Somatosensory evoked potentials elicited by stimulation of lower-limb nerves in amyotrophic lateral sclerosis

Electroencephalography and clinical Neurophysiology 104 (1997) 333–342

Somatosensory evoked potentials elicited by stimulation of lower-limb nerves in amyotrophic lateral sclerosis Michel Georgesco a,b,c,*, Antoine Salerno a,c, William Camu c a

Laboratoire d’Electromyographie, Service de Neurologie B, Hoˆpital Gui de Chauliac, 34295 Montpellier Cedex 5, France b INSERM U 300 (Prof. J.J. Le´ger), Faculte´ de Pharmacie, 34060 Montpellier, France c Service de Neurologie B (Prof. M. Billiard), Hoˆpital Gui de Chauliac, 34295 Montpellier Cedex 5, France Accepted for publication: 10 March 1997

Abstract To determine lower limb somatosensory modifications in amyotrophic lateral sclerosis (ALS), we studied somatosensory evoked potentials (SEPs) elicited by stimulation of tibial posterior nerves (TP), sural nerves (SN), saphenous internous nerves (SA), and medial plantar nerves (PL) of both limbs in 24 ALS patients, and compared the results with those from 17 normal subjects. Responses were recorded according to the international 10–20 system. Normal sensory conduction velocities of SN, SA and PL and H reflexes in soleus muscles were prerequisites for patient inclusion in this study. The results showed marked alterations in SEPs cortical components of all lower limb nerves, which could be related to abnormal sensory transmission (after spinal N22), or cortical abnormalities. We put forward the hypothesis of impairment of pyramidal control of the sensory system and Clark’s column involvement to explain such anomalies. It was concluded that SEPs abnormalities in the lower limbs are a common feature in ALS.  1997 Elsevier Science Ireland Ltd. Keywords: Amyotrophic lateral sclerosis; Lower limb evoked potentials; Pyramidal tract; Dysfunction; Sensory system

1. Introduction Previous studies of somatosensory evoked potentials (SEPs) in amyotrophic lateral sclerosis (ALS) have given contradictory results: some reports showed abnormalities in SEPs elicited from upper and lower limbs (Dustman et al., 1979; Cosi et al., 1984; Bosch et al., 1985; Dasheiff et al., 1985; Radtke et al., 1986; Georgesco et al., 1989; Subramaniam and Yannikas, 1990; Zanette et al., 1990; Zanette et al., 1996), while others revealed no SEPs disturbances in ALS (Matheson et al., 1983). We thus decided to study SEPs in ALS patients, particularly in the light of our previous findings (Georgesco et al., 1994) of abnormalities after median and tibialis posterior nerve (TP) stimulation. In the present study, we investigated SEPs elicited from sural (SN), saphenous internous (SA), medial plantar (PL)

* Corresponding author.

0168-5597/97/$17.00  1997 Elsevier Science Ireland Ltd. All rights reserved PII S0168-5597 (97 )0 0018-X

and TP in ALS patients’ nerves to check whether they were involved as noted with TP.

2. Subjects and methods 2.1. Patients Twenty-four patients (10 females and 14 males) were included in this study, which had received the approval of the local ethical committee. The criteria were as defined in the ‘Escorial’ meeting of the World Federation of Neurology (Brooks, 1994), including: progressive muscular weakness, upper and/or lower motor neuron degeneration, diffuse neurogenic EMG signs with normal sensory and motor conduction velocities, biological and radiological examinations excluding other diseases that mimic ALS, e.g. cervico-arthrosic myelopathy, monoclonal gammapathy, hyperthyroidism and hyperparathyroidism, lead intoxication, paraneoplastic syndromes or multifocal motor neuropathy (Table

EEP 96615

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M. Georgesco et al. / Electroencephalography and clinical Neurophysiology 104 (1997) 333–342

2.2. Methods

Table 1

Patients

Gender

Site of onset

WFN criteria

Age at onset (years)

Interval between onset and SEPs (months)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

F F F F F M M M M M F F F F F M M M M M M M M M

Bulbar Bulbar Bulbar Bulbar Bulbar Bulbar Bulbar Bulbar Bulbar Bulbar Spinal Spinal Spinal Spinal Spinal Spinal Spinal Spinal Spinal Spinal Spinal Spinal Spinal Spinal

Definite Definite Probable Probable Probable Definite Definite Probable Definite Definite Definite Probable Probable Probable Definite Definite Definite Definite Probable Definite Probable Probable Probable Probable

68 67 71 78 55 65 53 73 68 60 58 62 70 68 78 53 37 51 65 64 46 82 57 56

10 12 6 6 9 8 36 3 8 11 9 5 4 9 24 14 24 6 9 6 6 2 3 3

Normal H reflex of soleus muscle (H latency 34.2 ± 1.9 ms, M latency 6.4 ± 1.2 ms) and sensory nerve conductions of SN (48.7 ± 4.18 m/s), SA (50.1 ± 4.2 m/s) and PL (49.2 ± 6.9 m/s) nerves as measured in our laboratory were prerequisites for patient inclusion in this study. Conduction velocities were antidromically evaluated in both legs. The stimulating electrode for the PL nerve was placed on the plantar surface of the big toe to ensure strict cutaneus stimulation of the nerve. To elicit SEPs, all nerves were stimulated through a cutaneous electrode, with a 0.2 ms rectangular electrical shock, with proximal cathodes located: for TP, behind the internal maleolus; for SA, in the anterior part of the internal maleolus; for SN, behind the external maleolus; and for PL, in the plantar zone of the big toe. For the four cutaneous nerves, sensory thresholds were determined first; then stimulation intensities were adjusted to 2.5 times the sensory threshold without eliciting pain. For TP, it was enhanced until a slight movement of the big toe occurred. The stimulation frequency was 1.9 cycles/s. Recordings were performed through cutaneous electrodes located: for peripheral recordings: (1) nerve potential (for TP, SN and PL) active electrode at the popliteal fossa, 4 cm above the popliteal crease (PF), reference on the medial surface of the knee (K); (2) spinal potentials: active electrode on the spinous processes of T12, reference on the controlateral iliac crest (Ic); (3) on the scalp: 20 electrodes placed, according to the 10–20 international system (Fp1, Fz, Fp2, F8, F4, F3, F7, C4, Cz, C3, T3, T4, T6, T5, P4, Pz, P3, O2, Oz, O1) with a linked earlobe reference. Impedance was kept below 5 kW. The band pass was set between 1.5 Hz and 5 kHz. For each nerve, 500 artefact-free responses were averaged on a Pathfinder Plus Nicolet device. Analysis time was 50 ms poststimulus for the recording at the popliteal fossae and lumbar spine and 80 ms poststimulus for

1). In 10 patients, the site of onset of the disease was bulbar. The youngest was 37 and the oldest 82 years old at the onset of the disease (mean age 63.17 ± 8.24). The mean height was 166.04 ± 7.13 cm. The delay between onset of ALS and the SEPs investigations ranged from 2 to 36 months. As control, data of lower limb SEPs in 17 age-matched normal subjects (7 females and 10 males) were compared (mean age 61.56 ± 8.83 and mean height 169.28 ± 6.8 cm). Table 2 SEPs: mean amplitudes and latencies in normal subjects N1

P1

Right L

Left

N2

Right

Left

P2

Right

Left

N3

Right

Left

Right

Left

A

L

A

L

A

L

A

L

A

L

A

L

A

L

A

L

A

L

A

TP 33.5 SEM 1.6

0.3 0.1

34.7 1.8

0.8 0.32

39.2 1.8

2.3 0.9

39.5 1.4

2.5 1

49 1.3

2.1 0.9

49.2 1.9

2 0.7

59.9 1.8

1.5 0.6

60.7 2.5

1.3 0.7

72.4 2.5

2.8 1.1

72.8 2.8

2.7 1.3

SN 36.5 SEM 2

0.5 0.2

37.2 2.7

0.6 0.3

42 2.5

1.9 0.6

42.1 2.1

2 0.7

53.3 2.1

1.9 0.8

53.2 2

2.1 0.7

64.2 2.7

1.2 0.7

65.9 2.9

1.2 0.6

75.5 2.5

1.6 0.9

76.2 2.6

1.2 0.7

SA 37.1 SEM 2.7

0.4 0.2

36.7 2.5

0.4 0.2

42.3 2.3

1.2 0.4

42 1.9

1.2 0.5

54 2.4

1.9 0.8

54.2 2

1.8 0.7

66.1 3

1 0.5

66.7 2.5

1.5 0.5

76.9 2

0.7 0.4

77.3 1.6

0.8 0.5

PL 42.2 SEM 2.5

0.6 0.2

42.3 2.5

0.4 0.2

48.2 2.4

1.6 0.5

47.9 2

1.6 0.6

58.1 2.8

1.7 0.7

58.7 2.4

1.8 0.6

68.9 2.8

0.7 0.5

69.3 2.3

0.5 0.3

77.2 1.7

1.3 1

77.3 1.4

1.2 0.7

A, amplitude of potentials (mV); L, latencies (in ms).

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peaks recorded from the scalp. Peaks were labelled in order of their appearance on the scalp: P for positive and N for negative deflections. Examinations were replicated twice to check the reproducibility of the responses. Peak amplitudes were determined in the channel where they were maximal (measured baseline-to-peak) and latencies in the channel where they were shortest. We used Student’s t test for statistical analysis of the results. All values exceeding 2.5 SEM those recorded in normal subjects were considered abnormal.

For all nerves tested, we recorded the following deflections: a negative N1, a positively labelled P1, followed by a second negative N2, a second positive P2 and a terminal negative N3 (Table 2 shows the mean values with SEM for all peaks recorded on the scalp). N1 was missing in 2 subjects after TP stimulation, 3 subjects after SN and PL and 8 subjects after SA stimulation. P1 and P2 were always recorded. N2 was missing in 2 subjects (1 for the left TP and left PL). N3 was missing in 2 subjects for TP and SA (1 right and 1 left), PL-N3 was missing in 7 subjects (4 right and 3 left). No statistical differences were noted in N1 latencies between the left and right side.

3. Results

The maximal amplitude of P1 was found as follows:

3.1. Normal subjects

•

After stimulation of TP, SN and PL, nerve potentials recorded at the popliteal fossae were always present for TP and SN (TP mean latencies in ms, 9.5 ± 0.6, SN 9.2 ± 0.8); for PL it was present in few subjects (in 6 subjects, PL mean latency was 15.3 ± 1.4); for this reason the PL nerve potential at the popliteal fossae was not reliable. The spinal potential (labelled N22) was recorded in all subjects, except once for TP and SN, twice for PL and three times for SA. The mean latencies (in ms) were: TP 23.1 ± 1.1, for SN 24.2 ± 1.6, for SA 23.3 ± 0.2 and PL 30.7 ± 2.1.

•

For TP: in 14 subjects in Cz (10 times bilaterally and 4 times on the left), in 2 subjects between Cz– Pz (1 bilaterally and 1 on the right) and in the following positions each in 1 subject: between Fz–Cz (on the right), PZ–O2 (on the right), CZ– P4 (on the right), in C4 (on the right) and in 2 subjects in PZ (one on the right and one on the left). For SA: in 12 subjects in Cz (9 times bilaterally and in 3 subjects unilaterally: 1 on the left and 2 on the right), in 4 subjects between Cz–C4 (2 on the left and 2 on the right), in 2 subjects between Cz–Pz (one on the right and one on the left), in 2 subjects

Table 3 TP-SEPs in ALS patients Patient Right side N1

Left side P1

N2

P2

N3

N1

P1

N2

P2

N3

L

A

L

A

L

A

L

A

L

A

L

A

L

A

L

A

L

A

L

A

1 2 3 4 5 6 7 8 9 10

– – – 35.6 31.9 – – –

– 43.4 42.4 43.2 39 47.8 44.9 48.4 – 45.2

– 2.9 2.1 3.9 4.2 2.2 2.5 2.6 43.9 3.9

– – 56.9 52.5 42.9 – – – 4.2 50.7

– – 1.3 0.3 0.5 – – – 50.4 0.6

– – 67.1 66.1 – – 61.1 68.1 1.2 64.2

– – 2.3 3.6 – – 2.5 3.9 4.5 5.1

– – – 73.3 – – – – 4.5 79.6

– – – 0.1 – – – – – 1.9

– – – 36.6 – – – – – –

– – – 0.6 – – – – – –

– 45.5 – 44.7 40.1 35.1 – – 42.4 46.5

– 1.8 – 2.5 3.1 5.1 – – 2.8 4.3

– 59.3 – 57.5 – – – – 50.9 54.9

– 0.4 – 0.3 – – – – 1.7 0.6

– 72.1 – 68.1 – – 51.5

– 2.1 – 1.6 – – 4.6

–

– – – 0.5 0.6 – – – – –

67.3 69.7

3.3 4.4

– – – 74.4 – – – – – –

– – – 0.9 – – – – – –

11 12 13 14 15 16 17 18 19 20 21 22 23 24

36.1 – – – – 36.4 – – – – – – – –

0.5 – – – – 0.8 – – – – – – – –

38.3 – – – 49.4 48.1 – – 49.9 – 37.9 51.7 41.1 –

2.3 – – – 2.4 1.8 – – 3.7 – 2.4 2.2 3.1 –

45.5 – – – – 55.4 – – 55.9 – 45.5 62.1 53.1 –

0.2 – – – – 0.3 – – 0.5 – 0.8 0.3 0.7 –

61.9 57.5 – – 55.6 – 60.6 64.2 – – 48.8 – 67.3 –

3.7 4.2 – – 2.6 – 2.4 1.6 – – .1 – 2.5 –

76.7 – – – – 68.6 71.5 – – – – 78.8 –

0.8 – – – – 1.7 0.8 – – – – 0.3 –

34.8 – – – – – – – – – – 36.9 – –

1.2 – – – – – – – – – – 0.3 – –

36.7 – – – 40.3 39.3 48.4 – – – 41.1 55.4 38.5 –

3.9 – – – 2.2 1.8 1.8 – – – 2.1 3.2 3.9 –

42.4 – – – – 48.1 55.9 – – – 48.4 – – 47.8

1.3 – – – – 0.1 0.3 – – – 0.2 – – 0.2

58.2 72.1 60.3 – 62.4 – 67.1 – – – – – – 66.1

3.8 3.9 3.9 – 2.4 – 2.5 – – – – – – 3.5

72.8 71.5 67.2 – 78.1 – 76.4 – – – – – – –

1.9 3.8 0.1 – 1.5 – – – – – – – – –

A, amplitude of potentials (mV); L, latencies (in ms); –, absence of potentials; bold character represents significant increased latency of potential.

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Table 4 SS-SEPs in ALS patients Patient Right side N1

Left side P1

N2

P2

N3

N1

P1

N2

P2

N3

L

A

L

A

L

A

L

A

L

A

L

A

L

A

L

A

L

A

L

A

1 2 3 4 5 6 7 8 9 10

– 37.1 – – – 36.4 36.9 – 37.1 41.8

– 2.1 – – – 0.9 1.5 – 0.1 0.6

– 48.1 44.5 – 48.4 45.8 49.1 – 46.8 47.3

– 1.1 2.6 – 1.6 2.3 2.3 – 2.9 3.4

50.1 60.8 54.6 – 54.1 55.1 – – 58.2 55.1

0.2 0.4 0.3 – 0.7 0.4 – – 0.4 2.9

67.2 68.4 70.9 – 68.6 – – – 70.9 70.5

3.1 0.5 2.7 – 1.9 – – – 3.9 8.2

– – – – – – – – – –

– – – – – – – – – –

– – – – – – – – – –

– – – – – – – – – –

– – 50.9 50.7 46.8 38.2 – – – 43.7

– – 3.4 2.3 2.2 3.7 – – – 3.6

– – 60.1 59.1 55.1 56.7 – – – 52.5

– – 0.3 0.6 0.66 2.3 – – – 2.7

– – 73.3 65.3 9.4 70.2 – – – 75.5

– – 2.6 1.7 1.9 2.9 – – – 8.6

– – – – – – – – – –

– – – – – – – – – –

11 12 13 14 15 16 17 18 19 20 21 22 23 24

– – – – – – 35.8 – – – – – – –

– – – – – – 0.9 – – – – – – –

42.4 – 48.8 – – – 59.5 49.1 – – 43.9 54.1 – 52.3

2.1 – 2.3 – – – 2.2 2.8 – – 2.7 1.8 – 1.5

56.9 – 57.2 – – – 68.6 56.9 – – – 65.8 – 60.1

0.5 – 0.9 – – – 0.9 1.5 – – – 0.3 – 1.6

61.1 – – – – – 76.2 67.6 – – – 71.8 – –

0.5 – – – – – 2.6 3.6 – – – 1.9 – –

– – – – – – – 79.3 – – – – – –

– – – – – – – 1.6 – – – – – –

– – – – – – – – – – – – – –

– – – – – – – – – – – – – –

36.7 – – 43.4 – – 49.9 48.4 – 51.5 46.5 47.8 – 45.2

2.1 – – 3.7 – – 1.9 1.5 – 2.2 2.2 1.8 – 2.6

48.6 – – 53.6 – – 67.9 54.3 – – – 58.8 – –

0.6 – – 4.1 – – 0.4 0.7 – – – 0.9 – –

64.7 – – – – – 76.4 68.6 – – – – – 52.5

2.5 – – – – – 1.1 2.6 – – – – – 2.4

– – – – – – – – – – – – – –

– – – – – – – – – – – – – –

A, amplitude; L, latitude; –, absence of potentials; bold character represents significant increased latency of potential.

•

•

in C3 (2 on the left) and in the following position each in 1 subject: T4 (on the right), T5 (on the right), P4 (on the left), Fz (on the left SA) and C4 (on the right). For SN: in 14 subjects in Cz bilaterally and in 2 subjects unilaterally (1 right and one left side), in 2 subjects between Cz–Pz (1 bilaterally and 1 on the left) and in 1 subject in Pz (on the right). For PL: in 11 subjects in Cz bilaterally and in 3 subjects unilaterally (only on the left), in 2 subjects in C4 (on the right), in 2 others between C3–CZ (on the left), and in the following position each in 1 subject: between P3–O2 (on the right), Pz–O2, in Pz in T6 (on the right), and Cz–Pz (on the left).

The cortical amplitude ratio of the P1/nerve distal amplitude was: for SN, right 0.1 and left 0.1; for SA, right 0.2 and 0.2 left and for PL, right 0.2 and left 0.2. The TP-P1 cortical amplitude/nerve potential ratio at the popliteal fossae was 3.04 right and 3.9 left. 3.2. Patients Nerve potentials following TP, SN stimulation were always present. The mean latencies were (in ms): for TP: 9.9 ± 1.1 and for SN 9.4 ± 0.9. The spinal potentials (N22) were present in all patients except in 2 subjects for TP and

SN, in 3 patients for SA and PL. The mean latencies (in ms) were: for TP 22.7 ± 2.05, for SN 23.3 ± 1.5, for SA 24.08 ± 0.3 and for PL 30.05 ± 2.7. All patients investigated presented severe impairment of cortical components in at least one nerve. When all peaks were taken into consideration, there were extensive abnormalities in all patients. Tables 3, 4, 5, and 6 show the overall results for N1, P1, N2, P2 and N3. N1 followed by P1 were recorded: for TP in 5 patients; for SN in 10 patients; for SA in 6 patients and for PL in 3 patients. P1 latency was abnormal for TP in 2 patients, for SN in 1, for SA in 3 patients and for PL in 2 patients. P1 were recorded without N1: for the TP in 14 patients, for SN in 11 patients; for SA in 13 patients, and for PL in 11 patients. The P1 latency was modified: for TP in 9 patients, for SN in 3 patients, for SA in 5 patients and for PL in 8 patients. N1 and P1 were absent for TP in 12 patients; for SN in 14 patients; for SA in 13 patients; for PL in 15 patients. The total number of patients for which N1 was absent in at least one side was 22 for TP, 22 for SN, 24 for SA and in 24 for PL. The mean latencies for N1 were: for TP: on the right 35 ± 1.1 ms, on the left 36 ± 0.7 ms; for SN: on the right

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M. Georgesco et al. / Electroencephalography and clinical Neurophysiology 104 (1997) 333–342 Table 5 SN-SEPs in ALS patients Patient Right side N1

Left side P1

N2

P2

N3

N1

P1

N2

P2

N3

L

A

L

A

L

A

L

A

L

A

L

A

L

A

L

A

L

A

L

A

1 2 3 4 5 6 7 8 9 10

– – – 41.1 36.9 43.9 – – – –

– – – 0.7 0.4 0.8 – – – –

– – 45.5 47.1 40.1 51.5 – – – 44.8

– – 2.8 2.9 2.3 3.4 – – – 5.8

– – 55.1 55.4 48.4 58.8 – – – 51.7

– – 0.4 0.6 0.4 0.6 – – – 5.1

– – 66.8 63.7 – 70.2 – – – 70.7

– – 1.9 3.6 – 4.4 – – – 10.4

– – 77.7 – – – – – – –

– – 0.2 – – – – – – –

– 43.4 – – – – – – – –

– 0.7 – – – – – – – –

43.4 46.1 41.3 – 47.8 – – 52.8 – 45.2

1.9 1.5 2.8 – 2.5 – – 1.9 – 5.6

51.7 58.8 58.3 – – – – 59.5 – 50.9

0.7 0.8 0.8 – – – – 0.4 – 3.8

70.7 – 72.5 – – – – 68.4 – 72.5

4.9 – 3.2 – – – – 2.9 – 10.8

– – – – – – – – – –

– – – – – – – – – –

11 12 13 14 15 16 17 18 19 20 21 22 23 24

37.7 – – – 38.7 – 44.4 – – – 38.7 – – –

0.6 – – – 1.1 – 0.2 – – – 1.1 – – –

40.6 – 50.7 – 44.7 41.9 49.9 47.7 – – 48.8 49.7 – –

1.8 – 2.3 – 1.6 2.7 2.7 2.4 – – 0.9 2.4 – –

45.2 – 53.3 – – 48.1 65.3 50.4 – – – 61.9 – –

0.3 – 1.1 – – 0.9 0.8 0.4 – – – 0.2 – –

62.7 – 63.4 – – – 70.5 66.3 – – – 72.8 – –

2.4 – 3.4 – – – 1.8 2.2 – – – 1.9 – –

– – – – – – – – – – – – – –

– – – – – – – – – – – – – –

– 40.6 42.9 – – – 43.6 41.6 – – – – – –

– 0.3 0.5 – – – 0.4 0.3 – – – – – –

38.2 39.9 47.3 – – 43.2 47.3 40.6 52.8 – – – – –

2.4 4.3 3.1 – – 1.3 2.9 1.9 2.9 – – – – –

50.4 – – – – 47.1 61.4 51.7 – – – – – –

0.2 – – – – 0.3 0.1 0.1 – – – – – –

63.2 – 56.4 – – – 71.8 66.8 – – – – – –

2.7 – 1.3 – – – 1.8 3.3 – – – – – –

– – – – – – – 73.3 – – – – – –

– – – – – – – 1.2 – – – – – –

A, amplitude; L, latitude; –, absence of potentials; bold character represents significant increased latency of potential.

40 ± 2.5 ms, on the left 42.2 ± 1.8 ms; for SA: on the right 38.5 ± 2.3 ms and 1 patient on the left 37.1 ms; for PL: on the right 45.8 ± 2.7 ms, on the left 45.2 ± 1.3 ms. Compared to normal, no statistical differences were noted for N1-TP, for N1-SA on the right side and for N1-PL. The mean latency for N1-SN in patients with prolonged N1 compared to control was P = 0.00536 for the right side and P = 0.000628 for the left. In some subjects, SEP showed a late component with latencies close to the P2 of normal subjects. This component was present in 6 patients for TP, in 1 patient for SA on the right and in 1 patient for PL on the left. The P2 was never observed following SN stimulation. N3 for all nerves were recorded in 10 patients for TP, 2 patients for SN, 1 patient for the right PL and 1 for the right SA. The cortical amplitude ratio of P1/nerve distal amplitude was: for SA on the right 0.4 and on the left 0.5, for SN on the right 0.2 and on the left 0.2 and for PL on the right 0.3 and on the left 0.2. The TP-P1 cortical amplitude /nerve potential ratio on the popliteal fossae was 3.7 right and 4.4 left. When considering the clinical forms: P1 was absent in the defined forms: for TP in 5 patients (3 bilaterally and 1 for the right and 1 for the left), for SN in 7 patients (3 bilaterally, 2 for the right and 2 for the left), for SA in 7 patients (3

bilaterally, 1 for the right and 3 for the left) and for PL in 9 patients (6 bilaterally, 1 for the right and 2 for the left). In the probable form, P1 was absent: for TP in 7 patients (4 bilaterally and 3 for the left), for SN in 9 patients (4 bilaterally, 2 for the right and 3 for the left), for SA in 7 patients (4 bilaterally, 2 for the right and 1 for the left) and for PL in 8 patients (4 bilaterally, 3 for the right and 1 for the left). In the bulbar forms, P1 was absent: for TP in 4 patients (1 bilaterally and 3 for the left), for SN in 7 patients (2 bilaterally, 3 for the right and 2 for the left), for SA in 6 patients (2 bilaterally, 1 for the right and 3 for the left) and for PL in 5 patients (3 bilaterally, 2 for the right). In the spinal forms, P1 was absent: for TP in 8 patients (6 bilaterally, 1 for the right and 1 for the left), for SN in 9 patients (4 bilaterally, 2 for the right and 3 for the left), for SA in 8 patients (5 bilaterally, 2 for the right and 1 for the left) and for PL in 12 patients (7 bilaterally, 2 for the right and 3 for the left). In Fig. 1, SEPs of the right and left TP nerve were present but not after stimulation of other nerves. When the recording was limited to only the TP nerve, ‘normal SEPs’ results were obtained. In Fig. 2, dissociations occurred on the right and left side: on the right side, P1-SEPs of the TP nerve were present while stimulation of the PL was ineffective; the contrary was obtained in the lower left limb.

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Fig. 1. A 56-year-old male. Probable ALS with spinal form. SEPs performed after a 3-month evolution. The time base for PF-K and T12-Ic recordings was 10 ms/div. and 13 ms/div. for all scalp recordings. Negative deflection = up. No SEPs were recorded except after TP stimulation.

4. Discussion This work demonstrates that SEPs elicited by stimulation of lower limb nerves (TP, PL, SN and SA) are severely impaired in ALS patients. The proportion of altered TPSEPs was identical to results obtained in our preliminary work. Different anatomical modifications of the peripheral nerve were reported in ALS (Kennedy, 1971; Dyck et al., 1975; Kawamura et al., 1981). We do not think that these lesions were present in our patients because peripheral sensory nerve conductions, H reflexes, nerve potentials re-

corded at the popliteal fossae and spinal N22 of all nerves recorded in T12 were comparable to those of normal subjects (percentage of deflections recorded, morphology, amplitudes and latencies). In our work, different patterns of N1 and P1 alterations were noted: (a) patients without any recordable deflections on the scalp; (b) patients without N1 but with detectable P1 (which could be normal or delayed); (c) patients with detectable N1 followed by normal or altered P1. The absence of N1 observed in our patients could have resulted from technical problems, i.e. the earlobe reference which is known to diminish N1 amplitude (Yamada et al.,

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Fig. 2. A 71-year-old female. Probable ALS with bulbar form. SEPs performed after a 6-month evolution. The time base for PF-K and T12-Ic recordings was 10 ms/div. and 13 ms/div. for all scalp recordings. Negative deflection = up. Note that on the right side SEPs were recorded after TP stimulation and absent after PL stimulation: opposite results on the left side.

1982; Desmedt and Cheron, 1983). Nevertheless, we think that this is related to the disease since the proportion of patients without a clear recordable N1 was high compared to controls. This suggests that sensory transmission of SEPs for lower limbs was impaired in ALS after N22 as N1 is considered to be generated by thalamo-cortical radiation (Seyal et al., 1983). This impairment could explain the absence of all SEPs components or the delayed P1. Anatomical data support this hypothesis for TP-SEPs since they transmit muscular afferences mediated by Clark’s column (Burke et al., 1981, 1982; Brodal, 1981; York, 1985) which is altered in ALS (Averback and Crocker, 1982; Williams et al., 1990). However, this does not apply to SA, SN and PLSEPs which are of cutaneous origin and should be trans-

mitted by the dorsal column funiculi (Brodal, 1981) as they are spared in ALS except in familial forms (Lawyer and Netsky, 1953; Hirano et al., 1967; Castaigne et al., 1972). In our work, the mean latency of SN-N1 in patients with N1 recorded was prolonged on both sides, indicating that transmission after spinal N22 was impaired for this nerve; this may explain the SEPs disturbances recorded. Considering the pathways mediating this afference in the spinal cord, this alteration is not supported by anatomical data in ALS. The normal N1 latencies in some patients suggests that sensory transmission for SEPs was not modified up to the thalamo-cortical radiations. The fact that the following P1 was altered indicated that in these patients SEPs impairment takes place at the cortical level. Anatomical and experimen-

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Table 6 PL-SEPs in ALS patients Patient Right side N1

Left side P1

N2

P2

N3

N1

P1

N2

P2

N3

L

A

L

A

L

A

L

A

L

A

L

A

L

A

L

A

L

A

L

A

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

– – – – – – – – – – – – – – – – 43.6 – – –

– – – – – – – – – – – – – – – 0.3 – – –

43.7 48.1 – 47.3 54.1 – – – – 54.3 – – – – – – 48.4 50.2 53.8 –

2.3 2.5 – 2.3 2.1 – – – – 3.7 – – – – – – 1.8 2.2 4.3 –

– – – 60.3 – – – – – 61.9 – – – – – – 55.9 60.8 58.2 –

– – – 0.1 – – – – – 1.1 – – – – – – 0.3 0.3 0.5 –

– – – 68.9 – – – – – 77.5 – – – – – – 67.1 67.6 – –

– – – 2.7 – – – – – 3.1 – – – – – – 2.5 1.4 – –

– – – – – – – – – – – – – – – – 76.4 – – –

– – – – – – – – – – – – – – – – 0.1 – – –

– – – 47.5 – – – – – – – – – – – – – – – –

– – – 0.2 – – – – – – – – – – – – – – – –

54.6 52.3 54.3 55.1 55.9 – – – 51.5 54.6 – – – 58.2 – – – – – –

1.6 2.2 2.3 2.3 1.1 – – – 2.7 4.1 – – – 3.7 – – – – – –

– – 65.4 61.1 59.5 – – – 62.7 62.4 – – – 72.1 – – – – – –

– – 1.1 1.5 0.3 – – – 0.6 2.1 – – – 2.1 – – – – – –

– – 76.9 – 65.5 – – – – – – – – – – – 61.1 – – –

– – 1.1 – 1.6 – – – – – – – – – – – 2.1 – – –

– – – – – – – – – – – – – – – – – – – –

– – – – – – – – – – – – – – – – – – – –

21 22 23 24

– 49.9 – 43.9

– 0.4 – 0.9

– 56.9 – 48.8

– 2.6 – 2.4

– 59.8 – –

– 0.5 – –

– – – –

– – – –

– – – –

– – – –

44.4 – –

0.6 – –

50.2 51.2 – 50.2

2.5 1.6 – 2.4

56.7 56.2 – 55.6

0.4 0.2 – 0.2

– 62.1 – 72.8

– 1.8 – 1.7

– – – –

– – – –

A, amplitude; L, latitude; –, absence of potentials; bold character represents significant increased latency of potential.

tal data demonstrated pyramidal cell modifications, but no sensory cell alterations in the cortical area (Davison, 1941; Udaka et al., 1986; Smith, 1960; Murayama et al., 1991; Kiernan and Hudson, 1991; Kew et al., 1993, 1994; Pioro et al., 1994). No sensory disturbances in the cortical area could thus explain SEPs abnormalities in ALS. They may result from pyramidal cell dysfunctions: Peterson et al. (1995) recently demonstrated the involvement of pyramidal cells of cortical layer III in SI in the elaboration of SEPs following median nerve stimulations in monkeys. If these pyramidal cells are altered, SEP disturbances could be expected. We hypothesize that the impairment responsible for SEP abnormalities involved the modified relation between the pyramidal system and sensory area cells, since: (a) many experimental data indicate influences of the motor cortex on the sensory ascending system in animals and man (Kuypers, 1958; Magni et al., 1959; Towe and Jabbur, 1961; Gordon and Jukes, 1964; Jones and Powel, 1968; Rinvik, 1968; Ku¨nzle, 1976; Coquery, 1978; Dyhre-Poulsen, 1978; Rustioni et al., 1979). The main effect is inhibitory and can be exerted at different levels: dorsal horn, dorsal column nuclei and thalamus. Facilitatory effects have also been reported by some authors (Towe and Jabbur, 1961; Winter, 1965). (b) Recently, Seyal et al. (1993) reported enhancement of cortical SEPs after magnetic brain stimulation, attributed to pyramidal cell synchronization, resulting from the shock.

(c) In our patients, the massive absence of subcortical and cortical components of TP, SA and PL-SEPs, and prolonged latencies of subcortical components in SN-SEPs were not supported by sensory abnormalities indicated in the anatomical data. Our results showed that, in some patients, TP-SEPs were present while PL-SEPs were lacking and vice versa. This implies that each nerve stimulated can elicit its own independent cortical generator. TP-SEPs are made of muscular afferences (Burke et al., 1981) and PL-SEPs of sensory afferences. This suggests that each kind of afference has its own cortical representation. This is compatible with anatomical data in the monkey, where different cortical representations have been described in SI, according to the afferences stimulated (for more details, see Mountcastle, 1984). In conclusion, abnormal lower limb SEPs in ALS is a common feature. Two explanations are proposed: lesion of Clark’s column and dysfunction of the influence exerted by the pyramidal system on the ascending sensory pathways. Both are possible for alteration of TP-SEPs.

Acknowledgements We thank Thierry Chemineau for the iconography. This

M. Georgesco et al. / Electroencephalography and clinical Neurophysiology 104 (1997) 333–342

investigation was supported by a grant from the Association Franc¸aise contre les Myopathies and INSERM U 300.

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