Brain. (1992) 115, 1167-1180
RELATIONSHIP BETWEEN ELECTROMYOGRAPHIC ACTIVITY AND CLINICALLY ASSESSED RIGIDITY STUDIED AT THE WRIST JOINT IN PARKINSON'S DISEASE by
R. J. MEARA and
F. w.
J. CODY 2
(From the 'Department of Neurology, Manchester Royal Infirmary and the 2Department of Physiological Sciences, University of Manchester, Manchester, UK)
The electromyographic (EMG) patterns recorded from wrist muscles during manually applied, repetitive flexion and extension movements of the wrist joint, used for simultaneous clinical assessment of rigidity, were studied in patients with Parkinson's disease and healthy subjects. Recordings were made whilst patients/subjects attempted voluntarily to relax the muscle of the arm whose wrist joint was manipulated. Individual patients were investigated before and at varying times after their routine daily medication as their clinical rigidity underwent associated modulations. It was often possible to induce additional alterations in clinical rigidity by instructing patients to perform an activation or Jendrassik-like manoeuvre (clenching the contralateral fist). In rigid patients, the approximately sinusoidal wrist displacements (60 deg, 1 — 1.5 Hz) typically elicited pronounced, cyclic modulations of EMG activities in wrist flexors and extensors; increases in EMG activity were phase-locked to the respective periods of muscle stretch. Stretch-related EMG activity reduced or disappeared as rigidity was abolished by drug therapy. The EMG patterns of patients showing cogwheel rigidity featured discrete, phasic bursts superimposed upon more generalized stretch-related increases in activity. In healthy subjects, showing no clinical rigidity, the pronounced cyclic modulations of EMG activity characteristic of rigid patients were absent during similar manually applied wrist displacements. Quantitative EMG measurements for individual patients, made 'on' and 'off medication and as their rigidity fluctuated, indicated that mild (grade 1) and moderate (grade 2) rigidity was consistently associated with increased stretch-related activity compared with non-rigid conditions. Pair-wise statistical analysis indicated such increases in EMG to be significant. Similarly, the ratios of EMG activities in the stretched versus released muscles were significantly greater for grades 1 and 2 rigidity than in the absence of rigidity. Overall, the present findings support the view that enhancement of stretch reflex activity has a major role in the genesis of parkinsonian rigidity.
INTRODUCTION
The pathophysiology of rigidity in Parkinson's disease remains obscure. Two main types of explanation have been advanced. First, that parkinsonian rigidity is of reflex origin (Pollock and Davis, 1930); secondly, that changes in the intrinsic mechanical properties of muscle are mainly responsible (Dietz et al., 1981). The former hypothesis is supported by the classical findings that rigidity is abolished following both dorsal root section (Foerster, 1921) and the intramuscular injection of local anaesthetic (Walshe, 1924); taken together, these observations suggest that activation Correspondence to: Dr F. W. J. Cody, Department of Physiological Sciences, Stopford Building, University of Manchester, Manchester M13 9PT, UK. © Oxford University Press 1992
Downloaded from http://brain.oxfordjournals.org/ by guest on March 23, 2016
SUMMARY
1168
R. J. MEARA AND F. W. J. CODY
METHODS Subjects Nine patients with Parkinson's disease, of mean age 60 ± 5 (SD) yrs, and 10 healthy subjects, of mean age 62 ± 6 yrs, were studied. The clinical details of the patients, together with their medication, are given in Table 1. All patients had a clear response to levodopa therapy; each was studied when 'off and 'on' therapy. In two patients clinical rigidity, unlike bradykinesia, was not reduced by medication. Experimental arrangement Application of wrist displacement. The subject sat in a chair with the forearm pronated and pointing forwards. The pronated arm was abducted at the shoulder and the elbow was flexed to an angle of 90 deg. Pillows on a horizontal platform supported the elbow and forearm at a comfortable height below the shoulder; the hand protruded unsupported into space beyond the platform. The examiner (R.J.M.) used one hand to apply forcible extension and flexion movements, identical to those routinely performed
Downloaded from http://brain.oxfordjournals.org/ by guest on March 23, 2016
of reflex pathways by afferent input from muscle receptors is essential for the expression of rigidity. Although the H-reflex, tendon jerk and 'short-latency' stretch reflex pathways appear to operate normally (Angel and Hofmann, 1963; Dietrichson, 1971; Tatton and Lee, 1975, but see Noth et al., 1988; Rack, 1990), it is generally agreed that 'longlatency' stretch reflex activity is enhanced in Parkinson's disease (Tatton and Lee, 1975). However, despite early reports of a quantitative association between long-latency stretch responses and rigidity (Lee and Tatton, 1975; Mortimer and Webster, 1979), numerous recent investigations reappraising this issue have failed to confirm such a clear-cut relationship (Berardelli et al., 1983; Rothwell et al., 1983; Cody et al., 1986; Meara and Cody, 1989). Thus, the present concensus is that whilst exaggerated stretch reflex activity plays a part in the generation of parkinsonian rigidity the importance of its contribution is uncertain. It should be recognized, however, that the precise experimental conditions employed in these laboratory studies may have differed in crucial respects from those used in standard neurological examination. The forcible displacements of the joint being investigated, usually driven by a motor or comparable mechanical actuator, were often linear and quite unlike the rhythmic, approximately sinusoidal movements applied manually by a clinical examiner; additionally, patients were often required to produce a steady background contraction rather than to attempt to relax. Thus, disparities in the balance of excitation of the various classes of sensory receptors and the prevailing 'set' of the central neural pathways are to be expected. These could lead to the essential reflex mechanisms operating during clinical testing remaining undetected. The present experiments were undertaken to address this problem by the novel but straightforward approach of recording electromyographic (EMG) activities and displacement during actual clinical testing of rigidity at the wrist and relating these to the rigidity simultaneously appreciated by the examiner. Furthermore, individual patients were studied before and at varying times after their rigidity was reduced or abolished by routine medication. In this way, any association between muscle activity and rigidity could be more reliably identified without recourse to pooling unpaired data where intersubject variability might obscure an underlying relationship. The present findings provide strong evidence that stretch reflexes of wrist muscles are enhanced in Parkinson's disease and that increased reflex activation of these muscles is an important contributor to the genesis of clinically assessed rigidity at this joint.
19 14
7
8
11
16
5
50
64
68
55
64
71
61
66
G.W.
P.M.
J.B.
J.A.
F.P.
L.J.
T.E.
D.B.
20
17
18
20
13
1
1
1
1
1
1
2
0.5
Rigidity 1
++
++
+ .+ +
++
++
++
++
+++
+++
Bradykinesia
Off medication
0
0
(+)
0
0
(+)
0
(+)
0
Tremor
0
0
0.5
0
0
0
0
0.5
Rigidity 0
0
+
+
0
0
+
+
0
0
0
0
0
0
0
0
0
+ +
Tremor
Bradykinesia
On medication Drugs S HOqds S 275 1 or 2 bd 0 50 mg tds S 110 tds O 50 mg tds M 250 tds P 5 mg tds S 110 qds B 5 mg tds S 110 one daily S 110 1 or 2 tablets tds Br 10 mg tds O 50 mg tds SP six times Se 20 mg daily SI 10 six times B 5 mg tds S 275 1 or 2 tablets qds B 5 mg tds Se 10 mg daily SP qds Se 10 mg daily
Rigidity, bradykinesia and tremor were assessed when patients were 'off and 'on' medication. Rigidity gradients (on five-point scale, see Methods) are for the wrist and were obtained under resting conditions. The values listed refer to the greatest degree of rigidity during flexion or extension. Bradykinesia and tremor were graded on a five-point scale: 0 = absent; (+) => intermittent; + = mild; + + = moderate; + + + = severe. Drugs: S = Sinemet 110/275; SP = Sinemet plus; M = Madopar 250; Se = Selegiline; Br = Bromocriptine; B = Benzhexol; O = Orphenadnne; P =• Procyclidine. Abbreviations for doses: bd = twice daily; tds = three times daily; qds = four times daily.
11
5
9
22
8 16
Webster rating
Duration (yrs)
Ase (yrs) 64
Patients G.T.
TABLE 1. CLINICAL DETAILS OF PATIENTS
Downloaded from http://brain.oxfordjournals.org/ by guest on March 23, 2016 •
z
Z
7?
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•
RELATIONSHIP BETWEEN ELECTROMYOGRAPHIC ACTIVITY AND CLINICALLY ASSESSED RIGIDITY STUDIED AT THE WRIST JOINT IN PARKINSON'S DISEASE by
R. J. MEARA and
F. w.
J. CODY 2
(From the 'Department of Neurology, Manchester Royal Infirmary and the 2Department of Physiological Sciences, University of Manchester, Manchester, UK)
The electromyographic (EMG) patterns recorded from wrist muscles during manually applied, repetitive flexion and extension movements of the wrist joint, used for simultaneous clinical assessment of rigidity, were studied in patients with Parkinson's disease and healthy subjects. Recordings were made whilst patients/subjects attempted voluntarily to relax the muscle of the arm whose wrist joint was manipulated. Individual patients were investigated before and at varying times after their routine daily medication as their clinical rigidity underwent associated modulations. It was often possible to induce additional alterations in clinical rigidity by instructing patients to perform an activation or Jendrassik-like manoeuvre (clenching the contralateral fist). In rigid patients, the approximately sinusoidal wrist displacements (60 deg, 1 — 1.5 Hz) typically elicited pronounced, cyclic modulations of EMG activities in wrist flexors and extensors; increases in EMG activity were phase-locked to the respective periods of muscle stretch. Stretch-related EMG activity reduced or disappeared as rigidity was abolished by drug therapy. The EMG patterns of patients showing cogwheel rigidity featured discrete, phasic bursts superimposed upon more generalized stretch-related increases in activity. In healthy subjects, showing no clinical rigidity, the pronounced cyclic modulations of EMG activity characteristic of rigid patients were absent during similar manually applied wrist displacements. Quantitative EMG measurements for individual patients, made 'on' and 'off medication and as their rigidity fluctuated, indicated that mild (grade 1) and moderate (grade 2) rigidity was consistently associated with increased stretch-related activity compared with non-rigid conditions. Pair-wise statistical analysis indicated such increases in EMG to be significant. Similarly, the ratios of EMG activities in the stretched versus released muscles were significantly greater for grades 1 and 2 rigidity than in the absence of rigidity. Overall, the present findings support the view that enhancement of stretch reflex activity has a major role in the genesis of parkinsonian rigidity.
INTRODUCTION
The pathophysiology of rigidity in Parkinson's disease remains obscure. Two main types of explanation have been advanced. First, that parkinsonian rigidity is of reflex origin (Pollock and Davis, 1930); secondly, that changes in the intrinsic mechanical properties of muscle are mainly responsible (Dietz et al., 1981). The former hypothesis is supported by the classical findings that rigidity is abolished following both dorsal root section (Foerster, 1921) and the intramuscular injection of local anaesthetic (Walshe, 1924); taken together, these observations suggest that activation Correspondence to: Dr F. W. J. Cody, Department of Physiological Sciences, Stopford Building, University of Manchester, Manchester M13 9PT, UK. © Oxford University Press 1992
Downloaded from http://brain.oxfordjournals.org/ by guest on March 23, 2016
SUMMARY
1168
R. J. MEARA AND F. W. J. CODY
METHODS Subjects Nine patients with Parkinson's disease, of mean age 60 ± 5 (SD) yrs, and 10 healthy subjects, of mean age 62 ± 6 yrs, were studied. The clinical details of the patients, together with their medication, are given in Table 1. All patients had a clear response to levodopa therapy; each was studied when 'off and 'on' therapy. In two patients clinical rigidity, unlike bradykinesia, was not reduced by medication. Experimental arrangement Application of wrist displacement. The subject sat in a chair with the forearm pronated and pointing forwards. The pronated arm was abducted at the shoulder and the elbow was flexed to an angle of 90 deg. Pillows on a horizontal platform supported the elbow and forearm at a comfortable height below the shoulder; the hand protruded unsupported into space beyond the platform. The examiner (R.J.M.) used one hand to apply forcible extension and flexion movements, identical to those routinely performed
Downloaded from http://brain.oxfordjournals.org/ by guest on March 23, 2016
of reflex pathways by afferent input from muscle receptors is essential for the expression of rigidity. Although the H-reflex, tendon jerk and 'short-latency' stretch reflex pathways appear to operate normally (Angel and Hofmann, 1963; Dietrichson, 1971; Tatton and Lee, 1975, but see Noth et al., 1988; Rack, 1990), it is generally agreed that 'longlatency' stretch reflex activity is enhanced in Parkinson's disease (Tatton and Lee, 1975). However, despite early reports of a quantitative association between long-latency stretch responses and rigidity (Lee and Tatton, 1975; Mortimer and Webster, 1979), numerous recent investigations reappraising this issue have failed to confirm such a clear-cut relationship (Berardelli et al., 1983; Rothwell et al., 1983; Cody et al., 1986; Meara and Cody, 1989). Thus, the present concensus is that whilst exaggerated stretch reflex activity plays a part in the generation of parkinsonian rigidity the importance of its contribution is uncertain. It should be recognized, however, that the precise experimental conditions employed in these laboratory studies may have differed in crucial respects from those used in standard neurological examination. The forcible displacements of the joint being investigated, usually driven by a motor or comparable mechanical actuator, were often linear and quite unlike the rhythmic, approximately sinusoidal movements applied manually by a clinical examiner; additionally, patients were often required to produce a steady background contraction rather than to attempt to relax. Thus, disparities in the balance of excitation of the various classes of sensory receptors and the prevailing 'set' of the central neural pathways are to be expected. These could lead to the essential reflex mechanisms operating during clinical testing remaining undetected. The present experiments were undertaken to address this problem by the novel but straightforward approach of recording electromyographic (EMG) activities and displacement during actual clinical testing of rigidity at the wrist and relating these to the rigidity simultaneously appreciated by the examiner. Furthermore, individual patients were studied before and at varying times after their rigidity was reduced or abolished by routine medication. In this way, any association between muscle activity and rigidity could be more reliably identified without recourse to pooling unpaired data where intersubject variability might obscure an underlying relationship. The present findings provide strong evidence that stretch reflexes of wrist muscles are enhanced in Parkinson's disease and that increased reflex activation of these muscles is an important contributor to the genesis of clinically assessed rigidity at this joint.
19 14
7
8
11
16
5
50
64
68
55
64
71
61
66
G.W.
P.M.
J.B.
J.A.
F.P.
L.J.
T.E.
D.B.
20
17
18
20
13
1
1
1
1
1
1
2
0.5
Rigidity 1
++
++
+ .+ +
++
++
++
++
+++
+++
Bradykinesia
Off medication
0
0
(+)
0
0
(+)
0
(+)
0
Tremor
0
0
0.5
0
0
0
0
0.5
Rigidity 0
0
+
+
0
0
+
+
0
0
0
0
0
0
0
0
0
+ +
Tremor
Bradykinesia
On medication Drugs S HOqds S 275 1 or 2 bd 0 50 mg tds S 110 tds O 50 mg tds M 250 tds P 5 mg tds S 110 qds B 5 mg tds S 110 one daily S 110 1 or 2 tablets tds Br 10 mg tds O 50 mg tds SP six times Se 20 mg daily SI 10 six times B 5 mg tds S 275 1 or 2 tablets qds B 5 mg tds Se 10 mg daily SP qds Se 10 mg daily
Rigidity, bradykinesia and tremor were assessed when patients were 'off and 'on' medication. Rigidity gradients (on five-point scale, see Methods) are for the wrist and were obtained under resting conditions. The values listed refer to the greatest degree of rigidity during flexion or extension. Bradykinesia and tremor were graded on a five-point scale: 0 = absent; (+) => intermittent; + = mild; + + = moderate; + + + = severe. Drugs: S = Sinemet 110/275; SP = Sinemet plus; M = Madopar 250; Se = Selegiline; Br = Bromocriptine; B = Benzhexol; O = Orphenadnne; P =• Procyclidine. Abbreviations for doses: bd = twice daily; tds = three times daily; qds = four times daily.
11
5
9
22
8 16
Webster rating
Duration (yrs)
Ase (yrs) 64
Patients G.T.
TABLE 1. CLINICAL DETAILS OF PATIENTS
Downloaded from http://brain.oxfordjournals.org/ by guest on March 23, 2016 •
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Z
7?
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