Stefano Corna

SELECTIVE DEPRESSION OF MEDIUM-LATENCY LEG AND FOOT MUSCLE RESPONSES TO STRETCH BY AN ALPHA 2-AGONIST IN HUMANS

1. In standing humans, toe‐up rotation of a platform induces a short‐latency (SLR) and a medium‐latency response (MLR) in both soleus (Sol) and flexor digitorum brevis (FDB) muscles. Toe‐down rotation evokes a MLR in the tibialis anterior (TA). The SLR is the counterpart of the monosynaptic stretch reflex, but the origin of the MLR is still debated. By means of tizanidine (an alpha 2‐adrenergic receptor agonist) we tested the hypothesis that the MLR is relayed by group II afferent fibres, since animal data indicate that tizanidine or stimulation of monoaminergic brainstem centres decrease the excitability of spinal interneurones supplied by those fibres. In addition, we compared the effect of the drug on these responses with that induced by stabilization of posture. 2. Eight subjects received tizanidine (150 micrograms kg‐1 orally) or placebo, in a single‐blind design. Platform rotations were delivered prior to administration and for 3 h afterwards. Both TA‐ and FDB‐MLRs decreased in size, starting from about 1 h after tizanidine administration. Sol‐SLR was unaffected. Response latencies were unchanged. Placebo induced no changes in any response. In each subject, the extent of TA‐MLR depression induced by holding onto a frame and by tizanidine was superimposable. 3. The selective effect of tizanidine on MLR supports the notion that it is relayed through group II afferent fibres. The similar effects of holding and tizanidine on the response suggests that it is modulated by monoaminergic centres.

Standing on a continuously moving platform: is body inertia counteracted or exploited?

Abstract We describe the characteristics of displacement of the head and hip in normal young subjects standing on a moving platform undergoing continuous sinusoidal horizontal translation in the antero-posterior direction, at frequencies ranging from 0.1–1 Hz. The head, hip and malleolus were marked by light-emitting diodes (LEDs), and the displacement of each LED was quantified by (1) the measure of the shift during each cycle of translation, (2) the standard deviation (SD) of the path travelled during the whole trial, (3) the power spectrum (PS) of the signal and (4) the cross-correlation (CC) between pairs of LED signals. At each frequency of translation, with eyes open (EO), the displacement of head was smaller than that of hip, and the displacement of hip was smaller than that of malleolus. With eyes closed (EC), this order was reversed. The peak value of the CC functions of the pairs malleolus/head, malleolus/hip and hip/head decreased by passing from low to high frequency of translation, under both visual conditions, and decreased more for the pair malleolus/head than malleolus/hip. The lags between body segment displacements ranged between 30 ms and 150 ms, on average, the former segment of each pair preceding the latter. The fast Fourier transformation of hip and head displacement showed a power spectrum peak at the frequency imposed by the platform translation. The peak was larger with EC than EO. With EC, another peak appeared at 0.2 Hz, possibly corresponding to the respiratory frequency. We conclude that, when vision was allowed, subjects behaved as a non-rigid, non-inverted pendulum, and stabilised head in space. When vision was denied, head oscillated more than the platform, especially at low translation frequencies. Therefore, the strategy of balance control shifted from a pendulum to an inverted-pendulum behaviour, passing from active head-and-trunk control to maximal body compliance to the perturbation.

Subjective perception of body sway

OBJECTIVES AND METHOD The relation between body sway recorded through a stabilometric platform and the subjective report of steadiness was studied in 20 young and 20 elderly subjects and 20 neuropathic and 20 parkinsonian patients standing upright. The trials were performed under two stances (feet apart, feet together) and two visual conditions (eyes open, eyes closed). At the end of each trial, subjects scored their performance on a scale from 10 (complete steadiness) to 0 (fall). RESULTS In all subjects, independently of the stance conditions, the larger the body sway the smaller the reported score. The function best fitting this relation was linear when sway was expressed on a logarithmic scale. The scoring reproducibility proved high both within and across subjects. Despite the different body sways and scores recorded under the different visual and postural conditions (eyes closed >eyes open, feet together>feet apart) in all groups of subjects and patients, the slopes of the relations between sway and score were broadly superimposable. In the normal subjects, the scores were slightly higher during eyes open than eyes closed trials for corresponding body sways. This was interpreted as a sign of perception of greater stability when vision was allowed. Parkinsonian patients swayed to a similar extent as normal subjects, and their scores were accordingly similar, both with eyes open and eyes closed. Neuropathic patients swayed to a larger extent than normal subjects, and their scores were matched appropriately. Although the slope of their relation with eyes closed was not different from that of normal subjects, with eyes open it was steeper and similar to that with eyes closed, suggesting that these patients did not feel more stable when they could take advantage of vision. CONCLUSIONS The subjective evaluation of body sway, irrespective of stance condition, age, neuropathy, and basal ganglia disease, reflects the actual sway, and is inversely proportional to the logarithm of the sway value. The remarkable similarity of the relation between score and sway across the various groups of subjects with eyes closed indicates a common mode of sway evaluation, possibly based on integration of several sensory inputs. All groups except neuropathic patients seem to take advantage of the redundancy of the inputs. Basal ganglia integrity does not seem to have a role in the evaluation of sway.

Unilateral displacement of lower limb evokes bilateral EMG responses in leg and foot muscles in standing humans

During upright stance, foot dorsiflexion induced by the movement of a supporting platform elicits a short-(SLR) and a medium-latency response (MLR) in both the soleus and the flexor digitorum brevis muscles; foot plantarflexion elicits a MLR in the tibialis anterior. The SLR is the counterpart of the stretch reflex, but no general agreement exists about the origin of the MLR, though recent results suggest that it is transmitted through group II afferent fibres. Animal studies have shown that group II fibres impinge on interneurones projecting contralaterally as well as ipsilaterally, whereas group I fibres impinge on interneurones which project mainly ipsilaterally. Therefore, we compared the changes in amplitude and latency of the SLRs and MLRs in the right and left limb during postural perturbations induced while subjects maintained both feet on the platform (both-on condition) or while they maintained only one foot on the platform and the other on firm ground (one-on condition). Under the both-on condition, the pattern of EMG responses described above occurred bilaterally. Under the one-on condition, both SLRs and MLRs occurred in the displaced leg. However, whereas the SLRs did not change in amplitude compared with the both-on condition, the MLRs decreased in amplitude to about 50%. MLRs were also present in the non-displaced leg. They were not preceded by any SLR but showed a further decrease in size with respect to the corresponding responses in the perturbed leg. Latency of the MLRs of the perturbed leg increased by about 5 ms passing from the both-on to the one-on condition. In the latter condition, a further increase of 5 ms was observed in the nonperturbed leg with respect to the displaced one. The occurrence of the MLRs but not of the SLRs in the contralateral non-displaced leg is in keeping with the notion that crossed neural pathways fed by spindle group II afferent fibres subserve the MLRs. The changes in latency of the MLRs under the one-on condition compared with both-on give a cue about the synaptic delays along the neural circuit and the time taken by the afferent impulses to cross the spinal cord.

The functional effectiveness of neck muscle reflexes for head-righting in response to sudden fall

Abstract Reflex head-righting in normal and labyrinthine-defective (LD) subjects was compared to identify the relative functional effectiveness of vestibular-collic and cervico-collic myotactic reflexes. To restrict stimuli largely to the head and neck, subjects lay supine, supported up to the shoulders on a horizontal bed with their head supported in a sling over the edge. The head fell freely as the sling was released with an electromagnetic catch. Head drops were delivered with the subjects instructed to relax and accept the fall passively or to actively right the head as fast as possible. With both instructions, righting responses in normal subjects commenced with electromyographic (EMG) bursts in the sternocleidomastoid (SCM) at 24.5 ms latency, which was reflected in a deceleration of the downwards head velocity. The latency of the earliest EMG responses in LD subjects was 67.4 ms, accompanied by similar deceleration. It is assumed that the earliest response in normal subjects is vestibular, whereas in LDs the SCM stretch reflex is the earliest response. These reflexes are followed at circa 100 ms by more intense EMG activity due to voluntary movement, but braking of head fall is evident before voluntary activity takes effect. Righting was more effective in normal subjects than in LDs, and when “active” normal subjects made more vigorous righting responses than when “passive”; whereas active righting in LDs was no better than passive. The results demonstrate that reflex responses contribute significantly to head-righting. The vestibular contribution gives an advantage over stretch reflexes alone and also assists in voluntary enhancement of reflex responses.

Afferent control of walking: Are there distinct deficits associated to loss of fibres of different diameter?

OBJECTIVES To compare the gait pattern in patients affected by different types of neuropathy. METHODS We recruited healthy subjects (HS, n=38), patients with Charcot-Marie-Tooth disease type 1A (CMT1A) (n=10) and patients with diabetic neuropathy (DNP) (n=12). Neuropathy impairment score and neuropathy score were assessed. Body sway during quiet stance, and spatio-temporal gait parameters were recorded. RESULTS Most patients had reduced or absent tendon-tap reflexes. Strength of foot dorsiflexor muscles (p<0.05) and conduction velocity (CV) of leg nerves (p<0.0001) were more impaired in CMT1A than DNP, whereas joint-position sense was more affected (p<0.05) in DNP. Body sway while standing was larger in DNP compared to CMT1A and HS (p<0.01 and p<0.0001 respectively). During gait, the distribution of foot sole contact pressure was abnormal in CMT1A (p<0.05) but not in DNP. Velocity and step length were decreased, and foot yaw angle at foot flat increased, in DNP with respect to CMT1A and HS (both variables, p<0.001). Gait velocity and step length were decreased (p<0.005) also in CMT1A, but to a smaller extent than in DNP, so that the difference between patient groups was significant (p<0.0005). Duration of the double support was protracted in DNP compared to CMT1A and HS (p<0.0005). For DNP only, velocity of gait and duration of single support were correlated (p<0.05) both to sway path and lower limb muscle strength. CONCLUSIONS Changes in both body sway and stance phase of gait were larger in DNP than CMT1A, indicating more impaired static and dynamic control of balance when neuropathy affects the small in addition to the large afferent fibres. Diminished somatosensory input from the smaller fibres rather than muscle weakness or foot deformity plays a critical role in the modulation of the support phase of gait. SIGNIFICANCE The analysis of balance and gait in patients with neuropathy can offer a tool for understanding the nature and functional impact of the neuropathy and should be included in their functional evaluation.

The complex role of spindle afferent input, as evidenced by the study of posture control in normal subjects and patients

Abstract This report reviews recent findings from our laboratory on the connectivity of the group II spindle afferent input and the role played by these afferents in the control of quiet and perturbed human stance. At variance with group Ia fibres, which subserve the monosynaptic stretch reflex, the group II fibres, after having entered the spinal cord, make synamptic contacts with a short chain of interneurons which impinge on homonymous motoneurons. Analysis of the short- and medium-latency responses evoked in foot and leg muscles by perturbations of upright stance under different experimental conditions has revealed a role of group II fibres in the production of the medium-latency response. The conduction velocity of group II spindle afferent fibres and their central delay have also been estimated. Furthermore, data from normal subjects and from neuropathic and hemiparetic patients are in favour of a prevailing role of the input from group II fibres in the afferent control of quiet and perturbed stance. Since Ia fibres innervate receptors more sensitive to the veolocity of muscle stretch, and II fibres innervate receptors more sensitive to the absolute value of muscle length, it is hypothesised that the major role of the latter in the reflex control of stance reflects the slow velocity and amplitude of sway during quiet upright posture. Indirect evidence supports the conclusion that, also in humans, monoaminergic descending pathways from brainstem nuclei modulate the excitability of the circuits mediating the group II input.

Circumferential versus Hand-held Laser Scanner Method for the Evaluation of Lower Limb Volumes in Normal-weight and Obese Subjects

Circumferential measurement (CM) for lower limbs volume computation is a simple and accurate method; however, its reliability depends on the operator’s skills. Recent studies support the use of a new technique for an accurate and reliable measurement of body segments based on 3D laser scanner method (LS3D). The detection of the limb volume in obese patients can be tricky, due to the excess of masses that may hamper the identification of anatomical landmarks. In this study, we wanted to compare CM and LS3D in terms of circumferential measures and volumes of lower limbs in normal-weight and in obese subjects. We measured lower limb volumes in 21 female obese and in 11 female healthy subjects with both methods. Our data show statistically significant differences in terms of volume as detected by CM and LS3D. In the comparison between methods, the control group had showed a higher number of parameters statistically different in comparison with the obese. The reason is related to the shape of the limb: whereas in lean subjects the leg shape is anatomically defined, in obese subjects the presence of fat layers masks the anatomical landmarks with the leg shape closely resembling a cone figure. In this latter case, the Frustum formula seems to better approximate the volume. LS3D presents with the advantage of detecting gibbousness and uneven limb shapes, i.e. in patients lymphedema, which can be overlooked by the Frustum formula. Our data suggest that LS3D may represent a suitable tool for clinical applications, especially for pre-post evaluations.

Do Secondary Spindle Afferent Fibres Play a Role in the Late Response to Stretch of Leg Muscles in Humans

Upright stance perturbations induced by a movable platform elicit reflex responses in lower limb muscles (Figure 1). Foot dorsiflexion evokes a short- (SLR) and a medium-latency response (MLR) in both soleus (Sol) and flexor digitorum brevis (FDB) muscles. Foot plantarflexion evokes a MLR in the tibialis anterior (TA). While the SLR is considered to be the counterpart of the stretch reflex (Siliotto, Grasso, Nardone & Schieppati, 1995), no general agreement exists about the origin of the MLR. It has been suggested to be either a spinal response transmitted through group II afferents (Dietz, 1992) or a long-loop reflex initiated by Ia afferents (Fellows, Domges, Topper, Thilmann & Noth, 1993). Inspired by the hypothesis that SLR and MLR are transmitted through different neural circuits, we studied a) the effect of height and age on the latency of the responses, b) the modulation of response size induced by changes in the postural “set”, c) the peripheral conduction velocity of the responsible fibres and the central delay of the responses, d) the effect of a substance known to selectively depress the transmission through group II-recipient interneurones in the cat.