Altered long-term health-related quality of life in patients following patella fractures: a long-term follow-up study of 49 patients.

INTRODUCTION: The primary aim was to investigate the health-related quality of life (HRQOL) in patients treated for a patella fracture. The explorative aim was to report the associations between HRQOL, knee osteoarthritis, muscle strength and gait function. METHODS: The study design was a cohort study. Patients who were treated for patella fractures at Aalborg University Hospital, Denmark between January 2006 and December 2009 were identified. Patients between the age of 18 and 80 were included. The main outcome was assessed by the EQ5D-5L questionnaire. Classifications by Sperner and Kellgren/Lawrence were applied to evaluate osteoarthritis. Moreover, functional outcomes were evaluated by: KOOS, muscle strength and gait analysis. RESULTS: Forty-nine patients were included with a mean follow-up time of 8.5 years. The mean age was 53.9 years. The mean EQ5D-5L index value was 0.741, and was significantly worse compared to a reference population. X-rays taken at the time of diagnosis and the time of follow-up showed progression towards a higher degree of osteoarthritis in the injured knee for both the patellofemoral and tibiofemoral joints. Patients demonstrated significantly lower knee extension strength in the injured leg compared to the non-injured leg (P = 0.011). No significant difference in gait speed and cadence were observed compared to the reference population. Knee osteoarthritis, muscle strength and gait patterns were not associated with HRQOL (R < 0.35). CONCLUSION: At 8.5 years following a patella fracture, HRQOL was significantly worse compared to an age-matched reference population.

In humans IL-6 is released from the brain during and after exercise and paralleled by enhanced IL-6 mRNA expression in the hippocampus of mice.

AIM: Plasma interleukin-6 (IL-6) increases during exercise by release from active muscles and during prolonged exercise also from the brain. The IL-6 release from muscles continues into recovery and we tested whether the brain also releases IL-6 in recovery from prolonged exercise in humans. Additionally, it was evaluated in mice whether brain release of IL-6 reflected enhanced IL-6 mRNA expression in the brain as modulated by brain glycogen levels. METHODS: Nine healthy male subjects completed 4 h of ergometer rowing while the arterio-jugular venous difference (a-v diff) for IL-6 was determined. The IL-6 mRNA and the glycogen content were determined in mouse hippocampus, cerebellum and cortex before and after 2 h treadmill running (N = 8). RESULTS: At rest, the IL-6 a-v diff was negligible but decreased to -2.2 ± 1.9 pg ml(-1) at the end of exercise and remained low (-2.1 ± 2.1 pg ml(-1) ) 1 h into the recovery (P < 0.05 vs. rest). IL-6 mRNA was expressed in the three parts of the brain with the lowest content in the hippocampus (P < 0.05) coupled to the highest glycogen content (3.2 ± 0.8 mmol kg(-1) ). Treadmill running increased the hippocampal IL-6 mRNA content 2-3-fold (P < 0.05), while the hippocampal glycogen content decreased to 2.6 ± 0.6 mmol kg(-1) (P < 0.05) with no significant changes in the two other parts of the brain. CONCLUSION: Human brain releases IL-6 both during and in recovery from prolonged exercise and mouse data suggest that concurrent changes in IL-6 mRNA and glycogen levels make the hippocampus a likely source of the IL-6 release from the brain.

Is the human masticatory system devoid of recurrent inhibition?

The aim of the present study was to investigate the existence or otherwise of a functional recurrent inhibitory system (Renshaw cell system) in the motoneurons that innervate human masticatory muscles. In a previous study, L: -acetylcarnitine (L: -Ac), a substance known to potentiate recurrent inhibition in humans was found to alter, in a specific way, the discharge variability, and the synchronous activity of motor units depending on the presence or absence of recurrent inhibition in the corresponding motoneuron pool. Using a similar paradigm, we have recorded the tonic discharge activity of motor unit pairs from the masseter muscle during voluntary isometric contraction while subjects were undergoing continuous intravenous saline (SAL, NaCl 0.9%) perfusion. Following a brief baseline-recording period, the subjects were given a test injection of either L: -Ac or isotonic saline (SAL) in a double blind manner. The variability, synchronization, and coherence between the motor unit discharges were analysed during three successive periods: pre-injection, during injection, and post-injection, each lasting 2-3 min. Neither L: -Ac nor SAL injection induced a significant change in the inter-spike interval (ISI) or the coefficient of variation of the ISIs in the motor units tested. There were also no significant changes in the pattern of synchronous activity or in the coherence, which reflects the common frequency content of the unit discharges. Reminiscent of what had been observed previously with motoneurons without recurrent inhibition in the Abductor Digitorum Minimi muscle, the lack of effects of L: -Ac injection on the firing behaviour of masseter motoneurons may suggest that classical Renshaw cell inhibition is lacking in this motoneuron pool.

Motor unit synchronous firing as revealed by determinism of surface myoelectric signal.

Information on motor strategies can be extracted from the surface electromyogram (EMG) by non-linear methods. The percentage of determinism (%DET) obtained from recurrence quantification analysis (RQA) may be a sensitive variable to detect synchronous motor unit behaviour. The purpose of the present study was to validate this methodology by comparing it with an established technique estimating the degree of synchronization of pairs of voluntary activated motor units from the correlation of their firing in the time-domain. Single motor unit activity was recorded in extensor carpi radialis (ECR) muscle by pairs of tungsten microelectrodes inserted into the muscle belly. Cross-correlation analysis was performed in order to determine synchronization peak area by computing synchronous impulse probability. Surface EMG activity was recorded in parallel by electrodes placed over the skin of the same muscle and %DET was used as a measure of synchronous activity. The %DET appeared to be a valid measure of synchronization yielding results comparable to those obtained with cross-correlation analysis. Increases in %DET (t = 64.59, P < 0.0001) highly correlated (r2 = 0.70, P = 0.0013) with pharmacologically induced increases in the synchronization activity of pairs of ECR motor units (t = 8.71, P < 0.0001). RQA may be used as an alternative methodology for testing synchronous motor unit behaviour from surface EMG under physiological and pathological conditions.

Changes in the tonic activity of wrist extensor motor units induced by stimulating antagonistic group I afferents in humans.

The question as to whether the firing patterns of low- and high-threshold motor units in the extensor carpi radialis muscles are affected differently by group I afferents from the wrist flexors depending on the motor task being performed was investigated in six subjects. The motor units were voluntarily activated during a task consisting of either selectively contracting the wrist extensor muscles or co-activating the wrist and finger antagonist muscles by clenching the hand around a manipulandum. The motor units (n=40) were identified on the basis of their firing thresholds, their macro-potential areas, and their twitch contraction times. The effects on the motor-unit tonic activity of stimulating the wrist flexor afferents were assessed in terms of the changes in the firing probability, which were analysed after computing peri-stimulus time histograms using the cumulative sum procedure. Median nerve stimulation induced four main changes in the tonic firing pattern of the extensor motor units. An early, short-lasting increase in the firing probability (event E1) was found to occur in the high-threshold motor units, either in both tasks (6/13) or only during hand clenching (2/13). A short-latency decrease in the firing probability (event E2) was found to occur in all the motor units, the amount of which increased from the fast- to slowly contracting motor units, especially during hand clenching. A later decrease (event E3) followed by a large, late increase (event E4) in the tonic activity of the motor units was found to occur in all the motor units, without any task-dependent effects. All these various events were consistently observed in 12 pairs of motor units, each consisting of one slowly and one fast-contracting motor unit, which were tested simultaneously. These findings suggest that median nerve stimulation may selectively alter the tonic firing patterns of identified extensor motor units, depending on their functional characteristics (recruitment threshold, motor unit macro-potential area, contraction time) rather than on the excitatory drive to the motoneurone pool. The possible origins of these various events are discussed, and it is argued that, in the wrist extensor and flexor muscles that act as synergists during manipulatory finger movements and gripping tasks, the spinal pathways which assist the voluntary command may selectively modulate the firing patterns of identified motor units, to fit the requirements of the on-going motor task.

Selective enhancement of motoneurone short-term synchrony during an attention-demanding task.

Recent experiments on monkeys suggest that attention-related changes in the synchronous activity of neurones occur in the motor cortex. In humans, the clinical data available suggest that the weak synchronization of the motor unit firing observed during voluntary contraction might reflect the activity of the motoneurone cortico-spinal afferents. The present study was therefore designed to investigate how the synchronous motor-unit activity might depend on the attention required in performing a motor task. Twenty-five motor unit pairs were tested in the right extensor carpi radialis muscles of five right-handed subjects, who were instructed to keep both motor units firing tonically while trying to maintain the extension force as constant as possible using visual feedback set either at low or high gain. Fifteen motor unit pairs (60%) showed a greater amount of synchronous activity, without any consistent changes in the motor unit firing rates, when the subjects were monitoring the force at high gain. In addition, the mean value and the steadiness of the force did not differ significantly between the two tasks. The amplitude of the motor units' contractile force extracted by spike-triggered averaging did not change consistently despite the slight increase in the synchronous impulse probability observed under the high-gain conditions. Changes in synchrony affected slowly contracting, low-threshold motor units as well as fast-contracting, high-threshold motor units. The most noteworthy finding was that these changes actually focused on a narrow component of the synchronous activity (within a period of less than 4 ms) in keeping with the short-term synchronization process. This suggests that common inputs, possibly of cortical origin, may have contributed more greatly to controlling the motoneurone firing pattern in the motor task which required the subjects to pay more attention.

Inhibition versus facilitation of the reflex responsiveness of identified wrist extensor motor units by antagonist flexor afferent inputs in humans.

The question of whether Ia reciprocal inhibition might depend on the motor task and on the type of motor unit activated was investigated in the human extensor carpi radialis muscles. Ia reciprocal inhibition induced by stimulating the median nerve (conditioning stimulation) was estimated by measuring the changes in the firing probability of 37 extensor motor units in response to the radial nerve stimulation (100 test stimuli) delivered 1 ms after the conditioning stimulation. Six subjects were asked to perform a task consisting of either selectively contracting their wrist extensor muscles or co-activating their wrist and finger antagonist muscles by clenching their hand around a manipulandum. In the control recordings (test stimulation alone), the mean response probability of the 37 motor units was found to be greater during hand clenching. The motor units were identified on the basis of their force thresholds, their macro-potentials, and their twitch contraction times. The data obtained in the control recordings were consistent with the size principle. In the recordings where the responses were conditioned by applying median nerve stimulation, the response probability of the motor units with low force thresholds, small macro-potential areas, and long twitch contraction times tended to decrease, in line with the presence of Ia reciprocal inhibition, whereas the response probability of the motor units with higher force thresholds, larger macro-potential areas, and shorter twitch contraction times tended to increase. The median nerve stimulation may therefore have altered the efficiency with which the extensor Ia inputs recruited the homonymous motoneurones in the pool. The flexor group I afferents activated while the median nerve was stimulated had inhibitory effects on the slow contracting motor units, and facilitatory effects mainly on the fast contracting motor units. Both of these effects were stronger during hand clenching, in which the numerous cutaneous receptors of the palm and fingertips are liable to be activated. Besides their own effects on the excitability of the various types of motor units, cutaneous inputs are known to potentiate the Ib interneurones. In addition, the effects of the conditioning stimulation were superimposed on the tonic activity of the Ia and Ib afferents from the flexor wrist and finger muscles. This may explain why both the inhibitory and facilitatory effects of the median nerve stimulation were enhanced during hand clenching.

Task dependence of Ia presynaptic inhibition in human wrist extensor muscles: a single motor unit study.

OBJECTIVE: Task-dependent changes in the Ia presynaptic inhibition generated by flexor group I afferents were investigated in 25 identified motor units (MUs) located in human extensor carpi radialis (ECR) muscles. METHODS: Seven subjects had to voluntarily contract their ECR muscles either alone during isometric wrist extension or concurrently with their wrist and finger flexor muscles while clenching their hand around a manipulandum. The MU reflex responses to the radial nerve stimulation (test stimulation) yielded narrow peaks in the post-stimulus time histograms (PSTH). The Ia presynaptic inhibition induced while stimulating the median nerve (conditioning stimulation) 20 and 40 ms before the radial nerve was assessed from the changes in the contents of the first 0.5 ms in the peaks. RESULTS: With both stimulation intervals, the Ia presynaptic inhibition, as assessed from the first 0.5 ms of the PSTH peaks, was consistently weaker during hand clenching. With both motor tasks, the Ia presynaptic inhibition was strongest at the 20 ms interval, in which it showed a downward gradient, working from slow to fast contracting MUs. With both intervals, the presynaptic inhibition was consistently weaker during hand clenching. The decrease in the Ia presynaptic inhibition observed at the 40 ms conditioning-test interval was less pronounced during wrist extension. CONCLUSION: It is suggested that the reason why Ia presynaptic inhibition was weaker during hand clenching may have been that this task involved numerous cutaneous inputs originating from the palm and finger tips. During gripping tasks, these cutaneous inputs may therefore contribute to adjusting the wrist stiffness by relieving the presynaptic inhibition.

Dual task-related changes in the synchronous activity of wrist extensor type-identified motor units in humans.

The coupling between the firings of 33 pairs of motor units tested in the extensor carpi radialis muscles was evaluated by cross-correlation analysis and compared during isometric wrist extension and hand clenching. A slightly greater amount of synchrony was observed during hand clenching (0.042 +/- 0.024 vs 0.035 +/- 0.017 synchronous impulses per trigger). This trend did not reach however the level of significance and the changes were actually found to be heterogeneous: in 15 out of the 33 pairs tested, synchronous activity with a narrow coupling (4.6 +/- 2.4 ms) consistent with short-term synchrony was greater during hand clenching whereas in nine other pairs, synchronous activity with a broader dispersion (9.0 +/- 4.5 ms) was reduced. These opposite changes could not be explained in terms of changes in the firing pattern of the motor units and were found instead to correlate with the motor units' biomechanical properties. Motor units with high recruitment thresholds and fast rising twitches showed predominantly an increase in synchrony; whereas the motor unit pairs with low recruitment thresholds and slow twitches showed either an increase or a decrease. The enhanced short-term synchrony suggests that common inputs distributed to motoneurones of all types were more effective during hand clenching whereas the decrease in weakly coupled synchronous activity suggests that other inputs synchronized at a pre-synaptic level and distributed more specifically to motor units recruited at low force levels were less effective. The possible origins of the inputs reflected in the dual changes are discussed in terms of the supra-spinal and peripheral pathways controlling the wrist extensor motoneurones during wrist extension and hand clenching.

Distribution of presynaptic inhibition on type-identified motoneurones in the extensor carpi radialis pool in man.

The question was addressed as to whether the magnitude of Ia presynaptic inhibition might depend on the type of motor unit activated during voluntary contraction in the wrist extensor muscles. For this purpose, we investigated the effects of applying electrical stimulation to the median nerve on the responses of 25 identified motor units to radial nerve stimulation delivered 20 ms after a conditioning stimulation. The reflex responses of the motor units yielded peaks in the post-stimulus time histograms with latencies compatible with monosynaptic activation. Although median nerve stimulation did not affect the motoneurone net excitatory drive assessed from the mean duration of the inter-spike interval, it led to a decrease in the contents of the first two 0.25 ms bins of the peak. This decrease may be consistent with the Ia presynaptic inhibition known to occur under these stimulation conditions. In the trials in which the median nerve was being stimulated, the finding that the response probability of the motor units, even in their monosynaptic components, tended to increase as their force threshold and their macro-potential area increased and as their twitch contraction time decreased suggests that the median nerve stimulation may have altered the efficiency with which the Ia inputs recruited the motoneurones in the pool. These effects were consistently observed in seven pairs of motor units each consisting of one slow and one fast contracting motor unit which were simultaneously tested, which suggests that the magnitude of the Ia presynaptic inhibition may depend on the type of motor unit tested rather than on the motoneurone pool excitatory drive. The present data suggest for the first time that in humans, the Ia presynaptic inhibition may show an upward gradient working from fast to slow contracting motor units which is able to compensate for the downward gradient in monosynaptic reflex excitation from 'slow' to 'fast' motor units. From a functional point of view, a weaker Ia presynaptic inhibition acting on the fast contracting motor units may contribute to improving the proprioceptive assistance to the wrist myotatic unit when the contraction force has to be increased.

Mechanical cutaneous stimulation alters Ia presynaptic inhibition in human wrist extensor muscles: a single motor unit study.

Reflex responses were evoked by radial nerve stimulation in 25 single motor units in the extensor carpi radialis muscles of seven subjects during voluntary isometric wrist extension. The responses consisted of narrow peaks in the post-stimulus time histograms with latencies compatible with monosynaptic activation. When the skin of the palm and finger tips was continuously swept using a soft rotating brush, the purely monosynaptic components of the motor unit responses, as assessed from the contents of the first two 0.25 ms bins of the peak, were found to increase. This increase did not affect the motoneurone net excitatory drive, as assessed by measuring the mean duration of the inter-spike intervals. The cutaneous inputs activated by the brush may have reduced the tonic presynaptic inhibition exerted on the Ia afferents homonymous to the extensor motor units tested. To further investigate whether Ia presynaptic inhibition was involved, the responses of the extensor motor units were conditioned by stimulating the median nerve 20 ms earlier, using a protocol which is known to induce Ia extensor presynaptic inhibition originating from flexor Ia afferents. The median nerve stimulation did not affect the motoneurone excitatory drive, but led to a decrease in the responses of the extensor motor units to the radial nerve stimulation, especially in the purely monosynaptic components. This decrease was consistent with the Ia presynaptic inhibition known to occur under these stimulation conditions. The cutaneous inputs activated by the brush were found to reduce the Ia presynaptic inhibition generated by the median nerve stimulation, without affecting the distribution of the Ia presynaptic inhibition among the various types of motor units tested. The present data suggest that cutaneous inputs from the palm and finger tips may relieve the Ia presynaptic inhibition exerted on the wrist extensor motor nuclei, and thus enhance the proprioceptive assistance to fit the specific requirements of the ongoing motor task.

Ia presynaptic inhibition in human wrist extensor muscles: effects of motor task and cutaneous afferent activity.

The task-dependence of the presynaptic inhibition of the muscle spindle primary afferents in human forearm muscles was studied, focusing in particular on the modulation associated with the co-contraction of antagonist muscles and the activation of cutaneous afferents. The changes known to affect the motoneuron proprioceptive assistance during antagonist muscle co-activation in human leg and arm muscles were compared. The evidence available so far that these changes might reflect changes in the presynaptic inhibition of the muscle spindle afferent is briefly reviewed. The possible reasons for changes in presynaptic inhibition during the antagonist muscle co-contraction are discussed. Some new experiments on the wrist extensor muscles are briefly described. The results showed that the changes in the Ia presynaptic inhibition occurring during the co-contraction of the wrist flexor and extensor muscles while the hand cutaneous receptors were being activated (the subject's hand was clenched around a manipulandum) could be mimicked by contracting the wrist extensor muscles alone while applying extraneous stimulation to the hand cutaneous receptors. It is concluded that besides the possible contribution of inputs generated by the co-contraction of antagonist muscles and by supraspinal pathways, cutaneous inputs may play a major role in modulating the proprioceptive assistance during manipulatory movements.

Electromechanical coupling and synchronous firing of single wrist extensor motor units in sporadic amyotrophic lateral sclerosis.

Electrical and contractile properties of motor units (MU) were studied in the extensor carpi radialis muscles during voluntary contraction. The discharge of 234 single MUs was recorded in 11 patients with sporadic amyotrophic lateral sclerosis (ALS) and compared with that of the 260 MUs recorded in 12 healthy control subjects. Characteristics of the MU twitches and of the macro-potentials, the electromechanical coupling and the synchronization of the motor neurone discharges, were compared. In 5 patients (population ALS1), the twitch contraction force and macro-MUP area values were much larger than those of the controls. In the 6 other patients (population ALS2), the twitch force was considerably depressed, whereas the macro-MUP area was slightly, but significantly, increased. In ALS1, as well as in ALS2, the electromechanical coupling was much weaker than in the controls, and the fast-contracting MUs were more severely affected than the slowly contracting MUs. The motoneuronal synchronization was assessed by performing cross-correlation analysis on MUs discharges, and was used as an index to the strength of the common motoneuronal inputs. The rate of occurrence of synchronous firing was conspicuously lower in both populations of patients than in the control group. This might reflect the loss of corticospinal projections that occurs in ALS. The data are discussed in terms of the time course of motor neurone axonal sprouting, and in terms of the neuronal and muscular dysfunction possibly involved in ALS disease.

Proprioceptive control of wrist extensor motor units in humans: dependence on handedness.

The effectiveness of the monosynaptic proprioceptive assistance to the wrist extensor motoneurone activity was investigated during voluntary contraction in relation to the subjects' handedness. The reflex responses of 411 single motor units to homonymous tendon taps were recorded in the wrist extensor carpi radialis muscles in both arms of five right-handed and five left-handed subjects. In the right-handed subjects, the motor unit reflex responses were clearly lateralized in favour of their right arm, whereas no side-related differences were observed in the left-handed subjects, whatever the motor units' mechanical properties and firing rates. When the muscle spindle sensitivity was by-passed by electrically stimulating the primary afferents in both arms of three right-handed and three left-handed subjects, no side-related differences were observed in the Hoffmann reflex (H-reflex) amplitude in either of the two lateralization groups. The effectiveness of the primary afferent synapses on to the motoneurones therefore does not seem to depend on the subject's handedness. Without excluding the possibility of structural changes being involved at the periphery, the comparisons carried out on the data obtained using electrical vs mechanical stimulation suggest that the asymmetrical effectiveness of the proprioceptive assistance observed in favour of the right arm in the right-handed subjects might result from either the gamma or beta drive being more efficient. This asymmetry might result from the preferential use of the right hand in skilled movements. In a predominantly right-handed world, however, left-handed people might tend to develop the ability to use their right arm almost as skillfully as their preferred left arm, which could explain the symmetrical effectiveness of the proprioceptive assistance observed here in the left-handers' wrist extensor muscles.

Firing pattern of type-identified wrist extensor motor units during wrist extension and hand clenching in humans.

1. Single motor unit activity was investigated in the extensor carpi radialis muscles during voluntary isometric contraction involving either the coactivation of the wrist agonist extensor muscles (wrist extension) or the coactivation of the wrist and finger antagonist extensor and flexor muscles (hand clenching). 2. The motor units were found to be activated at a similar level of motoneurone pool drive during both wrist extension and hand clenching, as indicated by the fact that the EMG activity at which they were recruited was practically the same in both cases (mean +/- S.D.: 20 +/- 26 and 21 +/- 25 mV, respectively). In addition, the net excitatory drive exerted on the motoneurones, as assessed from the mean interspike intervals, did not differ significantly between the two tasks (mean +/- S.D.: 104.57 +/- 17.24 and 103.01 +/- 16.26 ms, for wrist extension and hand clenching, respectively). 3. However, the discharge variability, in terms of the coefficient of variation of the interspike intervals, was slightly but significantly greater during hand clenching than during wrist extension (0.213 +/- 0.049 and 0.198 +/- 0.045, respectively). This increase involved all types of motor units, regardless of their contractile force. 4. We suggest that the greater motoneurone discharge variability observed during hand clenching may be attributable to an increase in the synaptic noise. This increase might be due to the activation of numerous afferent pathways mediating reciprocal interactions between antagonist motoneurone pools, as well as to the activation of hand cutaneous receptors that play a major role in the regulation of handling and gripping motor activities.

Task-dependence of muscle afferent monosynaptic inputs to human extensor carpi radialis motoneurones.

The task-dependence of homonymous muscle afferent inputs was investigated in motor units of the extensor carpi radialis muscles during voluntary isometric contraction involving either the activation of agonist extensor muscles (wrist extension) or the co-activation of antagonist extensor and flexor muscles (hand clenching). The effectiveness of the muscle afferent monosynaptic inputs was tested by delivering either tendon taps or electrical stimulation to the radial nerve. In both cases, the motor unit responses, which took the form of narrow peaks in the peri-stimulus time histograms, were found to be significantly greater during hand clenching. The parallel enhancement of the responses to both mechanical and electrical stimulations observed during hand clenching could not be explained in terms of changes in the muscle spindle responsiveness. The enhancement of the motor units' responsiveness was apparent during the first 0.5 ms of the peaks in the peri-stimulus time histograms, taken to be uncontaminated by any polysynaptic components. It may therefore have reflected an increase in the amplitude of the excitatory monosynaptic potentials generated by the muscle spindle primary afferents. This is interpreted in terms of changes in the presynaptic inhibition, which might be depressed as the result of the large-scale activation of palm and finger cutaneous afferents liable to occur during hand clenching.

[Complete atrioventricular block disclosing Fabry's disease]. / Bloc auriculo-ventriculaire complet révélateur de maladie de Fabry.

Fabry's disease is a hereditary sex-linked sphinglopidosis characterised by abnormal cellular lipid overload in most organs due to deficiencies in enzymes implicated in the catabolism of certain neutral glycolipids. There are two main clinical forms; cardiovascular manifestations usually congestive cardiac failure, and renal manifestations progressing to renal failure and death due to uraemic coma. The authors report a case presenting with juvenile, symptomatic complete infrahisian atrioventricular block. They describe the different cardiovascular complications of Fabry's disease from a review of the medical literature.

The "size principle" and synaptic effectiveness of muscle afferent projections to human extensor carpi radialis motoneurones during wrist extension.

The question of whether muscle spindle afferents might control human motoneurone activity on the basis of the "size principle" during voluntary contraction was investigated by recording the discharge of single motor units (n = 196) in wrist extensor muscles while stimulating the homonymous muscle spindles by means of tendon taps. The mechanical stimuli were delivered with a constant post-spike delay of 80 ms so that the resulting afferent volleys could be expected to reach the motoneurones towards the end of the inter-spike interval (mean +/- SD duration: 124.7 +/- 11.9 ms). In the six subjects tested, the response probability was found to be significantly correlated with the motor units' functional parameters. Differences in twitch rise times, twitch amplitudes, recruitment thresholds and macro-potential areas were found to account for 18%, 9%, 6% and 2% of the differences in the response probability observed within the whole population of motor units tested. These differences could not be due to differences in firing rate for two reasons: first, the motor units were found to discharge with a similar range of inter-spike intervals whatever their functional characteristics; secondly, the weak positive correlation observed between the response probability and the motor unit firing rate showed parallel regression lines between the late-recruited fast-contracting motor units and the first-recruited slowly contracting motor units, but the y-intercept was significantly higher in the latter case. This confirmed that the responses of the first-recruited slowly contracting motor units tended to be larger whatever the firing rates. In most of the pairs tested in the same experiment, the motor units which had the lowest recruitment thresholds, longest contraction times, smallest contraction forces or smallest motor unit macro-potentials tended to produce the largest responses, which also had the longest latencies. Taking the response latency to be an index of a motoneurone's conduction velocity and therefore of its size, the data obtained with this index and with other functional indices such as the twitch rise times and amplitudes, the macro-potential areas and the recruitment thresholds-can be said to be fully consistent with the "size principle", as previously found in anaesthetized animals. It can be inferred that the presynaptic inhibition which is liable to take action during voluntary contraction does not seem to alter the graded distribution of the muscle afferent projections to human wrist extensor motoneurones.