Pathophysiological mechanismsin cerebral palsy

Journal ofNeurology, Neurosurgery, and Psychiatry, 1979, 42, 606-618

Pathophysiological mechanisms in cerebral palsyH. S. MILNER-BROWN AND RICHARD D. PENN

From the Departments of Physiology and Neurosurgery, Rush-Presbyterian-St Luke's Medical Center,Chicago, Illinois, USA

SUMMARY To investigate some of the pathophysiological mechanisms in cerebral palsy, surfaceelectromyograms (EMG) were recorded from pairs of flexor/extensor muscles during bothvoluntary and passive flexion/extension of upper and lower limbs of 20 patients. Elbow, knee,or ankle joint angles were measured simultaneously, as well as the force required to flex/extendthe limbs passively at frequencies of 0.1-1.0 Hz. In addition, single motor units were recordedfrom the first dorsal interosseous muscles of six of the patients. Almost all patients showed re-sistance to passive movements (hypertonia). This hypertonia did not necessarily impair voluntaryflexion/extension movements if alternating EMG activity was maintained in at least one of thepairs of flexor/extensor muscles involved in the movement. In six severely involved patients,there was a complete breakdown in the reciprocal relationship between reciprocally acting pairsof flexor/extensor motoneurones, which resulted in synchronous activation (co-contractions) offlexor/extensor muscles during both voluntary and passive movements. In these patients thehyperactive segmental reflex added to the disabling effects of co-contractions during voluntarymovements. Single motor units recorded from patients with dystonic movements were recruitedwith variable delays (2-10 s) and usually discharged intermittently at high frequencies (60-120/s).This abnormal motor unit discharge pattern may relate to pathology of the basal ganglia.

Cerebral palsy is a term used to denote a widerange of motor abnormalities which result fromdamage to the developing or immature brain.Chronic electrical stimulation of the cerebellarcortex was introduced as a means of improvingmotor function in patients with motor systemabnormalities, including the various forms ofcerebral palsy (Cooper, 1973; Cooper et al., 1973).Clinical and neurophysiological changes afterchronic cerebellar stimulation have been reported(Cooper et al., 1976; Upton and Cooper, 1976;Davis, 1977; Larson, 1977; Penn and Etzel, 1977;Fisher and Penn, 1978; Gottlieb et al., 1978;McLellan et al., 1978). However, some of theneurophysiological changes were not related tothe clinical changes, which made it more difficultto explain the effects of chronic cerebellar stimula-tion on the motor system. Part of the problemmay be that in cerebral palsy the aetiological

Address for correspondence and reprint requests: Dr H. S. Milner-Brown, Department of Physiology, Rush-Presbyterian St Luke'sMedical Center, 1753 West Congress Parkway, Chicago, Illinois60612, USA.Accepted 27 December 1978

factors, location of lesions, and consequent mani-festations are diverse; and the clinical classifica-tions and terminology are inadequate.To study the pathophysiological basis of the

motor abnormalities and any changes which mayoccur because of cerebellar stimulation, we deviseda series of simple physiological tests which thepatients could perform without difficulty. Thispaper reports on the results of these tests on 20cerebral palsy patients and the pathophysiologicalbases of the abnormalities.

Methods

A simple protocol was used so that cven severelyinvolved patients could be studied. Although theco-operation of the patients was necessary, theirfull attention was not required in all the tests.The procedures were designed to test the "reflex"responses of the upper and lower limbs to passivemovements and how they might be related to thevoluntary movement deficits and the involuntarymovements.

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Pathophysiological mechanisms in cerebral palsy

MEASUREMENT OF ELECTRICAL AND MECHANICALPARAMETERSDuring voluntary movements, surface electro-myograms (EMG) from a pair of flexor/extensormuscles and the joint angles were recorded; theforce required to move the limb was also recordedduring passive movements.

Joint anglesThe patient was first comfortably seated in a chair.A goniometer employing a linear potentiometerfor measuring joint angles was positioned arounda joint (elbow, knee, or ankle), and secured withVelcro straps.

ForceThe force required to flex and extend the elbowor knee was measured with a strain gauge bondedon a metal bracket. This "force-bracket" wasstrapped around the wrist or ankle and occasion-ally the foot. The limb was then manually movedby gripping the handle on the force bracket.

EMG recordingA pair of circular disc surface electrodes filledwith conducting cream were attached to the belliesof pairs of flexor/extensor muscles, using adhesiverings and surgical tapes. During movement aroundthe elbow joint, EMGs were recorded from thebiceps/triceps, during flexion/extension of kneejoint, EMGs were recorded from quadriceps/hamstring muscles, and finally when the ankle wasdorsiflexed/plantarflexed, EMGs were recordedfrom triceps surae/anterior tibial muscles. TheEMGs were amplified by a Tektronics 2AG1 unitwith 60-600 Hz bandwidth, and filtered by a thirdorder low-pass filter with 100 Hz cut-off.

Voluntary and passive movementsPatients were asked to flex/extend their elbowsat slow rates (0.1 to 0.5 Hz) 10 times and at theirfastest rates: EMG from biceps/triceps and elbowjoint angles were recorded on a Hewlett-Packard(HP3964A) tape recorder. The elbow was thenpassively flexed/extended 10 times at frequenciesof 0.1, 0.2, 0.5, and 1.0 Hz and the angle, force,and EMG activity measured. The frequencieswere restricted to less than 2 Hz because thepatients were not capable of voluntary movementsat faster rates. The procedure was then repeatedat the knee joint. The effect of muscle length on

passive responses was studied in a few patients byvarying the knee joint angle. In patients whocould dorsiflex/plantarflex their ankles volun-tarily, voluntary and passive movements aroundthe ankle joint were investigated. Each recording

session lasted one to one and a half hours, depend-ing upon the extent of motor disability, the co-operation, and mood of the patient.

Motor unitsSingle motor units were recorded from six patientsaged 15 to 27 years with a TECA (TG-4) EMGapparatus, an FM tape recorder, and a signaldiscriminator. The patients were seated in awheelchair with one arm resting on a board ontop of a bed. The force transducer (Grass FT.03)was clamped rigidly to a metal rod fixed to theboard. The output from the transducer amplifier(Grass 7P-122) was connected to a calibrateddigital multimeter so that the force exerted on thetransducer could be read directly. A bipolar needleelectrode (DISA 13K80) was inserted into the firstdorsal interosseous muscle and positioned so thatthe discharge of single motor units would be dis-tinguished at a moderate level of voluntarycontractions. In one patient motor unit potentialswere recorded from tibialis anterior muscle.The electrical activity was (i) amplified (input

impedance 100 megohms), (ii) filtered with a lowfrequency cut-off of 32 Hz and a high frequencycut-off of 3.2 kHz, (iii) fed through a delay lineand trigger level, (iv) fed into a discriminatorwhich gave out a pulse any time the selectedmotor unit discharged, (v) displayed on anoscilloscope, and (vi) recorded on the FM taperecorder.

Patients were provided with audiovisual feed-back of the electrical signals and were asked tomaintain a continuous discharge of the singlemotor unit for about 30 s and then to increase thefiring frequency of the same motor unit by in-creasing the force. At each recording sessionwhich lasted 30 minutes, 5 to 10 motor unitpotentials were recorded at different force levels.The DC force, the motor unit impulses recorded

with the needle, and the discriminator pulses wereplayed back through a photosensitive chart re-corder (Kodak Linograph 1895), and the dischargefrequencies computed. The figures from themotor unit potential studies were retraced becausethe direct photographic prints of the traces on thephotosensitive paper proved unsatisfactory.

Patients

There were three sources of patients: (i) sixpatients who were already undergoing chroniccerebellar stimulation, (ii) five patients who werepossible candidates for cerebellar implants, and(iii) nine patients from schools and hospitals forhandicapped children. In all cases the protocol

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H. S. Milner-Brown and Richard D. Penn

was presented in writing to the staff of the hospi-tals and schools, the patients (as appropriate), andtheir families. Furthermore, a clinical researchco-ordinator fully discussed the details of theprocedure with staff, patients, and families. Beforetesting, consent forms approved by our MedicalCenter Committee on Human Investigation weresigned by the adult patients. In the case of minorsand the severely involved, the consent forms weresigned by a parent or legal guardian.

Terminology

In view of the diversity and complexity of"spasticity" and "rigidity" (Landau, 1974), the useof any of these terms will be restricted only tothe initial neurological classification.

Results

Data from only six patients will be presentedbecause their combined data completely representall the pathophysiological mechanisms that wereobserved in the 20 patients studied.

CASE 1This 26 year old man (DO) was quadriplegic,athetoid, dystonic, and unable to walk. He wasbeing treated with chronic cerebellar stimulation,but the stimulator was turned off 12 hr beforetesting. This patient was so severely involved thatany improvement due to the stimulation will notbe taken into consideration.

Upper limb movementsThe patient was asked to flex/extend his elbowvoluntarily and Fig. IA shows the resulting elbowangle, biceps and triceps EMGs. Compared withthe normal subject (Fig. IB) two abnormalitieswere obvious: (i) the movement was not con-tinuous, but jerky and decomposed, and (ii) thephasic EMG activity in the biceps/triceps didshow abundant coactivation. In order to get abetter understanding of the nature of thisabnormal electrical discharge pattern, singlemotor unit potentials were recorded from thispatient, which will be presented later.The elbow was flexed/extended manually using

the metal bracket attached to the wrist at fre-

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Fig. 1 Voluntary flexion/extension of elbow joint: (A) patient DO, (B) normal subject.Voluntary flexion/extension of knee joint: (C) patient DD, (D) normal subject. Upper traces arejoint angles, middle and bottom traces are EMGs from pairs of flexor/extensor muscles. InA and C note the synchronous EMG activity in pairs of flexor/extensor muscles; in D there wasreciprocal EMG activity between quadriceps and hamstrings. Note the EMG calibration wasafter amplication of 1000 and filtering.

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quencies of 0.2, 0.5, and 1.0 Hz. The forcerequired to move the limb through an angle of10° was computed as a measure of the resistanceto passive movement. Figure 2A and B shows theelbow angle, force and biceps EMG recordingsfrom this patient at 0.2 and 0.5 Hz. The meanforce was computed from the peak-to-peak ampli-tudes of 10 force traces; the resistances to passivemovement were 260 g/ 100 at 0.2 Hz and 320 g/ 100at 0.5 Hz.The distortion of both the angle and force

traces at 0.5 Hz was due to the involuntary move-ments, which suggests that the dystonic phenom-enon may be potentiated by a hyperactivesegmental reflex mechanism depending upon thefrequency of movement. This effect was observedin five other patients.The resistance to passive elbow movements of

this patient and another patient with similarabnormal behaviour are compared with twonormal subjects in Fig. 2C. In all four subjectsthe force required to move the limb increased with

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increasing velocity of stretch, but the forces weremore than twice as large in the two patients.

Lower limb movementsVoluntary flexion/extension of the knee was jerky,and continuous EMG activity was seen in bothquadriceps and hamstrings; in addition, multipleperiods of phasic discharges occurred (Fig. IC).When the resistance to passive movements wascompared with that of a normal subject an in-crease in resistance with increasing velocity ofpassive stretch was demonstrated in both, althoughthe forces were again twice as large in the patient.Motor unit activity recorded from the above

patient (DO) and a second patient (PP) will bepresented here. Motor unit potentials recordedfrom the other four patients with no dystonicmovements fired normally at 6-15/s.

In patient DO the characteristic discharge ofthe few motor units recorded from the first dorsalinterosseous muscle was as follows (Fig. 3A): (i)motor units fired in bursts of high frequencies

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are the elbow joint angles, the second traces, the force required to flex/extend elbowcontinuously at 0.2 Hz (A) and 0.5 Hz (B), and the third traces are EMGs recorded frombiceps. (C) Plot of force required to flex/extend elbow passively at different frequencies;two patients and two normal subjects. Patients' frequencies were 0.2, 0.5, and 1.0 Hz;normal subjects' frequencies were 0.5, 1.2, and 3 Hz. Force computed at 1.0 Hz was

190 and 230 g/10° for normal subjects, 730 and 750 g/10° for patients.

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IsFig. 3 Motor unit potentials recorded from the first dorsal interosseous muscles of two patients.Upper traces represent signal discriminator pulses triggered by larger motor units. Second trace is

motor unit activity recorded by needle electrodes during voluntary effort. (A) patient DO showshigh frequency discharges of 60/s lasting only 100 ms. (B) patient PP: intermittent firing of motor

unit potentials at high frequencies (60-120/s). The fluctuating baselines are due to involuntarymovement. The figure was retraced because the direct photographic prints of the traces on thephotosensitive paper proved unsatisfactory.

(60/s), which often lasted for only 100 ms; (ii)although the patient tried to maintain a steadyvoluntary contraction variable periods (0.5-2 s) ofmotor unit inactivity were observed; (iii) variabledelays (2-10 s) in motor unit recruitment occurred.

Patient PP is a 27 year old man, quadriplegicwith rigidity and dystonic movements. The firingpattern of his motor units was investigated fromthe first dorsal interosseous and anterior tibialmuscles. Figure 3B shows a 5 s recording ofmultiple motor unit potentials from the first dorsalinterosseous muscle while the patient was askedto exert a continuous force on a transducer placedbetween his thumb and first finger. The abnormalfiring characteristics were: (i) a delay in motorunits recruitment of 2-5 s, (ii) intermittent firingof motor units, and (iii) brief (0.25 s) high fre-quency (60-120/s) phasic bursts. The possiblerelationship between this abnormal firing patternand lesions in the basal ganglia will be discussed.

CASE 2This 27 year old woman (SS) was spastic,quadriplegic, and unable to walk.

Upper limb movementsFigure 4A shows the angle, biceps, and tricepsEMGs during voluntary flexion/extension (Fl/Ext)of her elbow at 0.2 Hz. Triceps EMG showedalternating activity during extension while bicepsEMG was continuous and random during bothflexion/extension. There were also periods ofsimultaneous increase in electrical activity in bothbiceps and triceps during extension, indicatingco-contraction of this pair of flexor/extensormuscles.

Resistance to passive flexion/extension of theelbow at 0.5 and 1.0 Hz were 230 g/ 100 and300 g/100 respectively; these were larger thancorresponding average values of 150 g/ 100 and190 g/ 100 recorded from normal women of com-parable size and age. A comparison of the reflexEMG responses of the flexors and extensors indi-cated that, while the threshold frequency ofstretch for eliciting a reflex response in theextensors (triceps) was less than 0.2 Hz, negligiblereflex EMG was recorded from the flexors (biceps)at 1.0 Hz. Hence in this patient there was anincrease in extensor motoneurone reactivity com-

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2s IsFig. 4 Patient SS. First (top) traces are elbow angles, second and third traces are biceps and tricepsEMGs respectively. (A) Voluntary flexion/extension of elbow, (B) passive flexion/extensioni at 1.0 Hz.Note the lack of reciprocal activity in biceps, with periods of synchronous EMG activity in bothbiceps and triceps during extension.

pared to normal subjects as well as a relative in-crease in extensor reactivity compared to flexors.

Lower limb movementsContractures limited knee movements to 100, andlittle EMG activity was recorded from thequadriceps and hamstring muscles.The knee joint could be moved passively through

only 200. The resistance to movement was 2.3 kg/100 at 0.5 Hz (cf 1.0 kg/100 recorded fromnormal subject). The lack of significant reflexEMG responses from quadriceps and hamstringsindicated that the increased resistance was due tothe contractures, not to hyperactive stretchreflexes.

CASE 3This 10 year old boy (TP) was quadriparetic,mildly "spastic," and able to walk.

Upper limb movementsThe patient did not have any difficulty with yol-untary flexion/extension at the elbow (Fig. 5A).However, overlapping EMG activity betweenbiceps and triceps muscles was recorded duringextension. Such an alternating pattern of EMGactivity from the triceps is normal: but, at a fre-quency of 0.5 Hz, the electrical activity was ex-cessive compared with normal subjects (Fig. IB),suggesting hyperactive extensor motoneuroneactivity.

Figure SB shows elbow angle, biceps, and tricepsEMG during passive flexion/extension at 1.0- Hz.Triceps EMG 'activity occurred during passiveflexion only, the biceps showed a random con-tinuous pattqrn of EMG activity. The resistance

to passive movements of 330 g/100 at 1.0 Hz, wasgreater than the corresponding 200 g/100 com-puted for normal subjects. The resistance (com-puted as the force required to move the limbthrough 100) showed the normal pattern of in-crease in resistance with increasing frequency ofpassive movement (Fig. 5C).Thus this patient showed (i) an increase in the

reactivity of extensors during both voluntary andpassive movements, (ii) a low threshold frequencyfor producing reflex ENMG response in the triceps(<0.1 Hz), and (iii) an increased resistance topassive movement. In contrast to case 2 thepatient had no difficulty in flexing and extend-ing his elbow. This implies that an increase inreactivity may not necessarily impair movementprovided either the flexors or extensors of theparticular joint retain the normal pattern of alter-nating EMG during voluntary flexion/extension.

Lower limb movementsFigure 6A is a record of the knee joint angle,quadriceps (extensors), and hamstrings (flexors)EMG, during voluntary flexion/extension of theknee at 0.5 Hz. While the hamstrings showedalternating EMG activity, the quadriceps had amore continuous tonic EMG activity with inter-mittent periods of increased electrical activity.

Passive flexion/extension at 0.1 Hz producedreflex EMG responses in the hamstrings. Theresistance to passive movements at 0.5 Hz was620 g/ 100 and within the normal range. Theresistance increased with the frequency of passivemovements. Figure 6B demonstrates the dynamicspindle sensitivity at 0.5 Hz, and also tonic EMGactivity when the limb was held stationary for

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Fig. 5 Patient TP. (A) Voluntary, (B) passive flexion/extension of elbow joint. Toptraces are elbow joint angles, second and third traces are the biceps and triceps EMGs.(C) plot of resistance to passive movements (computed as Force/JO0 angle) at threefrequencies (0.1, 0.5, and 1.0 Hz). Triceps EMGs alternate but the biceps EMGs arenot reciprocal, which is normal.

about 3 s; this response could be a reflection ofspindle sensitivity to static stretch. At 0.8 Hz,tonic and phasic EMG responses occur suggestingincreased excitability of spindle afferent nerves orflexor motoneurones or both. Indeed, F responsestudies have suggested a relative increase in flexormotoneurone excitability states in some cerebralpalsy patients (Fisher and Penn, 1978; Fisher, 1978).The effect of muscle length changes on reflex

responses was tested by varying the knee jointangle and recording the EMG responses fromquadriceps and hamstrings during passive flexion/extension (Fig. 6D). Increasing hamstrings musclelength facilitated reflex responses in the ham-strings (flexors); on the other hand in the quad-riceps (extensors) a decrease in reflex responsewith increasing quadriceps muscle length couldnot be demonstrated. Assuming that these staticmuscle length changes are detected by spindlesecondary endings, the results obtained were notcompatible with the known properties of sec-ondary endings.

Finally, test of ankle movements revealed amajor deficit in voluntary dorsiflex/plantarflexmovements.

CASE 4This 17 year old youth (SH) was quadriplegic,"spastic," and unable to walk.

Upper limb movementsThe patient could flex and extend voluntarily hiselbow without difficulty. This was demonstratedby the continuous sinusoidal pattern of the angletrace in Fig. 7A. The biceps EMG activity hadthe normal alternating pattern during flexion only.The triceps EMG, however, was not reciprocallyrelated, and periods of triceps EMG activityduring flexion were seen. This was the reverseof what was observed in cases 2 and 3 (Figs. 4and 5).The computed resistance to passive flexion/

extension at 0.5 Hz was 280 g/100. This value wasgreater than the normal values of 150-180 g/100,indicating an increased resistance to passive move-ment. This result further supports the earlier sug-gestion that this type of hypettonia may notnecessarily i¶pair voluntary movgment if one ofthe pair of flexor and extensor mnuscles involvedin the movement retained a norinal alternatingpattern of activation during contraction and re-

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Pathophysiological mechanisms in cerebral palsyA

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2s IsFig. 6 Case 3, TP. Voluntary flexion/extension of knee joint (A). Passive flexionlextension of knee joint at 0.5 Hz (B) and 0.8 Hz (C). (D) Passive knee flexion/extension at different angles (muscle lengths). In (A) and (D) top trace, angle; middletrace, quadriceps EMG; bottom trace, hamstrings EMG. (B) and (C) top trace, angle;middle trace, force; bottom trace, hamstrings EMG. In A, quadriceps EMG is lessprominent and not reciprocally related to hamstrings EMG. B and C demonstrate thesensitivity of the muscle spindles to dynamic and static stretch. D illustrates facilitationof hamstrings reflex responses with increasing muscle length; the quadriceps responsesmay reflect an abnormality.

laxation. This observation was made in five otherpatients.

Lower limb movementsThe knee joint angle, quadriceps, and hamstringsEMG are illustrated in Fig. 7C. Little EMGactivity was recorded from the quadriceps; onthe other hand the hamstring EMG was con-tinuous and prominent with irregular periods oflarge phasic bursts.A highly significant increase in resistance to

passive movement was found. The force requiredto move the knee joint through 10° was 1.8 kg,compared to average normal values of 700 g/100.The effect of muscle length changes on reflexeswas similar to case 3 (Fig. 6D).

CASE 5This 10 year old boy (RS) was "spastic," quadri-plegic, and unable to walk.

Upper limb movementsThe patient could flex/extend his elbow voluntarilywithout difficulty. There was alternating increasedEMG activity in biceps during flexion with back-ground activity during extension. The triceps wassilent at low frequencies (0.2 Hz). The resistanceto passive movement at 0.5 Hz was increased to360 g/100 (normal 150-180 g/100). The com-puted forces were linearly related to frequency ofmovement.

Lower limb movementsHe could flex/extend his knee joint voluntarilythrough only 200 and at a slow rate (0.1 Hz).Synchronous reflex EMG activity occurred in bothquadriceps (extensors) and hamstrings (flexors)during passive movements (Fig. 8A and B). Bothflexors and extensors showed reflex responses tostretch of the flexors. This reflex response patternwas observed in seven other patients.


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Fig. 7 Patient SH (A) voluntary, (B) passive flexion/extension of elbow joint, showing fromthe top trace downwards, elbow joint angle, biceps, and triceps EMGs. (C) voluntary, (D)passive flexion/extension of knee joint, showing from the top trace downwards, knee jointangle, quadriceps, and hamstrings EMGs. The synchronous phasic bursts of EMG recordedfrom the hamstrings and quadriceps during passive movements at 1.0 Hz (D) was the mostdistinct abnormal feature, in addition to the continuous triceps EMG activity.

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Fig. 8 Case 5, RS. A comparison between reflex responses of the flexors (hamstrings) andextensors (quadriceps) of the knee. The knee joint was continuously flexed and extended throughan angle of 500 (upper trace); surface EMGs were recorded from quadriceps and hamstrings.A and B frequencies approximately 0.1 Hz and 0.5 Hz respectively. Note the synchronous EMGresponses recorded from quadriceps and hamstrings.

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When passive knee flexion was carried outslowly over a period of time (10 s), there was asudden "give" (clasp knife reaction). This reactionoccurred during both passive and voluntaryflexion, and the patient was quite aware of hisability to bend his knees after a delay period.

CASE 6This 27 year old woman (LG) was "spastic,"quadriplegic, and unable to walk.

Upper limb movementsFigure 9A demonstrates the pattern of EMGactivity in the biceps and triceps during voluntaryflexion/extension of the elbow. The continuousEMG activity in the biceps during both flexion/extension was abnormal. The alternating EMGactivity in the triceps appeared normal. However,at that slow rate of movement (0.4 Hz) the EMGactivity was more prominent than usual and sug-gested a decreased threshold and increased re-activity of extensor motoneurones.There was a decrease in the threshold fre-

quency for eliciting a reflex EMG response topassive movements. The threshold frequency was0.1 Hz for triceps and 0.2 Hz for biceps. Theresistance to passive movements increased withincreasing frequency as in normal subjects, butagain the force computed was more than twice aslarge as normal. The increased resistance was inpart the result of the increased reactivity of bothflexor and extensor motoneurones, indicated bythe EMG responses (Fig. 9B). In spite of theincreased resistance to passive movements, thepatient could flex and extend her elbow volun-tarily continuously and smoothly at 0.5 Hz. Thisfurther strengthens the earlier suggestion that

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hypertonia may not always impair voluntarymovements.

Discussion

Several pathophysiological mechanisms were evi-dent in these studies.

HYPERTONIAAlmost all patients demonstrated an increasedresistance to passive flexion/extension movementswhich increased linearly with frequency of move-ment. Therefore, even if there was a pathologicalincrease in fusimotor activity, the normal dynamicsensitivity of the primary endings of musclespindles to phasic stretch was not disrupted.Indeed, in a study in which ramp stretches wereused to test the sensitivity of spindles in the calfmuscles, no significant difference in dynamicspindle sensitivity were observed in "spastic" ascompared with normal subjects (Hagbarth et al.,1973). Hence, any hyperactive stretch reflexesmight be attributed to increased reactivity ofspinal neurones. Although hypertonia was acommon feature, the variability in the pattern ofreflex EMG would suggest diversity in the under-lying pathophysiological mechanisms. In mostpatients a threshold frequency could be definedbelow which no reflex EMG activity was producedas previously observed by Burke and Lance (1973).The threshold frequency varied from 0.1 Hz to1.0 Hz in different patients, and in the same patientthere were differences between upper and lowerlimbs and between pairs of flexor/extensor muscles.The reflex EMGs recorded from pairs of flexor/extensor muscles during passive movements alsovaried from completely reciprocal, through partial

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Fig. 9 Patient LG: (A) voluntary (B) pausive flexion/extension of the elbow joint. Upper traces, elbowangle; middle and bottom traces, biceps and triceps EMG respectively. A, at the frequency of 0.4 Hz theEMG activity from the triceps was prominent. B, EMGs reflect increased reactivity of biceps/tricepsmotoneurones, as well as synchronous reflex activation.


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overlap, to complete synchrony. The synchronousEMG activity frequently seen suggests an ab-normal situation in which the segmental reflexpathways of a pair of flexor/extensor musclesare "wired up" together. This observation hasbeen made in triceps surae and anterior tibialmuscles during sinusoidal oscillations of the ankleat 3-12 Hz, in a similar group of cerebral palsypatients (Gottlieb et al., 1978). The cause of thisabnormality is not clear. Possibly it is due to anabnormal synaptic action at the interneuronaland/or motoneuronal level because of abnormaldescending inputs from the pyramidal system andbrainstem centres, or abnormal spinal neuronaldevelopment as a result of injury at birth.

VOLUNTARY MOVEMENTSThe deficiency in voluntary motor capabilitiesvaried considerably. The simple test of voluntaryflexion/extension movements used in evaluatingthe level of voluntary function produced a numberof diverse abnormal patterns of electrical activityin the muscles involved. Firstly, in the mildly in-volved limbs, normal alternating electrical activitywas maintained in either flexor or extensormuscles. However, the corresponding antagonistmuscle was often electrically active throughoutthe movements and at all frequencies. Secondly,in five patients the voluntary flexion/extensionmovements were performed at low frequencies(0.1 Hz) without apparent difficulty, and reciprocalEMG activity was maintained in the pair of flexor/extensor muscles being used. As the frequencyof movement increased, there was a variablethreshold frequency at which a complete break-down in reciprocal innervation occurred, and co-contractions appeared in the pair of musclesinvolved in the movement. The overlapping con-tractions impaired movement. Thirdly, in sixseverely involved patients there was simultaneousEMG activity in pairs of flexor/extensor musclesat the initiation of movement which resulted inco-contractions of these muscles, severely impair-ing movements. These diverse abnormal patternsare probably only a small proportion of the motorabnormalities that occur in cerebral palsy.

EFFECT OF HYPERTONIA ON VOLUNTARY MOVEMENTDo the above positive symptoms create the nega-tive symptoms? The importance of hyperactivestretch reflexes in "spasticity" has been empha-sised traditionally. This emphasis derives partlyfrom the enormous physiological work on reflexesdating back to Sherrington, and partly on theirusefulness in diagnosis. This study has shown thepotentially comnplex, abnormal, segmental mech-

anisms that may be operating, and also indicatedthat in certain situations the resulting hypertoniamay not necessarily impair smooth voluntarymovements. In fact, this conclusion was reachedin a study in which the relationship betweenstretch reflexes and voluntary movement wasexamined in patients with cerebrovascular lesions(Sahrmann and Norton, 1977). These observationsmight also explain partly why reduction of posi-tive symptoms through medication did not im-prove the negative symptoms that were the primeconcern of the patients (Landau et al., 1960;McLellan, 1977).The possible relationship between the abnormal

segmental mechanisms and the voluntary motordeficit should depend on the pathophysiologicalmechanisms inhibiting voluntary movement. Themechanisms will in turn depend on the locationand the extent of lesions. An important factorfound in this study was the frequency dependenceof the pathophysiological mechanisms. If thethreshold frequency for producing co-contractionsin a pair of flexor/extensor muscles during vol-untary movements was comparable to thethreshold frequency for eliciting synchronousreflex EMG activity in the same muscles, thehyperactive segmental reflexes would further in-hibit voluntary movement. This could haveoccurred in some of the patients, particularlythose with dystonia. Since lesions in the basalganglia result in co-contractions of pairs of flexor/extensor muscles (Denny-Brown, 1962; 1968;Yanagisawa and Goto, 1971; Brooks, 1975), onewould expect such lesions to be all the more dis-abling when segmented reflexes are hyperactive.

BASAL GANGLIA AND VOLUNTARY MOVEMENTMotor unit potentials recorded from patients withdystonic movements showed a delay in recruit-ment and discharged intermittently at high fre-quencies up to 120/s. The delay in motor unitrecruitment and intermittent firing have beenobserved previously only in Parkinsonism patientswhere nigrostriatal lesions are dominant (Petajanand Jarcho, 1975; Milner-Brown et al., 1979).This abnormal motor unit firing pattern may wellbe characteristic of lesions of the basal ganglia,specifically the striatum. The high frequency dis-charges are in some ways similar to the dischargepattern of motor units in normal subjects during"ballistic" contractions (Desmedt and Godaux,1977). Since motor units recruited d4uring ballisticcontractions have a lower force threshold com-pared to slow continuous activity, this may ex-plain why dystonic movements (which are ballistic)impair smooth voluntary movements. The diffi-

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culty which such patients have in dischargingmotor units in a normal continuous pattern at8-20/s (Milner-Brown et al., 1973a, b) necessaryfor producing slow smooth movements might beexpained further by considering Kornhuber's sug-gested function of the basal ganglia. According toKornhuber (1974), "the basal ganglia serves as aramp generator for slow voluntary smooth move-ments." Hence, lesions in the basal ganglia, par-ticularly involving the striatum (Delong, 1974),would severely affect slow controlled movementscompared with ballistic movements. Consequentlyballistic movements-for example, dystonia-willresult even when slow continuous movements aredesired. During dystonic movements synchronousactivations of pairs of flexor/extensor musclesoccur and are potentiated by hyperactive seg-mental reflex mechanisms.We may conclude from this study that a number

of complex pathophysiological mechanisms areinvolved in cerebral palsy. When chronic cere-bellar stimulation is used to try to improve motorfunction in these patients, such simple physio-logical tests are useful in delineating some of thepathophysiological mechanisms before cerebellarimplant, and also in evaluating any physiologicalchanges that may occur after chronic cerebellarstimulation. The variability in response to stimu-lation may relate to the specific pathology of themotor system, and by these tests we may be ableto identify the patients who will respond best.

We acknowledge gratefully financial support fromthe Susman-Asher Research Foundation, UnitedCerebral Palsy and Rush-Presbyterian-St Luke'sMedical Center. We also wish to thank the patientswho participated in the project, Dr Morris Fisherfor reviewing the manuscript, and Ms Linda Lodgefor typing the manuscript.

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Pathophysiological mechanismsin cerebral palsy

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