A A
01 02
N N
N N
Not performed
Al A2
N N
12
17
M
111 B
No corneal clouding
Abnormal
01 02
N N
A A
01 02
N N
A A
Bilateral moderate CoHL
Al A2
-
No corneal clouding
Not performed
01 02
N N
N N
01 02
N N
N N
Bilateral severe CHL
13
9
M
111 B
?
?
?
N
N
N
N
N
N N
N N
N N
A
N
N
?
N A
N N
N
?
?
3
4
V
A
5
7
IV
-
-
Peak intervals 111- 1V 111 V
1-
N N
N N
N N
N N
N N
A A A
A A
A A
N N
A A
A
N N
A A
N N
A A
N
N
N
N
N
N N
N N
N N
N N
N N
A
?
Not performed
AMP = Amplitude, LAT = Latency, CHL = Conductive hearing loss, CoHL = Combined hearing loss, N = Normal, A = Abnormal, - = Absence of response, ? = Poorly defined response * Fundus oculi was normal in all patients
electrodes from the vertex referred to the earlobe ipsilateral to stimulation side. Two separate sets of 2500 responses were averaged with an Ote Biomedical Neuroaverager, type 1239 (band-pass 160-3,000 Hz; analysis time 10 ms). Latencies to the first five positive peaks and the 1-111, 111-V and I-V time intervals were measured. Results deviating more than 2.5 SDs from the control mean values were considered abnormal.
RE
10 ~V +
Eight patients underwent routine pure tone audiometry, tympanometry and acoustic reflex determination. Results Table 1 shows the results obtained in 13 patients with MPSs investigated by FVEP, ERG and BAEP. Impairment of FVEPs was found in 6 patients (Cases 3, 5, 7, 8, 11, 12). In four ofthese an abnormal response was recorded on both occipital areas stimulating one eye at a time. The major P component was found to have prolonged latency in two of these cases (Cases 5 and 11) and reduced amplitude in one (Case 7); it was absent in Case 8 (Fig. 1). In this subject right eye stimulation resulted in a normal potential on both occipital areas, while controlateral stimulation failed to evoke any response. In one patient (Case 12) an increase of the major P latency was observed in 02 and 01 with stimulation of both eyes. Finally, in one case (Case 3), a not clear potential of irregu-
5 IJV
LE +
I
o
I
I
I
I
I
100
200
300
400
500 ms
Fig.l
FVEP recordingfrom 02-Czand Ol-Czto rightand lefteyestimu-
lation in patient 8. Note the absence of a clear response on both areas by left eye stimulation.
Downloaded by: Universite Laval. Copyrighted material.
84
Early Abnormalities in the Mucopolysaccharidoses
Neuropediatrics 21 (1990)
85
RE
RE
1 5 1.N
RL I
I
100
200
I
o
500
2
4
I
I
6
8
10
ms
ms
Fig. Z FVEP recording from 02~Cz and Ol-Cz to right and left eye stimulation in patient 3. Note the irregular morphology of the potential derived fram 02-Cz by stimulating both eyes.
-,
Fig. 4 BAEP recording from A 2-Cz to right ear stimulation and A I-Cz to left ear stimulation in patient 1. The response in A2-Cz is difficult to recognize, while only wave I of the potential is recognizable in A I-Cz.
RE
A -C Z 2
v
I
RE 12
LE
A1-C z
t'v
+
4
6
8
+
LE i
2
v
I
o
i
2
i
i
4
6
8
10
ms Fig. 3 BAEP recording from A 2-Cz to right ear stimulation and A I-Cz to left ear stimulation in patient 3. Note in A I-Cz the increased latency of all waves and normal interpeak intervals.
ms Fig. 5 BAEP recording from A 2-Cz and A I-Cz to homolateral ear stimulation in patient 8. Note the prolonged 1II wave latency with increased 1-111 interval on both sides.
lar waveform was derived from 02 with stimulation of both eyes (Fig. 2). ERG was performed in six patients. ERG was normal in three patients (Cases 3, 5, 7) showing abnormal FVEPs. Further in Case 12, with abnormal FVEPs, the ERG showed a moderate reduction mainly of the photopie ERG amplitude. Finally a moderate reduction of the scotopic and photopie ERG amplitude was present in one case (Case 1). In patient 2, both ERG and FVEP were normal.
4. increase of interpeak intervals and/or increase of absolute latencies of one or more deflections in Cases 7, AI, A 2, 8, AI, A2 (Fig. 5). One of these two patients presented mild conductive hearing loss, while the other one was not audiologically tested.
BAEPs were abnormal in 9 of 11 patients (Cases 1-5, 7-9, 12). Abnormalities consisted in: 1. delayed absolute latency of all waves including wave land normal interpeak intervals in Cases 3, AI, (Fig. 3),4, AI; 2. delayed latency of wave I with difficult identification of successive potentials in Cases 1, AI (Fig. 4), 4, A2; 3. all waves which were not clearly identifiable (Cases 1, A 2, 2, AI, 5, 9, A2, 12, A2, AI);
All the patients with abnormal BAEPs showed loss of hearing of varying degrees, due to conductive dysfunction except in Case 12 were a combined hearing loss was present.
Discussion Electrophysiological techniques have recentIy found wide application in the study of pediatric patients affected by neurodegenerative diseases, in some instances, providing a
Downloaded by: Universite Laval. Copyrighted material.
+
Neuropediatrics 21 (1990)
useful diagnostic clue. Only in a few cases, however, this approach has been extended to patients with lysosomal storage disorders, and results of different studies have not been completely conclusive. ERG and FVEPs were investigated in children affected by mucopolysaccharidoses by Harden and Pampiglione (4), who found no evident anomalies in most of the subjects studied before the age of 10 years. By contrast, another study (1) demonstrated frequent ERG anomalies in a group of patients, ranging in age from 3 to 21.5 years, affected by mucopolysaccharidoses I, 11 and 111. Moreover, BAEPs anomalies were detected by Muenzer (5) in patients with mucopolysaccharidoses. In this study we investigated different systems by combining several electrophysiological techniques (FVEPs, ERG, BAEPs). Abnormal FVEPs were observed in 6 of 10 patients under 10 years of age, and five of them showed abnormalities on both occipital areas after either unilateral or bilateral stimulation. In four of these patients, the neurological damage was likely localized at the optic nerve since ophthalmological examination and ERG were normal. In an another subject abnormal ERG suggested primary retinal involvement. In the sixth patient a retrochiasmallesion was suggested by unilateral FVEP abnormalities after stimulation of both eyes. All these patients presented normal neurological examination. BAEPs were also performed in 11 of these patients, and were found to be abnormal in 8. In five of these the abnormalities started from wave I, suggesting peripheral damage. The hypothesis seems confirmed by the presence of conductive or combined hearing loss when performing audiological tests in all these patients. A brainstem localization of the damage in the three other patients is, however, suggested by the delay of the absolute or interpeak latence of the components following the normal wave 1. In addition, in two of these patients only a mild conductive loss of hearing was present. It is therefore possible that the presence of a more severe peripheral damage seen in the other patients could mask a concomitant central pathology at BAEP examination. On the other hand, the presence of mixed peripheral and central abnormalities in these patients has been recently observed by others (5).
A. Perretti et al
Our results confirm that electrophysiological techniques might provide useful information about neurological involvement in mucopolysaccharidoses; in fact PEV and BAEP anomalies were detectable in most of our neurologically normal patients, suggesting that electrophysiological techniques are sensitive enough to detect minimal involvement of the nervous system in MPS. Moreover, these techniques enabled us to localize the neurologieallesions precisely. In conclusion, our results suggest that the COffibined use of electrophysiological techniques is a good test in detecting early neurological abnormalities in MPS, which are not revealed by physical examination or other techniques, even in non-cooperative subjects. Finally, as already suggested by ehen et al (2), this approach could also be effective in monitoring the progression of degenerative diseases such as MPS.
References Caruso, R. C., M. 1. Kaiser-Kup[er,]. Muenzer, H. Ludwig, M. A. Zasloff, P. A. Mercer: Electroretinographic findings in the mucopolysaccharidoses. Ophthalmology 93 (1986) 1612-1616 2 Chen, Y. ]., T. Kurokawa, A. Mitsudome, T. Hanai, O. Narazaki, K. Ueda: Brainstem auditory evoked potentials in children with neurodegenerative diseases. Eur. J. Pediatr. 145 (1986) 471-474 3 Harden, A.: Maturation of the visual potentials. Clinical Application of Cerebral Evoked Potentials in Paediatric Medicine. Amsterdam, Excerpta Medica, 1982 4 Harden, A., G. Pampiglione: Visual evoked potentials, electroretinogram and electroencephalogram studies in progressive neurometabolic "storage" diseases of childhood. Visual evoked potentials in man: new developments. Oxford Clarendon Press, 1977 5 Muenzer,].: Mucopolysaccharidoses. Adv. Pediatr. 33 (1986) 296-302 1
P. Strisciuglio, M.n.
Dept. of Pediatrics 2nd School of Medicine University of Naples Via S. Pansini 5 1-80131 Naples, ltaly
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86
Detection of Early Abnormalities in the Mucopolysaccharidoses by the Use of Visual and Brainstem Auditory Evoked Potentials By A. Perretti1, A. Petrillo 1, L. Pelosi1, P. Balbi1, G. Parenti2, A. Riemma2 and P. Strisciuglio2 1Department of Clinical
Neurophysiology and the 2Department of Pediatrics, 2nd School of Medicine, University of Naples, ltaly
Patients and methods Abstract
The presence of these abnormalities in most neurologically normal patients suggests that electrophysiological techniques provide a useful tool for detecting early abnormalities.
Keywords Mucopolysaccharidoses - Brainstem auditory evoked potentials - Flash visual evoked potentials
Introduction Mucopolysaccharidoses (MPS) are lysosomal disorders characterized by the storage of mucopolysaccharides in various organs and tissues. They have been classified into different types, according to the clinical presentation and the specific enzyme deficiency. In most types nervous system involvement is responsible for the most devastating effects of the disease. In the past years different authors have investigated individual CNS functions (1, 4), in MPS using electrophysiological techniques, but none of these studies adopted a multimodal approach. The purpose of this study was to explore visual and auditory systems in a group of patients with MPS by flash visual evoked potentials (FVEPs), brainstem auditory evoked potentials (BAEPs), and electroretinography (ERG), in order to detect the presence of early abnormalities and to evaluate the extent of impairment of the systems.
Received lune 27, 1989; accepted August 14, 1989 Neuropediatrics 21 (1990) 83-86 © Hippokrates Verlag Stuttgart
Thirteen patients (1 female and 12 males, mean age 6 years; ·range 3-17 years) with different forms of MPS (3 MPS/IS, 1 MPS IH/S, 6 MPS 11, 3 MPS 111 B, Table 1) were examined. In all patients the diagnosis was based on specific enzyme deficiency. Neurological examination was normal in all patients. One patient affected by the mild form of MPS 11 (Case 5) presented generalized seizures. Mild mental retardation was present in five patients (3 MPS 11 mild form; 2 MPS 111 B) moderate in two (1 MPS WS and 1 MPS 111 B) and severe in two patients affected by the severe form of MPS 11. Visual evoked potentials were obtained in all patients by stimulating each eye in turn with a white light flash. Stimulus frequency was 1 Hz. Cortical responses were recorded via Ag/AgC12 12 mm surface disc electrodes placed 1 cm lateral to 01 and 02 (International 10-20 System) both referred to an electrode located at the vertex (CZ). Two trials of 100 responses with stimulation of each eye, were averaged by an Otebiomedical Neuroaverager (Type 1239). Filter bandpass was 0.5-300 Hz and analysis time 500 ms. The averaged responses were recorded by a Nikon camera. The peak latency to the main positive component (major P) was calculated and amplitude was measured peak-to-peak from this wave to the major N component (3). Patient results were compared with data from 13 age-matched normal subjects examined in our laboratory. Values deviating by more than 2.5 SDs from those controls were considered abnormal. All patients underwent ophthalmological examination which included fundus oculi and ocular anterior chamber examination. Electroretinographic examination (ERG) was performed in 6 patients. Pupils were dilated with 1 % tropicamide and the ERG was recorded monocularly by a Henkes active corneal electrode referred to an Ag/AgC12 disc electrode placed at the external canto palpebralis and a ground electrode on the forehead. Light flashes were generated with a LACE electronics FST 1 photostimulator and a band pass of 1-250 Hz was used. Scotopic, previa retinal adaptation, white and red oscillatory potentials and white and red flicker ERG were performed. The responses were analyzed with a bioaverager (Nicolet CA 1000 system). ERG amplitudes were compared to those of controls. Brainstem auditory evoked potentials were obtained in 11 patients. Alternate clicks (100 IlS in duration) at 60-80 dB above the click hearing threshold were delivered to each ear in turn from a Camel Stereo Earphon GE 505, at a rate of 10/s. Recordings were performed via Ag/AgC12 12 mm disc
Downloaded by: Universite Laval. Copyrighted material.
Flash visual evoked potentials (FVEPs) and brainstem auditory evoked potentials (BAEPs) were performed in 13 children (aged 3-1 7 years) affected by mucopolysaccharidoses (MPSs). FVEPs and BAEPs were abnormal in 6 and 9 patients, respectively.
Neuropediatrics 21 (1990) Table 1
Case
Clinical and electrophysiological findings in 13 patients with MPS.
lAge (years) I 5
2
3 4
A. Perretti et al
5 5 7
IType MPS
I Sex IF I IS M M
M
IS IS I HIS
I VISUAL
Abnormalities (*)
I Co rneaI co I udin g Corneal clouding Corneal clouding Corneal clouding
I ERG
FVEPs Right eye major P AMP LAT
Left eye major P AMP LAT
BAEPs Absolute latencies
I Audiological
IAboa n rm I
o1
I Bilateral
examination
N N
N N
o1
02
02
N
N N
01 02
N N
N N
01 02
N N
01 02
N
N
N
-
01 02
Not performed
01 02
N
N
N
N
01 02
N N
01 02
Normal Normal
N
N N N N
I
1I
1II
?
severe CHL
Al A2
A -
N N
Bilateral mild CHL
Al A2
N
N
N
N
Left mild CHL
Al A2
A N
A N
A N
N
Bilateral severe CHL
Al A2
A A
A
A
ABilateral A severe CHL
Al A2
-
Not performed
Al A2
N
Bilateral mild CHL
Al A2
N N
A A
Not performed
Al A2
N N
N N
Not performed
Al A2
N -
N N
M
11 mild
No corneal clouding
Normal
01 02
N N
6
3
M
11 mild
No corneal clouding
Not performed
01 02
Not performed
11
No corneal clouding
Normal
mild
01 02
N N
N N
01 02
A A
"
mild
No corneal clouding
Not performed
01 02
N N
N N
01 02
-
11 severe
No corneal clouding
Not performed
01 02
Not performed
severe
No corneal clouding
Not performed
01 02
N N
N N
01 02
N N
N N
Not performed
Al A2
Not performed
8
5
M
M
9
6
M
10
13
M
N N
N
11
5
M
111 B
No corneal douding
Not performed
01 02
N N
A A
01 02
N N
N N
Not performed
Al A2
N N
12
17
M
111 B
No corneal clouding
Abnormal
01 02
N N
A A
01 02
N N
A A
Bilateral moderate CoHL
Al A2
-
No corneal clouding
Not performed
01 02
N N
N N
01 02
N N
N N
Bilateral severe CHL
13
9
M
111 B
?
?
?
N
N
N
N
N
N N
N N
N N
A
N
N
?
N A
N N
N
?
?
3
4
V
A
5
7
IV
-
-
Peak intervals 111- 1V 111 V
1-
N N
N N
N N
N N
N N
A A A
A A
A A
N N
A A
A
N N
A A
N N
A A
N
N
N
N
N
N N
N N
N N
N N
N N
A
?
Not performed
AMP = Amplitude, LAT = Latency, CHL = Conductive hearing loss, CoHL = Combined hearing loss, N = Normal, A = Abnormal, - = Absence of response, ? = Poorly defined response * Fundus oculi was normal in all patients
electrodes from the vertex referred to the earlobe ipsilateral to stimulation side. Two separate sets of 2500 responses were averaged with an Ote Biomedical Neuroaverager, type 1239 (band-pass 160-3,000 Hz; analysis time 10 ms). Latencies to the first five positive peaks and the 1-111, 111-V and I-V time intervals were measured. Results deviating more than 2.5 SDs from the control mean values were considered abnormal.
RE
10 ~V +
Eight patients underwent routine pure tone audiometry, tympanometry and acoustic reflex determination. Results Table 1 shows the results obtained in 13 patients with MPSs investigated by FVEP, ERG and BAEP. Impairment of FVEPs was found in 6 patients (Cases 3, 5, 7, 8, 11, 12). In four ofthese an abnormal response was recorded on both occipital areas stimulating one eye at a time. The major P component was found to have prolonged latency in two of these cases (Cases 5 and 11) and reduced amplitude in one (Case 7); it was absent in Case 8 (Fig. 1). In this subject right eye stimulation resulted in a normal potential on both occipital areas, while controlateral stimulation failed to evoke any response. In one patient (Case 12) an increase of the major P latency was observed in 02 and 01 with stimulation of both eyes. Finally, in one case (Case 3), a not clear potential of irregu-
5 IJV
LE +
I
o
I
I
I
I
I
100
200
300
400
500 ms
Fig.l
FVEP recordingfrom 02-Czand Ol-Czto rightand lefteyestimu-
lation in patient 8. Note the absence of a clear response on both areas by left eye stimulation.
Downloaded by: Universite Laval. Copyrighted material.
84
Early Abnormalities in the Mucopolysaccharidoses
Neuropediatrics 21 (1990)
85
RE
RE
1 5 1.N
RL I
I
100
200
I
o
500
2
4
I
I
6
8
10
ms
ms
Fig. Z FVEP recording from 02~Cz and Ol-Cz to right and left eye stimulation in patient 3. Note the irregular morphology of the potential derived fram 02-Cz by stimulating both eyes.
-,
Fig. 4 BAEP recording from A 2-Cz to right ear stimulation and A I-Cz to left ear stimulation in patient 1. The response in A2-Cz is difficult to recognize, while only wave I of the potential is recognizable in A I-Cz.
RE
A -C Z 2
v
I
RE 12
LE
A1-C z
t'v
+
4
6
8
+
LE i
2
v
I
o
i
2
i
i
4
6
8
10
ms Fig. 3 BAEP recording from A 2-Cz to right ear stimulation and A I-Cz to left ear stimulation in patient 3. Note in A I-Cz the increased latency of all waves and normal interpeak intervals.
ms Fig. 5 BAEP recording from A 2-Cz and A I-Cz to homolateral ear stimulation in patient 8. Note the prolonged 1II wave latency with increased 1-111 interval on both sides.
lar waveform was derived from 02 with stimulation of both eyes (Fig. 2). ERG was performed in six patients. ERG was normal in three patients (Cases 3, 5, 7) showing abnormal FVEPs. Further in Case 12, with abnormal FVEPs, the ERG showed a moderate reduction mainly of the photopie ERG amplitude. Finally a moderate reduction of the scotopic and photopie ERG amplitude was present in one case (Case 1). In patient 2, both ERG and FVEP were normal.
4. increase of interpeak intervals and/or increase of absolute latencies of one or more deflections in Cases 7, AI, A 2, 8, AI, A2 (Fig. 5). One of these two patients presented mild conductive hearing loss, while the other one was not audiologically tested.
BAEPs were abnormal in 9 of 11 patients (Cases 1-5, 7-9, 12). Abnormalities consisted in: 1. delayed absolute latency of all waves including wave land normal interpeak intervals in Cases 3, AI, (Fig. 3),4, AI; 2. delayed latency of wave I with difficult identification of successive potentials in Cases 1, AI (Fig. 4), 4, A2; 3. all waves which were not clearly identifiable (Cases 1, A 2, 2, AI, 5, 9, A2, 12, A2, AI);
All the patients with abnormal BAEPs showed loss of hearing of varying degrees, due to conductive dysfunction except in Case 12 were a combined hearing loss was present.
Discussion Electrophysiological techniques have recentIy found wide application in the study of pediatric patients affected by neurodegenerative diseases, in some instances, providing a
Downloaded by: Universite Laval. Copyrighted material.
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Neuropediatrics 21 (1990)
useful diagnostic clue. Only in a few cases, however, this approach has been extended to patients with lysosomal storage disorders, and results of different studies have not been completely conclusive. ERG and FVEPs were investigated in children affected by mucopolysaccharidoses by Harden and Pampiglione (4), who found no evident anomalies in most of the subjects studied before the age of 10 years. By contrast, another study (1) demonstrated frequent ERG anomalies in a group of patients, ranging in age from 3 to 21.5 years, affected by mucopolysaccharidoses I, 11 and 111. Moreover, BAEPs anomalies were detected by Muenzer (5) in patients with mucopolysaccharidoses. In this study we investigated different systems by combining several electrophysiological techniques (FVEPs, ERG, BAEPs). Abnormal FVEPs were observed in 6 of 10 patients under 10 years of age, and five of them showed abnormalities on both occipital areas after either unilateral or bilateral stimulation. In four of these patients, the neurological damage was likely localized at the optic nerve since ophthalmological examination and ERG were normal. In an another subject abnormal ERG suggested primary retinal involvement. In the sixth patient a retrochiasmallesion was suggested by unilateral FVEP abnormalities after stimulation of both eyes. All these patients presented normal neurological examination. BAEPs were also performed in 11 of these patients, and were found to be abnormal in 8. In five of these the abnormalities started from wave I, suggesting peripheral damage. The hypothesis seems confirmed by the presence of conductive or combined hearing loss when performing audiological tests in all these patients. A brainstem localization of the damage in the three other patients is, however, suggested by the delay of the absolute or interpeak latence of the components following the normal wave 1. In addition, in two of these patients only a mild conductive loss of hearing was present. It is therefore possible that the presence of a more severe peripheral damage seen in the other patients could mask a concomitant central pathology at BAEP examination. On the other hand, the presence of mixed peripheral and central abnormalities in these patients has been recently observed by others (5).
A. Perretti et al
Our results confirm that electrophysiological techniques might provide useful information about neurological involvement in mucopolysaccharidoses; in fact PEV and BAEP anomalies were detectable in most of our neurologically normal patients, suggesting that electrophysiological techniques are sensitive enough to detect minimal involvement of the nervous system in MPS. Moreover, these techniques enabled us to localize the neurologieallesions precisely. In conclusion, our results suggest that the COffibined use of electrophysiological techniques is a good test in detecting early neurological abnormalities in MPS, which are not revealed by physical examination or other techniques, even in non-cooperative subjects. Finally, as already suggested by ehen et al (2), this approach could also be effective in monitoring the progression of degenerative diseases such as MPS.
References Caruso, R. C., M. 1. Kaiser-Kup[er,]. Muenzer, H. Ludwig, M. A. Zasloff, P. A. Mercer: Electroretinographic findings in the mucopolysaccharidoses. Ophthalmology 93 (1986) 1612-1616 2 Chen, Y. ]., T. Kurokawa, A. Mitsudome, T. Hanai, O. Narazaki, K. Ueda: Brainstem auditory evoked potentials in children with neurodegenerative diseases. Eur. J. Pediatr. 145 (1986) 471-474 3 Harden, A.: Maturation of the visual potentials. Clinical Application of Cerebral Evoked Potentials in Paediatric Medicine. Amsterdam, Excerpta Medica, 1982 4 Harden, A., G. Pampiglione: Visual evoked potentials, electroretinogram and electroencephalogram studies in progressive neurometabolic "storage" diseases of childhood. Visual evoked potentials in man: new developments. Oxford Clarendon Press, 1977 5 Muenzer,].: Mucopolysaccharidoses. Adv. Pediatr. 33 (1986) 296-302 1
P. Strisciuglio, M.n.
Dept. of Pediatrics 2nd School of Medicine University of Naples Via S. Pansini 5 1-80131 Naples, ltaly
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