OBJECTIVES To investigate cerebral vasomotor reactivity in five patients with limb shaking transient ischaemic attacks by using transcranial Doppler sonography.
METHOD Attacks with transient limb shaking were unilateral in four patients and bilateral in one. Internal carotid arteries on the side opposite the abnormal limb movements showed three 90–95% stenoses and three occlusions as assessed by cerebral angiography in three and magnetic resonance angiography and ultrasound in one case each. Reactivity of cerebral resistance vessels was studied by measuring peak mean velocities in the middle cerebral artery (MCA) before and after the application of CO2 enriched air. Reference values were obtained from 25 normal subjects.
RESULTS During hypercapnia peak mean velocities slightly decreased in five MCAs (steal phenomenon) and remained unchanged in one MCA opposite the abnormal movements, whereas the other MCAs showed normal reactivities.
CONCLUSION The delineation of an exhausted cerebral vasoreactivity in all hemispheres opposite the involuntary limb movements suggests that haemodynamic failure is the cause of transient ischaemic attacks with limb shaking.
- transient ischaemic attack transcranial Doppler ultrasound
Statistics from Altmetric.com
Attacks of brief, repetitive shaking movements of the limbs are an unusual manifestation of transient cerebral ischaemia, resembling simple focal motor seizures.1-3 As opposed to jacksonian seizures, transient ischaemic attacks with limb shaking never extend to the face or trunk, show no tonic contraction, tonic-clonic jerking, or march.1-4 Further, limb shaking is often precipitated by standing up or walking, and is promptly alleviated by assuming a supine position.2-4 Since the first description by Fisher,5 subsequent findings have firmly established the association of limb shaking transient ischaemic attacks with severe occlusive carotid artery disease.1-4 6 The movements have been reported to cease after carotid endarterectomy and superficial temporal artery-middle cerebral artery (STA-MCA) anastomoses.1 3 4 These findings1-6suggest that transient haemodynamic failure in the presence of maximally dilated resistance vessels of the brain might be involved in the pathogenesis of the abnormal limb movements. With the exception of one case report4 no haemodynamic studies have been performed to investigate cerebral vasomotor reactivity in patients with limb shaking. Recognition of the mechanism, however, is important for the administration of the appropriate treatment. Transcranial Doppler sonography (TCD) is a well established technique for the assessment of vasomotor reactivity of the brain.7-9 The aim of this investigation was to evaluate cerebral vasomotor reactivity in five patients with limb shaking transient ischaemic attacks by using TCD.
Patients and methods
The clinical and laboratory findings are based on five patients (two women, three men; mean age 64 (range 53–73) years with limb shaking transient ischaemic attacks. Vasomotor reactivity was investigated by measuring peak mean flow velocity (V) in both MCAs before and after the administration of carbon dioxide (CO2reactivity). A TC 2000S ultrasound device (EME, Uberlingen, Germany) equipped with a 2 MHz monitoring probe was used as reported previously. Ten CO2 reactivities were calculated for each patient according to the formula ((VMCA hypoventilation: VMCA normoventilation x 100) - 100)/(PCO2 hypoventilation - PCO2hyperventilation).7 Reference values (mean 3.60 (2 SD 1.78)) were obtained from previously reported 25 normal subjects.10
The extracranial cerebral arteries were investigated using colour duplex imaging; carotid stenoses and occlusions were evaluated according to previously published criteria.11 Cerebral arteries were also imaged by intra-arterial digital subtraction angiography in patients 1, 2, and 4, and by magnetic resonance angiography in patient 5. North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria were used for definite grading of carotid stenoses.12 Patients 1–4 had CT and patient 5 had MRI of the brain.
All patients had EEGs in the supine position. In patients 1–4 attempts were made to induce limb shaking transient ischaemic attacks by having the patients stand up for several minutes. Measurements of blood pressure during a five minute recumbent position and the first three minutes on assuming an upright position were done in all patients. A⩾20 mm Hg decrease of systolic and mean blood pressure was assumed to be normal.13
No patient had a history of convulsive disease or orthostatic hypotension. The cerebrovascular risk factors included arterial hypertension in all, a history of smoking and hypercholesterolaemia in four, and diabetes mellitus, coronary artery disease, and peripheral artery disease in one patient each.
The patients had multiple episodes of involuntary limb movements lasting seconds to minutes.
The movements occurred on or shortly after arising from supine to standing in all patients, and also from supine to sitting in patients 3 and 4. Limb position was not a provocative factor.
Limb movements were present on one side in four patients and on both sides in patient 3. They affected the elbow, wrist, and sometimes the shoulder in all patients, and in patients 2–5 also the knee and hip. No involvement of truncal, neck, and facial muscles was seen. The movements were described as “shaking” and “trembling”, and were estimated to be rhythmic with a frequency of 5–9 Hz. Patient 1 sometimes showed dystonic posturing of his right hand during the spells. No tonic contraction, tonic-clonic jerking, jacksonian march, or choreoathetotic movements were noticed. Patients 2, 4, and 5 had mild weakness during seconds up to minutes after the spells. Two patients also had other transient ischaemic attacks on the side of limb shaking. These transient ischaemic attacks consisted of dysarthria and brachiofaciocrural weakness in patient 2, and of brachiofacial weakness in patient 5. Neurological examination in patients 2 and 5 disclosed mild motor hemipareses on the side of the involuntary movements.
Ultrasonic, radiological, and EEG characteristics are given in table 1. The VMCA remained unchanged in one and slightly decreased in five hemispheres opposite to the limb shaking transient ischaemic attacks providing CO2 reactivities of −0.47 (SD 0.38) (for comparison10 CO2 reactivity of healthy volunteers was 3.60 (SD 0.90), and for patients with unilateral and bilateral high grade stenoses or occlusions of the carotid arteries it was 1.47 (SD 0.68) and 0.57 (SD 0.26), respectively). During standing only patient 1 developed shaking movements of his right arm, while the EEG remained unchanged. After one minute he lay down and the symptoms subsided within a few seconds. On changing from the recumbent to the upright position no patient had abnormal falls in blood pressure or complained of lightheadedness or vertigo.
Patient 1 had been treated with carbamazepine and patient 5 with phenytoin before our evaluation, each without any benefit. Treatment and clinical outcome are reported in table 2.
In patients with normal carotid arteries increases in VMCA occur during hypercapnic challenge as the cerebral resistance vessels dilate.7 In our five patients VMCAs of the six hemispheres opposite to the involuntary limb movements showed no increase during CO2 inhalation suggesting that the corresponding resistance vessels were already maximally dilated.8 In five of the six hemispheres VMCAs even decreased during hypercapoia, which may indicate a steal effect. Absent and especially negative CO2reactivities are rare in patients with high grade stenoses or occlusions of the carotid arteries, because CO2 reactivity is either normal or impaired in most cases.8 10Interestingly, Tatemichi et al 4 also reported a negative CO2 reactivity measured by intracranial Doppler in a patient with limb shaking transient ischaemic attacks. Smithet al 14 used xenon-enhanced CT to correlate changes of cerebral blood flow induced by acetazolamide with the pattern of collateral flow in patients with carotid artery disease. They found that a negative flow reactivity was significantly associated with a dependence on leptomeningeal collaterals indicating a state of maximal haemodynamic compromise.
In summary, our data support clear evidence that our patients had an exhausted vasomotor reactivity in the hemispheres opposite to the abnormal limb movements.
It has been shown that the compromise of cerebral vasomotor reactivity in cases of severe carotid artery obstruction results from the presence of an unfavourable network of intracranial and extracranial collaterals.15 16 Hypertension may have further impaired vasomotor reactivity in our patients, because animal17 and human18 studies suggest that arterial hypertension decreases cerebral vasoreactivity.
A seizure mechanism related to transient cerebral ischaemia has been discussed as a possible explanation for the shaking movements as Heisset al 19 recorded epileptic activity from cortical neurons of monkeys subjected to acute ischaemia. In our and previous series the involuntary movements affected the limbs only and showed no tonic contraction, tonic-clonic jerking, or jacksonian march, and no epileptic activity during or between the attacks.1 3 4 6 These findings strongly argue against a seizure mechanism as the cause of limb shaking transient ischaemic attacks.
We found no evidence of orthostatic hypotension in our patients. Thus orthostatic hypotension seems not to be a prerequisite for the development of attacks with limb shaking, which is in accordance with the findings of other reports.1 3 4 6 Tatemichiet al 4 have shown in a patient with limb shaking transient ischaemic attacks and exhausted vasoreactivity of the brain that cerebral blood flow passively declines with decreasing blood pressure. Scheinberg and Stead20 found a 21% decrease in cerebral blood flow that accompanied a change in posture from supine to 65° in normal subjects. The results of our study and the studies of Tatemichi et al 4 and Scheinberg and Stead20 suggest that transient decreases of cerebral perfusion pressure and blood flow, as occurring for example, during an alteration from the supine to the upright position, might be the cause of limb shaking transient ischaemic attacks.
In two of our three conservatively treated patients the involuntary movements persisted until the patients died six to eight months later. Conversely, limb shaking abolished spontaneously within three months in the third conservatively treated patient. This probably resulted from an enhancement of collateral blood supply as Widder et al 9 have recently demonstrated that vasomotor reactivity of the brain may spontaneously improve. After carotid endarterectomy the shaking movements disappeared in patient 4, whereas patient 2 died seven days after the operation from an intracerebral haematoma that was most likely caused by a hyperperfusion syndrome.21 The outcome for our patients is very similar to previously reported findings.1 3 4 Limb shaking transient ischaemic attacks disappeared in only one of four conservatively treated patients during a follow up ranging from several weeks to 18 months.1 3 6 Conversely the abnormal movements ceased in all patients after carotid endarterectomy.1 3 Limb movements were abolished in six and reduced in three of nine patients treated with STA-MCA anastomoses.1 3 Taken together these data suggest that surgical revascularisation may be more beneficial in reducing or abolishing the limb movements than conservative treatment. Because an exhausted cerebral vasoreactivity is a risk factor for the development of a hyperperfusion syndrome after carotid surgery,21patients with limb shaking transient ischaemic attacks should be kept under careful postoperative surveillance.
In conclusion, we have shown that vasomotor reactivity was exhausted in all cerebral hemispheres opposite to the involuntary movements, suggesting that transient haemodynamic insufficiency may be the cause of limb shaking transient ischaemic attacks. Clinicians should be aware of this unusual condition and search for the presence of severe occlusive carotid artery disease and abnormal vasomotor reactivity of the brain as such patients may benefit from an appropriate therapy.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.