Influence of basal ganglia on upper limb locomotor synergies. Evidence from deep brain stimulation and L-DOPA treatment in Parkinson's disease.

Clinical evidence of impaired arm swing while walking in patients with Parkinson's disease suggests that basal ganglia and related systems play an important part in the control of upper limb locomotor automatism. To gain more information on this supraspinal influence, we measured arm and thigh kinematics during walking in 10 Parkinson's disease patients, under four conditions: (i) baseline (no treatment), (ii) therapeutic stimulation of the subthalamic nucleus (STN), (iii)L-DOPA medication and (iv) combined STN stimulation and L-DOPA. Ten age-matched controls provided reference data. Under baseline conditions the range of patients' arm motion was severely restricted, with no correlation with the excursion of the thigh. In addition, the arm swing was abnormally coupled in time with oscillation of the ipsilateral thigh. STN stimulation significantly increased the gait speed and improved the spatio-temporal parameters of arm and thigh motion. The kinematic changes as a function of gait speed changes, however, were significantly smaller for the upper than the lower limb, in contrast to healthy controls. Arm motion was also less responsive after L-DOPA. Simultaneous deep brain stimulation and L-DOPA had additive effects on thigh motion, but not on arm motion and arm-thigh coupling. The evidence that locomotor automatisms of the upper and lower limbs display uncorrelated impairment upon dysfunction of the basal ganglia, as well as different susceptibility to electrophysiological and pharmacological interventions, points to the presence of heterogeneously distributed, possibly partially independent, supraspinal control channels, whereby STN and dopaminergic systems have relatively weaker influence on the executive structures involved in the arm swing and preferential action on those for lower limb movements. These findings might be considered in the light of phylogenetic changes in supraspinal control of limb motion related to primate bipedalism.

The association between impaired turning and normal straight walking in Parkinson's disease.

Turning whilst walking was investigated by gait analysis in a group of Parkinson's Disease (PD) patients with mild clinical impairment and no significant abnormalities in stride parameters and kinematics of steady-state, linear walking. Comparison with age-matched controls demonstrated that patients approached turns with a slower step and completed turning with a greater number of steps. Moreover, the normal cranio-caudal sequence, whereby rotation of the head toward the intended direction of travel is followed by rotation of the trunk, was replaced by nearly simultaneous rotation of head and trunk and decreased relative head excursion after the second turning step. The evidence of abnormal inter-segmental coordination during turning in mildly affected, normally walking patients suggests that task-specific pathophysiological mechanisms, not necessary related to basic locomotor deficits, underlie disturbed directional changes in PD. Furthermore, turning-related neural systems may be more vulnerable to functional impairments associated with PD, as compared with linear walking. Hierarchically higher control levels involved in the turning ability may explain the observed unexpected association.

The heel-contact gait pattern of habitual toe walkers.

We used kinematic, kinetic and EMG analysis to compare the spontaneous heel-contact gait patterns of 13 children classified as habitual toe walkers (HTWs) and age-matched controls. In the HTWs, the incidence of spontaneous heel-contact strides during a single recording session ranged from 15% to 92%, with no correlation with age, passive ankle joint excursion, walking speed and trial order. Hallmarks of the heel-contact strides were premature heel-rise, reversal of the second rocker, relative shortening of the loading response and anticipation and enhancement of the electromyographic (EMG) activity normally observed in the triceps surae (TS) during the first half of the stance phase. This variant of the locomotor program is different from the walking patterns observed in normally developing toddlers and children with cerebral palsy (CP). It does not necessarily reflect a functional adaptation to changes in the rheological properties of the muscle-tendon complex.

Spasticity and 'spastic' gait in children with cerebral palsy.

The current notion of spasticity as a velocity-dependent increase of muscle response to imposed stretch was mainly derived from studies performed under stationary experimental conditions. To address the issue of a spastic muscle behaviour under dynamic conditions, we conceived a novel approach, aimed at quantitatively assessing motor output over the lengthening periods which take place during unperturbed functional movements. Application to the analysis of overground walking in children with spastic cerebral palsy (CP) revealed that, for representative lower limb muscles, the relationship between EMG levels and estimated muscle lengthening rate displays either increased gain or reduced velocity threshold. Parallel measurement of gait kinetics frequently showed congruent increase of the mechanical resistance to joint rotation. Abnormalities preferentially targeted the lengthening contractions occurring around the ground contact period of the stride. The pathophysiological profile of what is clinically defined as 'spastic' gait in CP children did not only consist of dynamic spasticity, as described above. Most often it resulted from the simultaneous contribution of other factors, including paresis, co-contraction, immature and non-neural components.

Alterations of ocular motility in cerebellar pathology. An electro-oculographic study.

Saccadic as well as smooth pursuit movements were studied by means of electro-oculograms in a group of 14 patients affected by cerebellar diseases. Ten patients had cerebellar atrophies, and four had undergone surgery for cerebellar tumors. Loss of gain of the pursuit system and metric alteration of saccades were the most striking abnormalities observed. Dysmetria was shown to be related to the amplitude of the movement and to the sector of the perimeter within which the movement occurs (movements occurring in the more eccentric sector were more disturbed). A tendency to produce saccades slower than normal was noted in patients affected by olivopontocerebellar atrophy. The clinical and pathophysiological significance of this finding is discussed with particular reference to Wadia-Swaami hereditary ataxia.

Natural cutaneous stimulation induces late and long-lasting facilitation of extensor motoneurons in the cat.

An investigation was made of the effects of physiological cutaneous stimulation on the excitability of extensor motoneurons in spinal unanesthetized cats. The time course of changes in the monosynaptic reflex (MSR) amplitude of the soleus (Sol) and gastrocnemius medialis (GM) and lateralis (GL) was studied after conditioning stimulation with air jets (delivered to different regions of the skin of the ipsilateral hind limb), pinpricks, or stretching of the skin of the heel induced by passive rotation of the tibio-tarsal joint. Low-intensity electrical stimulation of the sural or saphenous nerves was also employed in order to condition the MSRs of the triceps surae muscles. Hair bending, skin indentation or stretching, as well as electrical nerve stimulation, can induce a similar biphasic excitability cycle of the extensor MSRs, characterized by an early inhibition followed by a late facilitatory period (LFP). The LFP started approximately 20 ms after the arrival of the cutaneous afferent volley, and lasted about 80 ms. Conditioned MSRs could attain values corresponding to 200% or more of controls. The receptive field of the LFP evoked by the air jet proved to be as large as the whole leg and foot skin surface. No significant differences were found in the extent of the late facilitation in the MSRs of Sol, GM and GL, conditioned by electrical stimulation. The LFP was also present, after conditioning stimulation of the same types as above, in intact (and spinal) chloralose-anesthetized cats.

Chronic cluster headache: response to lithium treatment.

A clinical trial of lithium carbonate was undertaken in a group of 20 patients suffering from chronic cluster headache. Blood levels of lithium were determined at regular intervals to monitor the therapeutic dosage. Lithium was found to be an effective prophylactic agent for chronic cluster headache patients. The effectiveness of lithium was evident in less than a week after the beginning of treatment. It is not clear in what way lithium may act on cluster headache.

Neurological and pharmacological evaluation of a case of stiff-man syndrome.

A typical case of stiff-man syndrome was studied neurophysiologically and pharmacologically focusing the attention on a central disorder, either spinal or suprasegmental. The results support the hypothesis that a gamma type of hypertonia is one of the causes of the stiff-man syndrome, ruling out the participation of the Renshaw circuits. The syndrome should be considered a central disorder of the descending pathways that control and modify gamma activity and the startle reaction mechanisms, especially affecting the circuits that use Gabaergic mediators.

5-OH-Tryptophane in migraine: clinical and neurophysiological considerations.

The clinical effects of the protracted treatment with 5-OH Tryptophane (5-HTP) of some patients with chronic migraine are compared with other patients with acetylsalicylic acid. The pain threshold was neurophysiologically determined in migraneous on patients whose response to 5-HTP therapy was specially good. The results with 5-HTP can be accounted for by an action of the substance on the serotonin turnover with activation of the serotoninergic antinociceptive system.

Relationship between clinical and electrophysiological findings and indicators of heavy exposure to 2,3,7,8-tetrachlorodibenzo-dioxin.

In this study the prevalence rate of peripheral neuropathy in a population living in an area polluted with 2,3,7,8-tetrachlorodibenzo-dioxin (dioxin-TCDD) was determined. Of the 723 subjects invited to the first screening in 1977, 470 (65%) attended. At the second screening in 1978, of the 710 invited subjects, 319 (45%) attended. Prevalence rate ratios for peripheral neuropathy and the associated 95% confidence limits were calculated for subgroups determined by the presence of (i) predisposing factors to neuropathy (alcoholism, diabetes, occupational exposure to neurotoxic agents, etc) or (ii) conditions thought to result from exposure to dioxin-TCDD such as chloracne or abnormal serum hepatic enzyme levels. The prevalence rate of peripheral neuropathy among those subjects with predisposing factors and among those with chloracne or abnormal serum hepatic enzyme levels was nearly three times greater than among those without these manifestations. The results derived from this study may be useful qualitative pointers for identifying subjects at risk in the neurological follow-up.

Modelling the triceps surae muscle-tendon complex for the estimation of length changes during walking.

The triceps surae muscle-tendon complex has been modelled by many authors seeking to estimate the change in muscle length that occurs in locomotion. The objective of the present study is to assess to what extent the commonly adopted assumptions of foot rigidity and pure sagittal motion are acceptable. A model of the triceps surae muscle-tendon complex was implemented by taking into account all possible movements between forefoot and rear foot. Length and velocity curves from a 3-dimensional gait analysis were obtained from six normal subjects. The angle between forefoot and rear foot proved to be changeable with stride (11.8 degrees +/- 4.7 SE). The effect on the length and velocity estimation was analysed by comparing the curves obtained by our model to those obtained by a model in which the foot is considered to be a rigid body. Significant differences were found for the soleus muscle length at late stance/early swing and late swing phases, and for the soleus muscle velocity at early stance phase. The length and velocity curves were also compared to curves calculated on a pure sagittal projection. No changes were observed, except for an offset of 1-3 mm caused by the general external rotation of the foot (which is also present in standing). The curves appeared superimposable when referred to the standing upright position. Care needs to be taken, however, when extending the above results to the clinical application, where foot deformity and deviation from a normal pattern of motion can occur.

Moment-angle relationship at lower limb joints during human walking at different velocities.

The coupling between joint kinematics and kinetics during level walking was analysed by plotting joint angles vs. joint moments about the hip, knee and ankle in nine normal male subjects walking at three different velocities. The curves obtained were reproducible, and variability among subjects was relatively low. Counterclockwise loops corresponded to energy produced, and clockwise loops to energy absorbed at the joint; both loops are described in different phases of the stride cycle. At increasing walking velocity some of the loops narrowed, thus revealing the possibility of energy recovery. Analysis of individual diagrams revealed that consistent portions of the moment-angle loops can be described as a sequence of quasi-constant slope phases, separated by transition periods where quasi-isometric changes in joint moment occur. This figure, which was particularly evident of the hip and ankle joints, is reminiscent of a mechanical system with elastic components, which, in different phases of the rhythmic locomotion activity, moves along discrete status levels characterized by specific length-tension relationships. Implications of the above results in terms of the neurol control of joint properties during active movement are discussed.

Effect of L-dopa and subthalamic nucleus stimulation on arm and leg swing during gait in Parkinson's Disease.

The effects of subthalamic nucleus (STN) stimulation and L-dopa administration on the arm and leg swing movements associated with overground walking were studied in a group of patients with idiopathic Parkinson's disease (PD). Ten patients undergoing deep brain stimulation and twenty controls were tested using 3D kinematic motion analysis. Parkinsonian patients under basal conditions walked more slowly and with reduced arm and leg swing compared to controls. Moreover, they displayed significant impairments of the normal interlimb coordination. Both STN stimulation and L-dopa increased the walking speed and the amplitude of arm and leg swing movements. Additional improvements of the coordination between upper and lower limb were documented by reductions of the phase-shift between arm and ipsilateral leg motion, with displacement toward the control range (perfect counterphase). STN stimulation alone and L-dopa alone produced similar effects on the variables analyzed. The combination of the two treatments, instead, yielded additive effects on the gait speed and a slight increase of the upper and lower limb range of motion, in the absence of further improvements in the inter-segmental coordination. Moreover, whereas the increased arm swing could be accounted by the sole adoption of a higher gait speed, both the increment of the leg movement amplitude and the decreased interlimb phase shift appeared to imply an additional effect, possibly related to the treatment. These results may suggest that differential supraspinal controls operate on the neural networks subserving upper and lower limb motion during human walking.

Impact of subthalamic nucleus stimulation on the initiation of gait in Parkinson's disease.

The effects of subthalamic nucleus (STN) stimulation on the anticipatory postural actions associated with the initiation of gait were studied in ten patients with idiopathic Parkinson's disease undergoing therapeutic deep brain stimulation. Kinematic, dynamic and electromyographic analysis was performed before and while subjects were starting gait in response to an external cue. Effects of STN stimulation on the standing posture preceding the go signal included significant improvement of the vertical alignment of the trunk and shank, decrease of the hip joint moment, backward shift of the center of pressure (CoP) and reduction of abnormal tonic and/or rhythmic activity in the thigh and leg muscles. Responses to bilateral STN stimulation were more consistent than those evoked by unilateral stimulation. Moreover, comparison between postural changes induced by STN stimulation applied prior to the gait initiation cue and during simple quiet standing revealed more significant responses in the former condition. Effects on the actual gait initiation process included shortening of the imbalance phase, larger backward/lateral displacement of CoP and more physiological expression of the underlying anticipatory muscular synergy. Additional changes were shortening of the unloading phase, shortening of the first-swing phase and increase in the length of the first step. Results demonstrate substantial influence of STN stimulation on functionally basic motor control mechanisms. In particular, the evidence of more significant responses upon attention-demanding conditions and the remarkable effects on postural programmes sub-serving feed-forward regulation of the onset of complex multijoint movements, suggests a consistent action on postural sub-systems relying on cognitive data processing and internal models of body mechanics.

A motor programme for the initiation of forward-oriented movements in humans.

1. The EMG sequence activated before the initiation of a number of fast forward-oriented voluntary movements was analysed quantitatively in normal subjects. 2. The sequence consisted of an initial inhibitory component directed to the soleus motor nucleus, followed by a second excitatory one directed to the tibialis anterior (TA). 3. The spectrum of functional utilization included motor tasks in which the prime movers are leg and thigh muscles (initiation of gait, rising on tip-toes), thigh and trunk muscles (fast-forward bending of the trunk, standing up) and upper-limb muscles (forward throw or catch). 4. In a same motor task and across the different motor tasks, performed at various speeds, the latency of soleus inhibition and TA activation with respect to the onset of movement co-varied according to a linear function, indicating a close temporal correlation between the two components. 5. In all the movements investigated, the earliest mechanical effect was a backward displacement of the centre of foot pressure in the sagittal plane. 6. Soleus inhibition alone and TA burst alone were each able to produce a backward displacement of the centre of foot pressure, but the effect was significantly slower after soleus inhibition. 7. The spatio-temporal parameters of the sequence were modulated according to the pre-existing postural conditions. For the gait initiation protocol, increasing initial forward leaning led to a decrease in the amplitude of soleus inhibition and the TA burst, and to a change in their relative time delays. Modulation was different on the two sides. We could define a postural boundary as the degree of forward leaning beyond which the full sequence is no longer called into action. 8. The spatio-temporal parameters of the sequence were pre-set according to the requirements of the forthcoming movement. In the gait initiation protocol, the amplitude and synchronization of the TA burst were directly correlated with velocity of movement, while the relative delay between soleus inhibition and TA activation was inversely correlated. Modulation on the two sides differed. We could define a velocity boundary as the velocity of movement below which the full sequence is no longer called into action. 9. We suggest that the EMG sequence described can be considered a motor programme that, through direct action on the position of the centre of foot pressure (the variable primarily controlled), will precisely adjust the configuration of forces external to the body, allowing the contraction of the prime mover(s) to interact appropriately with them for the production of a specific, forward-oriented movement.

Excitability of the soleus H-reflex arc during walking and stepping in man.

In eight normal subjects, the excitability of the soleus (Sol) H-reflex was tested in parallel with Sol length changes, EMGs of leg and thigh muscles and ground contact phases, during three different pacing movements: bipedal treadmill walking, single limb treadmill walking, and single-limb stepping on one spot. A computerized procedure was used which compensated for changes in stimulus effectiveness that occurred during free motion. In the three paradigms examined, significant excitability modulations were observed with respect to a control level determined in standing weight-bearing position. During bipedal treadmill walking, excitability was decreased in the early stance, maximally enhanced in the second half of the stance, and again decreased during the end-stance and the whole swing phase, with a minimum value around the toe off period. The main modulation pattern was retained during single-limb treadmill walking. During single-limb stepping on one spot, the stance-phase increase in excitability and the swing phase depression were still present. However, in the second half of the swing phase, reflex responsiveness returned to reference level, which was maintained during the subsequent contact period. Moreover, a decrease in reflex excitability was detected around the mid-stance. The time course of the described modulations was only partly correlated with the EMG and length changes of the Sol muscle. Furthermore, in the three movements tested, during the early stance phase, the excitability of the H-reflex arc did not correspond to the one expected on the basis of the available H-reflex studies performed under static conditions. It is suggested that, at least in certain stride phases (e.g. around the early contact period), an active regulation affects the transmission in the Sol myotatic arc during the pacing movements investigated.