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doi:10.

1093/brain/awq009 Brain 2010: 133; 915–922 | 915

BRAIN
A JOURNAL OF NEUROLOGY

Limb-shaking transient ischaemic attacks in


patients with internal carotid artery occlusion:
a case-control study
Suzanne Persoon, L. Jaap Kappelle and Catharina J. M. Klijn

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Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands

Correspondence to: Suzanne Persoon, MD


Department of Neurology,
University Medical Centre Utrecht,
G03.228,
Heidelberglaan 100,
3584 CX Utrecht, The Netherlands
E-mail: s.persoon@umcutrecht.nl

Limb-shaking is a specific clinical feature of transient ischaemic attacks that has been associated with a high-grade stenosis or
occlusion of the internal carotid artery. The aim of this study was to describe the clinical characteristics of limb-shaking in
patients with internal carotid artery occlusion and to investigate whether patients with limb-shaking have a worse haemody-
namic state of the brain than patients with internal carotid artery occlusion without limb-shaking. We included 34 patients
(mean age 62  7 years, 82% male) with limb-shaking associated with internal carotid artery occlusion and 68 sex- and
age-matched controls with cerebral transient ischaemic attack or minor disabling ischaemic stroke associated with internal
carotid artery occlusion, but without limb-shaking. We investigated clinical characteristics, collateral pathways on contrast
angiograms and carbon dioxide-reactivity measured by transcranial Doppler. The results showed that limb-shaking usually
lasted less than 5 min and was often accompanied by paresis of the involved limb. Compared with controls, patients with
limb-shaking more frequently had symptoms precipitated by rising or exercise (odds ratio 14.2, 95% confidence interval
4.2–47.9), more frequently had recurrent ischaemic deficits after documented internal carotid artery occlusion (but before
inclusion in the study) (odds ratio 8.2, 95% confidence interval 2.3–29.3), more often had leptomeningeal collaterals (odds
ratio 6.8, 95% confidence interval 2.0–22.7), and tended to have a lower carbon dioxide-reactivity (mean 5%  16 versus
12%  17; odds ratio 0.97 per 1% increase in carbon dioxide-reactivity, 95% confidence interval 0.94–1.00). In conclusion,
limb-shaking transient ischaemic attacks in patients with internal carotid artery occlusion can be recognized by their short
duration, are often accompanied by paresis and precipitated by rising or exercise and are indicative of an impaired haemody-
namic state of the brain.

Keywords: transient ischaemic attack; stroke; carotid artery diseases; haemodynamics


Abbreviations: EC/IC = extracranial/intracranial; ICA = internal carotid artery; MCA = middle cerebral artery; TCD = transcranial
Doppler; TIA = transient ischaemic attack

Received October 28, 2009. Revised December 15, 2009. Accepted December 21, 2009. Advance Access publication February 15, 2010
ß The Author (2010). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.
For Permissions, please email: journals.permissions@oxfordjournals.org
916 | Brain 2010: 133; 915–922 S. Persoon et al.

The protocol for the current study was prepared after collection of
Introduction all data, but before the analysis was performed. For each patient with
limb-shaking we randomly selected two controls, matched for sex and
Several case reports have described limb-shaking as a rare clinical
age, who had presented during the same period with cerebral TIA
feature of transient ischaemic attacks (TIAs) (Firlik et al., 1996;
(lasting524 h) or moderately disabling ischaemic stroke (modified
Leira et al., 1997; Niehaus et al., 1998; Zaidat et al., 1999; Rankin scale 4 3) associated with ICA occlusion, but who had not
Klempen et al., 2002; Schulz and Rothwell, 2002; Cheshire and reported limb-shaking. The ICA occlusion was demonstrated by the
Meschia, 2006; Kiechl et al., 2007). Limb-shaking has been char- absence of filling of the ICA by contrast angiography, or in one patient
acterized by brief, jerky, coarse, involuntary movements involving by absence of flow in the ICA on magnetic resonance angiography.
an arm or leg (Fisher, 1962; Baquis et al., 1985) and has been The degree of an additional stenosis in the contralateral ICA, ipsilateral
associated with high-grade stenosis or occlusion of the internal external carotid artery or vertebral artery was measured according to
carotid artery (ICA). Small observational studies have shown the North American Symptomatic Carotid Endarterectomy Trial criteria
(Fox, 1993). Patients with an ICA occlusion caused by a dissection or a
impaired cerebral blood flow or cerebrovascular reserve capacity
radiation-vasculopathy were not included. In patients and controls, we
in patients with limb-shaking and ICA stenosis or occlusion in
investigated the presence of vascular risk factors as listed in Table 2.
comparison with normal controls (Yanagihara et al., 1985;
The mean arterial blood pressure was calculated by two times the

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Levine et al., 1989; Tatemichi et al., 1990; Firlik et al., 1996; diastolic pressure plus the systolic pressure divided by 3, and expressed
Baumgartner and Baumgartner, 1998). Whether patients with in mmHg. All patients underwent MRI or CT of the brain to investigate
ICA stenosis or occlusion with limb-shaking have a worse flow the presence of a symptomatic infarct. Infarcts were considered symp-
state of the brain than patients with ICA stenosis or occlusion tomatic if the location corresponded with the patients’ symptoms and
without limb-shaking is unknown. Since the large extracranial– were classified as territorial, watershed, large subcortical or lacunar
intracranial (EC/IC) bypass trial showed no benefit of EC/IC (diameter 4 15 mm) (Damasio, 1983).
bypass surgery for prevention of stroke in patients with an ICA
occlusion (The EC/IC Bypass Study Group, 1985), several studies Collateral blood flow
have suggested that EC/IC bypass surgery may be of benefit in a
Patients had contrast angiography to confirm the ICA occlusion and to
subgroup of patients with impaired cerebral perfusion (Grubb
visualize the collateral blood flow patterns. Collateral blood flow path-
et al., 1998; Garrett et al., 2009). In that perspective, it may be
ways were studied for the symptomatic hemisphere. We considered
important to recognize limb-shaking on the basis of the history collateral blood flow via the ophthalmic artery as present if selective
and to investigate whether this specific subtype of TIA is asso- catheterization of the common carotid artery showed filling of intra-
ciated with haemodynamic impairment. The purpose of this cranial arteries distal to the carotid siphon via the external carotid
study was to describe the clinical characteristics of limb-shaking artery. Collateral pathways via the anterior communicating artery or
in patients with TIA or moderately disabling stroke associated with the posterior communicating artery were considered present if these
an occlusion of the ICA and to investigate whether patients with collateral pathways showed filling of the anterior or middle cerebral
limb-shaking have a worse haemodynamic state of the brain than artery (MCA) branches ipsilateral to the symptomatic ICA occlusion.
patients with symptomatic ICA occlusion without limb-shaking. Leptomeningeal collaterals were considered present if pial branches
from the posterior cerebral artery extending as far as the vascular
territory of the MCA or anterior cerebral artery (beyond the usual
posterior cerebral artery territory) were visualized on the angiogram
Materials and methods after selective catheterization of one of the vertebral arteries (Fig. 1)
(Brozici et al., 2003).
Patients
Between 1995 and 2008 we collected data from 313 patients with TIA
Transcranial Doppler CO2-reactivity
or minor ischaemic stroke with, at most, moderately disabling cerebral Transcranial Doppler (TCD) was performed with measurement of the
or retinal ischaemic symptoms (modified Rankin scale 43) (Banks and CO2-reactivity to investigate cerebrovascular reserve capacity. Details
Marotta, 2007) associated with ICA occlusion, who were referred to of this protocol have been described before (Klijn et al., 2000). The
the Department of Neurology, University Medical Centre Utrecht, The CO2-reactivity after carbogene inhalation was the relative change in
Netherlands. All patients had been symptomatic in the 6 months prior blood flow velocity in the MCA and expressed as a percentage. A
to the time of referral. Data, including the presence of limb-shaking, CO2-reactivity of 520% was considered abnormal, since this value
had been collected prospectively by two vascular neurologists (L.J.K. corresponds with the mean CO2-reactivity minus two times the stan-
and C.J.M.K.). Limb-shaking was defined as brief, jerky, coarse, invol- dard deviation (SD) in normal controls (Klijn et al., 2001).
untary movements of an arm or leg or both (Baquis et al., 1985). All
patients were specifically asked for these symptoms of limb-shaking,
and if present they were interviewed in detail about the duration,
Data analysis
frequency and location of the limb-shaking, the presence of weakness We compared clinical characteristics, vascular risk factors, the presence
accompanying the limb-shaking, and for precipitating factors such as and type of cerebral infarcts, the presence of a stenosis or occlusion in
rising, exercise, coughing, a meal, hyperextension of the neck, transi- the contralateral ICA, external carotid artery or vertebral arteries, col-
tion from a cold to warm environment or taking anti-hypertensive lateral blood flow pathways, and CO2-reactivity between patients with
medication. In addition, we documented whether additional cerebral and without limb-shaking and expressed differences as odds ratios
or retinal ischaemic symptoms (retinal infarction or transient monocular (ORs) with 95% confidence intervals (CIs). In a subgroup-analysis,
blindness) were present. patients with limb-shaking TIAs were compared with control patients
Limb-shaking TIAs Brain 2010: 133; 915–922 | 917

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Figure 1 Angiogram of a 57-year-old patient with a left ICA occlusion and almost daily limb-shaking TIAs from the left hemisphere;
(A) left ICA occlusion and severe stenosis of the ipsilateral common carotid artery (black arrow), (B) selective catheterization of the left
common carotid artery shows filling of MCA branches (white arrow) via the ophthalmic artery (black arrow) in the left hemisphere;
(C) selective catheterization of the right common carotid artery shows limited filling of MCA branches (black arrow) via the anterior
communicating artery, (D) selective catheterization of the left vertebral artery shows filling of some MCA branches via the posterior
communicating artery (black arrow) and filling of leptomeningeal collateral vessels (white arrow), originating from the posterior cerebral
artery.

with TIAs without limb-shaking (excluding control patients with limb-shaking, 28 (82%) of the 34 patients noticed a transient
ischaemic stroke). We used logistic regression analysis to study the paresis of their arm or leg. In 14 (41%) patients, limb-shaking
effect of the time interval between the patient’s last ischaemic symp- occurred subsequent to precipitating factors such as rising, exer-
toms and the CO2-reactivity measurement on the association between cise or coughing (Table 1). Table 2 shows the characteristics of the
limb-shaking TIAs and CO2-reactivity and expressed this adjusted
patients with limb-shaking and of controls. The presence of vas-
association as OR per 1% increase in CO2-reactivity. Finally, we
cular risk factors was similar in patients with limb-shaking and
assessed the relationship between CO2-reactivity and leptomeningeal
collaterals by a multivariable regression model. The study was
controls, except for a history of hypertension that we found
approved by the institutional review board of the University Medical more often in patients with, than in those without, limb-shaking
Centre Utrecht. TIAs (OR 4.3, 95% CI 1.5–12.5). All patients with limb-shaking
also reported symptoms other than limb-shaking; 27 (79%)
patients had additional TIAs without limb-shaking (reported symp-
Results toms, isolated or combined, were paresis of a limb in 24, sensory
symptoms in 12, dysphasia in 6 and dysarthria in 2 patients), and
Of the 313 patients with symptomatic ICA occlusion, 34 (11%) seven (21%) patients had additional permanent deficit caused by
reported limb-shaking. The characteristics of limb-shaking are a minor ischaemic stroke characterized by isolated or combined
shown in Table 1. The duration of limb-shaking was shorter symptoms of paresis of a limb in six, sensory symptoms in one,
than 5 min in the majority of patients. Most patients reported and dysphasia in four patients. In the control group, 22 (32%)
multiple episodes of limb-shaking. The arm was more frequently patients had presented with cerebral TIA and 46 (68%) patients
involved than the leg. In almost one-third of patients the arm and with ischaemic stroke. Compared with controls, patients with
leg shook simultaneously. Most patients demonstrated shaking of limb-shaking more frequently presented with TIAs than with
their whole limb and not just the hand or foot. During or following ischaemic stroke (OR 8.1, 95% CI 3.0–21.4), and more
918 | Brain 2010: 133; 915–922 S. Persoon et al.

Table 1 Clinical characteristics of limb-shaking events 520% ipsilateral to the ICA occlusion in 24 (83%) patients with
among 34 patients with occlusion of the ICA limb-shaking and in 43 (68%) patients without limb-shaking (OR
2.2, 95% CI 0.7–6.7). On average, CO2-reactivity in patients with
Number
of cases limb-shaking (mean 5%  16) tended to be lower than in those
without limb-shaking (mean 12%  17; OR 0.97 per 1% increase
Duration
in CO2-reactivity, 95% CI 0.94–1.00). The median time interval
51 min 13
1–5 min 15
between the most recent symptom and the CO2-reactivity mea-
45 min 3 surement was 18 (range 0–140) days in patients with limb-shaking
Unknown 3 and 57 (range 0–206) days in patients without limb-shaking. After
Frequency of limb-shaking TIAs adjustment of the OR for this time interval, the finding of a lower
1 episode 5 CO2-reactivity in patients with limb-shaking TIAs lost significance
2–5 episodes in a month 18 in comparison with controls (adjusted OR 0.98 per 1% increase in
45 episodes in a month 11 CO2-reactivity, 95% CI 0.95–1.01).
Side of limb-shaking In the subgroup analysis of patients with limb-shaking TIAs in
Right 21

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comparison with control patients with TIAs without limb-shaking
Left 13
(excluding control patients with ischaemic stroke) leptomeningeal
Location
Arm only 15 collaterals were more frequent in patients with limb-shaking (21 of
Leg only 5 25, 84%) compared with patients without limb-shaking (6 of 16,
Arm and leg together 9 38%; OR 8.8, 95% CI 2.0–38.1). The mean CO2-reactivity in
Sometimes arm only, sometimes leg only, 5 patients with limb-shaking TIAs was significantly lower than the
sometimes together mean CO2-reactivity in patients with TIAs without limb-shaking
Part of the arm (5%  16 versus 17%  18; OR 0.96 per 1% increase in CO2-
Whole arm 25
reactivity, 95% CI 0.92–0.99). Also in this subgroup analysis,
Lower arm and hand 2
the association between limb-shaking and a low CO2-reactivity
Hand only 2
Part of the leg was dependent on the time interval (adjusted OR 0.96 per 1%
Whole leg 19 increase in CO2-reactivity, 95% CI 0.93–1.00).
Only foot 0 In a multivariable analysis including the factors lepto-
Strength during or following limb-shaking meningeal collaterals and CO2-reactivity, the significant relation-
Paresis 28 ship between leptomeningeal collaterals and limb-shaking (OR
Normal strength 2 7.0, 95% CI 1.7–28.4) remained, as well as the trend for a
Unknown 4 lower CO2-reactivity in patients with than in those without
Precipitating factorsa 14
limb-shaking (OR 0.96 per 1% increase in CO2-reactivity, 95%
Rising 8
CI 0.92–1.00). This trend was no longer apparent after adjustment
Hyperextension of neck 1
for the time interval between the last symptoms and TCD
Transition from cold to warm environment 1
Exercise 5 (adjusted OR 0.97 per 1% increase in CO2-reactivity, 95% CI
Meal 0 0.92–1.01).
Coughing 4
Recent start of antihypertensive medication 1

a Precipitating factors were present in 14 patients. Four patients had two and one
patient had three precipitating factors.
Discussion
This study shows that limb-shaking in patients with ICA occlusion
usually lasts less than 5 min, is often accompanied by paresis of
often had additional retinal ischaemic symptoms (OR 3.6, 95% the involved limb and is often, but not necessarily precipitated by
CI 1.2–10.6). Precipitating factors that may compromise cerebral activities that may compromise cerebral perfusion such as rising,
perfusion, such as rising or exercise, were more often—but not exercise or coughing. In comparison with patients with ICA occlu-
always—present in patients with limb-shaking than in controls (OR sion without limb-shaking, patients with limb-shaking are about
14.2, 95% CI 4.2–47.9). Patients with limb-shaking TIAs more seven times more often dependent on leptomeningeal collaterals
frequently had recurrent ischaemic deficits after documented ICA and tended to have a lower CO2-reactivity. Compared with con-
occlusion (but before inclusion in the study) than control patients trols with TIAs without limb-shaking and no ischaemic stroke, the
without limb-shaking (OR 8.2, 95% CI 2.3–29.3). Patients with patients with limb-shaking TIAs had a significantly lower mean
limb-shaking less often had an infarct on their MRI or CT com- CO2-reactivity. The time period between the last symptoms and
pared to controls (OR 0.2, 95% CI 0.1–0.6) and more often a the CO2-reactivity measurement was shorter in patients with than
stenosis or occlusion in one of the vertebral arteries (OR 4.0, 95% in patients without limb-shaking, probably because patients with
CI 1.5–10.4). Patients with limb-shaking were seven times more limb-shaking TIAs more frequently had recurrent ischaemic deficits
often dependent on leptomeningeal collaterals than controls (OR after documentation of the ICA occlusion, which contributed to
6.8, 95% CI 2.0–22.7, Table 3). We found a CO2-reactivity their relatively low CO2-reactivity.
Limb-shaking TIAs Brain 2010: 133; 915–922 | 919

Table 2 Characteristics of patients with symptomatic ICA occlusion with (n = 34) and without (n = 68) limb-shaking,
matched for age and sex

Limb-shaking group (n = 34) Control group (n = 68)


Mean age (years  SD) 62  7.6 62  7.3
Male 28 (82%) 56 (82%)
Cigarette smoking in the last 5 years 29 (85%) 49 (72%)
Hypertensiona 29 (85%)b 39 (57%)
Hyperlipidaemiac 30 (88%) 60 (88%)
Diabetes mellitus 6 (18%) 17 (25%)
History of ischaemic stroke (46 months ago) 7 (21%) 11 (16%)
History of ischaemic heart disease 9 (27%) 19 (28%)
History of peripheral vascular disease 14 (41%) 23 (34%)
History of vascular disease in first-degree relative 26 (77%) 43 (63%)
Clinical features
Cerebral TIA without limb-shaking 27 (79%)b 22 (32%)

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Ischaemic stroke 7 (21%) 46 (68%)
Additional retinal ischaemic symptoms 10 (29%)b 7 (10%)
Ischaemic symptoms after documented occlusion 31 (91%)b 38 (56%)
Precipitating factorsd 16 (47%)b 4 (6%)
Mean arterial pressure (mmHg  SD) 112 15 116  16
Infarcts
Symptomatic infarcte 16/33 (48%)b 54/68 (79%)
Territorial 3 (19%) 19 (35%)
Watershed, cortical 6 (38%) 19 (35%)
Watershed, deep 0 (0%) 2 (4%)
Large subcortical 3 (19%) 5 (9%)
Lacunar 4 (25%) 9 (17%)
Cerebropetal arteries
Contralateral ICA occlusion 5/34 (15%) 12/68 (18%)
Contralateral ICA stenosis 50–99% 7/34 (21%) 27/68 (40%)
Stenosis 550% or occlusion ipsilateral of ECA 6/33 (18%) 8/67 (12%)
Stenosis 550% or occlusion of vertebral artery 15/27 (56%)b 15/63 (24%)

a Defined as a blood pressure 4160/95 mmHg or the current use of anti-hypertensive medication.
b Comparison patients with and without limb-shaking, P50.05.
c Defined as patients with either a history of hyperlipidaemia, patients on drugs because of hyperlipidaemia or patients with levels of cholesterol, triglycerides, or high
density lipoprotein cholesterol beyond the normal ranges.
d In 14 patients the limb-shaking was precipitated by activities that may compromise cerebral perfusion, in two patients only additional TIAs without limb-shaking were
precipitated by rising. In the control-group symptoms were precipitated by rising in two patients and by exercise in two patients.
e 94 patients had an MRI scan of their brain, seven patients a CT scan and in one patient a recent CT or MRI scan could not be performed.
ECA = external carotid artery.

Compared with previous small case series of 5–12 patients hyperkinetic movements such as hemidystonia and hemichorea-
(Baquis et al., 1985; Yanagihara et al., 1985; Baumgartner and hemiballism have also been described in relation to TIA or stroke
Baumgartner, 1998), we were able to identify a relatively large (Ghika-Schmid et al., 1997; Shimizu et al., 2001; Kim, 2001; Salah
group of patients with limb-shaking. We confirmed that Uddin, 2004), but they are exceedingly rare with a prevalence of
limb-shaking TIAs occur in about 10% of patients with occlusion 1% in acute stroke (Ghika-Schmid et al., 1997). In addition, those
of the ICA (Bogousslavsky and Regli, 1986). The underlying mech- hyperkinetic movement disorders seem to be related to an ischae-
anism of limb-shaking is unclear, but most studies suggest that the mic lesion in the basal ganglia or thalamic nuclei in the majority of
shaking movements are caused by transient focal cerebral ischae- patients (Ghika-Schmid et al., 1997; Kim, 2001), whereas a spe-
mia (Baquis et al., 1985; Yanagihara et al., 1985; Tatemichi et al., cific location of cerebral ischaemia in patients with limb-shaking
1990; Firlik et al., 1996; Baumgartner and Baumgartner, 1998; has not been found thus far.
Salah Uddin, 2004). Limb-shaking TIAs may resemble epileptic Previous studies concluded that limb-shaking TIAs are likely to
seizures but can be distinguished by a normal level of conscious- be caused by a low flow state of the brain and not by emboli,
ness, precipitation of symptoms by specific circumstances that may based on diminished vasomotor reactivity by TCD (Tatemichi
lower cerebral blood flow in patients with ICA occlusion, such as et al., 1990; Baumgartner and Baumgartner, 1998; Niehaus
rising or exercise, the absence of tonic contractions or a march of et al., 1998) and cerebral blood flow by Xenon inhalation
symptoms, no involvement of the face or trunk, and no epileptic (Yanagihara et al., 1985; Tatemichi et al., 1990). However, of
discharges on an EEG (Yanagihara et al., 1985; Baumgartner and patients with ICA occlusion in general, 12% had an exhausted
Baumgartner, 1998; Schulz and Rothwell, 2002). Various other and 29% a diminished CO2-reactivity when investigated by TCD
920 | Brain 2010: 133; 915–922 S. Persoon et al.

Table 3 Comparison of collateral blood flow pathways and TCD CO2-reactivity between patients with ICA occlusion with
(n = 34) and without (n = 68) limb-shaking

Limb-shaking group (n = 34) Control group (n = 68) Odds ratio (95% CI)
Collateral flow via anterior communicating artery 18/28 (64%) 44/56 (79%) 0.5 (0.2–1.3)
Collateral flow via posterior communicating artery 21/24 (88%) 30/44 (68%) 3.3 (0.8–12.8)
Collateral flow via ophthalmic artery 20/30 (67%) 23/52 (44%) 2.5 (0.99–6.4)
Leptomeningeal vessels 21/25 (84%) 21/48 (44%) 6.8 (2.0–22.7)
CO2-reactivity in %a (mean  SD) 5  16 12  17 0.97 (0.94–1.00)b

a CO2 -reactivity on the symptomatic side could be measured in 29 patients with limb-shaking and in 63 patients without limb-shaking. In three patients TCD could not be
performed and we had to exclude six patients because of an absent temporal bone window and one control patient with ischaemic stroke as an outlier with a CO2-reactivity
of 127%.
b CO2 -reactivity is expressed as OR per 1% increase in CO2-reactivity.

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(Widder et al., 1994). Studies that included only symptomatic collaterals in the flow state of the brain needs further investigation
patients with an ICA occlusion found an impaired flow state of (Brozici et al., 2003; Liebeskind, 2003), we suggest that the find-
the brain in 48 to 79% of patients, irrespective of the presence of ing of leptomeningeal collaterals in the majority of patients with
limb-shaking (Webster et al., 1995; Grubb et al., 1998; Vernieri limb-shaking supports the haemodynamic origin of limb-shaking
et al., 1999). In agreement with these studies, we found a dimin- TIAs. Because of the relationship between leptomeningeal collat-
ished CO2-reactivity in 68% of patients without limb-shaking. The erals and cerebrovascular reactivity (Smith et al., 1994; Muller and
patients with limb-shaking had a relatively lower CO2-reactivity. Schimrigk, 1996; Hofmeijer et al., 2002), we included both vari-
When we restricted the analysis to patients with TIAs only, exclud- ables in a multivariable model and showed that the presence of
ing patients who presented with ischaemic stroke, the lower CO2- leptomeningeal collaterals was independently associated with the
reactivity in patients with limb-shaking TIAs became even more presence of limb-shaking, and we still found a trend for a lower
prominent. This may be explained by the fact that in general, CO2-reactivity in patients with limb-shaking.
patients with ischaemic stroke associated with ICA occlusion Theoretically, patients with limb-shaking TIAs could benefit from
more often have a low CO2-reactivity than patients with TIAs treatment aimed at improving the cerebral perfusion. A few small
(Vernieri et al., 1999). Since most patients with limb-shaking case series described a decreased frequency or complete cessation
TIAs had recurrent episodes of symptoms, their time interval of limb-shaking TIAs after EC/IC bypass or carotid endarterectomy
between the last TIA and the TCD was shorter than for the (Baquis et al., 1985; Yanagihara et al., 1985; Tatemichi et al.,
patients without limb-shaking. In some patients CO2-reactivity 1990; Baumgartner and Baumgartner, 1998). The preliminary
improves spontaneously over time (Widder et al., 1994), and results of the Japanese EC/IC Bypass Trial (JET Study Group,
therefore we adjusted for the time interval between the last symp- 2002) showed a just significantly (P = 0.046) lower incidence of
toms and TCD. This analysis showed that a short time period since recurrent stroke in patients with symptomatic ICA or MCA stenosis
the last TIA contributes to the relatively low CO2-reactivity in or occlusion and haemodynamic compromise who underwent EC/
patients with limb-shaking. IC bypass surgery in comparison with medically treated patients,
Another important finding was that patients with limb-shaking but definite results have not yet been published in the English
more often had leptomeningeal collaterals than patients with ICA literature. The results of the Carotid Occlusion Surgery Study
occlusion without limb-shaking. Several previous studies have (Grubb et al., 2003), which investigates the beneficial effect of
shown that leptomeningeal collaterals were more often present superficial temporal artery/MCA bypass surgery in patients with a
in patients with a low cerebral blood flow (Powers et al., 1987) symptomatic ICA occlusion and an increased oxygen extraction
or impaired cerebrovascular reactivity (Smith et al., 1994; Muller fraction, are expected in 2014.
and Schimrigk, 1996; Hofmeijer et al., 2002) compared with This study has some limitations. First, we do not have clinical
patients without haemodynamic compromise, whereas one study follow-up data of all patients with symptomatic ICA occlusion. As
of 17 patients with an increased oxygen extraction fraction and 30 a result, we could not determine the predictive value of the pres-
patients with a normal oxygen extraction fraction found that the ence of limb-shaking for the risk of recurrent ischaemic stroke.
pattern of collaterals was not associated with an increased oxygen Since limb-shaking is an uncommon feature that may be difficult
extraction fraction (Derdeyn et al., 1999b). However, in this study to diagnose, reliable information on the long-term outcome of
only two patients had pial leptomeningeal collaterals (retrograde patients with limb-shaking is difficult to obtain. Second, we mea-
filling of MCA branches to the level of the insula). Both of these sured the haemodynamic state of the brain indirectly by TCD
two patients had an increased oxygen extraction fraction. Another CO2-reactivity, and measurement of the haemodynamic state of
study showed that the presence of collateral flow by the ophthal- the brain, including oxygen extraction fraction, by means of
15
mic artery or leptomeningeal vessels was significantly associated O-PET studies would have provided valuable additional informa-
with an increased oxygen extraction fraction, but that this rela- tion (Derdeyn et al., 1999a). Third, we may have underestimated
tionship was confounded by the presence of cerebral infarcts the presence of deep watershed ischaemic lesions as seven
(Yamauchi et al., 2004). Although the role of leptomeningeal patients did not have an MRI but a CT instead. In addition,
Limb-shaking TIAs Brain 2010: 133; 915–922 | 921

we only classified the symptomatic infarcts, whereas patients with perfusion in patients with carotid occlusion. Stroke 1999b; 30:
1025–32.
ICA occlusion often have asymptomatic ischaemic lesions in the
Firlik AD, Firlik KS, Yonas H. Physiological diagnosis and surgical treat-
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Fourth, the current study inevitably had some element of retro- 607–11.
spective ascertainment of the data, as it was not yet designed at Fisher CM. Concerning recurrent transient cerebral ischemic attacks. Can
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Kiechl S, Furtner M, Knoflach M, Werner P, Willeit J. Kaleidoscopic vision
The authors thank Professor L.R. Caplan, MD, Beth Israel and a jerking leg on the ski slope. Lancet 2007; 370: 1878.
Deaconess Medical Centre, Boston, USA, for his valuable com- Kim JS. Delayed onset mixed involuntary movements after thalamic
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Funding ease: report of two cases. Neurosurgery 2002; 51: 483–7.
Klijn CJ, Kappelle LJ, van der Grond J, Visser GH, Algra A, Tulleken CA,
Netherlands Heart Association (grant number 2003B263 to S.P.); et al. Lack of evidence for a poor haemodynamic or metabolic state of
Netherlands Organization for Health Research and Development the brain in patients with haemodynamic clinical features associated
with carotid artery occlusion. Cerebrovasc Dis 2001; 12: 99–107.
(grant number 907-00-103 to C.J.M.K.).
Klijn CJ, Kappelle LJ, van Huffelen AC, Visser GH, Algra A, Tulleken CA,
et al. Recurrent ischemia in symptomatic carotid occlusion: prognostic
value of hemodynamic factors. Neurology 2000; 55: 1806–12.
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