Movement Disorders Vol. 6, No. 1, 1991, pp. 49-54 0 1991 Movement Disorder Society
Motor and Sensory Evoked Potentials in Progressive Supranuclear Palsy G . Abbruzzese, M. Tabaton, M. Morena, D. Dall’Agata, and E. Favale Department of Neurology, University of Genoa, Italy
Summary: Motor potentials evoked in the biceps, thenar, and tibialis anterior muscles by electrical stimulation of the scalp and of the spinal regions were recorded in 12 patients with progressive supranuclear palsy (PSP) and in a control group. Abnormalities of central motor conduction for at least one muscle were present in five patients (41.7%), characterized by a long illness duration. The central sensory conduction time of the median nerve was normal, but five patients showed a depressed frontal N30 wave. These findings support the possible occurrence of functional damage to the corticospinal tracts and to the supplementary motor area in PSP. Key Words: Progressive supranuclear palsy-Motor evoked potentials-Sensory evoked potentials-Supplementary motor area.
PATIENTS AND METHODS
Progressive supranuclear palsy (PSP) is a degenerative disorder involving basal ganglia, dentate nucleus, periaqueductal gray matter, and other brain stem nuclei (1). The occurrence of pyramidal signs (brisk tendon jerks or extensor plantar responses) has been suggested as a late finding in PSP ( 2 4 , but the underlying damage to the corticospinal tracts has not been proven definitely by pathological findings or investigated by electrophysiological studies. The introduction of the technique of noninvasive electrical stimulation of the brain and spinal cord ( 5 ) has allowed a direct approach to the functionality of central motor pathways in patients with motor disturbances (for a review, see 6). We investigated the functional integrity of the corticospinal system in a group of patients with PSP by recording motor evoked potentials (MEPs). Additionally, sensory evoked potentials (SEPs) have been studied, their possible relevance stemming from previous observations of the frontal SEP pattern abnormalities in other extrapyramidal disorders (7-9).
Twelve patients, eight women and four men aged 58-75 years, were observed after informed consent. The diagnosis of PSP was based on four clinical criteria required for inclusion: ophthalmoplegia with down-gaze abnormalities; at least two of the following features: axial dystonia and rigidity, pseudobulbar palsy, bradykinesia, frontal lobe signs, andlor postural instability with falls backward; gradual development of the disease with poor response to levodopa treatment; and normal computed tomography scan, except for a slight diffuse atrophy. Patients underwent complete routine laboratory tests and were carefully examined to exclude the occurrence of any other condition that might impair central motor conduction, such as cervical spondylosis (10). The main features of the patients are reported in Table l . Twelve normal subjects, matched for age (mean 63.7, SD 6.6; range, 54-74 years) and height were also studied as a control group. The motor cortex and the cervical (or lumbar) region were stimulated by single electric shocks delivered by a Digitimer D180 stimulator supplying a maximum of 750 V with a time constant of 50-100 p,s. For cortical stimulation, surface electrodes (Ad
Address correspondence and reprint requests to Prof. G. Abbruzzese, Clinica Neurologica Universita’, Via A. De Toni, I16132 Genova, Italy.
49
50
G . ABBRUZZESE ET A L . TABLE 1. Clinical .features of patients with PSP ~
Duration, mo
Patiendsex/ age, yr
Axial dystonia
Postural instability
+++ +++ ++ + ++ ++ +++ + + + +++ + ++ +++ ++ + ++ ++ ++ ++ ++ ++ +++ -~~ a - , absent; + , mild; + + , moderate; + + + , severe. 32 36 36 96 8 12 48 12 12 36 24 96
1/M/66 2lFl66 3lFl75 4lFl58 5IFl70 61FI69 11Fl69 8lFl59 9Ml61 101Fl61 1l M 7 6 12lFl68
++a
Bulbar signs
+++ ++ + +++ + + +
-
++
-
Frontal signs -
++ + ++ + + + +
-
Pyramidal signs
-
+
-
++
-
++ + + +
MEPs
Frontal SEP
N N N A N A A A N N N A
N N N A A N N A A A N N
~
PSP, progressive supranuclear palsy; MEP, motor evoked potential; SEP, sensory evoked potential; N, normal; A, abnormal.
AgCl cups) were fixed to the scalp, with the cathode on the vertex and the anode 7 cm down on a line between the vertex and the external auditory meatus to activate the upper limb muscles, and the anode on the vertex and the cathode 6 cm anteriorly to activate the lower limb muscles. Cervical and lumbar surface electrodes were placed, respectively, over the processes of C4-TI and D12-L4, the anode being proximal to the cathode. The MEPs were recorded bilaterally by surface electrodes placed on the biceps, thenar, and tibialis anterior muscles. Electromyography (EMG) activity was amplified (53 Hz-3 kHz, - 3 dB), displayed on the screen, and stored on a floppy disk of an AIM 65 Rockwell computer for later analysis. Cortical stimulation was performed during slight background contraction of the target muscles, while spinal stimulation was performed at rest. Onset latency, duration, and peak-to-peak amplitude of MEPs were measured with a cursor on the computer display, and the central motor conduction time (CMCT) was determined by subtracting the shortest latency of the cervical (or lumbar) MEPs from the shortest latency of the cortical MEPs. Absence of the cortical response at maximum stimulation intensity or the occurrence of CMCT values exceeding the upper confidence limit (mean + 2.5 SD) of normal controls was adopted as the abnormality criterion. Somatosensory evoked potentials after median nerve stimulation at the wrist (0.2-ms square waves delivered with a frequency of 1 Hz and an intensity just above motor threshold) were recorded from cervical (between the second and the third cervical spines), parietal (3 cm behind the vertex and 7 cm
Movement Disorders, Vol. 6 , N o . I , 1991
from the midline), and frontal (4 cm in front of the vertex and 5 cm from the midline) electrodes with an earlobe reference. At least three series of 256 responses were averaged over 50-100 ms by an AIM 65 Rockwell computer (bandpass, 16-3,000 Hz; sampling rate, 10 kHz per channel) with automatic rejection of samples with excessive EMG interference. Peak latencies and peak-to-peak amplitudes (cervical N 13-following positivity, parietal N20-P27, frontal P22-N30) were measured with a cursor on the computer display. The central conduction time (CCT) of the lemniscal pathway was calculated as the difference between latencies of cervical N13 and parietal N20, and its upper confidence limit was determined as the mean + 2.5 SD of normal controls. Further details on experimental procedures have been reported elsewhere (9,lO). The results were statistically analyzed. RESULTS MEPs The mean CMCTs for biceps, thenar, and tibialis anterior muscles were not significantly different between PSP patients and normal controls (Table 2), but abnormalities of central motor conduction for at least one muscle were observed in five patients (41.7%). Cortical MEPs were absent bilaterally in the tibialis anterior muscles (Fig. 1, lower trace) and unilaterally in the biceps and thenar muscles of one subject. The CMCT exceeded the upper confidence limit of normal controls in two cases (unilaterally) for the biceps, in four cases (two bilaterally) for the
51
EVOKED POTENTIALS IN PSP TABLE 2. Central motor conduction times (CMCTs) in PSP patients CMCT, ms Patient
Biceps
Thenar
Tibialis
R L
4.48 4.80
5.44 5.12
14.08 14.08
R L
5.44 5.44
5.76 5.76
11.52 11.52
R L
4.48 4.80
5.76 6.08
13.12 13.12
R L
6.72"
7.20
n.m.
n.m.
n.m. n.m.
R L
4.80 4.80
5.76 5.44
14.08 14.08
R L
5.12 5.00
6.72 5.12
16.68 13.76
R L
4.80 4.80
5.44 5.76
12.00 16.68
R L
5.44 5.12
6.72 6.72
13.44 13.44
R L 10 R L 11 R L 12
4.80 4.80
5.12 5.44
13.76 13.76
4.80 4.48
5.12 4.80
12.16 12.16
5.44 5.12
6.40 6.40
12.80 12.80
R
6.40 5.44 5.10 0.54
7.36 7.04 5.93 0.73
16.40 14.40 13.63 1.44
4.87' 0.34 5.72
5.64' 0.33 6.47
13.15' 1.18 16.10
1 2 3 4
5 6 7
8
9
L Mean SD Control mean SD Upper confidence limit' ~
~
PSP, progressive supranuclear palsy; R, right; L, left; n.m., not measurable because of absence of cortical motor evoked potentials. " Italics indicate that CMCT exceeded upper confidence limit of normal controls. t-test for unpaired data: not significant. Upper confidence limit, mean + 2.5 SD.
'
thenar (Fig. 1, upper traces), and in two cases (unilaterally) for the tibialis anterior (Table 2). Patients with MEP abnormalities were characterized by a significantly longer illness duration (always above 4 years) and by an increased occurrence of pyramidal signs, such as pathologically brisk tendon jerks in three subjects and extensor plantar responses in one (Table 1).
SEPs The mean value of the CCT (N 13-N20 interval) of the lemniscal pathway was not different from that of normal controls and no patient exceeded the upper confidence limit (Table 3). Parietal (N20-P27) SEPs of large amplitude were usually observed (PSP, 8.64 ? 4.67 pV; NC, 4.93 ? 1.42 pV; t = 3.12, p
Motor and Sensory Evoked Potentials in Progressive Supranuclear Palsy G . Abbruzzese, M. Tabaton, M. Morena, D. Dall’Agata, and E. Favale Department of Neurology, University of Genoa, Italy
Summary: Motor potentials evoked in the biceps, thenar, and tibialis anterior muscles by electrical stimulation of the scalp and of the spinal regions were recorded in 12 patients with progressive supranuclear palsy (PSP) and in a control group. Abnormalities of central motor conduction for at least one muscle were present in five patients (41.7%), characterized by a long illness duration. The central sensory conduction time of the median nerve was normal, but five patients showed a depressed frontal N30 wave. These findings support the possible occurrence of functional damage to the corticospinal tracts and to the supplementary motor area in PSP. Key Words: Progressive supranuclear palsy-Motor evoked potentials-Sensory evoked potentials-Supplementary motor area.
PATIENTS AND METHODS
Progressive supranuclear palsy (PSP) is a degenerative disorder involving basal ganglia, dentate nucleus, periaqueductal gray matter, and other brain stem nuclei (1). The occurrence of pyramidal signs (brisk tendon jerks or extensor plantar responses) has been suggested as a late finding in PSP ( 2 4 , but the underlying damage to the corticospinal tracts has not been proven definitely by pathological findings or investigated by electrophysiological studies. The introduction of the technique of noninvasive electrical stimulation of the brain and spinal cord ( 5 ) has allowed a direct approach to the functionality of central motor pathways in patients with motor disturbances (for a review, see 6). We investigated the functional integrity of the corticospinal system in a group of patients with PSP by recording motor evoked potentials (MEPs). Additionally, sensory evoked potentials (SEPs) have been studied, their possible relevance stemming from previous observations of the frontal SEP pattern abnormalities in other extrapyramidal disorders (7-9).
Twelve patients, eight women and four men aged 58-75 years, were observed after informed consent. The diagnosis of PSP was based on four clinical criteria required for inclusion: ophthalmoplegia with down-gaze abnormalities; at least two of the following features: axial dystonia and rigidity, pseudobulbar palsy, bradykinesia, frontal lobe signs, andlor postural instability with falls backward; gradual development of the disease with poor response to levodopa treatment; and normal computed tomography scan, except for a slight diffuse atrophy. Patients underwent complete routine laboratory tests and were carefully examined to exclude the occurrence of any other condition that might impair central motor conduction, such as cervical spondylosis (10). The main features of the patients are reported in Table l . Twelve normal subjects, matched for age (mean 63.7, SD 6.6; range, 54-74 years) and height were also studied as a control group. The motor cortex and the cervical (or lumbar) region were stimulated by single electric shocks delivered by a Digitimer D180 stimulator supplying a maximum of 750 V with a time constant of 50-100 p,s. For cortical stimulation, surface electrodes (Ad
Address correspondence and reprint requests to Prof. G. Abbruzzese, Clinica Neurologica Universita’, Via A. De Toni, I16132 Genova, Italy.
49
50
G . ABBRUZZESE ET A L . TABLE 1. Clinical .features of patients with PSP ~
Duration, mo
Patiendsex/ age, yr
Axial dystonia
Postural instability
+++ +++ ++ + ++ ++ +++ + + + +++ + ++ +++ ++ + ++ ++ ++ ++ ++ ++ +++ -~~ a - , absent; + , mild; + + , moderate; + + + , severe. 32 36 36 96 8 12 48 12 12 36 24 96
1/M/66 2lFl66 3lFl75 4lFl58 5IFl70 61FI69 11Fl69 8lFl59 9Ml61 101Fl61 1l M 7 6 12lFl68
++a
Bulbar signs
+++ ++ + +++ + + +
-
++
-
Frontal signs -
++ + ++ + + + +
-
Pyramidal signs
-
+
-
++
-
++ + + +
MEPs
Frontal SEP
N N N A N A A A N N N A
N N N A A N N A A A N N
~
PSP, progressive supranuclear palsy; MEP, motor evoked potential; SEP, sensory evoked potential; N, normal; A, abnormal.
AgCl cups) were fixed to the scalp, with the cathode on the vertex and the anode 7 cm down on a line between the vertex and the external auditory meatus to activate the upper limb muscles, and the anode on the vertex and the cathode 6 cm anteriorly to activate the lower limb muscles. Cervical and lumbar surface electrodes were placed, respectively, over the processes of C4-TI and D12-L4, the anode being proximal to the cathode. The MEPs were recorded bilaterally by surface electrodes placed on the biceps, thenar, and tibialis anterior muscles. Electromyography (EMG) activity was amplified (53 Hz-3 kHz, - 3 dB), displayed on the screen, and stored on a floppy disk of an AIM 65 Rockwell computer for later analysis. Cortical stimulation was performed during slight background contraction of the target muscles, while spinal stimulation was performed at rest. Onset latency, duration, and peak-to-peak amplitude of MEPs were measured with a cursor on the computer display, and the central motor conduction time (CMCT) was determined by subtracting the shortest latency of the cervical (or lumbar) MEPs from the shortest latency of the cortical MEPs. Absence of the cortical response at maximum stimulation intensity or the occurrence of CMCT values exceeding the upper confidence limit (mean + 2.5 SD) of normal controls was adopted as the abnormality criterion. Somatosensory evoked potentials after median nerve stimulation at the wrist (0.2-ms square waves delivered with a frequency of 1 Hz and an intensity just above motor threshold) were recorded from cervical (between the second and the third cervical spines), parietal (3 cm behind the vertex and 7 cm
Movement Disorders, Vol. 6 , N o . I , 1991
from the midline), and frontal (4 cm in front of the vertex and 5 cm from the midline) electrodes with an earlobe reference. At least three series of 256 responses were averaged over 50-100 ms by an AIM 65 Rockwell computer (bandpass, 16-3,000 Hz; sampling rate, 10 kHz per channel) with automatic rejection of samples with excessive EMG interference. Peak latencies and peak-to-peak amplitudes (cervical N 13-following positivity, parietal N20-P27, frontal P22-N30) were measured with a cursor on the computer display. The central conduction time (CCT) of the lemniscal pathway was calculated as the difference between latencies of cervical N13 and parietal N20, and its upper confidence limit was determined as the mean + 2.5 SD of normal controls. Further details on experimental procedures have been reported elsewhere (9,lO). The results were statistically analyzed. RESULTS MEPs The mean CMCTs for biceps, thenar, and tibialis anterior muscles were not significantly different between PSP patients and normal controls (Table 2), but abnormalities of central motor conduction for at least one muscle were observed in five patients (41.7%). Cortical MEPs were absent bilaterally in the tibialis anterior muscles (Fig. 1, lower trace) and unilaterally in the biceps and thenar muscles of one subject. The CMCT exceeded the upper confidence limit of normal controls in two cases (unilaterally) for the biceps, in four cases (two bilaterally) for the
51
EVOKED POTENTIALS IN PSP TABLE 2. Central motor conduction times (CMCTs) in PSP patients CMCT, ms Patient
Biceps
Thenar
Tibialis
R L
4.48 4.80
5.44 5.12
14.08 14.08
R L
5.44 5.44
5.76 5.76
11.52 11.52
R L
4.48 4.80
5.76 6.08
13.12 13.12
R L
6.72"
7.20
n.m.
n.m.
n.m. n.m.
R L
4.80 4.80
5.76 5.44
14.08 14.08
R L
5.12 5.00
6.72 5.12
16.68 13.76
R L
4.80 4.80
5.44 5.76
12.00 16.68
R L
5.44 5.12
6.72 6.72
13.44 13.44
R L 10 R L 11 R L 12
4.80 4.80
5.12 5.44
13.76 13.76
4.80 4.48
5.12 4.80
12.16 12.16
5.44 5.12
6.40 6.40
12.80 12.80
R
6.40 5.44 5.10 0.54
7.36 7.04 5.93 0.73
16.40 14.40 13.63 1.44
4.87' 0.34 5.72
5.64' 0.33 6.47
13.15' 1.18 16.10
1 2 3 4
5 6 7
8
9
L Mean SD Control mean SD Upper confidence limit' ~
~
PSP, progressive supranuclear palsy; R, right; L, left; n.m., not measurable because of absence of cortical motor evoked potentials. " Italics indicate that CMCT exceeded upper confidence limit of normal controls. t-test for unpaired data: not significant. Upper confidence limit, mean + 2.5 SD.
'
thenar (Fig. 1, upper traces), and in two cases (unilaterally) for the tibialis anterior (Table 2). Patients with MEP abnormalities were characterized by a significantly longer illness duration (always above 4 years) and by an increased occurrence of pyramidal signs, such as pathologically brisk tendon jerks in three subjects and extensor plantar responses in one (Table 1).
SEPs The mean value of the CCT (N 13-N20 interval) of the lemniscal pathway was not different from that of normal controls and no patient exceeded the upper confidence limit (Table 3). Parietal (N20-P27) SEPs of large amplitude were usually observed (PSP, 8.64 ? 4.67 pV; NC, 4.93 ? 1.42 pV; t = 3.12, p
