Prolonged intracortical delay of long-latency reflexes: electrophysiological evidence for a cortical dysfunction in multiple sclerosis

Convincing evidence suggests that long-latency reflexes (LLRs) are capable of testing the transcortical sensorimotor reflex arch. By subtracting the sum of the latencies of N20 (afferent branch) and transcranially elicited motor evoked potentials (MEP; efferent branch) from the LLR II latency, the cortical relay time (CRT) can also be obtained, which is alleged to represent the time required for the cortical sensorimotor integration. The aim of the present study was to investigate if a cortical dysfunction occurs in multiple sclerosis (MS). Median nerve somatosensory evoked potentials (SEPs), MEPs and LLRs were recorded from the upper limbs of 23, not severely disabled MS patients in acute phases of the disease. Eighteen age and sex matched healthy volunteers served as controls. N20, MEP, LLR II latencies were measured, and the CRT was calculated for each limb. The statistical comparison between patients and controls was only weakly significant by taking into account conduction times along either the afferent (N20) or the efferent (MEP) pathways. On the contrary, it turned out to be considerably significant if both branches of the transcortical sensorimotor reflex arch, together with the intracortical pathway, were simultaneously tested by means of the LLRs. Moreover, the patients showed a significantly higher CRT compared with that found in the control subjects. These findings are consistent with a prolonged intracortical delay of LLRs in the MS group and suggest the occurrence of conduction velocity slowing and/or synaptic transmission impairment along the sensorimotor intracortical pathway in MS.     

Long latency response of the mentalis muscle following transcranial magnetic stimulation with a circular coil in normal subjects

Short latency response (SLR), middle latency response and long latency response (LLR) are elicited in facial muscles by transcranial magnetic stimulation. Although it has been said that the LLRs are elicited by the trigeminal nerve stimulation, a trigeminofacial reflex is recorded easily in normal subjects by the electrical stimulation in orbicularis oculi muscles as a blind reflex, but a trigeminal-facial reflex recorded in orbicularis oris, namely a snout reflex, is more difficult to record in normal subjects. The aim of this study is to demonstrate the LLR of lower facial muscles (mentalis muscle) by the transcranial magnetic stimulation, using a circular coil. The transcranial magnetic stimulations were performed over parieto-occipital scalp with frequencies of random and 0.3 Hz in 11 normal subjects and the responses in the mentalis muscle were recorded. The LLR of the mentalis muscle was recorded in all 11 subjects following SLRs. The latency, duration and LLR/SLR ratio were 37.4 msec, 20.3 msec and 9.1%, respectively. The waveform of the LLR varied trial to trial showing habituation with a stimulation of 0.3 Hz. At this time the LLR of the masseter muscle was not recorded following this transmagnetic stimulation. It was suggested that the LLR of the mentalis muscle is recorded by the transcranial magnetic stimulation of the trigeminal nerve with a circular coil. The ease and reliability of their recording make it possible to apply this LLR clinically as well as a blink reflex.     

The relations between long-latency reflexes in hand muscles, somatosensory evoked potentials and transcranial stimulation of motor tracts

In 15 normal subjects the latency of electrically elicited long-latency reflexes (LLRs) of thenar muscles was compared with somatosensory evoked potentials (SEPs) after median nerve stimulation and with the latencies of thenar muscle potentials after transcranial stimulation (TCS) of the motor cortex. Assuming a transcortical reflex pathway the intracortical relay time for the LLR was calculated to be 10.4 +/- 1.9 msec (mean +/- S.D.) or 8.1 +/- 1.6 msec depending on the experimental conditions. The duration of the cortical relay time is not correlated with the peripheral or central conduction times, with body size or arm length. If the LLRs of hand muscles are conducted transcortically the long duration of the cortical relay time suggests a polysynaptic pathway.     

The diagnostic significance of long-latency reflexes in multiple sclerosis

Reflexes of thenar muscles after median or radial superficial nerve stimulation have been investigated in both hands of 47 patients with probable or definite multiple sclerosis (MS) and compared with somatosensory evoked potentials (SEPs) to median nerve stimulation. A delay or absence of long-latency reflexes (LLRs) was found as pathological patterns. The results after median or radial superficial nerve stimulation were usually both pathologic or both normal except in cases with latencies at the upper limit of normal values. Pathological results of reflex testing were obtained in 61% of the patients with probable MS and in 79% of those with definite MS. Abnormal SEPs were found in 44% of the patients with probable MS compared to 62% with definite MS. All cases which had pathologic SEPs also had pathologic LLR. Hence, LLR testing detected more abnormalities than the routine median nerve SEP testing that has been used.     

Correlation of somatosensory evoked potentials and long loop reflexes in patients with multiple sclerosis

Based on the results of somatosensory evoked potentials (SEPs) and long loop reflexes (LLRs) obtained from the 50 upper limbs of 25 normal controls by stimulating the median nerve, four regions were set up in a latency correlation diagram between N20 and LLR, which were assumed to mainly represent the afferent and the efferent functions, respectively. Seventy upper limbs of patients with multiple sclerosis, differently marked according to the presence or absence of pyramidal sign and/or impaired vibration sense, were plotted on the diagram. The regions to which the patient belonged turned out to be reasonably compatible with the neurological status of the patient. Simultaneous measurements of SEPs and LLRs are therefore useful to evaluate the afferent and efferent pathways in the central nervous system.     

Electrophysiological deterioration over time in patients with Huntington's disease.

In recent studies aimed at assessing the effects of original therapeutic strategies applied to patients with Huntington's disease (HD), we observed informative changes in electrophysiological results that recovered normal values in coherence with clinical improvement. However, longitudinal studies were lacking for determining whether electrophysiological test results evolve in parallel with clinical markers of the natural course of the disease and could consequently provide objective quantifiable markers of disease progression. For this purpose, electrophysiological testing was performed annually in a cohort of 20 patients with HD over a 2-year period (three examinations). The study included the recording of sympathetic skin responses and blink reflexes (BRs) to supraorbital nerve stimulation, long latency reflexes (LLRs) and somatosensory evoked potentials (SEPs) to median nerve stimulation, and cortical silent periods (CSPs) to transcranial magnetic stimulation. Clinical evaluation was based on the Total Functional Capacity scale (TFC) and the Motor part of the Unified Huntington's Disease Rating Scale (UHDRS). A significant deterioration with time was found for BR latency, LLR presence, various SEP parameters (parietal N20 peak amplitude and frontal N30 presence) and CSP duration. Attenuation of the N20 peak and CSP shortening correlated with functional decline, as assessed by the TFC score, whereas delayed BR and LLR abolition correlated with UHDRS Motor score deterioration. This study shows that several electrophysiological parameters are closely associated with dysfunction of various neural circuits in HD and could be useful markers of disease progression.     

Central and peripheral conduction times in multiple sclerosis

Somatosensory evoked potentials (SEPs) were recorded simultaneously from the cervical spine and scalp in 25 normal subjects and 105 patients with established or suspected multiple sclerosis (MS) using median nerve stimulation. The normal latency of the main peak of the cervical SEP (N14) following median nerve stimulation at the wrist was 13.7 +/- 0.8 msec. The peak latency of the first cortical event of the scalp SEP (N20) was 19.1 +/- 0.9 msec. The difference in these latencies (N20 -- N14) reflects a conduction time between the dorsal column nuclei and cortex. It measured 5.45 +/- 0.7 msec. The conduction times between the wrist and Erb's point and Erb's point and N14 measured 8.6 +/- 0.7 msec and 5.1 +/- 0.6 msec respectively. There was a 68.6% overall incidence of abnormalities of N14, N20 or (N20 -- N14) in the patients. This incidence was over 80% in definite and early probable or latent MS, 68.2% in progressive spinal MS and 40.0% in suspects. SEPs were also simultaneously recorded from the lower thoracic spine (T12) and scalp in a different group of 25 normal subjects using tibial nerve stimulation. The latency of the thoracic SEP (N21) was 21.4 +/- 1.5 msec and that of the first cortical event of the scalp SEP (P40) was 38.6 +/- 2.2 msec. The difference in these latencies (P40 -- N21) which reflects conduction between T12 and the cortex measured 17.2 +/- 1.7 msec. Conduction between the ankle and popliteal fossa was 7.0 +/- 0.65 msec and between the popliteal fossa and N21, it was 14.5 +/- 1.1 msec. All of a small group of MS suspects showed abnormality of P40 or (P40 -- N21).     

Experimental study of a late response recorded from the thoracic wall after phrenic nerve stimulation

ObjectivesThe phrenic nerve cervical stimulation induces an early motor diaphragmatic M response that may be recorded from the 7th ipsilateral intercostal space (ICS). Some responses with prolonged latency and of unclear origin can be recorded from the same recording site. The aim of the study was to determine the electrophysiological characteristics and the neuroanatomical pathways underlying the long-latency responses (LLRs) recorded from the 7th ICS.MethodsWe studied seven healthy volunteers, five patients with spinal cord injury and five patients with diaphragmatic palsy. All underwent phrenic nerve conduction study. An LLR was sought for at different stimulation sites using various stimulus intensities.ResultsA polyphasic LLR was recorded from the 7th ICS in all healthy subjects. It was mainly elicited by nociceptive stimulations, not only of the phrenic, but also of the median nerves. Its latency was longer than 70 ms, with a wide inter- and intra-individual variability. Amplitude was highly variable and some habituation phenomenon occurred. The LLR was retained in most tetraplegic patients after phrenic nerve stimulation, but absent otherwise. It was present in all patients with diaphragmatic palsy after phrenic nerve stimulation.ConclusionThe LLR is likely to be produced by both intercostal and diaphragm muscles. It is a polysynaptic and multisegmental spinal response, probably conveyed by small-diameter nociceptive A-δ and/or C fibres and modulated by a supraspinal control.SignificanceThe LLR recorded from the chest wall may constitute, by analogy with the nociceptive component of the lower limb flexion reflex in humans, a protective and withdrawal spinal reflex response.     

Cortical relay time for long latency reflexes in patients with definite multiple sclerosis

BACKGROUND: Long latency reflexes (LLR) include afferent sensory, efferent motor and central transcortical pathways. It is supposed that the cortical relay time (CRT) reflects the conduction of central transcortical loop of LLR. Recently, evidence related to the cortical involvement in multiple sclerosis (MS) has been reported in some studies. Our aim was to investigate the CRT alterations in patients with MS. METHODS: Upper extremity motor evoked potentials (MEP), somatosensory evoked potentials (SEP) and LLR were tested in 28 patients with MS and control subjects (n=22). The patients with MS were classified according to the clinical form (relapsing-remitting [R-R] and progressive groups). The MS patients with secondary progressive and primary progressive forms were considered as the "progressive" group. CRT for LLR was calculated by subtracting the peak latency of somatosensory evoked potentials (SEP) and that of motor evoked potentials (MEP) by transcranial magnetic stimulation from the onset latency of the second component of LLR (LLR2) (CRT = LLR2 - [MEP latency + N20 latency]) RESULTS: Cortical relay time was calculated as 7.4 +/- 0.9 ms in control subjects. Cortical relay time was prolonged in patients with MS (11.2 +/- 2.9 ms) (p<0.0001). The latencies of LLR, MEP and SEP were also prolonged in patients with MS. Cortical relay time was not correlated with disease severity and clinical form in contrast to other tests. CONCLUSIONS: Our findings suggested that CRT can be a valuable electrophysiological tool in patients with MS. Involvement of extracortical neural circuits between sensory and motor cortices or cortical involvement due to MS may cause these findings.     

Long latency EMG responses in early diagnosis of Huntington's chorea

Summary In healthy subjects, 2 EMG responses of the thenar muscles can be distinguished, elicited by electrical stimulation of the median nerve during an isometric contraction: an early spinal response (M₁) and a long latency response (LLR) (M₂); earlier studies have shown that in patients with Huntington's chorea (HC) this late EMG response is missing. LLR were studied in nine subjects at risk out of three families with definite HC. In 6 of them, LLR was clearly asymmetrical or absent on one or both sides, while normal LLRs were seen in the rest of the subjects studied; LLR abnormalities found in clinically free members of HC families may assist in early diagnosis of individuals who may later develop symptoms and may help in genetic counselling.     

Brain excitability and long latency muscular arm responses: non-invasive evaluation in healthy and parkinsonian subjects.

Thirty healthy and 35 volunteers affected by Parkinson's disease (PD) were examined. Long latency responses (LLRs) and short latency somatosensory evoked potentials (SEPs) after median nerve stimulation were respectively recorded from forearm flexor muscles, and from 19 scalp electrodes, during relaxation (condition 1), light and maximal muscle contraction (conditions 2 and 3). Linear interpolation of SEPs was performed to produce isopotential colour maps. Latencies and amplitudes of the V1-V2 component in LLR, as well as of parietal, central and frontal scalp SEPs were analysed in the 3 experimental conditions. Highly significant inverse correlation matched the frontal SEP to the LLR V2 component amplitudes, both in healthy and in PD subjects. However, the V2 component--which in the former group was reliably identifiable only in condition 3--was presented in conditions 1 and 2 in a high percentage of PD subjects who also showed an abnormally reduced frontal SEP during complete relaxation. Excitability changes of brain motor areas induced by a sensory input were tested as follows: the motor cortex was transcranially stimulated (TCS) by magnetic pulses with an intensity 10% below (A) or above (B) the threshold for twitch elicitation during complete relaxation of forearm muscles; TCS was randomly preceded (range 14-32 msec) by a shock to the median or ulnar nerve at the elbow with identical characteristics as for LLR elicitation. An initial epoch of 'inhibition' followed by a peak of 'facilitation' of the amplitude of motor responses to TCS was observed when conditioning stimuli to the median nerve preceded TCS by 14-20 and by 24-32 msec, respectively. Contrary to normals, conditioning stimulation of the median nerve did not significantly influence the excitability threshold to TCS in those parkinsonians with depressed frontal N30.     

Long-latency reflexes in contracted hand and foot muscles and their relations to somatosensory evoked potentials and transcranial magnetic stimulation of the motor cortex.

OBJECTIVE: The cortical relay time (CRT) for V2 of long-latency reflexes (LLRs) in the contracted thenar and short toe flexor muscles was studied. METHODS: LLRs and somatosensory evoked potentials (SEPs) were studied by electrical stimulation of the median or posterior tibial nerve. The CRT for V2 was calculated by subtracting the onset latency of cortical potentials in SEPs and that of motor evoked potentials (MEPs) by transcranial magnetic stimulation (TMS) from the onset latency of V2 in eight healthy subjects. RESULTS: The CRT for the thenar muscles was 11.4+/-0.9 ms (mean +/- SD), as the onset latency was 48.8+/-1.4 ms for V2, 16.0+/-1.2 ms for N20 and 21.3+/-1.1 ms for MEP, respectively. The CRT for the short toe flexor muscles was 3.0+/-1.3 ms, as the onset latency was 80.5+/-4.5 ms for V2, 35.3+/-1.8 ms for P38 and 42.2+/-2.0 ms for MEP, respectively. CONCLUSION: Significantly longer CRT for V2 for the thenar muscles (P<0.001, paired Student's t test) may indicate more synaptic relays as compared to that for the short toe flexor muscles.     

Long-latency reflexes in patients with Behçet's disease

Objective: Recent studies demonstrate that the subclinical involvement of motor pathways is frequently observed in patients with Behçet's disease (BD). Long-latency reflexes (LLR) provide information about the continuity of both ascending and descending neural pathways. Our aim was to evaluate the utility of LLR and somatosensory-evoked potentials (SEP) in demonstrating subclinical neural involvement in patients with BD. Methods: Twenty-nine patients with BD were studied by means of SEP and LLR. Bilateral median nerve SEPs and LLRs evoked by electrical stimulation of both median nerves were recorded. The latency of second component of LLR (LLR2), the duration of LLR2–HR (Hoffmann reflex, spinal reflex component of LLR) interval, peak to peak amplitude of LLR2 and the amplitude ratio of LLR2/HR were analyzed. The data obtained from patients were compared with those of 20 control subjects. Results: LLR2 latencies and the durations of LLR2–HR interval were significantly prolonged in patients with BD (p=0.001 for both parameters). Increased duration of LLR2–HR interval was the most frequent abnormality observed in the study (37.9%). Conclusion: Our findings suggest that LLR is a useful technique to demonstrate subclinical neural involvement in patients with BD.     

Brain dysfunction explored by long latency reflex: a study of adrenomyeloneuropathy

OBJECTIVES: We can assess brain function by measuring the cortical relay time (CRT) of long latency reflex (LLR) of hand muscle. We would study if measurement of CRT of LLR can explore the brain involvement of adrenomyeloneuropathy (AMN). METHODS: Two AMN patients were included in the study. Both of them had spastic gait and mild sensory deficits but normal mental function. The LLRs were provoked at the first dorsal interosseous muscle by electrical stimulation of the middle finger. We measured the latency of LLR and its CRT. RESULTS: Delayed LLR and prolonged CRT were noted in AMN patients, even though the magnetic resonance imaging of brain did not show any significant abnormalities. CONCLUSIONS: Measuring CRT of LLR reveals brain involvement of AMN patients, and it is an adjunct in the assessment of brain function though without specific anatomic diagnosis.     

Conduction time in central somatosensory pathways in man.

Simultaneous recording of the somatosensory evoked potential (SEP) from the neck and from the scalp allows investigation of conduction of somatosensory impulses within the central nervous system alone. The early components of the SEP produced by stimulation of the median nerve at the wrist were recorded from standardized electrode locations on the scalp and neck in 21 normal subjects. The peak latency of both the initial negative potential from the scalp, N20 (19.4 +/- 1.1 msec), and the major negative negative potential from the neck, N14 (13.8 +/- 0.9 MSEC), CORRElated positively with arm length and with height. The difference between the peak latencies of N20 and N14 (5.6 +/- 0.5 msec) was independent of both arm length and height. As the latency and distribution of N14 indicate that this potential probably arises from the dorsal column nuclei, the N20--N14 latency difference provides a measure of conduction time within central pathways which is independent of conduction time in the limbs and spinal cord. Recording of the SEP from the neck, simultaneously with that from the scalp, also facilitates clinical investigation of the somatosensory system.     

Developmental assessment of spinal cord and cortical evoked potentials after tibial nerve stimulation: effects of age and stature on normative data during childhood

Somesthetic information from lower extremities is processed by cerebral cortex after traversing the sensory pathways of peripheral nerve, spinal cord, brain-stem and thalamus. Clinical utility of somatosensory evoked potentials (SSEPs) during human development requires systematic analysis of normative data acquired during various stages of body growth and nervous system maturation. Accordingly, SSEPs after tibial nerve stimulation were studied in 32 normal awake children (1-8 years old) and compared with values obtained in young adults (18-40 years old). Potentials were recorded from the tibial nerve (N5), first lumbar spinous process (N14), seventh cervical spinous process (N20) and from the scalp, 2 cm behind the vertex (P28). In all children studied, the N5, N14 and N20 latencies were positively correlated with age and height yielding a predictive nomogram. An extremely variable electropositive cortical SSEP was recorded from Cz' which did not show a highly predictable linear relationship in association with a relatively poor correlation coefficient for height and age. It may be concluded that between 1 and 8 years of normal postnatal development, latencies reflecting peripheral nerve and lumbar spinal cord vary directly with height and age and can be represented by a simple cable model of a lengthening myelinated pathway. In contrast, the latency of the cortical SSEP reflects asynchronous maturation of elongating polysynaptic pathways and apparently requires a more complex model for prediction in order to enhance its clinical utility.     

The carpal tunnel syndrome: localization of conduction abnormalities within the distal segment of the median nerve.

Palmar stimulation was used to assess median nerve conduction across the carpal tunnel in 61 control patients and 105 patients with the carpal tunnel syndrome. With serial stimulation from midpalm to distal forearm the sensory axons normally showed a predictable latency change of 0.16 to 0.21 ms/cm as the stimulus site was moved proximally in 1 cm increments. In 47 (52 per cent) of 91 affected nerves tested serially, there was a sharply localized latency increase across a 1 cm segment, most commonly 2 to 4 cm distally to the origin of the transverse carpal ligament. In these hands, the focal latency change across the affected 1 cm segment (mean +/- SD: 0.80 +/- 0.22 ms/cm) averaged more than four times that of the adjoining distal (0.19 +/- 0.09 ms/cm) or proximal 1 cm segments (0.19 +/- 0.08 ms/cm). In the remaining 44 (48 per cent) hands, the latency increase was distributed more evenly across the carpal tunnel. Unlike the sensory axons the motor axons were difficult to test serially because of the recurrent course of the thenar nerve, which may be contained in a separate tunnel. The wrist-to-palm latency was significantly greater in the patients with carpal tunnel syndromes than in the controls for sensory (2.18 +/- 0.48 ms v 1.41 +/- 0.18 ms) and motor axons (2.79 +/- 0.93 ms v 1.50 +/- 0.21 ms). Consequently, there was considerable difference between the carpal tunnel syndromes and controls in SNCV (38.5 +/- 7.5 m/s v 57.3 +/- 6.9 m/s), and MNCV (28.2 +/- 4.5 m/s v 49.0 +/- 5.7 m/s). In the remaining distal segment, however, there was only a small difference between the two groups in sensory (1.48 +/- 0.28 ms v 1.41 +/- 0.22 ms) and motor latency (2.15 +/- 0.34 ms v 2.10 +/- 0.31 ms). The exclusion of the relatively normal distal latency made it possible to demonstrate mild slowing across the carpal tunnel in 36 (21 per cent) sensory and 40 (23 per cent) motor axons of 172 affected nerves when the conventional terminal latencies were normal. Sensory or motor conduction abnormalities were found in all but 13 (8 per cent) hands. Without palmar stimulation, however, an additional 32 (19 per cent) hands would have been regarded as normal.     

Peripheral and segmental spinal abnormalities of median and ulnar somatosensory evoked potentials in Hirayama's disease

OBJECTIVES: To investigate the origin of juvenile muscle atrophy of the upper limbs (Hirayama's disease, a type of cervical myelopathy of unknown origin). SUBJECTS: Eight male patients were studied; data from 10 normal men were used as control. METHODS: Median and ulnar nerve somatosensory evoked potentials (SEP) were recorded. Brachial plexus potentials at Erb's point (EP), dorsal horn responses (N13), and subcortical (P14) and cortical potentials (N20) were evaluated. Tibial nerve SEP and motor evoked potentials (MEP) were also recorded from scalp and spinal sites to assess posterior column and pyramidal tract conduction, respectively. RESULTS: The most important SEP findings were: a very substantial attenuation of both the EP potentials and the N13 spinal responses; normal amplitude of the scalp N20; and normal latency of the individual peaks (EP-N9-N13-P14-N20). Although both nerves were involved, abnormalities in response to median nerve stimulation were more significant than those in response to ulnar nerve stimulation. There was little correlation between the degree of alterations observed and the clinical state. Latencies of both spinal and cortical potentials were normal following tibial nerve stimulation. The mean latency of cervical MEP and the central conduction time from the thenar eminence were slightly but significantly longer in patients than in controls. CONCLUSIONS: The findings support the hypothesis that this disease, which is clinically defined as a focal spinal muscle atrophy of the upper limb, may also involve the sensory system; if traumatic injury caused by stretching plays a role in the pathogenesis, the damage cannot be confined to the anterior horn of the spinal cord.     

Magnetic stimulation of the descending and ascending tracts at the foramen magnum level

To test the possibility that stimulation over the foramen magnum activates ascending tracts as well as descending tracts, we studied 4 patients with myoclonic epilepsy all of whom had enhanced cortical long loop reflexes (LLRs) and 10 normal subjects, using our previously reported method (Ugawa et al., Ann. Neurol., 1994, 36: 618–624). For latency comparisons, peripheral nerve stimulation at the elbow and spinal motor root were also performed. In all patients, magnetic stimulation at the foramen magnum consistently elicited long loop reflexes as well as direct responses caused by stimulation of the descending tracts. In contrast, no LLRs were ever seen in any normal subjects. The latencies of both types of response were the same whether stimulation used upward or downward current in the brain, although the former was always more effective. This indicates that stimulation at the level of the foramen magnum activates ascending tracts as well as descending tracts at a fixed position. The threshold for LLRs was lower than that for activation of the descending tracts. This threshold difference is compatible with the hypothesis that large diameter fibers from muscle afferent conduct the central afferent volley for LLRs (Marsden et al., Brain, 1977, 100: 185–200).     

Long latency responses in pure sensory stroke due to thalamic infarction

Objectives – Our study was designed to clarify the role of the thalamus in the generation of the electrically elicited long-latency reflexes (LLR) in voluntarily activated hand muscles. Materials and methods – EMG responses of the thenar muscles were evoked by electrical stimulation of the median nerve at the wrist at motor threshold intensity in 10 patients with acute pure sensory stroke due to thalamic infarction. Concomitant recording of somatosensory evoked potentials (SEPs) was performed. The subjects were asked to steadily abduct the thumb at 20–30% of maximal force against a force transducer. Rectified and averaged EMG activities were recorded. Results – The LLR II was missing completely or significantly attenuated in the majority of the patients (9 of 10), of whom 3 also had delayed latency. Abnormal SEPs were documented in 7 patients (7 of 10). In the follow-up, 5 patients had partial reversal of LLR II. LLR II was still pathological in 1 fully recovered patient. Conclusion – Our results further confirm the transcortical generation of LLR II and imply that a thalamic relay is present in the afferent limb of the LLR.