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Biomedical subjects

J F Nielsen

Publications and source records attributed to J F Nielsen.

At least 19 recordsLinked to original sources

Peripheral and central effect of baclofen on ankle joint stiffness in multiple sclerosis.

The effect of baclofen on the soleus stretch reflex and peripheral muscle function was tested in 10 multiple sclerosis (MS) patients with spasticity in the lower extremities. Peroral baclofen (15-60 mg daily) induced a decrease in the twitch torque of the soleus muscle elicited by supramaximal nerve stimulation. The torque was 15.1 +/- 5.5 Nm with baclofen and 17.1 +/- 5.0 Nm without baclofen (P = 0.03). The slope of the background torque/EMG relation was also changed from 1.53 Nm/microV with baclofen to 1.13 NM/microV without it (P = 0.03), and the soleus stretch reflex threshold decreased from 11.4 degrees /s (3.1-62.8) to 6.2 degrees /s (3.1-25.1) without baclofen medication (P = 0.03) in the relaxed muscle. Furthermore, baclofen induced an approximately 20% decrease in the total stiffness at the ankle joint at all contraction levels due to a decrease in the short-latency stretch reflex. From a clinical point of view, the peripheral action of baclofen may be unfortunate. Spasticity is often accompanied by weakness, which may be the major cause of any disability. Consequently, reduction in spasticity by the central effect of baclofen may be counteracted by its influence on muscle properties. In addition, treatment of spasticity by baclofen may unmask weakness.

Adult↗

Post-exercise facilitation of compound muscle action potentials evoked by transcranial magnetic stimulation in healthy subjects.

Post-exercise facilitation (PEF) of motor evoked potentials (MEPs) was studied by transcranial magnetic stimulation in 15 healthy subjects following standardized and controlled isometric contraction of the biceps brachii muscle. PEF was highly dependent on the time delay (TD) from muscle relaxation to delivery of the magnetic stimulus and only to a minor degree on the duration of the maintained muscular contraction of 2, 4, and 6 s. In addition, PEF was unaffected by the contraction levels of 25%, 50%, and 100% of maximal voluntary contraction (MVC). There was a linear relationship between the log amplitude of the post-exercise MEPs and the TD. The time point at which PEF had vanished was calculated to be 15.2 s. In order to challenge the question whether segmental and/or suprasegmental mechanisms are primarily responsible for PEF, MEPs and H-reflexes were recorded from the soleus muscle following a sustained plantar flexion at the ankle joint in three healthy subjects. PEF of MEPs was present at a TD of 1000 ms following a sustained contraction of 6 s at a level of 50% of MVC. It was accompanied by a pronounced decrease in the soleus H-reflex amplitude at a TD of 1000 ms.

Action Potentials↗

Effect of ischemia and cooling on the response to high frequency stimulation in rat tail nerves.

In normal rat tail nerves the effect of temperature and ischemia on the response to long-term high frequency stimulation (HFS) (143 Hz) was studied. The effect of temperature was studied in two consecutive tests at 14 degrees C and 35 degrees C. Prior to the HFS the peak-to-peak amplitude (PP-amp) of the compound nerve action potential was 139 +/- 20 microV (mean +/- SD) and 127 +/- 37 microV at 35 degrees C and 14 degrees C, respectively (NS). After 15 min of HFS the PP-amp was reduced to 45.3 +/- 20.5% of baseline level at 14 degrees C as compared with 80.8 +/- 10.2% at 35 degrees C (p < 0.001). Applying ischemia to the rat tail, an additional fall of the PP-amp was seen after 15-20 min of HFS at both low (20 Hz) and high (143 Hz) stimulation frequencies. In conclusion, ischemia and cooling result in an impaired ability to transmit high frequency impulses.

Action Potentials↗

Baclofen increases the soleus stretch reflex threshold in the early swing phase during walking in spastic multiple sclerosis patients.

The effect of baclofen on walking performance was examined in nine spastic multiple sclerosis patients. In addition, nine healthy subjects were tested as controls. The modulation of the short latency soleus stretch reflex was closer to normal with baclofen compared to the recordings without baclofen, the modulation index being 74% (range: 60 - 100) with baclofen and 62% (range: 20 - 100) without baclofen, P=0.03. In healthy subjects the modulation index was 100% (range: 52 - 100). In the early swing phase the threshold of the soleus stretch reflex was significantly higher during baclofen medication being 139 deg/s (range: 63 - 302) compared with 93 deg/s (range: 37 - 187) without baclofen, P=0.004. The relation between the stretch velocity (input) and the amplitude of the stretch reflex (output) in early swing phase was unchanged being 0. 27 microVs/deg (range: 0.1 - 1.51) in patients with baclofen and 0. 24 microVs/deg (range: 0.08 - 0.79) without baclofen, P=0.25. Baclofen induced no change in input - output properties of the stretch reflex during walking compared with findings in a sitting position at matched EMG activity. There was a significant correlation between clinical spasticity score and stretch reflex threshold in the early swing phase (rho=-0.61, P=0.04) and between clinical spasticity score and the slope of the best linear fit in the early swing phase (rho=0.72, P=0.009).

Adult↗

Soleus long-latency stretch reflexes during walking in healthy and spastic humans.

The present study was carried out to investigate the long-latency soleus stretch reflexes M2 (peak latency of approximately 85 ms) and M3 (peak latency of approximately 115 ms) during walking in healthy and spastic multiple sclerosis (MS) patients. An 8 degrees stretch was applied to the ankle extensors of the left leg in 8 healthy subjects during normal walking speed and 9 spastic MS patients and 10 age-matched healthy subjects during slow walking. When present in walking healthy subjects, M2 and M3 were modulated in a similar way and with the same amplitudes as previously described for the short latency soleus stretch reflex (M1). The spastic patients' soleus M1 was significantly less modulated during walking. The patients' M2 long-latency response was modulated in the same way as the age-matched healthy subjects. All patients' M3 responses were absent or much suppressed during walking. The origin and functional importance of the short- and long-latency stretch reflexes in healthy and spastic persons are discussed in relation to the above findings and the behaviour of the stretch reflexes during matched isometric contractions. M3 is argued to be part of a transcortical reflex in healthy subjects.

Adult↗

Frequency-dependent conduction delay of motor-evoked potentials in multiple sclerosis.

Paired transcranial magnetic stimulation was applied in 33 multiple sclerosis (MS) patients and in 21 healthy controls. A major abnormality was found in latency of the second motor-evoked potential in MS patients. At interstimulus intervals of 75, 100, and 150 ms the central motor conduction time (CMCT) was significantly prolonged in MS patients to 139%, 150%, and 125% of the CMCT of a single magnetic stimulation (P=0.02, P=0.004, P=0.03), respectively. Voluntary contraction of the target muscle abolished the difference in latency independent of the degree of contraction. Stimulation intensity influenced the length of the interstimulus interval during which the maximal conduction delay was obtained. In MS patients there was no correlation between prolonged CMCT to a single magnetic stimulus and the frequency-dependent conduction delay to paired magnetic stimuli. It is hypothesized that the conduction delay of the conditioned response of paired magnetic stimuli in MS is of cortical origin and induced by abnormalities of the ascending volley to the neocortex.

Adult↗

Long-lasting depression of soleus motoneurons excitability following repetitive magnetic stimuli of the spinal cord in multiple sclerosis patients.

The effect of repetitive magnetic stimulation at the spinal level on the soleus H-reflex amplitude was evaluated in II MS patients with lower limb spasticity and in nine healthy subjects. In MS patients stimulation with a train of 16 stimuli at 25 Hz induced a decrease in amplitude to 61.2 +/- 25.7% of the unconditioned H-reflex amplitude at interstimulus interval (ISI) of 10-1000 ms (P < 0.01). The amount of decrease in H-reflex amplitude was highly dependent on the stimulation intensity and the placement of the coil, and to a lesser extent influenced by the stimulation frequency. No decrease in motor evoked potentials (MEPs) evoked by transcranial magnetic stimulation was seen following trains of 16 stimuli at mid-thoracic in contrast to the post-stimulation depression in H-reflex amplitude which could imply that mechanisms acting at presynaptic level were involved. In response to repetitive magnetic stimuli for 5 min, a long-lasting decrease in H-reflex amplitude to a level of about 70% of the pre-stimulation H-reflex amplitude occurred in MS patients (P < 0.01). A similar although not significant decrease was observed in healthy subjects. We propose that long-lasting depression of the soleus H-reflex amplitude after repetitive magnetic stimuli is due to long-term depression of the synaptic transmission.

Adult↗

Impaired stretch reflex and joint torque modulation during spastic gait in multiple sclerosis patients.

The modulation of the short latency stretch reflex of the soleus muscle during walking was investigated in seven spastic multiple sclerosis (MS) patients and nine healthy control subjects. Ankle joint stretches were applied by a system which can rotate that ankle joint in any phase of the step cycle during treadmill walking. The torque related to the muscle fibres contracting prior to the stretch and the passive tissues around the ankle joint were measured as the "non-reflex torque". At the same time the short latency stretch reflex-mediated EMG response was measured. The findings show that the stretch reflex modulation was impaired in spastic patients during walking. The stretch reflex modulation was quantified by a modulation index of an average 50% (range -5 to 100%) in the patients and 93% (78-100%) in the control subjects (P < 0.05). The passive stiffness of the ankle joint was at the same time increased in the patients (P < 0.05). It is proposed that the impaired modulation of the stretch reflex along with increased ankle joint stiffness contribute to the impaired walking ability in spastic MS patients.

Adult↗

Repetitive magnetic stimulation of cerebral cortex in normal subjects.

Changes of excitability in the neuraxis were studied in 11 healthy subjects with repetitive transcranial magnetic stimuli of the motor cortex at frequencies of 1-10 Hz. Following trains of four stimuli, compound muscle action potentials (CMAPs) were obtained from the flexor carpi radialis muscle. At an interstimulation interval (ISI) of 100-180 ms. the amplitudes of the CMAPs evoked by stimuli II and IV were inhibited as compared with the amplitude of the CMAPs evoked by the first stimulus. In contrast, the amplitude of the CMAPs evoked by stimulus III was almost unchanged. Changes in excitability depended on the stimulation intensity. Thus, it was demonstrated that the amplitude of the CMAPs evoked by stimulus III was reduced at low stimulation intensities (100 and 110% of threshold intensity) but normalized at higher stimulation intensities (120 and 130% of threshold intensity). Results of H-reflex studies indicated that excitability changes at the segmental level are not necessarily involved in the inhibition of the CMAPs evoked by stimuli II and IV at an ISI of 100 ms. It is proposed that long acting neurotransmitter modulation can explain part of the inhibition during repetitive magnetic stimulation, and that recruitment of different neurons, due to electric field differences, explains the dependence of excitability on stimulation intensity.

Adult↗

Logarithmic distribution of amplitudes of compound muscle action potentials evoked by transcranial magnetic stimulation.

Motor evoked potentials were recorded from the first dorsal interosseous muscle on the dominant side evoked by transcranial magnetic stimulation in 20 healthy volunteers. Amplitude data revealed skewness of distribution and variance heterogeneity. Natural logarithmic transformation of amplitude data results in normal distribution and ensures variance homogeneity. There was a negative first-order autocorrelation between consecutive recordings, which indicates that a stimulus-free interval of 5 s in consecutive stimulations is insufficient to ensure independent events. In a variability study, no systematic changes in latency and amplitude during day-to-day examinations or in consecutive examinations were found. There was a significant change in latency data (p = 0.02) during a gradual increase of constant elements in the stimulation procedure, whereas the amplitude data were unchanged. Estimation of random contributors to the total variability in the magnetic stimulation technique was performed. Intersubject differences were the major contributor to the variability of latency data but not to variability of logarithmic amplitude data. The variance estimates of different examiners' contribution to the variability was 0.02 for latency data and 0 for amplitude data. This indicates that staff members familiar with the principles in magnetic stimulation and following a thorough verbal and written instruction in the standardized examination procedure can perform the stimulation procedure without increasing the data variability.

Adult↗

A comparison of clinical and laboratory measures of spasticity.

Clinical evaluation of spasticity was performed in lower extremities in 35 ambulatory multiple sclerosis patients and compared with the soleus stretch reflex and the Hoffman reflex. There was no relation between the muscle tone score of dorsiflexion of the foot and the biomechanical/electrophysiological parameters. In contrast, the Achilles tendon reflex score was significantly related to the amplitude (rho = 0.411, P < 0.05) and the slope of the stretch reflex (rho = 0.523, P < 0.01). The clinical examination at the ankle joint revealed 33% normal reflex examinations but only 7% normal muscle tone examinations. In contrast, the number of normal examinations of patellar reflex and muscle tone at the knee joint were similar. It is concluded that the muscle tone score overestimates the amount of spasticity because of changes in the non-reflex properties of the spastic extremity and that a reflex score should be used as a clinical measure of spasticity. In addition, biomechanical/electrophysiological evaluation of spasticity at the ankle joint relates to the over-all total muscle tone and reflex scores of lower extremities in this group of MS patients.

Adult↗

Treatment of spasticity with repetitive magnetic stimulation; a double-blind placebo-controlled study.

The effect of repetitive magnetic stimulation on spasticity was evaluated in 38 patients with multiple sclerosis in a double-blind placebo-controlled study. One group was treated with repetitive magnetic stimulation (n = 21) and the other group with sham stimulation (n = 17). Both groups were treated twice daily for 7 consecutive days. Primary end-points of the study were changes in the patients self-score, in clinical spasticity score, and in the stretch reflex threshold. The self-score of ease of daily day activities improved by 22% (P = 0.007) after treatment and by 29% (P = 0.004) after sham stimulation. The clinical spasticity score improved -3.3 +/- 4.7 arbitrary unit (AU) in treated patients and 0.7 +/- 2.5 AU in sham stimulation (P = 0.003). The stretch reflex threshold increased 4.3 +/- 7.5 deg/s in treated patients and -3.8 +/- 9.7 deg/s in sham stimulation (P = 0.001). The data presented in this study supports the idea that repetitive magnetic stimulation has an antispastic effect in multiple sclerosis. Future studies should clarify the optimal treatment regimen.

Activities of Daily Living↗

Improvement of amplitude variability of motor evoked potentials in multiple sclerosis patients and in healthy subjects.

Variability of the amplitude of motor evoked potentials was studied in 33 multiple sclerosis (MS) patients and 21 healthy subjects. Normal probability plots revealed skewness of the distribution of amplitudes obtained from the abductor pollicis brevis (APB) muscle during muscle relaxation, muscle contraction, and by paired magnetic stimulation. Natural logarithmic transformation of amplitude data resulted in normal distribution. Negative first-order autocorrelations were established for consecutive recordings independent of the repetition rate tested (5 s, 8 s, 12 s, and 20 s). A given measurement had a tendency to be systematically followed by a measurement of a lower value, indicating that magnetic stimulations induce a long-lasting inhibitory effect on the excitability of the motor pathways. A significant decrease in amplitude variability was achieved by a controlled muscle contraction of the target muscle compared with an uncontrolled muscle contraction in MS patients. Paired magnetic stimulation halved the coefficient of variation of amplitude data compared with amplitude obtained during muscle relaxation, and is introduced to reduce amplitude variability in conditions where no collaboration is possible.

Adult↗

Motor pathway function in normoalbuminuric IDDM patients.

Central motor pathways were studied in 17 normoalbuminuric insulin-dependent diabetic (IDDM) patients who had been diabetic for more than 20 years, and compared with findings in 17 age-, sex-, and height-matched control subjects. The central motor conduction time was calculated from recordings of the compound muscle action potentials of the abductor pollicis brevis muscle after single transcranial and spinal root magnetic stimulation. The central motor conduction time from motor cortex to cervical spinal roots was 9.8 +/- 1.65 ms in diabetic patients and 10.1 +/- 1.48 ms in control subjects. In diabetic patients with neuropathy the central motor conduction time was 9.5 +/- 1.76 ms vs 10.1 +/- 1.56 ms in patients without neuropathy. The excitability of the motor pathways was studied by paired transcranial magnetic stimulation at interstimulation intervals of 30-1000 ms. In normal control subjects, an early facilitation of the amplitude of the compound muscle action potential at an interstimulation interval of 30 ms was found, while no facilitation was present in diabetic patients. In addition the compound muscle action potential latencies were prolonged at interstimulation intervals of 30-50 ms in diabetic patients. The changes of excitability did not correlate with the presence of peripheral neuropathy, metabolic control or diabetes duration. It is concluded that long-term normoalbuminuric IDDM patients have imparied excitability but normal central conduction time of the motor pathways.

Adult↗

A new high-frequency magnetic stimulator with an oil-cooled coil.

A new high frequency magnetic stimulator, Labmag, is described which may be used in clinical neurophysiology and for the treatment of spasticity in multiple sclerosis. In order to avoid heating of the coil during repetitive stimulation, an oil/air cooling system was employed. The magnetic stimulus waveform is a half cosine with a rise time of 200 microseconds and a pulse width of 400 microseconds induced by alternating capacitor voltage. The Labmag product was compared with a commercially available high frequency stimulator, MagPro. The electric fields induced by Labmag were half the size of those induced by MagPro at identical stimulus intensities. Using a leaky integrator to simulate the effects on neurons, only minor differences in integrated electric fields were observed. There were no changes of the electric fields in relation to coil geometry. A minor difference in electric fields (1.0 +/- 0.8%) was observed when the polarity of the capacitor voltage alternated. Compound muscle action potentials (CMAPs) evoked by transcranial magnetic stimulation were recorded from the first dorsal interosseous muscle (FDI) in eight subjects. Threshold intensities of CMAPs evoked by Labmag (58 +/- 7%) were significantly smaller (p < 0.05) than threshold intensities obtained with MagPro (63 +/- 8%). Peak-to-peak amplitudes, P-Pamps, of CMAPs were significantly smaller after single stimulations with Labmag at stimulation intensities of 130 and 140% of threshold intensity.

Adult↗

Inability of insulin to maintain normal nerve function during high-frequency stimulation in diabetic rat tail nerves.

The effect of insulin on the response to long-term high-frequency stimulation (HFS = 143 Hz for 20 min) was studied in mixed tail nerves of acute streptozotocin-induced diabetic rats. In consecutive tests, untreated diabetic rats showed a significant decrease in nerve conduction velocity (NCV) and peak-to-peak amplitude (P-Pamp) and the depression of the P-Pamp during HFS was augmented. In contrast, NCV and P-Pamp in the insulin-treated rats were unchanged from the prediabetic state, but the depression of the P-Pamp during HFS reached the same degree as in untreated rats. This implies that although insulin treatment of acute experimental diabetes is able to preserve a normal NCV and P-Pamp in the resting state, it is unable to preserve normal nerve function under stress produced by HFS. Monitoring of the axon membrane functional capacity may have clinical implications in the control of peripheral neuropathies.

Action Potentials↗

Standardization of facilitation of compound muscle action potentials using a modified myometer during magnetic stimulation in healthy volunteers.

In 20 normal subjects motor evoked potentials (MEPs) from first dorsal interosseous (FDI) were obtained following transcranial magnetic stimulation during relaxation and voluntary contraction of 2-20% of maximum. A new method to standardize facilitation of MEP using surface EMG and a modified myometer was used. The MEP amplitudes increased significantly at contraction levels of 2%, 10% and 15% of maximum. The latencies decreased significantly at contraction levels of 2%, 5% and 15%. Coefficients of variation of the amplitude decreased from 6.4% during relaxation to approximately 2% during facilitation. In contrast, coefficients of variation of take-off latencies (T-lat) increased significantly from 1.7% during relaxation to approximately 3% during facilitation. The variability of amplitudes and latencies was mainly due to inter-individual variation. The observations in the present study indicate that the actual contraction level should be precisely defined during transcranial magnetic stimulation.

Action Potentials↗