Characterization of gait parameters in patients with Charcot-Marie-Tooth disease.
The gait of five patients with Charcot-Marie-Tooth(CMT) disease was analyzed using light-emitting diodes and a force plate. The flexion-extension motions of the hips, knees, and ankles, as well as their moments (vector sums of forces acting at the joints) in the flexion-extension and abduction-adduction planes, were quantified. The gait of the CMT patients showed abnormalities consistent with both distal weakness (ankle dorsi- and plantar-flexors) and weakness of the hip abductor muscles. The latter weakness appeared to produce asymmetric hip moments and truncal instability in the mediolateral plane during ambulation. However, the extent to which the gait was abnormal appeared not to be exclusively related to the severity of the sensorimotor conduction deficits in the peripheral nerves. In the four patients for whom nerve conduction velocity studies were available, decrease in the lower-extremity distal conduction velocities and evoked motor amplitude potentials did not correlate with the severity and extent of the gait abnormalities.
Charcot-Marie-Tooth (CMT) disease is an autosomal dominant disorder whose principal clinical manifestations involve the peripheral nervous system., Although both the motor and sensory components of large peripheral nerves undergo demyelination and degeneration, the lower extremities are usually affected more than the upper. The rate at which the disease progresses allows patients either to deteriorate very slowly or to remain clinically stable for relatively long periods of time (i.e. decades). Eventually, they develop marked atrophy of the distal leg muscles with relative sparing of the trunk and proximal leg musculature (producing a 'champagnebottle' or 'stork-like appearance' of the legs).
In the previous work, we employed the technique of gait analysis to characterize the walking patterns of patients with myotonic dystrophy. This autosomal dominant genetic disorder is similar clinically to CMT disease, in that, it produces weakness and wasting of the distal leg muscles., In myotonic dystrophy patients, the distal weakness was associated with markedly abnormal oscillations of the hip in the antero-posterior plane. Hip motion varied widely from side to side from stride to stride. It remained unclear, however, whether or not the weakness of the distal leg muscles seen in myotonic dystrophy was the cause of the abnormal hip motion, and whether or not CMT patients would exhibit a similar phenomenon.
To help address these questions, we have examined the gait of 5 patients with weakness of the distal leg muscles, secondary to CMT disease.
Five patients were selected who presented clinical evidence of CMT disease of moderate severity,, namely (1) high-arched feet, (2) clinically evident atrophy of the tibialis anterior and peroneal muscles bilaterally, and (3) markedly slowed to absent motor and sensory nerve conduction velocities in the peripheral nerves of the lower extremities, with large motor unit potentials and minimal to no evidence of acute denervation of distal muscles. Each patient was ambulatory without devices in normal daily activities.
After providing informed consent, each patient had infrared-emitting diodes affixed so as to bracket the hips, knees, and ankles. Each ambulated down a runway at a self-selected speed which he or she found comfortable. The runway contained a force plate to record ground reaction forces, from which calculations of the moments (forces) acting at the hips, knees, and ankles could be made. Videotapes of each subject were also made. Data from all subjects were compared to the laboratory values for over 100 normal subjects (over 300 normal gait runs) who had no history or clinical evidence of musculoskeletal or neuromuscular disease.
(1) Joint motions in the antero-posterior plane:
In all the 5 patients, the ankle motion during stance phase was abnormal [Figure. 1] and [Figure. 2], [Table I]. In normals, there was a smooth, consistent pattern of progression from plantarflexion at heelstrike through dorsiflexion at midstance and then again into plantarflexion prior to toe off (dotted lines). The CMT patients began heel-strike with their ankles excessively plantar-flexed, and were able to move into full dorsi-flexion only late in stance phase, after a series of oscillations between dorsi - and plantarflexion. The knee in all 5 patients was excessively flexed at heel-strike [Figure. 1] and [Figure. 2]. It became more flexed as the foot moved toward foot-flat in stance phase, and did not extend to a normal degree later in stance phase, when flexion for leg pickup began earlier than normal prior to toe-off. Hip flexionextension motion was close to normal in both total range and motion pattern in 4 of the 5 patients ( [Table I] and [Figure. 1]. In one patient, however, the hips oscillated irregularly throughout the stance phase during their overall movement from flexion to extension, in an undulating pattern which differed between the left and right sides and from stride to stride [Figure. 2]. A similar pattern to that seen only in this CMT patient appears to characterize the hip flexion-extension motion of all myotonic dystrophy patients.
(2) Moments (forces) acting at joints A. Flexionextension:
In 4 of the 5 patients, the ankle flexion-extension moments were abnormal [Figure. 1]. Normals show a pattern of a relatively smoothly and steadily increasing dorsiflexion moment throughout most of stance phase (dotted line, [Figure. 1]. The CMT patients, in contrast, showed a sharp pause or reversal in the dorsi-flexion moment early in stance, and later in stance attained a peak dorsi-flexion moment value which was approximately 1/3 less than the normal value [Figure. 1]. This CMT pattern is consistent with weakness of the plantar-flexors of the foot (e.g. triceps surae complex), which normally must possess adequate strength to contract eccentrically during stance against 7-10% of body weight times height. In CMT patients, the gastro-soleus complex does not appear to be of sufficient strength to oppose properly the foot dorsi-flexion ground reaction force generated during mid-stance knee flexion, as the weight of the body passes over the foot.
All 5 patients showed evidence of excessively strong hip-flexion and knee-extension moment spikes, which occurred as the foot moved into the foot-flat position shortly after heel-strike [Figure. 1] and [Figure. 2]. The ground reaction force as the entire foot descends to the floor normally is not visible as a specific increase in ground reaction force after heel-strike, since eccentric lengthening of the foot dorsi-flexors damps the movement. In the CMT patients, however, this spike was visible at the hip and knee as larger-than-normal moment transients (with sharp fluctuations) as the foot slapped onto the ground. This pattern is consistent with weakness of the foot dorsi-flexors, principally the tibialis anterior, which must lengthen eccentrically after heel-strike prevent the foot from hitting the ground with excessive force.
All but the one patient with the hip-motion oscillations had moderately higher-than-normal increases in knee flexion moment during and after midstance. This pattern is consistent with the presence of a strong contraction of the quadriceps femoris muscle, which resists the flexion moment generated by ground reaction forces as the weight of the body passes over the knee [Figure. 1]. The knee moment in the one patient with the excessive and abnormal hipmotion oscillations [Figure. 2] remained extensor throughout the entire stance phase. In her case, the excessive extensor moment suggests very poor ability to resist stance-phase knee flexion with the quadriceps muscle. Instead, she ambulated with her trunk flexed forward in order to counterbalance the excessive knee flexion during stance (a 'crouched gait' typical also of children with spastic diplegia,. She may also have been using her hamstrings throughout stance phase to assist with hip extension and to help maintain a stable crouched posture.
Hip flexion-extension moments were essentially normal in phasing, timing, and magnitude in all 4 patients except the one with hip-motion oscillations [Figure. 1]. As noted above, hip moments in all patients were perturbed shortly after heel-strike by the 'foot slap' flexion spike as the foot hit the ground with greater-than-normal force. The flexion-extension hip moments in the patient with the flexion-extension hipmotion oscillations varied widely from stride to stride for both the left and right sides [Figure. 2]. In more than half of the recorded gait cycles, the hip moment remained flexor almost throughout the entire stance phase, achieving an extension force (of decreased magnitude) only just prior to the beginning of hip and knee flexion to initiate leg pickup. During the flexor phase of the hip moment, there were superimposed small irregular oscillations in moment magnitude.
B. Abduction-Adduction: The hip and knee abduction-adduction moments were consistently abnormal during essentially all gait runs for all CMT patients [Figure. 1] and [Figure. 2]. In normal patients, both hip and knee are subject throughout stance phase to a purely adduction moment, with a magnitude of 3-5% body weight times height for the knee and 5% for the hip. The moment pattern is typically W-shaped, with 2 peaks approximately equal in magnitude, one early and the other later in the stance phase. In all the CMT patients, the W-shaped adduction moment pattern was highly asymmetrical, as well as variable between sides and strides, usually with marked prominence of the first peak and diminution or truncation of the other [Figure. 1] and [Figure. 2]. This pattern is consistent with trunk lurch or rolling away form the swing side during stance phase, decreasing the adduction moment after its initial peak. In addition, all except the patient with the hip-motion oscillations (see below) had sharp Trendelenburg (abduction) spikes visible at both hip and knee shortly after heel-strike [Figure. 1]. These indicate that the trunk was being pulled rapidly away from the swing-phase leg at heel-strike, possible in an attempt to decrease the 'foot-slap' force which occurred as the foot hit the ground.
The magnitudes of the hip and knee adduction moments were within the normal range for 3 of the 5 patients [Figure. 1]. The patient with the hip-motion oscillations had quite variable (but high) hip adduction moments, 6-7% body weight times height, coupled with variable (but low) knee moments (1-3% body weight times height) [Figure. 2]. The other patients with abnormal magnitudes of hip and knee adduction moments during stance phase had relatively low moment values at both hips and knees, ranging from 3-4% at the hips to 2-3% at the knees. These moments were accompanied by, and possibly caused by, very strong Trendelenburg spikes (i.e., trunk shifts toward the stance-phase side, which would produce a counteropposing abduction force), with magnitudes of 4-6% body weight times height at the hip and 3-4% at the knee.
(3) Gait Cycle Parameters: In all 5 CMT patients, gait cycle parameters were within the ranges expected for normals [Table II] and [Figure. 3].
Clinically, one feature which has been reported to characterize CMT disease is weakness of the distal leg muscles, with relative sparing of the proximal leg musculature., Supporting this concept, two types of gait abnormalities observed in all the 5 patients studied here are consistent with weakness of both the foot dorsi-flexors (i.e. tibialis anterior) and plantarflexors (i.e. gastroc-soleus complex), as follows: (i) The 'foot slap' moment spikes seen in all patients at the hip and knee shortly after heel-strike indicate a decreased ability of the foot dorsi-flexors to lengthen eccentrically to allow the foot to proceed smoothly to a flat conFigureuration. (ii) The CMT gait also shows evidence of weakness of the foot plantar-flexors. The flexion-extension ankle wobble and moment irregularities seen as the foot proceeds through stance phase suggests poor ability of the gastroc-soleus muscle complex to contract eccentrically to damp this motion and moment. In addition, in 4 of the 5 patients, the absolute magnitude of the dorsi-flexion moment, which requires eccentric contraction of the plantarflexors to oppose it, was decreased by approximately 30%. The gait abnormalities observed here suggest another feature of CMT disease, one which is not generally believed to characterize it clinically. During normal gait, the adduction moments developed at the hip and knee in the stance phase limb are opposed by an eccentric contraction of the hip abductor muscles. Three features of CMT gait cause deviations from the normal hip and knee adduction moments and are consistent with weakness of the hip abductors: (i) the marked inconsistency of the adduction moments (i.e. between sides and strides), (ii) the irregular character of the moments, consistent with trunk roll causing high and low peaks around the beginning and end of the stance phase respectively, and (iii) the rapid trunk shift (Trendelenburg) away from the swing side shortly after heelstrike (with post-heelstrike trunk shift in one patient so prominent as to diminish markedly the magnitude of the adduction moments).
Despite the apparent weakness of their hip abductors, CMT patients do not necessarily demonstrate concomitant weakness of the hip extensors. Only one of the patients, the one with the gait which was most abnormal around all joints, showed hip-motion oscillations in the flexion-extension plane. Similar oscillations, which did not occur in the other 4 patients, were noted in another study which characterized the gait of patients with myotonic dystrophy. They are believed to result from inability of the hip extensors to deal with the flexion force imparted to the hip by the force of the entire foot striking the floor.
Of the 5 patients studied here, one stands out as having the greatest number and extent of gait abnormalities. She ambulated with a crouched gait, excessively flexed at the hip and knees, with her upper body flexed forward. She also rolled from side to side during the latter half of stance phase on each side. The observed motion and moment abnormalities included
(i) excessive and prolonged knee flexion throughout the stance phase, with trunk forward flexion to compensate for the knee flexion and probable quadriceps weakness, (ii) excessive and irregular foot dorsi-flexion throughout stance phase, (iii) marked variability and instability (oscillation) of the hip moment in the antero-posterior plane, with limited hip extension later in stance phase, (iv) marked variability of the hip moments in the flexion-extension (antero-posterior) plane, and (v) profound variability and instability of both hip and knee adduction moments in the medio-lateral (abduction-adduction) plane, due to trunk lean. These gait deviations in this patient strongly suggest that she had markedly subnormal strength, in particular of the foot dorsi-flexors, the triceps surae, the hip extensors, and the hip abductors. It is unclear why this particular patient has evolved clinically to the point of such severe and generalized weakness of both proximal and distal muscles of the lower extremities. One possibility was that she had the most severely affected lower-extremity motor nerves, with the poorest conduction velocities. To test this hypothesis, we examined conduction velocities in the peroneal and posterior tibial nerves of 4 of the patients, using traditional methods for recording nerve conduction parameters.,  The CMT patient with the poorest gait, and with the strongest evidence of generalized proximal and distal weakness, had recorded conduction velocities only 20% below the lower limit of normal, with amplitudes of evoked motor unit potentials ranging from 0.3-3.0 mv. In contrast, no evoked motor action potentials could be recorded from the muscles of 2 patients with much better gait patterns, and a third patient with a relatively good gait pattern had conduction velocities 50% and 80% below the lower limit of normal in the posterior tibial and peroneal nerves, respectively (amplitudes of evoked motor unit potentials, 0.1-0.6 mv).
The observed gait of all the CMT patients was compatible with weakness of the distal leg muscles, both tibialis anterior and triceps surae. Despite this weakness, however, and unlike the myotonic dystrophy patients with similar tibialis anterior weakness, 4 of the 5 CMT patients showed good control of their hips in the flexion-extension plane. Also unlike the myotonic patients, who show no evidence of hip abductor weakness, all the CMT patients appear to have weakness of the hip abductors, with resultant disordered hip and knee adductor moments and an exaggerated use of trunk motion in an attempt to compensate.
The data suggests a strong central, rather than peripheral, aetiology for the control of human gait in CMT disease. In these patients, the preservation of gait balance, reciprocity, and smoothness, as well as the ability to employ compensatory strategies when there are weaknesses of specific lower-extremity muscles, can be maintained even in the presence of relatively severe loss of sensorimotor conduction in the peripheral nerves.