The spasticity paradox: movement disorder or disorder of resting limbs?

BACKGROUND: Spasticity is defined/assessed in resting limbs, where increased stretch reflex activity and mechanical joint resistance are evident. Treatment with antispastic agents assumes that these features contribute to the movement disorder, although it is unclear whether they persist during voluntary contraction. OBJECTIVES: To compare reflex amplitude and joint resistance in spastic and normal limbs over an equivalent range of background contraction. METHODS: Thirteen normal and eight hemiparetic subjects with mild/moderate spasticity and without significant contracture were studied. Reflex and passive joint resistance were compared at rest and during six small increments of biceps voluntary contraction, up to 15% of normal maximum. A novel approach was used to match contraction levels between groups. RESULTS: Reflex amplitude and joint mechanical resistance were linearly related to contraction in both groups. The slopes of these relations were not above normal in the spastic subjects on linear regression. Thus, reflex amplitude and joint resistance were not different between groups over a comparable range of contraction levels. Spastic subjects exhibited a smaller range of reflex modulation than normals because of decreased maximal contraction levels (weakness) and significant increases of resting contraction levels. CONCLUSIONS: Spasticity was most evident at rest because subjects could not reduce background contraction to normal. When background contractions were matched to normal levels, no evidence of exaggerated reflex activity or mechanical resistance was found. Instead, reduced capacity to modulate reflex activity dynamically over the normal range may contribute to the movement disorder. This finding does not support the routine use of antispastic agents to treat the movement disorder.

The contribution of tremor studies to diagnosis of parkinsonian and essential tremor: a statistical evaluation.

This study statistically evaluated a set of commonly measured tremor parameters to determine their individual and combined ability to discriminate between essential tremor (ET) and Parkinsonian tremor (PT). Accelerometer and surface electromyographic (EMG) records of moderate to severe upper limb tremor in 20 patients with ET and 22 patients with PT were used to quantitatively compare tremor amplitude, frequency and pattern of muscle bursting in two resting and three non resting postures. The group statistics showed significant differences between ET and PT with respect to tremor frequency in all five postures, tremor amplitude at rest and muscle bursting patterns. Discriminant function analysis showed that no single parameter or combination of parameters was able to correctly classify all patients. Frequency was much more discriminating than amplitude or muscle bursting patterns in all limb postures. The best amplitude discrimination was obtained when the hand and forearm were both fully supported. Muscle bursting patterns were poorly discriminating and did not assist in correct classification of single patients. Group statistics confirmed a highly significant biological difference between the two tremor types. Optimal classification of single PT (86% correct) and ET (95% correct) patients was obtained using frequency and two selected amplitude parameters from the resting limb. Limb posture was an important variable in optimising the discriminative ability of tremor studies. The implications for routine tremor studies are summarised.

An automated form of video image analysis applied to classification of movement disorders.

Video image analysis is able to provide quantitative data on postural and movement abnormalities and thus has an important application in neurological diagnosis and management. The conventional techniques require patients to be videotaped while wearing markers in a highly structured laboratory environment. This restricts the utility of video in routine clinical practise. We have begun development of intelligent software which aims to provide a more flexible system able to quantify human posture and movement directly from whole-body images without markers and in an unstructured environment. The steps involved are to extract complete human profiles from video frames, to fit skeletal frameworks to the profiles and derive joint angles and swing distances. By this means a given posture is reduced to a set of basic parameters that can provide input to a neural network classifier. To test the system's performance we videotaped patients with dopa-responsive Parkinsonism and age-matched normals during several gait cycles, to yield 61 patient and 49 normal postures. These postures were reduced to their basic parameters and fed to the neural network classifier in various combinations. The optimal parameter sets (consisting of both swing distances and joint angles) yielded successful classification of normals and patients with an accuracy above 90%. This result demonstrated the feasibility of the approach. The technique has the potential to guide clinicians on the relative sensitivity of specific postural/gait features in diagnosis. Future studies will aim to improve the robustness of the system in providing accurate parameter estimates from subjects wearing a range of clothing, and to further improve discrimination by incorporating more stages of the gait cycle into the analysis.

Objective quantification of resting and activated parkinsonian rigidity: a comparison of angular impulse and work scores.

The clinical assessment of rigidity is influenced by a number of variables which limit the reproducibility of rating scores and the usefulness of comparisons between subjects. We evaluated an objective measure of rigidity which uses unpredictable but reproducible limb perturbations mimicking the waveform, rate, and amplitude of those used in the clinical examination; and evaluates total resistive force, thus avoiding assumptions about the relative influence of elastic, viscous, or inertial components of the measured resistive forces on the genesis of rigidity. We then used this measure to quantify the effects of an activation procedure on parkinsonian rigidity, because this forms an important but poorly understood part of the routine clinical examination. We studied 20 patients with a clinical diagnosis of Parkinson's disease and 10 age-matched control subjects. A torque motor was used to deliver reproducible, transient, sinusoidal perturbations varying between 1.0 and 1.5 Hz. To quantify rigidity, we calculated angular impulse scores, which reflect the relationship between change in total resistive torque and time. Angular impulse scores were compared with work scores, which have previously been found to correlate with clinical assessments of rigidity. All subjects were studied at rest and with activation. Angular impulse scores were more consistently correlated with rigidity and more clearly differentiated between patients and control subjects than work scores. Activation increased both clinical and objective rigidity scores; activated angular impulse scores ranged from approximately 100%-200% of resting values. When plotted against clinical rigidity scores, activated angular impulse scores lay on a continuum with resting values. We conclude that angular impulse is a valid objective measure of parkinsonian rigidity. Activation increases rigidity, but to varying degrees in different patients. To improve the sensitivity and reproducibility of clinical rigidity assessments, parkinsonian rating scales should include separate resting and activated scores.

Reflex inhibition following electrical stimulation over muscle tendons in man.

Electrical stimulation over selected muscle tendons in alert human subjects produced, in each muscle, a reflex inhibition of muscle activity. This inhibition, when maximal, was seen in the surface EMG as an interval of complete electrical silence during a sustained voluntary contraction. The inhibition was clearly visible in single sweeps and in averaged records. Its onset latency and duration were respectively, 56 +/- 4.9 and 46 +/- 11.8 ms in extensor digitorum communis, 71 +/- 6.1 and 46 +/- 10.5 ms in extensor pollicis brevis, 77 +/- 11.2 and 47 +/- 10.5 ms in extensor pollicis longus, 72 +/- 7.3 and 43 +/- 8.6 ms in abductor digiti minimi, and 97 +/- 3.5 and 43 +/- 2.8 ms in tibialis anterior. The inhibitory response was produced at low stimulus intensities (< 10 mA) without electrical (M wave) or mechanical (muscle twitch) signs of direct muscle stimulation. It therefore did not arise from stimulation of la afferents (muscle spindles). The response arose from tendons since it occurred at lowest threshold when stimulation was applied directly over the tendons of the five different muscles studied. At low stimulus intensities, the response declined sharply when the stimulating electrodes were moved to the skin immediately adjacent to the tendons. The response did not arise from skin afferents since it was also presented when stimuli were delivered to the tendon by subcutaneous needle electrodes and it was not reproduced by stimulation of cutaneous nerves in the region of the tendon. In another series of experiments on extensor pollicis brevis, five skin locations were stimulated while overlying the tendon and again while the skin was stretched so that they were lying 0.6-0.8 cm dorsal to the tendon. In these experiments the response was again greatly attenuated when the stimulation was not directly over the tendon, although the same cutaneous sites were stimulated. The inhibition was followed by a pronounced excitatory component (E1) of peak latency 120-140 ms. The results of the study provide evidence for a powerful autogenic inhibitory reflex in man. The evidence is consistent with the possibility that the response arises from Golgi tendon organ afferents.

Loss of tendon organ inhibition in Parkinson's disease.

Electrical stimulation via skin electrodes placed over human tendons results in a reflex inhibition of voluntary activity in the stimulated muscle, probably due to activation of Golgi tendon organ afferents. The characteristics of this response in the extensor digitorum communis (EDC) muscles of subjects with Parkinson's disease were compared with those in age-matched controls. The threshold of the inhibitory response was significantly increased in the patient population compared with controls (159 +/- 34 V for tremulous patients; 134 +/- 10 V for rigid patients, 90 +/- 5.5 V for age-matched controls and 70 +/- 16 V for all normals). The latency of the inhibitory wave was increased (onset latency was 68.01 +/- 5.5 ms in patients was 51.5 +/- 4.9 ms in controls). The duration of I was also increased in patients (60 +/- 20.8 ms) relative to controls (46 +/- 11.8 ms). This was associated with slow development of the inhibition with the result that maximal inhibition was delayed by approximately 20 ms. Other features of the patient response were its oscillatory character whereby the initial inhibitory and excitatory components were followed by further prominent peaks and troughs which gave the appearance of continuing response cycles. Such behaviour was not seen in normal records. Also electrical stimulation of the extensor muscle tendon produced concurrent records in the forearm flexor muscle, which resembled those from the stimulated muscle. This was in contrast to normal records which showed no response in the flexor. The possible contribution of a disorder of tendon organ reflexes to the rigidity and tremor of Parkinson's disease is discussed.

Reflex origin of parkinsonian tremor.

The 8-Hz wrist tremor seen in normal subjects results from an oscillation in the spinal stretch reflex arc but the resting 4-Hz tremor of Parkinson's disease is believed to result from synchronization of motor unit activity by periodic descending inputs driven by an oscillator which resides within the brain. Accelerometer and smoothed EMG (0.8 to 16.0-Hz pass) recordings of resting tremor were taken from the upper limbs of 10 volunteers with Parkinson's disease for several different limb positions and while the limb was fixed to prevent tremor movements. The smoothed EMG and accelerometer records produced a complex periodic waveform with prominent 4- and 8-Hz components. Spectral analysis of both records produced large peaks at those frequencies which were harmonically related. The appearance of the regular tremor waveform in accelerometer and smoothed EMG records was greatly altered by changes in limb posture in all patients. Fixing of the shoulder and elbow joints only, also altered the smoothed EMG waveform and reduced the tremor amplitude. Fixing of the entire limb removed all signs of synchronization of motor unit activity in raw and smoothed EMG records. Similarly, the prominent 4- and 8-Hz peaks, found in the smoothed EMG power spectra from trembling muscles, were eliminated if the limb was effectively prevented from trembling. These experiments showed that the synchronization of motor unit activity at Parkinson's tremor frequency is wholly dependent on the oscillation in limb position and thus proprioceptive reflex activity. It is suggested that the known properties of the 4-Hz resting tremor of Parkinson's disease can be attributed to a flip-flop oscillation involving the mutually inhibitory connections between the spinal stretch reflexes of antagonist muscles. The supraspinal contribution to the tremor may thus be confined to an "aperiodic" descending facilitation of spinal reflex pathways.

Normal strobe electroretinograms without pattern electroretinograms in albino rats.

Electroretinograms (ERGs) were obtained from pigmented and albino rats to step luminance changes of an unpatterned TV screen. Surround luminance was increased until the ERG became small and focal. In pigmented rats the ERG at on was positive, earlier, and about twice the amplitude of the negative ERG at off. All pigmented rats had pattern ERGs-0.5 cycles/deg in dark agouti rats and an octave less in hooded rats. Implicit peak times were similar to that of the sum of on plus off focal ERGs from the same animals (85 ms). In albino rats off responses were more like on. The resultant sum was consequently small. Both peak times were similar and did not move earlier than 120 ms as surround luminance increased. Pattern ERGs could not be recorded from albinos at any spatial frequency or surround luminance. These pigmented rat ERGs seem to have two major components. One follows luminance linearly; the other is a fully rectified nonlinearity with about one-third the amplitude. The albino rat retina apparently lacks the latter component. These deficiencies may occur in albinos of other species and be associated with their visual system abnormalities.

Selective block of Y optic nerve fibres in the cat and the occurrence of inhibition in the lateral geniculate nucleus.

A method of selectively blocking the larger nerve fibres in the optic nerve of the cat is described. The optic nerve is compressed between a small balloon and the inside of a small metal cylinder. The block is monitored by stimulating and recording on opposite sides of the blocked region. The t1 (Y) response can be eliminated usually with some loss of the t2 (X) response. Stimulation of the blocked optic nerve initially excites certain cells (r2 or X) in the dorsal lateral geniculate nucleus (d.l.g.n.) but this is followed by an inhibition of both r1 (Y) and r2 (X) cells. This inhibition is similar in time course to that produced by stimulation of t1 fibres, suggesting that the effect may be mediated via a similar mechanism. The effect is present in a preparation in which all t1 fibres have degenerated, removing the possibility that it might have been due to inadvertent stimulation of t1 fibres. Experiments on a small number of r2 (X) d.l.g.n. cells have confirmed the inhibitory effect of stimulation of the smaller optic nerve fibres on X cells.

Proprioceptors and normal tremor.

The tremor of the hand, rotating about the wrist joint, was measured using an accelerometer, and groups of muscle action potentials were simultaneously recorded from the wrist extensor muscles using surface electrodes. The accelerometer signal and the rectified, demodulated electromyogram were submitted to Fourier analysis in order to quantify the tremor in terms of its frequency components and the amplitudes of those components. The amplitudes of the 8-12 Hz peak in the frequency spectrum obtained from muscle electrical activity were compared (a) when the hand was held raised against gravity (i.e. the contraction was isotonic) with (b) when it was held raised, with the same force and in the same position against a rigid bar (i.e. the contraction was isometric). In the isotonic condition (a) a prominent 8-12 Hz peak was observed in the spectrum. In the isometric condition (b) the peak was small or absent. The conclusion is drawn that the grouping (synchronization) of motor unit action potentials underlying tremor cannot be due to any process in the central nervous system generating them and they depend on cyclic alterations in muscle length activating proprioceptors.