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Methods: One group of 45 controls was recruited and 60 PD patients in three groups: rigidities,
predominantly in the right, left and both legs. H-reflex (H) and muscle response (M) were recorded from
right and left soleus muscles during stimulations of the posterior tibial nerve at the popliteal fossa while lying
and standing. The H/M ratio was taken as an index for motoneuron excitability.
Results: Mean H/M ratios were significantly different on the right and left sides, modified by postural
changes in controls and PD patients. Analysis of variance showed that in healthy subjects the H/M ratio
was: standing.lying (right), lying.standing (left). In right leg rigidity patients, the H/M ratio was greatest
during standing, and smallest during lying. In left leg rigidity patients, the H/M ratios on the right and left
sides were equally independent of posture. In controls, left H/M.right while lying, ,right while standing. In
right leg rigidity patients, right H/M.left, but ,right in left leg rigidity patients, independent of posture.
There was no side difference in patients with rigidity in both legs.
Conclusions: (i) motoneuron excitability may show side and postural differences in healthy individuals and
PD patients; (ii) posture may be associated with lateralized motoneuron excitability in these subjects; and
(iii) Parkinsonian rigidity may have spinal motor origins.
Keywords: Parkinson’s disease, H-reflex, Motoneuron excitability, Posture, Laterality
estimate the motoneuron excitability. The H-reflex the alpha-motoneuron excitabilities from the right
amplitudes must be normalized to take into account and left sides of healthy individuals and cases with
variations due to skin resistance, subcutaneous fat one sided and both sided Parkinsonian rigidity.
levels, and the location of the stimulus electrode
before any comparison of the H-reflex amplitudes can Methods
be made. This is done by taking H/M.11 There were two categories of subjects voluntarily
The Hmax/Mmax ratio is commonly used as a participated in this study: healthy individuals and PD
dependent measure when data are being collected patients. These were divided into four groups. The
on more than one occasion.11 For these reasons we first category (group 1) consisted of 45 healthy
used the Hmax/Mmax as an index for the alpha- individuals (15 women and 30 men) with no known
motoneuron excitability changes during postural neurological signs and symptoms. The second cate-
conditions in healthy individuals and cases with PD, gory comprised 50 cases with PD (25 men and 25
instead of H-reflex amplitudes alone as used in the women). This category was divided into three groups:
other studies. patients with predominantly right leg rigidity (n522),
The alpha-motoneuron excitability assessed by the patients with predominantly left leg rigidity (n512),
H-reflex amplitude was also reported with regard to and patients with both leg rigidity (n516). The PD
Parkinsonian rigidity.12,13 These studies, however, patients were newly diagnosed and not yet taking
medication for their disease.
Published by Maney Publishing (c) W. S. Maney & Son Limited
Results
The subjects comprised four groups: healthy indivi-
duals (n545) aged 42–69 years (58.1¡6.5 years
with no known neurological signs or symptoms, PD
patients with predominantly right leg rigidity (n522)
aged between 44 and 72 years, PD patients with
Figure 2 Mean H/M ratios (ordinate) from right (A) and left
predominantly left leg rigidity (n512) aged between
51 and 65 years, and PD patients with rigidity in both
(B) soleus muscles, during lying (o) and standing ( ) of N
healthy subjects and PD patients with predominantly right or
legs (n516) aged 63–76 years. The right and left mean left leg rigidity (abscissa). Vertical lines above and below the
UPDRS motor subscores for rigidity were distributed mean H/M ratios: ¡95% confidence intervals.
among patients as follows: right UPDRS512.4¡2.5
and left UPDRS53.6¡3.1 for the patients with pre-
responses belonged to the M response (5.2 millise-
dominantly right leg rigidity, right UPDRS51.2¡0.9
conds) evoked only by alpha-efferent stimulation.
and left UPDRS512.6¡3.7 for the patients with
The H response had a much longer latency
predominantly left leg rigidity, right UPDRS5
(30.0 milliseconds) because of its reflex nature with
17.3¡3.5 and left UPDRS517.9¡6.6 for the patients
afferent–efferent connections and synaptic conduc-
with both leg rigidity. The difference between the mean
tion times.
ages of the normal subjects and patients was not
statistically significant (t51.4, df5103, P.0.10), Postural differences
indicating the groups participating in the present The mean right leg H/M ratios during lying and
study were age matched. standing of healthy subjects, and PD patients with
The M and H responses recorded from the right rigidity predominantly in the right and left leg were
soleus muscle of a healthy subject are depicted in compared in Fig. 2A. One-way ANOVA indicated
Fig. 1. As expected, the shortest latency of these that there were no significant differences between
rigidity the mean left H/M ratio was significantly Considering the side differences in relation to
greater than the mean right H/M ratio (F1, 10526.84, postural conditions, in the control subjects the alpha-
P,0.001). In patients with both leg rigidity, there was motoneuron excitability was significantly higher on
no significant difference between the mean right and the left than the right side during lying, but higher on
left H/M ratios (F1, 1450.48, P.0.45). the right than the left side during standing. These
Figure 3B illustrates the mean right and left H/M results are partly consistent with previous reports, with
ratios during standing of healthy subjects and higher motoneuron excitability on the left than the
patients with right, left, or both leg rigidity. right side during lying of the right handed healthy
ANOVA yielded significant differences between subjects.2 Thus, the asymmetric spinal motor excit-
groups for the right side (F3, 91518.71, P,0.001). ability in the lower extremities opposite to hand and
Post hoc tests for multiple comparisons indicated the foot preferences seems to be well established, but only
highest right H/M ratio for the patients with right leg when subjects are lying down.
rigidity, being higher than controls (P,0.001), It was previously argued2 that the discrepancy
patients with left leg rigidity (P,0.001), and both between hand and foot preference and motoneuron
leg rigidity (P,0.001). For the left H/M ratios, excitability in the lower extremities may be explained
ANOVA yielded significant differences between by a predominantly inhibitory action of the cerebral
groups (F3, 91559.43, P,0.001). According to post cortex on the contralateral extensor motoneurons.20
Published by Maney Publishing (c) W. S. Maney & Son Limited
hoc tests for multiple comparisons, the mean left H/M However, the subjects in these studies were lying
ratio was significantly greatest for the patients with down and no comparison was made for various
left leg rigidity, being greater than patients with right postural conditions other than lying prone. The
leg rigidity, both leg rigidity, and controls (P,0.001). above results now demonstrate that the opposite
With regard to right left differences during standing could be observed when the subjects changed their
upright (Fig. 3B), the mean right H/M ratio was posture from lying to standing, with higher moto-
significantly greater than the left H/M ratio in healthy neuron excitability on the right than the left. The
subjects (F1, 43528.82, P,0.001), and patients with mechanisms of this change in asymmetric motoenur-
right leg rigidity (F1, 20526.56, P,0.001), being onal excitability may be explained by supraspinal
significantly smaller in patients with left leg rigidity influences on the extensor motoneurones, but, as
(F1, 10549.12, P,0.001). There was no significant mentioned above, peripheral-segmental mechanisms
right–left difference in patients with both leg rigidity may be essential in the reverse change of spinal motor
(F1, 1450.56, P.0.45). asymmetry, i.e., following transition from lying to
standing posture.22
Discussion Lateralization in alpha-motoneuron excitability
The quintessence of this study was the side and depending upon the postural conditions was also
postural differences in the alpha-motoneuron excit- observed in the Parkinson’s patients in relation to
ability in healthy subjects and patients with PD in rigidity. The motoneuron excitabilities of the right
relation to one sided and both sided rigidities. and left sides were significantly greater during
In healthy individuals the mean right and left H/M standing than lying in patients with predominantly
ratios, as an index for the alpha-motoneuron excit- right leg rigidity. However, this was not the case for
ability, exhibited significant side differences that were the patients with predominantly left leg rigidity:
modified by postural changes: higher motoneuron the motoneuron excitabilities were not significantly
excitability during standing than lying on the right different from each other on the right and left sides
side, but lower excitability during standing than lying during lying and standing in these cases.
on the left side. This reversal in spinal motor These results, which are novel in the literature, may
asymmetry depending upon posture – reported for be due to exclusively right handedness and right
the first time in the literature – may be segmental as footedness of the subjects who participated in the
well as supraspinal in origin, suggesting the ‘mod- study, but there is no supporting information in the
ulatory effects of descending and segmental inputs on literature for this hypothesis. On the other hand, an
the excitability of the H-reflex circuit’.20 However, the increase in the alpha-motoneuron excitability in PD
H-reflex amplitudes have been shown to decrease was previously reported,23 but without considering
during standing in patients with a complete spinal the side differences and modulations by posture or
cord injury,21 suggesting a primary contribution of their combined actions, and indirectly measuring
peripheral sensory inputs to suppression of the so- the alpha-motoneuron excitability using the H-reflex
leus H-reflex while standing. Thus, the spinal motor amplitudes. We have also found that the mean right
asymmetry2 modified by postural conditions may leg H/M ratios during lying and standing of the
mainly have peripheral origins independent of sup- patients with left leg rigidity were not significantly
raspinal influences. different from those of the control subjects. This is
not consistent with reports about the increase of the results of the present work are also of predictive value:
alpha-motoneuronal excitability in PD. Accordingly, by simply examining the rigidity of legs (right, left or
the increase in the alpha-motoneuron excitability in both) one can predict the degree and lateralization of
PD may not be considered as a rule, provided that the the spinal alpha-motoenruon excitabilities, and this
affected sides during lying and standing are investi- may in turn be beneficial for the follow-up studies and
gated separately. Moreover, the mean right leg H/M may have therapeutical implications.
ratios of both legs of the patients exhibiting rigidity The increased alpha-motoneuron excitability, play-
predominantly in the left leg and both legs not ing a role in the mechanisms of the Parkin-
significantly different from healthy controls during sonian rigidity, may result from a decrease in the
lying and standing conditions. This finding is also not autogenetic Ib inhibition in PD, while the role of the
consistent with the view of an increased motoneuron presynaptic inhibition in Parkinsonian rigidity is
excitability in PD patients. controversial.24,25 These studies, however, did not
The results suggest that lateralization of the alpha- report any side differences modulated by postural
motoneuron excitability may be associated with changes. On the other hand, contrary to our results,
lateralization of Parkinsonian rigidity. Namely, the in other studies no statistically significant difference
mean H/M ratios from right and left sides were not was found between motoneuron excitabilities of the
significantly different from each other in patients with healthy subjects and Parkinson’s patients,25,26 but
Published by Maney Publishing (c) W. S. Maney & Son Limited
rigidity in both legs, indicating association of sym- these studies also did not consider the side differences
metric rigidity with symmetric motoneuron excitabil- in various postural conditions.
ity. In patients with predominantly left leg rigidity,
the mean left leg H/M ratios during lying and Conclusions
standing were significantly greater than the mean The excitability of the alpha-motoneurons innervat-
right leg H/M ratios during lying and standing; the ing the postural soleus muscle was assessed by taking
mean left leg H/M ratios in both postural conditions the mean H/M ratios in normal subjects, and PD
were significantly greater than in the controls, but the patients rigidity predominantly in the right, left or
mean right leg H/M ratios were not significantly both legs, to gain an insight into a possible
different from the controls. These results indicate contribution of the alpha-motoneuron excitability
association of the increased left leg rigidity in patients to the Parkinsonian rigidity. This is the first study
with predominantly left leg rigidity with a predomi- measuring the motoneuron excitability using the H/
nantly left sided increase in the alpha-motoneuron M ratio from right and left soleus muscles during
excitability, without any significant change in the lying and standing of healthy individuals and patients
right sided motoneuron excitability. With regard to with PD. The current literature did not report the side
the patients with predominantly right leg rigidity, the differences in motoneuron excitabilities during pos-
mean right leg H/M ratios during lying and standing tural changes, and methods such as the H-reflex
were significantly greater than for the controls, while amplitudes were used to measure the motoneuron
the mean left leg H/M ratio during standing was not excitability changes. A more appropriate method (H/
statistically different from the controls, but was M ratio) was used in the present work to directly
significantly smaller than in the controls during lying. measure the motoneuron excitability, and more
These results show an association of the strongly detailed information was obtained on the contribu-
right sided rigidity with an increase in the purely right tion of the alpha-motoneuron excitability to the
sided alpha-motoneuron excitability. origins of Parkinsonian rigidity by considering the
These never before reported results present direct side differences in various postural conditions. The
evidence for the contribution of asymmetric levels of strong association of the symmetric or asymmetric
the alpha-motoneuron excitabilities to the level of Parkinsonian rigidity with the symmetric or asym-
the asymmetric Parkinsonian rigidity. This contra- metric motoneuron excitability during lying and
dicts the notion of an overall motoneuron excit- standing compared to healthy controls provided
ability increase in PD found in studies that did not direct evidence for the spinal motor origins of the
consider the sides and the postural conditions, and rigidity in PD patients.
which used an unreliable method such as the H- The results are also of predictive value for the side
reflex amplitudes to measure the motoneuron excit- differences in alpha-motoneuron excitabilities by a
ability changes in patients with different levels of simple examination of the rigidities on the right and
Parkinsonian rigidity. left sides of the PD patients. These original, never
This is the first study presenting the asymmetric before reported results also accentuate the impor-
occurrence of the alpha-motoneuron excitabilities in tance of side differences under various postural
relation to the asymmetric distribution of Parkin- conditions, and may have implications for future
sonian rigidity in relation to postural changes. The research and follow-up studies with or without drugs.